Complications in Anesthesia, Second Edition

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Section Editors JOHN L. ATLEE, MD

TERRI G. MONK, MD

Professor of Anesthesiology Department of Anesthesiology Medical College of Wisconsin Milwaukee, Wisconsin

Professor Department of Anesthesiology Duke University Medical Center Durham, North Carolina

BRENDA A. BUCKLIN, MD

TIMOTHY E. MOREY, MD

Associate Professor of Anesthesiology Department of Anesthesiology University of Colorado Health Sciences Center Denver, Colorado

Associate Professor of Anesthesiology Department of Anesthesiology University of Florida College of Medicine Gainesville, Florida

MARK A. CHANEY, MD

MICHAEL J. MURRAY, MD, PHD

Associate Professor of Anesthesiology Department of Anesthesia and Critical Care University of Chicago Pritzker School of Medicine Chicago, Illinois

DONN M. DENNIS, MD, FAHA Joachim S. Gravenstein, MD, Professor of Anesthesiology Department of Anesthesiology University of Florida College of Medicine Gainesville, Florida Vice President-Pharmacology, ARYx Therapeutics, Inc. Santa Clara, California

JOHN ELLIS, MD Professor of Anesthesiology Department of Anesthesia and Critical Care University of Chicago Pritzker School of Medicine Chicago, Illinois

JOEL M. GUNTER, MD Professor of Clinical Anesthesia and Pediatrics Department of Anesthesia University of Cincinnati School of Medicine Attending Anesthesiologist Department of Anesthesia Children’s Hospital Medical Center Cincinnati, Ohio

ROSEMARY HICKEY, MD

Professor of Anesthesiology and Chair Department of Anesthesiology Mayo Clinic College of Medicine Jacksonville, Florida

NADER D. NADER, MD Associate Professor of Anesthesiology, Surgery and Pathology State University of New York at Buffalo School of Medicine Buffalo, New York

MICHAEL F. O’CONNOR, MD Associate Professor Department of Anesthesia and Critical Care University of Chicago Pritzker School of Medicine Chicago, Illinois

KERRI M. ROBERTSON, MD Associate Clinical Professor of Anesthesiology Chief, General, Vascular, High-Risk Transplant and Surgical Critical Care Medicine Division Chief, Transplant Services Duke University School of Medicine Department of Anesthesiology Durham, North Carolina

SCOTT R. SPRINGMAN, MD

Professor and Program Director Department of Anesthesiology University of Texas Health Science Center at San Antonio San Antonio, Texas

Professor Departments of Anesthesiology and Surgery University of Wisconsin Medical School Madison, Wisconsin

BRIAN M. ILFELD, MD

KEVIN K. TREMPER, MD

Associate Professor Department of Anesthesia University of California, San Diego San Diego, California

Professor and Chairman Department of Anesthesiology University of Michigan Medical Center Ann Arbor, Michigan

DONALD A. KROLL, MD, PHD

B. CRAIG WELDON, MD

Staff Anesthesiologist Department of Surgery Veterans Affairs Medical Center Biloxi, Mississippi

Associate Professor Department of Anesthesiology and Pediatrics Duke University School of Medicine Durham, North Carolina

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1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899

COMPLICATIONS IN ANESTHESIA, 2nd edition

ISBN-13: 978-1-4160-2215-2 ISBN-10: 1-4160-2215-5

Copyright © 2007, 1999 by Saunders, an imprint of Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Health Sciences Rights Department in Philadelphia, PA, USA: phone: (+1) 215 239 3804, fax: (+1) 215 239 3805, e-mail: [email protected]. You may also complete your request on-line via the Elsevier homepage (http://www.elsevier.com), by selecting ‘Customer Support’ and then ‘Obtaining Permissions’.

Notice Knowledge and best practice in this field are constantly changing. As new research and experience broaden our knowledge, changes in practice, treatment, and drug therapy may become necessary or appropriate. Readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of the practitioner, relying on his or her own experience and knowledge of the patient, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the Editors assumes any liability for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this book. The Publisher

Library of Congress Cataloging-in-Publication Data Complications in anesthesia / [edited by] John L. Atlee. -- 2nd ed. p. ; cm. Includes bibliographical references and index. ISBN 1-4160-2215-5 1. Anesthesia--Complications. I. Atlee, John L. [DNLM: 1. Anesthesia--adverse effects. 2. Anesthetics--adverse effects. WO 245 C7369 2007] RD82.5.C63 2007 617.9′6041--dc22 2006040549

Executive Publisher: Natasha Andjelkovic Developmental Editor: Jean Nevius Publishing Services Manager: Tina Rebane Project Manager: Amy Norwitz Marketing Manager: Dana Butler

Printed in the United States of America Last digit is the print number: 9 8 7 6 5 4 3 2 1

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To all who have contributed to this work, and to the patients we serve.

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Preface An ounce of prevention is worth a pound of cure. –ANONYMOUS The second edition of Complications in Anesthesia, like its first edition, is intended to provide all practitioners of anesthesia and critical care medicine with a comprehensive source of information for most complications that might be faced in clinical practice. Topics are addressed in ten sections: Pharmacology; General Anesthesia; Regional Anesthesia and Pain Management; Cardiothoracic and Vascular Surgery; Physiologic Imbalance and Coexisting Disease; Equipment and Monitoring; Pediatrics and Neonatology; Neurosurgery, Ophthalmology, and ENT; Other Surgical Subspecialties (subdivided into Obstetrics and Gynecology, General Surgery, Urologic Surgery, and Orthopedic Surgery); and Special Topics (subdivided into Postanesthesia Care Unit, Diagnostic or Therapeutic Intervention, and Medicolegal Aspects). Section Editors were selected based on their special expertise and knowledge of the topics addressed in each section. Each chapter is presented in a highly structured format (in accordance with problem-based learning) under the following headings and subheadings: Case Synopsis, Problem Analysis (divided into Definition, Recognition, Risk Assessment, Implications), Management, and Prevention; in chapters with more than one topic, each topic is addressed

using the same headings. Schematics, figures, and tables are used liberally to illustrate key points or to summarize important information. Key references are listed at the end of each chapter under “Further Reading,” avoiding in-text citations that might distract the reader. Some chapters contain footnotes that provide further explanations. In this way, the reader can gain useful insight into a topic of interest in the minimal amount of time and with maximal retention. Also, thumb indexing and liberal cross-referencing are intended to reduce the need for time-consuming index searches. Finally, under Further Reading, in text, or in footnotes, there are references to Web sites for more or updated information. In that way, the reader can keep abreast of new developments. I hope this unconventional treatment of complications in anesthesia and critical care will serve several purposes: first, to permit quick location and researching of topics of interest to busy practitioners in the least amount of time; second, to organize the thought processes involved in medical decisionmaking in an attractive format—i.e., akin to Sherlock Holmes’ “who done it?”; and third and most importantly, to reduce the risk to our patients for unexpected and untoward events. John L. Atlee, MD

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Contributors Mark Abel, MD

Lori A. Aronson, MD, FAAP

Clinical Assistant Professor, Department of Anesthesiology, Mount Sinai Medical Center, New York, New York Vaporizers

Assistant Professor of Clinical Anesthesia and Pediatrics, Department of Anesthesia, University of Cincinnati College of Medicine; Assistant Professor, Clinical Anesthesia and Pediatrics, Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio Hypoxemia

Gaury S. Adhikary, MD, FRCA Assistant Professor, Department of Anesthesiology, University of Michigan Hospitals, Ann Arbor, Michigan Carbon Dioxide Absorbers

Maurice S. Albin, MD, MSc (Anes) Professor of Anesthesiology, Department of Anesthesiology, University of Alabama School of Medicine, Birmingham, Alabama Venous Air Embolism

Stacey L. Allen, MD Assistant Professor of Anesthesiology, Department of Anesthesiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas Corneal Injury; Open Globe Injury

Steven J. Allen, MD Professor of Anesthesiology, Ohio State University College of Medicine; Chief Executive Officer, Columbus Children’s Hospital, Columbus, Ohio Autonomic Hyperreflexia

Jonathan M. Anagnostou, MD Associate Professor of Clinical Anesthesia, Department of Anesthesia, Indiana University School of Medicine; Staff Anesthesiologist, Medical Director of Respiratory Care, Department of Anesthesia, Respiratory Care, Indiana University Hospital, Indianapolis, Indiana Blood and Blood Products: Hepatitis and HIV

Maged Argalious, MD

John L. Atlee, MD Professor of Anesthesiology, Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin Adenosine; Disorders of Potassium Balance; Nonbarbiturate Anesthetics; Chemotherapeutic Agents; Cardiac Risk Assessment; Postobstruction Pulmonary Edema; Perioperative Tachyarrhythmias; Tachyarrhythmias with Ventricular Preexcitation; Long QT Syndromes and Ventricular Arrhythmias; Patients with Cardiac Rhythm Management Devices; Disorders of Water Homeostasis: Hyponatremia and Hypernatremia

Michael S. Avidan, MD Associate Professor of Anesthesiology and Surgery; Division Chief, CT Anesthesiology and CT Intensive Care, Washington University School of Medicine, St. Louis, Missouri HIV Infection and AIDS

Isaac Azar, MD Professor of Anesthesiology, Albert Einstein College of Medicine; Consultant, Department of Anesthesiology, Beth Israel Medical Center, New York, New York Scavenging Systems

James E. Baker, MD, FRCPC Assistant Professor and Anesthesiologist, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California Postoperative Pulmonary Hypertension

Staff Anesthesiologist, Departments of General Anesthesiology and Critical Care Medicine, Cleveland Clinic Foundation, Cleveland, Ohio Complications of Trauma Surgery

Narayan Baliga, MD

George A. Arndt, MD

Shahar Bar-Yosef, MD

Professor (CHS), Department of Anesthesiology, University of Wisconsin Medical School, Madison, Wisconsin Difficult Airway: Cannot Ventilate, Cannot Intubate

Assistant Professor, Department of Anesthesiology and Critical Care, Duke University School of Medicine, Durham, North Carolina Complications of Laparoscopic Surgery

Staff Anesthesiologist, Kenosha Hospital and Medical Center, Kenosha, Wisconsin Difficult Airway: Opiate-Induced Muscle Rigidity

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Contributors

Juliana Barr, MD

Lois L. Bready, MD

Associate Professor, Department of Anesthesiology, Stanford University School of Medicine, Stanford, California; Staff Intensivist and Anesthesiologist, Veterans Affairs Palo Alto Health Care System, Anesthesiology Service, Palo Alto, California Reversal Agents: Naloxone and Flumazenil

Professor and Vice Chair, Department of Anesthesiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas Corneal Injury

Curtis L. Baysinger, MD Associate Professor, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee Hypertensive Disorders of Pregnancy

Eric Bedell, MD Associate Professor, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas Posterior Fossa Surgery

Joan Benca, MD Associate Professor, Department of Anesthesiology, University of Wisconsin Hospital and Clinics, Madison, Wisconsin Bronchospasm

Patrick E. Benedict, MD Assistant Professor of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan Transesophageal Echocardiography

Thomas P. Broderick, MD Assistant Professor, Department of Anesthesiology, University of Wisconsin Hospital and Clinics, Madison, Wisconsin Preanesthetic Evaluation: Inadequate or Missing Test Result

David L. Brown, MD Edward Rotan Distinguished Professor and Chairman, Department of Anesthesiology and Pain Medicine, M.D. Anderson Cancer Center, Houston, Texas Celiac Plexus Block: Side Effects and Complications

Adrie Bruijinzeel, MD Assistant Professor, Department of Psychiatry, Evelyn and William McKnight Brain Institute, University of Florida College of Medicine, Gainesville, Florida Chemical Dependency: Opioids

Brenda A. Bucklin, MD Associate Professor of Anesthesiology, Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado Fetal Distress

Matthew D. Caldwell, MD David G. Bjoraker, MD Associate Professor, Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida Anaphylaxis and Anaphylactoid Reactions

Assistant Professor, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan Pulmonary Artery Pressure Monitoring

William R. Camann, MD Susan Black, MD Professor, Department of Anesthesiology, University of Alabama School of Medicine, Birmingham, Alabama Antidepressants

Associate Professor, Department of Anesthesia, Harvard Medical School; Director of Obstetric Anesthesia, Brigham and Women’s Hospital, Boston, Massachusetts Pulmonary Aspiration in the Parturient

Maria I. Castro, PhD William S. Blau, MD, PhD Associate Professor of Anesthesiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina Opioid Tolerance

Assistant Professor, Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas Class II Antiarrhythmic Drugs: β-Blockers—Heart Block or Bradycardia

Steffan Blumenthal, MD

Kevin P. Chan, MD

Assistant Professor, Department of Anesthesiology and Reanimation, Orthopedic University Clinic Balgrist/Zurich, Zurich, Switzerland Interscalene Nerve Block: Potential Severe Complications

Fellow in Cardiovascular Anesthesia, Stanford University School of Medicine, Stanford, California Nonbarbiturate Anesthetics

Mark A. Chaney, MD John C. Boncyk, MD Assistant Professor, Department of Anesthesiology, University of Wisconsin Hospital and Clinics, Madison, Wisconsin Perioperative Hypoxia

Associate Professor of Anesthesiology, Department of Anesthesia and Critical Care, University of Chicago Pritzker School of Medicine, Chicago, Illinois Perioperative Myocardial Ischemia and Infarction; Adverse Neurologic Sequelae: Central Neurologic Impairment; Hypercoagulable States: Thrombosis and Embolism

Alain Borgeat, MD Professor and Chief of Staff, Department of Anesthesiology and Reanimation, Orthopedic University Clinic Balgrist/Zurich, Zurich, Switzerland Interscalene Nerve Block: Potential Severe Complications

Amit V. Chawla, MD Consultant, Department of Anesthesia, Guy’s Hospital, London, United Kingdom Inspiratory and Expiratory Gas Monitoring

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David C. H. Cheng, MD, MSc, FRCPC

James C. Crews, MD

Professor and Chair, Department of Anesthesia and Perioperative Medicine, University of Western Ontario; Anesthesiologist in Chief, London Health Sciences Center and St. Joseph’s Health Care, London, Ontario, Canada Fast-Track Cardiac Surgery

Associate Professor of Anesthesiology, Section of Regional Anesthesia and Acute Pain Management, Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina Infectious Complications of Central Neuraxial Block

Deborah A. Davis, MD S. Devi Chiravuri, MD Assistant Professor, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan Rapid Fluid and Blood Delivery Systems

Gordon Lee Collins, MD Clinical Fellow, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri Complications after Pneumonectomy

Lois A. Connolly, MD Associate Professor, Department of Anesthesiology, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital, Milwaukee, Wisconsin Unstable Cervical Spine, Atlantoaxial Subluxation

D. Ryan Cook, MD Professor of Anesthesiology, Department of Anesthesiology, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania Hypoglycemia and Hyperglycemia

Clinical Professor of Anesthesiology, Department of Anesthesiology, Thomas Jefferson University – Jefferson Medical College, Philadelphia, Pennsylvania; Pediatric Anesthesiologist/Intensivist, Nemours Cardiac Center, A.I. duPont Hospital for Children, Wilmington, Delaware Pulmonary Hypertension

Martin L. De Ruyter, MD Associate Professor of Anesthesiology, Department of Anesthesiology, Kansas University School of Medicine, Kansas City, Kansas Hyperglycemia and Diabetic Ketoacidosis; Sarcoidosis

Hernando De Soto, MD Associate Professor, Department of Pediatric Anesthesia, University of Florida Health Science Center; Staff Anesthesiologist/Medical Director of the OR, Department of Anesthesiology, SHANDS Jacksonville, Jacksonville, Florida Difficult Pediatric Airway

Donn M. Dennis, MD, FAHA

Assistant Professor of Anesthesia, Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania School of Medicine; Associate Anesthesiologist, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Ophthalmic Problems and Complications

Joachim S. Gravenstein, MD, Professor of Anesthesiology, Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida; Vice PresidentPharmacology, ARYx Therapeutics, Inc., Santa Clara, California Class III Antiarrhythmic Drugs: Potassium Channel Blockers; Class IV Antiarrhythmic Drugs: Calcium Channel Blockers

Victoria Coon, CRNA, MS

Ronak Desai, DO

Scott D. Cook-Sather, MD

Perioperative Director and Anesthesiology Department Administrator, Kaiser Permanente, West Los Angeles, Los Angeles, California Quality Assurance; Cost Containment

Resident, CA-2, Department of Anesthesia and Critical Care, University of Chicago Pritzker School of Medicine, Chicago, Illinois Peripheral Vascular Surgery

John R. Cooper, Jr., MD

Cheryl DeSimone, MD

Clinical Associate Professor of Anesthesiology, University of Texas Health Science Center; Associate Chief, Cardiovascular Anesthesia; Co-Director, Cullen Cardiovascular Research Laboratories, Texas Heart Institute, Houston, Texas Troubleshooting Common Problems during Cardiopulmonary Bypass

Cyrus DeSouza, MB,BS, FANZCA

Associate Professor of Anesthesiology, Obstetrics and Gynecology, Department of Anesthesiology, Albany Medical College; Director of Obstetric Anesthesia, Albany Medical Center, Albany, New York Embolic Events of Pregnancy

Director of Clinical Research in Pediatric Anesthesia, Department of Anesthesiology, Massachusetts General Hospital, Boston, Massachusetts Sedation of Pediatric Patients

Acting Assistant Professor, Cardiothoracic Anesthesiologist, Department of Anesthesiology, University of Washington Medical Center, Seattle, Washington; Staff Specialist Anaesthetist, Department of Anaesthetics, St. Georges Hospital, Sydney, NSW, Australia Chronotropic Drugs

Douglas B. Coursin, MD

Clifford S. Deutschman, MD

Professor of Anesthesiology and Internal Medicine, Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Adrenal Insufficiency

Professor, Department of Anesthesia and Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania Sepsis, Systemic Inflammatory Response Syndrome, and Multiple Organ Dysfunction Syndrome

Charles J. Coté, MD

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Pema Dorje, MD

Brenda G. Fahy, MD, FCCP, FCCM

Clinical Assistant Professor, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan Arterial Blood Pressure Monitoring

Professor, Department of Anesthesiology, University of Kentucky; Director of Critical Care, Department of Anesthesiology, AB Chandler Medical Center, Lexington, Kentucky Disorders of Water Homeostasis: Hyponatremia and Hypernatremia

Anthony R. Doyle, BSc, MB,BS, FRCA Formerly, Visiting Instructor in Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan; Consultant Anaesthetist, Dorset County Hospital, Dorchester, United Kingdom Fires in the Operating Room

Kenneth Drasner, MD Professor, Department of Anesthesiology and Perioperative Care, University of California, San Francisco, San Francisco, California Local Anesthetic Neurotoxicity: Cauda Equina Syndrome

Catherine Drexler, MD Vice Chair, Department of Anesthesiology, ColumbiaSt. Mary’s-Milwaukee Campus, Milwaukee, Wisconsin Angioedema and Urticaria

Zhuang T. Fang, MD, MSPH Assistant Clinical Professor, Department of Anesthesiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California Unanticipated Hospital Admission and Readmission

Doron Feldman, MD Associate Professor of Clinical Anesthesiology, State University of New York at Buffalo School of Medicine; Attending in Anesthesiology, Children’s Hospital of Buffalo, Buffalo, New York The Hostile-Combative Patient

Lynne R. Ferrari, MD

Ellen Duncan, MD

Associate Professor, Department of Anesthesia, Harvard Medical School; Medical Director, Perioperative Services, Children’s Hospital, Boston, Massachusetts Adenotonsillectomy

Tejas Anesthesia, San Antonio, Texas Open Globe Injury

Matthew P. Feuer, MD

Martin W. Dünser, MD Resident in Anesthesiology and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Medical University Innsbruck, Innsbruck, Austria Vasopressors: Vasoconstrictor Drugs

Jörg Dziersk, MD, FRCA Assistant Professor of Anesthesiology, Department of Anesthesiology, University of Washington School of Medicine, Seattle, Washington Vasodilator Drugs

Michael P. Eaton, MD Associate Professor, Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, New York Proportioning Systems; Patient Warming Systems

Charles E. Edmiston, Jr., MS, PhD Associate Professor, Department of Surgery; Director, Surgical Microbiology Research Laboratory, Medical College of Wisconsin, Milwaukee, Wisconsin Nosocomial Infections: Bacterial Pneumonia

Staff Anesthesiologist, Department of Anesthesiology, Virginia Mason Medical Center, Seattle, Washington Spinal Anesthesia: Post–Dural Puncture Headache

Stephanie S. F. Fischer, MD Visiting Associate in Cardiothoracic and Critical Care, Division of Pediatric Anesthesiology, Duke University School of Medicine, Durham, North Carolina Cardiomyopathies

M. Pamela Fish, MB,ChB Associate Professor, Department of Anesthesiology, Stanford University School of Medicine, Stanford, California; Staff Physician, Veterans Affairs Palo Alto Health Care System, Palo Alto, California Antiemetic Drugs

Randall Flick, MD, MPH Assistant Professor of Anesthesiology and Pediatrics, Department of Anesthesiology and Pediatrics, Mayo Clinic College of Medicine; Chair, Section of Pediatric Anesthesiology, Mayo Clinic, Rochester, Minnesota Anterior Mediastinal Mass

Michael P. Ford, MD

Professor of Anesthesiology, Mount Sinai School of Medicine, New York, New York Vaporizers

Assistant Professor of Anesthesiology, Department of Anesthesiology, University of Wisconsin Medical School, Madison, Wisconsin Preanesthetic Evaluation: False-Positive Tests; Difficult Airway: Cannot Ventilate, Cannot Intubate

John Ellis, MD

Jennifer T. Fortney, MD

Professor of Anesthesiology, Department of Anesthesia and Critical Care, University of Chicago Pritzker School of Medicine, Chicago, Illinois Carotid Endarterectomy; Thoracic Aortic Aneurysm

Assistant Clinical Professor, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina Fat Embolism Syndrome

James B. Eisenkraft, MD

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James M. T. Foster, MD

Mark S. Gold, MD

Clinical Assistant Professor of Anesthesiology, Department of Anesthesiology, State University of New York at Buffalo School of Medicine; Director of Anesthesiology Services, Kaleida Health, Buffalo, New York The Hostile-Combative Patient

Distinguished Professor and Chief, Departments of Psychiatry, Neuroscience, Anesthesiology, Community Health and Family Medicine, Evelyn and William McKnight Brain Institute, University of Florida College of Medicine, Gainesville, Florida Chemical Dependency: Opioids; Chemical Dependency: Nonopioids

Melissa Franckowiak, MD Resident, Department of Anesthesiology, State University of New York at Buffalo School of Medicine, Buffalo, New York Cardioversion

Eugene B. Freid, MD Associate Professor, Departments of Anesthesiology and Pediatrics, University of North Carolina Hospitals, Chapel Hill, North Carolina Succinylcholine

Kimberly Frost-Pineda, MD Assistant in Psychiatry, Department of Psychiatry, Director of Public Health Research, University of Florida College of Medicine, Gainesville, Florida Chemical Dependency: Opioids; Chemical Dependency: Nonopioids

Jeffrey L. Galinkin, MD Associate Professor, Department of Anesthesia, Children’s Hospital, Denver, Colorado Fetal Intrauterine Surgery

Arjunan Ganesh, MD Assistant Professor of Anesthesia, Department of Anesthesia, University of Pennsylvania School of Medicine; Assistant Anesthesiologist, Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Upper Respiratory Tract Infection

Hind M. Gautam, MD Clinical Assistant Professor, Department of Anesthesiology, Veterans Affairs Medical Center, Buffalo, New York Magnetic Resonance Imaging

Rodolfo Gebhardt, MD

Stuart Grant, MD Assistant Professor, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina Continuous Nerve Blocks: Perineural Local Anesthetic Infusion

Glenn P. Gravlee, MD Professor, Department of Anesthesiology, Ohio State University Hospitals, Columbus, Ohio Hemodilution and Blood Conservation

Ivar Gunnarsson, MD Landspítali—háskólasjúkrahús, Reykjavik, Iceland Oxygen Flush Valve

Mary Ann Gurkowski, MD Professor of Anesthesiology, University of Texas Health Science Center at San Antonio; Clinical Staff/Director of Medical Students, Department of Anesthesiology/Crossappointed to Otorhinolaryngology, University Hospital; Attending Staff, Department of Anesthesiology, Audie Murphy Veterans Affairs Hospital, San Antonio, Texas Foreign Body Aspiration

Jacob Gutsche, MD Physician, Department of Anesthesia, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania Sepsis, Systemic Inflammatory Response Syndrome, and Multiple Organ Dysfunction Syndrome

Thomas S. Guyton, MD Staff Anesthesiologist, Methodist Healthcare of Memphis, Memphis, Tennessee Magnesium; Antibiotics

Assistant Professor of Clinical Anesthesiology, Department of Anesthesiology, Department of Clinical Anesthesiology, Veterans Affairs Medical Center, Buffalo New York Uncontrolled Pain

Ali Habibi, MD

Jeremy M. Geiduschek, MD

Saeed Habibi, MD

Clinical Professor, Department of Anesthesiology, University of Washington School of Medicine; Director, Clinical Anesthesia Services, Department of Anesthesiology, Children’s Hospital and Regional Medical Center, Seattle, Washington Intraoperative Cardiac Arrest

J. C. Gerancher, MD Associate Professor and Section Head, Regional Anesthesia and Acute Pain Management, Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina Epidural Anesthesia: Unintended Intrathecal Injection; Epidural Anesthesia: Unintended Subdural Injection

Adjunct Clinical Faculty, Anesthesiology, Stanford University School of Medicine, Stanford, California Antihistamines: H1- and H2-Blockers Chair, Department of Anesthesiology, Columbia– St. Mary’s–Milwaukee Campus, Milwaukee, Wisconsin Angioedema and Urticaria

Charles B. Hantler, MD Professor, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri Bradyarrhythmias

H. David Hardman, MD, MBA Assistant Clinical Professor, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina Extremity Tourniquets

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Contributors

Barry A. Harrison, MB,BS

Liana Hosu, MD

Assistant Professor of Anesthesiology, Department of Anesthesiology, Mayo Clinic College of Medicine, Jacksonville, Florida Hyperglycemia and Diabetic Ketoacidosis; Sarcoidosis

Assistant Professor of Anesthesia and Pediatrics, Department of Anesthesiology, University of Cincinnati College of Medicine; Staff Anesthesiologist, Department of Anesthesiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio Postoperative Apnea in Infants

Joy L. Hawkins, MD Professor of Anesthesiology and Director of Obstetric Anesthesia, University of Colorado School of Medicine, Denver, Colorado Nonobstetric Surgery during Pregnancy

Christopher M. B. Heard, MB,ChB, FRCA Research Assistant Professor, Department of Anesthesiology and Division of Pediatric Critical Care, State University of New York at Buffalo School of Medicine; Assistant Attending, Children’s Hospital of Buffalo, Buffalo, New York Magnetic Resonance Imaging; Alleged Malpractice; The HostileCombative Patient

Stephen O. Heard, MD Interim Chair, Professor of Anesthesiology and Surgery, University of Massachusetts Medical School, Worcester, Massachusetts Perioperative Care of Immunocompromised Patients

James R. Hebl, MD Assistant Professor, Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota Anticoagulants and Peripheral Nerve Block

Robert F. Helfand, MD Associate Professor, Cleveland Clinic Lerner College of Medicine; Staff Anesthesiologist; Vice Chairman, Department of General Anesthesiology; Section Head of Orthopedic Anesthesia, Glickman Urological Center, Cleveland Clinic Foundation, Cleveland, Ohio Thromboembolic Complications

Rosemary Hickey, MD Professor and Program Director, Department of Anesthesiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas Intracranial Hypertension

Kate Huncke, MD Clinical Associate Professor, Department of Anesthesiology, New York University School of Medicine, New York, New York Radiation Oncology

Samuel A. Irefin, MD Associate Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine; Staff Anesthesiologist, Department of Anesthesiology and Critical Care Medicine, Cleveland Clinic Foundation, Cleveland, Ohio Complications of Thyroid Surgery

William Jacobs, MD Associate Professor, Departments of Psychiatry and Anesthesiology, University of Florida College of Medicine, Gainesville, Florida Chemical Dependency: Opioids; Chemical Dependency: Nonopioids

Eric Jacobsohn, MB,ChB, MHPE, FRCPC Associate Professor of Anesthesiology, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri Complications after Pneumonectomy

J. Michael Jaeger, MD, PhD Associate Professor of Anesthesiology and Neurological Surgery; Director, Thoracic Anesthesia, Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville, Virginia Class IV Antiarrhythmic Drugs: Calcium Channel Blockers

George A. Higgins, BSN, MS, CRNA Adjunct Faculty, Department of Nursing, University of Southern California; Senior Nurse Anesthetist, Department of Anesthesiology, Department of Veterans Affairs Medical Center, Los Angeles, California Embolization Procedures

Scott Holliday, MD Resident, Department of Anesthesiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas Foreign Body Aspiration

William Hope, MD, PhD Assistant Professor, Department of Anesthesiology, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital East, Milwaukee, Wisconsin Laryngeal and Tracheal Injury

Michael F. M. James, MB,ChB, PhD, FRCA, FCA(SA) Professor and Head, Department of Anesthesia, University of Cape Town; Professor and Chief Anaesthetist, Department of Anaesthesia, Groote Schuur Hospital, Cape Town, Western Cape, South Africa Complications of Adrenal Surgery

Gregory M. Janelle, MD Assistant Professor, Chief of Cardiovascular Anesthesia, Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida Phosphodiesterase Inhibitors

David R. Jobes, MD Terese T. Horlocker, MD Professor, Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota Spinal Hematoma; Persistent Paresthesia

Professor of Anesthesia, Department of Anesthesia and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Complications of Massive Transfusion

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Nicola Jones, MA, MB,BS, DTM&H, MRCP, MRCPath, PhD Consultant in Microbiology and Infectious Diseases, Departments of Microbiology and Infectious Diseases, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom HIV Infection and AIDS

Shailendra Joshi, MD Assistant Professor of Anesthesiology, Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, New York Arteriovenous Malformation: Normal Perfusion Pressure Breakthrough

Zeev N. Kain, MD Professor of Anesthesiology, Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut Perioperative Psychological Trauma

Wendy B. Kang, MD Associate Professor and Chair, Residency Education Committee, Department of Anesthesiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas Retrobulbar Block

Shubjeet Kaur, MD Clinical Vice Chair, Department of Anesthesiology, University of Massachussets Memorial Medical Center, Worcester, Massachusetts Perioperative Care of Immunocompromised Patients

Robert D. Kaye, MD Assistant Professor of Clinical Anesthesiology and Pediatrics, State University of New York at Buffalo School of Medicine; Attending Anesthesiologist, Children’s Hospital of Buffalo, Buffalo, New York Alleged Malpractice

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Jonathan T. Ketzler, MD Associate Professor of Anesthesiology; Associate Director, Trauma and Life Support Center, Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Adrenal Insufficiency

Evan D. Kharasch, MD, PhD Assistant Dean for Clinical Research; Professor and Research Director, Department of Anesthesiology, University of Washington School of Medicine, Seattle, Washington Volatile Anesthetics: Organ Toxicity

M. Sean Kincaid, MD Resident, Department of Anesthesiology, University of Washington Medical Center, Seattle, Washington Head Injury

Kathryn P. King, MD Associate Clinical Professor, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina Methylmethacrylate

Kai T. Kiviluoma, MD, PhD Associate Professor, Department of Anaesthesiology, University of Oulu Faculty of Medicine; Head of the Department, Paediatric Anaesthesia, Oulu University Hospital, Oulu, Finland Disorders of Potassium Balance

Jerome M. Klafta, MD Associate Professor and Associate Chair for Education, Department of Anesthesia and Critical Care, University of Chicago Pritzker School of Medicine, Chicago, Illinois Mediastinal Masses

Pattricia S. Klarr, MD Paul E. Kazanjian, MD Clinical Assistant Professor, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan Fires in the Operating Room; Pulmonary Artery Pressure Monitoring

Clinical Assistant Professor, Department of Anesthesiology, University of Michigan Medical School; Associate Clinical Director, Department of Anesthesiology, University of Michigan Medical Center, Ann Arbor, Michigan Laser Complications

Jeffrey S. Kelly, MD

Sandra L. Kopp, MD

Associate Professor of Anesthesiology, Section of Critical Care, Wake Forest University School of Medicine, Winston-Salem, North Carolina Complications from Toxic Ingestion

Kevin J. Kelly, MD Professor and Chair, Department of Pediatrics; Associate Dean, School of Medicine, Children’s Mercy Hospital and Clinics, University of Missouri, Kansas City, Missouri Latex Reactions in Health Care Personnel

Instructor, Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota Supraclavicular and Infraclavicular Block: Pneumothorax

Donald A. Kroll, MD, PhD Staff Anesthesiologist, Department of Surgery, Veterans Affairs Medical Center, Biloxi, Mississippi Quality Assurance; Cost Containment; Adverse Outcomes: Withheld Information or Misinformation

Robert E. Kettler, MD

Kenneth Kuchta, MD

Associate Professor, Department of Anesthesiology, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital East, Milwaukee, Wisconsin Patients with Seizure Disorders; Latex Reactions in Health Care Personnel

Assistant Clinical Professor, Department of Anesthesiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California Misidentification of a Patient

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C. Dean Kurth, MD

Ray P. Liao, MD

Professor of Anesthesia and Pediatrics, University of Cincinnati College of Medicine, Anesthesiologist-in-Chief; Chair, Institute for Pediatric Research; Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio Postoperative Apnea in Infants

Acting Assistant Professor, Department of Anesthesiology, University of Washington School of Medicine, Seattle, Washington Inotropic Drugs

Spencer S. Liu, MD Arthur M. Lam, MD, FRCPC Professor of Anesthesiology, Department of Anesthesiology, University of Washington School of Medicine; Head of Neuroanesthesia, Harborview Medical Center, Seattle, Washington Head Injury

Jeffrey L. Lane, MD Assistant Professor of Clinical Anesthesia and Director, Human Simulation Laboratory, Department of Anesthesia, Indiana University School of Medicine; Staff Anesthesiologist, Clarian Health Partners, Indianapolis, Indiana Postoperative Respiratory Insufficiency

Clinical Professor of Anesthesiology, Department of Anesthesiology, Virginia Mason Medical Center, Seattle, Washington Spinal Anesthesia: Post–Dural Puncture Headache

Emilio B. Lobato, MD Professor of Anesthesiology, Department of Anesthesiology, University of Florida College of Medicine; Chief, Cardiovascular Anesthesia, Department of Anesthesia Service, Malcom Randall Veterans Affairs Hospital, Gainesville, Florida Digitalis

Robert G. Loeb, MD Paul B. Langevin, MD Associate Professor, Department of Anesthesiology, Veterans Affairs–West Haven, West Haven, Connecticut Chemotherapeutic Agents

Associate Professor of Anesthesiology, University of Arizona College of Medicine, Tucson, Arizona Flowmeters

Celeste M. Lombardi, MD Melissa A. Laxton, MD Assistant Professor of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina Pituitary Tumors: Diabetes Insipidus

Fellow in Interventional Pain Medicine, Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida Chronic Nonsteroidal Anti-inflammatory Drug Use

Prashant Lotlikar, MD Marcia M. Lee, MD, MBA Assistant Chief, Department of Anesthesiology, Kaiser Permanente–South Bay, Harbor City, California Awareness under Anesthesia

Clinical Assistant Professor, Department of Anesthesiology, University of Texas Health Science Center, Texas Heart Institute, Houston, Texas Troubleshooting Common Problems during Cardiopulmonary Bypass

Mijin Lee, MD Assistant Clinical Professor, Department of Anesthesiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California Anesthesia for Electroconvulsive Therapy

Peter J. Lee, MD, MPH Formerly, Assistant Professor, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan Central Venous Pressure Monitoring

Philip Levin, MD Associate Professor, Department of Anesthesiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California Postoperative Delirium

Jerrold H. Levy, MD Professor and Department Chair/Research, Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia Perioperative Hypertension

Ian Lewis, MB,BS, MRCP, FRCA Associate Professor, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan Surgical Diathermy and Electrocautery

Michelle L. Lotto, MD Assistant Professor of Anesthesiology, Department of General Anesthesiology and Critical Care Medicine, Cleveland Clinic Lerner College of Medicine; Associate Staff Anesthesiologist, Cleveland Clinic Foundation, Cleveland, Ohio Complications of Spinal Surgery

Katarzyna Luba, MD Assistant Professor of Clinical Anesthesiology, Department of Anesthesia and Critical Care, University of Chicago Pritzker School of Medicine, Chicago, Illinois Perioperative Management of Patients with Muscular Dystrophy

Stewart J. Lustik, MD Associate Professor of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, New York Proportioning Systems; Patient Warming Systems

Vinod Malhotra, MD Professor and Vice Chair for Clinical Affairs, Department of Anesthesiology, Weill Medical College of Cornell University, New York–Presbyterian Hospital, New York, New York Complications of Transurethral Surgery

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Christina M. Matadial, MD

Terri G. Monk, MD

Assistant Professor, Department of Anesthesiology, Leonard M. Miller School of Medicine at the University of Miami; Staff Physician, Department of Anesthesiology, Jackson Memorial Hospital, Miami, Florida Surgery in the Morbidly Obese

Professor, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina Intraoperative Penile Erection; Complications of Radical Urologic Surgery

Lisa M. Montenegro, MD Viktoria D. Mayr, MD Resident in Anesthesiology and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Medical University Innsbruck, Innsbruck, Austria Vasopressors: Vasoconstrictor Drugs

Assistant Professor of Anesthesiology, University of Pennsylvania School of Medicine and Children’s Hospital of Philadelphia; Attending Anesthesiologist, Department of Anesthesiology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Complications of Massive Transfusion

Deborah A. McClain, MD Chief, Anesthesiology Section, Veterans Affairs Medical Center, Biloxi, Mississippi Delayed Emergence

Thomas McCutchen, MD Assistant Professor, Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina Epidural Anesthesia: Unintended Intrathecal Injection; Epidural Anesthesia: Unintended Subdural Injection

David L. McDonagh, MD Resident, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina Autonomic Dysreflexia

Susan B. McDonald, MD Staff Anesthesiologist, Department of Anesthesiology, Virginia Mason Medical Center, Seattle, Washington Side Effects of Neuraxial Opioids

Lynda J. Means, MD Professor of Anesthesia and Surgery, Department of Anesthesia, Indiana University School of Medicine, Indianapolis, Indiana Postobstruction Pulmonary Edema in Pediatric Patients

Mark Meyer, MD Assistant Professor of Clinical Anesthesia, Department of Anesthesia, University of Cincinnati College of Medicine; Assistant Professor, Clinical Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio Perioperative Aspiration Pneumonitis

Mohammed Minhaj, MD Assistant Professor, Department of Anesthesia and Critical Care, University of Chicago Pritzker School of Medicine, Chicago, Illinois Adverse Neurologic Sequelae: Peripheral Nerve Injury

Vivek Moitra, MD Assistant Professor of Anesthesiology, Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, New York Carotid Endarterectomy

Timothy E. Morey, MD Associate Professor of Anesthesiology, Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida Magnesium; Antibiotics

Lucille A. Mostello, MD Assistant Professor of Anesthesiology and Pediatrics, Department of Anesthesiology, George Washington University School of Medicine; Staff Anesthesiologist, Department of Anesthesiology, Children’s National Medical Center, Washington, DC Latex Allergy

Isobel Muhiudeen-Russell, MD Professor, Department of Anesthesia, University of California, San Francisco, San Francisco, California Postoperative Pulmonary Hypertension

J. Thomas Murphy, MD, FRCPC Associate Professor, Department of Anesthesiology, University of Kentucky College of Medicine, Lexington, Kentucky Disorders of Water Homeostasis: Hyponatremia and Hypernatremia

Catherine Friederich Murray Research Associate, Department of Anesthesiology, Mayo Clinic College of Medicine, Jacksonville, Florida Parkinson’s Disease; Alzheimer’s Disease

Michael J. Murray, MD, PhD Professor of Anesthesiology and Chair, Department of Anesthesiology, Mayo Clinic College of Medicine, Jacksonville, Florida Parkinson’s Disease; Alzheimer’s Disease

David Muzic, MD Fellow in Cardiac Anesthesia, Department of Anesthesia and Critical Care, University of Chicago Pritzker School of Medicine, Chicago, Illinois Adverse Neurologic Sequelae: Central Neurologic Impairment

Nader D. Nader, MD Constance L. Monitto, MD Assistant Professor of Anesthesiology, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institute, Baltimore, Maryland Muscle Relaxants

Associate Professor of Anesthesiology, Surgery and Pathology, State University of New York at Buffalo School of Medicine, Buffalo, New York Uncontrolled Pain; Hemodynamic Instability; Cardioversion

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Contributors

Carsten Nadjat-Haiem, MD

Hector F. Nicodemus, MD

Assistant Professor, Department of Anesthesiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California Syringe Swaps

Pediatric Anesthesiologist, Department of Anesthesiology, Holy Cross Hospital, Silver Spring, Maryland Delayed Emergence in Pediatric Patients

Susan C. Nicolson, MD Mohamed Naguib, MB,Bch, MSc, FFARCSI, MD Professor, Department of Anesthesia, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa Myasthenic Disorders

Professor of Anesthesia, Department of Anesthesia, University of Pennsylvania School of Medicine; Division Director, Cardiothoracic Anesthesia, Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Upper Respiratory Tract Infection

Bhiken Naik, MD Fellow, Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida Intrathecal Opiates; Ketamine; Steroids

David A. Nakata, MD Associate Clinical Professor and Vice Chair, Residency Development, Department of Anesthesia, Indiana University School of Medicine, Indianapolis, Indiana Postoperative Peripheral Neuropathy; Intractable Nausea and Vomiting

Charles A. Napolitano, MD, PhD Associate Professor; Director, Division of Cardiothoracic Anesthesia; Co-Director, Residency Program, Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas Class II Antiarrhythmic Drugs: β-Blockers—Heart Block or Bradycardia

Susan H. Noorily, MD Clinical Professor, Department of Anesthesiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas Laryngoscopy and Microlaryngoscopy

Mark Nunnally, MD Assistant Professor, Department of Anesthesia and Critical Care, University of Chicago Pritzker School of Medicine, Chicago, Illinois Postoperative Acute Renal Failure; Metabolic Acidosis and Alkalosis

Christopher J. O’Connor, MD Associate Professor, Department of Anesthesiology, Rush University Medical Center, Chicago, Illinois Abdominal Aortic Aneurysm Repair

Michael F. O’Connor, MD Bradly J. Narr, MD Associate Professor and Chair, Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota Porphyrias

Associate Professor, Department of Anesthesia and Critical Care, University of Chicago Pritzker School of Medicine, Chicago, Illinois Thermally Injured Patients

Jerome F. O’Hara, Jr., MD Krishna M. Natrajan, MB,BS, FRCA Assistant Professor of Adult and Pediatric Cardiothoracic Anesthesiology, Department of Anesthesiology, University of Washington School of Medicine; Attending Anesthesiologist, Department of Anesthesiology, University of Washington Medical Center, Seattle, Washington Inotropic Drugs

Norah Naughton, MD Associate Professor of Anesthesiology and Associate Professor of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, Michigan Intracranial Pressure Monitoring

Patrick Neligan, MD Assistant Professor, Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Metabolic Acidosis and Alkalosis

Philippa Newfield, MD Assistant Clinical Professor of Anesthesia and Neurosurgery, University of California, San Francisco, School of Medicine; Attending Anesthesiologist, Department of Anesthesiology, California Pacific Medical Center, San Francisco, California Intracranial Aneurysms: Rebleeding; Intracranial Aneurysms: Vasospasm and Other Issues

Associate Professor, College of Medicine, Case Western Reserve University; Vice Chairman, Department of General Anesthesiology; Section Head of Anesthesia, Glickman Urological Center, Urology Department, Cleveland Clinic Foundation, Cleveland, Ohio Complications of Lithotripsy ..

Maria A. K. Ohrn, MD Anesthesiology Associates of North Florida, PA, North Florida Regional Medical Center, Gainesville, Florida Nondepolarizing Neuromuscular Relaxants

Nollag O’Rourke, MD Fellow in Obstetric Anesthesia, Department of Anesthesia, Brigham and Women’s Hospital, Boston, Massachusetts Pulmonary Aspiration in the Parturient

Sheela S. Pai, MD Assistant Professor, Department of Anesthesiology, Baylor College of Medicine; Staff Anesthesiologist, Department of Anesthesiology and Critical Care, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas Mechanical Assist Devices

Craig M. Palmer, MD Professor of Clinical Anesthesiology; Director, Obstetric Anesthesia, University of Arizona College of Medicine, Tucson, Arizona Preterm Labor

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C. Lee Parmley, MD, JD

William Prince, MD

Professor of Anesthesiology, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee Autonomic Hyperreflexia

Department of Anesthesiology, Kaiser Permanente Oakland Medical Center, Oakland, California Central Venous Pressure Monitoring

Lester T. Proctor, MD Komal Patel, MD Fellow in Cardiac Anesthesia, Department of Anesthesia and Critical Care, University of Chicago Pritzker School of Medicine, Chicago, Illinois Hypercoagulable States: Thrombosis and Embolism

D. Janet Pavlin, MD Professor, Department of Anesthesiology, University of Washington School of Medicine; Head of Teaching and Research in Ambulatory Anesthesia, Department of Anesthesia, University of Washington Medical Center, Seattle, Washington Postoperative Urinary Retention

Padmavathi Perala, MD Anesthesiologist, Department of Anesthesiology, Veterans Affairs Medical Center, Buffalo, New York Hemodynamic Instability

Patricia H. Petrozza, MD Professor of Anesthesiology, Associate Dean for Graduate Medical Education, Wake Forest University School of Medicine, Winston-Salem, North Carolina Pituitary Tumors: Diabetes Insipidus

Linda S. Polley, MD

Professor, Departments of Anesthesiology and Pediatrics, University of Wisconsin Medical School, Madison, Wisconsin Blood and Blood Products: Transfusion Reaction

Donald S. Prough, MD Professor and Chair, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas Perioperative Fluid Management; Posterior Fossa Surgery

M. J. Pekka Raatikainen, MD Division of Cardiology, Oulu University Central Hospital, Oulu, Finland Adenosine; Class III Antiarrhythmic Drugs: Potassium Channel Blockers

Lee M. Radke, DDS Assistant Professor, Oral and Maxillofacial Surgery, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital, Milwaukee, Wisconsin Dental Injuries

Sivam Ramanathan, MD

Associate Professor, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan Postpartum Hemorrhage

Professor of Anesthesiology, University of Pittsburgh School of Medicine, Magee-Womens Hospital, Pittsburgh, Pennsylvania Humidifiers; Peripartum Neurologic Complications

David Porembka, FCCM

James G. Ramsay, MD

Professor of Anesthesia, Surgery and Internal Medicine (Cardiology), Department of Anesthesiology; Associate Director of Surgical Intensive Care; Director of Perioperative Echocardiography, University of Cincinnati College of Medicine, Cincinnati, Ohio Postoperative Respiratory Failure

Professor of Anesthesiology, Program Director, Anesthesiology Critical Care Medicine, Department of Anesthesia, Emory University School of Medicine; Anesthesiology Service Chief, Department of Anesthesiology, Emory University Hospital, Atlanta, Georgia Central Venous Pressure Monitoring

Claudia Praetel, MD

Monica N. Riesner, MD

Research Fellow, Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, New York Nitrous Oxide: Neurotoxicity

Joseph Previte, MD Associate Professor of Pediatrics and Anesthesiology, Project Leader of Anesthesia Centricity IS, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio Anesthetic Complications of Fetal Surgery: EXIT Procedures; Perioperative Aspiration Pneumonitis

Lecturer, Obstetric Anesthesia, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan Postpartum Hemorrhage

Edward T. Riley, MD Associate Professor, Department of Anesthesia, Stanford University School of Medicine, Stanford, California Antihistamines: H1- and H2-Blockers

Pamela R. Roberts, MD, FCCM, FCCP Richard C. Prielipp, MD, FCCM JJ Buckley Professor and Chair, Department of Anesthesiology, University of Minnesota Medical School, Minneapolis, Minnesota Hypothyroidism: Myxedema Coma; Hyperthyroidism: Thyroid Storm

Professor and Division Chief, Critical Care Medicine, John A. Moffitt Endowed Chair, Department of Anesthesiology, University of Oklahama Health Science Center, Oklahoma City, Oklahoma Hypothyroidism: Myxedema Coma; Hyperthyroidism: Thyroid Storm

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Kerri M. Robertson, MD

Ramachandran Satya-Krishna, MD, FRCA

Associate Clinical Professor of Anesthesiology; Chief, General, Vascular, High-Risk Transplant and Surgical Critical Care Medicine Division; Chief, Transplant Services, Duke University School of Medicine, Department of Anesthesiology, Durham, North Carolina Postoperative Hepatic Dysfunction; Complications of Carcinoid Tumors; Complications of Deliberate Hypotension: Visual Loss

Lecturer, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan; Consultant, Department of Anaesthesia, John Radcliffe Hospital, Oxford, United Kingdom Anesthesia Circuit

Marnie Robinson, MD Assistant Professor of Anesthesiology and Pediatrics, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio Anesthetic Complications of Fetal Surgery: EXIT Procedures

John B. Rose, MD Director, Pain Management Service, Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Delayed Emergence in Pediatric Patients

Mark I. Rossberg, MD Assistant Professor of Anesthesiology, Department of Anesthesia and Critical Care Medicine, Johns Hopkins Medical Institute, Baltimore, Maryland Postintubation Croup

Scott R. Schulman, MD Associate Professor of Anesthesiology and Pediatrics, Division of Pediatric Anesthesia and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina Malignant Hyperthermia

Annette Schure, MD Anesthesiologist and Pediatric Anesthesiologist, Department of Anesthesia, Tufts-New England Medical Center, Boston, Massachusetts Thoracic Aortic Aneurysm

Jeffrey J. Schwartz, MD Associate Professor, Department of Anesthesiology, Yale University School of Medicine; Attending Physician, Department of Anesthesiology, Yale-New Haven Hospital, New Haven, Connecticut Electrical Safety

Christian Seefelder, MD David M. Rothenberg, MD Professor of Anesthesiology; Associate Dean, Academic Affiliations; Co-Medical Director, Surgical Intensive Care Unit, Rush University Medical Center, Chicago, Illinois Acute Pancreatitis

Assistant in Anaesthesia, Harvard Medical School; Instructor in Anaesthesia, Department of Anaesthesiology, Perioperative and Pain Medicine, Children’s Hospital, Boston, Massachusetts Air Emboli

Daniel D. Rubens, MB,BS, FANZCA

Rajamani Sethuraman, MD, FRCA

Assistant Professor, Department of Anesthesia, University of Washington School of Medicine, Children’s Hospital and Regional Medical Center, Seattle, Washington Intraoperative Cardiac Arrest

Consultant Anaesthetist, Department of Anaesthesia, Princess Alexandra Hospital, Essex, United Kingdom Intravenous Drug Delivery Systems

Christoph N. Seubert, MD Senthilkumar Sadhasivam, MD Assistant Professor in Anesthesia and Pediatrics, Department of Anesthesia, University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio Postoperative Nausea and Vomiting

Tetsuro Sakai, MD, PhD Resident, Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Complications in Orthopedic Outpatients Not Receiving Peripheral Nerve Blocks

Francis V. Salinas, MD Clinical Assistant Professor, Department of Anesthesiology, University of Washington School of Medicine; Staff Anesthesiologist, Department of Anesthesiology, Virginia Mason Medical Center, Seattle, Washington Local Anesthetic Systemic Toxicity

Theodore J. Sanford, Jr., MD Clinical Professor of Anesthesiology, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan Difficult Airway: Opiate-Induced Muscle Rigidity

Assistant Professor, Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida Barbiturates: Porphyrias

Jack S. Shanewise, MD Chief, Division of Cardiothoracic Anesthesiology, Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, New York Transesophageal Echocardiography

Kelly T. Shannon, MD Associate Professor of Anesthesiology, University of Pittsburgh School of Medicine; Associate Chief, Department of Anesthesiology, Magee-Womens Hospital, Pittsburgh, Pennsylvania Humidifiers

Gauhar Sharih, MD, FRCA Formerly, Visiting Instructor, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan; Specialist Registrar, Department of Anaesthetics, City Hospital, Birmingham, West Midlands, United Kingdom Inspiratory and Expiratory Gas Monitoring

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Aarti Sharma, MD, DA(UK)

Mark D. Stoneham, MD, FRCA

Assistant Professor of Anesthesiology, Department of Anesthesiology, Weill Medical College of Cornell University; Attending Anesthesiologist, Department of Anesthesiology, New York–Presbyterian Hospital, New York, New York Complications of Deliberate Hypotension: Visual Loss

Honorary Senior Clinical Lecturer, Nuffield Department of Anaesthesia, John Radcliffe Hospital, Oxford, United Kingdom Pulse Oximetry

Robert N. Sladen, MD Professor and Vice Chair, Department of Anesthesiology; Chief, Division of Critical Care, College of Physicians and Surgeons of Columbia University, New York, New York Postoperative Acute Renal Failure; Hypothermia

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E. Price Stover, MD* Clinical Assistant Professor, Department of Anesthesia, Stanford University Medical Center, Stanford, California Nonbarbiturate Anesthetics

Laura Stover, MD, MASc, FRCP(C)

Professor of Anesthesia, Department of Anesthesiology, Toronto General Hospital, Toronto, Ontario, Canada One-Lung Ventilation

Acting Instructor, Department of Anesthesiology, University of Washington School of Medicine; Acting Instructor, Department of Cardiothoracic Anesthesiology, University of Washington Medical Center, Seattle, Washington; Assistant Professor of Anesthesiology, Hamilton Health Sciences, Hamilton, Ontario, Canada Drugs Affecting the Renin-Angiotensin System

Tod B. Sloan, MD

Vijayendra Sudheendra, MD

Professor of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado Spinal Cord Injury

Clinical Instructor, Department of Surgery and Anesthesiology, Brown University School of Medicine; Staff Anesthesiologist, Miriam Hospital, Providence, Rhode Island; Chief of Anesthesia, East Bay Surgery Center, Swansea, Massachusetts Complications of Transurethral Surgery

Peter D. Slinger, MD

Jonathan H. Slonin, MD Chief Resident, Department of Anesthesiology, Leonard M. Miller School of Medicine at the University of Miami, Miami, Florida Surgery in the Morbidly Obese

Paul Smythe, MD Assistant Professor of Anesthesiology, University of Michigan Medical School; Adjunct Clinical Lecturer in Dentistry, Department of Oral and Maxillofacial Surgery/Hospital Dentistry, University of Michigan School of Dentistry, Ann Arbor, Michigan Intracranial Pressure Monitoring

Jennifer E. Souders, MD Clinical Associate Professor, Department of Anesthesiology, University of Washington School of Medicine, Seattle, Washington Venous Air Embolism

Scott R. Springman, MD Professor, Departments of Anesthesiology and Surgery, University of Wisconsin Medical School, Madison, Wisconsin Preanesthetic Evaluation: False-Positive Tests; Preanesthetic Evaluation: Inadequate or Missing Test Result

James M. Steven, MD Associate Professor of Anesthesia and Pediatrics, Department of Anesthesia, University of Pennsylvania School of Medicine; Chief Medical Officer, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Upper Respiratory Tract Infection

Robert K. Stoelting, MD Emeritus Professor and Chair, Department of Anesthesia, Indiana University School of Medicine, Indianapolis, Indiana Postoperative Peripheral Neuropathy; Intractable Nausea and Vomiting

Kevin J. Sullivan, MD Assistant Professor of Anesthesiology, Mayo Clinic College of Medicine; Clinical Assistant Professor of Pediatrics, University of Florida College of Medicine, Jacksonville; Staff Member, Department of Anesthesiology, Nemours Children’s Clinic; Staff Pediatric Anesthesiologist and Intensivist, Department of Anesthesia and Critical Care Medicine, Wolfson Children’s Hospital, Jacksonville, Florida Anticholinergics; Hypothermia in Pediatric Patients

Christer H. Svensén, MD Associate Professor, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas Perioperative Fluid Management

James F. Szocik, MD Associate Professor, Department of Anesthesiology, University of Michigan Medical School; Chair, Technical Support Committee, Department of Anesthesiology, University of Michigan Medical Center, Ann Arbor, Michigan Pipeline Source Failure

Kenichi A. Tanaka, MD Assistant Professor, Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia Perioperative Hypertension

Mark D. Tasch, MD Associate Professor of Clinical Anesthesia, Department of Anesthesia, Indiana University School of Medicine, Indianapolis, Indiana Pulmonary Aspiration

*Deceased

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Peter Tassani-Prell, MD

Karen M. Van Tassel, MD

Professor of Cardiac Anesthesia, Department of Anesthesia, German Heart Center Munich, München, Germany Anticoagulation Initiation and Reversal for Cardiac Surgery; Bleeding after Cardiac Surgery

Chief Resident, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina Malignant Hyperthermia

Lisa Thannikary, MD

Gurinder M. S. Vasdev, MB,BS

Adjunct Assistant Professor, Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida Intrathecal Opiates; Ketamine; Steroids

Klaus D. Torp, MD Assistant Professor of Anesthesiology, Department of Anesthesiology, Mayo Clinic College of Medicine, Jacksonville, Florida Perioperative Management of Dialysis-Dependent Patients

Laurence C. Torsher, MD Assistant Professor of Anesthesiology, Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota Perioperative Care for Patients with Hepatic Insufficiency (Cirrhosis)

Mark F. Trankina, MD Staff Anesthesiologist, Carraway Methodist Medical Center and University of Alabama Hospital at Birmingham, Birmingham, Alabama Class I Antiarrhythmic Drugs: Ventricular Proarrhythmia

Kenneth W. Travis, MD Associate Professor Emeritus, Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire Postobstruction Pulmonary Edema

Lawrence C. Tsen, MD Associate Professor of Anesthesia, Department of Anesthesia, Harvard Medical School; Director of Anesthesia, Center for Reproductive Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, Massachusetts Antepartum Hemorrhage

Avery Tung, MD Associate Professor, Department of Anesthesia and Critical Care, University of Chicago Pritzker School of Medicine, Chicago, Illinois Major Organ System Dysfunction after Cardiopulmonary Bypass; Mechanical Assist Devices; Thermally Injured Patients

Manuel C. Vallejo, MD, DMD Associate Professor, Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Peripartum Neurologic Complications

Gail A. Van Norman, MD Clinical Associate Professor of Anesthesiology, Affiliate Associate Professor of Medical History and Ethics, University of Washington School of Medicine, Seattle, Washington; Physician, Department of Anesthesiology, St. Joseph Medical Center, Tacoma, Washington Patient Confidentiality; Do-Not-Resuscitate Orders in the Operating Room; The Jehovah’s Witness Patient

Assistant Professor of Anesthesiology, Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota Cardiopulmonary Bypass in Pregnancy

Melissa M. Vu, MD Instructor of Anesthesiology, Department of Anesthesiology, Mayo Clinic College of Medicine, Jacksonville, Florida Hyperthermia

Mehernoor F. Watcha, MD Associate Professor of Anesthesia, Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania School of Medicine, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Postoperative Nausea and Vomiting

Eileen Watson, MD Clinical Assistant Professor, Department of Anesthesiology, State University of New York at Buffalo; Attending Anesthesiologist, Children’s Hospital of Buffalo, Buffalo, New York Hemodynamic Instability

B. Craig Weldon, MD Associate Professor, Department of Anesthesiology and Pediatrics, Duke University School of Medicine, Durham, North Carolina Cardiomyopathies; Emergence Agitation

Robert S. Weller, MD Associate Professor of Anesthesiology, Department of Anesthesiology, Wake Forest University School of Medicine; Staff Anesthesiologist, Department of Anesthesiology, North Carolina Baptist Hospitals, Inc., Winston-Salem, North Carolina Psoas Compartment Block: Potential Complications

Lynda Wells, MD Associate Professor of Anesthesiology, University of Virginia Health System, Charlottesville, Virginia Pediatric Neurosurgery

Volker Wenzel, MD, MSc Associate Professor of Anesthesiology and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria Vasopressors: Vasoconstrictor Drugs

Harshdeep Wilkhu, MD Clinical Assistant Professor, Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida Nonbarbiturate Anesthetics

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Contributors

Brian A. Williams, MD

Brian J. Woodcock, MD

Associate Professor, Department of Anesthesiology, University of Pittsburgh School of Medicine; Director of Outpatient Regional Anesthesia Service, Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania Complications in Orthopedic Outpatients Not Receiving Peripheral Nerve Blocks

Assistant Professor of Anesthesiology, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan Mechanical Ventilators

Glyn D. Williams, MB,ChB, FFA Associate Professor, Department of Anesthesia, Stanford University School of Medicine, Lucile Packard Children’s Hospital, Palo Alto, California Catheter Ablation for Arrhythmias

xxiii

Christopher C. Young, MD, FCCM Assistant Clinical Professor of Surgery, Associate Clinical Professor of Anesthesiology, Chief of Critical Care Medicine Division, Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina Hypothermia

William L. Young, MD

Assistant Professor, Departments of Anesthesiology and Pediatrics, University of Colorado School of Medicine, Denver, Colorado Antidepressants; Air Emboli

James P. Livingston Professor and Vice Chair, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco General Hospital, San Francisco, California Arteriovenous Malformation: Normal Perfusion Pressure Breakthrough

Eric P. Wittkugel, MD

Christine M. Zainer, MD

Associate Professor of Clinical Anesthesia and Critical Care; Staff Anesthesiologist; Director, Preoperative Services, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio Pediatric Laryngospasm

Assistant Professor of Anethesiology, Department of Anesthesiology, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital East, Milwaukee, Wisconsin Herbals and Alternative Medicine

Lisa Wise-Faberowski, MD

Mark A. Zakowski, MD David J. Wlody, MD Clinical Associate Professor of Anesthesiology and Vice Chair for Clinical Affairs, Department of Anesthesiology, State University of New York-Downstate Medical Center; Interim Chair, Department of Anesthesiology, Long Island College Hospital, Brooklyn, New York Postpartum Headache Other Than Post–Dural Puncture Headache

Gilbert Y. Wong, MD Assistant Professor of Anesthesiology and Consultant Physician, Division of Pain Medicine, Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota Celiac Plexus Block: Side Effects and Complications

Chief, Section of Obstetric Anesthesia, Department of Anesthesiology, Cedars-Sinai Medical Center, Los Angeles, California Peripartum Neurologic Complications

Paul B. Zanaboni, MD, PhD Anesthesiologist, St. John’s Mercy Health Care, St. Louis, Missouri Bradyarrhythmias

R. Victor Zhang, MD, PhD Assistant Professor, Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida a2-Adrenoreceptor Agonists

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Acknowledgments First, I wish to acknowledge the contributions to this work of my wife Barbara, my in-house administrative and editorial assistant. Thank you, Barbara! Your literary skills (you did major in English and minor in Philosophy) were much needed and greatly appreciated! I am deeply indebted to the Section Editors for this edition of Complications in Anesthesia, some of whom were Section Editors for the first edition as well. Organizing the topics for their sections or subsections, recruiting contributors, and seeing to it that the chapter manuscripts were submitted and pre-edited in a timely fashion were some of their tasks. Special appreciation goes to Natasha Andjelkovic (Executive Publisher), Jean Nevius (Senior Developmental Editor), and Amy Norwitz (Senior Project Manager). Once again, I salute Lewis Reines (former President of WB Saunders) and Leslie Day (former Medical Editor at WB Saunders), who in 1996-1997 convinced me of the need for this conceptually new work as a resource for busy practitioners in anesthesia and critical care. Finally, I express my sincere appreciation to John P. Kampine, MD, PhD, former Professor and Chair of the Department of Anesthesiology at the Medical College of Wisconsin, and to my colleagues in that department (some of whom have contributed to this work) for providing me the time and encouragement for yet again undertaking this work. John L. Atlee, MD

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PHARMACOLOGY

VASOACTIVE DRUGS

1

Vasodilator Drugs Jörg Dziersk Case Synopsis A 90-year-old man with severe aortic stenosis, stable angina, and pulmonary hypertension has surgery under general anesthesia for a femoral neck fracture. Owing to the associated cardiac morbidities, the anesthesiologist inserts a pulmonary artery catheter. Despite maintenance of normoxemia and mild hypocapnia, the patient’s pulmonary artery pressure rises from 60/25 to 70/35 mm Hg and is associated with signs of right ventricular strain. A nitroglycerin infusion is started at 0.2 μg/kg per minute. The pulmonary artery pressure returns to near baseline values, and the systemic blood pressure decreases from 125/90 to 75/30 mm Hg.

PROBLEM ANALYSIS Definition Left-sided heart disease (e.g., mitral valve disease, aortic stenosis, left ventricular failure) often causes significant pulmonary venous pressure elevation and leads to compensatory pulmonary artery (PA) hypertension. Chronic elevation of PA pressure promotes compensatory right ventricular (RV) hypertrophy and pulmonary vascular remodeling. This, in turn, results in increased pulmonary vascular resistance (PVR). For such patients, acute (or acute-on-chronic) increases in PA pressure are often poorly tolerated. The consequences are RV dilatation, significant tricuspid regurgitation, and reduced cardiac output secondary to reduced venous return and impaired left ventricular filling. Together, they may lead to a “downward spiral.” When RV systolic pressure exceeds aortic blood pressure, RV coronary perfusion is limited to diastole, which may further impair RV performance. Vasodilating drugs act by reducing the contraction of vascular smooth muscle cells through a reduction in cytoplasmic Ca2+ concentration [Ca2+]. Vascular smooth muscle relaxation may be mediated by the following: ●

●

●

● ●

●

Increased intracellular cyclic adenosine monophosphate (e.g., β2-adrenoceptor agonists, epoprostenol) Increased intracellular cyclic guanosine monophosphate (e.g., nitric oxide, nitroglycerin, sodium nitroprusside, brain natriuretic peptide) KATP channel-opening-related hyperpolarization (e.g., diazoxide) α1-Adrenoceptor antagonism (e.g., phentolamine) Ca2+ channel blockade (e.g., diltiazem, nicardipine, verapamil) Reduction of central sympathetic tone (e.g., clonidine)

Properties of an ideal vasodilator for perioperative use include (1) short onset time, (2) short to intermediate duration of action, (3) elimination independent of organ function (i.e., renal or hepatic), and (4) lack of serious side

effects or toxicity. At this time, there is no single drug that meets all these criteria. Clinical actions, mechanisms of action, and side effects of vasodilators currently available for intravenous or inhalational administration are listed in Table 1-1.

Recognition Systemic vasodilatation causes a decline in systemic blood pressure, the extent of which depends on circulating blood volume and venous return (cardiac preload), the adequacy of compensatory mechanisms (i.e., reflex increase in heart rate and contractility), and the cardiac ejection fraction (normal or reduced). The skin appears warm and may be flushed, with a shortened capillary refill time. Organ dysfunction may occur if systemic blood pressure is below the respective autoregulation threshold or if flow in a vascular territory is pressure dependent (e.g., in the presence of coronary artery disease, renal artery stenosis, head injury). Myocardial injury, acute renal failure, or neurologic deficits are typical examples of complications of systemic hypotension. Computation of systemic vascular resistance quantifies the average degree of vasodilatation (or vasoconstriction) in the whole body, but it requires a precise measurement of mean arterial pressure and central venous pressure, as well as a determination of cardiac output. A PA catheter equipped for thermodilution cardiac output is necessary. In the presence of PA hypertension, systemic vasodilatation may allow right-to-left shunting of blood through a patent foramen ovale, leading to a diminished arterial oxygen saturation. Reduced RV preload due to venous pooling and RV myocardial perfusion pressure may compromise RV performance and result in a low cardiac output state.

Risk Assessment Vasodilator therapy has an increased potential to cause complications in patients with the following conditions: ● ● ●

Hypovolemia Stenotic valvular lesions (especially severe aortic stenosis) Hypertrophic-obstructive cardiomyopathy 3

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Pharmacology

Vasodilators Available for Intravenous or Inhalational Administration

Drug Class and Drug*

Terminal Half-life

α1-Antagonists Labetalol

5-8 hr

Phentolamine

19 min (IV)

Urapidil†

2.7 hr

α2-Adrenoceptor Agonists Clonidine

8-16 hr

Donors Nitric oxide

6 sec

Nitroglycerin

2-8 min

Sodium nitroprusside

3-4 min

Blockers Diltiazem

3-6 hr

Nicardipine

8.6 hr (infusions ≥48 hr)

Verapamil

2-8 hr

Angiotensin-Converting 11 hr

Venous > arterial vasodilatation NO or S-nitrosothiol release by metabolism ⇒ activation of guanylyl cyclase Arterial ª venous vasodilatation NO release by red cell metabolism ⇒ activation of guanylyl cyclase

Bradycardia Drug fever Reflex tachycardia Hypoglycemia

Bradycardia Potentiates anesthetic/narcotic sedation Slow IV onset (30-60 min)

Arterial vasodilatation Vascular remodeling Inhibits generation of angiotensin II Stimulates kallikrein-kinin system

18 min

Cyanide toxicity, especially with higher doses and lengthy infusions Thiocyanate toxicity (lengthy infusions) Methemoglobinemia Reflex tachycardia

Vasodilatation unpredictable Little effect in PA HTN

Possibly severe (first dose) Acute renal failure ↑ K+, especially with renal failure No effect on PA HTN (given acutely) Slow IV onset (>15 min)

Severe systemic hypotension with IV dosing (common) Inhibition of platelet aggregation and adhesion Stimulates coughing (inhalational use)

5-10 min 3-5 min 13-30 min

Natriuretic Peptides

Inhibits platelet aggregation Pulmonary edema secondary to contaminants (NO2) and metabolites (peroxynitrite) Methemoglobinemia Tachyphylaxis Methemoglobinemia

Moderate negative inotrope AV conduction blockade Does not block L-type cardiac Ca2+ channels (little or no effect on contractility or AV conduction) Significant negative inotrope Depresses sinus node Blocks AV node conduction Longer half-life with chronic use

Activation of adenylyl cyclase ⇒↑cAMP

Prostaglandins with VSM Relaxing Effect

Brain natriuretic peptide

↓ Central sympathetic vasomotor tone Inhibits peripheral NE release

Block L-type Ca2+ channels Primary arterial dilators (no venodilatation at therapeutic doses)

Calcium Channel

Alprostadil (PGE1) Epoprostenol (PGI2) Iloprost

Arterial > venous vasodilatation Competitive adrenoceptor blockade (α1:β = 1:7) Competitive α1- = α2-adrenoceptor blockade Direct action on VSM Competitive α1-adrenoceptor blockade Competitive α2-adrenoceptor block

Side Effects and Problems

Activation of guanylyl cyclase ⇒↑cGMP

Nitric Oxide and

Enzyme Inhibitors Enalaprilat

Principal Action and Mechanism of Action

Arterial and venous vasodilatation Stimulation of natriuretic peptide receptor A ⇒ activation of guanylyl cyclase domain ⇒ ↑cGMP Inhibits renin-aldosterone axis

Miscellaneous Agents Adenosine

<10 sec

Stimulation of adenosine receptors ⇒ Direct vasodilatation (A2a, A2b, A3) Reduces central sympathetic vasomotor tone (A2a) Inhibits peripheral NE release (A1)

Bradycardia Bronchoconstriction Decreased glomerular filtration rate

Table continued on following page

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Vasodilators Available for Intravenous or Inhalational Administration—cont’d

Drug Class and Drug*

Terminal Half-life

Diazoxide

20-45 hr

Fenoldopam

5-10 min

Hydralazine

2-4 min

Principal Action and Mechanism of Action

Side Effects and Problems

Opens KATP channels ⇒ hyperpolarization and arteriolar vasodilatation Dopamine (DA1) agonist ⇒ arteriolar vasodilatation Arterial vasodilatation only

Sodium and water retention Hyperglycemia Reflex tachycardia Hypokalemia Nausea Slow IV onset (5-15 min) Reflex tachycardia (quite common) Sodium and water retention Lupus-like syndrome (slow acetylators)

*Drugs with vasodilator activity used principally for their sympathomimetic effects (e.g., β2-adrenoceptor agonists, phosphodiesterase-3 inhibitors) are not included. † Urapidil is widely used in Europe but is currently not available in the United States. AV, atrioventricular; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; HTN, hypertension; IV, intravenous; NE, norepinephrine; NO, nitric oxide; NO2, nitrogen dioxide; PA, pulmonary artery; PG, prostaglandin; VSM, vascular smooth muscle.

● ●

●

Intracardiac shunts Altered organ blood flow autoregulation (e.g., systemic hypertension, head injury) Perfusion territories with pressure-dependent blood flow (e.g., coronary artery disease, renal artery stenosis, aortic coarctation)

Besides their potential to cause inappropriate systemic hypotension, many vasodilators have other undesirable physiologic effects or toxicities (summarized in Table 1-1).

Implications Systemically administered vasodilators inhibit hypoxic pulmonary vasoconstriction. They may cause or aggravate hypoxemia during one-lung ventilation or in the presence of lung pathology (e.g., atelectasis, lung contusion, pneumonia), leading to increased ventilation-perfusion mismatch or intrapulmonary shunting. Pulmonary hypertension is associated with increased perioperative morbidity and mortality in cardiac surgery. The most recent ACC/AHA guidelines on Perioperative Evaluation for Noncardiac Surgery (2002) state: “although most experts agree that pulmonary hypertension poses an increased risk for noncardiac surgery, no organized study of the problem has been performed.”

MANAGEMENT Avoidance of vasodilator drug overdose is based on titration to effect with an intravenous infusion or repeated small bolus doses, depending on pharmacokinetics. Vasodilatorinduced hypotension can be treated by the following means: ●

● ●

●

Dose adjustment or (temporary) discontinuation of the responsible vasodilator Intravascular volume loading Head-down positioning or leg elevation (circumstances permitting) Judicious application of a (short-acting) vasoconstrictor

Management of PA hypertension begins with the elimination or modulation of factors known to increase PVR: ● ●

Hypoxemia Acidemia

● ●

High sympathetic tone High intrathoracic pressure

There is evidence that PVR begins to increase significantly when arterial PO2 falls below 60 mm Hg. Conversely, the existence of pulmonary vasodilatation with hyperoxia is controversial. However, there may be circumstances when the application of a high fraction of inspired oxygen (even 1.0) is indicated, if only to increase the margin of safety against hypoxemia. Pulmonary vasoconstriction occurs with an arterial pH of less than 7.35, irrespective of the cause of acidemia (respiratory versus metabolic). Moderate hyperventilation to an arterial PCO2 of 30 to 35 mm Hg and aggressive correction of any metabolic acidosis with sodium bicarbonate or tris(hydroxymethy) aminomethane (THAM) are advised. Extreme alkalosis (pH >7.5) may produce further pulmonary vasorelaxation but adversely affects oxygen delivery and enzyme function. High endogenous catecholamine levels cause pulmonary vasoconstriction through the stimulation of α1adrenoceptors. These high levels can be avoided or treated by providing adequate anesthetic depth and postoperative analgesia. Finally, it should be remembered that lung inflation above functional residual capacity causes a progressive increase in PVR. Ventilator settings should be adjusted, based on the patient’s pulmonary function, to provide adequate oxygenation and carbon dioxide elimination while keeping mean intrathoracic pressure to a minimum. Pharmacologic pulmonary vasodilatation without concomitant systemic vasodilatation, as was required in the case described here, can be attained in two ways: 1. Inhalation of a short-acting vasodilator, such as nitric oxide (NO) or prostacyclin (epoprostenol) 2. Coadministration of an intravenous pulmonary vasodilator (e.g., nitroglycerin, nitroprusside, epoprostenol) and a pulmonary vasculature-sparing vasoconstrictor (e.g., vasopressin or its synthetic analogue terlipressin). NO activates soluble guanylyl cyclase to increase cyclic guanosine monophosphate levels in vascular smooth muscle. It is inactivated by the heme moiety of hemoglobin and superoxide anions and has a blood half-life of approximately 6 seconds. Therefore, inhaled NO affects predominantly

PHARMACOLOGY

Table 1–1

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the tone of pulmonary vessels in ventilated lung areas but has negligible effects on systemic vascular resistance. Broader application is currently limited by its very high cost and the special equipment required for its administration. Prostacyclin (PGI2, epoprostenol) and its synthetic analogue iloprost are the most potent pulmonary vasodilators known. Their main application is continuous infusion in cases of severe pulmonary hypertension. Their vasodilator action is mediated by cyclic adenosine monophosphate. Intravenous administration frequently causes prohibitive systemic hypotension, but when administered via inhalation, the effectiveness is comparable to that of inhaled NO. Arginine vasopressin is a vasoactive nonapeptide produced in the hypothalamus. It is an agonist at three specific receptor types. Stimulation of the V1a receptor results in contraction of systemic vascular smooth muscle by means of an intracellular activation pathway shared with angiotensin II. Successful use of arginine vasopressin in vasodilatory shock after cardiopulmonary bypass and in hyperdynamic septic shock has been reported. The advanced cardiovascular life support guidelines of 2000 recommend vasopressin as an alternative to epinephrine in patients with refractory ventricular fibrillation. In contradistinction to the pulmonary vascular effects of other vasoconstrictors (e.g., α1adrenoceptor agonists, angiotensin II), vasopressin has been shown to cause pulmonary and cerebral artery vasodilatation, possibly through receptor-mediated local NO release. It may be the vasopressor drug of choice in patients with significantly elevated PVR or RV failure.

PREVENTION Preventing the complications of vasodilator use is based on an understanding of the patient’s pathophysiology and the pharmacology of available drugs. Vasodilators are used to advantage based on their specific profiles, always keeping in mind any undesired or dangerous side effects. For instance, in a patient with aortic stenosis and coronary artery disease, both systemic hypotension and tachycardia must be avoided. In the case described in this chapter, nitroglycerin would be a reasonable choice for treatment of

pulmonary hypertension, because it produces less relaxation of systemic resistance vessels than do other pulmonary vasodilators and does not cause a reflex tachycardia. Use of vasodilators in the perioperative period should take into account the common occurrence of hypovolemia due to preoperative fluid restriction, intraoperative fluid shifts or blood loss, and globally or regionally reduced sympathetic tone in anesthetized patients. Careful dose titration of vasodilators is advisable and is facilitated by using drugs with short half-lives. Vasodilator therapy for pulmonary hypertension coincides with the appropriate manipulation of physiologic factors known to affect PVR. Inhalational administration of NO or epoprostenol, if feasible, may help avoid unwanted systemic venodilatation or arterial vasodilatation effects. Finally, always keep in mind that adrenoceptor antagonists and vasodilators attenuate sympathetic responses, possibly masking the clinical signs of inadequate depth of anesthesia. The use of a depth-of-anesthesia monitor is encouraged, especially when neuromuscular blockers are used.

Further Reading Balser JR, Butterworth J: Cardiovascular drugs. In Hensley FA Jr, Martin DE, Gravlee GP (eds): A Practical Approach to Cardiac Anesthesia, 3rd ed. Philadelphia, JB Lippincott–Williams & Wilkins, 2003. Barnes PJ, Liu SF: Regulation of pulmonary vascular tone. Pharmacol Rev 47:87-131, 1995. Eagle KA, Berger PB, Calkins H, et al: ACC/AHA Guideline Update on Perioperative Cardiovascular Evaluation for Noncardiac Surgery, 2002. American College of Cardiology Web site available at http://www.acc.org/ clinical/ guidelines/perio/dirIndex.htm Frishman WH, Sonnenblick EH, Sica DH (eds): Cardiovascular Pharmacotherapeutics, 2nd ed. New York, McGraw-Hill, 2003. Katzung BG (ed): Basic & Clinical Pharmacology, 9th ed. New York, Lange Medical Books/McGraw-Hill, 2004. Malouf JF, Enriquez-Sarano M, Pellikka PA, et al: Severe pulmonary hypertension in patients with severe aortic valve stenosis: Clinical profile and prognostic implications. J Am Coll Cardiol 40:789-795, 2002. Olschewski H, Rose F, Schermuly R, et al: Prostacyclin and its analogues in the treatment of pulmonary hypertension. Pharmacol Ther 102:139-153, 2004. Reich DL, Bodian CA, Krol M, et al: Intraoperative hemodynamic predictors of mortality, stroke, and myocardial infarction after coronary artery bypass surgery. Anesth Analg 89:814-822, 1999.

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REGIONAL ANESTHESIA & PAIN PHARMACOLOGY MANAGMENT

Vasopressors: Vasoconstrictor Drugs

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Viktoria D. Mayr, Volker Wenzel, and Martin W. Dünser Case Synopsis A 73-year-old woman with a history of chronic arterial hypertension and coronary heart disease undergoes surgery for an infected hip prosthesis. Etomidate, fentanyl, and rocuronium are used to induce anesthesia. After induction, the patient’s arterial blood pressure (BP) suddenly drops to 60/40/30 mm Hg (systolic/mean/diastolic). Infusion of 1 L normal saline and two 5-mg intravenous bolus injections of ephedrine have no significant effect on BP. Continuous infusion of norepinephrine restores BP to a more normal range (105/74/58 mm Hg); however, simultaneously, the patient develops tachycardia with ventricular ectopic beats. After norepinephrine is increased to 0.35 μg/kg per minute, atrial fibrillation with a rapid ventricular response develops and results in a sustained reduction in arterial BP.

PROBLEM ANALYSIS Definition The first priority of perioperative cardiovascular care is to maintain adequate perfusion of vital organs. In addition to sufficient cardiac output, mean arterial BP must be maintained to secure organ perfusion pressure. Accordingly, arterial hypotension is either a mean arterial pressure (MAP) less than 60 mm Hg or a drop in MAP of more than 30% from preoperative values. Below a MAP of about 60 mm Hg, vascular autoregulation1 declines in the brain, kidneys, and parts of the gastrointestinal tract. For the heart, autoregulation is lost below a diastolic BP of 50 to 55 mm Hg, presuming a normal left ventricular end-diastolic pressure. With loss of autoregulation, vital organ perfusion becomes compromised. Fluids, inotropes, and vasopressors are used to treat hypotension in perioperative and critical care settings. After restoration of normovolemia and adequate cardiac output with intravenous fluids and inotropes, ongoing hypotension may require the use of vasopressors. Commonly used vasopressors in the perioperative setting are dopamine, norepinephrine, epinephrine, phenylephrine, ephedrine, and vasopressin (Table 2-1). All these drugs exert their effects by stimulating α-adrenergic and β-adrenergic receptors. These receptors are found not only in vascular and cardiac smooth muscle but also in the liver, platelets, leukocytes, bronchiolar smooth muscle, fat, and muscle.

1 The autoregulatory (AR) curve is shifted upward and to the right in chronic hypertension. In normotensives, flow is constant over the MAP range of 60 to 160 mm Hg. With chronic hypertension, the AR range is 80 to 180 mm Hg or higher. Below or above this, flow is directly proportional to MAP: flow increases for MAP values above the upper AR setpoint, and it decreases for values below the lower setpoint. For the heart, the AR curve is a diastolic BP of 50 to 150 mm Hg, presuming a normal left ventricular end-diastolic pressure (0 to 3 mm Hg). If the left ventricular enddiastolic pressure increases, the AR curve shifts upward and to the right.

Systemic inflammation or sepsis leads to high cytokine concentrations, with overproduction of nitric oxide. In turn, both membranous and cytosolic adrenergic receptor complexes are quantitatively and qualitatively down-regulated. These pathophysiologic adaptive mechanisms lead to reduced effects of endogenous or exogenous catecholamines, often necessitating the infusion of even higher catecholamine doses to ensure adequate vital organ perfusion. However, such high-dose catecholamine infusions may adversely affect the risk-benefit ratio of adrenergic vasopressor therapy beyond clinically acceptable ranges.

Recognition Institution of vasopressor therapy may have a number of untoward effects on major organ systems. Among the more common side effects of catecholamines are α1- and primarily β-adrenergic-mediated ventricular ectopy and tachyarrhythmia.2 High-dose vasopressor therapy with primary α-adrenergic agonists may increase pulmonary artery pressure. Aside from these effects, some catecholamine derivatives have specific side effects that may have an adverse impact on patient outcomes. For example, dopamine is known to reduce mucosal perfusion in the gastrointestinal tract. Although mesenteric blood flow significantly increases during therapy with dopamine, mucosal oxygenation deteriorates. This paradoxical effect is likely due to an intervillus shunt (i.e., shift of intestinal wall blood flow to the submucosa). Dopamine also influences the production and release of several hormones. Lengthy infusions may lead to reduced serum concentrations of prolactin, human growth hormone, and thyroid hormones.

2 A synergistic interaction between α1- and β-adrenoceptors has been implicated in the genesis of catecholamine-anesthetic ventricular arrhythmias: a1A-mediated slowing of Purkinje fiber conduction, with enhanced conduction at the Purkinje fiber–ventricular muscle fiber junction.

7

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Pharmacology

Effects of Vasopressor Drugs

Drug

Negative Effects

Positive Effects

Dopamine

Tachycardia Tachyarrhythmia Pulmonary artery vasoconstriction ↓ PaO2 (↑ O2 demand) ↑ Systemic vascular resistance Tachycardia Tachyarrhythmias ↑ O2 consumption Tachycardia Tachyarrhythmias ↑ O2 consumption Hyperglycemia ↑ Systemic vascular resistance ↑ O2 consumption

↑ Myocardial contractility ↑ Glomerular filtration rate

Norepinephrine

Epinephrine

Phenylephrine

Ephedrine

Tachycardia Indirectly mediated effects†

Vasopressin

Ischemic skin lesions Gut ischemia

↑ Myocardial contractility

↑ Cardiac index ↑ Stroke volume ↑ O2 delivery ↑ Cardiac index* ↑ Stroke volume* ↑ Cardiac output* ↑ O2 delivery ↑ Heart rate ↑ Cardiac output ↑ Mean arterial pressure ↑ O2 delivery ↑ Mean arterial pressure Heart rate‡ ↑ Mean pulmonary artery pressure ↑ Catecholamine requirements

*Venous constriction in venous capacitance bed augments venous return and cardiac preload, thereby increasing cardiac output. † Effects largely mediated by endogenous catecholamine release. ‡ No effect, or decrease due to baroreceptor stimulation caused by increased blood pressure.

Apart from reduced gastrointestinal blood flow, phenylephrine may reduce cardiac output. Although this is not a consistent finding, it may be explained by a baroreceptormediated reduced heart rate and possibly reduced contractility. Aside from substantial tachycardia and proarrhythmia potential, both epinephrine and norepinephrine may have significant metabolic side effects, including sustained hyperglycemia due to β-adrenergic stimulation of hepatic gluconeogenesis and down-regulation of peripheral insulin receptors. Further, epinephrine may lead to significant hyperlactatemia via the stimulation of muscular β receptors. Consequently, excessive stimulation of glycoclysis leads to the overproduction of lactate. Epinephrine is also known to cause a significant reduction in the hepatosplanchnic oxygen supply. Catecholamines stimulate α receptors to activate platelets and induce a hypercoagulable state. Such hypercoagulability may be aggravated by α-adrenergic-mediated vasoconstriction. Consequent thrombosis or vasoconstriction could further impair vital organ perfusion. Also, adrenergic receptor stimulation exerts several immune-modulating effects. Whereas α receptors mediate immune-suppressive effects by increasing tumor necrosis factor α, stimulation of β receptors improves immune function by releasing interleukin-10 to reduce dendritic cell migration. This influences antigen expression and contact hypersensitivity responses. Thus, a number of complications involving multiple organ systems may occur when administering catecholamines to support BP.

Risk Assessment The occurrence of adverse effects during vasopressor therapy with catecholamines depends not only on the doses used but

also on individual patient characteristics. Patients with coronary heart disease or congestive heart failure are more prone to develop tachyarrhythmias, myocardial ischemia, or myocardial infarction during therapy with catecholamine vasopressors. Owing to a reduced arrhythmogenic threshold in the elderly, catecholamine-induced tachyarrhythmias occur at much lower doses in older patients than in younger ones. Moreover, the α-receptor-mediated increase in pulmonary vascular resistance may significantly impair right heart function in patients suffering from chronic pulmonary hypertension or right ventricular failure. If fluids and inotropic therapy fail to restore normovolemia and sufficient cardiac output, complications caused by catecholamine vasopressor therapy may occur sooner and with greater severity than would otherwise be the case. In this circumstance, catecholamine vasopressors may produce tissue hypoxia by aggravating peripheral vasoconstriction and significantly interfering with vital organ perfusion. Thus, ensuring adequate cardiac output with fluids and inotropic support is the mainstay of cardiovascular therapy, before initiating any vasopressor treatment.

Implications Adverse effects of high-dose catecholamine therapy substantially alter the risk-benefit ratio of any vasopressor therapy. Further, they increase the risk for adverse perioperative outcomes. Especially in elderly patients and those with cardiac dysfunction, catecholamine-induced tachycardia may significantly increase myocardial oxygen demand, thereby causing ischemia or myocardial infarction. Vasopressor-induced increased myocardial oxygen consumption not only compromises oxygen availability but also significantly reduces cardiac output and systemic oxygen delivery.

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Chapter 2

Vasopressors: Vasoconstrictor Drugs

9

of new tachyarrhythmias (8.3%) compared with high-dose norepinephrine alone (54.3%). Although arginine vasopressin has no antiarrhythmic activity by itself, adding it to high-dose norepinephrine in patients with advanced vasodilatory shock after cardiopulmonary bypass can significantly reduce norepinephrine needs and facilitate spontaneous conversion of about 50% of new-onset tachyarrhythmias independent of antiarrhythmic therapy. In contrast to high-dose norepinephrine, the significantly lower heart rates after arginine vasopressin therapy in patients with advanced vasodilatory shock can substantially reduce myocardial oxygen demand. There is now evidence of improved myocardial performance with norepinephrine–arginine vasopressin, likely owing to the reduced need for norepinephrine. Adverse effects of arginine vasopressin include possible deterioration of hepatic function and reduced platelet counts; however, reduced platelet counts do not appear to lead to increased clinical bleeding. Effects of arginine vasopressin on gastrointestinal blood flow have been inadequately studied. Although some authorities fear gastrointestinal hypoperfusion, there is evidence that arginine vasopressin may actually improve gastrointestinal perfusion when given continuously at doses of 4 units/hour in patients with advanced vasodilatory shock. At present, because there are no data supporting a beneficial effect on patient outcomes with the administration of supplementary arginine vasopressin in cases of advanced vasodilatory shock, its use with catecholamine vasopressors to reduce the latter’s toxicity can be advised only as a last resort.

MANAGEMENT If vasopressors are not necessary, do not use them. However, do assure normovolemia and adequate inotropic therapy. If cardiac output is still inadequate, administer catecholamine vasopressors in the lowest possible doses. In patients with significant cardiovascular dysfunction, even this may not be possible. If this is the case, symptomatic therapy, such as that for new-onset tachyarrhythmias, is the only therapy for catecholamine-induced complications. Striking recent evidence suggests that supraphysiologic doses of hydrocortisone (200 to 300 mg/day) not only significantly improve cardiovascular function and reduce catecholamine requirements but also reduce mortality in patients with septic shock. Possible mechanisms include relief of relative adrenal insufficiency as well as unspecific, permissive effects leading to up-regulation of adrenergic receptors. Also, hydrocortisone may favorably alter several pathophysiologically relevant inflammatory pathways that contribute to cardiovascular failure. Adverse hydrocortisone effects appear to occur independent of the dosage used and include hypernatremia and hyperglycemia. It is unknown whether hydrocortisone-mediated immune modulation or aggravation of catabolic metabolism is clinically relevant. Arginine vasopressin is used as a supplementary vasopressor in the treatment of advanced vasodilatory shock. Several studies show that continuous arginine vasopressin (4 units/hour) significantly improves hemodynamic variables and reduces catecholamine vasopressor requirements. In these cases, combined arginine vasopressin–norepinephrine infusion leads to a significant reduction in the incidence

PREVENTION Assurance of adequate volume and inotropic therapy to guarantee sufficient cardiac output are the most important preventive measures to avoid catecholamine vasopressormediated complications. Infusion of high dosages of hydrocortisone may reduce the need for high-dose norepinephrine therapy and thus reduce catecholamine-associated complications. Also, recent evidence suggests that a supplementary continuous infusion of arginine vasopressin (4 units/hour) might contribute to improved hemodynamic stability, fewer norepinephrine-related complications, and higher survival rates, but only when started before norepinephrine doses exceed 0.6 μg/kg per minute.

Further Reading Annane D, Sebille V, Charpentier C, et al: Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862-871, 2002. Dellinger RP: Cardiovascular management of septic shock. Crit Care Med 31:946-955, 2003. Dunser MW, Mayr AJ, Ulmer H, et al: Arginine vasopressin in advanced vasodilatory shock: A prospective, randomized, controlled study. Circulation 107:2313-2319, 2003. Heyndrickx GR, Boettcher DH, Vatner SF: Effects of angiotensin, vasopressin, and methoxamine on cardiac function and blood flow distribution in conscious dogs. Am J Physiol 231:1579-1587, 1976. James JH, Luchette FA, McCarter FD, Fischer JE: Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 354:505-508, 1999.

PHARMACOLOGY

Catecholamine-induced tachyarrhythmias may further aggravate myocardial ischemia. In particular, the development of atrial fibrillation with a rapid ventricular response—the most common tachyarrhythmia with catecholamine therapy— exacerbates cardiovascular dysfunction due to a loss of atrial transport function and reduced ventricular filling. This can cause a substantial reduction in cardiac output, with a subsequent backward increase in pulmonary vascular resistance, leading to right ventricular failure and further deterioration of cardiovascular function. Reduced hepatic, splanchnic, or intestinal mucosal oxygen delivery with prolonged epinephrine or dopamine infusions can increase organ damage, facilitate endotoxin production, and exacerbate systemic inflammation and multiple organ dysfunction. Arterial lactate concentrations correlate with patient outcome, because hyperlactatemia may increase perioperative mortality irrespective of metabolic acidosis. Moreover, elevated serum glucose concentrations significantly contribute to adverse patient outcomes, especially among the critically ill. Theoretically, catecholamine-induced hypercoagulability may facilitate thrombus formation at the microcirculatory level, thus precipitating multiorgan system damage; however, there is no clinical evidence of this. Such hypercoagulability may also facilitate the evolution of perioperative myocardial infarction. Further, it is unknown whether adrenergic vasopressor-mediated immune modulation influences immune responses in the perioperative setting.

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Lorton D, Lubahn C, Bellinger DL: Potential use of drugs that target neuralimmune pathways in the treatment of rheumatoid arthritis and other autoimmune diseases. Curr Drug Targets Inflamm Allergy 2:1-30, 2003. Luckner G, Dunser MW, Jochberger S, et al: Arginine vasopressin in 316 patients with advanced vasodilatory shock. Crit Care Med 33:2659-2666, 2005. Maestroni GJ, Mazzola P: Langerhans cells beta 2-adrenoceptors: Role in migration, cytokine production, Th priming and contact hypersensitivity. J Neuroimmunol 144:91-99, 2003. Marik PE, Varon J: The hemodynamic derangements in sepsis: Implications for treatment strategies. Chest 114:854-860, 1998. Meier-Hellmann A, Reinhart K, Bredle DL, et al: Epinephrine impairs splanchnic perfusion in septic shock. Crit Care Med 25:399-404, 1997. Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Task Force of the American College of Critical Care

Medicine, Society of Critical Care Medicine. Crit Care Med 27: 639-660, 1999. Rudis MI, Basha MA, Zarowitz BJ: Is it time to reposition vasopressors and inotropes in sepsis? Crit Care Med 24:525-537, 1996. Schutz W, Anhaupl T, Gauss A: Principles of catecholamine therapy. 1. Characterization of clinically relevant sympathomimetics. Anasthesiol Intensivmed Notfallmed Schmerzther 35:67-81, 2000. Trager K, DeBacker D, Radermacher P: Metabolic alterations in sepsis and vasoactive drug-related metabolic effects. Curr Opin Crit Care 9:271-278, 2003. van den Berghe G, Wouters P, Weekers F, et al: Intensive insulin therapy in the critically ill patient. N Engl J Med 345:1359-1367, 2001. Zhang H, De Jongh R, DeBacker D, et al: Effects of alpha- and beta-adrenergic stimulation on hepatosplanchnic perfusion and oxygen extraction in endotoxic shock. Crit Care Med 29:581-588, 2001.

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Krishna M. Natrajan and Ray P. Liao

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3

Inotropic Drugs Case Synopsis A 72-year-old man with mitral regurgitation has mitral valve replacement. His preoperative transesophageal echocardiogram (TEE) reveals reduced left ventricular function and moderate pulmonary hypertension. Just before separation from cardiopulmonary bypass (CPB), a 50 μg/kg bolus of milrinone is given, followed by an infusion at 0.5 μg/kg per minute, along with epinephrine at 0.03 μg/kg per minute. The TEE reveals good left ventricular function with adequate filling after release of the aortic cross-clamp, but the patient cannot be weaned from CPB owing to low mean arterial pressure. Pulmonary artery catheter data show a cardiac index of 2.8 L/min/m2 and systemic vascular resistance of 550 dyne . sec . cm–5. The addition of vasopressin (4 units/hour) enables weaning from CPB, after which the heart rate is 94 beats per minute and the mean arterial pressure is 72 mm Hg.

PROBLEM ANALYSIS Definition Inotropic drugs (Table 3-1) are classified as (1) naturally occurring catecholamines (e.g., dopamine, epinephrine, norepinephrine), (2) synthetic catecholamines (e.g., dobutamine, isoproterenol), or (3) phosphodiesterase-3 inhibitors (e.g., amrinone, milrinone). They are commonly administered solely or used in combination to treat low-output syndromes that are frequently encountered in congestive heart failure and myocardial infarction and following openheart surgery. The primary effect of inotropic drugs is to increase contractility, which ultimately increases cardiac output and promotes tissue perfusion.

Recognition The case synopsis illustrates the need to tailor appropriate therapy. Depressed left ventricular function with elevated pulmonary artery pressure suggests the need for inotropic

Table 3–1

■

Inotropic Drugs

Digitalis Digoxin Digitoxin Ouabain Catecholamines Natural Epinephrine Norepinephrine Dopamine Synthetic Dobutamine Dopexamine Isoproterenol Synthetic noncatecholamines Indirect acting Ephedrine

Mephentermine Amphetamines Metaraminol Direct acting Phenylephrine Methoxamine Phosphodiesterase-3 inhibitors Amrinone Milrinone Enoximone Miscellaneous Calcium Glucagon Thyroid hormone

support, but with a drug that does not increase pulmonary vascular resistance (PVR). Milrinone is one option because it increases cardiac output and lowers PVR. However, it also significantly lowers systemic vascular resistance (SVR), which can jeopardize perfusion of the heart and other vital organs. Reduced SVR with milrinone may require therapy with a vasopressor, such as norepinephrine, epinephrine, phenylephrine, or vasopressin. Notably, vasopressin increases SVR without increasing pulmonary artery pressure.

Risk Assessment The primary goal of inotropic drugs is to improve myocardial contractility and increase cardiac output, vital organ perfusion, and tissue oxygen delivery (Table 3-2). However, these drugs have other effects that can be useful or problematic, depending on the circumstances. Their effects on SVR are important and can be used to divide the drugs into two groups: vasoconstrictors (epinephrine, norepinephrine, dopamine) and vasodilators (dobutamine, isoproterenol, milrinone). Epinephrine and norepinephrine are naturally occurring catecholamines used in cardiac emergencies. The inotropic and vasoconstrictive responses are mediated by the activation of adrenergic receptors. The effects of these drugs can be titrated to the desired level owing to their linear dose response, rapid (almost immediate) onset of action, and fast elimination. Dopamine is another inotrope with vasoconstrictive properties. Its positive inotropic effect is mediated by the release of norepinephrine from nerve terminals. Dopamine’s pharmacodynamic effect is dose dependent, and the hemodynamic profile with low, medium, and high doses can vary greatly among individuals, with higher doses commonly producing an increase in SVR. Dopamine has the theoretical advantage of selective renal and mesenteric vascular dilatation, thus enhancing renal blood flow and natriuresis while preventing mesenteric ischemia in low cardiac output states. However, the clinical value of this effect remains uncertain. Isoproterenol and its chemical derivative dobutamine are vasodilators. They act directly on β-adrenergic receptors 11

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Hemodynamic Profile of Inotropic Drugs

Drug

CO

HR

MAP

VR

SVR

PVR

MCO

Epinephrine Norepinephrine Dopamine Dobutamine Isoproterenol Milrinone

↑↑↑ ↑↑ ↑↑ ↑↑ ↑↑ ↑↑

↑↑↑ ↑↑ ↑↑ ↑↑ ↑↑↑ ←→

↑ ↑↑ ↑ ↓ ↓↓ ↓↓

↑ ↑↑↑ ↑ ↓ ↓ ↓↓

↑↑↑ ↑↑↑ ↑↑ ↓ ↓↓↓ ↓↓↓

↑ ↑↑ ↑↑ ↓↓ ↓↓ ↓↓↓

↑↑↑ ↑↑↑ ↑↑ ↑↑ ↑↑↑ ←→

CO, cardiac output; HR, heart rate; MAP, mean arterial pressure; MCO, myocardial oxygen consumption; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance; VR, venous return (preload). ↑, increase; ↓, decrease; ←→, unchanged.

to cause a positive inotropic response while decreasing SVR. Hypotension resulting from their use may require treatment with vasoconstrictors. Milrinone is a phosphodiesterase-3 inhibitor and prevents cyclic adenosine monophosphate (cAMP) degradation. It increases myocardial contractility in a linear doseresponse relationship without increasing myocardial oxygen consumption. The onset of action is slower than that of catecholamines, and its elimination half-life is longer, causing a prolonged duration of effect. Rapid administration produces vascular smooth muscle relaxation to reduce SVR and venous return. This can lead to hypotension, especially in hypovolemic patients. Concomitant use of volume loading and vasoconstrictors (e.g., phenylephrine, epinephrine, norepinephrine, vasopressin) attenuates milrinone’s potential for vasodilatation and hypotension. These inotropes are routinely used to treat the low cardiac output states often seen after CPB. The unique hemodynamic profile of each agent needs to be considered when deciding which inotrope, alone or in combination, will best facilitate a particular patient’s separation from CPB.

Implications Low cardiac output and hypotension following separation from CPB can reduce tissue perfusion and lead to vital organ dysfunction. The use of hemodynamic parameters and TEE identifies its cause. Treatment must be prompt and may require the administration of combined inotropes. The use of inotropes with vasodilator properties may necessitate the addition of a vasoconstrictor. Of the available vasoconstricting agents, vasopressin has the advantage of not increasing PVR. Arrhythmias resulting from inotropes can occur and should be monitored closely.

CPB is often complicated by post-CPB low cardiac output states that require inotropic support. Combined epinephrine and milrinone, which have different actions, increase cardiac contractility better than either agent alone. Epinephrine increases the formation of cAMP by activating adrenergic receptors, while milrinone reduces the rate of cAMP degradation by inhibiting the phosphodiesterase-3 enzyme. The cardiovascular actions and other effects of each of these drugs must be taken into consideration. At low doses, epinephrine has predominant β-adrenergic actions: positive inotropy and chronotropy. Milrinone is also a positive inotrope, and a systemic and pulmonary arterial vasodilator as well. A reduction in PVR may benefit patients with pulmonary artery hypertension. However, reduced SVR and systemic hypotension may require substantial volume loading and use of a vasoconstrictor, such as vasopressin, which has minimal effects on the pulmonary and splanchnic vasculature. Also, a reduction in either PVR or SVR may lead to a reflex increase in heart rate, mediated by pulmonary mechanoreceptors or aortic barorecptors, respectively. Phosphodiesterase-3 inhibitors (e.g., amrinone) have been associated with thrombocytopenia, possibly due to a metabolite-mediated toxic effect on platelets. However, milrinone appears to have a better safety profile. Further, like all positive inotropic agents, milrinone and epinephrine have the potential to initiate or aggravate troublesome arrhythmias. Causative or provocative factors, such as a concurrent physiologic imbalance and (perhaps) even the inotrope itself, must be quickly identified and corrected before significant hemodynamic compromise occurs.

PREVENTION ● ●

MANAGEMENT ●

●

●

●

TEE to assess left ventricular filling and function and maintain adequate preload and afterload Careful titration of inotropes to achieve adequate cardiac output and arterial pressure Vasoconstrictors as needed for low perfusion pressure due to vasodilator effects of inotropes Prompt correction of acid-base and electrolyte abnormalities

●

Ensure adequate preload and afterload Normalize metabolic parameters Titrate inotropic drugs precisely

TEE to assess left ventricular filling and function, preload, and afterload is often useful when weaning patients from CPB. Volume depletion should be corrected by the judicious use of fluids or blood products. It is also important to correct metabolic abnormalities, especially acidosis and hypokalemia. Inotropic support is commonly necessary for separation from CPB. The choice of inotropic agent or agents depends on surgical and patient factors. Precise titration of

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Further Reading Lehtonen LA, Antila S, Pentikainen PJ: Pharmacokinetics and pharmacodynamics of intravenous inotropic agents. Clin Pharmacokinet 43: 187-203, 2004.

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13

Levy JH, Bailey JM, Deeb GM: Intravenous milrinone in cardiac surgery. Ann Thorac Surg 73:325-330, 2002. Stoelting RK: Sympathomimetics: Pharmacology and Physiology in Anesthetic Practice, 3rd ed. Philadelphia, JB Lippincott, 1999, pp 259-277. Tisdale JE, Patel R, Webb CR, et al: Electrophysiologic and proarrhythmic effects of intravenous inotropic agents. Prog Cardiovasc Dis 38: 167-180, 1995.

PHARMACOLOGY

inotropic drugs is needed, especially when several drugs are used in combination.

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Case Synopsis Five years after heart transplantation, a 44-year-old man has laparoscopic cholecystectomy. After induction of anesthesia, the electrocardiogram (ECG) rhythm strip shows absent P waves and a wide QRS rhythm at a rate of 38 beats per minute (Fig. 4-1). Neither intravenous (IV) atropine (1.0 mg) nor ephedrine (10 mg) affects the rhythm or increases its rate. IV bolus epinephrine (200 μg) is given, followed by an IV infusion at 0.25 μg/kg per minute. The heart rate increases to 130 beats per minute, accompanied by frequent ventricular ectopic beats.

PROBLEM ANALYSIS Definition Epinephrine and other positive chronotropes, especially when given in large doses, can have deleterious effects in patients with cardiovascular disease. These effects include the following: ● ● ●

Untoward tachycardia and hypertension Generation of new or worse atrial or ventricular arrhythmias Increased myocardial oxygen consumption and ischemia due to increased heart rate and contractility and left ventricular wall stress

As the case synopsis illustrates, the effects in cardiac transplant patients are even more unpredictable or may be nonexistent owing to cardiac denervation. Consequently, only drugs that act directly on cardiac receptors should be used. Drugs such as atropine and ephedrine may be ineffective or unpredictable because they act indirectly to increase heart rate. Moreover, coronary atherosclerosis can occur in transplant recipients, with an incidence of up to 50% at 5 years. Without cardiac afferent innervation, ischemia in heart transplant recipients may be silent.

Recognition Bradycardia with absent P waves on the ECG can have many causes, including the following: ●

● ● ●

Sinoatrial (SA) exit block, sinus arrest, or sick sinus syndrome Atrioventricular (AV) junctional rhythm Idioventricular rhythm Slow atrial fibrillation or flutter

Also, P waves may be “buried” within the QRS complex with AV dissociation, such as in advanced second degree or third degree (complete) AV heart block. With third degree SA exit block, P waves are absent or have an altered morphology if a subsidiary atrial pacemaker has usurped atrial control. If so, they will be bifid, inverted, or flattened in leads with SA node origin (upright) P waves. On the surface ECG, third degree SA exit block is indistinguishable from sinus arrest. A subsidiary atrial, junctional, or ventricular pacemaker usually usurps ventricular control. Third degree SA exit block is distinguished from third degree AV block, which has the following features on ECG: ● ●

●

P waves present but with no relation to QRS complexes QRS complexes wide (ventricular origin or with ventricular aberration) or of normal width (AV junctional origin above bifurcation of bundle of His [common]) Slow ventricular escape rate (≈30 to 45 beats per minute)

Intraoperative bradycardia that is severe or that compromises the patient’s cardiac output or blood pressure must be treated aggressively. Assessment for reversible causes is important (Fig. 4-2) and must occur simultaneously with treatment. Temporary pacing and drug therapy are the two main options. Two different classes of drugs are commonly used to increase the heart rate: anticholinergics (e.g., atropine, glycopyrrolate) and adrenergic receptor agonists (e.g., ephedrine, epinephrine, isoproterenol, dopamine). Direct adrenergic agonists are more reliable than ephedrine. Isoproterenol is a nonselective β agonist with chronotropic, inotropic, and vasodilatory effects. It is usually recommended to treat bradycardia after heart transplantation, but care must be exercised in the presence of coronary artery disease. Isoproterenol increases myocardial osygen consumption and may reduce coronary perfusion pressure, worsening ischemia. Thus, isoproterenol is no longer part of

Figure 4–1 ■ Bradycardia and absent P waves with ventricular escape rhythm. (From Conover MB: Understanding Electrocardiography, 8th ed. St. Louis, Mosby, 2003.)

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Chronotropic Drugs

15 PHARMACOLOGY

Figure 4–2 ■ Algorithm for the management of intraoperative bradycardia. AV, atrioventricular. (Modified from Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6: Advanced cardiovascular life support. Section 7: Algorithm approach to ACLS emergencies. 7C: A guide to the international ACLS algorithms. Circulation 102 [8 Suppl]: I142-I157, 2000.)

the advanced cardiovascular life support algorithms for the emergency treatment of bradycardia. The side effects of atropine are as follows: ● ● ● ●

Excessive tachycardia; arrhythmias Pupillary dilatation, blurred vision, dry mouth Difficulty in micturition; decreased intestinal peristalsis Central anticholinergic crisis (e.g., ataxia, restlessness, delirium, coma) (This cannot occur with glycopyrrolate because it does not cross the blood-brain barrier.)

Atropine is ineffective in heart transplant patients owing to the lack of vagal innervation. In fact, in some cases, it may provoke bradyarrhythmias. Ephedrine acts predominantly by a presynaptic mechanism (i.e., indirect release of catecholamines) and may be unpredictable or ineffective owing to cardiac sympathetic denervation in heart transplant recipients. However, it offers some protection against many reflex-mediated causes of bradycardia and produces a high resting heart rate. Bradyarrhythmias occurring late

after heart transplantation, without an obvious reversible cause, may be a sign of ischemia or chronic rejection.

Risk Assessment ●

●

●

Heart transplant patients have denervated hearts and are prone to accelerated coronary vasculopathy. Effects of chronotropic drugs are unpredictable or nonexistent owing to cardiac denervation in heart transient recipients. Epinephrine can exacerbate ischemia by causing tachycardia, hypertension, increased contractility, and arrhythmias in patients with intact hearts, whether diseased or not.

Epinephrine is given as an IV bolus or infusion in emergencies. Typical starting infusion rates are 0.03 to 0.2 μg/kg per minute, with titration to the desired effect. The goal should be to restore the heart rate to greater than 60 beats per minute while avoiding excess tachycardia.

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However, temporary pacing is often the preferred treatment for nontransient, severe bradycardia and can be rapidly instituted via the noninvasive transcutaneous or transesophageal (atrial pacing only; requires intact AV conduction) route. Pacing is more predictable (i.e., precision titration of rate, can be turned “on” or “off ” as needed) than treatment with positive chronotropic drugs, which have the following disadvantages: ● ●

● ●

May cause excess tachycardia or arrhythmias May cause myocardial ischemia or decompensation (i.e., heart failure) May take time or fail to produce the desired effect May produce adverse drug effects that are compounded by the drugs used to treat them

Implications Tachycardia associated with severe ventricular ectopy must be treated urgently, because it may degenerate into ventricular tachycardia-fibrillation. Also, the potential for myocardial ischemia exists if myocardial oxygen consumption exceeds demand.

MANAGEMENT ●

● ●

Cease the epinephrine infusion and allow its plasma concentration to decrease. Prepare for temporary pacing if the bradycardia recurs. Assess for reversible causes of intraoperative bradycardia (see Fig. 4-2).

Low-dose epinephrine infusions may restore the heart rate without adverse effects. If drug therapy is ineffective, is contraindicated, or causes complications, pacing should be instituted. Temporary transcutaneous pacing is a class I therapy for the emergency treatment of severe bradycardia. If available, transesophageal atrial pacing is useful (with intact AV conduction). Arrangements should be made for the insertion of a temporary pacing pulmonary artery catheter or transvenous pacing catheter.

PREVENTION ●

●

Suspect coronary artery disease in heart transplant recipients more than 2 years post transplant. Recognize the implications of cardiac denervation for treating bradycardia with drugs.

●

●

●

Anticipate and avoid common reversible causes of intraoperative bradycardia. Avoid high doses of chronotropic drugs by carefully titrating smaller doses to effect. Use temporary pacing for severe bradycardia or when drugs fail.

Careful preoperative evaluation is important to identify patients at increased risk for bradycardia. Pretreatment with a chronotrope and avoidance of known causes of bradycardia may prevent tachycardia or arrhythmias from occurring. In some cases, pacing therapy is required preoperatively, depending on the underlying rhythm (e.g., advanced second degree or complete AV heart block). There are special considerations for heart transplant recipients who develop intraoperative bradycardia.

Further Reading Atlee JL, Pattison CZ, Mathews EL, et al: Transesophageal atrial pacing for intraoperative sinus bradycardia or AV junctional rhythm: Feasibility as prophylaxis in 200 anesthetized adults and hemodynamic effects of treatment. J Cardiothorac Vasc Anesth 7:436-441, 1993. Bernheim A, Fatio R, Kiowski W, et al: Atropine often results in complete atrioventricular block or sinus arrest after cardiac transplantation: An unpredictable and dose-independent phenomenon. Transplantation 77:1181-1185, 2004. Brawn JH, Taylor P: Muscarinic receptor agonists and antagonists. In Hardman JG, Limbird LE (eds): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York, McGrawHill, 2001, pp 155-174. Conover MB: Understanding Electrocardiography, 7th ed. St. Louis, Mosby, 1996. Gao SZ, Schroeder JS, Alderman EL, et al: Prevalence of accelerated coronary artery disease in heart transplant survivors: Comparison of cyclosporine and azathioprine regimens. Circulation 80:100-105, 1989. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6: Advanced cardiovascular life support. Section 5: Pharmacology. I: Agents for arrhythmias. Circulation 102 (8 Suppl): I112-I128, 2000. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6: Advanced cardiovascular life support. Section 7: Algorithm approach to ACLS emergencies. 7C: A guide to the international ACLS algorithms. Circulation 102(8 Suppl):I142-I157, 2000. Hoffman BB: Catecholamines, sympathomimetic drugs, and adrenergic receptor antagonists. In Hardman JG, Limbird LE (eds): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York, McGraw-Hill, 2001, pp 215-268. Quinlan JJ, Firestone S, Firestone LL: Anesthesia for heart, lung, and heartlung transplantation. In Kaplan JA, Reich DL, Konstadt SN (eds): Cardiac Anesthesia, 4th ed. Philadelphia, WB Saunders, 1999. Weinfeld MS, Kartashov A, Piana R, et al: Bradycardia: A late complication following cardiac transplantation. Am J Cardiol 78:969-971, 1996.

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5

Drugs Affecting the Renin-Angiotensin System Laura Stover Case Synopsis A 95-kg, 70-year-old man is scheduled to have left internal carotid endarterectomy. He takes nicardipine (50 mg/day) and irbesartan (150 mg/day), an angiotensin II receptor antagonist, for hypertension. He took his usual doses of both medications on the morning of surgery. Preoperative tests included a transthoracic echocardiogram that showed normal left ventricular systolic function and septal hypertrophy. Blood pressure and heart rate immediately before induction of anesthesia were 150/70 mm Hg and 56 beats per minute, respectively. After receiving 900 mL of crystalloid, he was induced slowly with sufentanil (45 μg), propofol (140 mg), and vecuronium (7 mg), with subsequent endotracheal intubation and anesthetic maintenance with oxygen and nitrous oxide (50:50) and a propofol infusion. Three minutes after induction, his blood pressure fell to 92/44 mm Hg. Despite repeated intravenous boluses of ephedrine (20 mg total), his blood pressure was 47/30 mm Hg 5 minutes after induction.

PROBLEM ANALYSIS Definition Renin-angiotensin system (RAS) antagonists include both angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists. These drugs are used with increasing frequency to treat hypertension and heart failure in selected patients. ACE inhibitors and angiotensin II receptor antagonists cause a blockage of the RAS that can adversely affect hemodynamics during anesthesia and surgery. Although anesthesia is not invariably associated with hemodynamic instability in RAS-blocked patients, unexpected episodes of refractory hypotension have been reported. Also, RAS antagonists, specifically ACE inhibitors, have been associated with potentially life-threatening angioedema of the head and neck. The RAS plays an essential role in the regulation of vascular tone and extracellular fluid volume. As shown in Figure 5-1, sympathetic stimulation via β1-adrenergic receptors, renal artery hypotension, and decreased sodium delivery to the distal tubules stimulate the release of renin by the kidney. Renin is a proteolytic enzyme that cleaves to the circulating substrate angiotensinogen to form angiotensin I, which has little intrinsic pharmacologic activity. Angiotensin I is converted immediately to angiotensin II via a reaction catalyzed by ACE, which is present in vascular endothelium and lung tissue. In the short term (e.g., intraoperatively), angiotensin II contributes to vascular homeostasis by increasing vascular (especially arteriolar) tone. It acts directly on angiotensin II receptors and indirectly by enhancing sympathetic adrenergic function to increase vascular tone, which is necessary to maintain adequate perfusion pressure in patients with hypovolemia or reduced cardiac output. In the longer term (e.g., hours to days), angiotensin II contributes to vascular

homeostasis by its effect on extracellular fluid volume. It causes the adrenal cortex to release aldosterone, a hormone that acts on the kidneys to increase sodium and fluid retention. Angiotensin II also stimulates the release of vasopressin (i.e., antidiuretic hormone) from the posterior pituitary, which causes the kidneys to increase fluid retention. Blocking angiotensin II–mediated increased vascular tone and relative reductions in intravascular volume in patients receiving RAS antagonists chronically may cause refractory hypotension following the induction of anesthesia. Angioedema of the oropharynx or larynx has been recognized as an unusual complication of ACE inhibitor therapy. ACE-induced angioedema usually manifests spontaneously within hours to days of the initiation of treatment and has been described in association with anesthesia and Sympathetic stimulation Hypotension Decreased sodium delivery Angiotensinogen

Kidneys

Renin

Angiotensin I

Cardiac and vascular hypertrophy

ACE

Adrenal cortex

Angiotensin II

Pituitary

Aldosterone

ADH Thirst Systemic vasoconstriction

Renal sodium and fluid retention

Increased blood volume

Figure 5–1 ■ The renin-angiotensin system. ACE, angiotensin-converting enzyme; ADH, antidiuretic hormone.

17

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endotracheal intubation. Edema of the tongue is commonly the presenting symptom, with involvement of the face, lips, floor of the mouth, pharynx, glottis, or larynx frequently observed. The precise mechanism of angioedema formation is uncertain. Because it is likely mediated by the kallikreinbradykinin system, it is probably a biochemical rather than an immunologic phenomenon. Bradykinin is a potent vasodilator that increases vascular permeability and produces tissue edema. Kinase II (which is identical to ACE) is the major tissue enzyme responsible for the breakdown of bradykinin. ACE inhibitors inhibit kinase II to prevent bradykinin breakdown. Angioedema associated with ACE inhibitor therapy may therefore be a result of inhibition of bradykinin inactivation by kinase II.

Recognition HYPOTENSION Recognition of RAS antagonist therapy as a contributor to hypotension relies on the exclusion of other intraoperative events that may produce hypotension. A heightened index of suspicion in patients chronically treated with these drugs, especially those with a history of severe hypotension or left ventricular diastolic dysfunction, is justified. The temporal relationship between cardiovascular instability and induction of anesthesia in patients chronically treated with RAS antagonists, along with the failure of ephedrine in usual doses (10 to 20 mg IV in adult patients) to resolve the hypotension, makes RAS antagonism a likely cause of hypotension. ANGIOEDEMA Recognition of ACE inhibition as the cause of angioedema relies on the exclusion of other perioperative events associated with swelling of the head and neck (e.g., allergy, anaphylaxis), as well as the knowledge that angioedema can occur (though infrequently) with ACE inhibitors. When it does occur, angioedema is usually temporally related to the initiation of ACE inhibitor therapy.

Risk Assessment HYPOTENSION A number of patient factors modify the risk of severe hypotension with the induction of anesthesia in those treated with RAS antagonists. Patients treated with other antihypertensive agents in combination with a RAS antagonist are more likely to have refractory hypotension on induction. Likewise, the combination of RAS antagonists and other vasodilator drugs (e.g., amiodarone) increases the risk for hypotension. Patients with “complete” RAS blockade, which is associated with high doses and recent administration, are more likely to be unstable on induction. Patients with a history of severe hypertension, especially those with left ventricular diastolic dysfunction (which amplifies the dependence of blood pressure on intravascular volume in patients receiving ACE inhibitors), are also at increased risk for refractory hypotension. Short-term preoperative RAS inhibition (1 to 2 days) in normotensive or mildly hypertensive subjects

is less likely to result in refractory hypotension on induction. Patients who continue therapy until the day of surgery are also at increased risk. One review found that the incidence of hypotension on induction of anesthesia in patients with a history of severe hypertension was 75% to 100% when ACE inhibitors were continued until the day of surgery. ANGIOEDEMA Angioedema involving the oropharynx or larynx is an unusual complication of ACE inhibitor therapy, occurring on average in 0.1% of patients taking captopril, lisinopril, or enalapril; the incidence in patients taking enalapril may be slightly higher (0.2%) than in those taking the other two drugs. Patients are at highest risk within the first week of starting an ACE inhibitor; a retrospective study of 36,000 patients receiving enalapril showed that 60% to 70% of cases of angioedema occurred within this period. However, angioedema has occurred suddenly after months to years of therapy, and about 20% of known cases of angioedema occurring in this context may involve severe symptoms (e.g., dyspnea, stridor, laryngospasm). Unfortunately, there are no characteristics to predict which patients will progress to lifethreatening airway compromise.

Implications Concerning the risk for refractory hypotension on induction of anesthesia in patients taking RAS antagonists, there is no consensus on continuing or discontinuing the drug in the immediate preoperative period. For this class of drugs, the elimination half-life does not necessarily predict the duration of action, making recommendations with respect to perioperative dosing difficult.

MANAGEMENT Hypotension If RAS blockade contributes significantly to refractory hypotension after induction of anesthesia, therapy relies on the prompt restoration of adequate systemic vascular resistance and venous tone1 with phenylephrine or vasopressin, as well as increased intravenous fluid administration. Remedial actions for managing hypotension related to RAS antagonists include discontinuing or reducing the dose of other agents that might contribute to hypotension. Advanced cardiovascular life support protocols should be invoked in the event of cardiovascular collapse.

Angioedema Most occurrences of ACE inhibitor–induced angioedema are mild and resolve spontaneously or with discontinuation of the drug. However, swelling may progress rapidly to include the posterior pharynx or larynx, causing partial or complete 1 Venoconstriction (venous capacitance bed) indirectly increases venous return and preload.

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Chapter 5

Drugs Affecting the Renin-Angiotensin System

19

time to allow the return of RAS activity. However, any risk reduction might be at the expense of optimal therapy for hypertension or heart failure. Identifying patients at the greatest risk for severe hypotension (those with severe hypertension or those receiving high doses of RAS antagonists, RAS antagonists in combination with other antihypertensives, or RAS antagonists chronically), along with intravenous fluid loading before the induction of anesthesia, may reduce the risk for refractory hypotension. Such pretreatment combined with the early use of vasopressors for hypotension believed to be caused by RAS blockade will shorten the duration of hypotension. Consistent with the foregoing, frequent blood pressure measurement immediately after induction (direct arterial pressure monitoring may be necessary) contributes to the earlier detection of severe hypotension.

Further Reading PREVENTION As noted earlier, there is no consensus regarding the management of patients receiving RAS antagonist therapy in the immediate preoperative period. Discontinuation of RAS antagonists during this period reduces the risk for hypotension with anesthesia induction, provided there is sufficient

Colson P, Ryckwaert F, Coriat P: Renin angiotensin antagonists and anesthesia. Anesth Analg 89:1143-1155, 1999. Dean DE, Schultz DL, Powers RH: Asphyxia due to angiotensin converting enzyme (ACE) inhibitor mediated angioedema of the tongue during the treatment of hypertensive heart disease. J Forensic Sci 46: 1239-1243, 2001. Kharash ED: Angiotensin-converting enzyme inhibitor–induced angioedema associated with endotracheal intubation. Anesth Analg 74:602-604, 1992.

PHARMACOLOGY

upper airway obstruction. The symptoms may progress despite aggressive therapy and may recur hours after apparent resolution. Angioedema caused by ACE inhibitors can be fatal. Management ranges from simply stopping the ACE inhibitor to endotracheal intubation or tracheostomy. Mild cases confined to the anterior tongue or lips generally resolve with discontinuation of the drug and administration of intravenous diphenhydramine and corticosteroids. More severe cases involving the pharynx and associated with dysphagia may require subcutaneous epinephrine, tracheal intubation, or both. As with any evolving process involving the airway, the potential for life-threatening airway obstruction dictates close observation and prompt intervention. Following resolution of the acute process, a note should be made in the patient’s medical record of this potentially lifethreatening adverse reaction to ACE inhibitor therapy, and the patient should receive appropriate counseling.

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CARDIAC DRUGS

Phosphodiesterase Inhibitors

6

Gregory M. Janelle Case Synopsis A 56-year-old man presents for emergent repair of an open olecranon fracture sustained in a motorcycle accident. There are no other signs of trauma. His past medical history is significant for hypertension, dyslipidemia, gastroesophageal reflux disease, and a 40-pack-year history of tobacco use. His father died from a myocardial infarction at age 60. He has no allergies and denies alcohol or other illicit drug use. Medications prior to admission include atorvastatin, ramipril, and esomeprazole. Baseline vital signs include blood pressure, 148/74 mm Hg; heart rate, 86 beats per minute; and respiration, 18 breaths per minute and nonlabored. An electrocardiogram (ECG) in the emergency room shows normal sinus rhythm with no evidence of ischemic changes. The patient refuses regional anesthesia. Preoperative medications include midazolam 2 mg and sodium bicitrate 30 mL. After uneventful induction of general anesthesia (thiopental, fentanyl, and succinylcholine), anesthesia is continued with isoflurane. After surgical stimulation, the patient has hypertension (180/100 mm Hg) and tachycardia (115 beats per minute). Concomitantly, there is 2-mm downsloping ST depression in lead V5 of a calibrated, monitored ECG. The end-tidal isoflurane concentration is increased from 0.8% to 1.2%, and intravenous esmolol (20 mg) and sublingual nitroglycerin spray (0.4 mg × 2) are also given. Within minutes, the patient’s blood pressure drops to 60/40 mm Hg and his heart rate increases to 90 beats per minute. While treating this, the anesthesiologist has the circulating nurse call the patient’s wife to inquire about unreported drug use. He learns that the patient was taking sildenafil for erectile dysfunction along with his other medications.

PROBLEM ANALYSIS Definition Intraoperative myocardial ischemia is potentially life threatening, especially if it is not recognized and promptly treated. It demands utmost vigilance on the part of the anesthesiologist. Intraoperative ischemia is defined as ST deviation, relative to the preoperative, reference ECG, of 0.2 mV or greater in one lead or 0.1 mV or greater in two contiguous leads and lasting at least 10 minutes. Once ischemia is diagnosed, the anesthesiologist must identify and aggressively treat the cause. Based on this definition of intraoperative myocardial ischemia, the patient described in the case synopsis had at least demand ischemia and likely significant underlying coronary artery disease (CAD) as well. The case synopsis also illustrates that aggressive treatment of hypertension, tachycardia, and myocardial ischemia by increasing the end-tidal concentration of isoflurane, along with esmolol and sublingual nitroglycerin, can lead to profound hypotension in patients also taking phosphodiesterase-5 (PDE-5) inhibitors. This hypotension may further aggravate myocardial ischemia by reducing coronary perfusion pressure. In this case, the anesthesiologist was not expecting 20

the sudden, profound hypotension that resulted from his treatment, which was quite reasonable given the ECG evidence, the circulatory changes, and the patient’s past medical history. Unfortunately, the patient had failed to report his use of sildenafil. Only further (indirect) inquiry by an astute and knowledgeable anesthesiologist led to the discovery of the likely proximate cause of the patient’s hypotension. Sildenafil citrate is a highly selective PDE-5 inhibitor that interacts with organic nitrates such as nitroglycerin to potentiate vascular smooth muscle relaxation, with the potential to cause profound blood pressure reduction. For this reason, organic nitrates are contraindicated if sildenafil has been taken in the preceding 24 hours.

Recognition PDE-5 breaks down cyclic guanosine monophosphate (cGMP). Therefore, PDE-5 inhibitors such as sildenafil are expected to increase available cGMP. The formation of cGMP is stimulated by guanylate cyclase, which in turn is stimulated by nitric oxide (NO). Nitroglycerin is a potent NO donor, although its effects are more prominent in the venous capacitance bed, except in very high doses. Nonetheless, nitroglycerin does dilate epicardial coronary

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Chapter 6

Risk Assessment Although the intraoperative hypotension experienced by the patient described in the case synopsis was probably due to an adverse interaction between nitroglycerin and the PDE-5 inhibitor sildenafil, intraoperative hypotension has many other causes unrelated to this interaction (Table 6-1) that are discussed elsewhere in this book. In addition, for this patient, increasing the end-tidal isoflurane concentration and giving intravenous esmolol compounded his hypotension. Refractory hypotension is also associated with angiotensin-converting enzyme (ACE) inhibitors and selective antagonists of angiotensin II receptors, such as olmesartan (see Chapter 5). Patients with preoperative sympathetic blockade or volume depletion due to fasting, blood loss, or diuretic therapy have a reduced venous capacitance. This reduces venous return and cardiac output and often compounds hypotension with the induction of anesthesia. For patients on ACE inhibitors, angiotensin II (a potent vasoconstrictor) does not counter such hypotension.

Table 6–1

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Causes of Intraoperative Hypotension Unrelated to Phosphodiesterase-5 and Nitroglycerin Interactions

Anesthetics (IV and volatile agents) Central neuraxial anesthesia (spinal, epidural) Myocardial ischemia and reperfusion injury Heart failure (systolic or diastolic) Cardiac rhythm disturbances Chronic adrenocortical insufficiency Overly aggressive use of diuretics Recent hemo- or peritoneal dialysis Volume depletion related to third-space loss Inadequate fluid resuscitation Severe hemorrhage; hemorrhagic shock Hemothorax; hemopericardium Reduced venous return secondary to caval compression Restrictive pericarditis; pericardial effusion Tumors compressing or restricting heart Tumors compressing or restricting great vessels Severe bronchospasm; pneumothorax Increased intrathoracic pressure Excessive tidal volumes or airway pressures Sepsis and septic shock Anaphylactic and anaphylactoid reactions Carcinoid syndrome Monitoring artifacts Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers

Phosphodiesterase Inhibitors

21

However, the timing of this patient’s hypotension makes it less likely that ramipril (an ACE inhibitor) was the primary agent that precipitated the profound decrease in blood pressure. The patient also had multiple risk factors for CAD: ● ● ● ● ●

Hypertension Age older than 50 years Dyslipidemia Tobacco abuse Strongly positive family history

Further, erectile dysfunction disproportionately affects patients with cardiovascular disease. Thus, one must consider that these patients may be receiving sildenafil or similar potent PDE inhibitors. As the case synopsis illustrates, patients may fail to report the use of these drugs. Finally, this patient had objective evidence of CAD: ECG changes consistent with ischemia associated with tachycardia and hypertension with surgical stimulation.

Implications The clinical effects of sildenafil and other PDE-5 inhibitors (e.g., tidalafil, vardenafil) are mediated by a local increase in available cGMP. This, in turn, leads directly to smooth muscle relaxation in the arteries, arterioles, and sinusoids of the corpus cavernosum. The net result with sildenafil alone is vasodilatation and enhanced erectile function. The reduction in systolic and diastolic blood pressure is modest (≈8 and 5.5 mm Hg, respectively). When given to healthy volunteers, sildenafil had no apparent orthostatic effects. Sildenafil has also been investigated as a potential treatment for pulmonary hypertension. In patients with severe congestive heart failure, sildenafil reduces mean pulmonary artery pressure and arteriolar resistance by 20% and 45%, respectively. However, the drug has no significant effect on the cardiac index, ejection fraction, or pulmonary capillary wedge pressure. The safety of sildenafil in patients with documented CAD has been the subject of numerous reports. In one recent controlled trial, patients with CAD receiving sildenafil reported improved erections and sexual performance but experienced more side effects (e.g., transient headache, hypertension, flushing, dyspepsia) compared with placebo. However, there were no serious drug-related cardiovascular effects. An American College of Cardiology–American Heart Association consensus statement asserts that the available evidence supports the general safety of sildenafil in patients with CAD. Patients should not receive PDE-5 inhibitors and nitrates concomitantly. In fact, the current sildenafil product label states that the use of nitrates with sildenafil is strictly contraindicated. The simultaneous administration of nitric oxide donors (e.g., nitroglycerin) results in a marked accumulation of cGMP. This occurs because nitrates increase the production of cGMP, whereas sildenafil prevents its breakdown. The net result is a pronounced reduction in blood pressure with symptomatic hypotension. Other drugs that attenuate or block compensatory hemodynamic responses, including β- or α-adrenergic blockers, ACE inhibitors, and angiotensin II receptor antagonists, can also dramatically

PHARMACOLOGY

arteries; also important to the anti-ischemic action of nitroglycerin are reduced venous return and decreased cardiac preload, which lessen myocardial wall stress and reduce oxygen consumption. Sildenafil is prescribed for erectile dysfunction because sexual stimulation normally results in the release of NO from nerves and endothelial cells in the corpus cavernosum and systemic blood vessels, and NO stimulates guanylate cyclase to promote the formation of cGMP. Both aging and peripheral vascular disease interfere with this process; hence, the rationale for prescribing sildenafil or other PGE-5 inhibitors.

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Pharmacology

exaggerate the adverse drug interaction between organic nitrates and PDE-5 inhibitors, especially when there is preexisting cardiovascular compromise. Twenty-one PDE genes have been cloned and belong to 11 PDE families based on their homology sequence and biochemical and pharmacologic properties. Table 6-2 depicts both experimental and clinical PDE inhibitors and their relative selectivity as inhibitors of PDE-1 through -11. Among these families, the PDE-3 inhibitors (e.g., enoximone, amrinone, milrinone, imazodan) are the most extensively studied group. By blocking the breakdown of cyclic adenosine monophosphate (cAMP), PDE-3 inhibitors reduce systemic and pulmonary arterial pressures. They also increase cardiac cAMP and Ca2+-induced Ca2+ release to increase myocardial contractility and the cardiac index, but without increasing myocardial oxygen consumption. Thus, PDE-3 inhibitors are considered positive inotropes and vasodilator agents. They have been used successfully in patients with advanced heart failure (both acutely and chronically) and as a bridge to cardiac transplantation. Thrombocytopenia limits the long-term use of amrinone, and the chronic use of milrinone has been associated with increased mortality in patients with New York Heart Association class III and IV heart failure. This mortality increase may be due to QTc prolongation with intravenous milrinone. The addition of a β-adrenergic blocking agent to low-dose milrinone therapy has been shown to reduce QTc prolongation and is associated with an improvement in patients’ functional status; however, sudden death was a relatively uncommon occurrence. Also, milrinone has been used to treat cerebral vasospasm associated with subarachnoid hemorrhage.

Table 6–2

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Experimental and Clinical Inhibitors of Phosphodiesterase and Their Relative Selectivity

Phosphodiesterase Inhibitor

Phosphodiesterase Selectivity (IC50)

IBMAX Papaverine EHNA Rolipram Dipyridamole

Nonselective (2-50 μM) Nonselective (5-25 μM) PDE-2 (1.0 μM) PDE-4 (2.0 μM) PDE-5 (0.9 μM) PDE-6 (0.38 μM) PDE-7 (9.0 μM) PDE-8 (4.5 μM) PDE-10 (1.1 μM) PDE-1 and -5 (0.1 μM) PDE-7 (35 μM) PDE-9 (1.15 μM) PDE-10 (1.0 μM) PDE-3 (1.0 μM) PDE-5 (3.9 nM) PDE-5 (0.76 μM) PDE-6 (0.15 μM) Nonselective (45-150 nM)

SCH51866

Enoximone Sildenafil Zaprinast Pentoxifylline

EHNA, erythro-9-[3-(2-hydroxynonyl)]adenine; IBMAX, 3-isobutyl-1-methylxanthine; IC50, concentration of PDE inhibitor with 50% activity against PDE; PDE, phosphodiesterase; SCH, succinylcholine. Adapted from Hetman JM, Robas N, Baxendale R, et al: Cloning and characterization of two splice variants of human phosphodiesterase 11A. Proc Natl Acad Sci U S A 97:12891-12895, 2000.

Inhibition of PDE-3 and PDE-4 may have therapeutic utility in reactive airway disease and for ameliorating pulmonary hypertension. PDE-4 inhibitors, such as compound A, cilomilast, and rolipram, also have anti-inflammatory and uterorelaxant effects. Finally, several commonly used drugs (e.g., papaverine, dipyridamole, pentoxifylline) appear to have significant nonselective PDE-inhibiting properties. Clinical effects of inhibition of the various PDE subtypes require further elucidation.

MANAGEMENT The management of perioperative myocardial ischemia and infarction is discussed in Chapter 76. Treatment for perioperative hypotension includes correction of the underlying pathophysiology and the administration of vasopressors if needed. For the patient described in the case synopsis, knowledge of all his preoperative medications would have permitted the recognition of potential drug-drug interactions (i.e., sildenafil-nitroglycerin) and prevented his profound hypotension. Therapy to counter nitroglycerin’s potentiation of sildenafil’s vasodilatory effect includes restoring intravascular volume by fluid resuscitation and increasing blood pressure with a vasoconstrictor such as phenylephrine, vasopressin, norepinephrine, epinephrine, or ephedrine. All are systemic arterial and venous vasoconstrictors, but phenylephrine and vasopressin have no β-adrenergic effects and would be the most judicious primary therapy in light of the patient’s predisposition for developing demand myocardial ischemia. Further, and importantly, by constricting the venous capacitance bed, α1 agonists such as phenylephrine and vasopressin increase venous return to augment preload and cardiac output. Refractory hypotension may necessitate the use of an intraaortic balloon counterpulsation device (see Chapter 98). Finally, administration of subsequent nitroglycerin doses is absolutely contraindicated.

PREVENTION Awareness is the key factor in preventing potentially lifethreatening drug-drug interactions. Unfortunately, erectile dysfunction still represents a social stigma in many cultures, which may prevent patients from reporting the problem and its treatment to their physicians and sexual partners. Sildenafil use increased by approximately 84% between 1998 and 2002. It was estimated that more than 14 million patients in the United States were taking sildenafil by 2001. With the advent of novel formulations of PDE-5 inhibitors and the reported growth in use among females and males between 18 and 45 years of age, it is likely that this number will well exceed 20 million patients by 2006. Although sildenafil is safe when taken by healthy patients, it should be administered with extreme caution in patients with cardiovascular disease. It is absolutely contraindicated in patients taking organic nitrates and those with hemodynamically significant aortic stenosis or hypertrophic obstructive cardiomyopathy. The cytochrome P-450 2C9 and 3A4

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Chapter 6

Further Reading Cheitlin MD, Hutter AM Jr, Brindis RG, et al: Use of sildenafil (Viagra) in patients with cardiovascular disease: ACC/AHA expert consensus document. Circulation 99:168-177, 1999. Hermann HC, Chang G, Klugherz BD, et al: Hemodynamic effects of sildenafil in men with severe coronary artery disease. N Engl J Med 342:1622-1626, 2000.

Phosphodiesterase Inhibitors

23

Hetman JM, Robas N, Baxendale R, et al: Cloning and characterization of two splice variants of human phosphodiesterase 11A. Proc Natl Acad Sci U S A 97:12891-12895, 2000. Jaski BE, Fifer MA, Wright RF, et al: Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure: Dose-response relationships and comparison to nitroprusside. J Clin Invest 75:643-649, 1985. Kulkarni SK, Patil CS: Phosphodiesterase 5 enzyme and its inhibitors: Update on pharmacological and therapeutical aspects. Methods Find Exp Clin Pharmacol 26:789-799, 2004. Landesberg G, Mosseri M, Wolf Y, et al: Perioperative myocardial ischemia and infarction: Identification by continuous 12-lead electrocardiogram with online ST-segment monitoring. Anesthesiology 96:264-270, 2002. Viagra (sildenafil citrate): US prescribing information. In Physicians’ Desk Reference, 57th ed. Montvale, NJ, Medical Economics, 2003, pp 2653-2656. Zusman RM, Morales A, Glasser DB, et al: Overall cardiovascular profile of sildenafil citrate. Am J Cardiol 83(Suppl):35C-44C, 1999.

PHARMACOLOGY

pathways are the primary pathways for the metabolism of sildenafil. Thus, potent inhibitors of the these cytochromes (e.g., cimetidine, erythromycin, digoxin, some statins) may increase sildenafil’s plasma concentration. In such patients, and in those with severely compromised renal or hepatic function, reduced starting doses of sildenafil have been advocated to reduce the incidence of significant untoward effects.

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7

Digitalis Emilio B. Lobato Case Synopsis A 70-year-old man is scheduled for a subtotal colectomy under general anesthesia. He has a history of anterior myocardial infarction and intermittent atrial fibrillation and is receiving digoxin. His preoperative serum digoxin and potassium concentrations are 1.5 ng/dL and 3.9 mEq/L, respectively. Preparation for surgery includes colonic enemas (given until clear). His digoxin is withheld. Soon after the patient is placed on mechanical ventilation, he develops atrioventricular junctional tachycardia (AVJT) at 95 to 100 beats per minute (Fig. 7-1). Pulse oximetry reveals an arterial blood oxygen saturation of 100%. The end-tidal carbon dioxide partial pressure is 22 mm Hg, and the serum potassium concentration is 3.0 mEq/L. Digitalis toxicity is the suspected cause of the AVJT. Intravenous potassium chloride is given, and ventilation is reduced. Eventually, AVJT gives way to sinus rhythm, and the surgical procedure continues uneventfully.

PROBLEM ANALYSIS

●

●

Definition The use of digitalis to treat congestive heart failure (CHF) has been eclipsed by the current widespread use of angiotensinconverting enzyme (ACE) inhibitors and β-blockers to treat this condition. Prospective, randomized clinical trials have shown conclusively that both ACE inhibitors and β-blockers reduce mortality, whereas digoxin does not. However, one meta-analysis of available clinical trials (2001) showed that digoxin had beneficial effects, even in patients treated with ACE inhibitors; these findings may extend to β-blockers, but specific data were lacking. The results of this meta-analysis strengthen the concept that digoxin still has beneficial clinical effects in symptomatic patients with CHF, including the ability to reduce hospitalizations. Further, most patients in these reviewed trials were also receiving diuretics. Thus, clinicians still offer digoxin to symptomatic patients or those at appreciable risk for hospitalization for CHF, with a reasonable expectation of some benefit. Digitalis increases myocardial contractility in patients with heart failure and reduces the ventricular rate in those with atrial fibrillation. Cardiac complications can result from therapeutic or toxic effects of digitalis, primarily due to inhibition of membrane Na+,K+-ATPase. Extracardiac complications usually involve the central nervous system and gastrointestinal tract. Monitoring serum concentrations of digoxin (normally, 0.9 to 2.0 ng/dL) may help prevent toxic effects; however, there is considerable overlap between digoxin’s toxic and therapeutic effects, especially with hypokalemia or increased sensitivity to its effects (e.g., patients with severe cardiac disease or hypothyroidism). To avoid sampling errors due to slow digoxin equilibration, blood must be drawn at least 4 hours after intravenous dosing or 12 hours after oral dosing. Elevated serum digoxin concentrations may be due to the following: ● ●

Overdose or increased bioavailability (e.g., digitalis gel caps) Reduced volume of distribution (especially in elderly patients)

24

Reduced excretion (e.g., renal failure, patients receiving quinidine) Displacement from binding sites (e.g., with calcium channel blockers)

Recognition Digitalis toxicity may be immediately apparent or difficult to recognize, especially if cardiac manifestations are due to underlying heart disease. The presenting signs and symptoms depend on whether the digitalis toxicity is acute or chronic. If acute, gastrointestinal symptoms may be prominent. If chronic, patients may present with nonspecific symptoms (e.g., weakness and malaise). However, the sole evidence of chronic toxicity may be new arrhythmias. CARDIAC MANIFESTATIONS Cardiac manifestations of digitalis toxicity (primarily arrhythmias) include the following: ● ● ● ● ● ● ●

Sinus bradycardia Ventricular premature beats Nonparoxysmal AVJT Wenckebach atrioventricular (AV) block Atrial tachycardia with varying AV block Bidirectional ventricular tachycardia Ventricular fibrillation

When interpreting electrocardiogram (ECG) findings in patients receiving digitalis, one must distinguish between

Figure 7–1 ■ Nonparoxysmal atrioventricular junctional tachycardia at 100 beats per minute. Negative P waves after each QRS complex indicate retrograde atrial capture.

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Chapter 7

●

● ●

●

T-wave changes (often the earliest sign), ranging from flattening to inversion or peaking of the terminal portion of the T wave Shortening of the Q-T interval ST-T segment flattening or depression, resulting in the classic concave (“scooped”) appearance (often more pronounced in ECG leads with tall R waves) Increased U-wave amplitude

Also, a slowed but irregular ventricular rate in atrial fibrillation implies a therapeutic digitalis effect. Regularization of the ventricular rate suggests toxicity and is usually due to the development of AV junctional rhythm (rate ≤70 beats per minute) or AVJT (rate >70 beats per minute). Cardiac complications can also result from the therapeutic effects of digitalis and include the following: ●

●

●

Increased risk for ventricular tachycardia and ventricular fibrillation in patients with Wolff-Parkinson-White syndrome and atrial fibrillation. Digitalis shortens refractoriness and speeds conduction in accessory AV conducting pathways. This may lead to preferential accessory pathway conduction and a greatly increased ventricular rate with atrial fibrillation (see Chapter 80). The latter can exceed 300 beats per minute and is limited solely by accessory pathway refractoriness. If this rate is sustained, there is a strong potential for early degeneration into ventricular tachycardia or ventricular fibrillation. Increased ventricular outflow tract obstruction in patients with asymmetrical ventricular septal hypertrophy, due to the positive inotropic effects of digitalis. Aggravation of myocardial ischemia in patients with coronary artery disease; this is “demand” ischemia due to digitalis-increased myocardial oxygen consumption.

Digitalis is ill-advised in any of these circumstances. The associated risks outweigh any potential benefits. ECG signs of toxicity occur in 5% to 20% of patients receiving digitalis. Almost any arrhythmia can result from the direct toxic or neurally mediated electrophysiologic effects of digitalis on cardiac muscle or the specialized conducting tissues (Table 7-1). The most common arrhythmia

Table 7–1

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Digitalis

in patients with sinus rhythm is the appearance of ventricular extrasystoles. With atrial fibrillation, regularization of the ventricular rate occurs due to the development of AV junctional rhythm or AVJT; this may be the first manifestation of digitalis toxicity. In fact, the development of accelerated AV junctional rhythm or idioventricular rhythm in patients with AV heart block is highly suggestive of digitalis toxicity. Two other arrhythmias are characteristically identified with digitalis toxicity: 1. Paroxysmal atrial tachycardia with AV heart block. This is due to increased atrial conduction time and reduced refractoriness, along with AV node conduction block. 2. Bidirectional ventricular tachycardia. In this case, QRS complexes alternate between two distinctly different morphologies. In some leads, distinct R and S waves alternate between each other. Table 7-2 lists arrhythmias associated with digitalis toxicity in decreasing order of frequency. Worsening of preexisting CHF is often the first symptom of digitalis-induced arrhythmias and should alert the clinician to possible toxicity. EXTRACARDIAC MANIFESTATIONS Extracardiac manifestations of digitalis toxicity include the following: ●

●

●

Gastrointestinal symptoms, including nausea, vomiting, diarrhea, and increased salivation, from stimulation of central vagal nuclei Central nervous system manifestations (more common in the elderly), including blurred vision, abnormal color perception (e.g., green halos), hallucinations, and frank delirium Acute life-threatening hyperkalemia, occurring with severe digitalis overdose and caused by paralysis of the Na+-K+ pump and outward intracellular K+ leak

Risk Assessment Knowledge of factors that may alter digitalis pharmacokinetics or myocardial sensitivity and thus predispose patients to digitalis toxicity is of paramount importance (Table 7-3). Elderly patients are at greater risk than younger ones, and

Electrophysiologic Effects of Therapeutic and Toxic Digitalis

Tissue

Therapeutic Effects

Clinical Manifestations

Toxic Effects

Clinical Manifestations

Sinus node

Slows sinus rate

Sinus bradycardia

Sinus pause; SA conduction block

Atrium

None

None

AV node/AVJ

↓ Conduction time

Purkinje fibers

↓ Refractoriness; ↑ repolarization ↓ Refractoriness

↓ Ventricular rate; ↑ P-R interval None; ST-T segment depression ↓ Q-T interval

Sinus pause or arrest; SA conduction block ↑ Conduction; ↓ refractoriness AV heart block; ↑ AVJ automaticity ↑ Automaticity; DADtriggered activity ↑ Automaticity; DADtriggered activity

Ventricle

25

↑ Atrial rate (atrial flutter/fibrillation) Mobitz type I-II second or third degree heart block; AVJR or AVJT VPB; VT VPB; VT

AV, atrioventricular; AVJ, atrioventricular junction; AVJR, atrioventricular junctional rhythm; AVJT, atrioventricular junctional tachycardia; DAD, delayed after depolarization; SA, sinoatrial; VPB, ventricular premature beats; VT, ventricular tachycardia.

PHARMACOLOGY

normal and toxic effects. Normal ECG changes with therapeutic levels of digitalis include the following:

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Table 7–2

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Digitalis-Caused Arrhythmias in Decreasing Order of Frequency

Premature ventricular beats Accelerated AV junctional rhythm or tachycardia Wenckebach (Mobitz type I) AV block Sinus bradycardia or arrest Atrial tachycardia with variable AV block* Bidirectional ventricular tachycardia* Atrial flutter Ventricular fibrillation *Almost always due to the toxic effects of digitalis. AV, atrioventricular.

reduced body mass lowers the volume of distribution for digitalis. Other drugs administered concomitantly may interact with digoxin and affect serum concentrations. Also, a progressive decline in renal function and reduced serum albumin may elevate serum digoxin concentrations, as does reduced creatinine clearance if no adjustment in dosage is made. Importantly, dialysis is not effective for clearing digoxin. In hypothyroidism, the activity of membrane Na+,K+ATPase is reduced, which means that lower digoxin doses are needed to achieve a therapeutic effect, and toxicity can occur with usual doses. Hypoxemia enhances digitalis’s acceleration of lower pacemaker activity and may trigger arrhythmias from delayed afterpotentials. In patients receiving digitalis, ectopic beats or tachycardia can be exacerbated by the concomitant use of β-adrenergic agonists and diuretics. Hypokalemia potentiates the effects of digitalis owing to impaired Na+-K+ pump function. Low serum K+ concentrations increase the binding of digitalis to myocardium. Hypomagnesemia reduces the activity of membrane Na+,K+ATPase and may increase kaliuresis and cause hypokalemia. Hypercalcemia increases digitalis activity by increasing intracellular Ca2+. In addition, many drugs and other factors interact with digoxin to alter its pharmacokinetics, displace it from tissue binding sites, or reduce its clearance to increase serum drug concentrations (see Table 7-3).

Table 7–3

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Factors that Predispose to Digitalis Toxicity

Older age Electrolyte imbalance (hypokalemia, hypomagnesemia, hypercalcemia) Renal insufficiency Severity of heart disease Hypoxemia Hypothyroidism Drug interactions Angiotensin-converting enzyme inhibitors Benzodiazepines Quinidine or quinine Calcium channel blockers Erythromycin Cyclosporine Amiodarone

Implications Digitalis toxicity constitutes a serious condition that merits hospitalization. Hemodynamic deterioration with associated arrhythmias in patients with significantly impaired cardiac function may cause acute hemodynamic decompensation. In addition to hemodynamic compromise, some arrhythmias themselves are life threatening. Therefore, early recognition of the toxic effects of digitalis is imperative. Some extracardiac manifestations may be debilitating and may, in fact, precipitate arrhythmias. In surgical candidates, all but the most urgent procedures should be postponed until the digitalis toxicity has been resolved.

MANAGEMENT The treatment of digitalis toxicity depends on the severity of the clinical manifestations (Table 7-4). However, all patients suspected of digitalis intoxication should have an assessment of serum electrolytes, potassium, magnesium, and calcium, as well as a determination of serum digoxin concentration. For patients with mild symptoms, temporary discontinuation of the drug, cardiac monitoring, and supportive measures are sufficient. For patients with severe or lifethreatening arrhythmias (complete heart block, ventricular tachyarrhythmias), in addition to discontinuing digitalis, the administration of potassium chloride (in the absence of hyperkalemia) and magnesium sulfate should be considered. For heart block, 1 mg of atropine is usually effective in counteracting the vagal effects of digoxin. For ventricular arrhythmias, in addition to monitoring serum levels, lidocaine is the drug of choice, with a loading dose of 1 to 2 mg/kg, followed by an infusion of 1 to 2 mg/minute. Phenytoin was used in the past but, owing to its myocardial depressant properties and its tendency to produce hypotension when given intravenously, has largely been replaced by digoxin-specific antibodies (Digibind). There is no evidence to support the use of amiodarone to treat ventricular tachycardia or to prevent recurrences of ventricular fibrillation in patients with digitalis toxicity. At least in theory, the complementary electrophysiologic actions of amiodarone and digitalis to promote sinus bradycardia and increase sinoatrial and AV node conduction times and refractoriness might promote or precipitate asystole. More important is that amiodarone is known to

Table 7–4

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Management of Digitalis Toxicity

Withhold further digitalis Assess electrolytes (K+, Ca2+, Mg2+) Administer potassium chloride in the absence of hyperkalemia Administer magnesium sulfate Treat bradyarrhythmias Atropine Temporary or (possibly) permanent artificial pacing Treat ventricular arrhythmias Lidocaine Phenytoin (diphenylhydantoin) Digoxin-specific antibodies (Digibind)

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PREVENTION Knowledge of the multiple factors that affect digoxin pharmacokinetics and pharmacodynamics is important to avoid

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its toxic effects. Regular determination of serum digoxin concentrations and dose adjustments in patients with conditions that increase the risk of digitalis toxicity are important measures, especially in the elderly.

Further Reading Antman EM, Wenger TL, Butler VP Jr, et al: Treatment of 150 cases of life-threatening digitalis intoxication with specific Fab antibody fragments: Final report of a multicenter study. Circulation 81:1744-1750, 1990. Fenster PE, White NW Jr, Hanson CD: Pharmacokinetic evaluation of the digoxin-amiodarone interaction. J Am Coll Cardiol 5:108-112, 1985. Hauptman PJ, Kelly RA: Digitalis. Circulation 99:1265-1270, 1999. Hood WB Jr, Dans AL, Guyatt GH, et al: Digitalis for treatment of congestive heart failure in patients in sinus rhythm. Update of Cochrane Database Syst Rev 3:CD002901, 2001; PMID: 11687032. Kelly RA, Smith TW: Recognition and management of digitalis toxicity. Am J Cardiol 69:108G-119G, 1992. Ma G, Brady WJ, Pollack M, et al: Electrocardiographic manifestations: Digitalis toxicity. J Emerg Med 20:145-152, 2000. Ooi H, Colucci WS: Pharmacological treatment of heart failure. In Hardman JG, Limbird LE (eds): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York, McGrawHill, 2001, pp 901-932. Spratt KA, Doherty JE: Principles and practice of digitalis. In Messerli FH (ed): Cardiovascular Drug Therapy, 2nd ed. Philadelphia, WB Saunders, 1996, pp 1136-1146.

PHARMACOLOGY

increase serum digoxin levels. Systemic clearance of digoxin is significantly prolonged owing to reduced renal and nonrenal clearance, which lengthens its half-life of elimination by approximately 20%. However, amiodarone does not appear to affect the volume of distribution for digoxin. Electrical countershock (direct-current cardioversion) is contraindicated because it can exacerbate the severity of arrhythmias. Administration of digoxin-specific antibodies (Digibind) is the treatment of choice for life-threatening arrhythmias and for digoxin-induced refractory hyperkalemia. The use of an antibody rapidly reduces the percentage of unbound digoxin in the serum from 75% to less than 5%. The antibody-digoxin complex then undergoes renal excretion. Side effects are infrequent but include allergic reactions and rebound toxic digoxin effects in patients treated with inadequate doses of Digibind. Importantly, conventional serum assays for digoxin cannot distinguish between free and bound digoxin; thus, serum digoxin concentrations appear markedly elevated following Digibind treatment. The results of treatment are monitored by manifestations of clinical improvement; however, free digoxin determinations can be obtained in patients who show a poor response to treatment.

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Anticholinergics Kevin J. Sullivan Case Synopsis A 1-year-old child weighing 10 kg is in the pediatric intensive care unit with respiratory failure and a difficult airway. Prior attempts at laryngoscopy and endotracheal intubation have been unsuccessful, and mask ventilation is difficult. The infant, who becomes hypoxic and bradycardic during resuscitation efforts, is unintentionally given 4 mg of intravenous atropine, instead of the 0.2 mg that was ordered. Endotracheal intubation is performed to reverse the respiratory failure and hypoxia. Shortly thereafter, the patient is noted to be tachycardic (225 beats per minute), with warm, red, dry skin and fever (39°C). He appears disoriented, agitated, and inconsolable.

PROBLEM ANALYSIS Definition Because infants and young children have a relatively enhanced vagal tone compared with adults, vagotonic physiologic perturbations, such as airway instrumentation, can result in bradycardia. Thus, in pediatric anesthesia and critical care settings, bradycardia can be seen during laryngoscopy and induction of anesthesia with volatile inhalational agents (most commonly halothane), as well as with hypoxemia and elevated intracranial pressure. Bradycardia and the consequent reduced cardiac output can be prevented by premedication with oral, intravenous, or intramuscular anticholinergic drugs. In the case synopsis, an inadvertently high dose of atropine (about 20-fold too high) was given to increase the patient’s heart rate during bradycardia. Anticholinergic (antimuscarinic) toxicity is commonly seen in infants and young children after the accidental ingestion of belladonna alkaloids and their synthetic congeners, antiparkinson medications, histamine receptor antagonists, tricyclic antidepressants, and phenothiazines. For persons of all ages, the ingestion of plants that contain large quantities of belladonna alkaloids can cause anticholinergic toxicity. Such plants include deadly nightshade (Atropa belladonna), jimsonweed (Datura stramonium), and angel’s trumpet (Brugmansia candida). Anticholinergics used in anesthesia include atropine, glycopyrrolate, and scopolamine. They compete with neurally released acetylcholine to attach to muscarinic cholinergic receptors and block the effects of acetylcholine, and they antagonize muscarinic agonist actions at noninnervated muscarinic cholinergic receptors. Further, presynaptic muscarinic receptors on adrenergic nerve terminals inhibit norepinephrine release. Thus, muscarinic antagonists (anticholinergics) can enhance sympathetic activity. Except for the fact that quaternary ammonium compounds (glycopyrrolate) do not readily cross the blood-brain barrier to exert central nervous system (CNS) actions, there is little difference in the qualitative actions of atropine, glycopyrrolate, and scopolamine. However, some quantitative differences in effect may be seen. For example, both atropine and scopolamine have a shorter duration of action than glycopyrrolate. Further, the 28

antisialagogue effects of glycopyrrolate and scopolamine are greater than those of atropine. In addition, heart rate is most increased by atropine, then by glycopyrrolate, and least by scopolamine. Finally, although both atropine and scopolamine are tertiary amines that readily cross the blood-brain barrier, they differ in CNS effects: atropine causes CNS stimulation, whereas scopolamine produces sedation and amnesia. Human tissues vary with respect to both the density and the type of muscarinic receptors present. Five subtypes of muscarinic receptors have been identified (M1, M2, M3, M4, M5), each with a different location and function. For example, M1 receptors are found in the cerebral cortex, sympathetic ganglia and postganglionic neurons, and some presynaptic sites. M2 receptors are present in myocardium, smooth muscle cells, and some presynaptic sites. M3 receptors are found in exocrine glands, and M4 receptors in heart. M5 receptors are found mostly in brain. All muscarinic receptor subtypes interact with heterotrimeric, guanine nucleotide-binding regulatory proteins (G proteins) linked to cellular effectors. Although selectivity is not absolute, stimulation of M1 or M3 receptors causes hydrolysis of polyphosphoinositides and mobilization of intracellular Ca2+, which is due to interaction with a G protein (Gq) that activates phospholipase C. The latter causes a variety of Ca2+-mediated events, either directly or via phosphorylation of target proteins. In contrast, M2 and M4 muscarinic receptors inhibit adenylyl cyclase and regulate specific ion channels (e.g., enhancement of K+ conductance in cardiac atrial tissue) through subunits released from pertussis toxinsensitive G proteins (G1 and G0). These are distinct from the G proteins used by the M1 and M3 receptors. Finally, M5 receptors may inhibit M-type (KCNQ2/KCNQ3) K+ channels via the activation of a common G protein.

Recognition Table 8-1 lists the effects of anticholinergics in various organ systems. Appreciation of the range of organ systems affected by anticholinergic drugs is required to maximize their benefits while minimizing side effects. Drugs in common use (atropine, scopolamine, glycopyrrolate) are nonselective muscarinic receptor antagonists. They have similar side effects, but to a varying extent. As stated earlier, atropine and

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Clinical Effects of Anticholinergic Drugs

Cardiovascular effects (observed at moderate doses) Increased rate of sinoatrial (SA) node discharge Decreased rate of SA node discharge (low doses of atropine) Enhanced atrioventricular node conduction Little or no effect on ventricular function Little effect on peripheral vasculature Cutaneous vasodilatation in high doses Respiratory effects (observed at low doses) Drying of respiratory secretions Relaxation of bronchial smooth muscle Increased anatomic dead space Central nervous system effects (observed at larger doses) Wide range of symptoms, from sedation and depression to agitation and delirium Gastrointestinal effects (observed at larger doses) Decreased salivation Reduced gastric secretions and motility Decreased lower esophageal sphincter tone Ophthalmic effects (observed at moderate doses) Mydriasis Cycloplegia Genitourinary effects (observed at larger doses) Decreased ureter and bladder tone Urinary retention Thermoregulation effects (observed at small doses) Inhibition of sweat gland secretions (function most sensitive to anticholinergics) Elevated temperature

scopolamine cross the blood-brain barrier, whereas glycopyrrolate does not. Scopolamine is more sedating than atropine but causes less of a heart rate increase; similar to atropine, it is a moderately potent antisialagogue. Glycopyrrolate is the most potent antisialagogue, causes moderate tachycardia, and is nonsedating. The pharmacologic effects of anticholinergics used in anesthesia are summarized in Table 8-2. Another anticholinergic agent, ipratropium (Atrovent), is used primarily in pulmonary care. This drug was introduced

Table 8–2

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Pharmacologic Effects of Anticholinergics Used in Anesthesia

Atropine Causes greater vagolysis than glycopyrrolate Increases heart rate and enhances atrioventricular node conduction Paradoxical slowing of heart rate at low doses Little sedation Moderately potent antisialagogue Glycopyrrolate Moderate vagolytic effect on heart, but less than that of atropine No sedation (charged quaternary amine; does not cross blood-brain barrier) Highly potent antisialagogue Scopolamine Marked sedation-amnesia (tertiary amine structure; lipid soluble; crosses blood-brain barrier) Most likely to cause central anticholinergic syndrome (easily reversed with physostigmine) Moderately potent antisialagogue

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in the 1980s and reestablished anticholinergics as a therapy for bronchospastic disorders. Although ipratropium is structurally similar to atropine and has similar actions if given parenterally, it is a quaternary ammonium compound. Ipratropium is poorly absorbed when inhaled and has few extrapulmonary effects, even with very large inhaled doses. When inhaled, 90% of ipratropium is swallowed, and only 1% of the total dose is absorbed systemically. When given to normal volunteers, the drug provides almost complete protection against bronchospasm induced by a variety of provocative agents. However, in asthmatics, the results can vary. Whereas the bronchospastic effects of some agents (e.g., methacholine, sulfur dioxide) are completely blocked, there is little blocking of leukotriene-induced bronchoconstriction. Also, unlike atropine, ipratropium has no negative effect on ciliary clearance. In general, this drug and other anticholinergics are more effective in chronic obstructive pulmonary disease, especially when cholinergic tone is high. The development of new drugs that affect specific muscarinic receptor subtypes will provide more effective therapy with fewer adverse or troublesome side effects than the drugs used today. The child in the case synopsis displayed many of the signs and symptoms of anticholinergic toxicity, which can be divided into two types: CNS and peripheral antimuscarinic. CNS toxicity can manifest as agitation, delirium, seizures, or coma. Systemic anticholinergic effects are most prominent in tissues or organs with dense parasympathetic innervation and include tachycardia; dry mucous membranes; urinary retention; dry, flushed skin; dilated pupils with cycloplegia; fever; and ileus. The child in the case illustrated the typical findings accompanying anticholinergic overdose in pediatric patients. Although the cause of his condition was known, the differential diagnosis includes other potentially lifethreatening conditions (Table 8-3). Physical examination and the natural history of the disease process should allow the clinician to differentiate among these conditions. Physical and laboratory findings of anticholinergic toxicity that help exclude other conditions are summarized in Table 8-4. Although the conditions in the differential diagnosis share overlapping features with anticholinergic toxicity, the combination of abolition of pupillary responses and sweating is very specific for anticholinergic toxicity. Many clinicians confuse anticholinergic toxicity with the diametrically opposed toxidrome associated with anticholinesterase poisoning, which results in excessive cholinergic tone. Physician familiarity with toxic syndromes due to anticholinesterase poisoning has increased dramatically with the proliferation of chemical weapons of mass destruction. In contrast to the symptoms and signs of anticholinergic

Table 8–3

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Differential Diagnosis of Anticholinergic Toxicity

Hypoxemia and/or hypercarbia Sepsis Malignant hyperthermia Thyroid storm (crisis) Pheochromocytoma Carcinoid syndrome

PHARMACOLOGY

Table 8–1

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Pharmacology

Distinguishing Features of Anticholinergic Toxicity*

Relatively normal arterial O2 and CO2 tensions (rules out hypoxemia and hypercarbia) Cycloplegia (pupillary light reflexes remain intact for most other conditions) Mydriasis (pupils may also be dilated in MH due to elevated circulating catecholamines) Anhidrosis; warm, red skin (sweating is preserved in other disorders within the differential diagnosis; see Table 8-3) Lack of muscle rigidity (commonly seen with MH) No ventricular arrhythmias (not characteristic of carcinoid syndrome, but common with MH, pheochromocytoma, and thyrotoxicosis) Minimal to modest increase in end-tidal CO2 due to hyperthermia (usually far greater with MH or thyrotoxicosis) Mild (or no) hypertension (as in MH), or paroxysmal, severe hypertension (thyroid storm, pheochromocytoma, or carcinoid tumor†), especially with gland or tumor manipulation Mild to no metabolic acidosis (far more severe in MH) *In anesthetized patients, the modulatory effects of anesthesia must be considered. † Serotonin released by carcinoid tumors has little if any direct effect on the heart. However, positive chronotropic and inotropic effects, and possibly arrhythmias, may occur with the release of norepinephrine. Effects of serotonin on the peripheral vasculature include both vasoconstriction and vasodilatation. MH, malignant hyperthermia.

overdose, poisoning with carbamate insecticides or organophosphates leads to CNS excitation and excessive nicotinic and muscarinic receptor activation. CNS signs include ataxia, restlessness, agitation, convulsions, and coma. Muscarinic signs include excessive salivation, perspiration, vomiting, diarrhea, abdominal cramps, tenesmus, bradycardia or heart block, pupillary constriction, lacrimation, wheezing, hypotension, blurred vision, and urinary and fecal incontinence. Nicotinic signs include muscle twitching, fasciculations, cramping, paralysis, respiratory compromise, and subsequent cardiac arrest.

Risk Assessment Patients with heart disease are at far greater risk for anticholinergic complications. In this respect, atropine and glycopyrrolate produce more vagolysis than scopolamine does, causing a much greater increase in the sinus rate and speed of atrioventricular (AV) node conduction. An increased heart rate is more dangerous in patients with coronary artery disease and valvular or subvalvular restrictive cardiac lesions (e.g., aortic and mitral valve stenosis, idiopathic hypertrophic subaortic stenosis). Further, in patients with functional accessory AV pathways and a history of AV reciprocating tachycardia or atrial flutter or fibrillation (e.g., WolffParkinson-White syndrome), atropine or glycopyrrolate (especially in a relative overdose) may precipitate dangerously fast tachyarrhythmias (see Chapter 80). Also, because both drugs facilitate AV node conduction, they are contraindicated in patients with supraventricular tachyarrhythmias, especially atrial flutter or fibrillation.

Implications Anticholinergics exert their effects in many organ systems (see Table 8-1). Therapeutic effects in one organ system may be accompanied by undesirable side effects in others. Careful selection of the anticholinergic agent and its dose allows the clinician to target the appropriate organ system and simultaneously minimize undesirable side effects in other organ systems (see Table 8-2). Although atropine is considered relatively safe and benign in adults, an atropine overdose is very dangerous in pediatric

patients, especially infants. Deaths due to anticholinergic poisoning have been reported with doses as low as 2 mg of atropine in infants. Anticholinergics have complex gastrointestinal actions. Salivary gland secretions are reduced and are the most sensitive to cholinergic block. Gastric secretions are also reduced, but this requires larger doses. Both gastrointestinal motility and lower esophageal sphincter tone are reduced. However, it is important to remember that anticholinergic premedication does not confer protection against aspiration of gastric contents and chemical or bacterial pneumonitis. Also, the function of a number of other organs can be impaired by anticholinergic therapy. In the eye, anticholinergic drugs can precipitate narrow-angle glaucoma. Individuals with a shallow anterior chamber can suffer acute increased intraocular pressure due to impaired drainage via the canal of Schlemm. Postsurgical patients, especially elderly men with prostatic hypertrophy, are at risk for severe urinary retention after taking anticholinergics. Further, confusion, agitation, and delirium are CNS side effects of anticholinergics that cross the blood-brain barrier (scopolamine, atropine). Patients at greatest risk for mental status changes are those at the extremes of age, those with preexisting abnormalities of mental status, and those taking drugs with significant anticholinergic properties (e.g., antiparkinson drugs, phenothiazines, tricyclic antidepressants, butyrophenones, antihistamines, cycloplegics, antispasmodics). Impaired thermoregulation due to the inability to sweat can result in hyperpyrexia. Children and infants are especially vulnerable owing to their high metabolic rate and immature thermoregulatory mechanisms. It is clear that hyperpyrexia involves an impaired ability to dissipate heat through sweating. Whether there is a central effect on thermal regulation remains unclear. Finally, atropine and glycopyrrolate are commonly given with or prior to anticholinesterase drugs to reverse nondepolarizing neuromuscular blockade. Because of similarities in onset of drug action, atropine is commonly administered with edrophonium, which has a very rapid onset. Similarly, glycopyrrolate is often administered with neostigmine because both have a slower onset and a longer duration of action. By selecting an anticholinergic that matches the anticholinesterase drug’s onset and duration of action, heart

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MANAGEMENT Most complications related to anticholinergic drugs are self-limited and can be effectively treated with supportive care. For example, urinary retention in elderly men may require short-term or intermittent bladder catheterization. However, some complications, such as fast sinus or nonparoxysmal atrial tachycardias in patients with myocardial ischemia or infarction, aortic or mitral valve stenosis, or idiopathic hypertrophic subaortic stenosis, require prompt treatment. Therapeutic options include β-blockers and calcium channel antagonists. If paroxysmal supraventricular tachycardia is likely, adenosine is useful. However, the current advanced cardiovascular life support guidelines advise early cardioversion for most hemodynamically disadvantageous tachyarrhythmias, rather than a trial of drugs (see Chapter 79). Likewise, severe hyperthermia should be treated aggressively with cooling blankets and, if needed, immersion in ice water and irrigation of body cavities with cold saline. With careful consideration of the underlying medical history and the pharmacodynamics of the various anticholinergics, it is possible to maximize the benefits of this class of medications while minimizing undesirable side effects of therapy.

PREVENTION Prevention of the side effects of anticholinergic drugs begins with an appreciation of the fact that they affect different

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organ systems with different intensities (see Tables 8-1 and 8-2) but do so in a predictable, dose-related fashion. To avoid complications, it is most important to recognize that certain subsets of patients are at greater risk for morbidity related to the use of anticholinergic drugs. Therefore, it is crucial to evaluate the specific vulnerabilities of the patient, delineate the goals of anticholinergic therapy, and select a drug with a pharmacodynamic profile that most closely suits the goals of therapy.

Further Reading Brown JH, Taylor P: Muscarinic receptor agonists and antagonists. In Hardman JG, Limbird LE (eds): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York, McGrawHill, 2001, pp 155-173. Das G: Therapeutic review: Cardiac effects of atropine in man: An update. Int J Clin Pharmacol 27:473-477, 1989. Feldman MD: The syndrome of anticholinergic intoxication. Am Fam Physician 34:113-116, 1986. Friesen RH, Lichtor JL: Cardiovascular depression during halothane anesthesia in infants: A study of three induction techniques. Anesth Analg 61:42-45, 1982. Goyal RK: Muscarinic receptor subtypes: Physiology and clinical implications. N Engl J Med 321:1022, 1989. Gross NJ: Ipratropium bromide. N Engl J Med 319:486-494, 1988. Guo J, Schofield GG: Activation of muscarinic M5 receptors inhibits recombinant KCNQ2/KCNQ3 K+ channels expressed in HEK293T cells. Eur J Pharmacol 462:25-32, 2003. Mirakhur RK: Antagonism of the muscarinic effects of edrophonium with atropine or glycopyrrolate. Br J Anaesth 57:1213-1216, 1985. Moss J, Glick D: The autonomic nervous system. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 617-677. Patton WDM: The principles of drug action. Proc R Soc Med 53:815-820, 1965. Polak RL: Effects of hyoscine on the output of acetylcholine into preferred cerebral ventricles on cats. J Physiol 181:317-323, 1965.

PHARMACOLOGY

rates that are too fast or too slow can be avoided. It also appears that lower doses of anticholinergics are required to antagonize the weaker and shorter-lived muscarinic effects of edrophonium compared with those of neostigmine.

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Adenosine M. J. Pekka Raatikainen and John L. Atlee Case Synopsis A 63-year-old man with a history of transient ischemic attacks is admitted to the hospital for elective surgery. His medications include aspirin 250 mg/day orally and dipyridamole 75 mg orally three times a day. During the operation under regional anesthesia, a regular supraventricular tachycardia (SVT) is observed. The tachycardia terminates after intravenous bolus adenosine (12 mg) and is followed by a long sinus pause and angina-like pain (Fig. 9-1).

PROBLEM ANALYSIS Definition The first step is to determine whether the signs or symptoms are due to tachycardia. If they are, the existing advanced cardiovascular life support guidelines advise immediate cardioversion rather than a trial of antiarrhythmic drugs. If cardioversion is not indicated (e.g., ectopic atrial tachycardia), the guidelines stress making a specific diagnosis and identifying patients with impaired cardiac function (ejection fraction <40%). Importantly, the 2000 guidelines downplay the use of adenosine to differentiate wide QRS tachycardia due to ventricular aberration versus ectopy. This unnecessarily exposes patients to adenosine’s unpleasant side effects, possibly worsens arrhythmias, and may destabilize heart rate and pressure. However, given the history of the patient described in the case synopsis, the circumstances, and the apparent suddenness of onset, it was reasonable to administer adenosine to terminate this regular, narrow QRS complex tachycardia, especially because it was associated with apparent ST segment

depression in the lead depicted. The advantage of adenosine (versus intravenous calcium channel antagonists, such as verapamil or diltiazem, or β-blockers) for the chemical conversion of sudden-onset, narrow QRS tachycardia is related to its rapid action and ultrashort half-life. Although adenosine rarely causes severe side effects, minor adverse effects such as facial flushing and chest discomfort are frequently observed. In the majority of patients, these are well tolerated and resolve rapidly without intervention. However, the concomitant administration of drugs that inhibit the elimination of adenosine from blood, and the presence of some clinical conditions (e.g., asthma), may render some patients more susceptible to the development of severe adverse effects with adenosine.

Recognition Endogenous adenosine is involved in numerous physiologic and pathophysiologic processes in mammalian organs and tissues. Most, if not all, of these actions are mediated by specific cell surface receptors (A1-, A2A-, A2B-, and A3-adenosine receptors). Because of the ubiquitous nature and distribution of these receptors, administration of adenosine to terminate SVT may cause adverse effects unrelated to the heart. Following are the most common patient complaints after the administration of adenosine: ● ●

A

B

Rhythm strip during the tachycardia

20 sec after 12 mg adenosine bolus

●

5.5 s

Figure 9–1 ■ A, Intraoperative rhythm strip from the patient described in the case synopsis (paper speed, 25 mm/second). It shows a regular, narrow QRS tachycardia (180 beats per minute). B, Rhythm strip 20 seconds after the administration of intravenous bolus adenosine (12 mg). Sinus arrest lasting 5.5 seconds occurs after termination of the tachycardia. The patient was receiving dipyridamole, which is a potent nucleoside transport blocker and likely potentiated adenosine’s effects. In later ambulatory electrocardiographic recordings and electrophysiologic testing, there was no evidence of sinoatrial node dysfunction.

32

Facial flushing Dyspnea Chest discomfort

Less common side effects are nausea, lightheadedness, headache, dizziness, and palpitations. These adverse side effects often occur concomitantly with tachycardia termination and persist for 2 to 3 minutes. Many, but not all, of these effects are attributable to vasodilatation with activation of the A2adenosine receptors. For example, facial flushing is caused by cutaneous vasodilatation. Direct stimulation of carotid chemoreceptors and cardiac pain receptors may explain respiratory stimulation and the sensation of dyspnea and chest discomfort (angina-like pain), respectively. Adenosine may also cause bronchoconstriction, especially in asthmatics. Like all antiarrhythmics, adenosine may be proarrhythmic, provoking new or worse arrhythmias. Given the potent depressant effects of adenosine in the sinoatrial (SA) and atrioventricular (AV) nodes, it is not surprising that adenosine

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● ● ● ● ● ● ● ●

Sinus bradycardia; transient sinus arrest Transient AV block Supraventricular premature beats Atrial flutter Atrial fibrillation Ventricular premature beats Nonsustained VT Torsades de pointes–type polymorphic VT

The potent negative chronotropic (slowed sinus rate) and dromotropic (slowed AV node conduction) effects of adenosine explain its ability to cause pronounced bradycardia or sinus arrest or AV heart block. The induction of atrial flutter or fibrillation by adenosine appears to be due to shortening of atrial repolarization and refractoriness. Although the drug effectively terminates most paroxysmal SVT, some reports have demonstrated its proarrhythmic potential, including the induction of VT. However, the mechanisms of adenosine-induced ventricular premature beats and nonsustained or even sustained VT are less clear. Adenosine has no known direct effect on ventricular myocytes. Thus, it seems unlikely that adenosine exerts a direct proarrhythmic effect, at least in normal ventricles. Further, ventricular premature beats are not specific for adenosine but may also be seen after termination of SVT by calcium channel blockers (e.g., verapamil, diltiazem) or AV node ablation. Some reports suggest that termination of SVT by adenosine may occasionally lead to the development of torsades de pointes polymorphic VT. Adenosine markedly slows the sinus and ventricular rates and, when given intravenously, leads to increased sympathetic discharge. In fact, adenosine has been used to reproduce clinical torsades de pointes in patients with congenital long Q-T interval syndrome during electrophysiologic testing. Thus, one might speculate that an adenosineslowed ventricular rate and an increased sympathetic discharge interact adversely to facilitate early afterdepolarizations, the proximate cause of ventricular tachyarrhythmias in experimental models. One group attempted to define the proarrhythmic effects of adenosine used to terminate 187 episodes of SVT in 127 patients admitted to the emergency room over a 5-year period. In two thirds of cases, adenosine induced ventricular ectopy after successful termination of SVT, including premature ventricular beats and nonsustained VT, both of which were transient and self-terminating. Based on morphologic criteria, more than half the arrhythmias appeared to originate in the inferior left ventricular septum, which may be more susceptible to adenosine’s proarrhythmic effects. Although this high incidence of ventricular arrhythmias was surprising, no further intervention was required. These proarrhythmic

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33

effects may be due to abnormal electrophysiologic mechanisms facilitated by adenosine-increased sympathetic discharge. To recognize transient or sustained ventricular proarrhythmias after the administration of adenosine for the treatment of paroxysmal SVT, one should monitor the electrocardiogram (ECG) continuously for at least 2 minutes following each intravenous adenosine bolus.

Risk Assessment The reported incidence of adverse extracardiac symptoms after an intravenous bolus injection of adenosine ranges from less than 30% to more than 70%. Proarrhythmic effects are less common; for example, the incidence of atrial fibrillation is 1% to 5%, and the incidence of ventricular premature beats is approximately 10% to 30%. Only occasionally do case reports describe more severe proarrhythmic actions. However, it is known that interactions with drugs inhibiting adenosine metabolism and some clinical conditions may sensitize patients to the effects of adenosine and thus render them susceptible to more severe adverse effects. For example, in patients receiving dipyridamole, the cellular uptake of adenosine is blocked, and the half-life of the nucleoside is markedly prolonged. Consequently, these patients are much more vulnerable to the development of prolonged bradycardia, AV node conduction disturbances, and extracardiac adverse effects. Likewise, patients with preexisting AV node conduction disturbances, sick sinus syndrome, myocardial ischemia, and cardiac allografts are more sensitized to the cardiac effects of adenosine, and asthmatic patients are more susceptible to adenosine-induced bronchoconstriction. In view of the finding that abrupt slowing of the heart rate may cause torsades de pointes VT, adenosine, like any other agent that promotes the development of sudden bradycardia, may be arrhythmogenic in patients with long QT syndrome. Factors and clinical conditions that predispose patients to the adverse effects of adenosine include the following: ●

●

● ● ● ●

Medications that inhibit the elimination of adenosine from blood (e.g., dipyridamole) Myocardial ischemia (especially inferior myocardial infarction or ischemia) Heart transplantation Preexisting AV node conduction disturbances Preexisting SA node disease Acquired or congenital long QT syndrome

Nevertheless, compared with calcium channel antagonists, β-blockers, and other antiarrhythmic agents, adenosine has many important advantages related to its rapid onset of action and less severe and shorter-lived adverse effects. Initial experience also indicates that adenosine can be relatively safely administered to patients in whom the use of calcium channel antagonists may be hazardous (e.g., those with heart failure, ischemic heart disease, WolffParkinson-White syndrome, or wide-complex tachycardia or those taking β-blockers). In addition, adenosine may still have utility for differentiating wide QRS complex SVT from VT and for identifying the arrhythmogenic mechanism of a variety of tachycardias, especially in the cardiac catheterization laboratory during electrophysiologic testing (Fig. 9-2). However, as stated earlier, for arrhythmias involving

PHARMACOLOGY

often causes transient sinus bradycardia and AV block. In fact, adenosine’s efficacy in terminating AV nodal reentrant tachycardia and AV reciprocating tachycardia depends on the production of transient AV block. In addition to commonly associated bradyarrhythmias, clinicians report that adenosine occasionally induces atrial fibrillation, ventricular premature beats, brief episodes of nonsustained ventricular tachycardia (VT), and torsades de pointes VT (a polymorphic VT in association with Q-T interval prolongation; see Chapter 81). The following proarrhythmias have been observed after the intravenous administration of adenosine:

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Tachycardia Adenosine Termination • • • •

Transient suppression

AVNRT, AVRT cAMP-dependent VT SNRT Atrial tachycardia

• Sinus tachycardia • Atrial tachycardia

No effect • • • •

Reentrant and automatic VT Atrial flutter Atrial fibrillation Atrial tachycardia

Figure 9–2 ■ Possible effects of adenosine on cardiac arrhythmias. Because important diagnostic information can be obtained during the drug’s peak effect, the cardiac rhythm should be monitored by electrocardiogram for at least 2 minutes after each adenosine bolus. Rapid intravenous bolus adenosine (6 mg, followed by 12 mg if necessary) terminates more than 90% of supraventricular tachycardias that involve the atrioventricular (AV) node, including AV nodal reentrant tachycardia (AVNRT) and AV reentrant tachycardia (AVRT) involving the AV node and accessory AV conduction pathways. Some catecholamine-dependent (e.g., cyclic adenosine monophosphate [cAMP]) ventricular tachycardia (VT) and sinoatrial node reentrant tachycardia (SNRT) are also terminated by adenosine. Depending on the tachycardia mechanism and the location of the arrhythmogenic focus, the effect of adenosine on atrial tachycardias can vary considerably. Although adenosine may terminate some atrial tachyarrhythmias, it can also precipitate atrial fibrillation or flutter.

severe hemodynamic compromise, immediate cardioversion is recommended rather than a trial of antiarrhythmic drugs.

Implications Among the drugs used for the acute treatment of paroxysmal SVT, adenosine appears to be the least likely to cause significant adverse hemodynamic effects. It can also be used safely throughout the perioperative period. However, caution is necessary when administrating adenosine to patients receiving dipyridamole or other agents that inhibit the elimination of adenosine. Likewise, patients with myocardial ischemia, SA or AV node dysfunction, and cardiac allografts seem to be sensitized to both the therapeutic and the adverse effects of adenosine.

restore sinus rhythm in patients with ischemia-induced AV node block during the early phase of inferior myocardial infarction. They can also relieve angina-like pain in patients treated with adenosine. The principles for the management of proarrhythmias associated with adenosine administration are outlined in Figure 9-3. With hemodynamically unstable AV heart block or bradyarrhythmias, cardiopulmonary resuscitation must be started without delay. Likewise, patients with adenosineinduced tachyarrhythmias and hemodynamic compromise require emergency direct-current cardioversion. Otherwise, an adenosine receptor antagonist (e.g., theophylline, aminophylline) is the initial drug of choice. The recommended dose of theophylline is 150 to 250 mg as a slow intravenous bolus injection (approximately 100 mg/minute). If bradycardia or AV block does not respond to theophylline, adrenergic drugs, atropine, or cardiac pacing may be effective. If antiarrhythmic drugs are used to treat adenosine-induced tachyarrhythmias, they should be selected according to the type or mechanism of tachycardia. However, cardioversion is generally preferred to drugs.

PREVENTION There are only a few absolute contraindications for the use of adenosine. Adenosine should not be administered to patients with second or third degree AV block or sick sinus syndrome unless the patient has a pacemaker. In addition, patients with asthma or severe obstructive pulmonary disease probably should not be given adenosine. When administering adenosine therapeutically, physicians should be aware of important drug interactions. Drugs that inhibit the metabolism of adenosine, either by blocking the nucleoside transporter or by directly inhibiting adenosine-metabolizing enzymes (adenosine kinase and adenosine deaminase), significantly prolong the half-life of the adenosine and dramatically potentiate its effects. For example, the concurrent use of dipyridamole potentiates the effects of adenosine by a factor of four. Accordingly, clinicians

Adenosine-induced proarrhythmia

Bradyarrhythmia

MANAGEMENT Because of adenosine’s extremely short half-life, any adverse effects caused by its intravenous bolus injection are usually transient and require observation only. Again, to recognize transient or sustained ventricular proarrhythmias after the administration of adenosine for paroxysmal SVT, the ECG must be monitored continuously for at least 2 minutes after each injection. The nonselective A1- and A2-adenosine receptor antagonists aminophylline and theophylline are highly effective in reversing any unfavorable side effects of adenosine injection or infusion. In addition, these agents have been used to

Tachyarrhythmia

Hemodynamically stable?

Hemodynamically stable?

NO YES

NO YES

Theophylline

Theophylline CPR Theophylline Adrenergic drugs Cardiac pacing Atropine

Sinus rhythm?

Immediate DC shock; CPR

Sinus rhythm? NO YES

NO YES Successful

Antiarrhythmic drugs DC shock

Successful

Monitor for further arrhythmias Figure 9–3 ■ Algorithm for the management of proarrhythmias associated with the administration of adenosine. CPR, cardiopulmonary resuscitation; DC, direct current.

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●

●

● ●

●

●

Identify and correct factors that may predispose patients to proarrhythmia and other adverse effects. Reduce the dosage in patients receiving dipyridamole or other agents that inhibit the elimination of adenosine. Reduce the dose when using central vascular access. Always use incremental adenosine dosing, starting with a low initial dose. An unnecessarily large initial dose will not improve adenosine’s efficacy in terminating SVT but will certainly increase the risk for adverse effects. Warn patients about adenosine’s common side effects and reassure them that these effects will resolve within 2 minutes. Monitor the ECG continuously for several minutes after each intravenous bolus of adenosine. This facilitates early diagnosis and treatment of proarrhythmia and may provide valuable diagnostic information.

In summary, an understanding of the pharmacologic basis of adenosine’s actions (pharmacokinetics and drug

Adenosine

35

interactions), combined with meticulous attention to minimizing the factors predisposing to adverse effects, is crucial to this drug’s safe and effective use.

Further Reading Bertolet BD, McMurtrie EB, Hill JA: Theophylline for the treatment of atrioventricular block after myocardial infarction. Ann Intern Med 123:509-511, 1995. Blomström-Lundqvist C, Scheinman MM, Aliot EM, et al: ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias—executive summary. J Am Coll Cardiol 42:1493-1531, 2003. Camm AJ, Garratt CJ: Adenosine and supraventricular tachycardia. N Engl J Med 325:1621-1629, 1991. Celiker A, Tokel K, Cil E, et al: Adenosine induced torsades de pointes in a child with congenital long QT syndrome. Pacing Clin Electrophysiol 17:1814-1817, 1994. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6: Advanced cardiovascular life support. Section 5: Pharmacology. I: Agents for arrhythmias. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation 102(8 Suppl):I112-I128, 2000. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6: Advanced cardiovascular life support. 7D: The tachycardia algorithms. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation 102(8 Suppl):I158-I165, 2000. Harrington GR, Froelich EG: Adenosine-induced torsades de pointes. Chest 103:1299-1301, 1993. Pelleg A, Pennock RS, Kutalek SP: Proarrhythmic effects of adenosine: One decade of clinical data. Am J Ther 9:141-147, 2002. Raatikainen MJP, Dennis DM, Belardinelli L: Cardiac electrophysiology of adenosine: Cellular basis and clinical implications. In Pelleg A, Belardinelli L (eds): Effects of Extracellular Adenosine and ATP on Cardiomyocytes. Austin, Tex, RG Landes, 1998, pp 87-132. Sylven C: Mechanisms of pain in angina pectoris: Critical review of the adenosine hypothesis. Cardiovasc Drug Ther 7:745-759, 1993. Tan HL, Spekhorst HH, Peters RJ, et al: Adenosine induced ventricular arrhythmias in the emergency room. Pacing Clin Electrophysiol 24:450-455, 2001. Wesley RC Jr, Turnquest P: Torsades de pointe after intravenous adenosine in the presence of prolonged QT syndrome. Am Heart J 123:794-796, 1992.

PHARMACOLOGY

recommend that the initial dose of adenosine in patients receiving dipyridamole should not exceed 1 mg, compared with the typical initial dose of 6 mg rapidly administered via a peripheral vein. It is also advisable to use lower-than-usual doses if adenosine is given via a central vein or to patients with myocardial ischemia or to cardiac transplant recipients. In contrast, larger doses (≥12 mg) may be needed to terminate SVT in patients receiving adenosine receptor antagonists such as aminophylline or theophylline. The response to adenosine may be attenuated in patients who consume food or drink containing methylxanthines (e.g., coffee, cola, chocolate). Although no severe interactions with anesthetic drugs have been reported, it may be important to recognize that benzodiazepines block nucleoside transport in the brain, albeit to a lesser extent than dipyridamole. Adenosine may also lower anesthetic requirements (reduced minimum alveolar concentration) and potentiate nondepolarizing neuromuscular blockade. The following actions may help prevent adverse effects associated with the use of adenosine:

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Class I Antiarrhythmic Drugs: Ventricular Proarrhythmia

10

Mark F. Trankina Case Synopsis A 56-year-old man with stable angina and paroxysmal atrial fibrillation is scheduled for ambulatory inguinal hernia repair. He takes sublingual nitroglycerin as needed, quinidine (400 mg four times a day), and metoprolol (50 mg/day). His preoperative electrocardiogram (ECG) shows normal sinus rhythm at 60 beats per minute, with a corrected Q-T interval of 490 msec and possible left atrial enlargement. He refuses regional anesthesia. He is induced with fentanyl (150 μg), thiopental (350 mg), and succinylcholine (100 mg). His airway is secured without difficulty. However, the pulse oximeter malfunctions within minutes of induction. A sporadic carotid pulse is felt, and the ECG shows twisting of QRS complexes around the isoelectric baseline (Fig. 10-1).

PROBLEM ANALYSIS Definition The Cardiac Arrhythmia Suppression Trial (CAST) in 1989 and CAST II in 1992 tested the idea that chronic suppression of lesser ventricular arrhythmias (e.g., ventricular premature beats and nonsustained ventricular tachycardia) by class I antiarrhythmics would reduce mortality in survivors of myocardial infarction. Such arrhythmias were believed to be the inciting events for lethal (malignant) ventricular arrhythmias such as sustained ventricular tachycardia (VT) or ventricular fibrillation. Although encainide and flecainide reduced the incidence of lesser ventricular arrhythmias, they also conferred excess mortality (7.7% in the treatment group versus 3.0% in placebo groups). This excess mortality was attributed to proarrhythmia. Further, deaths in the treatment group were equally distributed throughout the treatment period, suggesting that the proarrhythmic response could occur any time after the start of drug therapy. Proarrhythmia is defined as the provocation of new or worse arrhythmias by antiarrhythmic drugs. The incidence can be as high as 9% to 10% with some class IA, IB, IC, or III drugs and is lowest (2% to 3%) with amiodarone (a class III antiarrhythmic that also has class I, II, and IV actions). Ventricular proarrhythmia manifests as (1) incessant monomorphic VT or polymorphic VT without Q-T interval prolongation or (2) polymorphic VT with Q-T interval prolongation, or torsades de pointes (TDP). Because the patient in the case synopsis had Q-T prolongation, his arrhythmia was TDP (see Fig. 10-1). Early afterdepolarizations (EADs) are believed to be the inciting mechanism for TDP. EADs are oscillations in the transmembrane potential of ventricular myocytes that occur during the repolarization phase. EADs are caused by the blockage of outward potassium (K+) 36

repolarization currents; however, this blockage also leads to Q-T interval prolongation and increased ventricular refractoriness. This is conducive to reentry of excitation, the likely sustaining mechanism for TDP. However, because the increase in refractoriness is uneven (greater in some ventricular fibers than in others), VT induced by EADs has a multiform rather than a uniform morphology. Ischemia-related regional differences in cardiac conduction delay and refractoriness promote ventricular reentry. Ischemia also leads to heterogeneity in antiarrhythmic drug concentrations in myocardium, which augments ischemic cellular electrophysiologic changes. However, the reentry circuits are larger (i.e., macroreentry versus microreentry), and the associated VT is often monomorphic as opposed to polymorphic. When polymorphic VT occurs in patients without Q-T interval prolongation, it is simply polymorphic VT; in association with Q-T interval prolongation, it is TDP. Both have the same ECG appearance (see Fig. 10-1). Mechanisms for the development of clinical arrhythmias include automaticity, which refers to spontaneous cardiac impulse formation without the need for prior stimulation; it can be normal or abnormal. Normal automaticity occurs in the sinoatrial node (the primary pacemaker) or in latent pacemakers (e.g., subsidiary atrial or Purkinje fibers). Abnormal automaticity can occur in any myocardial fiber type, although it usually occurs in fibers that do not normally exhibit automaticity, such as atrial and working ventricular muscle fibers. Such fibers manifest automaticity only if their cell membrane potentials become depressed by the effects of disease, drugs, or imbalance (i.e., the loss of cell membrane potential). At these low cell membrane potentials, ionic currents responsible for automaticity become activated. Arrhythmias ascribed to enhanced normal automaticity are atrioventricular (AV) junctional and ventricular escape rhythms with advanced second degree or complete (third degree) AV heart block or increased AV node refractoriness.

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Class I Antiarrhythmic Drugs: Ventricular Proarrhythmia

37 PHARMACOLOGY

Figure 10–1

■

Torsades de pointes after induction of general anesthesia. Note “twisting” of the QRS complexes around the isoelectric baseline.

Those ascribed to abnormal automaticity include automatic atrial and AV junctional tachycardia, as well as accelerated idioventricular rhythm or tachycardia following cardiopulmonary bypass or in patients with acute coronary syndromes. Triggered activity is initiated by depolarizing oscillations in the cell transmembrane potential (afterdepolarizations) that occur before EADs or after full cell repolarization (delayed afterdepolarizations). Thus, triggered activity is the result of a preceding impulse or series of impulses, without which electrical quiescence occurs. Not all afterdepolarizations reach the threshold potential for a regenerative action potential. However, if they do, they can trigger further afterdepolarizations and thus become self-perpetuating. Arrhythmias caused by digitalis toxicity are triggered by delayed afterdepolarizations. Some ectopic atrial tachycardia may also be triggered. As already noted, there is strong evidence that EADs and EAD-triggered activity are the cause of polymorphic VT associated with congenital or acquired long QT syndromes (e.g., TDP). Some causes of EADs are listed in Table 10-1. In addition, there has been a great deal of controversy over the Food and Drug Administration’s “black box” warning about the clinical significance of Q-T prolongation due to droperidol, a drug that has been used safely for decades by anesthesiologists and other health care providers. A more comprehensive listing of drugs associated with TDP (and thus likely causes of EADs) can be found in Chapter 81 or on the Web site http.//www.torsades.org.

Table 10–1

■

Causes of Early Afterdepolarizations and Triggered Activity

α-Adrenergic stimulation Imbalance Hypoxia Hypercarbia Acidosis Hypokalemia Anitarrhythmic drugs Quinidine Ibutilide Sotalol Local anesthetics Bupivacaine Etidocaine Miscellaneous Cesium

Recognition The Vaughan-Williams antiarrhythmic drug classification divides drugs into four classes based on their principal mode of action: class I, sodium channel blockers; class II, β-adrenergic blockers; class III, potassium channel blockers; and class IV, calcium channel blockers. Class I antiarrhythmic drugs are further subdivided into classes IA, IB, and IC. Signs of toxicity caused by class I antiarrhythmics include the following: ●

●

● ●

●

Lengthened Q-T interval (class IA) or widened QRS complexes (class IC) manifesting as proarrhythmia Long Q-T interval (corrected Q-T interval of 440 to 450 msec) History of dizziness or syncope preoperatively Change in dosing or the recent initiation of antiarrhythmic therapy Occurrence of TDP (see Fig. 10-1)

Class IA Antiarrhythmic Drugs. All class I antiarrhythmics are sodium channel blockers, and some also affect the currents involved in action potential repolarization. Class IA drugs (e.g., quinidine, procainamide, disopyramide) reduce action potential upstroke velocity and prolong its duration. The kinetics of these drugs’ onset and offset of effect are of intermediate rapidity (<5 seconds). Class IB Antiarrhythmic Drugs. Class IB drugs (e.g., mexiletine, phenytoin, lidocaine) do not reduce upstroke velocity, but they do shorten action potential duration. They have fast onset and offset kinetics (<500 msec). Class IC Antiarrhythmic Drugs. Class IC drugs (e.g., flecainide, propafenone, moricizine) reduce upstroke velocity (primarily by slowing conduction) and also prolong refractoriness somewhat. They have slow onset and offset kinetics (10 to 20 seconds). The Vaughan-Williams classification is still widely used, but it has many limitations because of the complexity of drug actions. The “Sicilian gambit’’ (see Further Reading) provides a more realistic view. Some drugs exert greater effects at slow rates than at fast rates (reverse use dependence); this is particularly true of drugs that lengthen repolarization (class IA). Thus, the Q-T interval becomes prolonged at slow rates rather than at fast rates, which is exactly the opposite of what an ideal antiarrhythmic drug should do. Prolongation of refractoriness should be increased at fast rates to interrupt or prevent a reentrant tachycardia and minimal at slow rates to avoid precipitating TDP.

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Finally, it is important to remember that anesthesiologists must evaluate the patient with a rhythm disturbance, not the rhythm disturbance itself. Some arrhythmias are hazardous to the patient regardless of the clinical setting, whereas others are hazardous because of the clinical setting (e.g., anesthesia and surgery, acute coronary syndromes, post cardiopulmonary bypass).

Risk Assessment Conditions associated with Q-T interval prolongation and thus predisposition to TDP are listed in Table 10-2. A variety of commonly prescribed drugs belonging to many different therapeutic classes, including antiarrhythmics, antibiotics, antihistamines, and prokinetic drugs, can adversely prolong cardiac repolarization. However, arrhythmias related to drug-induced Q-T prolongation do not occur in every patient treated with such drugs; they occur only in susceptible patients. It has been postulated that these individuals may be silent carriers of genes responsible for congenital long QT syndromes. Up to 70% of these patients have normal Q-Tc intervals until exposed to a Q-T interval–prolonging drug. The primary objective of pharmacologic therapy for a patient with a cardiac arrhythmia is to achieve an effective and well-tolerated plasma drug concentration as quickly as possible and to maintain that concentration for as long as required without producing adverse effects. In many circumstances (but not with all drugs), the plasma concentration after equilibration correlates with the pharmacodynamic and adverse effects of the drug. However, the therapeutic concentration for any given patient is the amount of drug required to suppress or terminate the specific cardiac arrhythmia without producing adverse side effects.

Table 10–2

■

Factors that Predispose to Q-T Interval Prolongation

Congenital or acquired long QT syndromes Coexisting disease Hypothyroidism Cardiomyopathies Bradycardia Physiologic imbalance Hypokalemia Hypomagnesemia Hypocalcemia Antiarrhythmics Class IA, IC, and III drugs Combined class IA and III drugs Other drugs Potassium-wasting diuretics Tricyclic antidepressants Phenothiazines Erythromycin Terfenadine Astemizole Liquid protein diets For a more complete listing, see Chapter 81 or go to http.//www.torsades.org.

Given the fact that automaticity, triggered activity, or reentry can cause cardiac arrhythmias, the mechanisms by which antiarrhythmic agents suppress cardiac arrhythmias can be postulated. Antiarrhythmic agents can slow the spontaneous discharge frequency of an automatic pacemaker by depressing the slope of diastolic depolarization, shifting the threshold voltage toward zero, or hyperpolarizing the resting membrane potential. Mechanisms by which different drugs suppress normal or abnormal automaticity may not be the same. In general, most antiarrhythmic drugs in therapeutic doses depress automaticity at ectopic sites while minimally affecting automaticity of the sinus node. However, calcium channel blockers (e.g., verapamil) and β-blockers (e.g., propranolol) can depress the sinus rate, and drugs that exert vagolytic effects (e.g., disopyramide, quinidine) can increase the sinus rate. Drugs can also suppress early or delayed afterdepolarizations to eliminate triggered arrhythmias. Proarrhythmia with antiarrhythmic drugs is an important clinical problem. Electrophysiologic mechanisms include prolongation of repolarization, development of delayed after depolarizations (e.g., arrhythmias with digitalis toxicity) or EADs (to initiate TDP), or alterations in conduction and refractoriness that are conducive to reentry and the initiation or maintenance of VT or ventricular fibrillation. The acquired form of Q-T interval prolongation (see Table 10-2) is caused by various agents and conditions that reduce the magnitude of outward repolarizing K+ currents, enhance inward depolarizing Na+ or Ca2+ currents, or both, which leads to the development of EADs that initiate TDP. Proarrhythmic events can occur in as many as 5% to 10% of patients. Congestive heart failure increases proarrhythmic risk. In one recent study, patients with atrial fibrillation receiving antiarrhythmic drugs had a 4.7 relative risk of cardiac death if they had a history of heart failure, compared with a 3.7 relative risk among those not receiving antiarrhythmic drugs. Patients without a history of congestive heart failure had no increased risk of cardiac mortality during antiarrhythmic drug therapy. Reduced left ventricular function, treatment with digitalis and diuretics, and longer pretreatment Q-T interval are often seen in patients who develop drug-induced ventricular fibrillation. Usually the proarrhythmic events occur within several days of beginning drug therapy or after a change in dosage and are manifest by the development of VT, Q-T interval prolongation, or TDP (long QT syndrome). Doses for class I antiarrhythmic drugs are listed in Table 10-3. Proarrhythmic effects are likely additive when multiple drugs are used. Mortality with TDP is approximately 30%. With acquired long QT syndromes, the therapeutic challenge is to maintain prolonged repolarization but interrupt the arrhythmogenic cascade.

MANAGEMENT It is possible that multiple drugs have a cumulative effect in provoking EADs and TDP. Antiarrhythmics may paradoxically produce malignant ventricular tachyarrhythmias via proarrhythmia, and preoperative antiarrhythmic treatment does not preclude the generation of more ominous perioperative arrhythmias. The ECG should be carefully scrutinized

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Dosing for Class I Antiarrhythmic Agents

Drug

IV Loading

IV Maintenance

PO Loading

PO Maintenance

Quinidine Procainamide Disopyramide Lidocaine Mexiletine Tocainide Phenytoin Flecainide Propafenone Moricizine

6-10 mg/kg at 0.3-0.5 mg/kg/min 6-13 mg/kg at 0.2-0.5 mg/kg/min 1-2 mg/kg over 15-45 min 1-3 mg/kg at 20-50 mg/min 500 mg 750 mg 100 mg q5min to <1000 mg 2 mg/kg 1-2 mg/kg

600-1000 mg 2-6 mg/min 1 mg/kg/hr 1-4 mg/min 0.5-1.0 g/24 hr

300-600 mg q6h 500-1000 mg NA 400-600 mg 400-600 mg 1000 mg

300-600 mg q6h 350-1000 mg q3-6h 100-400 mg q6-8h NA 150-300 mg q6-8h 400-600 mg q8-12h 100-400 mg q12-24h

600-900 mg 300 mg

150-300 mg q8-12h 100-400 q8h

100-200 mg q12h

NA, not applicable.

preoperatively for signs of toxic effects caused by drugs (e.g., prolonged Q-Tc interval or widened QRS complex). Specific management for TDP includes the following: ●

● ●

●

●

Atrial or ventricular pacing to increase the K+ current and shorten refractoriness at faster heart rates Intravenous bolus magnesium sulfate Lidocaine by intravenous bolus (does not prolong the Q-T interval) Calcium channel blocker by intravenous bolus (if other interventions fail) Cautious use of isoproterenol to increase the heart rate if pacing is not available

PREVENTION Prevention includes providing a stress-free perioperative period (to the extent possible) to reduce myocardial ischemia and related increased dispersion of myocardial refractoriness. In addition, the following points should be noted: ● ●

●

●

Regional anesthesia is advised. Consider cardiology reevaluation for drug dosing and appropriateness. Consider stopping quinidine before anesthesia administration. Avoid conditions that prolong the Q-T interval (see Table 10-2).

Booker and colleagues have provided a comprehensive review of anesthetic management for patients with

congenital and acquired long QT syndromes, including specific recommendations for the perioperative management of such patients.

Further Reading Atlee JL: Drug treatment for arrhythmias. In Atlee JL (ed): Arrhythmias and Pacemakers: Practical Management for Anesthesia and Critical Care Medicine. Philadelphia, WB Saunders, 1996, pp 154-204. Atlee JL: Overview of mechanisms for arrhythmias. In Atlee JL (ed): Arrhythmias and Pacemakers: Practical Management for Anesthesia and Critical Care Medicine. Philadelphia, WB Saunders, 1996, pp 25-58. Booker PD, Whyte SD, Ladusans EJ: Long QT syndrome and anaesthesia. Br J Anaesth 90:349-366, 2003. Charbit B, Albaladejo P, Funck-Brentano C, et al: Prolongation of QTc interval after postoperative nausea and vomiting treatment by droperidol or ondansetron. Anesthesiology 102:1094-1100, 2005. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. The Cardiac Arrhythmia Suppression Trial II investigators. N Engl J Med 327:227-233, 1992. Preliminary report: Effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. The Cardiac Arrhythmia Suppression Trial (CAST) investigators. N Engl J Med 321:406-412, 1989. Soroker D, Ezri T, Szmuki P, et al: Perioperative torsades de pointes ventricular tachycardia induced by hypocalcemia and hypokalemia. Anesth Analg 80:630-633, 1995. Tan HL, Hou CJ, Laver MR, et al: Electrophysiologic mechanisms of the long QT interval syndromes and torsades de pointes. Ann Intern Med 122:701-714, 1995. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology: The Sicilian gambit: A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. Circulation 84:1831-1851, 1991.

PHARMACOLOGY

Table 10–3

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Class II Antiarrhythmic Drugs: β-Blockers—Heart Block or Bradycardia

11

Charles A. Napolitano and Maria I. Castro Case Synopsis A 60-year-old woman with a history of mitral valve stenosis and atrial fibrillation is scheduled for abdominal hysterectomy. Her current medications include verapamil and digoxin. Following induction of anesthesia with etomidate and maintenance with sevoflurane, oxygen, fentanyl, and vecuronium, her ventricular rate increases acutely to 140 beats per minute. Esmolol therapy results in acute bradycardia (30 beats per minute). Electrocardiogram (ECG) monitoring reveals third degree atrioventricular (AV) heart block with regular, wide QRS complexes.

PROBLEM ANALYSIS Definition β-Blockers are commonly used in the management of arrhythmias, hypertension, and heart failure. However, by producing β-adrenergic block, they have the potential to cause sinus bradycardia or sinoatrial (SA) or AV heart block at the AV node. These effects can be aggravated by drugs used during anesthesia (e.g., potent volatile anesthetics, high-dose opiates, local anesthetic toxicity, succinylcholine). Some β-blockers also have vasodilator activity (e.g., carvedilol, labetalol) and may be better tolerated in patients with heart failure. Sinus bradycardia in adults is a heart rate less than 60 beats per minute with a rhythm that originates in the SA node. Third degree AV heart block is the complete absence of impulses conducted from the atria to the ventricles, with the ventricles controlled by impulses originating in subsidiary (latent) cardiac pacemakers located distal to the site of block. If the site of conduction block is perinodal (SA exit block or AV node block), the heart rate typically ranges from 45 to 55 beats per minute, and the QRS interval is of normal duration (~−120 msec). Infranodal block (below the AV node) is characterized by a ventricular rate of 30 to 40 beats per minute and wide QRS complexes. The conduction defect depicted in the case synopsis represents infranodal third degree block with slow secondary pacemaker activity; this can lead to cardiac arrest. Although the third degree AV heart block in this case likely resulted from synergistic depression of AV node function by esmolol (a class II antiarrhythmic) and verapamil (a class IV antiarrhythmic), the other drugs, including digoxin, sevoflurane, and fentanyl, likely contributed. Esmolol, a shortacting β1-selective adrenergic antagonist (β-blocker), is indicated when immediate control of the heart rate or blood pressure is needed and prolonged β-blockade is undesirable. The peak onset of action (6 to 10 minutes) and short halflife (8 minutes) make esmolol appropriate for the management 40

of perioperative tachyarrhythmias. Like all β-blockers, esmolol reduces the sinus rate and AV node conduction time while increasing AV node functional refractoriness. Owing to its inhibitory effects on AV node conduction, verapamil, a calcium channel antagonist, is also useful for reducing the ventricular rate in patients with atrial flutter or fibrillation. However, the effects of verapamil can be potentiated by the concomitant use of β-blockers. As mentioned, the use of sevoflurane, digoxin, and fentanyl, and possibly the surgical procedure itself, likely contributed to the development of heart block in this case. To maintain cardiac output and prevent left ventricular failure or pulmonary edema, tight control of left ventricular preload, heart rate, and systemic vascular resistance is critical for patients with mitral or aortic stenosis and restrictive cardiomyopathies. Thus, the selection of etomidate as an anesthetic induction agent was, at least in theory, a good choice, because etomidate minimizes reflex increases in heart rate and generally maintains systemic vascular resistance and blood pressure within normal limits. However, like other potent inhalational agents, sevoflurane reduces systemic vascular resistance and preload (by dilating the venous capacitance bed to decrease venous return) and may have contributed to the intraoperative increase in ventricular rate via a reflex increase in adrenergic tone. Further, it may have contributed to the third degree AV block and bradycardia by direct effects on AV node conduction and refractoriness. Other potent volatile anesthetics, with the possible exception of desflurane, may also decrease the rate of AV node conduction and SA node discharge. Digoxin’s central actions stimulate vagal tone to reduce heart rate and increase AV node conduction time and refractoriness. Fentanyl, especially at high doses, may inhibit AV node function by causing centrally increased parasympathomimetic and reduced sympathomimetic tone. Finally, peritoneal retraction slows the heart rate and AV node conduction by increasing vagal tone. Thus, any of these factors could have exacerbated the effects of verapamil and esmolol on SA and AV node function.

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Recognition ECG monitoring is the definitive means of detecting bradycardia or AV conduction block. Sinus bradycardia (<60 beats per minute) or asystole is easily recognized on ECG. AV node or infranodal third degree conduction block requires closer ECG inspection (Fig. 11-1). With AV node or perinodal heart block, P waves are dissociated from the QRS complex, but with an AV junctional pacemaker and normal conduction through the ventricles. The QRS complex is of normal ~120 msec duration). In contrast, with infranodal width (~ block, conduction from latent pacemakers below the AV node or His bundle leads to wide QRS complexes. Other, less reliable methods of detecting bradycardia or heart block include the following: ●

●

●

Pulse oximetry plethysmographs reveal a reduced heart rate and possibly reduced arterial oxygen saturation. Capnography may show low end-tidal carbon dioxide values due to reduced pulmonary flow. Noninvasive blood pressure monitoring may reveal hypotension and a reduced heart rate or may simply provide a default “error” message.

Figure 11–1 ■ Atrioventricular (AV) block. Diagrammatic representation of the conduction pathology and resultant electrocardiogram. S-A, sinoatrial. (Adapted with permission from the American Heart Association: Textbook of Advanced Cardiac Life Support, 2nd ed. New York, AHA, 1990; and Netter FH: CIBA Collection of Medical Illustrations. West Caldwell, New Jersey, CIBA Medical Education Division, 1987.)

●

●

Invasive blood pressure monitoring reveals reduced frequency and possibly amplitude of the arterial waveform. Palpation of peripheral pulses indicates decreased frequency and intensity of the pulses.

Although these modalities can assist in assessing the hemodynamic impact of bradycardia, only ECG allows definitive diagnosis of its cause.

Risk Assessment Although the incidence of new intraoperative heart block is unknown, its incidence in animal and prospective clinical studies appears to be greater when antagonists and β-blockers are used in combination. The potential risk of developing bradyarrhythmias and AV node conduction disturbances in patients receiving β-blockers varies. It is greatest with verapamil, somewhat less with diltiazem, and least with dihydropyridine (DHP) calcium channel antagonists such as nicardipine, amlodipine, and nifedipine. DHP calcium channel antagonists have a much higher affinity for L-type Ca2+ channels in vascular smooth muscle as opposed to cardiac myocytes. Animal studies show synergism between the cardiac electrophysiologic effects of β-blockers and calcium channel antagonists (e.g., verapamil, diltiazem). When the latter are given at low doses, propranolol enhances their effect on heart rate and AV node conduction. When given at high doses

PHARMACOLOGY

Although this patient had third degree AV heart block and severe bradycardia, any condition within the spectrum of bradycardia (including asystole) could have occurred. Anesthesiologists must be prepared for this possibility with the appearance of severe bradycardia.

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with verapamil or diltiazem, propranolol causes significant heart block, hypotension, or left ventricular dysfunction. Clinical studies support the findings in animal models. In patients with chronic stable angina, therapy with a β-blocker and verapamil (versus diltiazem or nifedipine) causes a significant (10% to 15%) increase in the incidence of adverse cardiac or hemodynamic effects (bradycardia, heart block, hypotension, syncope, or congestive heart failure). However, diltiazem in combination with various β-blockers does not cause significant AV heart block, although it does increase the risk for P-R interval prolongation and bradycardia. Also, intraoperative bradycardia, first degree AV block, and AV junctional rhythms occurred more often in patients having coronary artery bypass graft surgery who took nonDHP calcium channel antagonists and β-blockers before surgery. Finally, transient AV block after aortic cross-clamp release during coronary artery bypass surgery was significantly increased in patients receiving preoperative propranolol (5% higher) or propranolol-nifedipine (15% higher). Patients whose medical treatment may include a β-blocker, calcium channel antagonist, or both are listed in Table 11-1. Other preoperative and intraoperative factors that place patients at increased risk for heart block during anesthesia and surgery are listed in Tables 11-2 and 11-3.

Implications Bradycardia with AV heart block can lead to severe hemodynamic compromise. In the absence of SA node activity, cardiac arrest is possible if perinodal or ventricular escape rhythms do not occur promptly. Severe hypotension due to reduced heart rate and lack of AV synchrony may cause myocardial ischemia. Heart failure may follow if cardiac output is not maintained by a compensatory increase in stroke volume. Hypotension, increased pulmonary artery pressure, and increased left ventricular end-diastolic pressure

Table 11–2

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Patient Populations Managed with β-Blockers or Calcium Channel Blockers

Coronary Artery Disease Chronic stable angina or previous myocardial infarction Native coronary arteries or autografts prone to spasm Perioperative management of myocardial ischemia in selected patients

Arrhythmias Prevention or treatment of supraventricular tachyarrhythmias (especially paroxysmal supraventricular tachycardia) Prevention or treatment of focal ventricular tachycardia in patients without structural heart disease (e.g., right ventricular outflow tract tachycardia, idiopathic left ventricular tachycardia*)

Cardiovascular Disease Hypertension Heart failure (β-blockers along with other drugs, such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers) Symptomatic patients treated with β-blockers for mitral valve prolapse *Focal ventricular tachycardias that originate in the left ventricular outflow tract, epicardium, or midseptum.

Preoperative Risk Factors for the Development of Intraoperative Heart Block

Age older than 60 years Chronic administration of β-blockers, calcium channel antagonists, amiodarone, or other drugs that prolong AV node or AV conduction (e.g., class IC antiarrhythmics, long-acting local anesthetics) Underlying conduction system disease (e.g., congenital heart disease, repair of atrial secundum defects, repair of transposition of the great vessels) Electrolyte or metabolic imbalance (e.g., hyperkalemia, hypothermia) Systemic disease (e.g., hypothyroidism-myxedema, intracardiac rheumatoid nodules, rheumatic heart disease) Preexisting heart disease (e.g., coronary artery disease, idiopathic degeneration or fibrosis, aortic or mitral valve surgery, Lyme disease, bacterial endocarditis, chagasic myocarditis,* calcific aortic stenosis) Preoperative bradycardia (<60 beats per minute) Myocardial infiltrative processes (e.g., sarcoidosis, amyloidosis, scleroderma) *Common in Central and South America. AV, atrioventricular.

have been observed in both animal and clinical studies of combined β-blocker and non-DHP calcium channel antagonist therapy.

MANAGEMENT After verification of third degree AV heart block and hemodynamic assessment, optimal oxygenation, ventilation, and perfusion are ensured by increasing the fraction of inspired

Table 11–3 Table 11–1

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Intraoperative Risk Factors Associated with the Development of Atrioventricular Heart Block

Drugs β-blockers Calcium channel antagonists High-dose volatile anesthetics or opiates IV anesthetic drugs (e.g., propofol, high-dose opiates, succinylcholine) Anticholinesterase therapy Digitalis glycosides IV amiodarone or sotalol Class IA or IB antiarrhythmic drugs, especially high IV doses

Increased Vagal Tone or Stimulation Peritoneal retraction or retraction of ocular muscles Direct laryngoscopy and endotracheal intubation Urinary bladder catheterization Esophageal instrumentation Baroreceptor reflex activation with acute hypertensive episodes (e.g., aortic cross-clamp application) Rectal or cervical dilatation

Imbalance Hypoxia Hypothermia Hyperkalemia

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● ●

● ● ● ●

●

● ● ● ● ●

Ephedrine 5 to 10 mg intravenously (IV); repeat if necessary Atropine 0.4 mg IV or glycopyrrolate 0.2 mg IV (up to a total of 2 or 1 mg IV, respectively, if necessary) Calcium 250 mg IV; repeat up to a total of 1 g if necessary Epinephrine 10 mg IV; repeat with increased doses as needed Isoproterenol 1 to 10 mg/minute IV Perform noninvasive (transcutaneous) pacing before instituting invasive transvenous pacing; noninvasive esophageal atrial pacing is ineffective in third degree AV block. Perform cardiopulmonary resuscitation if systolic blood pressure is 40 to 50 mm Hg (while attempting or repeating the above measures). Anticipate adverse drug interactions. Maintain hemodynamic stability. Perform intraoperative hemodynamic monitoring. Select drugs to treat tachycardia. Consider cardioversion in place of drugs for symptomatic supraventricular tachycardia.

PREVENTION The patient in the case synopsis developed third degree AV heart block after esmolol was given to control a rapid ventricular rate with atrial fibrillation. Her preexisting heart disease required the avoidance of extreme increases or decreases in heart rate to maintain hemodynamic stability and vital organ perfusion. Prevention of hemodynamic instability in such patients requires careful preoperative assessment, anticipation of adverse drug interactions, and attention to surgical or procedure-related interventions that might lead to wide fluctuations in heart rate or blood pressure. In addition to a thorough history and physical examination and the necessary laboratory tests, the preoperative assessment should include knowledge of the patient’s baseline heart rate, blood pressure, and intravascular volume status. Anesthesiologists should be able to anticipate adverse events and must be prepared to manage them early to minimize complications. Intraoperatively, care should be taken to ensure an adequate depth of anesthesia and analgesia and to maintain appropriate hydration. The placement of a Swan-Ganz catheter or intraoperative transesophageal echocardiography to monitor cardiac hemodynamic parameters should be considered for high-risk patients. If significant tachycardia develops in a patient receiving a non-DHP calcium channel antagonist, a reduced dose of esmolol (0.1 to 0.25 mg/kg) can be given to minimize any synergistic effect. To terminate

reentrant supraventricular tachycardia involving the AV node, adenosine (6 to 12 mg IV) can be used; it is an ultra-shortacting nucleoside with an efficacy equal to or better than that of the DHP calcium channel antagonists. Other alternatives are diltiazem (0.25 to 0.35 mg/kg IV), neostigmine (1 mg IV), edrophonium (10 mg IV), or phenylephrine (50 to 100 μg IV); vagal maneuvers (e.g., carotid sinus massage, Valsalva’s maneuver, ocular massage); or medications the patient is already receiving (e.g., verapamil 1.25 to 2.5 mg or digoxin 0.125 to 0.5 mg IV). Although synergistic effects with β-blockers are most often reported with verapamil, heart block is a theoretical possibility with any of the previously mentioned drugs, particularly when they depress AV node function by different cellular mechanisms. Finally, early direct-current cardioversion is the treatment of choice for atrial fibrillation or flutter causing hemodynamic compromise due to a rapid ventricular response.

Further Reading Atlee JL: Perioperative cardiac dysrhythmias: Diagnosis and management. Anesthesiology 86:1397-1424, 1997. Auerbach AD, Goldman L: Beta-blockers and reduction of cardiac events in noncardiac surgery: Scientific review. JAMA 287:1435-1444, 2002. Baraka AS, Taha SK, Yasbeck VK, et al: Transient atrioventricular block after release of aortic cross-clamp. Anesth Analg 80:54-57, 1995. Devereaux PJ, Beattie WS, Choi PT, et al: How strong is the evidence for the use of perioperative beta-blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials. BMJ 331:313-321, 2005. Henling CE, Slogoff S, Kodal SV, et al: Heart block after coronary artery bypass: Effects of chronic administration of calcium-entry blockers and β-blockers. Anesth Analg 63:515-520, 1984. Hoffman BB: Catecholamines, sympathomimetic drugs, and adrenergic receptor antagonists. In Hardman JG, Limbird LE (eds): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York, McGraw-Hill, 2001, pp 215-268. Kapur PA, Matarazzo DA, Fung OM, et al: The cardiovascular and adrenergic actions of verapamil or diltiazem in combination with propranolol during halothane anesthesia in the dog. Anesthesiology 66:122-129, 1987. Kerins DM, Robertson RM, Robertson D: Drugs used for the treatment of myocardial ischemia. In Hardman JG, Limbird LE (eds): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York, McGraw-Hill, 2001, pp 843-870. Krum H: Tolerability of carvedilol in heart failure: Clinical trials experience. Am J Cardiol 93:58B-63B, 2004. Lopez-Sendon J, Swedberg K, McMurray J, et al: Task Force on BetaBlockers of the European Society of Cardiology. Expert consensus document on beta-adrenergic receptor blockers. Eur Heart J 25: 1341-1362, 2004. McMurray JJ, Pfeffer MA: Heart failure. Lancet 365:1877-1889, 2005. Messerli FH, Grossman E: Beta-blockers in hypertension: Is carvedilol different? Am J Cardiol 93:7B-12B, 2004. Oates JA, Brown NJ: Antihypertensive agents and the drug therapy of hypertension. In Hardman JG, Limbird LE (eds): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York, McGraw-Hill, 2001, pp 871-900. Priebe HJ: Perioperative myocardial infarction—aetiology and prevention. Br J Anaesth 95:3-19, 2005. Schwartz AB, Moskowitz RM, Klausner SC: The electrophysiological effects of nicardipine hydrochloride in man. Can J Cardiol 3:14-17, 1987. Strauss WE, Parisi AF: Combined use of calcium-channel and beta-adrenergic blockers for the treatment of chronic stable angina: Rationale, efficacy, and adverse effects. Ann Intern Med 109:570-581, 1988.

PHARMACOLOGY

oxygen to 1.0 and discontinuing the use of volatile anesthetics. If the blood pressure and cardiac output are not adequate, cardiopulmonary resuscitation should be started immediately. The surgeon should discontinue any maneuvers that could increase vagal tone (e.g., peritoneal retraction) until the condition has been resolved. The treatment of mild (sinus bradycardia) to severe (asystole) complications includes the following:

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12

M. J. Pekka Raatikainen and Donn M. Dennis Case Synopsis A 76-year-old woman with a history of paroxysmal atrial fibrillation is admitted to the hospital for elective surgery. Her antiarrhythmic medication is 80 mg of sotalol twice daily. Before the operation, she has a sudden syncopal attack, and an electrocardiogram (ECG) shows a wide QRS self-terminating tachycardia.

PROBLEM ANALYSIS Definition The patient’s medical history and ECG (Fig. 12-1) are consistent with drug-induced Q-T prolongation and proarrhythmia. It is well known that prolongation of ventricular repolarization (i.e., long Q-T interval), the electrophysiologic basis for class III antiarrhythmic drug action, can paradoxically cause polymorphic torsades de pointes (TDP). TDP is a polymorphic ventricular tachycardia (VT) that occurs in the setting of Q-T interval prolongation; in the absence of Q-T prolongation, it is known as simply polymorphic VT. With TDP or polymorphic VT, the distinctive ECG pattern is characterized by a continuous twisting of the QRS axis around the isoelectric ECG baseline.

Although the precise mechanisms underlying TDP are unclear, most experimental and clinical evidence suggests that triggered activity initiated by early afterdepolarizations, along with delayed ventricular repolarization, provokes the onset of TDP. In general, TDP manifests as brief, repetitive episodes of self-terminating VT. Unabated, it can deteriorate into ventricular fibrillation.

Recognition The diagnosis of drug-induced long QT syndrome and TDP (see also Chapter 81) is based on the characteristic ECG findings and the patient’s medical history. In particular, special attention should be focused on concurrent use of other Q-T–prolonging drugs, including class IA antiarrhythmics (e.g., quinidine), macrolide antibiotics (e.g., erythromycin), nonsedating antihistamines (e.g., terfenadine), and psychotropic drugs (e.g., antipsychotics, tricyclic antidepressants). A more complete listing can be found at http:// www.torsades.org. ECG features of long QT syndrome include the following: ●

0.80 s

A Rhythm strip during the tachycardia

● ●

Prolonged ventricular repolarization (Q-Tc >0.44 second) Alternating T waves or prominent U waves Increased dispersion of ventricular repolarization (Q-T dispersion) ECG features of drug-induced TDP include the following:

●

0.56 s

B ECG (lead II) before the syncope Figure 12–1 A, Electrocardiogram (ECG) rhythm strip obtained from a 76-year-old woman immediately after syncope. Note the extremely long Q-T interval (0.80 second) immediately before the onset of the arrhythmia and twisting of the QRS axis around the isoelectric baseline during the tachycardia (220 beats per minute) (paper speed 25 mm/second). B, ECG (lead II) from the same patient showing a significant prolongation of the Q-T interval (Q-Tc = 0.56 second) during normal sinus rhythm (62 beats per minute) (paper speed 25 mm/second). After cessation of class III antiarrhythmic drugs (sotalol 80 mg twice daily), the Q-Tc interval returned to a value of 0.40 second.

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Polymorphic tachycardia (160 to 250 beats per minute), with characteristic twisting of the QRS axis around the isoelectric ECG baseline Characteristic “short-long-short” initiation sequence (i.e., R-R intervals) Initiation frequently caused by extra systoles with a long coupling interval

In patients with acquired long QT syndrome, TDP typically follows long pauses, whereas in patients with congenital (idiopathic) long QT syndrome, the initiation of TDP is commonly associated with an increase in catecholamines and heart rate (e.g., stress, fright, physical exercise).

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Risk Assessment Experience with the perioperative use of class III antiarrhythmic agents is limited, and there is little information on interactions between these drugs and anesthetic agents. The major perioperative complications related to long-term therapy with class III antiarrhythmics include proarrhythmia (e.g., TDP) and noncardiac amiodarone interactions and toxicity. The latter is discussed in more detail later in this chapter.

studies have yet to be conducted, one could speculate that anesthetics that reduce heart rate, depress atrioventricular (AV) node conduction, and lengthen ventricular repolarization might increase the proarrhythmic effects of class III antiarrhythmic drugs during surgery. Given the data indicating that patients with acquired long QT syndrome may suffer from variant forms of the congenital syndrome (e.g., electrically silent gene defects that manifest only with Q-T interval–prolonging drugs), genetic analyses of genes encoding the cardiac sodium and potassium channels may provide valuable information about the risk of drug-induced proarrhythmias. The following ECG findings before anesthesia indicate an increased risk for perioperative proarrhythmia: ● ● ● ● ● ●

Excessive prolongation of the Q-T interval Increased Q-T interval dispersion T-wave alternans or prominent U waves Polymorphic premature ventricular complexes Sinus bradycardia and AV conduction disturbances Abrupt slowing of the heart rate (e.g., conversion of atrial fibrillation to normal sinus rhythm)

PROARRHYTHMIC RISK

AMIODARONE INTERACTIONS

The following factors predispose to the development of class III antiarrhythmic drug-induced TDP during anesthesia:

Several groups have noted a greater incidence of cardiac rhythm and conduction disturbances (e.g., atropineresistant bradycardia, slow AV junctional rhythms, complete AV heart block, pacemaker dependency), an increased need for perioperative circulatory support (including inotropes or intra-aortic balloon counterpulsation), and more noncardiac complications in patients receiving amiodarone. However, perioperative hemodynamic instability with amiodarone and a poor response to inotropic drugs may be explained, in part, by the drug’s antiarrhythmic actions. In addition to class III activity, these include sodium channel blockade (class I), noncompetitive blockade of β- and α-adrenergic receptors (class II), and inhibition of calcium channels (class IV). The reader is referred to Chapters 10, 11, and 13, respectively, for complications related to these antiarrhythmic classes of drugs. The role of general anesthetic agents in the development of amiodarone’s pulmonary toxicity remains controversial. Although some groups have found a higher incidence of postoperative acute respiratory distress syndrome and other pulmonary disorders in patients receiving amiodarone, others have been unable to show this relationship. Nonetheless, pulmonary toxicity is the most feared long-term complication of amiodarone therapy and should not be forgotten in the risk assessment of patients receiving this drug.

● ●

● ● ●

●

Female gender Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, severe hypocalcemia) Structural heart disease and myocardial ischemia Excessive dosing Genetic defects behind the enzymes metabolizing the drug or defective cardiac ion channels responsible for congenital long QT syndrome (see Chapter 81) Drug interactions or simultaneous use of drugs that prolong ventricular repolarization

Critical values for Q-T prolongation are lacking. Available data indicate that Q-T dispersion (i.e., difference between the longest and shortest Q-T intervals assessed by 12-lead ECG) may predict the proarrhythmia more accurately than absolute Q-T interval prolongation or the latter corrected for heart rate (Q-Tc interval). For example, amiodarone—which, unlike the other class III agents, prolongs the Q-T interval uniformly (i.e., does not increase Q-T interval dispersion)—has a significantly lower proarrhythmic risk (2% to 3%) than the other class III antiarrhythmics (5% to 10%). Other factors that may explain amiodarone’s lower proarrhythmic risk compared with “pure” class III antiarrhythmics (which selectively inhibit cardiac potassium channels) include a heart rate–independent action on ventricular repolarization, and β-adrenergic blocking, α-adrenergic blocking, and calcium channel blocking properties. The incidence of TDP with amiodarone is only 0.7%, whereas sotalol and quinidine induce TDP in about 5% and 8% of cases, respectively. Further, in contrast to sotalol and ibutilide (a class III antiarrhythmic), acute intravenous amiodarone seldom if ever prolongs the Q-T interval. However, in the setting of electrolyte abnormalities, bradycardia, or abrupt changes in the heart rate, the proarrhythmic risk increases significantly. Thus, although definitive clinical

AND

TOXICITY

Implications Owing to their potent cardiac electrophysiologic properties, class III drugs not only exhibit important antiarrhythmic actions but also have the potential to induce life-threatening proarrhythmias, typically TDP. Therefore, anesthesiologists should be familiar with the adverse effects of these drugs and their interactions with other Q-T interval–prolonging drugs and anesthetics. Also, amiodarone has special implications in terms of pulmonary complications.

PHARMACOLOGY

Although TDP may present as a monomorphic VT in a single monitored ECG lead, confusion with monomorphic ventricular arrhythmias is rare when a 12-lead ECG is obtained. The characteristic “short-long-short” initiation sequence and the patient’s medical history help distinguish TDP from other forms of polymorphic VT. Importantly, these other forms of polymorphic VT occur without ECG evidence of Q-T interval prolongation, and often in the setting of an acute coronary syndrome (e.g., myocardial ischemia or infarction, reperfusion injury).

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MANAGEMENT Actions to take when treating drug-induced TDP include the following: ●

● ●

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Immediate electrical cardioversion in hemodynamically unstable patients Infusion of magnesium sulfate (MgSO4) Interventions that shorten the Q-T interval and prevent pause-dependent bradycardia (preferably atrial or ventricular overdrive pacing, or atropine or isoproterenol) Alleviation of electrolyte disturbances and bradycardia (preferably with temporary pacing) and other permissive factors Withdrawal of any offending drugs, along with correction of imbalance

Therapy of drug-induced TDP must focus on immediate TDP termination and the prevention of early recurrence. If TDP causes early hemodynamic collapse, it must be treated with prompt direct-current cardioversion or defibrillation, depending on whether the ECG R or S waves are distinct (cardioversion) or not (defibrillation). Other therapy includes intravenous MgSO4, which is effective against TDP even in patients with normal serum magnesium levels. MgSO4 is given as a 1- to 2-g intravenous bolus. If necessary, it is repeated after 10 to 15 minutes, followed by continuous intravenous infusion at 3 to 20 mg/minute for 24 to 48 hours. If this is ineffective, atropine, isoproterenol, or overdrive pacing is used to prevent long sinus pauses to shorten the Q-T interval. Isoproterenol infused at a dose that maintains the ventricular rate at about 90 beats per minute (1 to 8 μg/minute) may suppress TDP within minutes. However, given this drug’s proarrhythmic actions and other adverse effects, isoproterenol should be used only while pacing is instituted, especially in patients with ischemic heart disease. Preferably, temporary atrial or ventricular overdrive pacing is initiated at a rate of 120 to 130 beats per minute and adjusted to the lowest effective rate. Temporary pacing should be continued until the offending drug is completely eliminated. The role of antiarrhythmic drugs in the treatment of TDP is controversial. In experimental preparations and in some patients, calcium channel blockers, lidocaine, mexiletine, and recently developed potassium channel openers (e.g., nicorandil, pinacidil) have been effective. However, the clinical evidence is marginal and has yet to be verified in large prospective clinical studies. Drugs that prolong ventricular repolarization should be avoided in the therapy of acquired long QT syndrome. Once acute TDP episodes have been controlled, attention should focus on identifying and correcting predisposing metabolic and electrolyte factors and eliminating causative drugs. In patients with congenital long QT syndrome, β-blockers are the drugs of choice, and catecholamines must be avoided. Patients receiving class III antiarrhythmics, especially amiodarone, may be more vulnerable to the development of perioperative bradycardia, AV node conduction disturbances, and circulatory failure. If these conditions do not respond

to atropine, adrenergics, or other positive chronotropes, cardiac pacing or intra-aortic counterpulsation should be instituted.

PREVENTION Prevention includes the following measures: ●

●

●

●

●

Identify and correct any factors that predispose patients to proarrhythmia (e.g., electrolyte imbalance, bradycardia, myocardial ischemia). Stop any drugs that prolong the Q-T interval (e.g., macrolide antibiotics, nonsedating antihistamines, tricyclic antidepressants). Consider reassessing the dosage or withdrawing class III antiarrhythmics and postponing elective operations, especially if the Q-Tc is greater than 0.60 second. Consider regional anesthesia in patients receiving amiodarone. Monitor hemodynamic and respiratory functions throughout the perioperative period.

Q-T prolongation with class III antiarrhythmic drugs is a therapeutic end point. Mechanisms by which this effect becomes proarrhythmic are not easily separated from antiarrhythmic actions. Thus, the cornerstone of preoperative risk reduction in patients receiving class III antiarrhythmics is identification and elimination of predisposing risk factors. Of special importance is correction of electrolyte imbalance and withdrawal of drugs that cause additional Q-T interval prolongation (e.g., macrolide antibiotics, nonsedating antihistamines, tricyclic antidepressants). Likewise, patient reassurance and adequate sedation and analgesia can eliminate preoperative catecholamine increases and help prevent abrupt changes in heart rate during the induction of anesthesia. Amiodarone is the most effective intravenous antiarrhythmic for life-threatening arrhythmias. However, its extremely long elimination half-life and serious adverse extracardiac effects (especially with chronic therapy) make it the most complicated of the class III agents. Importantly, amiodarone significantly augments the cardiac depressant effects of general anesthesia. In addition, amiodaroneassociated pulmonary toxicity may become apparent during emergence and recovery from general anesthesia. Attention to these shortcomings and careful intraoperative monitoring of respiratory and hemodynamic parameters should help anesthesiologists avoid these severe complications. Some case reports suggest that regional anesthesia is preferable in patients receiving amiodarone, but this remains to be confirmed in controlled clinical studies. Likewise, although some experimental data suggest that intravenous anesthetics have different effects on ventricular repolarization in acquired (drug-induced) long QT syndrome, until clinical trials are completed, no specific advice can be given on the selection of general anesthetics for patients receiving class III antiarrhythmics. Finally, because most patients receiving class III agents have severe arrhythmias and other cardiac disease, it is prudent to consult a cardiologist before anesthesia and surgery.

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Atlee JL: Perioperative cardiac dysrhythmias: Diagnosis and management. Anesthesiology 86:1397-1424, 1997. Balser JR: The rational use of intravenous amiodarone in the perioperative period. Anesthesiology 84:974-987, 1997. Belardinelli L, Antzelevitch C, Vos MA: Assessing predictors of drug-induced torsades de pointes. Trends Pharmacol Sci 24:619-625, 2003. Haverkamp W, Breithardt G, Camm AJ, et al: The potential for QT prolongation and proarrhythmia by non-antiarrhythmic drugs: Clinical and regulatory implications. Report on a policy conference of the European Society of Cardiology. Eur Heart J 21:1216-1231, 2000.

Priori SG, Napolitano C: Genetic defects of cardiac ion channels: The hidden substrate for torsades de pointes. Cardiovasc Drugs Ther 16: 89-92, 2002. Roden DM: Drug-induced prolongation of the QT interval. N Engl J Med 350:1013-1022, 2004. Shah RR: Pharmacogenetic aspects of drug-induced torsades de pointes: Potential tool for improving clinical drug development and prescribing. Drug Saf 27:145-172, 2004. Viskin S, Justo D, Halkin A, et al: Long QT syndrome caused by noncardiac drugs. Prog Cardiovasc Dis 45:415-427, 2003. Wolbrette DL: Risk of proarrhythmia with class III antiarrhythmic agents: Sex-based differences and other issues. Am J Cardiol 91:39D-44D, 2003.

PHARMACOLOGY

Further Reading

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13

J. Michael Jaeger and Donn M. Dennis Case Synopsis An obese 48-year-old woman with a history of hypertension treated with diltiazem undergoes a laparoscopic cholecystectomy. Following insufflation of the abdomen with carbon dioxide, she becomes hypertensive and develops sinus tachycardia at a rate of 110 beats per minute; the tachycardia is unresponsive to deepening the level of anesthesia with isoflurane and fentanyl. Propranolol 1 mg is administered intravenously. The patient develops a marked sinus bradycardia, with a P-R interval of 0.24 second on the electrocardiogram (ECG), and becomes hypotensive.

PROBLEM ANALYSIS Definition This case illustrates many of the common toxic effects of L-type (long-lasting) calcium channel antagonists (specifically the class IV antiarrhythmic drugs verapamil and diltiazem) or of interactions between calcium channel antagonists and other cardiodepressant drugs. The marked bradycardia, first degree atrioventricular (AV) node block, and hypotension are manifestations of the pharmacologic interaction of several drugs, most notably diltiazem and propranolol. Each drug has a depressive effect on conduction in both the sinoatrial (SA) node and the AV node, although by different cellular mechanisms. However, both diltiazem and propranolol have little effect on ventricular conduction (Fig. 13-1). Although therapeutic doses of diltiazem and propranolol by themselves generally do not produce this magnitude of response, the concurrent use of a calcium channel antagonist and a β-receptor antagonist can lead to cardiovascular collapse, particularly when other cardiac depressants (e.g., volatile inhalational anesthetics) are involved. Such patients require heightened vigilance by anesthesiologists because AV node conduction blockade can reduce the compensatory reflex increase in cardiac output observed with pathophysiologic conditions (e.g., hypercarbia, hypoxemia, hypovolemia, anemia). In addition to SA and AV node conduction block, this drug combination can precipitate acute heart failure in patients with cardiac disease and limited functional reserve. Both L-type (e.g., verapamil, diltiazem, nifedipine) and T-type (transient) calcium channel antagonists (e.g., mibefradil) have been implicated as the cause of adverse drug interactions. They alter the pharmacokinetics and pharmacodynamics of a wide variety of drugs, including carbamazepine, neuromuscular blockers, digoxin, quinidine, statins, theophylline, and volatile inhalational anesthetics (Table 13-1). 48

Recognition The toxic effects of class IV antiarrhythmic drugs, or their interactions with other depressants of cardiac conduction, can be recognized by the following ECG features: ● ●

● ●

Sinus bradycardia (<60 beats per minute) P-R intervals greater than 0.2 second (first degree block) or P waves not always followed by QRS complexes (second degree block) Normal QRS complex duration (£ 0.1 second) Normal Q-T interval relationships and ST segment configurations unless myocardial ischemia is present

Note that the QRS complex and ST segment remain normal in duration and configuration. This distinguishes direct toxicity by class IV antiarrhythmics or indirect toxicity through their interaction with other depressants of myocardial conduction (e.g., β-blockers) from other disturbances of conduction (e.g., bundle branch or fascicular block, myocardial ischemia). In addition, the interaction of calcium channel antagonists with other drugs should not be confused with preexisting conditions that can have a similar clinical presentation. For example, sick sinus syndrome, preexisting AV node block of varying degrees, amyloidosis, myotonic dystrophy, or cardiomyopathy may confound the ECG diagnosis, although the clinical history and presentation should allow clarification.

Risk Assessment The following factors influence the risk of toxicity: ● ● ●

Therapeutic spectrum Clinical pharmacology Mechanism of action

Verapamil and diltiazem are widely used to treat and prevent supraventricular tachycardias, to limit ventricular rates with atrial fluttter or fibrillation, and as adjuncts for the

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SA Node Action Potential Purkinje Fiber Action Potential (Bundle Branch)

SA Node ↓ conduction

Verapamil & AV Node Diltiazem ↓↓ conduction His Bundle/Bundle Branches AV Node Action Potential

↓ contractility

Table 13–1

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Verapamil & Diltiazem

Selected Drug Interactions with Calcium Channel Antagonists

Drug Antiarrhythmics Amiodarone (AM)

Adenosine Quinidine β-Blockers Atenolol Metoprolol Propranolol Carbamazepine Clonidine Cyclosporine Digoxin Lithium Magnesium sulfate Midazolam Phenytoin Quinidine Rifampin Statin drugs Succinylcholine Theophylline Vecuronium Volatile anesthetics Desflurane Enflurane Halothane Isoflurane Sevoflurane

49

Nature of Interaction

Effect of Interaction

Possible potentiation of AM class IV activity at SA and AV nodes* Possible increase in L-type Ca2+ channel block by AM in vascular smooth muscle* Additive effect ↓ Clearance

AV node block and hypotension; possible bradycardia Prolonged bradycardia AV node block

Noncompetitive Potentiation Potentiation ↓ Clearance Additive effect ↑ Serum concentration Modest ↑ serum concentration Synergism Potentiation ↓ Clearance ↑ Serum concentration ↑ Serum concentration ↑ Clearance of verapamil ↑ Serum concentration Potentiation ↓ Clearance Potentiation

Hypotension; AV node block Hypotension; AV node block Hypotension; AV node block Neurotoxicity; Hypotension; AV node block Nephrotoxicity AV node block Muscle weakness, ataxia Muscle weakness, hypotension Profound and prolonged sedation Neurotoxicity Potentiate hypotensive effects Supraventricular tachycardia Rhabdomyolysis Possible prolonged effect Theophylline toxic effects Prolonged neuromuscular block

Unknown† (possible ↓ heart rate?) Potentiation Potentiation Potentiation Unknown

No reported interactions in humans† Rare AV node block ↓ Cardiac output, AV node block No significant interactions in humans No reported interactions in humans†

*Speculation. † MEDLINE database search Sept 27, 2005: no reports of adverse interactions in animal models or humans. AV, atrioventricular; SA, sinoatrial.

PHARMACOLOGY

Figure 13–1 ■ Cardiac conduction system, with examples of “slow-response” action potentials recorded from the sinoatrial (SA) and atrioventricular (AV) nodes and a “fast-response” action potential recorded from a Purkinje fiber in a bundle branch. Note the smaller action potential upstrokes characteristic of slow-conducting SA and AV node (i.e., slow-response) cells versus the much faster and larger action potential upstroke typical of fast-conducting (i.e., fast-response) Purkinje fibers. Atrial and ventricular muscle fibers also have fast-response action potentials (not shown), similar to those of Purkinje fibers. Verapamil and diltiazem have a greater impact on the conduction of slow-response action potentials in the heart. Contractility is also reduced because of the reduced influx of calcium ions during the cardiac action potential plateau.

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treatment of vasospastic angina and essential hypertension. Although the probability of having to administer an anesthetic to a patient taking either of these calcium channel antagonists is high, actual clinical experience reveals that doing so is generally not a significant problem for anesthesiologists. Nonetheless, the potential for problems exists, and vigilance is important. In large clinical trials, verapamil and diltiazem caused the following cardiovascular abnormalities, in decreasing order of frequency: first degree AV block (2.4%), bradycardia (1.7%), second or third degree AV block (0.8%), and congestive heart failure (<1% to 1.8%). Understanding the clinical problem and identifying patients at risk for complications require an appreciation of the relevant cardiac electrophysiology and pharmacology of all classes of calcium channel antagonists. Six types (T, L, N, P/Q, and R) of mammalian voltage-dependent calcium channels (VDCCs) have been identified. They are distinguishable by location and electrophysiologic characteristics (voltage thresholds for activation; kinetics of channel opening and closing). VDCCs have been classified into two general groups: (1) high-voltage-activated (HVA) calcium channels (threshold activation = −40 to −10 mV), and (2) low-voltage-activated (LVA) calcium channels (threshold activation = −60 to −70 mV). HVA channels include calcium channels of the L, N, P/Q, and R types, whereas LVA channels include only the T type. At times, the R-type channel is classified as an intermediate voltage activated (IVA) calcium channel with threshold activation voltages being intermediate between those of HVA and LVA. Key characteristics of the different types of calcium channels include the following: ●

●

●

●

●

●

T-type calcium channels include a heterogeneous group of Transient (or low voltage) activated–type calcium channels, which are primarily located in the SA and AV nodes, cardiac Purkinje cells, and central nervous system. L-type calcium channels are Long-lasting voltage-gated channels located in both excitable and nonexcitable tissue, which are responsible for normal myocardial and vascular smooth muscle contractility. The alpha-1 subunit of L-type calcium channel is the binding site for calcium channel blockers (e.g., dihydropyridine [DHP]-based calcium channel antagonists. N-type calcium channels are widely distributed in Neural tissue. Omega toxins inhibit the function of these types of calcium channels by changing their voltage dependence. P-type calcium channels were first identified within the Purkinje cells of the cerebellum. They play a role in regulating neuronal stimulation-secretion coupling. Q-type calcium channels are located in neurons. Because Q- (letter derived from the following letter of P) type current is rapidly inactivated, it requires prior blockade of P- and N-type calcium current components to isolate this current for study. R-type calcium channels are located in neurons. They are inhibited by the marine snail toxin, omega conotoxin MVIIC. A notable feature of the R-type channels is their resistance to all known calcium channel blockers. The R-type current (which was named after the following letter of Q, or Remaining channel) is defined as the residual

HVA calcium current observed after the application of toxins that selectively block N, L, P, and Q-type currents. Calcium channels in cardiac muscle and vascular smooth muscle cells are generally of the T and L types, which impart distinct characteristics to the cardiac action potential and influx of calcium into the cell. The T-type channel contributes significantly to the slow upstroke of the action potential found in the SA and AV nodes and, therefore, controls one of the pacemaker currents responsible for the initiation of the heartbeat. This channel exists in ventricular muscle but plays a less significant role in initiating the action potential. The L-type calcium channel produces the plateau of the cardiac action potential and is responsible for the influx of extracellular Ca2+ into the cell. This influx of extracellular Ca2+ is thought to serve as the trigger for the release of internally stored (sarcolemmal) Ca2+. The latter leads to cardiac contraction. The entire process is known as excitation-contraction coupling. Verapamil and diltiazem alter the function of L-type but not T-type calcium channels. Hence, they have a greater impact on the conduction and repolarization of cardiac action potentials (especially within the SA and AV nodes) and on the influx of extracellular Ca2+ than they do on the initiation of cardiac (or smooth) muscle action potentials (see Fig. 13-1). At first, this might seem counterintuitive, given that sinus bradycardia is occasionally observed with verapamil (less often with diltiazem). However, for heartbeats to occur, the SA node must first generate an action potential. In turn, it must be propagated to surrounding atrial muscle and the rest of the heart in a properly synchronized fashion. As more and more L-type calcium channels become blocked, SA node impulse formation slows, and SA conduction and refractoriness increase. Together, these lead to failure of SA node impulse formation and propagation. Reduction of the magnitude of extracellular Ca2+ influx— through fewer functional L-type calcium channels or a shorter duration of their open state—also reduces the strength of cardiac contraction. Because L-type calcium channels are also found in vascular smooth muscle, inhibition of excitation-contraction coupling here leads to vasodilatation. Whereas verapamil affects primarily cardiac L-type calcium channels, diltiazem affects L-type calcium channels in both cardiac and vascular smooth muscle. Finally, the dihydropyridine (DHP) calcium channel blockers (e.g., nifedipine, nicardipine, nimodipine) are highly selective for L-type calcium channels in vascular smooth muscle. Among the L-type calcium channel blockers, verapamil (a diphenylalkylamine) and diltiazem (a benzothiazepine) markedly depress AV node conduction and increase refractoriness, whereas the DHP calcium channel blockers mentioned earlier are primarily vasodilators and have minimal to no effect on SA or AV node tissue or cardiac contractility. Verapamil and diltiazem are useful for treating reentrant supraventricular tachycardias involving the AV node and for achieving ventricular rate control in most patients with atrial flutter or fibrillation. They are also used as therapy for essential hypertension and chronic stable angina, especially vasospastic angina. However, DHP calcium channel blockers are increasingly used in these conditions, especially for patients who are also receiving β-blockers.

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Increased AV node refractoriness with non-DHP calcium channel blockers increases the risk for high-degree AV block when combined with other drugs that also slow AV node conduction. Although this list is lengthy, it includes any drugs that are vagomimetic (e.g., opioids, anticholinesterases, digoxin) or sympatholytic (β-receptor antagonists, clonidine), as well as other drugs (e.g., adenosine, amiodarone, volatile inhalational anesthetics). Accentuation of high-degree AV heart block can lead to cardiovascular collapse. Also, because non-DHP calcium channel blockers have the potential to increase the ventricular rate with atrial flutter or fibrillation and precipitate fatal ventricular tachyarrhythmias, diltiazem or verapamil should not be used in patients with Wolff-Parkinson-White syndrome or its variants, especially when the state of accessory pathway refractoriness is unknown. Essentially, accessory pathways are extensions of atrial muscle and have similar electrophysiologic properties (i.e., they are “fast-response” fibers). Thus, accessory pathway conduction is not blocked, nor is its refractoriness increased. However, both conduction and refractoriness at the AV node are impaired by diltiazem or verapamil. Because low-dose non-DHP calcium channel blockers (diltiazem more so than verapamil) cause vascular relaxation and hypotension before significant AV node block, reflex tachycardia can occur and cause angina in susceptible patients with nonvasospastic (fixed) coronary artery disease. Also, patients with limited cardiovascular reserve (i.e., cardiomyopathy) are at risk for acute worsening of heart failure when subjected to the additional negative inotropic effect of non-DHP calcium channel blockers. Last, aside from their cardiac effects, calcium channel blockers may significantly inhibit hepatic cytochrome enzymes and alter hepatic or renal blood flow and drug binding. Thus, the pharmacologic properties of a wide variety of drugs may be affected (see Table 13-1). This problem was most pronounced with mibefradil, a T-type calcium channel blocker that was developed for the treatment of hypertension and chronic stable angina. Because mibefradil was a very potent inhibitor of CYP3A4, the single most important P-450 enzyme for metabolizing therapeutic agents, it caused many severe adverse drug reactions and was removed from the market. One interesting drug-drug interaction with mibefradil was increased blood levels of HMG-CoA reductase inhibitors (statin cholesterol-lowering agents) that depended on CYP3A4 for metabolic clearance (e.g., lovastatin, simvastatin, atorvastatin), leading to severe rhabdomyolysis.

MANAGEMENT Because bradycardia, AV block, and hypotension can occur in patients receiving regional or general anesthesia, the first step is to determine the level of consciousness and then the adequacy of the airway and ventilation. Administer 100% oxygen and, if bradycardia is hemodynamically significant, immediately send for a transcutaneous or transvenous pacing device. Transesophageal atrial pacing is ineffective with

high-degree (second or third degree) AV node block. Secure the airway if necessary. In the interim, attempt to reduce as many negative chronotropic, dromotropic, and inotropic influences as possible by decreasing (or turning off) the inspired concentration of volatile inhalational agents and ceasing the manipulation of any organs (e.g., bowel, reproductive organs, eyes) known to elicit vagal responses. Atropine can be given as a first-line drug to reduce vagal tone and enhance SA and AV node conduction. If the patient remains hypotensive and does not respond to atropine, β-sympathomimetic drugs, such as epinephrine or isoproterenol, are used to enhance SA and AV node conduction if pacing is not yet available, especially if reduced myocardial contractility is evident. Intravenous calcium chloride has been used successfully in cases of deliberate verapamil overdose. In some cases, high-degree AV heart block resistant to pharmacologic intervention may require cardiac pacing. Once stabilized, the patient requires prolonged monitoring because the α-elimination half-life of calcium channel blockers ranges from 10 to 35 minutes (depending on age), and the β-elimination half-life is 5 to 12 hours. Depending on the duration of calcium channel blocker therapy, the latter parameter is variable and may increase to 16 hours or more with hepatic insufficiency.

PREVENTION Prevention relies on a full understanding of the patient’s underlying pathophysiology and the effects of all concurrent drugs, including antiarrhythmics, calcium channel blockers, β-adrenergic blockers, opiates, and digitalis; automaticity of the sinus node; subsidiary atrial, AV junctional, or ventricular escape pacemakers; electrophysiologic properties of specialized atrial, AV, and ventricular conducting tissues (i.e., conduction times and refractoriness); and potential interactions with any drugs used during anesthesia or in perioperative settings. Take the following specific precautions: ●

●

●

●

●

Assess the patient’s history (duration of drug use, dose, side effects, response). Determine the presence of heart failure or arrhythmias by a focused cardiac and pulmonary examination, and assess a 12-lead ECG for arrhythmias and AV conduction abnormalities. Use caution if block of the cardioaccelerator nerves is anticipated (e.g., activation of vagal, cardioinhibitory reflexes), and evaluate whether regional anesthesia might be preferable to intravenous or inhalation general anesthesia. If inhalation anesthesia is chosen, isoflurane, sevoflurane, or desflurane is preferable to enflurane or halothane in patients receiving calcium channel blockers (or β-adrenergic blockers). Use careful opiate dosing. Use of muscle relaxants must be guided by neuromuscular function monitoring.

Many patients receiving calcium channel blockers have successfully undergone a variety of surgical procedures under both regional and general anesthesia. Although the

PHARMACOLOGY

Implications

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safety of these drugs in perioperative settings is supported by the paucity of reports of adverse outcomes, calcium channel blockers have a recognized potential to cause significant adverse events in perioperative settings. Given recent clinical trials showing the safety and efficacy of calcium channel blockers for the treatment of cardiovascular disease, anesthesiologists can expect to see a substantial increase in the number of patients receiving these drugs. Large prospective, controlled clinical trials (e.g., the INVEST trial) have shown that (1) for patients with hypertension, therapy with calcium channel blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers reduces the risk for diabetes more effectively than does therapy with β-blockers and diuretics; and (2) for patients with hypertension and coronary artery disease, therapy with sustainedrelease verapamil or trandolapril was as clinically effective as atenolol-hydrochlorothiazide.

Further Reading Altier C, Zamponi GW: Targeting Ca2+ channels to treat pain: T-type versus N-type. Trends Pharmacol Sci 25:465-470, 2004. Atlee JL: Perioperative cardiac dysrhythmias: Diagnosis and management. Anesthesiology 86:1397-1424, 1997.

Atlee JL, Hamann SR, Brownlee SW, et al: Conscious state comparisons of the effects of the inhalation anesthetics and diltiazem, nifedipine, or verapamil on specialized atrioventricular conduction times in spontaneously beating dog hearts. Anesthesiology 68:519-528, 1988. Bakris GL, Gaxiola E, Messerli FH, et al: Clinical outcomes in the diabetes cohort of the International Verapamil SR-Trandolapril [INVEST] study. Hypertension 44:637-642, 2004. Durant NN, Nguyen N, Katz R, et al: Potentiation of neuromuscular blockade by verapamil. Anesthesiology 60:298-303, 1984. Elmslie KS: Neurotransmitter modulation of neuronal calcium channels. J Bioenerg Biomembr 35:477-489, 2003. Opie L: Calcium channel antagonists in the treatment of coronary artery disease: Fundamental pharmacological properties relevant to clinical use. Prog Cardiovasc Dis 38:273-290, 1996. Packer M, Meller J, Medina N, et al: Hemodynamic consequences of combined beta-adrenergic and slow calcium channel blockade in man. Circulation 65:660-668, 1982. Pepine CJ, Cooper-Dehoff RM: Cardiovascular therapies and risk for development of diabetes. J Am Coll Cardiol. 44:509-512, 2004. Reves JG, Kissin I, Lell W, et al: Calcium entry blockers: Uses and implications for anesthesiologists. Anesthesiology 57:504-518, 1985. Rosenthal T, Ezra D: Calcium antagonists: Drug interactions of clinical significance. Drug Saf 13:157-187, 1995.

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Disorders of Potassium Balance

REGIONAL ANESTHESIA & PAIN PHARMACOLOGY MANAGMENT

ADJUNCT THERAPY

14

John L. Atlee and Kai T. Kiviluoma Case Synopses Hypokalemia A 56-year-old man with chronic renal failure underwent cardiopulmonary bypass (CPB) for coronary artery revascularization. His pre-CPB serum potassium (K+) concentrations ranged between 5.5 and 6.6 mEq/L. After separation from CPB, the patient had frequent premature atrial beats and nonsustained ectopic atrial tachycardia (≤15 seconds). Lead II of the monitored electrocardiogram (ECG) revealed prominent U waves (Fig. 14-1). Repeated post-CPB serum K+ concentrations were 4.5 and 4.7 mEq/L. Hyperkalemia A 74-year-old man with severe coronary artery disease had coronary artery bypass grafting with five distal anastomoses. Because of impaired myocardial function (ejection fraction 22%), a high-dose glucose-insulin-potassium infusion was started intraoperatively. Postoperatively the patient was hemodynamically stable, and he was extubated 12 hours after surgery. However, 2 days later, ventricular arrhythmias, peaked T waves, and transient second degree atrioventricular (AV) block developed.

PROBLEM ANALYSIS Definition HYPOKALEMIA There is a lack of consensus over what constitutes hypokalemia. Although a number of studies have addressed this issue, many fall short because (1) a single K+ value is not confirmed, (2) there is no information regarding the patient’s usual range of K+ values (i.e., is the hypokalemia acute or chronic?), and (3) possible confounding effects of concurrent diseases and other metabolic imbalances are not considered. As the case synopsis illustrates, the reported “normal” serum K+ values may be misleading unless interpreted within the context of the patient’s history and clinical status. Notably, the patient has ECG changes and arrhythmias consistent with hypokalemia, despite seemingly “normal” serum K+ concentrations of 4.5 and 4.7 mEq/L.

speed of repolarization and reduce action potential duration. In moderate hyperkalemia, these actions may even reduce the likelihood for arrhythmias. The increase in K+ permeability with hyperkalemia decreases the rate of spontaneous diastolic (phase 4) depolarization in the sinus node and subsidiary pacemakers to cause bradycardia and even asystole at very high extracellular K+ concentrations. AV and intraventricular conduction abnormalities are also observed with severe hyperkalemia. This latter group of patients has

ECG

ECG

ART

HYPERKALEMIA With regard to the patient described in the case synopsis, it is probable that after stopping glucose-insulin treatment, a new balance between intracellular and extracellular K+ concentrations was established. Because up to 98% of the total body potassium pool is located intracellularly, dramatic changes in serum K+ may be observed. Normal values for serum K+ range from 3.5 to 5.3 mEq/L. Hyperkalemia increases myocardial membrane permeability to K+ to increase the

PAP

Figure 14–1 ■ Electrocardiogram changes after separation from cardiopulmonary bypass. Note the prominent U waves (arrows). (From Atlee JL: Arrhythmias and Pacemakers. Philadelphia, WB Saunders, 1996, p 90.)

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a very high risk of developing fatal arrhythmias, including persistent ventricular fibrillation or asystole. Excessive serum K+ concentrations not only profoundly affect the electrical properties of the heart but also cause severely depressed myocardial contractility. These myocardial effects of hyperkalemia are potentiated in patients with concomitant hypocalcemia or hyponatremia.

Recognition HYPOKALEMIA Low serum K+ concentrations can exist without significant associated ECG changes. The following are common ECG changes with acute hypokalemia (serum K+ ≤ 3.0 mEq/L) in normokalemic patients (serum K+ 3.5 to 4.5 mEq/L): ●

●

● ● ●

The appearance of U waves (see Fig. 14-1, lead II), which may fuse with T waves to cause apparent Q-T interval prolongation “Bowl-shaped” (concave or scooped) ST segment depression (see the last four QRS complexes in Fig. 14-1, lead II) Increased amplitude of QRS complexes (see Fig. 14-1, lead II) Flattened or inverted T waves Arrhythmias: atrial or ventricular extrasystoles or ectopic atrial tachycardia

plasma K+ concentrations exceed 5.5 mEq/L (Fig. 14-2). These T-wave changes are seen most clearly in the precordial leads of the ECG. With more severe hyperkalemia, the P-Q interval is prolonged, the QRS amplitude is decreased, and the QRS interval widens (usually seen at potassium concentrations > 6.5 mEq/L). Ultimately, the P wave disappears. With preterminal hyperkalemia, the markedly widened QRS complex merges with the T wave, giving the ECG a “sine-wave” appearance (see Fig. 14-2). Ventricular flutter, fibrillation, or asystole usually ensues shortly thereafter. The correlation between the degree of hyperkalemia and tissue effects is better at higher K+ concentrations than at lower ones. Thus, widening of the QRS complex more reliably predicts serum K+ levels than does peaking of the T wave. Although ECG changes can be detected during the early phase of hyperkalemia, a high index of clinical suspicion and serial measurement of serum K+ concentrations are essential for the definitive diagnosis of hyperkalemia and to avoid the morbidity and mortality associated with it.

Aside from arrhythmias and ECG changes, hypokalemia can affect cardiovascular, central nervous system, neuromuscular, renal, or metabolic function (Table 14-1). HYPERKALEMIA To recognize hyperkalemia, one must be aware of the possibility. It is confirmed by measuring serial serum K+ concentrations. Also, the ECG is analyzed for the following features: ● ●

●

Peaking and narrowing of the T wave Progressive widening of the QRS complex as hyperkalemia worsens Prolongation of the P-Q and disappearance of P waves

The earliest manifestation of hyperkalemia is peaking and narrowing of the T wave. This is usually observed when Table 14–1

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Effects of Hypokalemia

Cardiovascular Autonomic neuropathy with postural hypotension Impaired contractility and vasopressor responses Potentiation of toxic effects of digitalis

Neuromuscular and Central Nervous System Potentiation of neuromuscular blockade Weakness and lethargy Peripheral neuropathy and hyporeflexia Respiratory depression Confusion and depression

Renal and Gastrointestinal Polyuria; reduced urine concentrating ability Hypoperistalsis

Metabolic Glucose intolerance Potentiation of hypomagnesemia and hypocalcemia

Figure 14–2 ■ Schematized electrocardiogram (ECG) changes accompanying acute changes in serum potassium (K+) concentration. Note flattening of the T wave and prominent U waves with hypokalemia. As the serum K+ increases toward hyperkalemia, there is a small reduction in the QRS amplitude, QRS complex widening, P-R interval prolongation, reduced P-wave amplitude, and increased T-wave amplitude. Finally, the QRS and T waves merge, giving the ECG a sine-wave appearance. (From Sandøe E, Sigurd B: Arrhythmia. St. Galen, Belgium, Fachmed AG, 1984, p 403.)

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Table 14–2

HYPOKALEMIA Hypokalemia is more likely than hyperkalemia to cause clinically important arrhythmias. It often results from excessive dialysis, thiazide or loop diuretics, mechanical hyperventilation, or therapy with insulin or β-adrenergic agonists. Cellular repolarization abnormalities and loss of transmembrane potential with hypokalemia alter cardiac conduction and refractoriness to facilitate reentry. They are also conducive to disturbed automaticity or triggered activity. Arrhythmias caused by severe hypokalemia resemble those accompanying digitalis toxicity (see Chapter 7) and likely have similar mechanisms. Arrhythmias include atrial and ventricular extrasystoles, ectopic atrial tachycardia, reentrant (paroxysmal) supraventricular tachycardia, and AV heart block. These are not caused by changes in serum K+ concentration per se, but rather by changes in the ratio between intra- and extracellular K+. This is the most important determinant of resting cell membrane potential and cellular electrophysiologic properties. Only extreme extracellular K+ changes (<2.7 or >10 mEq/L) significantly depolarize cell transmembrane potential in atrial, Purkinje, or ventricular muscle fibers. However, loss of transmembrane potential is conducive to automatic, triggered, or reentrant arrhythmias. Between these values, transmembrane potential increases toward more normal values. Further, electrophysiologic changes due to K+ imbalance are likely heterogeneous, with some cells or tissues affected more than others. Thus, the patient described in the first case synopsis was likely relatively hypokalemic, because his pre-CPB serum K+ concentrations ranged from 5.5 to 6.5 mEq/L. Indeed, treatment with intravenous potassium chloride (KCl) restored this patient’s serum K+ concentration to his normal range and abolished the U waves, ectopic atrial beats, and nonsustained ectopic atrial tachycardia. HYPERKALEMIA Causes of hyperkalemia are listed in Table 14-2. Surgery or underlying pathophysiology can cause large changes in potassium excretion and balance. Patients receiving potassium therapy or potassium-sparing diuretics preoperatively are at risk for the development of intra- and postoperative hyperkalemia. Renal failure also renders patients extremely susceptible to hyperkalemia. Patients with advanced renal failure do not respond normally to aldosterone. Thus, their ability to excrete potassium is impaired. Cell disruption of any kind causes intracellular potassium leak and is often associated with hyperkalemia. Hyperkalemia is commonly associated with major trauma, large surface area third-degree burns, and rhabdomyolysis. During hemolytic processes, massive amounts of potassium are liberated over a short period. Reperfusion of ischemic areas can mobilize potassium, and hyperkalemia is worsened by ischemic acidosis. Anesthesiologists commonly encounter these problems in patients having vascular surgery that requires the application of an aortic cross-clamp. Succinylcholine muscle depolarization causes transient increases in serum K+ that are especially dangerous in the setting of chronic hyperkalemia. Owing to a proliferation in

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Causes of Hyperkalemia

Potassium supplementation and potassium-sparing diuretics Acute or chronic renal insufficiency Trauma and large burns Succinylcholine Neuromuscular disorders, myopathies, muscle denervation, massive muscle injury, tetanus Hemiplegia or paraplegia Diffuse head injury and encephalitis Rhabdomyolysis, hemolysis, or massive blood transfusions Primary or secondary hypoaldosteronism Addison’s disease (chronic adrenocortical insufficiency) Angiotensin-converting enzyme inhibitors Prostaglandin synthetase inhibitors Heparin therapy or digitalis poisoning Respiratory or metabolic acidosis

the number of nicotinic receptors or alterations in the kinetics of potassium channel opening (i.e., the channels remain open longer), succinylcholine may cause life-threatening increases in serum K+ concentrations in a variety of disorders, especially large surface area third-degree burns, spinal cord injury leading to hemi- or quadriplegia, and neuromuscular diseases. Potassium distribution between the intra- and extracellular spaces is strongly pH dependent. A 0.1 decrease in pH causes about a 1.0 mEq/L increase in serum K+. Thus, acidemia of metabolic or respiratory origin can cause severe hyperkalemia by moving intracellular K+ out of the cell. Hypoventilation and respiratory acidosis are important causes of hyperkalemia during anesthesia. Likewise, diabetic ketoacidosis due to insulin-dependent diabetes, especially when compounded by acidosis due to circulatory or hemorrhagic shock, is a common cause of hyperkalemia in emergency rooms. However, despite seeming hyperkalemia, these patients actually have total body K+ depletion. A number of other conditions can cause clinically significant hyperkalemia, albeit more rarely. Massive blood transfusion can cause hyperkalemia by liberating potassium accumulated during blood preservation. Massive amounts of citrate can also bind calcium and worsen the cardiac effects of hyperkalemia. In addition, digitalis preparations have the potential to cause clinically significant hyperkalemia by inhibiting the Na+,K+-ATPase pump.

Implications HYPOKALEMIA There is no unequivocal serum K+ concentration below which the risk for arrhythmias is certain. The development of clinically significant hypokalemia is context sensitive and depends on the following factors: ● ●

●

Concurrent disease and associated pathophysiology Nature of the planned surgery or other therapeutic intervention Acute imbalance imposed by the circumstances of anesthesia and surgery

The last can include stress-induced catecholamine surges, exaggerated temperature changes, impaired ventilation and oxygenation, and the effects of drugs and other interventions.

PHARMACOLOGY

Risk Assessment

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Therefore, the decision to proceed with elective surgery in the face of chemical evidence of hypokalemia depends on many factors: whether the condition is acute or chronic, its effect on perioperative risk, the urgency of the planned surgery or intervention, and the implications of the associated imbalance and the patient’s current medications.

●

●

●

HYPERKALEMIA Concerns about anesthesia and surgery in a patient with hyperkalemia (especially if acute) involve the risk of cardiac electrical and mechanical dysfunction: ● ● ● ● ●

First, second, and third degree AV heart block Potential for bradycardia and asystole Ventricular and AV junctional escape rhythms Ventricular fibrillation Decreased contractility

Hyperkalemia can impair cardiac function by causing disturbances of cardiac rhythm or mechanical dysfunction. Although cardiac electrophysiologic abnormalities related to hyperkalemia can cause many different types of arrhythmias, heart block and bradycardia are most common. However, ventricular extrasystolic beats, ventricular fibrillation, and asystole are also possible. Importantly, far more adverse events occur with rapid changes in serum K+ concentration than with chronic hyperkalemia.

Based on the available evidence and the realization that context-sensitive and adequately powered outcome studies are lacking, we suggest the following guidelines for patients with hypokalemia. WHETHER ●

●

MANAGEMENT The decision to proceed with surgery or other major therapeutic interventions requiring anesthesia in patients with hypo- or hyperkalemia remains controversial. However, it is now clear that the duration of hypo- or hyperkalemia is more important than some arbitrary serum K+ value. Chronic imbalances are much better tolerated than their acute counterparts. Other considerations before proceeding with surgery in patients with hypokalemia or hyperkalemia include the following: ●

● ●

● ●

Severity and urgency of the planned surgery or therapeutic intervention Presence of associated physiologic or metabolic imbalances Presence of concurrent systemic disease that may be aggravated by acute hypokalemia or hyperkalemia, especially cardiovascular and central nervous system afflictions Presence of uncontrolled hypertension Presence of renal insufficiency, heart failure, or coronary heart disease

Hypokalemia Roizen and Fleisher addressed some unresolved issues concerning the perioperative management of patients with hypokalemia: ●

●

In patients with modest hypokalemia, should surgery be delayed to subject them to the risks of intravenous or even oral K+ supplementation therapy? What is the definition of modest hypokalemia: less than 3.4 mEq/L? less than 3.0 mEq/L?

Is modest hypokalemia context sensitive? That is, is modest hypokalemia (however defined) safe for some surgeries but not for others (e.g., coronary artery bypass grafting)? Are some individuals more sensitive than others to even minor K+ depletion? Are risk measures for modest hypokalemia (e.g., ventricular premature beats per hour) appropriate and context sensitive? (Such frequency might be more meaningful for patients with evolving myocardial infarction or following cardiopulmonary bypass.)

●

TO

PROCEED

WITH

ANESTHESIA

AND

SURGERY

Serum K+ below 2.5 mEq/L: Confirmed serum K+ values less than 2.5 mEq/L, especially if associated with ECG changes or arrhythmias, justify the delay of all but truly emergency interventions requiring anesthesia, owing to the increased risk of periprocedural complications. This delay provides the time needed to determine the cause and chronicity of the imbalance and to correct it. Serum K+ between 2.5 and 3.0 mEq/L: Confirmed values in this range, especially when associated with ECG changes consistent with hypokalemia or the anticipated presence of other factors that increase the risk for perioperative arrhythmias (Table 14-3), justify the postponement of elective surgery in order to identify the cause of hypokalemia and correct the imbalance. Emergent and urgent procedures can proceed as the imbalance is being corrected. Serum K+ between 3.1 and 3.5 mEq/L: With serum K+ values in this range, provided there has not been an acute decrease of 1.5 mEq/L or more, there is little risk of significant arrhythmias without overt digitalis toxicity, catecholamine excess, acute myocardial infarction, heart

Table 14–3

■

Risk Factors for Perioperative Arrhythmias

Unstable coronary artery disease Chronic pulmonary disease Hypertensive urgencies* or emergencies† NYHA class III or IV or ACC/AHA stage C or D heart failure‡ Acute or chronic renal failure Morbid obesity Malnutrition or cachexia Excess catecholamines Autonomic dysfunction Sick sinus syndrome Increased intracranial pressure *Subacute or chronic stage 2 blood pressure increase to ≥160/100 mm Hg; no end-organ damage. † Acute stage 2 blood pressure increase with evidence of end-organ damage. ‡ New York Heart Association (NYHA): class I—no symptoms of heart failure (HF) at rest; class II—HF symptoms with ordinary exertion; class III—HF symptoms with less than ordinary exertion; class IV—HF symptoms at rest. The American College of Cardiology/American Heart Association (ACC/AHA) staging emphasizes the evolution and progression of HF: stage A—high risk for developing HF, but no structural heart disease; stage B—structural heart disease (SHD), but no HF symptoms; stage C—SHD and past or current HF symptoms; stage D—end-stage heart disease and need for advanced HF treatment (continuous inotropes, mechanical circulatory support, cardiac transplantation, hospice care).

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POTASSIUM REPLACEMENT Treatment for hypokalemia, especially with arrhythmias, consists of K+ repletion, correction of alkalosis, and removal of drugs that are likely to exaggerate its effects (e.g., insulin, potassium-wasting diuretics, β2-adrenergic agonists, catecholamines). If total body K+ is depleted, as with chronic hypokalemia, oral repletion is prudent. For intravenous repletion, KCl is used because coexisting chloride depletion may limit the ability of the kidney to conserve K+. KCl is administered cautiously (no more than 10 to 20 mEq/hour), especially if the absolute deficit and its acuteness are not known. However, if the deficit is known to be acute and large (e.g., the result of massive diuresis or overly aggressive dialysis), intravenous KCl can be administered more rapidly; however, this should be done with simultaneous ECG monitoring. Special care should be exercised during K+ repletion in patients with diabetes, acidemia, and renal tubular acidosis and in those receiving angiotensin-converting enzyme inhibitors, β-adrenergic blockers, or nonsteroidal anti-inflammatory agents. All these conditions and drugs delay the movement of K+ into cells and could lead to significant hyperkalemia. Finally, keep in mind that hypomagnesemia is commonly associated with hypokalemia; it aggravates the effects of the latter by impairing K+ conservation. Hypomagnesemia is common in critically ill patients with chronic ethanolism, acute myocardial infarction, diarrhea, cachexia, malnutrition, and starvation. It is also common following CPB and dialysis and in patients receiving digitalis or chronic diuretic therapy.

Hyperkalemia It is unknown what a safe concentration of K+ is in patients with hyperkalemia. In experimental hyperkalemia, there is good correlation between the magnitude of serum K+ increases and ECG changes (see Fig. 14-2). In clinical hyperkalemia, however, abnormalities of impulse formation and propagation may occur at lower K+ concentrations than in experimental hyperkalemia; in addition, the correlation between serum K+ concentration and ECG changes is not as reliable. However, if hyperkalemia is associated with conduction disturbances, arrhythmias, or reduced contractility, acute therapy is warranted, as follows: ●

●

●

●

Antagonize the cardiac effects of K+ with intravenous calcium gluconate or chloride. Redistribute K+ into the cells with β-adrenergic agonists, sodium bicarbonate, hyperventilation, or glucose-insulin. Remove K+ from the body with furosemide or potassiumbinding resin (Kayexalate). Use hemo- or peritoneal dialysis.

In emergencies, one must rapidly reduce the extracellular concentration of K+ to counteract its effects on myocardial function. Although normalizing total body K+ is the long-term goal of therapy, calcium gluconate or chloride is used acutely to antagonize the effects of increased K+ on cardiac cell membranes. Insulin and β-adrenergic agents redistribute K+ intracellularly and produce a positive inotropic effect.

Disorders of Potassium Balance

57

Correction of acid-base imbalance and moderate alkalosis have the same effect. Sodium bicarbonate (1 to 2 mEq/kg) and moderate hyperventilation (pH 7.45 to 7.50) are also effective for acutely lowering serum K+. Infusion of glucose (1.5 g/kg) and insulin (1 unit/3 g glucose) are relatively rapid means of moving K+ intracellularly. One must measure serum K+ repeatedly, because marked hypokalemia can result from overly rapid intracellular K+ shifts. Total body K+ content is reduced with loop diuretics (e.g., furosemide) or cation exchange resins (e.g., Kayexalate). The latter bind K+ in the gut. Although both therapies are effective, their actions develop more slowly. Thus, they are used after initial treatment in emergencies. Dialysis (hemodialysis or peritoneal dialysis) or hemofiltration (our preference) is indicated in patients with severe renal insufficiency or when physiologic stability cannot be achieved by other means.

PREVENTION In the critically ill patient, sequential perioperative measurement of serum K+ and arterial blood gases for acid-base status is important. Although hypokalemia can be easily treated by giving potassium, the principles of potassium homeostasis must be kept in mind. Before and during anesthesia, it is often wise not to treat mild hypokalemia (K+ ≤ 3.0 to 3.4 mEq/L), or to do so very slowly (≤10 mEq KCl/hour). Circulatory insufficiency can cause tissue hypoperfusion and severe metabolic acidosis, which in turn moves intracellular K+ to the extracellular space. Respiratory acidosis acts similarly. In hyperkalemic patients, succinylcholine should be avoided because it causes a transient rise in serum K+. This rise can be dramatic and potentially lethal if succinylcholine is given to patients with large surface area burns, certain neuromuscular disorders (see Chapters 23 and 153), or a large mass of denervated muscle (i.e., spinal hemiplegia or paraplegia).

Hypokalemia One must be knowledgeable about the causes of hypokalemia and its associated conditions. Also, one must have a high index of suspicion for this condition in critically ill patients or those receiving chronic therapy with potassium-wasting diuretics (e.g., patients with hypertension or heart failure). Finally, one must be able to recognize the ECG signs of hypokalemia and monitor the ECG for evidence of its development.

Hyperkalemia Clinical awareness of the possibility of hyperkalemia is the most important factor in preventing it and its complications. To this end, take the following steps: ● ● ● ● ● ●

Identify patients at risk. Monitor the ECG for signs of hyperkalemia. Measure serial serum K+ concentrations. Monitor acid-base status. Avoid unnecessary potassium supplementation. Avoid respiratory or metabolic acidosis and succinylcholine.

PHARMACOLOGY

failure, or other significant comorbidities. In other words, there is no compelling reason to delay elective surgery or other therapeutic interventions to correct the imbalance.

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Preoperative use of potassium supplementation or the use of potassium-sparing diuretics must be kept in mind. During anesthesia, continuous ECG monitoring and end-tidal carbon dioxide monitoring are essential; with the latter, respiratory acidosis can be avoided. With suspected hyperkalemia, T-wave changes usually manifest well before heart block, bradycardia, escape rhythms, or deterioration in myocardial contractile function. Widening of the QRS complex indicates more severe changes. Asystole or ventricular fibrillation occurs with extreme hyperkalemia or after inadvertent intracardiac administration of potassium.

Further Reading Atlee JL: Perioperative cardiac arrhythmias. Anesthesiology 86:1397-1425, 1997. Atlee JL: Perioperative Cardiac Dysrhythmias, 2nd ed. Chicago, Year Book Medical Publishers, 1990, pp 128-129.

Cox M: The renal system and metabolic function. In Carlson RW, Geheb MA (eds): Principles and Practice of Medical Intensive Care, 3rd ed. Philadelphia, WB Saunders, 1993, pp 1155-1334. Davis RF: Etiology and treatment of perioperative cardiac arrhythmias. In Kaplan JA, Reich DL, Konstadt SN (eds): Cardiac Anesthesia, 4th ed. Philadelphia, WB Saunders, 1999, pp 177-213. Juurlink DN, Mamdani MM, Lee DS, et al: Rates of hyperkalemia after publication of the randomized aldactone evaluation study. N Engl J Med 351:543-551, 2004. Roizen MF, Fleisher LA: Anesthetic implications of concurrent diseases. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 1017-1149. Winkler AW, Hoff HE, Smith PK: Electrocardiographic changes and concentration of potassium in serum following intravenous injection of potassium chloride. Am J Physiol 124:478-483, 1948.

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REGIONAL ANESTHESIA & PAIN PHARMACOLOGY MANAGMENT

15

Magnesium Thomas S. Guyton and Timothy E. Morey Case Synopsis While recovering from hip surgery, a 54-year-old man suffering from alcoholism experiences recurrent episodes of ventricular tachycardia that are resistant to therapy with lidocaine. His serum magnesium level is 1.1 mEq/L. While receiving intravenous magnesium sulfate replacement, the patient complains of feeling hot and has difficulty breathing. Within 15 minutes of initiating replacement therapy, the patient has a respiratory arrest.

PROBLEM ANALYSIS Definition MAGNESIUM HOMEOSTASIS Magnesium is the fourth most abundant cation in the body, with total body stores of about 2000 mEq. Normal serum magnesium (Mg2+) concentrations are between 1.4 and 2.1 mEq/L, equivalent to 1.7 and 2.5 mg/dL, respectively (see Table 15-1 for unit conversions). Serum Mg2+ concentrations correlate poorly with total body stores, reflecting less than 1% of the amount stored. Gastrointestinal absorption in the duodenum and jejunum represents the principal source of Mg2+ (8 to 9 mEq/day). The amount of Mg2+ lost from the body via gastrointestinal secretions is relatively constant (2 mEq/day). In contrast, the kidney can dramatically affect losses in response to lowered serum Mg2+ concentrations due to reabsorption of Mg2+ in the proximal renal tubules and the loop of Henle. ROLE

IN

CELLULAR FUNCTION

Magnesium serves as an essential cofactor for many important cellular enzymes (e.g., adenylyl cyclase, Na+,K+-ATPase). In addition, the magnesium complex with adenosine triphosphate serves as a substrate for the enzymatic reaction mediating muscle contraction and relaxation. Magnesium also regulates cellular function by antagonizing the cellular effects of calcium and modulating several potassium currents (Table 15-2).

Increased serum Mg2+ concentrations cause vascular smooth muscle relaxation by directly competing with Ca2+ to inhibit muscle contraction. Alterations in serum Mg2+ concentrations affect multiple organ systems. For example, hypermagnesemia produces relaxation of vascular smooth muscle by directly competing with Ca2+ to inhibit smooth muscle contraction, increasing the release of prostacyclin and decreasing catecholamine release after sympathetic stimulation. At the motor neuromuscular junction, increased Mg2+ causes presynaptic inhibition of Ca2+ release; this facilitates acetylcholine release, which depresses sarcolemmic excitability. In the heart, reduced Mg2+ slows the heart rate owing to suppressed automaticity and depressed atrioventricular conduction. Hypermagnesemia also reduces the amplitude of early afterdepolarizations to oppose triggered arrhythmias (see later). In the brain, increased Mg2+ serves as an anticonvulsant by blocking neuronal Ca2+ channels associated with the N-methyl-D-aspartate receptor. ROLE

IN

THERAPEUTICS

Magnesium infusions may be therapeutic in the case of triggered ventricular arrhythmias. They are also used as adjunct therapy for atrial fibrillation in cardiac surgery, as tocolytic agents in preterm labor, and to prevent seizures with preeclampsia. The frequency of automatic or triggered ventricular arrhythmias with hypomagnesemia (e.g., torsades de pointes, digitalis ventricular arrhythmias) is reduced by intravenous magnesium infusions that double the serum Mg2+ concentration. Thus, such infusions may increase inwardly

Table 15–2 Table 15–1

■

Unit Conversions for Magnesium Compounds and Serum Concentrations

Compound

Unit Conversions

Magnesium sulfate (MgSO4) Magnesium oxide (MgO) Magnesium acetate (MgC4H6O4) Magnesium chloride (MgCl2) Serum concentrations (all compounds)

1 1 1 1 1

g = 8.13 mEq of Mg2+ g = 46 mEq of Mg2+ g = 9.35 mEq of Mg2+ g = 9.75 mEq of Mg2+ mg/dL = 0.83 mEq/L = 0.415 mmol/L

■

Mechanisms for Magnesium’s Effect on Cellular Function

Ca2+ Antagonism Modulates handling of Ca2+ by sarcoplasmic reticulum Inhibits Ca2+ influx into myocyte through sarcolemmal channels Modulates second messenger system (i.e., adenyl cyclase– adenosine monophosphate) Competes with Ca2+ for high affinity site on actin

K+ Current Enhances function of Na+,K+-ATPase Blocks outward K+ current to result in an increase in inward rectifying K+ current Mediates inwardly rectifying properties

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rectifying potassium currents to reduce the amplitude of the early afterdepolarizations that serve as the triggers for torsades de pointes. Proposed mechanisms for magnesium’s effect on digitalisinduced ventricular arrhythmias include improved function of the Na+,K+-ATPase pump and reduction in the amplitude of delayed afterdepolarizations owing to a reduction in the intracellular rise of Ca2+. However, most ventricular arrhythmias are due to reentry and do not respond to intravenous magnesium. In contrast, preoperative β-blockers and calcium channel antagonists with adjunct Mg2+ therapy can reduce the occurrence of atrial fibrillation in postoperative cardiac surgery patients. Hypomagnesemia can result from hemodilution with cardiopulmonary bypass and diuretic therapy. Finally, increasing the serum Mg2+ concentration by 4 to 6 mEq/L has been used to decrease uterine activity in preterm labor and to prevent seizure activity in women diagnosed with preeclampsia.

Recognition HYPOMAGNESEMIA Alterations in serum Mg2+ concentrations are often occult and occur along with alterations in other serum electrolytes, such as calcium and potassium. Hypomagnesemia is best diagnosed by recognizing those conditions associated with it (e.g., chronic ethanol abuse, diuretic or digitalis therapy). Hypomagnesemia alone does not result in electrocardiogram changes; however, the associated disturbances in calcium and potassium may do so. HYPERMAGNESEMIA Hypermagnesemia is most often diagnosed by associating the timing of adverse effects with the administration of magnesium. In patients with gastrointestinal diseases leading to increased absorption or renal failure leading to decreased excretion, large doses of cathartics, antacids, or analgesics containing magnesium salts may result in significant hypermagnesemia. Under these conditions, the temporal association with magnesium administration is often not apparent. Hypermagnesemia is also diagnosed by recognizing the progressive pattern of its adverse effects and then confirming that suspicion with serum Mg2+ measurements. Hypermagnesemia can produce the following adverse effects: ● ● ● ● ● ● ●

Generalized vasodilatation Lethargy Muscle weakness Respiratory depression Sinus bradycardia Atrioventricular block Asystole

Table 15-3 lists common adverse effects of hypermagnesemia and the associated serum Mg2+ concentration at which these effects first appear. It is noteworthy that the serum concentration at which a particular adverse reaction occurs in a given individual varies considerably, depending on the associated metabolic disturbances.

Table 15–3

■

Correlation between Serum Magnesium Concentration and Systemic Effects

Concentration (mEq/L)

Systemic Effects

<0.8

1.4-2.1 3-4

5-6

10 20 >25

Arrhythmias may be resistant to therapy When associated with hypocalcemia: disorientation, muscle twitching, choreiform movements, seizures Normal range Flushing 7%-13% increase in PR interval 0%-11% increase in QRS interval No change in Q-T interval Slight reduction in blood pressure Slight increase in heart rate 10% reduction in FEV1 and FVC Blurred vision from diminished accommodation and convergence Lethargy Loss of deep tendon reflexes Respiratory arrest Atrioventricular conduction block Progressive QRS widening and bradycardia Cardiac arrest

FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity.

Risk Assessment HYPOMAGNESEMIA Hypomagnesemia has an incidence of 470 per 1000 individuals suspected of having serum electrolyte abnormalities. Persons with congestive heart failure who are treated with diuretics and digitalis have a 7% to 37% incidence of hypomagnesemia. Alcoholics have a 30% to 40% incidence of hypomagnesemia. HYPERMAGNESEMIA Hypermagnesemia has an incidence of 57 per 1000 individuals suspected of having serum electrolyte abnormalities. Because of the kidney’s remarkable ability to reduce the reabsorption of magnesium, respiratory and cardiac arrests are extremely rare during continuous magnesium infusions for arrhythmias, tocolysis, or seizure prevention in preeclampsia. To prevent the adverse effects of hypermagnesemia, it is best to avoid administering magnesium to individuals with renal failure. In individuals with congestive heart failure, a therapeutic regimen consisting of 0.3 mEq/kg of magnesium given as an intravenous bolus over 10 minutes, followed by a continuous infusion of 0.08 mEq/kg per hour, resulted in serum Mg2+ concentrations of 3.5 mEq/L. In women with preeclampsia, an intravenous bolus of 32 mEq of magnesium sulfate over 20 minutes, followed by 16 mEq/hour, resulted in average serum Mg2+ levels of 4 to 6 mEq/L.

Implications Ventricular arrhythmias resulting from increased automaticity or triggered activity due to magnesium deficits

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The best prevention for hypermagnesemia is to not give magnesium-containing salts or compounds to patients with renal failure. Magnesium-containing compounds include the following: ● ● ●

The key to the management of both hypomagnesemia and hypermagnesemia is recognition. Hypomagnesemia can be treated either orally or parenterally. Table 15-1 gives the elemental content of the various magnesium-containing formulations used to treat hypomagnesemia. In patients with normal renal function, 16 to 32 mEq of magnesium sulfate can be infused intravenously over 30 minutes to 1 hour for rapid correction or over 8 to 24 hours for slower correction. As stated earlier, serum Mg2+ represents less than 1% of the total body stores of magnesium. Thus, achieving sustained elevations in serum Mg2+ concentrations with hypomagnesemia involves multiple doses to replete total body stores. In contrast, the treatment of hypermagnesemia includes any or all of the following: ● ●

●

●

●

Removal of all potential ex vivo sources of magnesium In cases of respiratory arrest, intubation and support of ventilation Administration of furosemide and magnesium-free salt solutions to increase the renal excretion of magnesium Calcium chloride (5 to 10 mEq every 5 to 10 minutes) to antagonize hypermagnesemia Dialysis with magnesium-poor dialysate

61

PREVENTION

●

MANAGEMENT

Magnesium

Cathartics (e.g., magnesium citrate) Antacids (e.g., magnesium oxide) Analgesics (e.g., buffered aspirin) Magnesium supplements

During the administration of cathartics to individuals with gastrointestinal disturbances (e.g., paralytic ileus, ulcerative colitis, perforated duodenal ulcer), massive amounts of magnesium absorption can occur.

Further Reading Dube L, Granry JC: The therapeutic use of magnesium in anesthesiology, intensive care and emergency medicine: A review. Can J Anaesth 50: 732-746, 2003. Ducceschi V, Di Micco G, Sarubbi B, et al: Ionic mechanisms of ischemiarelated ventricular arrhythmias. Clin Cardiol 19:325-331, 1996. Hazelrigg SR, Boley TM, Cetindag IB, et al: The efficacy of supplemental magnesium in reducing atrial fibrillation after coronary artery bypass grafting. Ann Thorac Surg 77:824-830, 2004. Kelepouris E, Agus ZS: Hypomagnesemia: Renal magnesium handling. Semin Nephrol 18:58-73, 1998. Sibai BM: Magnesium sulfate prophylaxis in preeclampsia: Lessons learned from recent trials. Am J Obstet Gynecol 190:1520-1526, 2004. Surawicz B: The interrelationship of electrolyte abnormalities and arrhythmias. In Mandel WJ (ed): Cardiac Arrhythmias: Their Mechanisms, Diagnosis, and Management. Philadelphia, JB Lippincott, 1995, pp 89-109.

PHARMACOLOGY

clearly warrant the replacement of those deficits. The use of magnesium infusions to reduce the risk of acute myocardial infarction is controversial and is still under investigation. The use of magnesium for preterm labor tocolysis seems to be a safe alternative to β-sympathomimetics. In comparison to phenytoin, magnesium appears to be more efficacious in preventing seizures in women with preeclampsia.

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Perioperative Fluid Management

16

Donald S. Prough and Christer H. Svensén Case Synopses Case 1 A 72-year-old man is scheduled to undergo transverse colectomy and primary reanastomosis for a nonobstructing carcinoma. He has a history of hypertension that is well controlled by a diuretic and is otherwise healthy. Case 2 A 35-year-old woman is scheduled to undergo laparoscopic cholecystectomy for cholelithiasis. Other than mild obesity (preoperative weight, 88 kg), she is healthy.

PROBLEM ANALYSIS Definition Complications are related to either insufficient or excessive fluid therapy, and in both instances, complications can range from relatively minor to life threatening. Recent studies strongly suggest that both the frequency and the importance of complications of perioperative fluid therapy have been underestimated in the past. Life-threatening complications of insufficient fluid therapy are hypoperfusion and related vital organ system complications. Acute renal failure and multisystem organ failure are associated with the worst outcomes. Less serious complications are postoperative thirst, dizziness, nausea, vomiting, fatigue, and drowsiness. Postoperative exercise capacity and pulmonary function may be transiently impaired by insufficient fluid therapy. The most feared complication of excessive fluid therapy is primary or secondary pulmonary edema. With primary pulmonary edema, there is increased venous return and right ventricular preload. This leads to increased right ventricular outflow and pulmonary artery flow and, ultimately, increased pulmonary capillary hydrostatic pressure. If this increase is sufficient and sustained, it can cause pulmonary alveolar capillary leak and alveolar flooding. This mechanism is similar to that associated with naloxone overreversal of opiates (see Chapter 33). Secondary pulmonary edema is due to left ventricular overload and “forward” (cardiogenic) failure. This is more likely in patients with at least some left ventricular functional impairment. Less threatening but still bothersome late complications related to excessive fluid therapy include peripheral edema, periorbital edema, and impaired gastrointestinal function or wound healing. These occur after discharge from the postanesthesia care unit or in the intensive care unit and are thus less readily apparent to anesthesia personnel.

complications of insufficient fluid administration have been emphasized for the past 40 years. In the 1960s, Shires and colleagues emphasized the concept that extracellular fluid volume was decreased during hemorrhage or major surgery and required replacement with crystalloid fluids. As a consequence of their studies, infusion of large amounts of crystalloids became the standard of care for combat casualties during the Vietnam conflict. This new treatment method was associated with an apparent reduction in the rate of renal failure and was subsequently adopted for the perioperative management of civilian surgical patients. Morris and associates reported in 1991 that of 72,757 admissions to nine regional trauma centers, only 78 patients (0.11%) required dialysis for acute renal failure, perhaps as a result of more liberal fluid therapy. Yet as the perioperative administration of larger crystalloid volumes became more prevalent, “shock lung” or the “Da Nang lung syndrome,” now termed acute respiratory distress syndrome (ARDS), was clinically recognized. Although a strict cause-and-effect relationship between increased fluid resuscitation and ARDS has never been established, the possible association has troubled clinicians. In 1999, Arieff reported 13 patients who developed postoperative pulmonary edema. Of these, 10 were generally healthy, and 3 had serious medical comorbidities. However, collectively, the group had a net fluid retention of 67 mL/kg within the first 24 intraoperative and postoperative hours. An accompanying retrospective review of the surgical experience during 1 year at a major teaching hospital found that among 8195 patients having major inpatient surgery, 7.6% developed postoperative pulmonary edema. One third of these patients had no preexisting comorbidity. The overall mortality rate was 11.9%, and the mortality rate among those without comorbidities was 3.9%. Based on this single-institution experience, Arieff projected that between 8300 and 74,000 patients die from perioperative pulmonary edema in the United States each year.

Historical Perspective

Recognition

Because fluid restriction was the predominant strategy of perioperative fluid management until the mid-1960s, the

Clinicians can easily recognize the extremes of insufficient or excessive fluid therapy. Hypotension, tachycardia, and oliguria

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Perioperative Fluid Management

63

Urine output often declines precipitously during moderate to severe hypovolemia. Therefore, in the absence of glycosuria or diuretic administration, a urine output of 0.5 to 1.0 mL kg−1 hr−1 during anesthesia suggests adequate renal perfusion. Arterial pH may decrease only when tissue hypoperfusion becomes severe. Cardiac output may remain normal, despite severely reduced regional blood flow. Mixed venous oxygen saturation is a specific indicator of poor systemic tissue and vital perfusion; however, it reflects average perfusion in multiple organs and cannot supplant regional monitors such as urine output.

·

·

Risk Assessment Anesthesia personnel have considerable experience and expertise in recognizing patients at high risk for the extremes of perioperative hypovolemia and hypervolemia. Preoperative determination of the patient’s American Society of Anesthesiologists (ASA) physical status and assessment of the likely duration and magnitude of physiologic stress imposed by the planned surgery can be accomplished quickly. However, to date, anesthesia training has not adequately emphasized the relationship between intraoperative fluid therapy and (1) mild symptomatic outcomes (e.g., nausea, vomiting, drowsiness) or (2) less immediate but more important outcomes (e.g., integrity of bowel anastomosis, likelihood of satisfactory wound healing or postoperative wound infection). As further evidence accumulates, anesthesia personnel should approach fluid management for all patients with the expectation that careful attention to the rate and volume of fluid administration will improve the postoperative course.

Implications The potential complications of improper perioperative fluid management suggest that additional studies in certain patient populations are needed to develop specific and comprehensive fluid management algorithms. The input needed to develop such algorithms is now available for patients undergoing colon surgery or laparoscopic cholecystectomy. Brandstrup and colleagues randomized 172 elective colon surgery patients to restrictive or standard perioperative fluid management. In the fluid-restricted group, the primary measure was maintenance of preoperative body weight. All patients underwent combined epidural and general anesthesia. Important details of the standard (liberal) and restrictive protocols are detailed in Table 16-1. By design, the fluidrestricted group received less perioperative fluid and acutely gained less than 1 kg, in contrast to more than 3 kg in the standard fluid therapy group. More important, total postoperative complications were 33% in the fluid-restricted group and 51% in the standard fluid therapy group. Cardiopulmonary complications were also significantly reduced in association with fluid restriction (7% in the restricted group versus 24% in the liberal group), as were tissue healing complications (16% in the restricted group versus 31% in the liberal group). Holte and coworkers randomized 48 ASA I to II patients having laparoscopic cholecystectomy to receive either 15 or 40 mL/kg of lactated Ringer’s solution intraoperatively. They found that the higher dose was associated with improved

PHARMACOLOGY

are obvious, though not specific, signs of hypovolemia; pulmonary edema is an obvious but not specific sign of hypervolemia. Recognition of subtle hypovolemia or hypervolemia is often more difficult. The clinical assessment of blood and extracellular volume begins with the recognition of deficit-generating situations, such as bowel obstruction, preoperative bowel preparation, chronic diuretic use, sepsis, burns, and trauma. Physical signs suggesting hypovolemia include oliguria, supine hypotension, and a positive tilt test. Although oliguria implies hypovolemia, hypovolemic patients may be nonoliguric, and normovolemic patients may be oliguric because of renal failure or stressinduced endocrine responses. Supine hypotension implies a blood volume deficit of more than 30%, although a normal arterial blood pressure could represent relative hypotension in an elderly or chronically hypertensive patient. A positive tilt test is defined as an increase in heart rate of at least 20 beats per minute and a decrease in systolic blood pressure of 20 mm Hg or more when a patient assumes the upright position. However, young, healthy subjects can withstand acute loss of 20% of blood volume while exhibiting only postural tachycardia. In contrast, orthostasis may occur in 20% to 30% of elderly patients, despite normal blood volume. Laboratory evidence that suggests hypovolemia or extracellular volume depletion includes azotemia, low urinary sodium, metabolic alkalosis (if hypovolemia is mild), and lactic acidosis (if hypovolemia is severe). Hematocrit is virtually unchanged by acute hemorrhage until fluids are administered or fluid shifts from the interstitial to the intravascular space occur. Blood urea nitrogen (BUN), normally 8 to 20 mg/dL, is increased by hypovolemia, high protein intake, gastrointestinal bleeding, or accelerated catabolism; it is reduced by severe hepatic dysfunction. Serum creatinine (SCr), a product of muscle catabolism, may be misleadingly low in elderly adults, females, and debilitated or malnourished patients; however, in muscular or acutely catabolic patients, it may exceed the normal range (0.5 to 1.5 mg/dL). A BUN/SCr ratio exceeding the normal range (10 to 20) suggests dehydration. In prerenal oliguria, enhanced sodium reabsorption should reduce urinary [Na+] to 20 mEq/L or less. Enhanced water reabsorption should increase the urine concentration (urine osmolality >400; urine-plasma creatinine ratio >40:1). However, sensitivity and specificity of these urinary variables may be misleading. Assessment of the adequacy of intraoperative fluid resuscitation integrates multiple clinical variables, including sodium concentrations, estimates of intraoperative blood loss and monitoring of heart rate, blood pressure, urine output, arterial oxygenation, and pH. Visual estimation of intraoperative blood loss is notoriously inaccurate. Moreover, tachycardia is an insensitive, nonspecific indicator of hypovolemia. In patients receiving potent inhalational anesthetics, maintenance of a satisfactory blood pressure implies adequate intravascular volume, as does a central venous or pulmonary artery occlusion pressure within the normal range (6 to 12 mm Hg). However, during profound hypovolemia, indirect blood pressure measurements may underestimate direct arterial pressure. Another advantage of direct arterial pressure monitoring may be the recognition of increased systolic blood pressure variation accompanying positive-pressure ventilation with hypovolemia.

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Restricted versus Liberal Perioperative Fluids

Group

Restricted Fluids

Liberal Fluids

Preload Maintenance Third-space fluid replacement Blood replacement

None 5% dextrose in water None Hydroxyethyl starch 1:1 for blood loss ≤1500 mL; components for blood loss >1500 mL

Hydroxyethyl starch 0.9% normal saline 0.9% normal saline 0.9% normal saline or hydroxyethyl starch for blood loss £1500 mL; components for blood loss >1500 mL

From Brandstrup B, Tonnesen H, Beier-Holgersen R, et al: Effects of intravenous fluid restriction on postoperative complications: Comparison of two perioperative fluid regimens—a randomized assessor-blinded multicenter trial. Ann Surg 238:641-648, 2003.

postoperative pulmonary function and exercise capacity, reduced neurohormonal stress response, and improvements in nausea, general sense of well-being, thirst, dizziness, drowsiness, fatigue, and balance function.

MANAGEMENT For the patients described in the case synopses, there is enough class I evidence from randomized clinical trials to propose appropriate approaches to perioperative fluid therapy (although one clinical trial for each condition would be insufficient to support formal standards or guidelines). For the 72-year-old man having transverse colectomy, a reasonable option is to manage fluids as in the trial conducted by Brandstrup and colleagues. Using that approach, the patient would receive no preload and minimal crystalloid during induction. Postinduction hypotension, if it developed, would be treated with a pressor while awaiting the onset of surgical stimulation. Maintenance fluids would consist of 5% dextrose in water, and no additional fluid would be given to cover third-space losses. All blood loss would be replaced with 6% hydroxyethyl starch in a ratio of 1:1 unless blood loss exceeded 1500 mL, in which case blood components would be given as appropriate. (For details on the management of changes in blood pressure unrelated to blood loss and other perturbations, such as oliguria, the original publication by Brandstrup’s group should be consulted.) In addition, it is essential to note that in patients undergoing colon surgery, laparoscopic cholecystectomy, or other surgery, it may be necessary to modify the preoperative fluid management plan. For the 35-year-old woman undergoing laparoscopic cholecystectomy, the fluid strategy would be diametrically opposite. Infusing 40 mL/kg of crystalloid over the course of the case would likely exceed what such patients typically receive, but the available evidence suggests that this approach is associated with improved postoperative symptoms. Also, there are important differences between laparoscopic cholecystectomy and colon surgery: ●

Postoperative cardiovascular, pulmonary, infectious, and wound complications occur much less commonly with laparoscopic cholecystectomy than with colon surgery. Thus, the goals of fluid therapy may be quite different for the two types of surgery.

●

In contrast to colon surgery, in which fluid sequestration and blood loss are common, laparoscopic cholecystectomy is associated with minimal fluid sequestration and usually minimal blood loss. Also, based on Brandstrup’s study, it is likely that replacement of blood loss with colloid limits postoperative hypovolemia.

So far, clinical trials have examined the influence of relative extremes of fluid therapy in only two types of surgery. It is likely that subsequent trials will examine more intermediate fluid restriction in colon surgery and less liberal fluid administration in laparoscopic cholecystectomy.

PREVENTION Prevention of the complications of insufficient or excessive perioperative fluid administration requires a multifaceted, flexible approach. A reasonable starting point for the fluid management of individual patients is to plan to replicate a strategy that has been effective in a prospective, randomized clinical trial in a similar population of patients undergoing the same procedure. In addition, each perioperative fluid plan must take into account the physiologic status of the individual patient. If no trials are available for identical surgical procedures, fluid management is based on trials in similar patients and adjusted for the invasiveness of the planned surgery (e.g., amount of tissue manipulation and trauma leading to increased third-space losses, amount of associated bleeding). Also, ambulatory patients without cardiovascular, pulmonary, or renal disease could reasonably be managed with a strategy similar to that used by Holte and coworkers in patients undergoing laparoscopic cholecystectomy. Data reported by Yogendran and associates suggest that such a strategy is advantageous, although improved outcomes in their trial were attained with less isotonic crystalloid preload (20 mL/kg). In patients undergoing major surgical procedures other than bowel surgery, the fluid strategy used by Brandstrup’s group might be used; bowel surgery may impose some procedure-specific constraints. One possible refinement of fluid management in major surgical procedures is better monitoring of fluid requirements. In that regard, studies in which esophageal Doppler monitoring (EDM) was used to measure descending aortic flow are provocative. EDM also quantifies the percentage of time that the descending aortic flow is systolic (i.e., corrected

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Further Reading Arieff AI: Fatal postoperative pulmonary edema: Pathogenesis and literature review. Chest 115:1371-1377, 1999. Brandstrup B, Tonnesen H, Beier-Holgersen R, et al: Effects of intravenous fluid restriction on postoperative complications: Comparison of two perioperative fluid regimens—a randomized assessor-blinded multicenter trial. Ann Surg 238:641-648, 2003. Gan TJ, Soppitt A, Maroof M, et al: Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology 97:820-826, 2002. Hirsch EF: United States Navy surgical research Republic of Vietnam 19661970: A retrospective review. Mil Med 152:236-240, 1987.

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65

Holte K, Klarskov B, Christensen DS, et al: Liberal versus restrictive fluid administration to improve recovery after laparoscopic cholecystectomy: A randomized, double-blind study. Ann Surg 240:892-899, 2004. Knight RJ: Resuscitation of battle casualties in South Vietnam: Experiences at the First Australian Field Hospital. Resuscitation 2:17-31, 1973. Lipsitz LA: Orthostatic hypotension in the elderly. N Engl J Med 321: 952-957, 1989. Morris JA Jr, Mucha P Jr, Ross SE, et al: Acute posttraumatic renal failure: A multicenter perspective. J Trauma 31:1584-1590, 1991. Perel A: Assessing fluid responsiveness by the systolic pressure variation in mechanically ventilated patients. Anesthesiology 89:1309-1310, 1998. Rooke GA, Schwid HA, Shapira Y: The effect of graded hemorrhage and intravascular volume replacement on systolic pressure variation in humans during mechanical and spontaneous ventilation. Anesth Analg 80:925-932, 1995. Shires GT, Brown FT, Canizaro PC: Distributional changes in extracellular fluid during acute hemorrhagic shock. Surg Forum 11:115, 1960. Shires GT, Coln D, Carrico J, et al: Fluid therapy in hemorrhagic shock. Arch Surg 88:688-693, 1964. Shires GT, Williams J, Brown F: Acute changes in extracellular fluid associated with major surgical procedures. Ann Surg 154:803-810, 1961. Stoneham MD: Less is more . . . using systolic pressure variation to assess hypovolaemia. Br J Anaesth 83:550-551, 1999. Tavernier B, Makhotine O, Lebuffe G, et al: Systolic pressure variation as a guide to fluid therapy in patients with sepsis-induced hypotension. Anesthesiology 89:1313-1321, 1998. Venn R, Steele A, Richardson P, et al: Randomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures. Br J Anaesth 88:65-71, 2002. Yogendran S, Asokumar B, Cheng DC, et al: A prospective randomized double-blinded study of the effect of intravenous fluid therapy on adverse outcomes on outpatient surgery. Anesth Analg 80:682-686, 1995. Zaloga GP, Hughes SS: Oliguria in patients with normal renal function. Anesthesiology 72:598-602, 1990.

PHARMACOLOGY

flow time). For example, Gan and colleagues randomized 100 patients undergoing surgery in which the predicted blood loss was greater than 500 mL to fluid management based on conventional criteria versus EDM (the treatment group). In the latter, 6% hydroxyethyl starch was given in 200-mL increments to increase corrected flow time if it was less than 0.35 second. The treatment group had a shorter hospital length of stay and resumed eating solid food more quickly. Venn and associates randomized 90 patients having repair of proximal femoral fractures to one control and two treatment groups: (1) conventional fluid management (control), (2) repeated challenges with colloid guided by central venous pressure monitoring, or (3) the same colloid challenges guided by EDM. Both treatment groups had significantly fewer episodes of intraoperative hypotension and were discharged from the hospital sooner than the controls. Importantly, noninvasive EDM was equivalent to more invasive central venous pressure monitoring for assessing intraoperative fluid requirements.

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Volatile Anesthetics: Organ Toxicity

17

Evan D. Kharasch Case Synopsis A 53-year-old woman has laser excision of vocal cord papillomas under anesthesia with halothane and spontaneous ventilation. She has had several prior excisions, including one a month earlier, all with halothane; all were uneventful. However, 1 week after this surgery, she develops fever, nausea, and malaise, along with severe jaundice and markedly elevated serum transaminase concentrations.

PROBLEM ANALYSIS Definition Organ toxicity caused by volatile anesthetics is the result of alterations in cellular structure or function that persist beyond the period of anesthetic administration and elimination. Of greatest concern with volatile anesthetics are hepatic toxicity and renal toxicity. Not discussed here, but worthy of mention, is the potential for volatile inhalational anesthetics to interact with desiccated carbon dioxide absorbents to form potentially toxic compounds, such as carbon monoxide and compound A. Pulmonary and renal toxicity can occur, and fires and explosions have also been reported. (For more details, see the works by Baum and Woehlck listed under “Further Reading.”) HEPATIC TOXICITY Hepatic toxicity occurs most commonly after halothane administration, but it has also been observed with less frequency after enflurane, isoflurane, sevoflurane, and desflurane. Halothane causes two types of liver damage: ● ●

Fulminant hepatic necrosis (“halothane hepatitis”) Mild subclinical hepatotoxicity

Fulminant hepatic necrosis is clinically characterized by fever and jaundice, with grossly elevated serum transaminase levels. Liver biopsies show massive centrilobular necrosis. Today, fulminant hepatic necrosis is considered an immune phenomenon that is initiated by oxidative metabolism of halothane to an intermediate. This subsequently binds to liver proteins and induces trifluoroacetylation, which renders the proteins antigenic. These antigens stimulate the formation of antibodies that, on re-exposure to halothane (or enflurane, isoflurane, or desflurane), initiate immunemediated hepatic necrosis. Such necrosis is rare, occurring in 1 in 6000 to 35,000 persons after halothane administration and in 2 in 1 million persons after enflurane; there have been a few reports of cases after isoflurane and one confirmed case after desflurane. Hepatic dysfunction after sevoflurane 66

administration has also been reported, but it is not thought to represent immune-mediated necrosis, and the relationship to anesthesia is unknown. Mild hepatotoxicity occurs commonly after halothane administration (approximately 25% of cases) but not after the administration of other volatile anesthetics. It is characterized by mild, transient elevations in serum transaminase and glutathione-S-transferase concentrations and altered postoperative drug metabolism. However, clinically evident hepatocellular disease is not a characteristic of mild hepatic toxicity. Rather, it is attributed to reductive (anaerobic) halothane metabolism, with reactive metabolites causing lipid peroxidation and binding to cytochrome P-450. The two forms of hepatic anesthetic toxicity are thought to be unrelated. ACUTE RENAL FAILURE Acute renal failure is a common perioperative problem, but it is now rarely the direct result of volatile anesthetics. Several terms require definition: ●

●

●

●

●

Renal failure is a reduction in renal function sufficient to cause alterations in serum biochemistry; it may be oliguric, nonoliguric, or polyuric. Renal insufficiency is a lesser reduction in renal function with normal serum biochemistry. Oliguria is urine output less than 20 mL/hour (in a 70-kg adult) and implies renal failure. Nonoliguric renal failure is more common than oliguric failure, and it is thought to represent a milder renal insult. Polyuria is urine output greater than 100 mL/hour (in a 70-kg adult).

Both oliguric and nonoliguric renal failure may be postrenal (obstructive), prerenal (renal hypoperfusion due to hypovolemia, hypotension, decreased renal blood flow, or cardiovascular surgery), or intrinsic (caused by nephrotoxins such as aminoglycosides, myoglobin, hemoglobin, radiocontrast media, or nonsteroidal anti-inflammatory agents). Polyuric renal failure with reduced concentrating ability is due to either central diabetes insipidus (insufficient antidiuretic

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Recognition Fulminant hepatic necrosis manifests clinically as fever, nausea, anorexia, chills, malaise, and rash that appear 3 to 6 days postoperatively, followed by severe jaundice that occurs 6 to 10 days postoperatively. Laboratory manifestations include grossly elevated serum transaminase levels, hyperbilirubinemia, and prolonged prothrombin time, but these are not specific for the disease. Pathologic findings include centrilobular and midzonal necrosis, but again, these findings are not specific. Mild hepatotoxicity after halothane is usually clinically silent, consisting of only mild, reversible increases in liver enzymes (aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, and glutathione-S-transferase) on laboratory studies. These elevations appear 1 to 2 days postoperatively and usually resolve within days. However, levels may remain elevated for up to 2 weeks. A specific diagnosis of anesthetic-related hepatitis is difficult at best. Both the clinical presentation and the morphologic features strongly resemble those of viral hepatitis. Indeed, the incidence of occult perioperative hepatitis (viral, infectious, alcoholic) is 1 in 700, and in 30% of these cases, postoperative jaundice develops; this is far greater than the incidence of anesthetic-related fulminant hepatitis. Positive serologic markers for hepatitis A, B, C, or D or other infectious agents (e.g., cytomegalovirus, Epstein-Barr virus) may help exclude anesthesia as the cause of postoperative hepatitis, but negative serologic findings are inconclusive, especially if infection is recent. A few laboratories can detect antitrifluoroacetylated protein antibodies in serum, which favors a diagnosis of anesthetic-related hepatitis. However, the assay lacks sufficient specificity and is not routinely available. Hepatitis C is the most common cause of postoperative hepatitis, but hepatic ischemia, other drugs, transfusion, and cholestasis should also be excluded. The clinical characteristics of renal insufficiency and acute renal failure were listed earlier. Differentiation of central and nephrogenic diabetes insipidus is based on response to water deprivation and vasopressin. The cause of oliguric

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67

renal failure is determined by the BUN-creatinine ratio, urine sodium and osmolality, urine-plasma osmolality, urineplasma creatinine, fractional excretion of sodium, and response to volume challenge. The diagnosis of renal failure specific to a volatile anesthetic is extremely rare in the postmethoxyflurane era.

Risk Assessment Clinical risk factors for fulminant hepatic necrosis include the following: ● ● ● ● ●

Repeated halothane exposure Prior history of postanesthetic fever or jaundice Obesity Female sex Middle age

Halothane is oxidatively metabolized by cytochrome P-450 2E1. Thus, enzyme induction (alcohol, isoniazid, obesity) increases antigen formation and increases risk, whereas enzyme inhibition (disulfiram) reduces metabolism. Multiple, repeated exposures at short intervals (<6 weeks) is the greatest risk factor for halothane hepatitis. Children are at greatly diminished risk, for unknown reasons, even after repeated halothane exposure. Liver disease itself is not a risk factor for halothane hepatitis. Clinical risk factors for mild hepatotoxicity are those that increase reductive halothane metabolism. Halothane is reduced anaerobically by P-450 3A4 and 2A6; thus, enzyme induction (e.g., by barbiturates, phenytoin, valproic acid) increases metabolism, as does reduced hepatic blood flow. The latter is further reduced by halothane. Although enflurane, isoflurane, and desflurane also cause neoantigen formation, the degree of such formation is far less than with halothane, so the risk of hepatitis with these agents in halothane-sensitized patients is far less. The only clearly identified clinical risk factors for postoperative renal failure are the following: ●

● ●

Poor preoperative renal function (increased BUN or creatinine levels) Advanced age Cardiac failure

Treatment and prevention of hypovolemia and preoperative hydration are primary goals in ameliorating the cardiovascular and renal blood flow effects of volatile anesthetics in general. Mechanical ventilation and positive endexpiratory pressure are other factors peripherally related to volatile anesthetics that diminish renal function. Although not pertinent to contemporary anesthesia, certain inducers of drug metabolism (barbiturates, isoniazid, ethanol) potentiate methoxyflurane metabolism and toxicity.

Implications Fulminant hepatic necrosis after halothane is fatal in nearly half of all cases. There are no known clinical implications of mild hepatotoxicity. Perioperative acute renal failure accounts for half of all patients who require acute dialysis and is associated with a 50% mortality rate. This has remained unchanged for decades.

PHARMACOLOGY

hormone secretion, usually due to pituitary dysfunction) or nephrogenic diabetes insipidus (renal unresponsiveness to antidiuretic hormone). Anesthesia-related renal insufficiency is often prerenal and is caused by hypotension or altered renal perfusion. It is limited to the duration of the anesthetic and is reversible. Renal failure specifically attributable to anesthetic agents has been observed only with methoxyflurane, which can cause vasopressin-resistant polyuria, hypernatremia, hyperosmolality, and dehydration; it also increases blood urea nitrogen (BUN) and creatinine levels. Methoxyflurane nephrotoxicity is due to dose-related methoxyflurane metabolism. Associated plasma fluoride concentrations range from greater than 50 to 80 μM. A mild but reversible concentrating defect following prolonged enflurane use has been noted. Direct nephrotoxicity has not been observed with enflurane, isoflurane, desflurane, or sevoflurane, even with systemic fluoride concentrations far exceeding 50 μM. The role of systemic fluoride concentrations as a factor in nephrotoxicity has been discounted.

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MANAGEMENT There is no specific management for either fulminant hepatic necrosis or mild hepatotoxicity. No therapy is needed for mild hepatotoxicity, whereas only supportive therapy and orthotopic liver transplantation are available for hepatic necrosis. Treatment for acute renal dysfunction includes restoration of normovolemia and renal blood flow; administration of mannitol, loop diuretics (controversial), dopamine, and fenoldopam (experimental); and dialysis.

PREVENTION No measures for the prevention of mild hepatotoxicity are necessary. The only fail-safe method of preventing fulminant hepatic necrosis is total avoidance of halothane, enflurane, isoflurane, and desflurane in patients previously exposed to halothane. Hepatitis is rare in children and in adults with only a single exposure to halothane. A conservative approach is to avoid halothane in patients with known risk factors for fulminant necrosis, especially recent halothane anesthesia. The ultraconservative approach is to avoid halothane altogether. The single most effective measure to prevent postoperative renal failure is to minimize renal ischemia by maintaining

renal perfusion. Maintenance of adequate hydration is essential. Mannitol may be an effective prophylactic.

Further Reading Baden JM, Mazze RI: Polyuria. In Gravenstein N, Kirby RR (eds): Complications in Anesthesiology, 2nd ed. Philadelphia, LippincottRaven, 1996, pp 493-498. Baum JA, Woehlck HJ: Interaction of inhalational anaesthetics with CO2 absorbents. Best Pract Res Clin Anaesthesiol 17:63-76, 2003. Brown BR: Inhalation anesthesia and hepatic injury. In Gravenstein N, Kirby RR (eds): Complications in Anesthesiology, 2nd ed. Philadelphia, Lippincott-Raven, 1996, pp 701-710. Dooley JR, Mazze RI: Oliguria. In Gravenstein N, Kirby RR (eds): Complications in Anesthesiology, 2nd ed. Philadelphia, LippincottRaven, 1996, pp 479-491. Gut J, Christen V, Frey N, et al: Molecular mimicry in halothane hepatitis: Biochemical and structural characterization of lipoylated autoantigens. Toxicology 97:199-224, 1995. Novis BK, Roizen MF, Aronson S, et al: Association of preoperative risk factors with postoperative acute renal failure. Anesth Analg 78: 143-149, 1994. Pearson JD, Gelman S: Liver complications after anesthesia. In Benumof JL, Saidman LJ (eds): Anesthesia and Perioperative Complications. St. Louis, Mosby–Year Book, 1992, pp 413-433. Prough DS, Zaloga G: Hypovolemia and renal dysfunction. In Benumof JL, Saidman LJ (eds): Anesthesia and Perioperative Complications. St. Louis, Mosby–Year Book, 1992, pp 434-465. Ray DC, Drummond GB: Halothane hepatitis. Br J Anaesth 67:84-99, 1991. Woehlck HJ: Sleeping with uncertainty: Anesthetics and desiccated absorbent. Anesthesiology 101:276-278, 2004.

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18

Nitrous Oxide: Neurotoxicity Claudia Praetel Case Synopsis Two weeks after surgery for prostate adenoma, a 69-year-old man developed ascending paresthesia of the limbs, severe ataxia, tactile sensory loss in the limbs and trunk, and absent tendon reflexes. After a second surgical intervention, the patient became confused. Four months after onset, the patient demonstrated paraplegia, severe weakness of the upper limbs, cutaneous anesthesia sparing the head, and confusion.

PROBLEM ANALYSIS Definition Nitrous oxide (N2O) has been safely used for anesthesia for almost 140 years, since it first became available in compressed gas cylinders in 1868. However, there are increasing reports of the neurotoxic potential of N2O associated with recreational use, with chronic occupational exposure in unscavenged environments, and after exposure during general anesthesia. A small subset of patients routinely seen during preoperative anesthetic assessment may indeed be at high risk for postoperative neurologic deterioration if exposed to N2O. Schilling postulated that N2O may precipitate neurologic disease in patients with unrecognized vitamin B12 deficiency. The patient described in the case synopsis was diagnosed with previously unrecognized pernicious anemia with subacute combined degeneration of the spinal cord after exposure to N2O anesthesia. Marié and coworkers published this case report in 2000. During the past 20 years, numerous welldocumented case reports have substantiated this potentially devastating complication. Table 18-1 highlights recent reports of neurologic complications after N2O in both children and adults.

Lack of methionine can also result in defective myelination and demyelination. Neurologic sequelae include paresthesias, peripheral neuropathy, and subacute combined degeneration of both the posterior and lateral columns of the spinal cord. Subacute combined degeneration is reversible if diagnosed and treated early with cobalamin. Psychological symptoms such as memory loss, disorientation, and depression have been described. These conditions may be observed with or without macrocytic changes in erythrocytes.

Risk Assessment Inhibition of methionine synthase by N2O anesthesia does not cause a problem in healthy individuals with sufficient vitamin B12 stores. However, any patient with even subclinical deficits of vitamin B12 is at increased risk for the development of myeloneuropathy because occult cobalamin deficiency, combined with subsequent N2O exposure, compounds inhibition of the methionine synthesis pathway. Insufficient availability of cobalamin may have the following causes: ●

●

Recognition N2O is a potent oxidant. It irreversibly oxidizes methylcobalamin through inhibition of the methionine synthesis pathway, thereby inactivating the active form of vitamin B12. The latter is essential for methionine synthase, the key enzyme for converting homocysteine to methionine (an essential amino acid) using tetrahydrofolate (the bioactive form of folate) as the methyl source. Therefore, insufficient availability of either cobalamin1 or folate results in a decrease of methionine, with the accumulation of homocysteine. N2O also directly inactivates methionine synthase, possibly due to the production of free radicals. Inhibition of methionine synthase activity has deleterious consequences for DNA synthesis, leading to megaloblastic changes in all rapidly dividing cells, macrocytosis in erythroid precursors, and ineffective erythropoiesis.

●

Inadequate intake (e.g., alcoholics, long-term strict vegetarians, breast-fed infants of vitamin B12-deficient mothers) Impaired absorption (e.g., gastric atrophy, long-term use of drugs that interfere with acid production, Crohn’s disease, lack of intrinsic factor due to autoimmune destruction of parietal cells or after surgery such as gastrectomy and gastric bypass) Rare congenital disorders (e.g., deficiencies of transcobalamin II, familial selective vitamin B12 malabsorption)

Folate deficiency is very rare due to the dietary fortification of wheat and corn grains with folic acid. Inherited defects in folate metabolism (5,10-methylenetetrahydrofolate reductase deficiency) are a contraindication to N2O exposure. 1 The terms cobalamin and vitamin B12 are used interchangeably as generic terms for all the cobalamides active in human beings. Preparations of vitamin B12 for therapeutic use contain either cyanocobalamin or hydroxocobalamin, because only these derivatives remain active following storage.

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Selected Case Reports of Neurologic Complications after Nitrous Oxide (N2O) Anesthesia

Reference

Demographics

Onset Time and Symptoms

Findings

Selzer et al

3 mo old; excisional biopsy (45 min); 4 days later, tumor resection (270 min), for a total N2O exposure time of 315 min 8 mo old; laparoscopic orchiopexy; N2O exposure of 180 min

25 days: hypotonia, ataxic ventilation, absent reflexes

Methylenetetrahydrofolate reductase deficiency; died 46 days postoperatively

6 days: hypotonia, fine motor tremor, athetoid movements

Profound dietary cobalamin deficiency (<20 pg/mL); hyperhomocysteinemia; normal folate levels; megaloblastic abnormalities in bone marrow Severe dietary cobalamin deficiency (<45 pg/mL); normal folate levels; MRI revealed diffuse cerebral atrophy Cobalamin deficiency (135 pmol/L); borderline anemia; abnormal Schilling test; MRI revealed signal changes of posterior spinal columns; SSEP showed severe spinal cord conduction disturbance; EMG and NCS showed mixed polyneuropathy Normal cobalamin level (<166 pmol/L); low folate; macrocytic, hyperchromic anemia; bone marrow exam revealed megaloblastic hematopoiesis; MRI showed signal changes in posterior columns along cervical cord segments: EMG and NCS showed mild demyelinative polyneuropathy Macrocytic anemia; MRI revealed signal changes in posterior and lateral spinal columns

Felmet et al

McNeely et al

4 mo old; repair of cranisynostosis; N2O exposure of 80 min

3 wk: hypotonia, lethargy, feeding difficulty, severe acidosis, dehydration 2 mo: gait imbalance, lower extremity paresthesias

Ilnicziky et al (case 1)

57-yr-old man; cranial artery bypass; duration of N2O exposure unspecified

Ilnicziky et al (case 2)

52-yr-old man; gallbladder removal; duration of N2O exposure unknown

1 wk: paresthesias in both feet, ascending to trunk and upper extremities; weakness and clumsiness in all limbs

Sesso et al

63-yr-old woman; gallbladder removal; N2O exposure of 80 min

1 day: rapidly ascending paresthesias in hands/feet 2 mo: moderate tabetic-spastic gait, with impaired proprioception and sensation

EMG, electromyography; MRI, magnetic resonance imaging; NCS, nerve conduction velocity study; SSEP, somatosensory evoked potentials.

Implications A recently published multicenter study in Great Britain examined blood samples of 1562 patients aged 65 to 74 years and 75 years or older. Among men, 11% and 24%, respectively, were at high risk of vitamin B12 deficiency; the corresponding numbers were slightly lower for women (9% and 17%, respectively). Similar results were reported for the United States. This high prevalence of borderline or low vitamin B12 concentrations in the elderly (due to the decline in digestive efficiency, atrophic gastritis, and the ubiquitous use of acid-reducing drugs) is particularly worrisome because the clinical presentation varies considerably and rarely includes all the classic features. Hematologic signs of macrocytosis and anemia are often missing. Apparently, a dissociation of neurologic and hematologic findings is common. Cobalamin deficiency in young adults is uncommon, except among strict long-term vegetarians. The potential risks of N2O are increased in children with enzyme disorders and noncompliance with vitamin supplements, as described in a patient with phenylketonuria. There is growing evidence that markers such as holotranscobalamin II, methylmalonic

acid, and total serum homocysteine constitute a better index of early cobalamin deficiency and allow the differentiation between storage depletion and functional deficiency. Presently, these tests are very expensive and are not used as routine assays to investigate functional vitamin B12 status. Low cobalamin status is significantly correlated to increased plasma homocysteine, which is recognized as an independent atherothrombotic risk factor. The latency in onset of neurologic symptoms following exposure to N2O may confound the true incidence of this anesthesia-related complication.

MANAGEMENT The preoperative risk assessment should include careful attention to the following: ● ●

● ●

Hematologic abnormalities (e.g., anemia, macrocytosis) Increased prevalence of subclinical vitamin B12 deficiency in the elderly Rare genetic enzyme disorders Diet (strict vegetarian or vegan)

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● ● ●

●

History of gastric or small bowel surgery (e.g., gastric bypass in the morbidly obese, resection of the terminal ileum in Crohn’s disease) Inflammatory bowel disease Long-term use of antacids, histamine (H2) receptor antagonists, or proton pump inhibitors (e.g., aluminum and magnesium hydroxide, ranitidine, omeprazole) Severe depression in the elderly Unexplained neurologic symptoms Previous exposure to inhaled anesthesia (including N2O) that was associated with postoperative neurologic complications Increased prevalence of folate deficiency in patients with chronic liver disease or malabsorption syndromes, longterm use of anticonvulsants (e.g., valproic acid, phenytoin), and antimetabolite therapy (e.g., methotrexate)

PREVENTION Avoidance of N2O anesthesia in patients with an elevated risk of cobalamin deficiency appears prudent in view of the possibly serious neurologic sequelae. The fact that subclinical or clinical deficits are not always accompanied by hematologic changes deserves special emphasis. Routine N2O use may be detrimental to patients with marginal cobalamin status. Vitamin pretreatment of at-risk patients is an option, but an impractical one, because anesthesiologists generally see patients immediately before surgery. Optimal management of patients with confirmed or suspected cobalamin deficiency includes an anesthetic regime devoid of N2O. N2O-induced postoperative neurologic complications are preventable with

Nitrous Oxide: Neurotoxicity

71

a proper focus on the recognition of preexisting vitamin B12 deficiency as outlined here.

Further Reading Badner NH, Freeman D, Spence JD: Preoperative oral B vitamins prevent nitrous oxide-induced postoperative plasma homocysteine increase. Anesth Analg 95:787, 2002. Clarke R, Refsum H, Birks J, et al: Screening for vitamin B12 and folate deficiency in older persons. Am J Clin Nutr 77:1241-1247, 2003. Deleu D, Hanssens Y, Louon A: Nitrous oxide-induced cobalamin deficiency. Arch Neurol 58:134-135, 2001. Felmet K, Robins B, Tilford D, Haflick SJ: Acute neurologic decompensation in an infant with cobalamin deficiency exposed to nitrous oxide. J Pediatr 137:427-428, 2000. Hadzic A, Glab K, Sanborn KV, Thys DM: Severe neurologic deficit after nitrous oxide anesthesia. Anesthesiology 83:863-866, 1995. Herrmann W, Geisel J: Vegetarian lifestyle and monitoring of vitamin B12 status. Clin Chim Acta 326:47-59, 2002. Ilniczky S, Jelencsik, Kenéz J, Szirmai I: MR findings in subacute combined degeneration of the spinal cord caused by nitrous oxide anaesthesia— two cases. Eur J Neurol 9:101-104, 2002. Marié RM, Le Biez E, Busson P, et al: Nitrous oxide anesthesia-associated myelopathy. Arch Neurol 57:380-382, 2000. McNeely JK, Buczulinski B, Rosner DR: Severe neurological impairment in an infant after nitrous oxide anesthesia. Anesthesiology 93:1549-1550, 2000. Nunn JF: Clinical aspects of the interaction between nitrous oxide and vitamin B12. Br J Anaesth 59:3-13, 1987. Royston BD, Nunn JF, Weinbren HK, et al: Rate of inactivation of human and rodent methionine synthase by nitrous oxide. Anesthesiology 68:213-216, 1988. Schilling RF: Is nitrous oxide a dangerous anesthetic for vitamin B12-deficient subjects? JAMA 255:1605-1606, 1986. Selzer RR, Rosenblatt DS, Laxova R, Hogan K: Adverse effect of nitrous oxide in a child with 5,10-methylenetetrahydrofolate reductase deficiency. N Engl J Med 349:45-50, 2003. Sesso RM, Iunes Y, Melo AC: Neuropathy following nitrous oxide anesthesia in a patient with macrocytic anaemia. Neuroradiology 41:588-590, 1999.

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Intrathecal Opiates Lisa Thannikary and Bhiken Naik Case Synopsis An otherwise healthy 26-year-old woman undergoes cesarean section for delivery of a breech infant. Spinal anesthesia is used, consisting of hyperbaric bupivacaine (12 mg) with preservative-free morphine (0.3 mg). The surgery is uneventful, and the infant has Apgar scores of 9 and 9 at 5 and 10 minutes, respectively. The patient remains in the recovery room for 2 hours and is then transferred to the floor. She is treated with diphenhydramine 50 mg intravenously (IV) for generalized pruritus 4 hours after surgery and promethazine 25 mg IV for vomiting 7 hours after surgery. Ten hours after surgery, she is found to be somnolent, with a respiratory rate of 6 breaths per minute, and is minimally responsive to deep tactile stimulation.

PROBLEM ANALYSIS Definition Intrathecal administration of opioids is an effective means of providing analgesia. A combination of opioids and local anesthetics is often administered intrathecally in an effort to reduce drug dosages while limiting the side effects of both classes of drugs. Morphine is commonly chosen for intrathecal administration, because a single dose may provide analgesia for up to 24 hours. Side effects of intrathecal opioids include early and late respiratory depression, nausea and vomiting, pruritus, sedation, and urinary retention (Table 19-1). Early respiratory depression occurs in the first 2 hours after intrathecal administration and is believed to be due to vascular uptake and redistribution. This occurs more often with lipophilic opioids such as fentanyl and sufentanil than with less lipophilic opioids such as morphine. Delayed respiratory depression occurs 6 to 12 hours after intrathecal administration and is believed to be the result of rostral spread of the opioid in the cerebrospinal fluid. The target receptors are likely located in the respiratory center of the brainstem. However, the occurrence of clinically significant respiratory depression is very low, typically less than 0.5%. Pruritus, either generalized or localized, occurs frequently in patients receiving intrathecal opioids. Although

Table 19–1

■

the mechanism is not fully understood, histamine release is not postulated to be a causative factor. Nausea and vomiting are believed to be due to rostral spread of the opioid in the cerebrospinal fluid. The opioid stimulates the vomiting center and the chemoreceptor trigger zone in the fourth ventricle. Sedation is believed to result from opioid spread through the cerebrospinal fluid to the thalamus, limbic system, or cerebral cortex. Sedation may be exacerbated by hypercarbia with carbon dioxide narcosis. Urinary retention is believed to be due to inhibition of sacral parasympathetic outflow. This results in relaxation of the bladder detrusor muscle and the concomitant inability to relax the sphincter.

Recognition The most serious complication of intrathecal opioid administration is delayed respiratory depression because it usually occurs when the patient is no longer under an anesthesiologist’s or intensivist’s care. In the operating room, labor suite, recovery room, or critical care unit, patients are more closely monitored than they are on the floor. It is also important to recognize that respiratory depression is often a late finding. Increasing somnolence, bradypnea, and smaller tidal volumes are early signs of respiratory compromise. Late signs are hypoxia, unresponsiveness, and cardiopulmonary arrest.

Cause and Treatment of Complications of Intrathecal Medications

Complication

Cause

Treatment

Early respiratory depression Late respiratory depression Pruritus Nausea, vomiting

Rapid vascular uptake and redistribution Rostral CSF spread to brainstem respiratory center Unknown (unlikely due to histamine release) Rostral CSF spread to vomiting center or chemoreceptor trigger zone in fourth ventricle Inhibited sacral parasympathetic outflow Rostral spread in CSF to thalamus, limbic system, or cortex; hypercarbia

Ventilatory support, naloxone Ventilatory support, naloxone Naloxone, antihistamines, propofol Naloxone, antiemetics, droperidol, transdermal scopolamine Naloxone (large doses), urinary catheterization Naloxone

Urinary retention Sedation

CSF, cerebrospinal fluid.

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Risk Assessment Careful selection of patients for the administration of intrathecal opioids is important. Patients at increased risk for respiratory depression include those who are debilitated or elderly, suffer from coexisting respiratory disease, and are placed in Trendelenburg’s position following intrathecal opioid injection. Also, patients receiving hydrophilic opioids, large or frequent doses of opioids, large-volume injections, and concomitant parenteral or oral sedatives are at increased risk for respiratory depression.

Implications Anesthesiologists commonly administer intrathecal opioids to provide postoperative analgesia. It is important to remember that side effects of intrathecal opioids can occur after the patient has left the anesthesiologist’s care. Good communication with the nursing staff caring for the patient is crucial for the prevention of many complications.

MANAGEMENT The immediate treatment for neuraxial opiate-induced respiratory depression is ventilatory support until the opiate is metabolized or pharmacologically antagonized. The patient must be ventilated with positive-pressure mask ventilation and 100% oxygen. Tracheal intubation and mechanical ventilation may be necessary in some patients. Opiate reversal is accomplished with small doses (40 to 80 μg) of parenteral naloxone. Repeated naloxone doses or infusions may be necessary because its half-life is shorter than that of intrathecal morphine. Also, advanced cardiovascular life support is required for patients with cardiac arrest due to narcotic-caused respiratory depression. Arterial blood gas measurements for carbon dioxide concentrations are helpful to ascertain the degree of inhibition of respiration or the adequacy of ventilation. Finally, narcotics administered by other routes (intravenous, oral, epidural, intramuscular) must be discontinued.

Intrathecal Opiates

73

PREVENTION The best way to prevent delayed respiratory depression in patients receiving spinal opioids is to not give parenteral opioids or other sedating medications until at least 24 hours after intrathecal administration. Pruritus and nausea are common side effects of intrathecal opioids and can be treated effectively with naloxone. If other drugs are used for the treatment of pain or side effects, it is important to use nonsedating ones, such as nonsteroidal anti-inflammatory drugs for patients with pain. Good communication between anesthesia and nursing personnel is essential to prevent and treat adverse sequelae of intrathecal opioid administration. Nursing staff must be educated about intrathecal opioid side effects and their appropriate management. One effective measure is to use a preprinted order signed by the anesthesiologist stating that the patient received intrathecal opioids and should not receive further sedating drugs for at least 24 hours without clearance from the anesthesia staff. Signs posted above the head of the patient’s bed indicating that intrathecal opioids have been used may also be helpful. Monitoring the patient at frequent intervals is critical to prevent significant respiratory depression. The patient must be assessed for rate and quality of respirations and level of sedation. For very high-risk patients, the usual floormonitoring interval may not be adequate. If so, the patient may have to be admitted to a unit where more staff are available to monitor the patient more closely. Pulse oximetry monitoring with data telemetry to a centralized nursing station is also helpful but may not be available to all patients or in all hospitals.

Further Reading Ballantyne JC, Loach AB, Carr DB: Itching after epidural and spinal opiates. Pain 33:149-160, 1988. Brill S, Gurman GM, Fisher A: A history of neuraxial administration of local analgesics and opioids. Eur J Anaesthesiol 20:682-689, 2003. Gustafsson LL, Schildt B, Jacobsen K: Adverse effects of extradural and intrathecal opiates: Report of a nationwide survey in Sweden. Br J Anaesth 54:479-485, 1982. Ready LB: Acute perioperative pain. In Miller RD (ed): Anesthesia, 5th ed. Philadelphia, Churchill Livingstone, 2000, pp 2323-2350. Reiz S, Westberg M: Side effects of epidural morphine. Lancet 2:203-204, 1980. Sinatra RS: Acute pain management and acute pain services. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in Clinical Anesthesia and Management of Pain, 3rd ed. Philadelphia, Lippincott-Raven, 1998, pp 793-835.

PHARMACOLOGY

Further, intrathecal opioids can impair the ventilatory response to carbon dioxide, which can exacerbate respiratory depression. A high index of suspicion and early recognition of delayed respiratory depression are paramount to timely and effective management. Otherwise, there may be fatal or permanent injuries.

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Barbiturates: Porphyrias Christoph N. Seubert Case Synopsis An anxious 24-year-old woman presents with nausea, vomiting, and abdominal pain and is scheduled for an exploratory laparotomy. The past medical history indicates a negative exploratory laparotomy 2 years ago. The patient’s blood pressure is 150/90 mm Hg and pulse is 105 beats per minute. The physical examination reveals abdominal tenderness. Electrolyte levels and white blood cell count are normal. With direct questioning about family history, the patient declares that her mother may have had porphyria.

PROBLEM ANALYSIS Definition Although barbiturates are widely used in anesthetic practice, they may cause an acute attack in susceptible patients with inducible porphyria. Porphyrias are a heterogeneous group of genetic disorders wherein genetic, physiologic, and environmental factors interact to cause disease. Although porphyrias can be classified on the basis of the underlying genetic defects involved in hemoglobin synthesis, the simple clinical division into inducible-acute and noninduciblechronic forms remains useful. An example of the latter is porphyria cutanea tarda (PCT), the most common form of porphyria. Apart from the friability of the patient’s skin and the association with hepatitis C, human immunodeficiency virus (HIV), and alcohol abuse, PCT presents no anesthetic concerns and does not restrict the choice of drugs. In contrast, all patients with acute porphyrias are at risk for porphyric crisis, particularly in the perioperative period. Drugs administered in the perioperative period for the condition requiring surgery, stress, or fasting may precipitate acute attacks of porphyria. If the attack goes untreated or unrecognized, it may be fatal. Conversely, control of precipitating factors or prompt treatment can avert or mitigate the attack and allow the safe conduct of surgery. Acute porphyrias, therefore, present important anesthetic concerns. Porphyrin synthesis occurs in all cells and is of particular importance in the bone marrow and liver. Porphyrins are essential components of proteins involved in the utilization, transport, and storage of oxygen. These proteins include the ubiquitous cytochrome oxidases of the respiratory chain, the hepatic cytochrome P-450 enzymes, and transport proteins such as hemoglobin. Synthesis of porphyrins involves a series of enzymes (Fig. 20-1). Genes for key enzymes of porphyrin synthesis are duplicated in the genome, allowing for separate regulation of heme synthesis in the bone marrow and the liver. In the liver, most heme is used for the production of cytochrome P-450 enzymes. Heme synthesis and P-450 production are regulated in a coordinated fashion. The four acute porphyrias are acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and δ-aminolevulinic acid dehydratasedeficient porphyria (ADP) (Table 20-1). The gene defects 74

that underlie the acute porphyrias are loss-of-function mutations and typically reduce enzyme activity by half. This reduction results in a pattern of inheritance that is either recessive for the rare ADP or dominant with variable penetrance for the three more frequent acute porphyrias. Although the location of the defective hepatic enzyme in the synthetic pathway for heme varies among the acute porphyrias (see Fig. 20-1), all four may present with acute attacks that are similar in terms of symptoms and treatment. It is not known why enzymatic defects in chronic or erythropoietic porphyrias do not lead to acute attacks. HCP and VP may cause accumulation of excess porphyrins in the skin, where excitation by ultraviolet light causes blistering and scarring skin lesions.

Recognition Acute attacks of inducible porphyria are difficult to recognize in the perioperative setting because symptoms may be nonspecific and varied. Typical symptoms are summarized in Table 20-2. Attacks rarely occur before puberty and seldom recur throughout adult life. They last for several days and are characterized by intense abdominal pain that is steady and poorly localized. The pain intensity contrasts sharply with the paucity of physical findings, sometimes resulting in emergent exploratory laparotomy. Nausea, vomiting, and decreased bowel sounds are common but do not dominate

Glycine + Succinyl CoA ALA Synthetase

negative feedback

Aminolevulinic Acid (ALA)

Heme

Porphobilinogen

Protoporphyrin

Hydroxymethylbilane

Protoporphyrinogen

Uroporphyrinogen

Coproporphyrinogen

Figure 20–1

■

Heme synthesis.

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75

Barbiturates: Porphyrias

Acute-Inducible Porphyrias Neurovisceral Symptoms

Photosensitivity

Autosomal recessive

++

–

Autosomal dominant Autosomal dominant Autosomal dominant

+++ ++ ++

– + +

Type

Incidence

Inheritance

δ-Aminolevulinic acid dehydratasedeficient porphyria (ADP) Acute intermittent porphyria (AIP) Hereditary coproporphyria (HCP) Variegate porphyria (VP)

Exceedingly rare (only 7 cases reported) 1:10,000 (higher in Scandinavia) Rare (1:1 million) 1:300,000 (higher in South Africa)

the clinical picture; fever, leukocytosis, and abdominal tenderness are usually absent. Acute attacks of inducible porphyria may involve the peripheral nervous system in the form of a proximally accentuated motor weakness. This weakness occasionally occurs after resolution of the abdominal pain and may resemble Guillain-Barré syndrome, without the characteristic albumin increase in cerebrospinal fluid. Cranial nerves and sensory nerves may be affected, and progression of neurologic involvement to respiratory and bulbar paralysis and death is possible. In a quarter of patients the central nervous system may be involved, resulting in psychiatric symptoms such as anxiety, hallucinations, and paranoia. Generalized seizures may occur as a neurologic manifestation of central nervous system involvement or as a manifestation of severe hyponatremia caused by inappropriate secretion of antidiuretic hormone or vomiting. If acute porphyria is suspected, the diagnosis can be confirmed by screening for and quantifying the porphyrin precursors δ-aminolevulinic acid and porphobilinogen in urine. Daylight can convert the colorless porphobilinogen to porphyrins, causing a darkening and red to purple discoloration of the urine. Resolution of symptoms is usually rapid, but weakness may persist for days or months. In asymptomatic patients, the perioperative diagnosis of acute porphyria relies on a detailed family history. Because the more frequent forms are all inherited as autosomal

dominant diseases, many susceptible patients know of blood relatives with a diagnosis of acute porphyria. In contrast, laboratory investigations may be negative because the patient’s metabolic situation is compensated. Positive diagnosis of porphyria therefore belongs in the hands of a specialist.1

Risk Assessment The prevalence of acute porphyrias (see Table 20-1) is difficult to estimate because as many as 80% of affected patients may never experience an acute attack in their lifetimes. The prevalence of AIP is estimated to be about 1 in 10,000 in North America but may be as high as 1 in 1000 in Scandinavia or in people of Scandinavian descent. Clinically, AIP accounts for three quarters of acute attacks. VP is less prevalent, except in South Africans of Dutch descent; more than 20,000 cases have been traced to a single immigrant couple. HCP is rare, with an estimated prevalence of 1 in 1 million. Only seven cases of ADP have been reported. More important to risk assessment than prevalence data is the fact that acute attacks are always multifactorial. Even prior uneventful exposure to porphyrinogenic drugs does not rule out a diagnosis of acute porphyria. A high index of suspicion is therefore justified if the constellation of symptoms (see Table 20-2) fits that of an acute attack of porphyria.

Implications Table 20–2

■

Symptoms of a Porphyric Crisis

Parameter Peripheral nervous system Sensory Motor Autonomic Central nervous system Psychiatric Endocrine Neurologic Miscellaneous Laboratory

Symptom

Failure to diagnose and treat an acute attack of porphyria confers up to a 10% risk of mortality. Such failure not only prolongs the attack but also puts the patient at risk of further morbidity from the following: ●

Abdominal pain Proximally accentuated weakness; may involve cranial nerves and respiratory muscles Tachycardia; hypertension Anxiety; hallucinations; paranoia SIADH Seizures Nausea, vomiting Increased ALA and PBG in urine; light-exposed urine turns dark red or pink

ALA, δ-aminolevulinic acid; PBG, porphobilinogen; SIADH, syndrome of inappropriate secretion of antidiuretic hormone.

●

●

●

●

●

Further up-regulation of hepatic heme synthesis, because of decreased glucose intake Progression of motor involvement to include respiratory muscles and cranial nerves Residual paresis that persists even after resolution of the attack Seizures, which may be treated with porphyrinogenic drugs Exposure to porphyrinogenic drugs for other supportive treatment Unwarranted surgery

1 Information can be found on the American Porphyria Foundation Web site: www.porphyriafoundation.com.

PHARMACOLOGY

Table 20–1

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MANAGEMENT Perioperative care of patients with porphyria involves more than the avoidance of barbiturates. Preoperative assessment should identify whether symptoms of an acute attack are present. In the absence of an acute attack, the anesthetic prescription should consist of nonporphyrinogenic drugs. Details, as well as additional measures to minimize the risk of an acute attack, are discussed later. If the preoperative assessment suggests an acute attack of porphyria, both symptomatic and specific therapies should be instituted in an appropriate inpatient setting.

Acute Attack of Porphyria in the Perioperative Period Therapy for acute attacks of porphyria consists of three interventions: (1) administration of hematin and (2) administration of glucose, both of which inhibit δ-aminolevulinic acid synthase and thus correct the metabolic abnormality; and (3) identification and removal of the precipitating factor to decrease enzyme induction. Hematin (Panhematin, Ovation Pharmaceuticals, Deerfield, Ill) contains alkaline heme from processed human red blood cells. It is a lyophilized powder that is best reconstituted in albumin to form a stable solution and minimize thrombophlebitis and anticoagulation. Depending on the severity of an attack, hematin is given at a dose of 3 to 4 mg/kg for up to 4 days. Hematin replenishes the hepatic heme pool and normalizes the activity of the heme synthesis pathway by providing negative feedback (see Fig. 20-1). Given the mortality risk and the potential for severe or protracted neurologic symptoms with acute attacks of porphyria, hematin therapy should be initiated as early as possible. Glucose, at a dose of 300 to 400 g/day, is less effective than hematin but has been shown to decrease the excretion of porphyrin precursors. Furthermore, fasting and lowcarbohydrate diets can precipitate acute attacks. Although glucose is effective when administered enterally, the nausea and decreased intestinal motility accompanying an acute attack make parenteral administration more feasible. Finally, identification and removal of precipitating factors should include a careful assessment of the patient’s drug therapy to determine the safety implications of such drugs in a patient with suspected acute porphyria (Table 20-3). Given that the causes of an acute attack may be multifactorial, complete removal of all precipitating factors may not be possible. Supportive therapy focuses on the symptoms associated with the attack. Pain is treated with opiates, and electrolyte imbalances are corrected. Cranial nerve involvement may require aspiration prophylaxis, whereas involvement of respiratory muscles may require mechanical ventilation or close monitoring in an intensive care unit. Seizures present a particular challenge because barbiturates, phenytoin, and some other antiseizure drugs are potent triggers for an acute attack. Hyponatremia should be excluded as a cause of seizures, and midazolam or clonazepam can be used safely to stop seizure activity.

Table 20–3

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Unsafe/Avoid Barbiturates Etomidate Phenytoin Valproic acid Succinimides Pyrazolones Clindamycin Erythromycin Doxycycline Sulfonamides Amiodarone

Safety of Drugs in Patients with Acute Porphyria Use with Caution/ Avoid Ketorolac Macrolides Tetracyclines Quinolones Hydralazine Calcium channel blockers

Probably Safe Opiates Neuromuscular blockers Glycopyrrolate Atropine Neostigmine Naloxone Midazolam Flumazenil Nitrous oxide Halothane Local anesthetics Procainamide β-Blockers Scopolamine Diphenhydramine Chlorpromazine

This list is incomplete, and unlisted drugs cannot be assumed to be safe. These categories are intended to provide guidance and not to replace the clinical judgment of the prescribing physician. Some drugs are categorized based on clinical experience, irrespective of the presence or absence of warnings in the package insert. Porphyrics should be treated with the minimum number of drugs necessary.

Anesthetic Management of Patients with Acute Porphyria Assessment of the safety profile of drugs in porphyria is difficult. On the one hand, drugs are the most frequent precipitating factor of acute attacks. On the other hand, not every exposure of susceptible patients to porphyrinogenic drugs results in an acute attack. Information about drug safety in porphyria is derived from three sources, listed in order of decreasing clinical applicability: (1) actual human cases that suggest a temporal or causal relationship, (2) animal models of induced porphyria, and (3) cell culture. The last two sources tend to overstate the risks to patients and frequently provide conflicting information.2 Volatile anesthetics, for example, are porphyrinogenic in animal models, but clinical experience with halothane and isoflurane suggests that they are safe to use. Many drugs can be used with caution, provided they are indicated and the potential benefits outweigh the risks. The anesthetic plan for patients with porphyria should avoid agents that are known to precipitate acute attacks (see Table 20-3). For general anesthesia, propofol is considered the induction agent of choice, whereas barbiturates and etomidate should be avoided. Muscle relaxants and opioids are safe. As stated earlier, volatile agents appear safe, although data on sevoflurane and desflurane are limited. Local and regional anesthesia can be used safely in patients with porphyria, but during an acute attack, autonomic instability, psychiatric symptoms, weakness, and hypovolemia

2 More detailed drug information and lists of safe and potentially unsafe drugs can be found on the following Web sites: http://web.uct.ac.za/depts/porphyria/professional/prof%20index.htm and http://www.porphyries.com.fr.

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PREVENTION Perioperative prevention of acute attacks in patients with acute porphyria requires careful planning and good communication among all caregivers. Admission on the night before surgery allows prophylactic administration of glucose, thus minimizing the impact of the preoperative fast. Reassurance and premedication can relieve anxiety and stress. Drug administration should be minimized, and each drug should be assessed for its risk of precipitating an acute attack. Because a delayed porphyric crisis may develop 3 to

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5 days after the precipitating event, discharge instructions should stress the symptoms of a porphyric crisis as reportable postoperative complaints. The workup for symptoms should include screening for and quantification of the urinary porphyrin precursors δ-aminolevulinic acid and porphobilinogen. Such an integrated approach allows for the safe conduct of surgery in patients with acute porphyria.

Further Reading Dover SB, Plenderleith L, Moore MR, et al: Safety of general anesthesia and surgery in acute hepatic porphyria. Gut 35:1112-1115, 1994. Elder GH, Hift RJ, Meissner PN: The acute porphyrias. Lancet 349:1613-1617, 1997. Harrison GG, Meissner PN, Hift RJ: Anesthesia for the porphyric patient. Anaesthesia 48:417-421, 1993. James MFM, Hift RJ: Porphyrias. Br J Anaesth 85:143-153, 2000. Palmieri C, Vigushin DM, Peters TJ: Managing malignant disease in patients with porphyria. Q J Med 97:115-126, 2004.

PHARMACOLOGY

may present relative contraindications. Clinical experience suggests that both amide- and ester-type local anesthetics are safe, even though lidocaine increases δ-aminolevulinic acid synthase activity in tissue culture.

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Ketamine Lisa Thannikary and Bhiken Naik Case Synopsis A 68-year-old man is brought to the operating room emergently for exploratory laparotomy after suffering a gunshot wound to the abdomen. He is tachycardiac with a heart rate of 114 beats per minute and hypotensive with a blood pressure of 86/47 mm Hg. He was resuscitated with 2 L of crystalloid in the emergency room. Although he was not intubated, he was unable to give any history owing to acute ethanol intoxication. A rapid-sequence induction with cricoid pressure is performed with intravenous ketamine (3 mg/kg) and succinylcholine (1.5 mg/kg). Intubation occurs without difficulty. Following intubation, the patient’s blood pressure decreases precipitously to 65/33, and an ST segment depression of 2 mm is noted in lead V5. The patient is treated with intravenous fluids and ephedrine, with minimal improvement in blood pressure. A transesophageal echocardiogram shows decreased myocardial contractility.

PROBLEM ANALYSIS Definition Ketamine is a phencyclidine derivative used for the induction of anesthesia; it provides anterograde amnesia as well as intense analgesia. It is the only induction agent that stimulates the sympathetic nervous system centrally, which can lead to an increase in blood pressure and heart rate of approximately 30% from baseline values. These hemodynamic effects are seen after 3 to 5 minutes of intravenous injection and slowly decrease to predrug levels after about 20 minutes. The cardiovascular stimulating effects can be blunted by the prior administration of benzodiazepines or concomitant use of inhalation agents. The mechanisms for the increase in hemodynamic variables are complex. Ketamine is believed to stimulate the central nervous system directly, leading to increased sympathetic outflow. Increased plasma levels of epinephrine and norepinephrine that occur after injection of the drug are also believed to play a role in increasing the heart rate and blood pressure. Ketamine has direct negative inotropic effects, however, that are usually overshadowed by the sympathetic stimulation. These negative inotropic effects are usually seen with depletion of endogenous catecholamine stores or with exhaustion of the sympathetic nervous system compensatory mechanisms in patients who are critically ill or in shock.

Recognition If a patient has an attenuated or blunted response to an induction dose of ketamine, the possibility of depleted catecholamine stores or exhausted sympathetic nervous system compensatory mechanisms, with unmasking of the direct myocardial depressant effects of ketamine, must be considered.

Risk Assessment Clinical scenarios in which the negative inotropic effects of ketamine can be unmasked include the following: ● ●

Prolonged critical illness Uncompensated shock

78

● ● ● ●

Inadequate volume resuscitation Underlying ischemic heart disease Chronic β-blocker therapy Cocaine use

Implications Ketamine antagonizes N-methyl-D-aspartate receptors. It also interacts with μ, δ, and κ opioid receptors, as well as with monoaminergic receptors, muscarinic receptors, and voltage-sensitive calcium channels. It produces dissociative anesthesia resembling a cataleptic state in which the patient is noncommunicative but appears awake. Because ketamine is a phencyclidine derivative, emergence delirium is possible, but this can be reduced with concomitant use of benzodiazepines. Ketamine has a rapid onset of action, a relatively short duration of action, and high lipid solubility. It does not bind significantly to plasma proteins and is initially distributed to highly perfused tissues, such as the brain. Ketamine rapidly crosses the blood-brain barrier owing to its high lipid solubility. Ketamine’s pharmacokinetic characteristics (Table 21-1), coupled with its sympathomimetic effects, make it an ideal induction agent for patients who are hemodynamically unstable.

Table 21–1

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Pharmacokinetic Properties of Intravenous Ketamine

Parameter

Value

pKa Protein binding (%) Distribution half-life (min) Distribution volume at steady state (L/kg) Clearance (mL/kg/min) Elimination half-life (hr) Breakdown product

7.5 12 11-16 2.5-3.5

Elimination

12-17 2-4 Norketamine (20%-30% potency of ketamine) Renal

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Ketamine

79

PREVENTION

MANAGEMENT

It is important to recognize risk factors that may lead to hypotension with the use of ketamine. In these patients, an alternative induction agent should be used.

Before induction of anesthesia, anesthesiologists should attempt to identify patients who might be at risk for developing a hypotensive response to ketamine. Patients with hypovolemic or hemorrhagic shock should be volume-resuscitated before induction, if possible. Invasive monitoring, including central venous pressure, pulmonary artery catheter, or transesophageal echocardiography, can be used in the perioperative period to optimize filling pressures and contractility. If the patient remains hypotensive after induction—despite adequate fluid resuscitation—an inotropic agent or pressor (or both) may be needed to ensure adequate perfusion pressure to the vital organs. The optimal inotropic agent in these patients is a direct-acting sympathomimetic, such as epinephrine or norepinephrine.

Further Reading Reich DL, Silvay G: Ketamine: An update on the first 25 years of clinical experience. Can J Anaesth 36:186-197, 1989. Rogers RJ: Intravenous anesthetic agents. In Kirby RR, Gravenstein N, Lobato EB, et al (eds): Clinical Anesthesia Practice. Philadelphia, WB Saunders, 2002, pp 636-637. Stoelting RK: Nonbarbiturate induction drugs. In Stoelting RK (ed): Pharmacology and Physiology in Anesthetic Practice. Philadelphia, Lippincott-Raven, 1999, pp 148-155. Tweed WA, Minuck MS, Mymin D: Circulatory response to ketamine anesthesia. Anesthesiology 37:613-619, 1972.

PHARMACOLOGY

Caution should be exercised, however, when using ketamine in the aforementioned high-risk patients.

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Nonbarbiturate Anesthetics Harshdeep Wilkhu, Kevin P. Chan, E. Price Stover, and John L. Atlee Case Synopsis A 53-year-old, 75-kg man with no significant past medical history or allergies is scheduled for a screening colonoscopy. During anesthetic induction he receives a bolus of propofol (80 mg) with additional propofol (170 mg) titrated in divided doses over the course of the procedure. The patient maintains spontaneous ventilation throughout the procedure. Upon completion of the procedure, the patient is responsive to verbal commands and is transferred to the recovery room. Ten minutes after arrival, the patient develops gross arrhythmic jerking of all limbs that appears to be a grand mal seizure.

PROBLEM ANALYSIS Definition In addition to ketamine (see Chapter 21), nonbarbiturate anesthetics include midazolam, etomidate, and propofol. Midazolam is more commonly used as a sedative-anxiolytic than as an intravenous (IV) anesthetic induction agent. Both etomidate and propofol are used as IV induction agents; the former is often preferred for patients with or at risk for hemodynamic instability.

Recognition MECHANISM

OF

ACTION

Midazolam is a benzodiazepine that increases the frequency of chloride channel opening by facilitating γ-aminobutyric acid (GABA) receptor binding, and it has an inhibitory effect on neural function. GABA is the principal central nervous system neuroinhibitory transmitter.

Table 22–1

■

Etomidate is an imidazole derivative. It inactivates the reticular activating system and may also increase GABA receptor availability. Propofol is an alkylphenol. It is presumed to act on GABA receptors in the central nervous system to increase the frequency of chloride channel opening. Thus, propofol too has a neuroinhibitory action. PHARMACOKINETICS Midazolam is water soluble in a buffered acid medium (pH = 3.5) and highly lipophilic at physiologic pH. Other pharmacokinetic data for propofol, etomidate, and midazolam are listed in Table 22-1. Etomidate is water soluble and is dissolved in 35% propylene glycol. Its short duration of action is the result of redistribution after an initial distribution time of 3 minutes. It is metabolized by the liver into inactive metabolites that are excreted by the kidneys (85%) and in the bile (13%). Age decreases its clearance, whereas in cirrhosis, clearance is normal but the volume of distribution and elimination half-time are doubled.

Pharmacokinetic Data for Propofol, Etomidate, and Midazolam Drug

Parameter

Propofol

Etomidate

Midazolam

Distribution half-life (min)

2-8

3-10

Elimination half-life (hr) Biotransformation Metabolites Excretion IV induction dose IV sedation dose IV maintenance dose

0.5-1.5 Hepatic; extrahepatic (lungs) Inactive Renal 1-2.5 mg/kg 10-75 μg/kg/min 50-150 μg/kg/min

Initial: 3 Late: 29 2-5 Hepatic Very weakly active Renal (85%); bile (13%) 0.2-0.5 mg/kg 5-8 μg/kg/min 10 μg/kg/min (with N2O-opiate)

80

1-4 Hepatic Inactive Renal 0.1-0.2 mg/kg 0.5-1 mg incremental dosing 0.05-0.1 μg/kg/min

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HEMODYNAMIC

AND

OTHER EFFECTS

Midazolam has little effect on hemodynamic parameters (Table 22-2). At a dose of 0.2 mg/kg, midazolam appears to be safe in patients with cardiovascular disease. Any increase in heart rate is likely a reflex-caused response to modestly decreased stroke volume and blood pressure, with reduced sympathetic tone secondary to anxiolysis. Hypovolemia accentuates these effects. In contrast, midazolam can cause apnea and decrease the ventilatory response to carbon dioxide (CO2), especially after bolus dosing. Also, midazolam is commonly given with an opiate (e.g., fentanyl, alfentanil) for sedation in the preoperative or ambulatory surgery holding area. Such opiates potentiate midazolam’s effect on respiration, so patients receiving this combination of drugs must be closely monitored for signs of respiratory insufficiency. Etomidate does not affect sympathetic activity or baroreflex function. It confers reliable hemodynamic stability in patients with or without cardiac disease. The myocardial oxygen (O2) supply-demand ratio is maintained. A slightly negative inotropic effect occurs with its solvent (propylene glycol), which likely explains any observed hemodynamic changes (see Table 22-2). In hemorrhagic shock models,

Table 22–2

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Nonbarbiturate Anesthetics

etomidate is associated with increased survival compared with thiopental. However, some studies suggest that the cardiovascular depression with etomidate is similar to that with propofol. Finally, etomidate is less likely to cause apnea or decrease the ventilatory response to CO2 than is midazolam. Propofol has potent cardiovascular depressant effects. It decreases mean arterial pressure by as much as 40% due to myocardial depression and vasodilatation. Preload and afterload are reduced secondary to decreased venous return and systemic vascular resistance, respectively. This is brought about by propofol’s action to reduce sympathetic tone and directly relax vascular smooth muscle. However, the myocardial O2 supply-demand balance is maintained. Propofol also impairs the vasoconstrictor reflex in acute hemorrhage. Propofol has neuroexcitatory side effects that range from mild, involuntary myoclonic limb movements to grand mal seizures; their timing is quite variable and may occur with induction, in the recovery room, or even many days afterward. However, most neuroexcitatory events related to propofol occur during induction or emergence from anesthesia, when both plasma and cerebral concentrations of the drug are in a dynamic state of flux. They also occur in a variety of scenarios: lengthy or short, major or minor surgical procedures; with or without a prior history of neurologic events.

Risk Assessment When choosing a nonbarbiturate anesthetic for short outpatient procedures, there are several options, including midazolam, etomidate, propofol, and ketamine (see Chapter 21). The most commonly used drug is propofol, owing to its rapid onset of action and recovery and lack of serious side effects. However, when choosing among these nonbarbiturates as IV induction agents, one must consider whether any of the following is present or possible: ● ●

Hypovolemia or circulatory shock Cardiovascular disease

Hemodynamic, Respiratory, and Other Effects of Propofol, Etomidate, and Midazolam Drug

Parameter

Propofol

Etomidate

Midazolam

Heart rate Mean arterial pressure Systemic vascular resistance Mean pulmonary artery pressure Cardiac index Stroke volume Myocardial contractility Apnea Ventilatory response to CO2 Bronchodilatation Nausea and vomiting Analgesia Pain on injection

↓ ↓↓ ↓↓ 0 ↓↓ ↓↓ 0/↓ ↑↑↑ ↓↓↓ + in COPD Decrease Minimal Severe

0/↑ 0/↓ 0/↓ 0/↑ 0/↑ 0/↓ 0/↓ ↑ ↓ 0 Increase Minimal Possible

0/↑ 0/↓ 0/↓ 0 0/↓ 0/↓ 0/↓ ↑↑ ↓↓ 0 Minimal Minimal Minimal

COPD, chronic obstructive pulmonary disease.

81 PHARMACOLOGY

Propofol is highly lipophilic and is formulated in a soybean oil–egg yolk–lecithin emulsion. Pharmacodynamic properties of propofol are dependent on the plasma concentration of the drug. The induction dose of propofol in adults is 1 to 2.5 mg/kg, producing blood concentrations of 2 to 6 μg/mL. Awakening is rapid even after prolonged infusions and typically occurs at plasma concentrations of 1.0 to 1.5 μg/mL. Steady-state propofol blood concentrations are generally proportional to infusion rates. The context-sensitive half-time of propofol is minimally influenced by infusion duration, owing to rapid metabolic clearance. Biotransformation occurs in the liver. Clearance exceeds hepatic blood flow, suggesting the existence of extrahepatic metabolism. Metabolites are secreted in the urine. Hepatic or renal dysfunction does not reduce the clearance of the parent drug.

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Respiratory insufficiency Central nervous system injury or impairment Hepatic or renal impairment and any related pharmacokinetic implications Drug interactions Full stomach or history of acid reflux

MIDAZOLAM As earlier noted, midazolam has minimal adverse cardiovascular effects and appears to be safe in patients with coronary or heart disease (at doses of 0.2 mg/kg); however, it has the potential to aggravate respiratory insufficiency (see Table 22-2). Other considerations include the following: ●

●

●

●

●

●

Hepatic biotransformation with inactive metabolites; renal excretion Slight reduction in cerebral O2 consumption, with little or no decrease in cerebral blood flow Small decrease in intracranial pressure (ICP); small increase in seizure threshold Maintains cerebral autoregulation; large decrease in intraocular pressure (IOP) Slower loss of consciousness and longer recovery period for return of cognitive functions Potential for coughing, hiccups, or involuntary skeletal muscle movements when used for induction of anesthesia

ETOMIDATE Etomidate has generally supportive and beneficial effects on both cardiovascular and cerebral function. However, as noted earlier, there is a slightly negative inotropic effect with its solvent (propylene glycol). Etomidate has minimal effects on ventilation and does not trigger histamine release. It is not an analgesic. Similar to the effects of midazolam, coughing, hiccups, or involuntary skeletal muscle movements (nonepileptogenic) may occur if etomidate is used for anesthetic induction. Although grand mal seizures have occurred with etomidate, it induces electroencephalographic burst suppression at high doses. Other considerations are the following: ● ● ●

●

●

● ●

●

Increased incidence of nausea and vomiting Irritation at peripheral vein injection site Clinically significant adrenocortical inhibition with prolonged infusions May reduce IOP, but this is counteracted by myoclonus, mydriasis, or coughing Unlikely to cause apnea or impair the ventilatory response to CO2 Hepatic metabolism; inactive metabolites; renal elimination Initial distribution half-life of 3 minutes and redistribution half-life of about 30 minutes Elimination half-life of 3 to 5 hours

inotropic effects are due to reduced myocardial intracellular calcium availability, caused by Ca2+ influx inhibition. Overall, propofol decreases sympathetic more than parasympathetic activity, leading to parasympathetic dominance. Propofol produces dose-dependent respiratory depression that acts in synergy with opioids and benzodiazepines. Further, it has a high potential to impair the ventilatory response to CO2 and cause apnea (see Table 22-2). Continuous infusions reduce both the tidal volume and the frequency of breathing; opiates potentiate this effect. Propofol has a bronchodilating effect, and it decreases the intraoperative incidence of bronchospasm with reactive airways disease. In February 2001 the Food and Drug Administration noted that abrupt discontinuation of propofol after prolonged infusion may result in agitation, tremulousness, and hyperirritability in pediatric patients. This led to a pediatric exclusivity labeling change: propofol is not indicated for prolonged use in the pediatric intensive care unit. Other effects to consider are the following: ●

●

● ●

●

●

●

●

Coughing, hiccups, and involuntary skeletal muscle movements with induction Vein irritation and pain on injection (lidocaine helps reduce this, but slow, incremental, “desensitizing” injections are more reliable)1 Antiemetic, antipruritic, and anxiolytic properties Reports of delayed seizures, hallucinations, and opisthotonos Formerly, anaphylactic reactions and bacterial growth were possible with the lipid solvent (less of a problem with the current formulation) Hepatic and possible extrahepatic biotransformation, with inactive metabolites and renal (85%) and bile (13%) excretion Reduction in cerebral O2 consumption, blood flow, and ICP and IOP No effect on seizure threshold, and not an analgesic

Implications The delayed onset of neurologic excitatory events (especially with etomidate or propofol) has serious implications for ambulatory surgery (outpatient) anesthesia practice. When patients are discharged home 1 to 2 hours after surgery or other procedures, they are at serious risk of harm to themselves or others. The patient or family can be traumatized during a seizure, and loss of the airway during this event can have dire consequences. Adverse neurologic sequelae also increase health care costs because many of these patients must be admitted to an intensive care unit to rule out serious pathology and undergo costly diagnostic studies (e.g., magnetic resonance imaging, computed tomography, electroencephalography). In addition, consultant care may be requested for these events.

PROPOFOL Propofol reduces systemic blood pressure by vasodilatation and negative inotropic effects. The inhibition of efferent sympathetic activity results in vascular smooth muscle relaxation and blood pressure reduction. Propofol’s negative

1 We have found that 1-, 2-, and 3-mL “desensitizing” increments of propofol spaced 30 to 45 seconds apart, followed by an IV “push” of the remaining induction dose, are effective at reducing the discomfort associated with propofol induction. Lidocaine (50 mg) can be either mixed with or given before propofol.

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Chapter 22

MANAGEMENT Selection of an appropriate nonbarbiturate IV induction agent must take the following issues into consideration: ●

Hypovolemia or hypotension due to hemorrhage ● Restore intravascular volume (preload) and use blood or blood products as needed. ● Optimize ventilation and oxygenation. ● Restore acid-base balance. ● Consider the use of vasoactive drugs. ● Initiate invasive monitoring, transesophageal echocardiography, or both, if needed. ● Choose a nonbarbiturate anesthetic and method of delivery according to the aforementioned considerations.

●

Airway management ● Use awake intubation followed by an IV induction agent or inhalational anesthetic. ● Assess the need for rapid or modified rapid-sequence intubation.

●

Increased ICP ● Choose an IV induction agent accordingly (propofol or etomidate decreases ICP). ● Consider hypocapnia, mannitol, and corticosteroids (see also Chapters 174 and 182).

Neuroexcitatory Events Initially, no treatment may be necessary because the majority of neuroexcitatory events resolve spontaneously. Benzodiazepines are the drugs of choice for events that do not resolve spontaneously. They depress spinal reflexes and reduce the spontaneous electrical activity in all regions of the brain and spinal cord. All benzodiazepines elevate the seizure threshold and thus are considered anticonvulsants. These drugs are quite safe and are rarely fatal, unless taken concomitantly with other sedatives. Second-line therapy for neuroexcitatory events is a barbiturate. This family of drugs depresses the activity of all excitable central nervous system tissue. In general, barbiturates possess a low therapeutic index, along with low selectivity. Hence, they must be dosed cautiously.

PREVENTION Avoidance of complications with nonbarbiturate IV induction agents requires attention to the following issues: ●

●

Hypovolemia and Airway Management

Increased Intracranial or Intraocular Pressure Midazolam, etomidate, and propofol exert a beneficial decrease in ICP, in contrast to ketamine, which increases

83

ICP and can produce emergence delirium. However, slower emergence with midazolam can hinder early postoperative neurologic assessment. Both midazolam and propofol decrease IOP. Etomidate has the same effect, but it can be counteracted by myoclonic activity, mydriasis, and cough caused by etomidate. Ketamine increases IOP.

●

Resuscitation begins with securing a compromised airway, optimizing O2 delivery, restoring intravascular volume, and correcting acidosis. A rapid-sequence induction is usually necessary to minimize the risk of aspiration. In the case of a difficult airway or an unstable cervical spine, awake intubation is indicated in a cooperative patient. The choice of an IV anesthetic is dictated by its cardiovascular, cerebrovascular, and pharmacokinetic effects (see Tables 22-1 and 22-2). Of the agents discussed here, etomidate is probably the safest agent for patients with significant hypovolemia or blood loss. However, regardless of which agent is selected, its dose must be reduced in the presence of significant hemorrhage or reduced intravascular volume, because either of these conditions will increase the amount of drug delivered to the heart or brain due to redistribution of blood flow to vital organs.

Nonbarbiturate Anesthetics

●

Volume repletion and administration of blood or blood products, if indicated Appropriate selection of the IV anesthetic induction agent. Consider time of onset and emergence, amnesia, analgesia, coronary and cerebral perfusion, systemic blood pressure, myocardial and cerebral O2 consumption, onset of apnea, and effects on ICP and IOP. Slow titration and adjustment of induction doses. Careful titration to effect generally prevents abrupt, deleterious changes in blood pressure, unless a rapid-sequence induction is indicated. If so, a vasopressor may be needed for the patient to tolerate the induction. Doses of IV induction agents should be adjusted based on the patient’s age, ideal weight, and hepatic and renal function. Side effects of and relative contraindications to the various IV anesthetic induction agents

For the patient described in the case synopsis, prevention of future neuroexcitatory events suggests that propofol (or etomidate) should not be administered to him in the future. This advice might also apply to patients with a history of neuroexcitatory events. However, no single diagnosis or combination of diagnoses has been implicated as the cause of such events. The seeming rarity of major neuroexcitatory events with administration of propofol or etomidate, along with the lack of reported long-term adverse sequelae, has resulted in their continued use in ambulatory and inpatient settings, especially propofol. The overall risk-benefit ratio for propofol is extremely low, and the decision whether to use the drug should not be based on reports of rare associated neurologic phenomena.

PHARMACOLOGY

Patients with cardiovascular disease or hypovolemia are at increased risk for cardiovascular collapse and myocardial ischemia or infarction after IV anesthesia induction (greatest risk with propofol, followed by midazolam and then etomidate). Hemorrhagic shock results in lactic acidosis, and hepatorenal lactate clearance must be maintained. End-organ perfusion in general must be preserved. Also, the risk of irreversible brain or ocular injury must be carefully evaluated during the selection of a rapid IV induction agent.

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Further Reading Dearlove JC, Dearlove OR: Cortical reflex myoclonus after propofol anaesthesia. Anaesthesia 57:834-835, 2002. Reves JG, Glass PSA, Lubarsky DA, et al: Intravenous nonopioid anesthetics. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 317-378.

Strachan AN, Raithatha HH: Propofol myoclonus. Can J Anaesth 43:536-537, 1996. Sutherland MJ, Burt P: Propofol and seizures. Anaesth Intensive Care 22:733-737, 1994. Walder B, Tramer MR, Seeck M: Seizure-like phenomena and propofol: A systematic review. Neurology 58:1327-1332, 2002.

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ANESTHETIC ADJUNCTS

23

Succinylcholine Eugene B. Freid Case Synopsis A 32-year-old woman undergoes emergent open reduction of bilateral femoral fractures sustained in a fall. Past history is pertinent only for mild, hemiparetic, static encephalopathy as a result of meningitis in infancy. Rapid-sequence induction of anesthesia with 20 mg of etomidate and 80 mg of succinylcholine is uneventful. At the end of the 2-hour procedure, she is clinically weak, with four diminished twitches and moderate fade on a train-of-four. She is extubated 1 hour after completion of surgery. Evaluation reveals a pseudocholinesterase activity of 95% and a dibucaine number of 25, which is consistent with an abnormal genetic variant of pseudocholinesterase.

PROBLEM ANALYSIS Definition The onset and offset characteristics of succinylcholine provide distinct advantages over other neuromuscular blocking drugs. Unfortunately, succinylcholine also has a number of well-described complications related to its mechanism of action or pharmacokinetics or that occur as an idiosyncratic effect (Table 23-1). Observations show that hyperkalemia and cardiac arrest develop soon after succinylcholine administration to patients with thermal injury, trauma, upper and lower motor neuron injuries, and various myopathies (Table 23-2). Prolonged relaxation may occur after succinylcholine administration because of the development of a phase II blockade or decreased metabolism. After a single large dose, repeated doses, or a prolonged continuous infusion of succinylcholine, the postjunctional receptor may not respond

normally to acetylcholine, even after the receptor-nicotinic channel has repolarized. This is termed a phase II block and is preferred to the terms dual block and nondepolarization block because phase II block does not imply a specific mechanism. Under normal circumstances, the short duration of the effect of succinylcholine is the result of rapid hydrolysis by pseudocholinesterase. Ninety percent of an intravenous dose of succinylcholine is rapidly hydrolyzed to a nearly inactive metabolite in the plasma and liver by pseudocholinesterase. Neuromuscular blockade terminates by the diffusion of succinylcholine from the end plate into the extracellular fluid because there is no pseudocholinesterase at the motor end plate. Pseudocholinesterase influences the onset and duration of action by controlling the rate of hydrolysis in plasma. A prolonged duration of succinylcholine neuromuscular block may occur when quantities of normal pseudocholinesterase are decreased or when an atypical or abnormal variant of pseudocholinesterase is present.

˜

Table 23–1

■

Complications of Succinylcholine Administration

Cardiovascular Tachycardia (ganglionic stimulation) Bradycardia, sinus arrest, junctional rhythm Hyperkalemia Fasciculations; myalgia* Myoglobinuria, elevated plasma creatine phosphokinase Sustained muscle contraction (myotonic dystrophy, congenital myotonia) Malignant hyperpyrexia Masseter muscle rigidity Prolonged relaxation Phase II block Inadequate pseudocholinesterase activity Increased intraocular pressure* Increased intracranial pressure Increased intragastric pressure* Histamine release

Table 23–2

■

Conditions Predisposing to Exaggerated Potassium Release with Succinylcholine

Thermal injury Traumatic injury Neurologic disease Spinal cord trauma Hemiparesis, lower motor neuron lesions Multiple sclerosis Stroke Guillain-Barré disease Encephalitis Central nervous system trauma Myopathy, muscular dystrophy Disuse atrophy Tetanus

*May be reduced with succinylcholine pretreatment (defasciculation).

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Recognition T-wave elevation, QRS complex prolongation and a sinusoidal QRS waveform (see Chapter 14, Fig. 14-2), and arrhythmias (ventricular tachycardia or fibrillation) occurring shortly after succinylcholine administration are the characteristic alterations seen on the electrocardiogram (ECG) in patients with hyperkalemia and exaggerated potassium (K+) release. Measurement of serum K+ concentrations confirms hyperkalemia. However, if the ECG is abnormal, treatment should precede confirmation of serum K+ concentrations. Prolonged relaxation after succinylcholine is indicated by apnea and neuromuscular weakness or paresis. The diagnosis is confirmed by characteristic findings on peripheral nerve stimulation, including a train-of-four (T4/T1) of less than 0.3 and the presence of fade and post-tetanic facilitation. The presence of low levels of normal pseudocholinesterase, or atypical or abnormal forms of pseudocholinesterase, leads to variable prolongation of neuromuscular blockade (Table 23-3). The presence of abnormal pseudocholinesterase is frequently recognized only after moderately or very prolonged blockade occurs in an otherwise healthy patient who received a normal dose of succinylcholine. Nerve monitoring characteristics typical of a phase II block should be expected when abnormal pseudocholinesterase is present due to the large concentration of unmetabolized succinylcholine at the neuromuscular junction.

Risk Assessment POTASSIUM RELEASE Under normal conditions, depolarization of skeletal muscle occurs at acetylcholine receptors at the motor end plate. Fluxes in sodium (Na+) and K+ after succinylcholine typically lead to an increase in serum K+ concentrations of up to 0.5 mEq/dL. In a number of pathologic conditions, however, exaggerated K+ release following succinycholine causes plasma K+ concentrations to rise excessively (see Table 23-2). In patients with denervation states, up-regulation of acetylcholine receptors leads to muscle supersensitivity. In effect, the entire muscle membrane acts as a motor end plate.

Table 23–3

■

The increased zone of permeability to Na+ and K+ leads to exaggerated movement of these ions after the administration of succinylcholine and consequent increased efflux of K+ from the myocytes into the extracellular fluid. The timing of the development of exaggerated K+ release with succinylcholine administration depends on the nature of the injury and follows the timing of the development of acetylcholine receptor supersensitivity. Typically, it begins 5 to 15 days after thermal injury or trauma, peaks at 20 to 60 days, and persists for up to 3 months. In patients with upper and lower motor neuron disease, it begins at 7 days and persists for about 6 months. Pretreatment with a nondepolarizing relaxant does not reliably abolish the hyperkalemic response. In infants and children, myopathy may be clinically unapparent and may be diagnosed only after succinylcholine-hyperkalemic cardiac arrest. In contrast, patients with static encephalopathies (e.g., cerebral palsy) typically do not have exaggerated K+ release after succinylcholine, because their nervous system damage is remote and stable. PHASE II BLOCK Clinically relevant phase II block can occur with total succinylcholine doses as low as 4 mg/kg in some patients, with either repeat dosing or continuous infusions. Such block may be evident with tetanic stimulation in highly sensitive (“fine”) muscle groups (e.g., extraocular muscles) before it occurs in the larger muscles involved in respiration. Development of tachyphylaxis, which manifests as an increase in the amount of infused succinylcholine, often occurs concurrently with the development of clinically relevant phase II block. PSEUDOCHOLINESTERASE Low pseudocholinesterase activity occurs in the newborn and the elderly; with pregnancy, liver disease, malignancy, or thermal injury; and with the use of certain medications (glucocorticoids, estrogens, echothiophate, bambuterol, phenelzine, and cyclophosphamide) and organophosphate pesticides. Pseudocholinesterase levels may drop precipitously

Characteristics of Normal, Atypical, and Abnormal Pseudocholinesterase

Pseudocholinesterase Type

Genotype

Duration of Clinical Block

Homozygous normal Heterozygous dibucaine Heterozygous fluoride Heterozygous silent Dibucaine fluoride Dibucaine silent Fluoride silent Homozygous dibucaine (atypical) Homozygous fluoride Homozygous silent

Eu Eu Eu Ea Eu Ef Eu Es Ea Ef Ea Es Ef Es Ea Ea Ef Ef Es Es

Normal Slightly prolonged Slightly prolonged Slightly prolonged Moderately prolonged Very prolonged Moderately prolonged Very prolonged Slightly prolonged Very prolonged

Dibucaine No.

Fluoride No.

80 60 75 80 50 20 65 20 65 —

60 50 50 60 50 20 35 20 35 —

Adapted from Pantuck EJ, Pantuck CB: Prolonged apnea following succinylcholine administration. In Azar I (ed): Muscle Relaxants. New York, Marcel Dekker, 1987, pp 206-229.

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Succinylcholine

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medicine specialist for an occult myopathy should be performed.

Prolonged Block Treatment for prolonged relaxation includes ensuring an adequate airway and gas exchange until phase II block is no longer evident (neuromuscular function monitoring) and adequate muscle strength is present. Pure phase II block is reversible with anticholinesterase. However, the block caused by succinylcholine overdose or with atypical or abnormal pseudocholinesterase is mixed (phase I and phase II block). In this case, anticholinesterase therapy may lengthen the duration of phase I block. Most practitioners simply continue ventilatory support until the block wanes and muscle strength has returned to its baseline level. With prolonged block due to atypical or abnormal pseudocholinesterase, ventilatory support must be continued until muscle strength returns. Although banked blood and plasma contain active pseudocholinesterase, the risk associated with their transfusion outweighs the possible benefit of reversing prolonged block. Patients suspected of having atypical or abnormal pseudocholinesterase should be tested for pseudocholinesterase activity and type and made aware of their condition. There should be a note in the patient’s chart indicating an “allergy” to succinylcholine, and the patient should wear a MedicAlert bracelet.

Implications The consequences of succinylcholine-induced hyperkalemia include arrhythmias and cardiac arrest. Prolonged relaxation after succinylcholine requires airway management and mechanical ventilation (with sedation) until the neuromuscular weakness subsides. Patients with atypical or abnormal pseudocholinesterase also demonstrate prolonged metabolism of mivacurium and ester local anesthetics. Because red blood cell esterase hydrolyzes esmolol, its metabolism is unaffected in patients with atypical or abnormal pseudocholinesterase.

MANAGEMENT Hyperkalemia Ventricular tachyarrhythmias and fibrillation are treated with standard advanced cardiovascular life support protocols. In addition, hyperkalemia must be aggressively treated with hyperventilation, calcium salts (chloride or gluconate), sodium bicarbonate, and epinephrine. Hyperventilation, bicarbonate, and β-adrenergic receptor agonists help drive K+ intracellularly, and calcium reduces the cellular effects of high K+ concentrations in the heart. Milder degrees of hyperkalemia are treated with hyperventilation, calcium salts, sodium bicarbonate, and parenteral or inhaled β-adrenergic receptor agonist therapy (albuterol or terbutaline). Glucose and insulin can also be used, but because their effects are more delayed, they are not considered first-line therapy. For children with hyperkalemic cardiac arrest, a postoperative evaluation by a neurologist or physical and rehabilitation

PREVENTION One way to prevent complications with succinylcholine is to avoid it altogether, unless there is a compelling indication for or advantage to its use. This is especially true in young children, who might have clinically unapparent myopathies. Rarely, an unexpected hyperkalemic response may occur, but with the avoidance of succinylcholine in at-risk patients, this should be quite unusual. With the availability of short- and intermediate-acting nondepolarizing agents, the need for large doses or infusions of succinylcholine should be uncommon. If repeated doses or infusions of succinylcholine are used, keeping the total dose under 5 to 6 mg/kg will help. During the preoperative evaluation, a family history of prolonged weakness or delay in awakening from anesthesia should be elicited. There are some geographic regions in which pseudocholinesterase exists because of its hereditary nature. In these regions, preoperative laboratory screening for pseudocholinesterase activity may be useful.

Further Reading Goldhill DR, Martyn JA Jr: Succinylcholine-induced hyperkalemia. In Azar I (ed): Muscle Relaxants. New York, Marcel Dekker, 1987, pp 93-113. Jensen FS, Viby-Mogensen J: Plasma cholinesterase and abnormal reaction to succinylcholine: Twenty years’ experience with the Danish Cholinesterase Research Unit. Acta Anaesth Scand 39:150-156, 1995. Larach MG, Rosenberg H, Gronert GA, et al: Hyperkalemic cardiac arrest during anesthesia in infants and children with occult myopathies. Am J Anesth 24:241-247, 1997.

PHARMACOLOGY

after plasmapheresis. Low levels of normal pseudocholinesterase generally do not prolong succinylcholine block to a clinically significant degree; this occurs only when normal pseudocholinesterase activity is reduced by at least 75% (normal, 4.9 to 12 IU/mL). In contrast, in patients with genetically atypical or abnormal pseudocholinesterase, the delay in return of normal neuromuscular function can range from mild (10 to 15 minutes) to severe (2 to 4 hours), depending on the variant. The difference among normal, atypical, and abnormal pseudocholinesterase variants is shown in the laboratory with compounds (e.g., dibucaine, fluoride) that inhibit benzoylcholine hydrolysis by pseudocholinesterase. The most common forms of abnormal pseudocholinesterase are the dibucaine-resistant and atypical variants (Eu Ea and Ea Ea, respectively). The homozygous atypical form (Ea Ea) occurs in 1 in 3200 patients, and the heterozygous form (Eu Ea) occurs in 1 in 480 patients. Dibucaine inhibits benzoylcholine hydrolysis by normal pseudocholinesterase by more than 70%; it inhibits benzoylcholine hydrolysis by the atypical (Ea Ea) form by less than 30%. Other forms of pseudocholinesterase include fluoride-resistant variants and a “silent” variant that shows neither dibucainenor fluoride-induced inhibition. Table 23-3 summarizes the characteristics of normal, atypical, and abnormal pseudocholinesterase variants.

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Levano S, Ginz H, Siegemund M, et al: Genotyping the butyrylcholinesterase in patients with prolonged neuromuscular block after succinylcholine. Anesthesiology 102:531-535, 2005. Martyn JA Jr, White DA, Gronert GA, et al: Up-and-down regulation of skeletal muscle acetylcholine receptors. Anesthesiology 76:822-843, 1992. Pantuck EJ: Plasma cholinesterase: Gene and variations. Anesth Analg 77:380-386, 1993.

Pantuck EJ, Pantuck CB: Prolonged apnea following succinylcholine administration. In Azar I (ed): Muscle Relaxants. New York, Marcel Dekker, 1987, pp 206-229. Viby-Mogensen J: Correlation of succinylcholine duration of action with plasma cholinesterase activity in subjects with the genotypically normal enzyme. Anesthesiology 53:517-520, 1980.

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PHARMACOLOGY

Nondepolarizing Neuromuscular Relaxants ..

Maria A. K. Ohrn Case Synopsis Following emergence and extubation after general anesthesia, a 52-year-old woman with a history of chronic renal insufficiency has a labored breathing pattern, including paradoxical movement of the chest wall and abdomen and intermittent upper airway obstruction.

peripheral nerve stimulation for 5 seconds or more, evidence exists of significant block at the neuromuscular junction. To prevent the overaccumulation of NDMR at the neuromuscular junction, one must consider the following:

PROBLEM ANALYSIS Definition Prolonged (residual) neuromuscular relaxant blockade is due to the presence of a nondepolarizing muscle relaxant (NDMR) at the neuromuscular junction beyond its expected duration of action. Residual neuromuscular relaxant block must be sufficient to cause motor weakness in response to peripheral nerve stimulation or to cause clinical signs of impaired muscle function. Unrecognized, residual neuromuscular relaxant block may cause respiratory insufficiency or arrest. Under controlled circumstances, each NDMR is metabolized, excreted, or both at a rate that can be predicted based on its pharmacokinetic profile. Clinically, however, it is important to recognize that coexisting disease processes, intraoperative events, and some concurrent drug therapy may prolong the duration of action of all NDMRs.

Recognition

■

●

●

Coexisting diseases or conditions that may affect any particular NDMR’s route of elimination or metabolism Expected recovery times with low or high doses of NDMRs (Table 24-1) Routine monitoring of neuromuscular function with a peripheral nerve stimulator

With train-of-four (T1/T4) stimulation, titration of twitch responses, and knowledge of the usual recovery time for specific NDMRs, clinicians can detect early evidence of impaired drug metabolism or excretion.

Risk Assessment Whether by known, unknown, or postulated mechanisms, all the following agents can potentiate the actions of NDMRs: ●

After anesthesia, if the patient is unable to sustain a head lift for at least 5 seconds or has fade with 50-Hz tetanic Table 24–1

●

● ●

Antibiotics (especially aminoglycosides) Loop diuretics (e.g., furosemide) Magnesium sulfate

Approximate Recovery Time to Baseline Twitch Height with Nondepolarizing Muscle Relaxants (NDMRs) Dose Range (mg/kg)

Recovery Time from Low Dose* (min)

Recovery Time from High Dose* (min)

0.1 0.05-0.08

50-130 (mean 91)

40-60 74-268 (mean 177)

Long-acting NDMRs Pancuronium† Doxacurium

Intermediate-acting NDMRs Vecuronium Rocuronium Atracurium† Cisatracurium‡

0.10 0.6-1.2 0.5 0.15-0.20

28-65 (mean 46)

0.25

11-29 (mean 19)

15-85 (mean 31)

25-45 38-160 (mean 67) 20-45 31-103 (mean 59)

Short-acting NDMRs Mivacurium†

*Approximate duration of recovery based on package inserts and variability in manufacturers’ definitions of recovery. Unless otherwise specified, the value given is for recovery to 25% of twitch height. † Range for recovery time from high dose is that until a first maintenance dose is needed. ‡ Value for recovery to 5% of twitch height.

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Lithium salts Calcium channel blockers Quinidine or procainamide

Along with drugs that may potentiate NDMR actions, there are patient factors that impair the metabolism or excretion of NDMRs. Renal or hepatic insufficiency can alter the duration of action of some NDMRs (Table 24-2). Intraoperative temperature fluctuations and acid-base imbalance also affect the pharmacokinetic and pharmacodynamic properties of NDMRs, which can make their duration of action and effects unpredictable.

avoid subsequent recall of unpleasant events due to partial or complete paralysis. Unrecognized residual neuromuscular blockade can cause further complications. With partial block, patients may have insufficient motor strength to protect the airway, increasing the risk for pulmonary aspiration. This can also cause respiratory insufficiency, hypercarbia, and hypoxemia. Collectively, these conditions may cause hemodynamic instability, arrhythmias, or respiratory arrest.

MANAGEMENT Implications It is known that some NDMRs (e.g., D-tubocurarine, atracurium, cisatracurium, doxacurium, metocurine, mivacurium) may cause nonimmunologic histamine release. The magnitude of this response is species dependent (e.g., greater in cats than in rats or dogs) and varies with the dose, the rapidity of injection, and, in clinical situations, the individual patient. Although the response may at first appear anaphylactic, any histamine release is more direct (anaphylactoid), often self-limited, and easily managed with judicious use of short-lived vasoconstrictors to counter the associated vasodilatation. Recent studies indicate that NDMRs account for more than half of all anaphylactoid reactions during general anesthesia. NDMRs, collectively, cause more such reactions than any other class of drugs commonly given during general anesthesia. However, the incidence of true anaphylaxis during anesthesia is quite low (estimated at 1 in 5000 to 1 in 25,000 cases). Concerning other NDMR complications, if these are recognized early enough, prolonged block can be managed without incident. If not (e.g., those that occur at the end of anesthesia), the need for patient care and the health care costs increase. Prolonged block can also increase operating room times, especially if patients must be extubated before admission to the postanesthetic care unit, as required in some ambulatory surgery centers. With severe NDMR overdose, postoperative mechanical ventilatory support may be needed for some time. If so, the patient must be sedated to

Table 24–2

■

Use of smaller NDMR doses titrated to twitch, train-of-four, and tetanic responses and early recognition of prolonged NDMR block are important for expectant management. If prolonged recovery from the initial intubating NDMR dose is detected, the cause of the drug’s reduced elimination or potentiation must be sought and corrected, if possible. Alternatively, in longer cases, subsequent use of shorteracting NDMRs with a different route of elimination may help address the problem, assuming that the cause of reduced metabolism or elimination of the first drug is known. Even so, at least initially, the kinetics of the second NDMR will be more like those of a longer-acting agent. For example, changing from pancuronium (a long-acting drug) to mivacurium (a short-acting drug) will not immediately alter the pharmacokinetics to those of mivacurium. Instead, mivacurium’s duration of action will be more similar to that of pancuronium. Not until several pancuronium halflives have passed will the pharmacokinetics resemble those of mivacurium. Also, combining steroid-derivative NDMRs (identified by the suffix “curonium”) with benzylisoquinolonederivative NDMRs (identified by the suffix “curium”) may have an initial supra-additive effect on the duration of action. If prolonged neuromuscular block is not detected until the case’s conclusion, the patient is kept sedated with nitrous oxide or low-dose volatile inhalation anesthesia. If the patient continues to show weakness, even with evidence for adequate neuromuscular relaxant reversal by head lift or peripheral nerve stimulation, an amnestic is given while arrangements are made for postoperative ventilatory support

Routes of Metabolism or Elimination for Neuromuscular Blocking Agents Route

Drug

Renal

Hepatic

Ester Hydrolysis*

Hoffman Eliminationt†

Pancuronium Doxacurium Vecuronium Rocuronium Atracurium Cisatracurium Mivacurium

Major Major Minor Minor Negligible Minor Minor

Intermediate Major Major Major Negligible Minor Minor

Negligible Negligible Negligible Negligible Major Negligible Major

Negligible Negligible Negligible Negligible Major Major Negligible

All categories were derived from data on elimination and metabolism from package inserts. ∗Plasma (pseudo) cholinesterase. † Butyrylcholinesterase and spontaneous (nonenzymatic) degradation.

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While in the postanesthesia care unit, the patient should remain sedated until head lift or results of peripheral nerve stimulation indicate adequate recovery of motor strength. An unfortunate occurrence is the one described in the case synopsis. Apparently, the patient was not adequately assessed before extubation, so the clinician was confronted with a patient struggling to breathe. Prompt action was needed to ensure adequate oxygenation and ventilation, which could be achieved with a face or laryngeal mask, while preparing for reintubation. The patient did not need additional muscle relaxation for reintubation, but she did require an amnestic agent.

of direct muscle stimulation is acceptable, bearing in mind that there are slight differences in recovery times among the various muscle groups. For example, the diaphragm and pharyngeal muscles recover relatively more quickly than the other muscle groups. The train-of-four response, which is preferred for intraoperative monitoring, poorly predicts adequate recovery from blockade. For clinical recovery of respiratory muscle function to occur, the T4/T1 ratio should be at least 0.7. Experienced clinicians, however, are unable to detect any fade with T4/T1 ratios as low as 0.3. Therefore, many patients are still significantly weak, based solely on train-of-four responses. Selecting double-burst stimulation or 5-second, 50-Hz tetanus, combined with clinical signs, provides far greater sensitivity for the detection of residual block. Even with anticholinesterase therapy, the time to full recovery is dependent on full metabolism and elimination of the NDMR. Further, there may be active metabolites. If these or the parent drug have slow metabolism or elimination, the recovery time can be even more delayed.

PREVENTION

Further Reading

Preventing prolonged neuromuscular blockade begins with the selection of an appropriate NDMR. An understanding of the comorbidities affecting hepatic or renal elimination of various NDMRs will help clinicians choose one that is not overly dependent on the liver or kidneys for its metabolism or elimination. Continual intraoperative surveillance of the magnitude of neuromuscular block requires a peripheral nerve stimulator and documentation of the time course for recovery of twitch, double-burst, train-of-four, and tetanic responses. This allows early detection of block prolongation. Ideally, the train-of-four response is measured after induction of anesthesia, but before giving a neuromuscular relaxant, whether succinylcholine or an NDMR. The peripheral nerve stimulator must be tested for adequate battery voltage, and it should display the current (amperes) delivered to the patient. Ballelectrode, hand-held peripheral nerve stimulators are not as reliable as those secured at one site with electrode gel adhesive pads. Any monitoring site that avoids misleading effects

Bevan DR, Donati F: Muscle relaxants. In Barash PG (ed): Clinical Anesthesia, 2nd ed. Philadelphia, Lippincott-Raven, 1996, pp 481-508. Erkola O, Rautoma P, Meretoja OA, et al: Mivacurium when preceded by pancuronium becomes a long-acting muscle relaxant. Anesthesiology 84:562-565, 1996. Goudsouzian NG: Muscle relaxants in children. In Coté CJ, Todres ID, Goudsouzian N, Ryan J (eds): A Practice of Anesthesia for Infants and Children, 3rd ed. Philadelphia, WB Saunders, 2001, pp 196-215. Mertes PM, Laxenaire MC, Alia F: Groupe d’Etudes des Reactions Anaphylactoides Peranesthesiques. Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000. Anesthesiology 99:536-545, 2003. Naguib M, Lien CA: Pharmacology of muscle relaxants and their antagonists. In Miller RD (ed): Miller’s Anesthesia, 6th ed. New York, Churchill Livingstone, 2005, pp 481-572. Nejman AM: Muscle relaxants. In Kirby R, Gravenstein N, Lobato E, Gravenstein J (eds): Clinical Anesthesia Practice, 2nd ed. Philadelphia, WB Saunders, 2002, pp 707-714. Plaud B, Debaene B, Lequeau F, et al: Mivacurium neuromuscular block at the adductor muscles of the larynx and adductor pollicis in humans. Anesthesiology 85:77-81, 1996. Viby-Mogensen J: Neuromuscular monitoring. In Miller RD (ed): Anesthesia, 4th ed. New York, Churchill Livingstone, 1994, pp 1345-1361.

● ●

●

Inability to sustain a head lift for at least 5 seconds Fade with 50-Hz tetanic stimulation lasting 5 seconds (the patient must be sedated, because this is extremely painful) Detectable difference in two responses elicited by doubleburst stimulation

PHARMACOLOGY

in the postanesthesia care unit. Evidence that a problem exists includes the following:

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Ali Habibi and Edward T. Riley Case Synopsis A 75-year-old man presents with acute urinary retention, tremors, blurred vision, and confusion. His past medical history is significant for allergic rhinitis, chronic renal failure, and hypertension. He is currently taking diphenhydramine and diltiazem.

Recognition

PROBLEM ANALYSIS Definition Antihistamines (H1-blockers) are a family of drugs used for hypersensitivity reactions of various types. Antihistamines are easily obtained, even without a prescription, but are not free of adverse side effects. Also, most first-generation H1-antagonists, such as diphenhydramine, inhibit muscarinic receptors to cause anticholinergic effects; the elderly are especially prone to these side effects of H1-blockers. Common side effects of first-generation antihistamines are sedation, confusion, tremors, blurred vision, diplopia, nervousness, insomnia, tinnitus, dry mouth, and dilated pupils. Second-generation H1-blockers (e.g., terfenadine, astemizole) can cause Q-T interval prolongation and torsades de pointes (see Chapter 81). H2-blockers can have significant effects on the hepatic metabolism of drugs and alcohol absorption.

Table 25–1

■

An overview of the side effects associated with antihistamines is provided in Table 25-1. A more detailed description of the physiology behind these effects follows. H1-BLOCKERS H1-receptor antagonists competitively inhibit the interaction of histamine with the H1-receptor, thereby inhibiting the vasodilator effects of histamine and preventing the occurrence of edema, flare, and wheal. H1-antagonists are taken primarily for acute allergies that present as rhinitis, urticaria, congestion, or conjunctivitis. However, H1-receptor antagonists may not oppose histamine-induced allergic bronchoconstriction, anaphylaxis, laryngeal edema, or angioedema. This is probably due to the involvement of other mediators (e.g., leukotriene, platelet-activating factor). H1-antagonists are well absorbed from the gastrointestinal tract, and they are metabolized by the hepatic microsomal

Adverse Reactions to Antihistamines First-Generation H1-Blockers

Second-Generation H1-Blockers

Cardiovascular

Tachycardia; no vasodilatation or vasoconstriction

Long Q-T interval; torsades de pointes

Nervous system

Adults: sedation, dry mouth, seizures, tremors, confusion Children: fixed, dilated pupils; flushed face; fever; possible coma Urinary retention; diarrhea, nausea, vomiting, constipation; no endocrine effects; allergic dermatitis (topical application)

Minimal

Reaction Type

Genitourinary, gastrointestinal, endocrine, skin, miscellaneous

Interactions

92

Potentiated by alcohol

Minimal genitourinary or endocrine effects; diarrhea or constipation

Potentiated by cytochrome P-450 inhibitors

H2-Blockers With rapid IV administration: decreased blood pressure, bradycardia, potential asystole Coma, headaches (famotidine), dizziness, drowsiness, confusion, seizures, agitation Transient ↑ serum creatinine; constipation or diarrhea; ↓ hepatic blood flow, gastric acidity; rare hepatotoxicity (ranitidine); gynecomastia; impotence (cimetidine); can facilitate bacterial infection Cimetidine inhibits cytochrome P-450; ↑ alcohol absorption

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H2-BLOCKERS Histamine binds to the H2-receptors located on the acidsecreting gastric parietal cells. This initiates a cascade that eventually increases the intracellular cyclic adenosine monophosphate (cAMP). Cyclic AMP activates the hydrogenpotassium pump, causing secretion of hydrogen ions. H2receptor antagonists are competitive inhibitors of histamine at H2-receptors, thereby reducing acid secretion. Currently there are several H2-blockers approved in the United States for the treatment of duodenal and gastric ulcer disease. They are all orally absorbed but have different degrees of bioavailability. Cimetidine and ranitidine are eliminated primarily by hepatic metabolism through cytochrome P-450 enzymes. Famotidine and nizatidine are primarily renally excreted.

Risk Assessment and Implications H1-BLOCKERS As noted earlier, the elderly are especially prone to the anticholinergic side effects of older H1-blockers. Urinary retention, confusion, hallucinations, tremors, dry mouth, and tachycardia may occur in older patients, even with moderate amounts of first-generation antihistamines. At higher doses, the central excitatory effects may cause convulsions. Concurrent ingestion of alcohol can potentiate the sedative effects of older H1-blockers. In contrast, second-generation H1-blockers have a minimal effect on muscarinic receptors. They do not cross the blood-brain barrier and thus have a less sedating effect. However, the second-generation H1-blockers (terfenadine, astemizole) can prolong the Q-Tc interval, which on rare occasion can cause polymorphic ventricular tachycardia. The latter in association with Q-Tc interval prolongation is known as torsades de pointes (see Chapter 81). Hepatic dysfunction or the coadministration of drugs that inhibit cytochrome P-450 (e.g., erythromycin, clarithromycin, ketoconazole, itraconazole) can also prolong the Q-Tc interval and trigger torsades de pointes. H2-BLOCKERS H2-blockers are relatively safe when the manufacturer’s prescribing guidelines are followed. Cimetidine inhibits cytochrome P-450. This can impair the metabolism and potentiate the actions of certain drugs (e.g., phenytoin,

Antihistamines: H1- and H2-Blockers

93

carbamazepine, quinidine, nifedipine, theophylline, warfarin, tricyclic antidepressants). Cimetidine and ranitidine inhibit the renal excretion of procainamide and its metabolite N-acylprocainamide to increase their plasma concentrations. Further, cimetidine, ranitidine, and nizatidine may potentiate the absorption of alcohol by inhibiting gastric alcohol dehydrogenase. Renal dysfunction can potentially increase the plasma levels of H2-blockers, which may contribute to a lower threshold for adverse effects.

MANAGEMENT Therapy for anticholinergic side effects of first-generation H1-blocking antihistamines is supportive. Each adverse effect must be addressed and treated separately. The drug causing the adverse side effects must be stopped immediately. With urinary retention, a Foley catheter should be inserted. If the patient has coronary artery disease or cardiovascular instability, tachycardia is treated with β-blockers or calcium channel blockers. The patient should be reassured about the transient central nervous system effects of diphenhydramine and closely monitored. Management for torsades de pointes with second-generation H1-blockers is discussed in Chapter 81.

PREVENTION Avoid giving antihistamines to patients at increased risk for their adverse side effects. First-generation H1-blockers should be avoided in the elderly. Patients receiving firstgeneration H1-blockers and H2-blockers should avoid alcohol. Second-generation H1-blockers should not be given to persons with Q-Tc interval prolongation; this advice may apply to those susceptible to ventricular tachyarrhythmias (or with a history thereof) as well, although there is no concrete evidence to back this recommendation. One must consider potential drug interactions (see Table 25-1), and doses should be adjusted on the basis of underlying renal or hepatic diseases.

Further Reading Feldman M: Pros and cons of over-the-counter availability of histamine-2 receptor antagonists. Arch Intern Med 153:2415-2418, 1993. Kosoglou T, Vlasses PH: Drug interactions involving renal transport mechanisms: An overview. Ann Pharmacother 23:116-122, 1989. Sax MJ: Clinically important adverse effects and drug interactions with H-2 antagonists: An update. Pharmacotherapy 7:110S-115S, 1987. Simons FER, Simons KJ: H1-receptor antagonist treatment of chronic rhinitis. J Allergy Clin Immunol 81:975-980, 1988. Simons FER, Simons KJ: The pharmacology and use of H1 receptorantagonist drugs. N Engl J Med 330:1663-1670, 1994. Woosley RL, Chen Y, Freiman JP: Mechanism of the cardiotoxic actions of terfenadine. JAMA 269:1532-1536, 1993.

PHARMACOLOGY

P-450 system. Most H1-antagonists induce hepatic microsomal enzymes to facilitate their metabolism. The metabolites, whether active or inactive, are renally excreted. The newer types of H1-receptor antagonists (secondgeneration or specific H1-blockers) were designed to eliminate the unwanted central nervous system and anticholinergic side effects of older H1-blockers.

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R. Victor Zhang Case Synopsis A 44-year-old woman presents for an abdominal incisional hernia repair. She is on several medications for hypertension, including oral clonidine (0.3 mg twice daily), which she did not take on the day of surgery. On preoperative examination, her blood pressure is 195/95 mm Hg, and her heart rate is 86 beats per minute. Surgery under general anesthesia proceeds uneventfully. On awakening, the patient has excellent pain control with narcotics, but her blood pressure has increased to 230/120 mm Hg, with a heart rate of 110 to 120 beats per minute. She is treated with intravenous (IV) boluses of labetalol and hydralazine and an IV infusion of esmolol. An IV bolus of clonidine 100 μg is also given but does not provide immediate hemodynamic improvement.

Mild respiratory depression Rebound hypertension on abrupt withdrawal

PROBLEM ANALYSIS

●

Definition

Hypotension and bradycardia during anesthesia are caused by the sympatholytic and anesthetic-sparing properties of α2-agonists. They often occur when dosages of other anesthetic agents and adjuncts are not properly adjusted in patients receiving α2-agonists. Transient hypertension after rapid IV injection of α2-agonists is due to direct binding with postsynaptic, vascular smooth muscle α2-adrenergic receptors. This causes vasoconstriction in peripheral resistance vessels via an endothelium-independent process. α2-Agonist-mediated respiratory depression is often mild, except at high doses or in association with other sedatives or narcotics. Rebound hypertension after abrupt cessation of α2-agonists is due to sympathetic hyperactivity. It occurs most often with clonidine, especially after prolonged use. It may produce a hypertensive crisis that is accompanied by other signs of sympathetic hyperactivity, such as nervousness, tachycardia, headache, and sweating.

The case synopsis typifies rebound hypertension after the abrupt withdrawal of clonidine in a patient with hypertension. The stress response associated with surgery under general anesthesia makes clonidine withdrawal more pronounced and difficult to control. Clonidine is a centrally acting α2-adrenoreceptor agonist (α2-agonist). It is commonly used by anesthesiologists and critical care physicians to treat patients with hypertension. In addition, it is used as a preanesthesia medication owing to its sedative, anxiolytic, hemodynamic, analgesic, antisialagogic, and anesthetic-sparing properties. A newer, more selective, and shorter acting α2-agonist, dexmedetomidine, has a similar pharmacologic profile to clonidine and is increasingly used in general anesthesia and intensive care settings. α2-Agonists reduce sympathetic tone, as well as plasma aldosterone and catecholamine concentrations and plasma renin activity. Perioperatively, these agents reduce heart rate, cardiac output, hypertension, and myocardial ischemia. They also improve survival in high-risk patients undergoing noncardiac surgery. Also, clonidine is used in conjunction with local anesthetics in neuraxial and peripheral nerve blocks to enhance and prolong analgesia. α2-Agonists are becoming more important as anesthetic adjuncts and analgesics. Clonidine is also used in therapy for withdrawal from alcohol, nicotine, and benzodiazepines, as well as in narcotic detoxification. Further, it has been used successfully in the treatment of migraine headaches, Tourette’s syndrome, attention-deficit disorder, premenstrual tension, and diabetic diarrhea. Perioperative use of α2-agonists is associated with adverse effects, including the following: ●

●

Increased incidence of hypotension and bradycardia during anesthesia Transient hypertension following rapid IV administration

94

●

Recognition Adverse effects of α2-agonists are related primarily to the extension of their pharmacologic activities, especially when compounded by the effects of anesthetics and anesthetic adjuncts. Thus, knowledge of potentially untoward perioperative physiologic effects is necessary for the recognition, management, and prevention of adverse effects of α2-agonists. These drugs exert their effects mainly via activation of presynaptic α2-adrenoreceptors in various locations in the central nervous system, especially within the brainstem. This results in a decreased efferent sympathetic outflow, with reduced blood pressure and heart rate, along with sedative, anxiolytic, and anesthetic-sparing effects that are often desirable during the perioperative period. Most adverse effects from α2-agonists are hemodynamic. In this case, early detection relies on close monitoring of blood pressure, heart rate, and electrocardiogram (ECG).

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Implications Bradycardia or hypotension from α2-agonists is usually mild. These conditions can be treated effectively with anticholinergics or positive chronotropes and therefore do not present serious problems. In contrast, severe bradycardia and hypotension are associated with a significant reduction in cardiac output and compromised perfusion to vital organs. Owing to the prevalence of hypertension and coronary artery disease in the elderly, these patients are at increased risk for myocardial and cerebral ischemia. Clonidine withdrawal is especially worrisome in the elderly. Rebound hypertension increases the risk of cerebral hemorrhage. Hypertension and tachycardia increase myocardial oxygen consumption, possibly leading to myocardial ischemia or infarction. Hypertension after rapid IV boluses of α2-agonists can be more pronounced in patients with hypertension. Although transient, this too increases the risk for adverse cardiovascular events. Mild sedation and respiratory depression can be well tolerated in healthy patients. However, those with hypertension or coronary artery disease are at increased risk for myocardial and cerebral ischemia.

Risk Assessment All α2-agonists cause sympatholysis, which results in decreased sympathetic outflow. Patients whose hemodynamic stability depends on increased sympathetic tone are at increased risk for severe hypotension with α2-agonists, especially those with anemia, hypovolemia, or heart failure. Patients with sinus node dysfunction or AV conduction delay or block are also at increased risk for severe bradycardia or complete AV block when treated with α2-agonists. Anesthetic adjuncts with sympatholytic properties, such as high doses of a potent narcotic, also increase the risk of bradycardia in patients receiving α2-agonists, especially during anesthesia induction. The risk of hypotension and bradycardia is also significantly increased if the anesthesiologist fails to take into account the anesthetic-sparing effect of α2-agonists and properly reduce the dose of IV or volatile anesthetic agents. Another risk factor for hypotension and bradycardia is renal insufficiency, which reduces the renal clearance of α2-agonists. Patients older than 65 years are also at increased risk for hypotension and bradycardia due to age-related renal insufficiency and reduced cardiovascular compensation. Transient hypertension after rapid IV injection of α2-agonists is enhanced in patients with hypertension, who are more sensitive to vasoconstrictors. Avoiding such rapid IV injections can reduce transient hypertension. Sudden cessation of clonidine can cause worrisome and sometimes severe rebound hypertension. The risk of this withdrawal response is higher in patients who have been chronically treated with clonidine, especially at high doses. It can occur from 8 to 36 hours after the last dose. Rebound hypertension is also possible after stopping guanfacine, another α2-agonist, but it occurs later (2 to 4 days) and with less frequency, presumably owing to its longer half-life. Respiratory depression from α2-agonists is often mild. However, at high doses or with other sedative-narcotics, deep sedation and respiratory depression can occur, especially in the elderly.

MANAGEMENT Bradycardia is treated effectively with IV anticholinergics (e.g., atropine, glycopyrrolate). IV ephedrine is also useful, especially with associated hypotension. However, ephedrine’s action is brief, so it may not be effective for bradycardia of long duration. Vasoconstrictors and IV fluids are used for α2-agonist-mediated hypotension. Because this is due to sympatholysis, α1-adrenergic agonists, especially phenylephrine, can reverse hypotension. Ephedrine has both α1and β-agonist effects and is sometimes used to reverse α2-agonist-mediated hypotension. The anesthetic-sparing effect of α2-agonists likely contributes to hypotension and bradycardia during induction or maintenance of general anesthesia. Hemodynamics are stabilized with IV fluids and vasoconstrictors, along with readjustment of anesthetic dosing. Transient hypertension from overly rapid IV injection of α2-agonists is often mild and followed by hypotension from central α2-adrenoreceptor activation. Treatment with long-acting antihypertensive agents can result in undesired hypotension. For rebound hypertension, labetalol is a good choice owing to its ability to block α- and β-adrenergic receptors. Labetalol alone might be inadequate to control hypertension and tachycardia; more selective β-blockers (e.g., metoprolol, esmolol, atenolol) are often needed to control tachycardia. β-Blockers should not be used alone, however, because they can worsen hypertension due to unopposed vasoconstriction from peripheral α-adrenergic activity. β-Blockers may even increase the risk of rebound hypertension with abrupt clonidine withdrawal. Vasodilators (e.g., hydralazine, dihydropyridine calcium channel blockers) are often required to control hypertension. Also, IV infusions of nitroglycerine or sodium nitroprusside are options for uncontrolled

PHARMACOLOGY

Sinus bradycardia is the most common form of bradycardia caused by α2-agonists. However, atrioventricular (AV) junctional and ventricular escape rhythms (bradycardia) and highdegree AV heart block can also occur. Therefore, the ECG is important for its ability to detect cardiac rhythm changes. Blood pressure and heart rate should be closely monitored in patients receiving α2-agonists, especially during induction and maintenance of anesthesia. For patients with poorly controlled hypertension, especially those on clonidine, an arterial line should be considered for perioperative blood pressure monitoring. The preoperative interview should focus on the patient’s history of hypertension and medications to control it, to identify those at high risk for clonidine withdrawal. Close monitoring of blood pressure and heart rate should continue for several hours postoperatively in such patients. In awake patients, other signs of clonidine withdrawal, such as nervousness, headache, and sweating, can aid in the diagnosis. Respiratory depression from α2-agonists is normally mild. Nevertheless, for patients sedated with an α2-agonist, respiratory rate and pulse oximetry must be monitored.

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severe hypertension. IV clonidine is another option, but it does not offer immediate relief for rebound hypertension and has the potential to aggravate hypertension transiently; subsequently, it may cause hypotension and bradycardia.

PREVENTION Awareness of the potential adverse effects of α2-agonists and their proper management is the key to preventing complications associated with their use. Dosages for IV anesthetic induction agents and volatile anesthetics must be adjusted downward. For patients at increased risk for bradycardia and hypotension, α2-agonists should not be used at all or should be given in smaller doses. Avoiding the rapid IV injection of clonidine or high doses of dexmedetomidine helps prevent transient hypertension with α2-agonists. To prevent adrenergic hyperactivity with withdrawal, patients receiving α2-agonists should continue therapy throughout the perioperative period. If the α2-agonist must be discontinued, this should be done over 1 week. For patients at risk for rebound hypertension, a transdermal clonidine patch may be applied preoperatively to abate perioperative sympathetic hyperactivity. Parenteral agents are also used to prevent rebound hypertension (e.g., labetalol, esmolol, propranolol, hydralazine, diltiazem, dihydropyridine calcium channel blockers, nitrates). Finally, severe respiratory depression is rare with therapeutic α2-agonist doses. For patients receiving other sedatives

or narcotics, these must be used with caution to avoid overly deep sedation or severe respiratory depression.

Further Reading Ghignone M, Calvillo O, Quintin L: Anesthesia and hypertension: The effect of clonidine on perioperative hemodynamics and isoflurane requirements. Anesthesiology 67:3-10, 1987. Ghignone M, Quintin L, Duke PC, et al: Effects of clonidine on narcotic requirements and hemodynamic response during induction of fentanyl anesthesia. Anesthesiology 64:36-42, 1986. Husserl FE, Messerli FH: Adverse effects of antihypertensive drugs. Drugs 22:188-210, 1981. Kamibayashi T, Maze M: Clinical uses of α2-adrenergic agonists. Anesthesiology 93:1345-1349, 2000. Levitan D, Massry SG, Romoff M, et al: Plasma catecholamines and autonomic nervous system function in patients with early renal insufficiency and hypertension: Effect of clonidine. Nephron 36:24-29,1984. Manhem P, Paalzow L, Hökfelt B: Plasma clonidine in relation to blood pressure, catecholamines, and renin activity during long-term treatment of hypertension. Clin Pharmacol Ther 31:445-451, 1982. Mercado DL, Petty BG: Perioperative medication management. Med Clin North Am 87:41-57, 2003. Talke P, Lobo E, Brown R: Systemically administered α2-agonist-induced peripheral vasoconstriction in humans. Anesthesiology 99:65-70, 2003. Talke PO, Lobo EP, Brown R, et al: Clonidine-induced vasoconstriction in awake volunteers. Anesth Analg 93:271-276, 2001. Weber MA: Discontinuation syndrome following cessation of treatment with clonidine and other antihypertensive agents. J Cardiovasc Pharmacol 2(Suppl 1):S73-S89, 1980. Weitz HH: Perioperative cardiac complications. Med Clin North Am 85:1151-1169, 2001. Wijeysundera DN, Naik JS, Beattie WS: Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications: A meta-analysis. Am J Med 114:742-752, 2003.

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MISCELLANEOUS DRUGS AND RELATED TOPICS

27

Anaphylaxis and Anaphylactoid Reactions David G. Bjoraker Case Synopsis A 40-year-old man has brachial plexus block with a lidocaine-tetracaine mixture containing a 1:200,000 concentration of epinephrine. Initially he complains of dizziness, difficulty breathing, and retrosternal chest discomfort. He rapidly develops acute respiratory distress and pulmonary edema, urticaria over the blocked extremity and shoulder, and marked hypotension.

another drug. Allergic drug reactions are generally not predictable, not dose dependent, and not related to the pharmacology of the drug.

PROBLEM ANALYSIS Definition Parenteral medications may cause anaphylaxis. Although it varies in severity, anaphylaxis is the most severe of the immediate hypersensitivity reactions. Anaphylactic shock refers to the complete cardiovascular collapse that may result. The classic anaphylactic reaction is mediated by immunoglobulin E (IgE) antibodies formed in response to prior exposure to a foreign antigen. In many cases, low-molecular-weight drugs are too small to be antigenic alone, but they may combine as haptens with endogenous protein carriers to form an antigenic complex. In the early 20th century, Richet and Portier administered large doses of sea anemone toxin to dogs. The animals survived the initial dose but died within minutes when given a minute dose weeks later. They termed this phenomenon anaphylaxis, indicating that attempted immunization failed to provide prophylaxis against sea anemone toxin. Anaphylactoid reactions may be clinically indistinguishable from anaphylactic reactions. The same chemical mediators released via the IgE-antigen pathway in anaphylaxis are also released by nonimmunologic mechanisms in anaphylactoid reactions.

CLINICAL MANIFESTATIONS

DRUG REACTIONS: ALLERGIC

AND

NONALLERGIC

Drug reactions are common during anesthesia, but less than 10% are true allergic reactions. Nonallergic drug reactions are generally predictable, dose dependent, and related to the known properties of the drug. Often the reactions are either enhanced desired effects or side effects of the drug resulting from overdosage, inadvertent route of administration, impaired elimination, low individual tolerance, or interaction with

ANAPHYLAXIS

The clinical manifestations of anaphylaxis depend on the route of administration of the antigen or hapten, as well as the exact type, quantity, and anatomic site of the various physiologic mediators released (Table 27-1) and the end-organ responses to them. These mediators result from the initial degranulation of mast cells and basophils and the ensuing biochemical events. Symptoms of anaphylaxis occur within 2 to 20 minutes of exposure to the antigen or hapten and may persist for up to 36 hours. Before induction and during regional anesthesia and monitored anesthesia care, both symptoms (Table 27-2) and signs (Table 27-3) of an allergic reaction can facilitate an early diagnosis. After the induction of general anesthesia, however, the patient cannot express symptoms and is hidden from view by the surgical drapes; in this case, serious respiratory and cardiovascular signs are often the first indicators of anaphylaxis. In addition, many signs, such as tachypnea, laryngeal edema, small increases in

Table 27–1

Recognition

OF

■

Mediators Released during Anaphylaxis

Complement (C3a, C5a anaphylatoxins) Heparin Histamine Kinins Leukoagglutinins Leukotrienes Lysosomal enzymes Platelet-activating factor Prostaglandins and other arachidonic acid metabolites Serotonin

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Symptoms of Anaphylaxis

Cutaneous Pruritus Burning Tingling Respiratory Nasal stuffiness Breathing difficulty Chest tightness, discomfort Cardiovascular Dizziness Malaise; confusion Retrosternal oppression Other Organ Systems Aura Nausea Abdominal pain

bronchial tone, and early decreases in systemic vascular resistance, may be obscured by anesthetic drugs and management. DIFFERENTIAL

AND

LABORATORY DIAGNOSES

Generally, the differential diagnosis of anaphylaxis is not difficult owing to the immediacy of the response after exposure to a foreign antigen or hapten. Because anaphylaxis is a systemic condition, signs in multiple organ systems differentiate it from a primary cardiac event or sudden exacerbation of bronchospasm in patients with asthma. Differentiation of anaphylactic and anaphylactoid reactions is academic, because the immediate medical management is identical.

Table 27–3

■

Signs of Anaphylaxis

Cutaneous Urticaria (hives); angioedema Erythema (flushing) Periorbital, facial edema Respiratory Coughing; sneezing Hoarseness Perioral and intraoral edema Laryngeal edema; stridor Intercostal and substernal retractions Cyanosis Tachypnea Wheezing Reduced pulmonary compliance Pulmonary edema Acute respiratory distress Cardiovascular Diaphoresis Hypotension Tachycardia Arrhythmias Reduced systemic vascular resistance Pulmonary hypertension Other Organ Systems Vomiting Diarrhea Acute intravascular coagulation

Laboratory diagnosis of anaphylaxis is retrospective, owing to the rapidity of its onset; after a reaction, however, several uncommon tests may substantiate its diagnosis. Circulating complement C3 and C5 activation products (C3a, C3d, and C5a) may be increased. IgE blood concentrations may be reduced, and plasma histamine concentrations may be briefly elevated. In addition, the concentration of tryptase, a protease released from mast cells, may be increased. If multiple drug exposures occur in close temporal proximity to an anaphylactic reaction, these tests will not assist in differentiating the causative agent.

Risk Assessment All patients receiving parenteral drugs are at risk for anaphylaxis, but those with a notable allergic history or atopy have a greater risk. The risk of an allergic reaction to a drug is approximately 1% to 3%. Anaphylaxis occurs in about 1 of 4000 to 25,000 anesthetic administrations. Table 27-4 lists drugs and other agents frequently used in the perioperative period that may cause anaphylactic or anaphylactoid reactions. For induction agents used in the United States, severe allergic reactions are uncommon. Neuromuscular relaxants are the most common cause of allergic reactions (about two thirds) during anesthesia. Neuromuscular relaxants such as atracurium, cisatracurium, tubocurarine, doxacurium, metocurine, and mivacurium occasionally cause signs of an allergic response due to nonimmunologic histamine release. Morphine, meperidine, and codeine also may release sufficient amounts of histamine to be confused with an allergic reaction. Other materials that come into contact with the patient, such as vascular graft material, methylmethacrylate bone cement, chlorhexidine, and latex rubber, have been implicated in anaphylactoid reactions. Latex allergy is the second most common cause of anaphylaxis during anesthesia (approximately one eighth of cases), and antibiotics are the third most common cause.

Implications An allergic reaction during anesthesia is usually unexpected and may range from a mild urticarial reaction to anaphylactic shock with cardiorespiratory arrest. Although a patient’s preexisting medical conditions may affect or otherwise complicate therapy, a fatal outcome can also occur in patients classified as status I or II by the American Society of Anesthesiologists (ASA) system.

MANAGEMENT Management of anaphylaxis and anaphylactoid reactions includes the following: ● ● ● ●

Removal or reduction of the offending agent Aggressive airway management Circulatory management: volume, epinephrine Adjunct pharmacologic management

If an anaphylactic or anaphylactoid reaction is suspected, the administration of any possible causative agents should

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Perioperative Drugs and Other Factors Associated with Anaphylactic or Anaphylactoid Reactions

Anesthetic Agents

Other Drugs and Miscellaneous Products

Induction agents used in the United States Barbiturates Benzodiazepines Etomidate Ketamine Propofol Induction agents not approved in the United States but used elsewhere Althesin Propanidid Neuromuscular relaxants Succinylcholine (see Chapter 23) Nondepolarizing neuromuscular relaxants (see Chapter 24) Opioids True allergic reactions and systemic anaphylactoid reactions to opioids are rare Anaphylactoid reactions have been reported after IV morphine or codeine (rare) Local anesthetics Para-aminobenzoic ester local anesthetics Amide local anesthetics (rare) Methylparaben or propylparaben preservatives Sulfite, bisulfite, or metabisulfite antioxidants

Antibiotics Aminoglycosides Amphotericin B Cephalosporins Nitrofurantoin Penicillin Tetracycline Vancomycin Intravenous fluids, blood products, volume expanders, hemostatics Albumin, dextran, hetastarch, purified protein fraction Aprotinin, protamine, vitamin K (phytonadione) Blood and blood products (all) Hypertonic solutions*: mannitol, sodium bicarbonate Dyes Isosulfan blue, methylene blue, iodinated radiopaque contrast dyes* Hormones Corticosteroids Insulin Vasopressin Immunosuppressive agents Cyclosporin FK-506 Antithymocyte globulin Latex Nonsteroidal anti-inflammatory drugs* Acetylsalicylic acid Aminopyrine Indomethacin Other drugs Chlorhexidine Chymopapain Streptokinase Tetanus antitoxin

*Usually anaphylactoid reactions.

be stopped immediately. Although a reaction is not strictly dose dependent, the less antigen or triggering agent administered, the better the situation. Also, use of a venous extremity tourniquet can prevent subcutaneously and intramuscularly administered antigenic or triggering material from reaching the central circulation. Oxygenation is monitored by pulse oximetry, and supplemental oxygen is used if necessary. Airway edema can progress rapidly, so the airway must be carefully and continuously monitored. Anesthesiologists should be predisposed to early endotracheal intubation. Discontinuation of general anesthesia is advised to help stabilize the circulatory dynamics, and rapid intravascular volume expansion should be started. Epinephrine is the drug of choice for hypotension because it attenuates associated mediator release and counters bronchospasm. In selecting a dose, the patient’s current hemodynamic state must be considered; doses range from an initial intravenous bolus of 0.2 to 1 μg/kg for moderate hypotension to 3 to 15 μg/kg intravenously for circulatory collapse. Repeated administration or an infusion is appropriate and often necessary. Other adjunct therapy may help after initial stability is achieved. If further antigen will likely be introduced into the

central circulation, antihistamines (e.g., diphenhydramine 0.5 to 0.7 mg/kg or cimetidine 4 to 6 mg/kg) and corticosteroids (e.g., methylprednisolone 15 to 25 mg/kg or hydrocortisone 4 to 15 mg/kg) should be considered. For bronchospasm, along with β-adrenergic aerosols (e.g., albuterol), aminophylline 5 to 6 mg/kg over 20 minutes, followed by an infusion at 0.5 to 1 mg/kg per hour, may be useful. Sodium bicarbonate is used to correct measured acidosis. The Joint Task Force on Practice Parameters has published diagnostic and management guidelines for anaphylaxis (see “Further Reading”). Although not limited to intraoperative anaphylaxis, these guidelines recognize that anaphylaxis is a significant perioperative problem, and they provide a broader context for patient care both before and after anesthesia.

PREVENTION Prevention includes avoiding risky practice patterns, as well as the following measures: ● ●

Intradermal skin testing Radioallergosorbent test (RAST)

PHARMACOLOGY

Table 27–4

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Leukocyte histamine release test Pharmacologic prophylaxis

The ultimate prevention of anaphylaxis and anaphylactoid reactions would be the elimination of exposure to all foreign materials, substances, and drugs, which of course is absurd. The practical approach is to prevent re-exposure to known allergens and to avoid risky patterns of practice, such as the repeated use of aprotinin or dextran infusions without the prior use of dextran 1 (Promit) or the use of a nonsteroidal anti-inflammatory drug when another such drug has caused a serious reaction. A careful history of prior incidents should be obtained, including review of the medical records and discussion with medical personnel who treated a previous reaction. If avoidance of a reactive drug compromises medical treatment, pretesting should be performed before actual use. Fortunately, an acceptable anesthetic regimen can almost always be formulated that excludes any questionable agents. Skin testing is the least expensive and most widely used method for pretesting anesthetic drugs. Fisher and Doig described intradermal skin testing for anesthetic agents and recommended dilution—usually a 1:1000 to 1:10,000 dilution of the commercial concentration. However, the irritant effect of the injection or direct histamine release by opioids or muscle relaxants may result in false-positive findings. Falsenegative findings are also possible, especially if the patient uses antihistamines or sympathomimetic preparations. Because anaphylaxis can occur in response to even small quantities (0.02 mL) of an agent, even when diluted 1000-fold, resuscitation agents and skilled personnel must be readily available. In vitro testing is much more convenient and completely safe for the patient. RAST is the most useful test and involves exposure of the patient’s serum to the questionable allergen. The latter is bound to an insoluble, drug allergen-matrix complex, and if the patient is capable of reacting to the allergen, his or her serum IgE will bind to the drug allergenmatrix complex as well. To measure the quantity of the patient’s serum IgE bound to the drug allergen-matrix complex, they are combined with radiolabeled antihuman IgE, and the radioactivity is measured. A low level of radioactivity indicates high occupation of the drug allergen-matrix complex by the patient’s serum IgE, or true allergy. Conversely, a high level of radioactivity indicates unlikely allergy. However, a deficiency of RAST is that many drug allergenmatrix complexes are not available commercially. Another in vitro test, the leukocyte histamine release test, does not require commercial allergen-matrix complexes. This test is conducted through direct exposure of a suspension of the patient’s leukocytes to the allergen. Histamine release is measured fluorometrically or with a radioenzymatic assay. For patients requiring treatment with a drug that has previously caused an allergic or anaphylactoid response, or

for atopic patients with multiple drug allergies, pharmacologic prophylaxis may be required. For anaphylactoid reactions to iodinated radiopaque contrast material, Greenberger and colleagues recommended the following protocol: ●

●

●

Ephedrine 25 mg and H1-receptor blockade (diphenhydramine 50 mg orally or intramuscularly) 1 hour before exposure Prednisone 50 mg 13 hours, 7 hours, and 1 hour before exposure Another 25 mg of oral ephedrine just before exposure, unless contraindicated

H2-blockade with cimetidine also was examined but was not found to be helpful. Recommendations for drug pretreatment in other situations are anecdotal and similar to those for radiocontrast material. H2-blockade in other circumstances can be achieved with 4 to 6 mg/kg of cimetidine or 1 to 2 mg/kg of ranitidine, preferably started 24 hours before exposure. Terbutaline, a β2-adrenergic agonist, and cromolyn sodium (which blocks the release of histamine and other autacoids from basophils and mast cells) have been proposed as prophylactic treatment, but their role in preventing anaphylactic or anaphylactoid reactions is unproved.

Further Reading Ebo DG, Hagendorens MM, Bridts CH, et al: Allergic reactions occurring during anaesthesia: Diagnostic approach. Acta Clin Belg 59:34-43, 2004. Fisher MM, Doig GS: Prevention of anaphylactic reactions to anaesthetic drugs. Drug Saf 27:393-410, 2004. Fukuda K: Intravenous opioid anesthetics. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 379-437. Greenberger PA, Patterson R, Tapio CM: Prophylaxis against repeated radiocontrast media reactions in 857 cases: Adverse experience with cimetidine and safety of β-adrenergic antagonists. Arch Intern Med 145:2197-2200, 1985. Gutstein HB, Akil H: Opioid analgesics. In Hardman JG, Limbird LE (eds): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York, McGraw-Hill, 2001, pp 569-619. Joint Task Force on Practice Parameters, American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology: The diagnosis and management of anaphylaxis: An updated practice parameter. J Allergy Clin Immunol 115:S483-S523, 2005. Levy JH: Anaphylactic Reactions in Anesthesia and Intensive Care, 2nd ed. Stoneham, Mass, Butterworth-Heinemann, 1992. Mertes PM, Laxenaire MC: Allergic reactions occurring during anaesthesia. Eur J Anaesthesiol 19:240-262, 2002. Moneret-Vautrin DA, Kanny G: Anaphylaxis to muscle relaxants: Rationale for skin tests. Allerg Immunol (Paris) 34:233-240, 2002. Pepys J, Whitwam JG, Baldo BA, et al: Anaphylactic/anaphylactoid reactions to anaesthetic and associated agents: Skin prick tests in aetiological diagnosis. Anaesthesia 49:470-475, 1994. Soetens FM: Anaphylaxis during anaesthesia: Diagnosis and treatment. Acta Anaesthesiol Belg 55:229-237, 2004. Terr AI: In vitro tests for immediate hypersensitivity. Annu Rev Med 39: 135-145, 1988.

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28

Antibiotics Case Synopsis A 23-year-old man presents for reduction and fixation of an open tibial fracture after falling off a horse. Following thiopental and succinylcholine administration and successful endotracheal intubation, anesthesia is maintained with isoflurane, nitrous oxide 50% and oxygen 50%, and fentanyl 2 μg/kg per hour. The surgeon requests that the patient be given vancomycin 1 g before incision. Three minutes after vancomycin is given, the patient suffers cardiovascular collapse.

PROBLEM ANALYSIS

●

●

Definition Anesthesiologists frequently administer antibiotic prophylaxis to surgical patients and should be knowledgeable about the indications, dosages, complications, and interactions between antibiotics and anesthetics and other medications used in the perioperative period. Antibiotics possess a diverse spectrum of side effects (Table 28-1) and interact with a number of anesthetic adjuvants. For these reasons, anesthesiologists must understand and anticipate possible complications associated with antibiotic administration. Vancomycin is a glycopeptide antibiotic commonly used for bacterial prophylaxis in orthopedic, neurologic, and vascular surgery and as an alternative antibiotic for patients who are allergic to penicillins and cephalosporins. An unusual feature of vancomycin is its ability to nearly double histamine release from basophils and cutaneous mast cells through a poorly understood dose-dependent mechanism that is neither immunologic nor cytotoxic. The liberated histamine causes dilatation of peripheral blood vessels and simultaneously increases cardiac output, stroke volume, and pulmonary artery pressure. However, peripheral vascular dilatation is the most prominent physiologic feature and may induce severe hypotension and cardiovascular collapse. There have been several reports of hypotension and cardiac arrest during concurrent vancomycin and anesthesia administration, but cardiovascular collapse can also occur in unanesthetized patients receiving vancomycin.

Recognition Recognition of vancomycin as the cause of hypotension relies primarily on the exclusion of other intraoperative events as the cause, the temporal relationship between cardiovascular instability and vancomycin infusion, and the observation of other manifestations of histamine release. Signs of elevated plasma levels of histamine include the following: ●

●

“Red neck” or “red man” syndrome, consisting of cutaneous flushing, erythema, urticaria, pruritus, and maculopapular rash primarily on the face, neck, arms, and chest Perioral, periocular, and facial edema

● ●

Bronchospasm due to stimulation of bronchial histamine receptors Hypoxia caused by histamine-induced inhibition of pulmonary vasoconstriction and subsequent formation of pulmonary shunts Systemic hypotension Pulseless electrical activity cardiac arrest (electromechanical dissociation)

In addition, a “pain and spasm” syndrome has been described following vancomycin infusion, but it is unknown whether this is a histamine-mediated complication or whether another mechanism is responsible. Anesthesiologists must be cognizant that contaminants in the vancomycin solution may cause a true anaphylactic reaction, although hypotension is much more likely to result from vancomycininduced histamine release.

Risk Assessment Because vancomycin-induced histamine release results from nonspecific degranulation of basophils or mast cells, it is classified as an anaphylactoid reaction, not anaphylaxis. That is, histamine liberation is mediated not by an immune system response but by an unclear mechanism. Consequently, a patient’s risk for hypotension and cardiovascular collapse is independent of previous exposure to vancomycin, may occur with the first dose, and does not increase with multiple administrations of the antibiotic. Hence, a patient with a history of “red man” syndrome or vancomycin-induced hypotension can safely receive this antibiotic if it is administered appropriately. Anesthesiologists may be concerned about a greater risk of hypotension when vancomycin and a volatile anesthetic are administered concurrently (i.e., vancomycin infusion after anesthetic induction), because both agents can potentially depress blood pressure. Although hypotension during vancomycin administration is more common in anesthetized than in nonanesthetized patients, this difference is probably due to more intensive monitoring and observer vigilance during anesthesia rather than an actual interaction between vancomycin and anesthetics. In one study investigating hypotension during concurrent vancomycin and anesthetic administration in adult patients undergoing orthopedic surgery (see Von Kaenel under “Further Reading”), no difference was noted (either before 101

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Complications of Antibiotics Used for Prophylaxis

Antibiotic

Common

Occasional

Rare

Aminoglycosides

Nephrotoxicity Ototoxicity

Peripheral neuritis Anaphylaxis Electrolyte disturbances

Cephalosporins

Painful when given IM

Rash Nausea, vomiting Potentiation of neuromuscular blockade Nausea Drug fever Diarrhea Phlebitis

Clindamycin

Erythromycin

Phlebitis when given IV Painful when given IM

Metronidazole

Nausea, vomiting Metallic taste Disulfiram-like reaction if alcohol consumed

Diarrhea Pseudomembranous colitis Rash Metallic taste Inhibition of neuromuscular transmission Potentiation of neuromuscular blockade Nausea, vomiting Diarrhea Pseudomembranous colitis Burning tongue Urethral/vaginal burning Dark urine Rash

Penicillin G, ampicillin

Rash Drug fever Diarrhea Leukopenia

Trimethoprim-sulfamethoxazole

Rash

Vancomycin

Phlebitis Severe pain when given IM

“Red man” syndrome “Pain and spasm” syndrome Hypotension Anaphylaxis Nephrotoxicity Ototoxicity

Anaphylaxis Hypotension Bronchospasm Angioedema Urticaria Anaphylaxis Cardiac arrest Erythema Granulocytopenia Thrombocytopenia

Long QT syndrome Fever Rash Eosinophilia Convulsions Ataxia Peripheral neuropathy Encephalopathy Cerebellar dysfunction Anaphylaxis Bronchospasm Angioedema Electrolyte disturbances Interstitial nephritis Erythema multiforme Diarrhea Aplastic anemia Neutropenia Thrombocytopenia Neutropenia

Adapted from Cheng EY, Nimphius N, Hennen CR: Antibiotic therapy and the anesthesiologist. J Clin Anesth 7:425-439, 1995.

or after anesthetic induction) in hemodynamic parameters, anesthetic depth, ephedrine use, or volume of intravenous fluid administration following an infusion of either vancomycin or a saline carrier solution over 30 to 60 minutes (Table 28-2). In contrast, children and patients undergoing cardiopulmonary bypass and coronary bypass grafting are apparently more sensitive to the vasodilating effects of vancomycin. Anesthetized pediatric patients demonstrated a 35% incidence of hypotension following vancomycin infusion. Likewise, 30% of adults undergoing cardiopulmonary bypass required a postbypass infusion of norepinephrine following the addition of vancomycin 500 mg to the cardiopulmonary bypass pump prime solution, compared with 7% in a control group given saline. However, vancomycin administration via aortic cannula using flow rates necessary for cardiopulmonary bypass (60 to 70 mL/kg per minute) is probably too rapid

to maintain hemodynamic stability even in some healthy patients. Critically ill patients have a diminished risk of vancomycininduced reactions compared with healthy patients presenting for elective procedures. Vancomycin 1 g infused over 30 minutes did not affect cardiac index, heart rate, blood pressure, pulmonary venous pressure, central venous pressure, systemic vascular resistance, or pulmonary vascular resistance in 16 hemodynamically stable patients who were given the antibiotic within 24 hours of coronary artery bypass grafting or cardiac valve replacement. Remarkably, little rise in histamine concentrations occurred, despite substantially elevated vancomycin concentrations. Failure to develop cardiovascular side effects may be explained in part by the depletion of histamine from its previous liberation in response to illness, perioperative stress, and protamine administration.

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Complications of Vancomycin Administration before or after Induction of Anesthesia in Studies Noting Adverse Events

Study (Year)

Subjects

No. Preinduction

No. Postinduction

Blomstedt et al (1988) Von Kaenel et al (1993)

Adults

—

169

Adults

17

19

Odio et al (1984) Romanelli et al (1993)

Children Adults

— 30*

20 30*

End Points (No. of Patients) “Red man” syndrome (6), hypotension (5), bronchospasm (1), hypoxia (1) No differences in HR, BP, end-tidal enflurane concentration, ephedrine use, IV fluid administration compared with placebo “Red man” syndrome (7), hypotension (1) No differences in HR, SBP, CVP, CO, SVR, or intraoperative fluid balance after anesthetic induction and before cardiopulmonary bypass, but higher HR and CO combined with lower BP, CVP, and SVR after cardiopulmonary bypass and surgery in patients receiving vancomycin compared with placebo; also, 9 of 30 patients receiving vancomycin required norepinephrine infusion, compared with 2 of 28 patients in the control group

*Patients received vancomycin both before anesthetic induction and at the initiation of cardiopulmonary bypass for coronary artery bypass grafting. BP, blood pressure; CO, cardiac output; CVP, central venous pressure; HR, heart rate; SBP, systemic blood pressure; SVR, systemic vascular resistance.

Consistent with this hypothesis is an investigation that demonstrated significantly elevated histamine concentrations in 28 patients who were studied immediately after multiple traumatic injuries and compared with a control group. Alternatively, critically or chronically ill patients may possess a diminished response to histamine stimulation when compared with the response of healthy volunteers or patients presenting for ambulatory surgery. For example, patients with cancer exhibit less pruritus and diminished wheal and flare responses following an intradermal histamine challenge. Regardless, anesthesiologists would be prudent to carefully monitor such patients during vancomycin administration, because even mild or moderate hypotension may be poorly tolerated in critically ill patients.

That is, treatment options should become more aggressive with later detection, greater histamine release, and more severe hypotension. Management options include the following: ● ● ●

● ● ●

●

Discontinue or slow the vancomycin infusion. Administer an intravenous fluid bolus. Discontinue or decrease concentrations of other agents that are capable of inducing hypotension (e.g., anesthetics, sodium nitroprusside). Administer H1-antihistamines (e.g., diphenhydramine). Consider inhaled β-agonists if bronchospasm is present. Administer vasopressors (e.g., ephedrine, phenylephrine, epinephrine) for severe hypotension. Initiate advanced cardiovascular life support maneuvers in the event of cardiac arrest.

Implications Vancomycin can be safely administered to patients in the perioperative period either before or after induction of anesthesia. Prudent anesthesiologists follow the manufacturer’s recommendations regarding the duration of vancomycin infusion, especially in patients at greater risk (e.g., children) or who poorly tolerate even mild hypotension (e.g., patients with aortic stenosis). Hemodynamic depression requires prompt detection and treatment to avoid potentially lifethreatening cardiovascular collapse.

MANAGEMENT Managing vancomycin-induced hypotension grows progressively more difficult the longer it takes to detect the drug’s toxic effects, and detecting the toxic effects grows progressively more difficult the longer the drug is administered.

PREVENTION Histamine release and the severity of reactions during vancomycin administration are directly dependent on the rate of infusion. Consequently, vancomycin should be infused over 60 minutes to minimize adverse reactions, as recommended by the manufacturer. In a study of nonanesthetized patients, rapid vancomycin infusion (1 g over 10 minutes) caused a 25% to 50% decrease in systolic blood pressure lasting 2 to 3 minutes in 11 of 56 patients, whereas no hypotension was observed in patients receiving a slow vancomycin infusion (1 g over 30 minutes). The key element is slow administration over 30 to 60 minutes, which may be impractical when attempting to complete a dose before surgical incision or tourniquet inflation. In this situation, preoperative infusion may be warranted if there is insufficient time to safely infuse vancomycin. Regardless, frequent monitoring

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of blood pressure; observation of skin color of the head, neck, and trunk; and auscultation of breath sounds are necessary for prompt detection and treatment of vancomycin’s toxic effects. Finally, some patients with extreme sensitivity to vancomycin may require this antibiotic to treat infections with multidrug-resistant organisms. In this situation, protocols for vancomycin desensitization have been developed to allow this patient population to safely receive intravenous vancomycin. This treatment revolves around gradual desensitization of mast cells by gradually increasing the serum concentration of vancomycin. This can be accomplished in as little as 24 hours for acutely ill patients. This preventive protocol is, of course, reserved for patients in duress and requires planning before the day of surgery if operative prophylactic vancomycin administration is envisioned.

Further Reading Cheng EY, Nimphius N, Hennen CR: Antibiotic therapy and the anesthesiologist. J Clin Anesth 7:425-439, 1995.

Levy JH, Kettlekamp N, Goertz P, et al: Histamine release by vancomycin: A mechanism for hypotension in man. Anesthesiology 67:122-125, 1987. Polk RE: Anaphylactoid reactions to glycopeptide antibiotics. J Antimicrob Chemother 27B:17-29, 1991. Romanelli VA, Howie MB, Myerowitz PD, et al: Intraoperative and postoperative effects of vancomycin administration in cardiac surgery patients: A prospective, double-blind, randomized trial. Crit Care Med 21:1124-1131, 1993. Sokoll MD, Gergis SD: Antibiotics and neuromuscular function. Anesthesiology 55:148, 1981. Stier GR, McGory RW, Spotnitz WD, Schwenzer KJ: Hemodynamic effects of rapid vancomycin infusion in critically ill patients. Anesth Analg 71:394-399, 1990. Von Kaenel WE, Bloomfield EL, Amaranath L, Wilde AA: Vancomycin does not enhance hypotension under anesthesia. Anesth Analg 76:809-811, 1993. Wazny LD, Daghigh B: Desensitization protocols for vancomycin hypersensitivity. Ann Pharmacother 35:1458-1464, 2001.

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Antidepressants MONOAMINE OXIDASE INHIBITORS Case Synopsis A 32-year-old woman with a 38-week intrauterine pregnancy presents for cesarean section due to failure to progress. The patient has a 2-year history of depression and is currently taking 15 mg of phenelzine orally, twice daily. The patient refuses general anesthesia. A lumbar epidural block is placed without complication, and a T6 level of anesthesia is achieved. The surgical procedure proceeds and is uneventful. In the recovery room, the nurse requests intravenous meperidine for postoperative shivering. Later, the anesthesiologist is informed that the patient is tachycardic, hypertensive, and hyperpyrexic.

PROBLEM ANALYSIS Definition Monoamine oxidase inhibitors (MAOIs) block oxidative deamination to cause the accumulation of endogenous catecholamines (serotonin, norepinephrine, and dopamine) at adrenergically active tissue sites (e.g., brain). This is the proposed mechanism for the antidepressant actions of MAOIs. Meperidine increases serotonin (5-hydroxytryptamine) and catecholamine concentrations in synaptic clefts by inhibiting their uptake. In combination, meperidine and MAOIs can lead to increased serotonin and catecholamine levels in brain and peripheral tissue sites, causing signs of sympathetic nervous system overactivity (e.g., hypertension, tachycardia, hyperpyrexia) and potentially coma.

Recognition Use of narcotics in patients receiving MAOIs can lead to one of three clinical presentations: 1. No adverse effects 2. Hypertension, hyperpyrexia, and tachycardia—a more common clinical presentation, especially with meperidine 3. Hypotension and loss of consciousness—reported with morphine sulfate

Risk Assessment Inhibition of approximately 80% of monoamine oxidase (MAO) activity is necessary to achieve a therapeutic antidepressant effect with MAOIs. There are two MAO enzymes (A and B), which differ in their tissue distribution (active sites) and preference for substrates. Because the brain contains predominantly MAO A (approximately 60% of the total), selective inhibitors could potentially minimize (or eliminate) the side effects associated with MAOIs. Two types of MAOI derivatives (hydrazine and nonhydrazine analogues) exist.

Implications The use of narcotics in the setting of MAOI treatment remains controversial. Morphine has been reported to cause adverse outcomes in patients taking MAOIs, presumably via histaminemediated release of catecholamines. In addition, MAOIs reduce intrahepatic enzyme function and thus can prolong the effects of other drugs. The most well-known adverse interactions, however, are those between MAOIs and meperidine; such adverse outcomes have been reported from at least 12 independent sources. Even the use of synthetic narcotics (e.g., fentanyl) that do not release histamine has been questioned. The synthetic opioids increase norepinephrine release and inhibit its reuptake in sympathetic nerve terminals. Fentanyl may also increase the release of serotonin. Despite three reports of adverse outcomes with fentanyl-based anesthesia in patients receiving MAOIs and having cardiac surgery, many other reports have described the safety of high-dose fentanyl in that setting. The newer selective MAOI moclobemide has not been associated with adverse outcomes in patients receiving morphine or synthetic opioids. Volatile anesthetics and intravenous agents, including ketamine, have also been used safely in patients receiving moclobemide. Although there is some concern about the use of local anesthetic solutions containing epinephrine in patients receiving moclobemide, data to support or refute this concern are unavailable. Hyperdynamic circulatory responses have been reported in patients receiving MAOIs who are given indirect-acting vasopressors such as ephedrine. Indirect-acting adrenergic agonists can cause an unpredictable release of catecholamines from presynaptic stores into the nerve terminal and lead to a grossly exaggerated sympathetic response. Therefore, these drugs are best avoided in patients receiving MAOIs. In contrast, MAOIs do not significantly alter the hemodynamic effects of exogenously administered direct-acting vasopressors such as phenylephrine.

MANAGEMENT The hyperdynamic circulatory responses elicited with the use of meperidine and indirect-acting sympathomimetic 105

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agents in patients receiving MAOIs can be controlled with the use of arterial vasodilators such as nitroprusside and nicardipine. In comatose patients, supportive care, including airway management, is imperative. Hypotensive episodes during surgery are best treated with reduced intravenous doses of phenylephrine or other direct-acting sympathomimetic agents.

PREVENTION The preceding considerations suggest the discontinuance of MAOIs 2 weeks before elective surgery to permit the synthesis of new MAO enzyme. However, the pharmacologic effects of nonhydrazine MAOIs are absent after the drug has been discontinued for 24 hours. The nonhydrazine MAOIs are reversible inhibitors of MAO and are not associated with

adverse outcomes during anesthesia and surgery. Thus, discontinuing such therapy is generally not warranted and must be carefully weighed against exacerbations of the underlying psychiatric illness. Neither general nor regional anesthesia is contraindicated in patients receiving nonhydrazine MAOIs. If central neuraxial regional anesthesia is chosen, however, volume loading before the introduction of sympathectomy is advised. Further, with hypotension, the use of direct-acting vasopressors is recommended. MAOIs have a minor role in terminating the release and action of norepinephrine at nerve terminals. For cardiac surgical patients, some authors recommend the use of benzodiazepines and β-adrenergic blockers with highdose narcotic anesthesia, whereas others recommend the use of etomidate or thiopental in doses appropriate to the patient’s hemodynamic status.

TRICYCLIC ANTIDEPRESSANTS Case Synopsis A 24-year-old man presents emergently to the operating room for surgical exploration of the abdomen after a motor vehicle accident. In the emergency room, the patient is very difficult to arouse and is intubated. Vital signs are stable except for mild tachycardia. The head computed tomography scan is normal, and no other injuries are noted. During induction of anesthesia with low-dose thiopental and pancuronium, the patient becomes extremely hypotensive and bradycardic, with wide QRS complexes on the electrocardiogram (ECG). Epinephrine (100 μg) is given, and profound sustained hypertension and tachycardia ensue. An attempt at arterial line placement reveals severe scarring on both wrists. Intravenous fluid resuscitation is initiated, and sodium nitroprusside 1 μg/kg per minute is administered. Later, the family reveals that the patient has had suicidal depression for at least 3 months and is taking imipramine.

PROBLEM ANALYSIS Definition Reduced concentrations of norepinephrine and serotonin in the central nervous system (CNS) are thought to underlie depression. Thus, the condition is effectively treated by agents that block catecholamine reuptake in the CNS. Although tricyclic antidepressants (TCAs) do this, they also bind to other CNS receptors (γ-aminobutyric acid [GABA], muscarinic, α-adrenergic, and histamine). In addition to CNS actions, TCAs have important cardiac implications. Depending on serum TCA concentrations, these drugs may exert proarrhythmic or antiarrhythmic properties. However, TCAs have not been implicated as a direct cause of left ventricular dysfunction.

Recognition The width of the QRS complex represents the relatively brief duration of phase 0 and phase I of the cardiac action potential (AP) relative to phases II, III, and IV (plateau, repolarization, and isoelectric phases, respectively). Phase 0 is the rapid depolarization phase that results from the influx of sodium

ions into the cardiac muscle and conducting fibers. Phase I is early, rapid depolarization that precedes the AP plateau phase (phase II). Phase I is believed to be due to several potassium repolarizing currents and to sodium “window” and calcium currents. Blockage of voltage-gated sodium channels that generate fast inward current required for AP phase 0 depends on the heart rate. Profound block, especially with toxic TCA concentrations, occurs at fast heart rates. However, such block accumulates over time and eventually leads to bradycardia with widened QRS complexes. Early signs of TCA toxicity are PR interval prolongation and T-wave flattening. Also, most patients display anticholinergic effects with TCAs, leading to an early increase in heart rate. However, bradycardia with wide QRS complexes may follow.

Risk Assessment QRS complex widening is the harbinger of seizures and cardiac arrhythmias with acute TCA intoxication. With therapeutic TCA concentrations, most patients show a 10% to 20% increase above their baseline heart rate due to TCAs’ anticholinergic effects. Further, PR and Q-Tc interval prolongation is not infrequent with therapeutic concentrations of TCAs.

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With TCAs, hypotension can occur due to bradycardia, volume depletion, or vasodilatation secondary to α-adrenergic receptor blockade. One’s first impulse might be to administer a direct-acting vasoconstrictor, such as phenylephrine or even epinephrine. However, the use of epinephrine can lead to profound hypertension and tachycardia (as illustrated in the case synopsis) in the presence of increased circulating concentrations of catecholamines with TCAs. Use of epinephrine in local anesthetic solutions should also be avoided. Increased circulating catecholamines may lead to ventricular tachycardia and arrest in the presence of halothane and pancuronium. Ketamine should also be avoided owing to its potential sympathomimetic effects. ECG evidence of Q-T interval prolongation precludes the use of stellate ganglion blocks for treating reflex sympathetic dystrophy. In fact, TCAs are an alternative but often overlooked therapy for these patients.

MANAGEMENT In the presence of ventricular arrhythmias, class IA antiarrhythmic agents (e.g., quinidine, procainamide, disopyramide) are of no benefit and in fact should not be used. TCAs and class IA antiarrhythmics have similar effects on the myocardium that are compounded by combined use, especially the risk for Q-T interval prolongation and proarrhythmia (i.e., torsades de pointes). In cardiac arrest, resuscitation should proceed as usual with intravenous lidocaine (a class IB agent) or amiodarone (the class III agent with the lowest proarrhythmia risk) and direct-current cardioversion for ventricular tachycardia or defibrillation for

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ventricular fibrillation. If cardiac arrest is due to ventricular tachycardia or fibrillation, epinephrine should be avoided. Assurance of ventilation and oxygenation, mechanical chest compressions, and early cardioversion or defibrillation are mandatory. If a vasopressor is needed, the best alternative may be vasopressin in reduced dosages. Then, attention should be directed toward the correction of acidosis and hypokalemia and the replacement of intravascular volume. Bradycardia or asystole may respond to atropine, but if not, temporary transcutaneous pacing is used. In a comatose patient, airway management is the primary concern, not only to ensure adequate ventilation and oxygenation but also to protect against pulmonary aspiration.

PREVENTION In the case of elective surgery, a preoperative ECG should be obtained in all patients receiving TCAs. Unless the history or physical examination reveals significant heart disease or heart failure, a preoperative echocardiogram is generally not necessary, because left ventricular function is usually well preserved in patients taking TCAs. Further, the preoperative discontinuation of TCAs is not warranted. However, close observation of the intraoperative ECG and knowledge and awareness of the drug’s cardiac implications are of utmost importance in the care of these patients. Drugs to avoid include direct-acting catecholamines, sensitizing inhalation agents (e.g., halothane more than enflurane; but sensitization unlikely with desflurane or sevofurane), induction agents that facilitate this interaction (e.g., thiopental), and intravenous agents such as ketamine (owing to its sympathomimetic actions).

SELECTIVE SEROTONIN REUPTAKE INHIBITORS Case Synopsis After an orthopedic procedure performed with an axillary block and sedation, a 28-year-old woman develops hyperthermia, hyperreflexia, and agitation in the recovery room. She is currently being treated with sertraline because of postpartum depression.

PROBLEM ANALYSIS

pathways) and channels (e.g., sodium, potassium), they have a significantly better safety profile than TCAs.

Definition

Recognition

Selective serotonin reuptake inhibitors (SSRIs) inhibit the presynaptic 5-hydroxytryptamine reuptake transport system. This leads to an acute increase in serotonin concentrations at the synaptic cleft. The therapeutic effects, which take approximately 2 weeks to develop, are the result of neuroadaptive changes that result in increased serotonin release and transmission. Because SSRIs are highly specific for serotonin and have less effect on other neurotransmitter systems (e.g., adrenergic, muscarinic, histamine, and dopaminergic

In patients receiving SSRIs, concurrent nonanesthetic drugs and some anesthetic drugs may cause adverse reactions, including the serotonin syndrome, which is identified by any three of the following symptoms: mental status changes, including agitation; hyperreflexia; diaphoresis; shivering; tremor; hypertension; oculogyric crisis (i.e., extreme eyeball rotation); diarrhea; and hyperthermia. Drugs that can cause adverse reactions or the serotonin syndrome in concert with SSRIs include the following:

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Nonanesthetic drugs: L-dopa, lithium, bromocriptine, fenfluramine, dextromethorphan, pethidine, and pentazocine can increase serotonin activity by blocking the reuptake or increasing the presynaptic release of serotonin. Anesthetic drugs: highly protein-bound anesthetic drugs (e.g., fentanyl, midazolam, local anesthetics) may increase the free (unbound) fraction of sertraline (Zoloft).

Risk Assessment SSRIs are the most frequently used antidepressants in the United States. Fluoxetine (Prozac) is the least specific of the SSRIs, especially at higher doses, and may be associated with greater CNS effects. Paroxetine (Paxil) is more specific but also has mild antimuscarinic effects. Sertraline (Zoloft) is the most specific SSRI.

Implications SSRIs inhibit cytochrome P-450 enzymes. Their use with drugs that have narrow therapeutic windows, including phenytoin, TCAs, tolbutamide, carbamazepine, clozapine, haloperidol, class IC antiarrhythmics (see Chapter 10), and warfarin, can cause clinically significant adverse drug interactions. Thus, for some surgeries, preoperative evaluation of coagulation status may be warranted. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) may occur in geriatric patients

and warrants preoperative evaluation for hyponatremia. Postoperative delirium can be confused with neuroleptic malignant syndrome, SIADH, and withdrawal of SSRIs.

MANAGEMENT Most adverse events associated with SSRIs are due to drug interactions. If this is the case, the preferred initial therapy is to discontinue the inciting drug. Supportive measures include cooling for hyperthermia, artificial ventilation for inadequate ventilation, clonazepam for myoclonus, anticonvulsants for seizures, and chlorpromazine for its antipyretic and sedative properties.

PREVENTION SSRIs should be continued perioperatively to prevent a withdrawal syndrome. Neither general nor regional anesthesia is contraindicated. SSRIs are metabolized by hepatic transformation involving the cytochrome P-450 enzyme and can potentially inhibit the metabolism of other drugs similarly metabolized. For example, prolonged sedation with midazolam has been observed in patients receiving SSRIs. Decreased analgesic effects of μ opioids, such as morphine, have also been noted with fluoxetine.

ST. JOHN’S WORT Case Synopsis A 19-year-old, otherwise healthy man undergoes general anesthesia with midazolam, propofol, fentanyl, rocuronium, and nitrous oxide for an appendectomy. The intraoperative course is uncomplicated, with a total anesthesia time of 1 hour. Later, in the recovery room, the patient is difficult to arouse. His pupils are equal and reactive but constricted. Despite the administration of naloxone and flumazenil, and normal electrolytes and arterial blood gas measures, he remains difficult to arouse. An hour and a half later, he is arousable and purposeful. Upon subsequent interview, he states that he uses St. John’s wort for depression.

PROBLEM ANALYSIS Definition Increasing numbers of surgical patients are taking herbal remedies that can complicate the perioperative period (see also Chapter 39). A survey of the general U.S. population reported a 380% increase in the use of herbal preparations over the past decade. Up to 22% of all surgical patients use homeopathic medications. St. John’s wort is an extract from the flowers and leaves of the plant Hypericum perforatum. It is used for the short-term treatment of mild to moderate depression but is not effective for major depression. Although St. John’s wort is used for other psychiatric conditions (e.g., anxiety), there is little

evidence to support its use outside of depression, and even then, its efficacy for clinical depression is controversial. Metaanalyses of some studies have reported response rates similar to those for placebo; others have shown efficacy comparable to that of conventional antidepressants. St. John’s wort appears to have fewer side effects than conventional antidepressants.

Recognition Six classes of compounds in St. John’s wort extracts are believed to be its active components: 1. 2. 3. 4.

Naphthodianthones (i.e., hypericin, pseudohypericin) Acylphloroglucinols (i.e., hyperforin, adhyperforin) Proanthocyanidins Flavanol glycosides

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Although hypericin was formerly believed to be the principal active compound in St. John’s wort, more recent evidence suggests that hyperforin is more important for its antidepressant effects. Hyperforin has the following actions: ● ●

● ●

●

Inhibition of serotonin reuptake Weak in vitro inhibition of MAO A and B (demonstrated in one report but not confirmed in several others) Inhibition of norepinephrine and dopamine reuptake High affinity for GABAA and GABAB receptors, as well as adenosine, dopamine, and benzodiazepine receptors Significant increase in the metabolism of many concurrently used drugs by induction of cytochrome P-450 microsomal enzymes to nearly double their metabolic activity

The most affected enzyme appears to be CYP3A4, which is responsible for the metabolism of more than half of clinical drugs subject to cytochrome P-450 oxidative metabolism. Interactions with the CYP3A4 substrates indinavir, ethinyl estradiol, and cyclosporin have been reported. This interaction led to a 50% reduction in cyclosporin concentrations in one series of organ transplant recipients. There have also been reports of acute heart transplant rejection. Other CYP3A4 substrates in perioperative use are alfentanil, midazolam, lidocaine, calcium channel blockers, and SSRIs. It is likely that metabolism of these drugs is also increased. Further, St. John’s wort induces CYP2C9. Its clinical substrates include nonsteroidal anti-inflammatory drugs, diphenylhydantoin (phenytoin), and, importantly, warfarin. Finally, St. John’s wort lowers digoxin serum concentrations by induction of the P-glycoprotein transporter. St. John’s wort can be associated with adverse drug reactions in patients undergoing anesthesia and surgery, including the development of serotonin syndrome. Because it increases serotonin levels, serotonin syndrome is most commonly seen in patients also taking TCAs and is even more problematic with MAOIs. Delayed emergence from anesthesia is a relatively common occurrence with St. John’s wort and is often due to potentiation of the effects of other drugs used in anesthesia. Less common is thromboembolic stroke in patients on warfarin. Metabolic imbalance is rare.

Risk Assessment Because the most active ingredient in St. John’s wort was formerly believed to be hypericin, most preparations are still standardized to hypericin content. However, extracts contain other active constituents, especially hyperforin. Because herbals such as St. John’s wort are not subject to stringent licensing regulations, the hypericin percentage does not guarantee the amounts or pharmacologic biopotential of any other components.

Implications The antidepressant effects of St. John’s wort are believed to be a synergistic combination of MAO inhibition, decreased serotonin reuptake, and GABA activity. The anesthetic

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implications are mostly theoretical, with rare case reports. Of greatest concern is the potential for a decreased response to inotropic agents, because long-term use of St. John’s wort alters G-protein coupling mechanisms and down-regulates adrenergic receptors.

MANAGEMENT Because of its effect on anesthetics and other drugs used in perioperative settings, the preoperative discontinuation of St. John’s wort is important. This is critical in certain organ transplant patients owing to the increased risk of rejection. Also included are patients receiving warfarin for prophylaxis of thromboembolic events. Further, delayed emergence from anesthesia has been associated with St. John’s wort. In particular, the sedative effects of agents acting at GABA receptors are potentiated by the preoperative use of St. John’s wort. Also, it inhibits norepinephrine reuptake and downregulates adrenergic receptors, thus increasing the risk of cardiovascular collapse.

PREVENTION The use of herbal medications cannot be discounted and must be addressed in the preoperative assessment. Because of the long median elimination half-lives of hyperphorin (9 hours), hypericin (43 hours), and pseudohypericin (25 hours), patients should be advised to discontinue the use of St. John’s wort 5 to 7 days before anesthesia and surgery, if possible.

Further Reading Ang-Lee M, Yuan C-S, Moss J: Complementary and alternative therapies. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 605-615. Atlee JL: Management of perioperative dysrhythmias. Anesthesiology 86:1397-1424, 1997. Atlee JL, Bosnjak ZJ: Mechanisms for cardiac dysrhythmias during anesthesia. Anesthesiology 72:347-374, 1990. Boehnert MT, Lovejoy FH: Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants. N Engl J Med 313:474-479, 1985. El-Ganzouri AR, Ivankovich AD, Braverman B, et al: Monoamine oxidase inhibitors: Should they be discontinued preoperatively? Anesth Analg 64:592-596, 1985. Glassman AH, Bigger JT: Cardiovascular effects of therapeutic doses of tricyclic antidepressants: A review. Arch Gen Psychiatry 38:815-820, 1981. Hodges PJ, Kam PC: The perioperative implications of herbal medicines. Anaesthesia 57:889-899, 2002. Kam PC, Chang GW: Selective serotonin reuptake inhibitors: Pharmacology and implications in anaesthesia and critical care medicine. Anaesthesia 52:982-988, 1997. Kudoh A, Katagai H, Takazawa T: Antidepressant treatment for chronic depressed patients should not be discontinued prior to anesthesia. Can J Anaesth 49:132-136, 2002. Mcfarlane HJ: Anesthesia and the new generation monoamine oxidase inhibitors. Anaesthesia 49:597-599, 1994. Scher CS, Anwar M: The self-reporting of psychiatric medications in patients scheduled for elective surgery. J Clin Anesth 11:619-621, 1999. Stack CG, Rogers P, Linter SPK: Monoamine oxidase inhibitors and anesthesia. Br J Anaesth 60:222-227, 1988.

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Case Synopsis A 45-year-old woman presents for elective cholecystectomy. During the preoperative consultation, she states that she had a lump removed from her breast 10 years earlier after “they found cancer under my arm.” She underwent six cycles of chemotherapy with radiation therapy, and the cancer has not recurred. She feels fine and denies any cardiac history.

modifiers (interleukin-2, granulocyte colony-stimulating factor [filgrastin], granulocyte-macrophage colonystimulating factor [sargramostim]); monoclonal antibodies (trastuzumab, rituximab, tositumomab)

PROBLEM ANALYSIS Definition CLASSIFICATION

AND

USE

There are numerous chemotherapeutic agents in use today. The major classes, along with their subclasses and some specific agents, are as follows: ●

●

●

● ●

● ●

Alkylating agents: nitrogen mustards (mechlorethamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil); ethylenimines and methylmelamines (triethylenemelamine [TEM], thiotepa [triethylene thiophosphoramide], altretamine [hexamethylmelamine]); alkyl sulfonates (busulfan); nitrosoureas (carmustine [BCNU], streptozocin); triazenes (dacarbazine) Antimetabolites: folic acid analogues (methotrexate); pyrimidine analogues (fluorouracil, floxuridine, cytarabine, gemcitabine); purine analogues (mercaptopurine, azathioprine, thioguanine, fludarabine phosphate, pentostatin, cladribine) Natural products and synthetic congeners: antimitotics (vinca alkaloids, paclitaxel and its more potent analogue docetaxel); epipodophyllotoxins (etoposide, teniposide); camptothecin analogues (the parent compound [camptothecin] had significant antitumor activity but was subsequently discarded in favor of analogues with less severe and more predictable toxicity, such as irinotrecan and topotecan); antibiotics (dactinomycin [actinomycin D], daunorubicin, doxorubicin, idarubicin), newer synthetic analogues of doxorubicin (valrubicin, epirubicin, mitoxantrone), bleomycins (bleomycin sulfate, mitomycin) Enzymes (L-asparaginase) Miscellaneous agents: platinum coordination complexes (cisplatin, carboplatin, oxaliplatin); hydroxyurea; procarbazine; mitotane Hormones: adrenocorticosteroids Aminoglutethimide and two newer classes of aromatase inhibitors (the enzyme that converts androgens to estrogens): analogues that block this conversion (formestane, exemestane) and the imidazole inhibitors (anastrozole, vorozole, letrozole); steroidals (progestins, estrogens and androgens, antiestrogens [tamoxifen, raloxifene], antiandrogens [flutamide, nilutamide, bicalutamide]); gonadotropin-releasing hormone analogues (leuprolide, goserelin, triptorelin, buserelin); biologic response

110

The potential perioperative complications associated with all chemotherapeutics cannot be addressed here. This chapter focuses on two commonly used anthracycline antibiotics and a synthetic analogue. Information about other important, representative chemotherapeutic agents is provided in Table 30-1. Anthracycline antibiotics and their derivatives are among the principal chemotherapeutics in use today. Daunorubicin (Cerubidine, daunomycin, rubidomycin) and doxorubicin (Rubex, Adriamycin) were first isolated from the fungus Streptomyces peucetius. Synthetic derivatives are available (e.g., idarubicin [Idamycin]). Although they differ slightly in chemical structure, daunorubicin and idarubicin are used, along with cytarabine (see Table 30-1), against acute myelogenous and lymphocytic leukemias. In fact, daunorubicin is among the most active drugs against acute myelogenous leukemia in adults. A daunorubicin citrate liposomal drug preparation (DaunoXome) is used to treat Kaposi’s sarcoma related to acquired immunodeficiency syndrome (AIDS). Doxorubicin has activity against acute leukemias, malignant lymphomas, and other human neoplasms. A doxorubicin liposomal product (Doxil) is used against AIDS-related Kaposi’s sarcoma. In contrast to daunorubicin, doxorubicin has activity against solid tumors. Along with cyclophosphamide, procarbazine, and vincristine (or others), it is critical for the successful treatment of Hodgkin’s and non-Hodgkin’s lymphomas. Doxorubicin is also used in regimens against breast and small cell lung carcinomas; adult and pediatric sarcomas (osteogenic, Ewing’s, soft tissue); cancer of the cervix or endometrium, prostate, testes, and head and neck; and plasma cell myeloma. However, the clinical value of these “parent” anthracycline antibiotics (daunorubicin, doxorubicin) is limited by an unusual and often irreversible cardiomyopathy that is directly related to the total amount of agent received. Thus, in the search for agents with higher antineoplastic activity but less cardiotoxicity, numerous derivatives have been prepared, some of which have shown promise in clinical studies: ● ● ●

Idarubicin (leukemia) Epirubicin (solid tumor chemotherapy) Mitoxantrone (prostate cancer, leukemia, high-dose chemotherapy)

Catalyzes the hydrolysis of L-asparagine (required by some neoplastic cells—e.g., acute lymphoblastic leukemia—for protein synthesis) to aspartic acid and ammonia, which deprives neoplastic cells of an essential amino acid, leading to cell death Antibiotic; cleaves DNA The drug in clinical use is a mixture of two copper-chelating peptides (bleomycin A2 and B2); interactions with O2 and Fe2+ lead to scission of DNA

L-Asparaginase

Busulfan Alkylating agent; few actions other (Myleran,Busulfex) than myelosuppression at conventional doses; at low doses, selective depression of granulocytopoiesis

Bleomycin (Blenoxane)

(Oncaspar, Elspar)

Anastrozole (Arimidex)

Antibiotic; binds to DNA to form highly stable drug-DNA complexes that block DNA transcription by RNA polymerase; this inhibits any rapidly proliferating cells Nonsteroidal; inhibits imidazole aromatase; effectively blocks the biosynthesis of estrogen

Mechanism of Antineoplastic Effect

Highly effective for ovarian or testicular germ cell tumors With cisplatin and vinblastine or etoposide, curative for testicular cancer With cisplatin and other agents, highly active for GU tract squamous cell, esophageal, and head and neck carcinomas Sometimes used as a component of therapy for Hodgkin’s and non-Hodgkin’s lymphomas For chronic granulocytic leukemia, expect remission in 85%-90% of patients after initial therapy; however, the drug has largely been replaced by interferon-α and hydroxyurea

Useful component of therapy for acute lymphoblastic leukemia and other lymphoid malignancies

Pediatric tumors: Wilms’ and Ewing’s tumors Additional activities: Kaposi’s sarcoma, choriocarcinoma, metastatic testicular sarcoma Primary therapy: estrogen or unknown receptor Postmenopausal, advanced, or metastatic breast cancer; recurrence of disease after tamoxifen

Important Indications

No androgenic effects; metabolized in liver; dosing unaffected by renal dysfunction; long half-life (50 hr); can be given orally once daily; suppresses estrogen to below detectable concentrations; has a favorable toxicity profile Hypoalbuminemia; hyperglycemia; thrombosis; less often, hemorrhagic events Most thromboses are in patients with gene defects: factor V Leiden; protein S, C, or AT III; low or ↑ homocysteine

With SC extravasation, marked local inflammation; very potent immunosuppressant

Clinical Considerations

Continued

Pulmonary toxicity (dry cough, fine Little myelosuppression; avoid high FiO2; rales, diffuse infiltrates leading judicious IV fluids in patients with to possibly fatal pulmonary fibrosis), pulmonary toxicity, especially with worsened by ↑ FiO2 fibrosis Skin toxicity: erythema, hyperkeratoses, hyperpigmentation, ulcerations, N/V Unusual toxicity in patients with lymphomas: severe hyperthermia and hypotension; then sustained cardiorespiratory arrest Nonimmune? Endogenous pyrogen? Low doses: cytotoxic action does not Allopurinol reduces renal damage from appear to extend to lymphoid or urate deposits GI tissues Expect lower leukocyte counts by High-dose regimens: pulmonary 3 wk, then a reduction in spleen fibrosis and hepatic veno-occlusive size in CML disease

Few effects on bone marrow or GI mucosa; severe toxicity due to antigenicity and protein synthesis inhibition; hypersensitivity reactions in 5%-20% of patients (may be fatal); deficient insulin or clotting factors

Reduced toxicity: acne (“androgenic skin”), alopecia, N/V

Myelosuppression (pancytopenia), N/V, anorexia, diarrhea, proctitis, cheilitis, ulcerations (oral and GI mucosa, skin), alopecia

Clinical Toxicities

Mechanisms, Uses, and Toxicities of Selected Chemotherapeutic Agents Other than Anthracycline Antibiotics

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Dactinomycin or actinomycin D (Cosmegen)

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Table 30–1

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112

Enters cells by diffusion – Replacement of Cl by water yields a positively charged molecule that may be responsible for drug activity; this can react with nucleic acids and proteins – Acquation is favored at low [Cl ]; – high [Cl ] stabilizes cisplatin Platinum complexes react with DNA, forming intra- and interstrand cross-links; DNA adducts inhibit replication and transcription of DNA breaks and miscoding; ability to form these adducts predicts efficacy Cyclophosphamide Most widely used alkylating drug; (Cytoxan, converted by liver P-450 enzymes Neosar) to acyclic aldophosphamide and 4-hydroxycyclophosphamide (tautomers that are in steady-state equilibration with each other); the latter is metabolized to inactive metabolites that may limit liver damage; aldophosphamide is converted in malignant cells to phosphoramide mustard and acrolein; the former, an alkylating agent, is antineoplastic Pretreatment with phenobarbital (which induces liver P-450 enzymes) enhances drug activation but does not affect its toxicity or therapeutic efficacy

Mechanism of Antineoplastic Effect Thrombocytopenia (prolonged) is possible Initially, rapid cell destruction leads to extensive purine catabolism and renal damage from precipitation of urates N/V in almost all patients Nephroxicity can be mostly prevented with hydration and diuresis Tinnitus and high-frequency hearing loss more frequent or severe with repeat dosing in children Peripheral neuropathy may worsen after repeated cycles of therapy Electrolyte imbalance (↓ Ca2+, Mg2+, K+, PO4) common and can cause tetany or promote arrhythmias Hemolytic anemia, hyeruricemia, and seizures Cardiac abnormalities have been reported Myelosuppression (platelet sparing), N/V, alopecia, SIADH, GI mucosal ulcerations and (less common) interstitial pulmonary fibrosis With high-dose IV therapy, renal, hepatic, and cardiac toxicities may occur; sterile hemorrhagic cystitis occurs in 5%-10% of patients secondary to acrolein

In AML, busulfan (high doses) + cyclophosphamide is given for bone marrow transplants Also used in polycythemia vera and myeloid fibrosis-metaplasia

Alone, for susceptible lymphomas and chronic leukemia Higher doses with other drugs: breast cancer, lymphomas Key drug in non-Hodgkin’s or Burkitt’s lymphoma Used with methotrexate (or doxorubicin) + fluorouracil after breast cancer surgery Other uses: multiple myeloma; lung cancers; cancer of the breast, ovaries, or cervix; childhood neuroblastoma or retinoblastoma As immunosuppressant: organ transplants, Wegener’s granulomatosis, rheumatoid arthritis, pediatric nephrotic syndrome

Combined chemotherapy with cisplatin, bleomycin, etoposide, and vinblastine is 85% curative for advanced testicular carcinoma If combined with paclitaxel, doxorubicin, or cyclophosphamide, it is beneficial in ovarian carcinoma Also produces responses in cancers of the head and neck, endometrium, small cell lung carcinoma, and some childhood neoplasms Sensitizes cells to cytotoxic effects of radiation therapy

Clinical Toxicities

Important Indications

No SC extravasation reactions or thrombophlebitis Reduce cystitis incidence with mesna + diuresis Stop drug if dysuria or hematuria occurs Hepatic P-450 required for activation; may be less effective with liver dysfunction Caution: renal dysfunction is possible; ample fluids advised, but water intoxication is possible Cyclophosphamide and others (mechlorethamine) prolong block with some muscle relaxants (i.e., act as anticholinesterases)

Prevent N/V with ondansetron and high-dose corticosteroids For electrolyte imbalance, use K+, Mg2+ repletion therapy Anaphylactic-like reactions may occur minutes after administration (facial edema, bronchospasm, tachycardia, hypotension) and are treated with IV epinephrine + corticosteroids or antihistamines.

Clinical Considerations

Mechanisms, Uses, and Toxicities of Selected Chemotherapeutic Agents Other than Anthracycline Antibiotics—cont’d

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Metabolism by cytochrome P-450 system (primarily by CYP3A4) mandates careful surveillance for possible drug-drug interactions

Periorbital and leg edema, muscle cramping, GI hemorrhage

Major toxicity: GI epithelium, bone marrow Patients possibly at risk for spontaneous hemorrhage or severe infections Side effects often last for weeks Chronic bone marrow suppression with renal dysfunction due to slow MTX excretion Other toxicities: alopecia, dermatitis, lung (interstitial pneumonitis), kidneys, defective oogenesis or spermatogenesis, teratogenesis or abortion

CML (with bcr-abl translocation); some GISTs (mostly stomach) and lymphoid CML; possibly some activity against other solid tumors As a single agent, imatinib has remarkable remission-inducing activity Some GIST subsets have mutations that confer in vitro resistance to imatinib Acute lymphoblastic leukemia in high doses in children Valuable for remission induction or consolidation and for maintaining remissions in leukemia; less valuable for adult leukemia, except for treatment or prevention of leukemic meningitis Intrathecal MTX: therapy or prophylaxis of meningeal leukemia, lymphoma, or carcinomas Proven value in choriocarcinoma and related trophoblastic tumors in women

Continued

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Potent immune suppressant that reduces platelets, hemoglobin, and leukocytes Eliminated renally via glomerular filtration and tubular secretion; ensure adequate hydration to avoid MTX precipitation in renal tubules; also, avoid drugs that decrease renal flow or are weak acids or direct nephrotoxins (NSAIDs, piperacillin, aspirin, cisplatin) Half of MTX is bound to plasma proteins and is displaced from plasma albumin by salicylates, chloramphenicol, sulfonamides, tetracyclines, and phenytoin

Response to therapy affected by proportion of drug converted to ara-CTP, which depends on relative activities of a number of anabolic or catabolic enzymes (see Chabner under “Further Reading”) Relationships exist between ara-CTP synthesis and its retention in leukemic cells, and remission duration in AML; cells’ ability to transport ara-CTP is another important factor in determining clinical response Owing to a rapid fall in plasma drug concentrations to levels less than those needed to saturate drug transport or activation processes, many clinicians use high-dose regimens to attain 20- to 50-fold higher serum levels; this has improved the induction of remissions

Best agent for inducing remissions As a potent myelosuppressant, in AML in children and adults; toxicity includes thrombocytopenia, as single therapy, remission rates severe leukopenia, and anemia with of 20%-40% reported, but more striking megaloblastic changes effective with anthracyclines or Causes fever, GI disturbances, mitoxantrone stomatitis, mild reversible hepatic Given as a single IV injection or by dysfunction, pneumonitis, and continuous infusion (varying dosage); dermatitis children may tolerate higher doses After intrathecal administration, than adults seizures and other neurotoxic Intrathecal ara-C has been used against manifestations can occur; also meningeal leukemia possible when high IV doses Liposomal ara-C (DepoCyt) appears (>3 g/m2) are given to patients to be as effective as IV ara-C ≥40 yr and/or with renal Especially useful for adult, acute dysfunction or abnormal alkaline nonlymphocytic leukemia phosphatase Used in aggressive non-Hodgkin’s lymphomas and for acute lymphocytic leukemia relapses in patients of all ages

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Cytarabine or ara-C Antimetabolite, pyrimidine analogue; (Cytosar-U, penetrates cells by a carrierTarabine PFS) mediated process; activated by conversion to ara-CMP (a 5′-monophosphate nucleotide), which reacts with nucleotide kinases to form diphosphatetriphosphate nucleotide residues (ara-CDP, ara-CTP), potent inhibitors of DNA polymerase; effects extend not only to DNA synthesis but also to repair Precise mechanism of cellular death is not understood; fragmentation of DNA is observed in ara-C–treated cells, and there is evidence of apoptosis in tumor and normal cells Kinetic properties also affect results of therapy Intracellular concentrations of araCTP must be at inhibitory levels for ≥1 cell cycle Response to ara-C is strongly affected by proportion of drug converted to ara-CTP Imatinib mesylate FMS-like TK 3 (FLT3) receptor exists (Gleevec) in myeloid and some lymphoid leukemias The bcr-abl translocation in CML encodes for abnormal TK, needed for cell proliferation and survival; it causes the Philadelphia chromosome abnormality in CML GISTs may harbor oncogenic TK mutations and are targets for TK receptor inhibitors such as imatinib Methotrexate Folic acid is an essential dietary (Folex, Mexate, factor; from it are derived Rheumatrex, tetrahydrofolate (TH4) cofactors others) that provide single carbon groups for the synthesis of precursors of DNA (thymidylate and purines) and RNA (purines) The enzyme DHFR is the primary site of action for MTX and most other folate analogues; MTX’s inhibition of DHFR leads to toxic effects via (1) partial depletion of TH4 cofactors needed for synthesis of purines and

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114 Natural antibiotic derived from Streptomyces acromogenes; also a nitrosourea alkylating agent that affects all stages of the mammalian cell cycle MNU has high affinity for insulinproducing β cells of pancreatic islets of Langerhans and causes diabetes in animal models

Important vinca alkaloids; cell cycle– specific agents that block cells in mitosis—specifically, binding to tubulin to block its ability to polymerize into microtubules; this disrupts microtubules of the mitotic apparatus to arrest cell

Vincristine (Oncovin, Vincasar PFS, others) and vinblastine (Velban)

thymidylate, (2) inhibition of folate-dependent enzymes required in thymidylate-purine metabolism, and (3) accumulation of a toxic DHFR inhibitory substrate—FH2 polyglutamate

Mechanism of Antineoplastic Effect

Vincristine and corticosteroids are first-line therapy for inducing remission of leukemia in children Adults with lymphomas (Hodgkin’s or non-Hodgkin’s) usually receive vincristine as part of a combined protocol

Also used in osteosarcoma and mycosis fungoides Part of combined therapy in Burkitt’s and non-Hodgkin’s lymphomas and in carcinomas of the breast, lung, head and neck, ovary, and bladder Also used in therapy of severe and disabling psoriasis Advanced and metastatic pancreatic islet cell tumors; beneficial response results in significant increase in 1-yr survival rate and doubling of median survival time Also shows promise as therapy with fluorouracil or dacarbazine for advanced carcinoid tumors

Important Indications

Liver dysfunction is often reversible but may lead to cirrhosis (e.g., chronic continuous therapy, as in psoriasis) Intrathecal use often causes inflammatory response in CSF or meningismus Seizures, coma, and death (rare occurrences) Nausea (common) Renal or hepatic toxicity in about two thirds of patients; renal toxicity is usually reversible, dose related, and cumulative, but may be fatal; proximal tubular damage is the most important effect; urinary protein assays are used to detect early toxicity; not given with nephrotoxic drugs Hematologic toxicity occurs in 20% of patients and includes anemia, leukopenia, and thrombocytopenia Vincristine: toxicity is predictable, cumulative, and mostly neurologic—extremity numbness or tingling and loss of deep tendon reflexes (early, common), followed by motor weakness; the former usually do not warrant an

Clinical Toxicities

Neurologic toxicity is avoided or reversed by stopping therapy or reducing the dosage when motor dysfunction first occurs Severe constipation or obstipation is prevented with laxatives or hydrophilic agents

Unmodified MNU (active moiety) causes delayed myelosuppression; streptozocin does not Also, MNU carbamoylates lysine residues of proteins; it is attached to these to alter specificity, distribution, and toxicity (e.g., carmustine and lomustine are lipophilic and cross the blood-brain barrier and are used for brain tumors; unlike streptozocin, they cause profound, cumulative myelosuppression)

Folinic acid (Leukovorin) does not reverse neurotoxicity

Clinical Considerations

Mechanisms, Uses, and Toxicities of Selected Chemotherapeutic Agents Other than Anthracycline Antibiotics—cont’d

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Vinblastine was once used with bleomycin and cisplatin to cure metastatic testicular tumors, but etoposide has largely replaced it Other indications for vinblastine are breast cancer, Hodgkin’s disease, Kaposi’s sarcoma, histiocytosis, neuroblastoma, and choriocarcinoma

immediate dose reduction, but motor loss dictates re-evaluation of therapy; vocal cord paralysis or extraocular muscle function loss is rare In high doses, vincristine can cause severe constipation or obstipation; intrathecal injection causes fatal CNS toxicity; SIADH occurs rarely Vinblastine: nadir of leukopenia occurs by 7-10 days, with recovery by 7 days; other toxicities include neurotoxicity (as for vincristine), GI disturbances, and SIADH; alopecia, oral mucositis, and dermatitis are rare; extravasation during injection may lead to cellulitis and phlebitis

Alopecia occurs in about 20% of patients but is always reversible (often without stopping therapy) Myelodepression (leukopenia, anemia, thrombocytopenia) is more common with vincristine than vinblastine Hyponatremia, high urinary Na+, and SIADH are occasionally seen In view of the rapid action of vinca alkaloids, one must prevent hyperuricemia with allopurinol Vinca alkaloids are extensively metabolized by the liver, so caution is advised in patients with decreased hepatic function Vinca alkaloids are very irritating to tissues

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PHARMACOLOGY

AML, acute myelogenous leukemia; AT, antithrombin; CML, chronic myelogenous leukemia; CSF, cerebrospinal fluid; DHFR, dihydrofolate reductase; FiO2, fractional inspired oxygen; GI, gastrointestinal; GIST, gastrointestinal stromal tumor; GU, genitourinary; IV, intravenous; MNU, methylated nitrosourea; MTX, methotrexate; N/V, nausea or vomiting; NSAIDs, nonsteroidal anti-inflammatory drugs; SC, subcutaneous; SIADH, syndrome of inappropriate antidiuretic hormone secretion; TK, tyrosine kinase. From Chabner BA, Ryan DP, Paz-Ares L, et al: Antineoplastic agents. In Hardman JG, Limbird LE (eds): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York, McGraw-Hill, 2001, pp 1389-1459; and www.pdr.net.

division in metaphase (microtubules are important for other cell functions as well: movement, axonal transport, phagocytosis) Without an intact mitotic spindle, chromosomes disperse throughout the cytoplasm (“exploded mitosis”) or cluster oddly Incorrect chromosomal segregation during mitosis causes cell death Normal and malignant cells exposed to these agents undergo changes characteristic of apoptosis

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Mitoxantrone (an anthracenedione) has significantly less cardiotoxicity than the anthracyclines. MECHANISM

OF

ACTION

The anthracycline antibiotics have three major biochemical effects that may explain their antineoplastic efficacy (if not their toxicity). First, they function as electron-accepting and electron-donating agents. They intercalate with the DNA helix to affect many of its functions. Single- and double-strand breaks and sister chromatid exchanges interfere with the transcription of RNA and the replication of DNA. As a result, toxicity occurs in the S phase of the cell cycle, but the cell dies on entering the G2 phase. Genetic material is exchanged between chromatids, which, in addition to causing breaks in the DNA strand, renders this material mutagenic and carcinogenic. Breaks in the helix occur because intercalation disturbs the action of topoisomerase II. Second, the anthracycline antibiotics produce free radicals, giving rise to potent alkylating agents. For example, with reduced NADPH, they react with cytochrome P-450 reductase to generate semiquinone radical intermediates. In the presence of oxygen, superoxide anion radicals form to generate reactive species (e.g., H2O2, NO, and OH–) that attack DNA. At least with doxorubicin, iron catalyzes free radical production. Insertion of these free radicals into the DNA helix may also cause breaks in the DNA sequence. Third, anthracycline antibiotics interact with cell membranes to form lipid peroxides. Peroxides alter cell membrane function and, therefore, cell function. Which of these three diverse actions is primarily responsible for the efficacy or toxicity of the anthracyclines is still a matter of speculation.

Recognition Patients almost invariably know their primary tumor type but may not know or recall exactly what drugs they received or their dosages. This is especially true when patients received complex chemotherapeutic regimens or were treated in the distant past. In addition, many patients now receive their chemotherapy as outpatients, and the specific protocol used may not be included in the medical record. As a result, anesthesiologists should at least be aware of the agents used to treat the more common malignancies and the side effects of some typically used antineoplastics. The goal of chemotherapy is to administer a dose of drug that maximizes the cytotoxic effect on neoplastic cells or tissues without impairing the patient’s lifestyle when the course of therapy is completed. However, these drugs may significantly reduce the patient’s functional reserve, which becomes apparent only in the perioperative period when the patient is physiologically stressed. Anesthesiologists should maintain a high index of suspicion that such a patient’s physiologic reserve may be significantly impaired (in spite of a healthy appearance) and be prepared to evaluate this condition appropriately and initiate the indicated remedial therapy.

Risk Assessment CLINICAL CONSIDERATIONS Daunorubicin, doxorubicin, epirubicin, and idarubicin are usually administered intravenously and are cleared by hepatic

metabolism and biliary excretion. Doxorubicin has biphasic clearance, with 3- and 30-hour half-lives of elimination. Idarubicin has monophasic clearance and a half-life of elimination of 15 hours. The clearance of all anthracyclines is delayed in patients with hepatic dysfunction, and at least a 50% reduction in dose should be considered in patients with abnormal serum bilirubin concentrations. Daunorubicin and doxorubicin are converted to a variety of less active or inactive products. Idarubicin is metabolized primarily to idarubicinol, which accumulates in plasma and resembles the parent compound in activity. Daunorubicin and doxorubicin are converted to their alcohols, aglycons, and other derivatives. Rapid uptake of these anthracyclines occurs in the heart, kidneys, lungs, liver, and spleen. The anthracyclines do not cross the blood-brain barrier. Superoxide dismutase and catalase help protect against anthracycline toxicity, an effect increased by exogenous antioxidants. Both daunorubicin and doxorubicin may impart a red color to urine. Appropriate care is exercised to prevent inadvertent extravasation during intravenous administration of anthracyclines because a severe local vesicant action and tissue necrosis may result. TOXICITY The anthracycline antibiotics cause myelosuppression. This results in leukopenia and, to a lesser degree, anemia and thrombocytopenia, reaching a nadir around 10 to 14 days after beginning therapy. Stomatitis, alopecia, and gastrointestinal symptoms are also common. The anthracycline antibiotics produce a dose-dependent cardiotoxicity that is unique to this class of drugs. This cardiotoxicity may be acute or chronic and is resistant to digitalis. Acute myocardial damage is often revealed by electrocardiogram (ECG), showing flattened T waves, ST segment depression, or cardiac rhythm disturbances (notably, sinus tachycardia and extrasystoles). Often, these are selflimited and rarely cause serious complications. However, life-threatening arrhythmias have occurred within hours of doxorubicin administration in some patients. Further, the cardiac ejection fraction may be depressed within 24 hours of a single dose of these agents, but even this is often transient and rarely problematic. The pericarditis-myocarditis syndrome is a potentially life-threatening manifestation of acute cardiotoxicity with anthracycline antibiotics. Features include severe conduction disturbances or arrhythmias and frank congestive heart failure (CHF), often associated with pericardial effusion. Although this usually occurs outside of perioperative settings, it may first manifest after anesthetic induction, with surgical stress, or in the postanesthetic or intensive care unit after anesthesia and surgery. Fortunately, pericarditismyocarditis syndrome is an uncommon occurrence. CHF that is unresponsive to cardiac glycosides is the hallmark of chronic cardiac toxicity with anthracycline antibiotics. It may develop years after the completion of chemotherapy but often develops within 6 months. Electron microscopy reveals cardiac mitochondrial changes, a reduction in myocardial fibrils, and cellular cardiac degeneration after the administration of these agents. On ECG, the QRS voltage is reduced, and the systolic time interval is prolonged. The extent of myocardial damage is directly proportional to

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EVALUATION

AND

WORKUP

The first and most important element when assessing risk in patients who are receiving (or have received) anthracycline antibiotic chemotherapeutics is a high index of suspicion for associated cardiotoxicity. This cannot be overemphasized. Often, these patients do not appear physically handicapped based on their history, physical examination, and routine laboratory test results. Only when their cardiac functional reserve is tested (e.g., during exercise stress testing) does it become apparent that further (i.e., perioperative) cardiac stress will be poorly tolerated. Once the anesthesiologist suspects that a patient has received a chemotherapeutic agent that could compromise cardiopulmonary function, every effort must be made to determine the regimen used, including the dose and pathway of concurrent or subsequent irradiation therapy. The drugs, their associated toxicities, and therapeutic implications (see Table 30-1) must be carefully assessed. This includes defining the patient’s baseline physiologic functional status and the anticipated insult from any surgical or other intervention requiring anesthesia. Radionuclide-gated blood pool studies may be the most sensitive test for detecting CHF, but an echocardiogram is a reasonable alternative. The patient should have an ECG and evaluation of the cardiac ejection fraction before the initiation of anthracycline chemotherapy and before each cycle of such therapy after cumulative doses of 400 mg/m2. No test can predict which patients will develop CHF with therapy. Acute or chronic toxicity is unpredictable. Common sense suggests reducing the cumulative dose in patients with preexisting heart disease. The preoperative evaluation should include the following: ● ● ● ●

Cumulative dose of drugs administered Date of final administration Associated therapy (e.g., irradiation? if so, how directed?) Results of cardiac functional evaluation (ECG, echocardiogram, multiple gated image analysis, exercise stress testing, or a combination) before therapy was initiated and 6 months after the last cycle of chemotherapy

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117

Because myocardial injury may progress for years after therapy, ideally, cardiac function should be evaluated within 1 month of interventions requiring anesthesia. However, given current cost concerns, this may not be justified unless the patient’s history suggests a deteriorating functional status. CONFOUNDING ISSUES

AND

VARIABLES

Irradiation of the mediastinum; exposure to cyclophosphamide, vincristine, or fluorouracil; or the addition of another drug can exacerbate the toxicity associated with these drugs. Indeed, in one study, all cases of CHF in patients who had received radiation therapy to the mediastinum occurred after anthracycline antibiotic doses of less than 315 mg/m2. Calcium channel blockers also may increase the risk for cardiotoxicity. As noted earlier, when CHF does develop, the mortality rate can exceed 50%. Dexrazoxane appears to reduce cardiotoxicity with the anthracycline antibiotics. Its addition to the regimen may allow higher cumulative doses of these agents. Newer anthracycline analogues (e.g., epirubicin, mitoxantrone, idarubicin) may have less cardiotoxicity but retain near full cytotoxic potential against some malignant cells. Thus, although they may have a narrower spectrum of action, they may be inherently safer. Finally, doxorubicin can cause red streaks near the infusion site (i.e., Adriamycin flare), even without extravasation of the vesicant. Also, doxorubicin can cause severe local toxic effects in irradiated tissues, even when chemotherapy and irradiation therapy are not concurrent.

Implications Cancer has now surpassed heart disease as the leading cause of death in the United States. Patients with cancer live longer and, increasingly, present to hospitals or ambulatory care facilities for treatment requiring an anesthesiologist’s services— anesthesia for surgical or other painful interventions, pain management, critical care, or treatment for disease progression, a new malignancy, or another problem. Regardless, patients who have received anthracycline antibiotics tolerate anesthetics or other myocardial depressants poorly, even without evidence of loss of myocardial function (e.g., reduced ejection fraction). Invariably, these patients have reduced inotropy that is difficult to assess with echocardiography or cardiac catheterization. If anesthesia is required for such patients, the anesthesiologist must give serious consideration to a regional anesthetic technique, if suitable. Perioperative care should include the following: ● ● ● ● ● ●

Limiting intravenous fluids Improving the inotropic state Reducing afterload to optimize cardiac output Careful selection of the intravenous induction agent Judicious use of invasive cardiovascular monitoring Availability of mechanical circulatory assistance, if needed (however, this intervention often proves minimally beneficial)

Although this chapter focuses on anthracycline-induced cardiotoxicity, anesthesiologists should be aware of the mechanisms of action, important indications, and clinical

PHARMACOLOGY

the cumulative dose of the anthracycline antibiotic or synthetic congeners. Although practical and completely reliable tests are unavailable, serious cardiomyopathy with doxorubicin occurs in 1% to 10% of patients with total doses less than 450 mg/m2 of body surface area (BSA). This risk increases to more than 20% of patients with total doses greater than 550 mg/m2 BSA. Such total dosage should rarely be exceeded, and then only with the concomitant administration of dexrazoxane (Zinecard), a cardioprotective, intracellular chelating agent (see “Confounding Issues and Variables”). The mortality rate with significant anthracycline-related cardiomyopathy can exceed 50%. Total doses as low as 250 mg/m2 can cause myocardial toxicity, as revealed by subendocardial biopsies. Children appear to be at even greater risk, because anthracyclines impair myocardial growth. Among pediatric patients, 5% to 10% will have overt CHF by the time they become adults, and subclinical cardiac dysfunction will develop in 40%. Finally, cardiac irradiation or the coadministration of high doses of cyclophosphamide or other anthracyclines may increase the risk of cardiotoxicity.

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toxicities and indications of other important and widely used chemotherapeutic agents (see Table 30-1).

the anesthesiologist will be able to tailor any anesthetics or drugs used for pain management to the needs of the patient.

MANAGEMENT

Further Reading

Therapy for anthracycline-induced CHF includes the following: ● ● ● ●

Diuretics Afterload reduction Low-sodium diet Bed rest

Therapy should also include cardiac glycosides, despite their limited benefit (anthracycline-induced cardiotoxicity is resistant to digitalis). Although these interventions may provide some symptomatic and functional improvement, the direct effects of cardiotoxicity are irreversible. Finally, because of the loss of contractile elements, mitochondrial damage, and unsatisfactory geometry of a dilated ventricle, the response to nondigitalis inotropes may be quite limited. An intensive care unit should be available postoperatively to receive the patient if needed.

PREVENTION There is no acceptable therapeutic alternative to chemotherapeutic drugs in many patients. Even after a successful course of chemotherapy, a patient may continue to require the services of an anesthesiologist for related or nonrelated surgery or other painful interventions or for chronic pain management. With the anthracycline antibiotics, prevention focuses on how best to minimize the risk for further depression of myocardial function. Thus, awareness that some myocardial injury has occurred and evaluation of its severity are critical to anesthetic or pain management. With such knowledge,

Capizzi RL: Principles of treatment of cancer. In Stein JH (ed): Internal Medicine, 4th ed. New York, Mosby–Year Book, 1994, pp 707-729. Chabner BA, Ryan DP, Paz-Ares L, et al: Antineoplastic agents. In Hardman JG, Limbird LE (eds): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York, McGraw-Hill, 2001, pp 1389-1459. Corless CL, Schroeder A, Griffith D, et al: PDGFRA mutations in gastrointestinal stromal tumors: Frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 23:5357-5364, 2005. de Mestier P, des Guetz G: Treatment of gastrointestinal stromal tumors with imatinib mesylate: A major breakthrough in the understanding of tumor-specific molecular characteristics. World J Surg 29:357-361, 2005. Di Cosimo S, Ferretti G, Fazio N, et al: Docetaxel in advanced gastric cancer—review of the main clinical trials. Acta Oncol 42:693-700, 2003. Kouvaraki MA, Ajani JA, Hoff P, et al: Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol 22: 4762-4771, 2004. Kvolik S, Glavas-Obrovac L, Sakic K, et al: Anaesthetic implications of anticancer chemotherapy. Eur J Anaesthesiol 20:859-871, 2003. McCollum AD, Kulke MH, Ryan DP, et al: Lack of efficacy of streptozocin and doxorubicin in patients with advanced pancreatic endocrine tumors. Am J Clin Oncol 27:485-488, 2004. Roizen MF, Fleisher LA: Anesthetic implications of concurrent disease. In Miller RD (ed): Miller’s Anesthesia, 6th ed. New York, Churchill Livingstone, 2005, pp 1017-1149. Selvin BL: Cancer chemotherapy: Implications for the anesthesiologist. Anesth Analg 60:425-434, 1981. Sternberg DW, Licht JD: Therapeutic intervention in leukemias that express the activated FMS-like tyrosine kinase 3 (FLT3): Opportunities and challenges. Curr Opin Hematol 12:7-13, 2005. Sun W, Lipsitz S, Catalano P, et al: Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281. J Clin Oncol 23: 4897-4904, 2005.

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Chemical Dependency: Opioids Mark S. Gold, Adrie Bruijnzeel, Kimberly Frost-Pineda, and William Jacobs Case Synopsis A 38-year-old anesthesiologist is found unresponsive and cyanotic in the call room after failing to return from a break in the case of a patient undergoing a craniotomy for tumor. Both fresh and recent venipuncture sites are found on his left forearm, along with a 1-mL insulin syringe and a rubber tourniquet.

PROBLEM ANALYSIS Definitions The American Medical Association defines an impaired physician as “one unable to fulfill professional or personal responsibilities due to psychiatric illness, alcoholism or drug dependency.” This definition is in stark contrast to that for a professional athlete or a pilot, who is defined as impaired if “he or she is unfit for duty, shows up at work underthe-influence, or with residual effects.” As defined in the Diagnostic and Statistical Manual of Mental Disorders, drug dependence is a maladaptive pattern of substance use leading to clinically significant distress or impairment. Individuals are considered to be drug dependent when three or more of the following behaviors exist within the same 12-month period: ●

●

●

●

●

●

●

Tolerance, which is the need for more of the drug to achieve intoxication or the desired effect, or a decreased effect with continued use of the same amount of the drug. Withdrawal, in which a characteristic withdrawal syndrome appears without the substance, or the same or similar substance is taken to relieve or avoid withdrawal. The drug is taken in larger quantities or over a longer period than was intended. There is a persistent desire or unsuccessful efforts to cut down or control use. A significant amount of time is spent in obtaining, using, or recovering from use. Important social, occupational, or recreational activities are reduced or stopped because of use. Use continues despite adverse consequences.

and denial are part of the disease of addiction. Naturally, the intensity of withdrawal depends on whether a tolerant and dependent person is given an antagonist (e.g., naloxone, naltrexone) to provoke withdrawal or whether opiates are slowly discontinued. Abrupt withdrawal from opiates often results in nausea, vomiting, diarrhea, goose flesh, dilated pupils, perspiration, increased vital signs (pulse rate, respiratory rate, blood pressure), bone and muscle aches, and a delusional fear that death will occur without opiates. These symptoms are associated with a very strong drive for the drug. Track marks and other physical evidence of parenteral use may be found during examination of a chemically dependent anesthesiologist. Most anesthesiologists, however, are quite adept at using needles and finding discreet intravenous injection sites. Patients, physician colleagues, and loved ones often recognize the drug seeking, acquisition, and consumption after it becomes clear that addiction is the cause of observed problems. Clinicians and experienced addicts recognize that a protracted syndrome, which may last for months and include episodes of sweats, night terrors, dysphoria, drug craving, and malaise, generally follows the acute withdrawal phase with its dramatic symptoms. Laboratory diagnosis is the gold standard. Drug testing is available and reliable when the correct methodology is used and the correct body fluid for the particular opioid being abused is tested. Thin-layer chromatography is the most inexpensive and commonly used comprehensive test. Enzyme-linked immunoassays can detect opiates, methadone, and propoxyphene even in the microgram or picogram per milliliter range. Gas chromatography with mass spectroscopy is a gold standard for testing. Blood testing using this method or radioimmunoassay is necessary for some very potent opioids (e.g., fentanyl).

Recognition

Risk Assessment

Although drug testing is used in emergencies because clinical diagnosis is so unreliable, a medical history and physical examination coupled with confirmatory laboratory testing are useful for diagnosing drug dependence. Direct observation of a health professional using drugs, inappropriately carrying or procuring drugs, or having withdrawal symptoms makes the diagnosis possible. This is so because lying

Opiates have been important analgesics and drugs of abuse for centuries. With the availability of parenterally administered opiates and the invention of the hypodermic syringe, opiate addiction and withdrawal distress are now major, worldwide public health problems. Drug dependence is a disorder characterized by compulsive drug use, tolerance, and withdrawal symptoms with cessation of drug use. 119

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The concept of drug tolerance was originally based on the observation that opioids lose their physiologic effects with repeated use. As tolerance develops, drug-dependent subjects progressively increase the dose of the drug to achieve the originally experienced euphoric effects. In the psychopharmacologic context, tolerance is an organism’s adaptive response to supraphysiologic levels of an exogenous substance. A major drawback of this adaptation is that on cessation of drug use, the physiologic adaptations remain unopposed and induce a physiologic withdrawal syndrome. After chronic opioid use, cessation can induce a severe physical withdrawal syndrome including diarrhea, hypertension, vomiting, and muscle cramps. Depression, dysphoria, or negative affective symptoms (e.g., anhedonia) are associated with the cessation of almost all drugs of abuse. Depression and suicide are common comorbidities with drug abuse and dependence. In contrast to drug use, drug dependence is characterized by loss of control over drug intake and the development of tolerance and withdrawal. Addiction among health professionals is a significant public health problem. Without treatment, impaired professionals harm themselves, their families, and their patients. Although treatment outcomes for physician addicts are remarkably positive, there is a dearth of research on the primary prevention of substance abuse and dependence in this population. Researchers have studied opioid-addicted physicians for decades, reported on the use of clonidine and naltrexone in this population, and followed them for many years after detoxification. Although physicians are overrepresented among prescription drug addicts, their rates of alcohol abuse and dependence are similar to those of appropriately matched controls. All medical schools and hospitals encounter cases of physician opioid abuse, dependence, and overdose. However, they attribute these events to poor self-regulation or ease of drug access. Substance abuse appears to be an occupational hazard among physicians, but why is this so? To become a physician, one must be a high achiever throughout high school and college to obtain the required grades and test scores for medical school admission. Additionally, potential physicians must continue to excel throughout medical school to gain internships and residencies. Physicians seem unlikely candidates for opioid injection and self-administration. However, they are 30 to 100 times more likely to become addicted to narcotics than the general population. One study estimated that 12.5% of male physicians are drug dependent, compared with 0.1% of men in the general population. Although alcohol-related disorders and cigarette smoking rates were comparable between physicians and other Harvard University graduates, physicians had higher rates of drug use and prescription drug abuse, depression, depression with substance abuse, and suicide than other age- and sex-matched professionals. At least 15% of all physicians will become markedly impaired during their careers. Stress and access have dominated the theories for physician use and dependence, but basic scientists who conduct research with cocaine or narcotics do not usually use these drugs themselves. Further, not all medical subspecialties are equally represented among physicians with substance use disorders (Fig. 31-1). Perhaps anesthesiologists suffer a high rate of drug abuse because they administer

Anesthesiologists

Psychiatrists

25% 20% 15% 10% 5% 0%

Florida MDs

Florida MDs with SUDs

Figure 31–1 ■ Substance use disorders (SUDs) among anesthesiologists and psychiatrists in Florida.

highly potent anesthetics or other drugs to patients; they also work in a confined space around the patient’s head and are exposed in the workplace to discarded drugs (e.g., narcotics, benzodiazepines) that can affect the brain, emotions, and behavior. This intriguing hypothesis merits further consideration in future investigations. Fentanyl and its analogues deserve special mention as a risk to anesthesiologists. Fentanyl abuse, overdose deaths, and dependence have been limited to health care professionals for many years. Fentanyl is a narcotic analgesic developed in the early 1960s by Janssen Pharmaceutica in Belgium. Like morphine, fentanyl is an opioid receptor agonist that preferentially binds μ-opioid receptors. Fentanyl’s chemical structure, however, is distinct from that of morphine analogues. Also, new and more potent fentanyl analogues have been developed. The most potent is 3-methylfentanyl, which is about 6000 times as potent as morphine and 600 times as potent as heroin. Unfortunately, these potent analgesics also have an extremely high abuse potential and have been associated with a large number of drug overdose deaths. Between 1979 and 1988, 108 drug overdose deaths were related to fentanyl analogues in California alone. The respiratory depressant effects of fentanyl, combined with its extreme potency, may account for the high number of overdose deaths. It has been reported that fentanyl concentrations vary between 1 and 10 ng/mL in the body fluids of those dying of fentanyl overdose, which is very low compared with the concentrations of other abused opioids. For example, free morphine concentrations in heroin overdose deaths vary between 462 and 1350 ng/mL. In 2004, prescription methadone, OxyContin-like analgesics, and fentanyl were more likely to cause an overdose death in Florida than was heroin.

Implications At the onset of therapy, a full medical and psychiatric evaluation helps predict the outcome of therapy. Intravenous drug abuse is associated with a number of medical conditions, including bacterial or viral endocarditis, hepatitis, acquired immunodeficiency syndrome, tuberculosis, cellulitis, cerebritis, wound abscess, sepsis, arterial thrombosis, renal infarction, and thrombophlebitis. The most common severe complications from intravenous drug use, however, are accidents, head injuries, memory failure, sexually transmitted diseases, seizures, depression, suicidal thinking, and suicide attempts. Opioid dependence is associated with a

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MANAGEMENT Detoxification and abstinence are the treatment of choice for physician addicts; replacement or maintenance treatments (e.g., methadone) are not used for this class of addicts. In the detoxification phase, clonidine not only provides an effective nonopiate treatment for opiate withdrawal but also allows a rapid progression from opiate dependence to maintenance, especially when coupled with naltrexone. Together, clonidine and naltrexone reduce the detoxification process from 14 days to 8 to 24 hours. This combination has rapidly become a new standard of treatment, along with opiate maintenance, detoxification and abstinence, 12-step fellowships, and therapeutic communities. Clonidine and naltrexone, however, also reveal the limitations of pharmacologic advances in the prevention and treatment of opiate addiction, for none of these treatments has greatly impacted the long-term natural history of the disease. Nevertheless, the treatment of physicians in specialized physician programs has been remarkably efficacious. Whereas most treatment programs for addicts have been shortened, physician and health care provider treatment programs have been extended to include inpatient, residential, and rehabilitation phases. Using these techniques, long-term treatment outcomes for physicians are far better than those reported for similarly diagnosed addicts in the general population. In the most recent study of randomly selected Physician Recovery Network physician addicts at 5 years, 91.4% had returned to work. This rate is comparable to the results of other studies of physician addicts. In summary, good management options exist to care for physicians addicted to narcotics and allow them to obtain meaningful recovery and return to their professional duties.

PREVENTION Our research confirms other studies’ findings that anesthesiologists have an increased rate of opiate abuse and dependence. Left untreated, addiction has numerous adverse health consequences for anesthesiologists, as well as their patients and families. Early detection is critical and makes outpatient treatment more successful. For prevention and early detection,

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consideration should be given to random testing until the cause is identified and remedied.

Further Reading Aach RD, Girard DE, Humphrey H, et al: Alcohol and other substance abuse and impairment among physicians in residency training. Ann Intern Med 116:245-254, 1992. American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. Washington, DC, American Psychiatric Press, 1994. Bohigian GM, Croughan JL, Sanders K: Substance abuse and dependence in physicians: An overview of the effects of alcohol and drug abuse. Mo Med 91:233-238, 1994. Gold MS: Opiate addiction and the locus coeruleus. Psychiatr Clin North Am 16:61-73, 1993. Gold MS, Frost-Pineda K, Pomm R: Is addiction an occupational hazard for anesthesiologists? College on Problems of Drug Dependence, 2004. Available online at http://biopsych.com:81/CPDD04_Web/ MeetProgAbSearch_04.html Gold MS, Miller NS: Intoxication and withdrawal from opiates and inhalants. In Miller NS, Gold MS, Smith DE (eds): Manual of Therapeutics for Addictions. New York, Wiley-Liss, 1992, pp 72-86. Gold MS, Redmond DE Jr, Kleber HD: Clonidine may relieve opiate withdrawal symptoms. JAMA 240:25-27, 1978. Goldberger BA, Merves ML, Frost-Pineda K, et al: Use, misuse and diversion of methadone and hydrocodone: The deaths continue to increase J Clin Pharmacol 43:83, 2003. Henderson GL: Blood concentrations of fentanyl and its analogs in overdose victims. Proc West Pharmacol Soc 26:287-290, 1983. Henderson GL: Designer drugs: Past history and future prospects. J Forensic Sci 33:569-575, 1988. Herridge P, Gold MS: Pharmacological adjuncts in the treatment of opioid and cocaine addicts. J Psychoactive Drugs 20:233-242, 1988. Jacobs WS, Hall JD, Pomm R: Prognostic factors for physician addiction outcomes at five years. J Addict Dis 22:140, 2003. Janssen PAJ: 1-Aralkyl-4-(n-aryl-carbonyl-amino)-piperidines and related compounds. US Patent Office No. 3,164,600, 1965. Koob GF: Neuroadaptive mechanisms of addiction: Studies on the extended amygdala. Eur Neuropsychopharmacol 13:442-452, 2003. Maguire P, Tsai N, Kamal J, et al: Pharmacological profiles of fentanyl analogs at mu, delta and kappa opiate receptors. Eur J Pharmacol 213:219-225, 1992. Miller NS, Mahler JC, Gold MS: Suicide risk associated with drug and alcohol dependence. J Addict Dis 10:49-61, 1991. Moriya F, Hashimoto Y: Distribution of free and conjugated morphine in body fluids and tissues in a fatal heroin overdose: Is conjugated morphine stable in postmortem specimens? J Forensic Sci 42:736-740, 1997. Repetto M, Frost-Pineda K, Gold MS: Pharmacological therapeutics for alcohol, cocaine and opioid intoxication and detoxification. In Miller NS, Wadland WC (eds): Addictions in Medicine: Principles and Practice. Hoboken, NJ, John Wiley & Sons, 2004. Shook JE, Watkins WD, Camporesi EM: Differential roles of opioid receptors in respiration, respiratory disease, and opiate-induced respiratory depression. Am Rev Respir Dis 142:895-909, 1990. Talbott GD, Richardson AC Jr, Mashburn JS, et al: The Medical Association of Georgia’s Disabled Doctors Program—a 5-year review. J Med Assoc Ga 70:545-549, 1981. Vaillant GE, Brighton JR, McArthur C: Physicians’ use of mood-altering drugs: A 20-year follow-up report. N Engl J Med 282:365-370, 1970. Van Bever WF, Niemegeers CJ, Janssen PA: Synthetic analgesics: Synthesis and pharmacology of the diastereoisomers of N-(3-methyl-1-(2phenylethyl)-4-piperidyl)-N-phenylpropanamide and N-(3-methyl1-(1-methyl-2-phenylethyl)-4-piperidyl)-N-phenylpropanamide. J Med Chem 17:1047-1051, 1974.

PHARMACOLOGY

very high death rate, with an annual incidence of about 10 per 1000 persons among those who are untreated. Death is most often due to overdose, accidents, injuries, or general medical complications. In some places, violence accounts for more opioid-related deaths than does overdose or human immunodeficiency virus infection. Beyond these medical issues, physician addicts are exposed to significant professional risk in medical credentialing and licensure, as well as marital and other personal problems.

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Chemical Dependency: Nonopioids Mark S. Gold, Kimberly Frost-Pineda, and William Jacobs Case Synopses Alcohol Dr. P is a 60-year-old white male anesthesiologist with a 40-year history of alcohol abuse. Five years ago, he was questioned about alcohol on his breath before starting an 8:00 AM case. He immediately took a blood alcohol concentration (BAC) test, which was below detectable limits, and proceeded with the case. Two years later, the operating room staff thought they detected the smell of alcohol on his breath; that time, his BAC was 0.12. Dr. P denied having had anything to drink since midnight but admitted to drinking vodka tonics the night before. He was referred to the state physician’s health program (PHP), where he was evaluated by an addictionologist certified by the American Society for Addictive Medicine. Dr. P successfully completed an intensive outpatient program and then entered into a monitoring agreement with the PHP. He actively participated in the facilitated group meetings and attended 12-step meetings but did not get a sponsor or work the steps. Random urine testing was negative until 1 month ago. Dr. P had had three drinks after his wife retired for the night and was selected for a random urine drug screen the following morning. He notified the PHP facilitator of his relapse before the positive result was reported. Tobacco Dr. K is a 62-year-old white male anesthesiologist with a 100 pack-year history of cigarette smoking. He has smoked two packs a day since age 12 and has suffered from chronic bronchitis and chronic obstructive pulmonary disease for at least the past 12 years. He has made numerous attempts to stop smoking—including cold turkey, hypnosis, and nicotine patch—without success. He now believes that he is “too old” to quit. He slipped on a wet floor in the operating room last week and fell against the anesthesia machine. Since then, he has had left-sided chest pain at the site of the impact and had a lateral chest film taken today. He reads the film himself and sees a cavitating lesion in the right upper lobe. Cannabis Dr. B is a 28-year-old black male anesthesiologist who joined a prestigious private practice after finishing his chief residency at a major university anesthesiology program. He immediately became a favorite of many surgeons and operating room staff. He was seen smoking cigars on his way home on a number of occasions. After 6 months in private practice, he purchased a new car that was valued at over $100,000. The following Friday, after finishing his cases and leaving the hospital, he was arrested for misdemeanor possession of marijuana and drug paraphernalia after a police officer saw his car pulled to the side of the road. Dr. B was caught with six rolled “joints.” The incident was discovered by his partners within 24 hours, and he was given no option but to self-report to the state PHP. He was evaluated and found to have a long history of polysubstance dependence that had evolved into cannabis dependence and alcohol abuse. He was treated in a long-term residential treatment program and entered into a 5-year monitoring agreement with the PHP. His license was placed on probation for 2 years after treatment and then restored to unencumbered active status. He returned to private practice after completing residential treatment. Cocaine Dr. W is a 44-year-old white male anesthetist who was reported to his state PHP after being seen snorting a white powder, presumed to be cocaine, in the men’s room during the hospital Christmas party. He was contacted 2 days after the party and denied any drug abuse. A urine drug screen was requested immediately, and Dr. W reluctantly complied. It was positive for benzyleconine, a cocaine metabolite. Dr. W was not allowed to continue working and, after an evaluation by an addiction psychiatrist, was admitted to a residential substance abuse treatment program. 122

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Definition Nonopiate abuse and dependence are common among health care professionals. Alcohol and tobacco are the most commonly abused chemical substances, but marijuana is the most commonly abused illicit chemical substance in the general population. It is widely believed that tobacco, alcohol, and marijuana are the most commonly abused substances among physicians. Alcohol dependence appears to be as common among physicians as among their age-, sex-, socioeconomicmatched controls. Cannabis abuse is quite common among medical students and younger physicians, and alcohol dependency is more common among older physicians. Although the abuse of other illicit or licit substances, such as cocaine, is not as prevalent, it may cause significant impairment and have detrimental effects on the lives of health care providers, their patients, and their families. Although the diversion and abuse of prescription drugs by physicians and other health care personnel are also a concern, this problem is not discussed here. Definitions for impairment and chemical (substance) dependence are found in Chapter 31. Substance dependence can have a number of negative impacts, including severe medical and legal implications. Chemical dependence can impair function in relation to acute intoxication, drug-seeking behavior, chronic dependence, and substance withdrawal. In this chapter, we focus on the recognition of nonopiate dependence—specifically, alcohol, tobacco, marijuana, and cocaine. Also, we consider behaviors associated with such substance use, the diagnosis of dependence, its implications, and the management and prevention of substance dependency.

Recognition and Risk Assessment DIAGNOSIS Several screening tests are available for the diagnosis of substance abuse, such as the CAGE and AUDIT programs for alcohol; these have now been modified for marijuana abuse. Clinical diagnosis of substance abuse is often difficult, because denial and lying are part of the disease of addiction. Denial is the hallmark of many initial clinical interviews. Physicians may admit to use, but only on occasion. They may quote the New York Times or High Times to defend their use, as opposed to a respected medical, addiction, or psychiatric text or journal. They may actually say that marijuana smoke is not dangerous to one’s health and deny any similarities to tobacco smoking or secondhand smoke. Among health care professionals, direct observation of drug use, possession, inappropriate procurement of drugs, or signs and symptoms of intoxication or withdrawal can help make the diagnosis. The diagnosis of abuse or dependence is based on Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria (see Chapter 31). The medical history and physical examination, along with confirmatory laboratory testing, are useful for diagnosis. Although there could be other reasons for changes in personality, family problems, infertility (males), withdrawal from social activities, and impaired ability to perform professional duties, a positive

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drug test moves a substance use disorder to the top of the differential diagnosis. Physicians rarely refer themselves to addiction specialists for drug abuse or dependence problems. Laboratory testing is the gold standard for confirming substance use and is also helpful during treatment. Drug testing cannot detect all marijuana, cocaine, or other illicit drug users, however. Random testing does not detect all substances of abuse and may not detect infrequent use. For example, even daily users have only a 50-50 probability of testing positive in any given month when urine testing is done eight times per year. Urine testing is standard for the evaluation and treatment of substance abuse; detection times for some common drugs of abuse are given in Table 32-1. There have also been advances in the testing of other biologic substrates, including hair, sweat, and oral fluid. Thin-layer chromatography and enzyme-linked antibody testing are the most comprehensive, inexpensive, and widely used drug screening tests, but combined gas chromatography with mass spectroscopy is the gold standard for drug testing. Marijuana impairment must be diagnosed with blood tetrahydrocannabinol (THC) concentrations. Random drug testing should be a mandatory part of all health care provider health programs. Laboratory tests may also help in the diagnosis of a chronic substance abuse problem, but they are usually performed late in the course of the disease. Heavy consumption of alcohol (e.g., one bottle of wine a day) for a few months almost always results in macrocytosis (mean corpuscular volume between 100 and 110 fL), even before anemia occurs. Alcohol-related liver disease may be reflected in abnormal serum γ-glutamyltransferase, aspartate transaminase, and alanine transaminase levels. In fact, unlike in other liver diseases, aspartate transaminase may be more than two times greater than alanine transaminase when alcoholic hepatitis is present. The Food and Drug Administration has also approved a new test that measures serum carbohydrate-deficient transferrin to identify long-term excessive alcohol use. ALCOHOL

AND

TOBACCO

Symptoms of alcohol or tobacco dependence include the following: ● ● ● ●

● ●

Impaired control over use Preoccupation with obtaining the substance Continued use, despite adverse consequences Distorted thinking, especially denial of substance dependency Development of tolerance to the effects Withdrawal symptoms when use is discontinued

Table 32–1

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Substance Detection Time in Urine

Substance

Detection Times

Amphetamines Barbiturates Benzodiazepines Cannabinoids Cocaine Opiates Phencyclidine

Up to 24 hr 5-10 days 5-7 days 1-3 days; greater with chronic use 1-3 days 1-3 days Up to 3 days

PHARMACOLOGY

PROBLEM ANALYSIS

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Although no specific constellation of symptoms is specific for the diagnosis of alcohol abuse or dependence, physical examination findings consistent with alcohol abuse are elevated blood pressure, evidence of physical harm, tremors, obstructive lung disease (due to concurrent tobacco use), and unexplained tachycardia, hepatosplenomegaly, or peripheral neuropathy. In contrast to alcohol, the health consequences of tobacco dependence generally take years to develop and are related primarily to lung cancer or chronic pulmonary disease. Just quitting smoking has immediate positive health effects, reduces the risk for adverse consequences over time, and increases the smoker’s life expectancy. (see www.cancer.org for more details). COCAINE A number of clinical and behavioral signs and symptoms of cocaine use are usually evident. Some are related to acute intoxication, and others appear after chronic use or during withdrawal (Table 32-2). Although cocaine is more commonly abused as a “street drug” (snorted as powder or smoked as crack), it is also used medicinally as a topical anesthetic and vasoconstrictor (e.g., in awake oral or nasal intubation). If so, health care professionals may have access to unadulterated cocaine, similar to fentanyl and other highly potent narcotics (see Chapter 31). Street cocaine is often adulterated or “cut” with other substances that have the potential to cause additional harm. MARIJUANA In the 1960s and 1970s, marijuana was perceived as a safe and natural drug that produced a “high” (euphoria) without the risk of negative side effects or addiction. Some young physicians still do not believe that marijuana dependence is possible and may smoke marijuana more frequently

Table 32–2

■

than cigarettes. Dependence on marijuana is related to the THC concentration in its smoke and the duration of use; signs of marijuana withdrawal can be provoked by the administration of a THC antagonist. Today, the THC concentration in “street” marijuana has been increased to encourage repeat use. Researchers at Harvard and Columbia have shown that with this increased potency, chronic marijuana use can lead to tolerance, dependence (even subhuman animal species will self-administer THC), and a distinct withdrawal syndrome. Marijuana is now one of the leading substances of abuse in persons institutionalized for the treatment of substance abuse. As defined in DSM-IV, marijuana intoxication begins with a feeling of being “high.” Symptoms vary but generally include grandiosity, euphoria, and inappropriate laughter. Acute use also causes difficulty with concentration and complex thought processes; distorted sensory and time perception; lethargy and sedation; and impaired judgment, memory (especially short-term memory), and motor performance. Marijuana use sometimes provokes anxiety and panic, which may require treatment. During and after intoxication, there is generally increased appetite, red eyes, dry mouth, and increased heart rate. As these effects subside, there is often depressed mood, anger, irritability, or social withdrawal. Experimental cannabinoid antagonists, which are now in clinical trials, appear to be the most effective treatment for the overeating and memory problems related to chronic marijuana dependence. The long-term health effects of marijuana smoke are difficult to determine because persons who use marijuana often use tobacco products as well. Recent studies have shown, however, that there are many carcinogens in marijuana smoke, which actually has 50% higher levels of tar and carcinogens than tobacco smoke does. Also, case-control studies have linked marijuana smoke to head and neck cancers.

Signs and Symptoms of Acute Cocaine Intoxication and Chronic Cocaine Abuse or Dependence Acute Cocaine Intoxication

Chronic Cocaine Abuse or Dependence

Signs

Clinical Symptoms

Physical and Mental Symptoms

Behavioral and Social Signs

Sociability—most users become overly “chatty” at low doses Hypervigilance Impaired judgment Grandiose thinking and plans Increased anxiety and tension Quick mood changes Increased libido

Blood pressure changes Breathing difficulties Dilated pupils Mental confusion Muscle weakness Tachycardia, chest pain Nausea or vomiting Psychomotor agitation or retardation, seizures Sweating or chills

Anxiety, delirium, depression, hallucinations, insomnia, memory loss, confusion, slurred speech, reflex changes, blackouts, acute vision changes, incoordination, dizziness, tremors, impotence Hypertension, irregular heartbeat, bradycardia Bronchitis, lingering colds and flu symptoms, frequent respiratory tract infections Bumps and bruises due to falls Craving for sweets or avoidance, loss of appetite, poor nutrition, liver enlargement Increased or reduced alcohol or drug tolerance Red, puffy face; red, swollen nasal mucosa

Car and boat accidents Problems with family or job (e.g., tardiness, absenteeism) Legal or financial problems Increased reliance on drugs Passive-aggressive behavior, suicidal thoughts or gestures, violent or aggressive behavior, suspiciousness

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Implications Maladaptive behavior problems are usually the first sign of chemical dependency. However, these often are not attributed to drug abuse until after an addiction is recognized. Health care professionals are generally better equipped than others to hide and deny substance abuse. Most often, family and social problems related to use occur far in advance of problems on the job. Health care professionals who are using drugs may experience changes in mood, energy level, and the ability to concentrate. They also miss work or arrive late. They may use the drug more often and at inappropriate times, taking more frequent breaks than their colleagues. In addition, they may have alcohol on their breath or smell of tobacco or marijuana smoke. Often family and friends become aware of the drug-seeking, -acquiring, and -consuming behaviors before patients and other physicians recognize the problems. Chemical-dependent health care professionals often have problems in their interpersonal relationships, and they are exposed to significant professional risk in terms of medical credentialing and licensure, as well as criminal investigations. A physician might come to attention by propositioning a prostitute or experiencing money problems related to gambling or purchasing drugs. However, these are late-stage behaviors. Early detection requires a high degree of suspicion both at the workplace and at home. Common severe complications from drug abuse include accidents, head injuries, memory failure, financial collapse, sexually transmitted diseases, seizures, depression, impulsivity, suicidal thinking, and suicide attempts. Negative affective symptoms (e.g., anhedonia), depression, and dysphoria are symptoms associated with the cessation of almost all drugs of abuse (see also Chapter 31). The chemical withdrawal syndrome specific to the drug of choice may be another sign of chronic use and dependence. The desire for the drug is probably greatest during withdrawal, because the addicted person wishes to alleviate unpleasant withdrawal symptoms. Health care professionals who abuse or become dependent on drugs have higher rates of depression, which may lead to suicide without intervention and treatment.

ALCOHOL

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TOBACCO

Alcohol and tobacco are the most widely used drugs. Alcohol is generally considered safe and may even have a beneficial effect when used in moderation. However, there are no established moderate or safe levels of tobacco use. People who smoke often drink, and those who abuse alcohol usually use tobacco; thus, dependence on both alcohol and tobacco is common. Tobacco smoking is the leading cause of death among alcoholics. Alcohol can also be potent and dangerous, causing more death and personal destruction than any other drug except for tobacco. Each year, alcohol misuse causes more than 100,000 deaths and injury to more than 2 million people; tobacco is reportedly responsible for more than 400,000 deaths annually. COCAINE The pathologic attraction to cocaine can be intense, with many experts agreeing that it is the most intense among the substances of abuse. Although detoxification is usually unnecessary, discontinuation is clinically significant and difficult to manage outside of a hospital or highly controlled environment. Craving for cocaine, anhedonia, feelings of helplessness, and drive for the drug make relapse likely. Animal self-administration models suggest that the amount of work or punishment an animal will expend or endure for a dose of cocaine is greater than for most other drugs. Once the physician addict discontinues the drug, treatment begins. We have reported on cocaine sniffing, cocaine injecting, and even crack addiction among physicians. Cocaine addiction is so profound and relapse so common that the DSM had to change the diagnostic criteria to allow addiction to be diagnosed in the absence of significant signs and symptoms of withdrawal. Addicted physicians often sign contingency contracts, agree to random and at least biweekly urine testing, and are sent to inpatient and residential treatment facilities. MARIJUANA Possessing, smoking, growing, and purchasing marijuana are all illegal. Physicians who do so are a phone call or two away from losing their licenses. This usually does not occur, however. Their spouses, children, or angry patients may call an anonymous tip line to report their behavior. Marijuana use may bring doctors into contact with other illicit drugs, leading to further experimentation. Sometimes, marijuana smoking or the use of other illicit substances brings physicians into contact with drug dealers and other criminals. Physicians are usually undertrained for this social network and may be easily blackmailed or robbed by their dealers or new “friends.”

MANAGEMENT Changes in thinking and behavior, along with a positive drug test, are usually taken as definitive evidence of substance abuse by hospital staffs, physician employment groups, and state physician health monitoring programs. Detoxification and abstinence, followed by involvement in 12-step fellowships and therapeutic communities, remain the treatment of choice for professional health care addicts. It is important

PHARMACOLOGY

People who become dependent on marijuana usually use it daily, often for months or years. When they try to stop using it, they often cannot do so for longer than 30 days. They are also easily angered by questions about their marijuana use, because they are psychopathologically attached to the substance. Often, this has a negative impact on their health, families, and careers. Moreover, they may choose parties, social contacts, or friends on the basis of whether marijuana is going to be available, and they may spend many hours each day thinking about using marijuana and later recovering from the effects. Further, they may smoke cigarettes or take psychostimulants in an attempt to reverse the effects of marijuana on their memory or performance. Dependence interferes with family life and work, but use continues despite the development of chronic problems, such as a smoker’s cough or psychological problems (e.g., excessive sedation resulting from repeated use of high doses), or social consequences.

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to note that detoxification is not sufficient treatment. Numerous treatment programs are designed to meet the special needs of addicted health care professionals. There are also a number of pharmacologic therapies that may be useful in the treatment of alcohol, tobacco, marijuana, and cocaine dependence (Table 32-3). Physicians have the best outcomes when there is long-term follow-up, random routine drug testing, 12-step group attendance, and individual follow-up with a psychiatrist and treatment facilitator.

Alcohol and Tobacco Both psychosocial and pharmacologic therapies can help in overcoming alcohol and tobacco addiction. Some of these can be purchased over the counter (e.g., nicotine replacements), but others require a prescription. For alcohol, a number of pharmacologic therapies have been approved for use in the United States, including disulfiram (Antabuse), naltrexone, and acamprosate.

Cocaine Treatment for cocaine dependence includes both residential and outpatient approaches. One primary approach is behavioral intervention. After stabilization, recovery begins with a learning process of breaking old habits, breaking ties with cocaine-using friends, and identifying “triggers” that increase the desire to use cocaine; once these triggers are identified, patients are encouraged to restructure their lifestyles to avoid them. Cognitive-behavioral coping skills provide another alternative that, in the short term, focuses on helping cocaineaddicted individuals become abstinent through a learning process. This therapy is compatible with a range of other treatments, such as pharmacotherapy. Active membership in 12-step programs, such as Narcotics Anonymous and Cocaine Anonymous, is one of the most beneficial tools for continued abstinence from cocaine and other drugs of abuse. For addicted health care professionals, regular random drug testing, a contract, and chronic follow-up care improve the long-term success of treatment. It is imperative that any positive drug tests be promptly identified and that any necessary changes in treatment plans be made quickly. Waiting can be associated with a rapid and complete relapse. Finally, cocaine abstinence and long-term use are associated with depression,

Table 32–3

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suicidal ideation, and suicide attempts; thus, cocainedependent physicians must be closely monitored.

Marijuana Treatments under study include use of the synthetic marijuana dronabinol (Marinol). This is similar to the use of methadone for heroin addicts. Relapse prevention is an important factor in the successful treatment of marijuana dependence. Recovering addicts must change their behaviors and be able to resist social and environmental cues for continued drug use. Psychosocial treatments, such as cognitive-behavioral therapy, can be successful. Pharmacologic therapies under study may be useful as maintenance therapy.

PREVENTION Prevention of substance abuse and dependence starts with abstinence—that is, no experimentation. Physicians are well educated and are therefore used as examples of the limitations of knowledge as a protective factor against addiction. Drug use, abuse, and dependence are now observed in medical students and house staff, not just in older practicing physicians. Physicians who have learned to balance their lives and manage their stress, anxiety, and workplace problems without drugs should mentor medical students to help them learn to do the same. Addiction among health care professionals is a significant public health problem that requires intervention. Without treatment, addiction leads to harm to self, family, and patients. At least 15% of all physicians will become markedly impaired sometime during their careers; however, there continues to be a dearth of research on the primary prevention of substance abuse and dependence among health care providers. Generally, the best way to prevent drug dependence is to prevent drug use in the first place. For example, there is a strong genetic risk for alcohol dependence among those who have a positive family history, especially among first-degree relatives. Such persons should refrain from using alcohol. Prevention of exposure to drugs and drug use during early childhood and adolescence is key to reducing later dependence. Prevention efforts and appropriate training should also be a focus in medical schools and other

Pharmacologic Treatment for Nonopioid Dependency

Substance

Pharmacologic Treatment

Alcohol

Antabuse—deters drinking by causing painful symptoms when alcohol is used Naltrexone—likely reduces craving and may reduce pleasurable effects of alcohol Acamprosate—reduces craving for alcohol and prevents relapse Nicotine replacement: gum, patch, inhaler, spray Detoxification: bupropion (Zyban, Wellbutrin)—originally prescribed as an antidepressant but now used primarily for smoking cessation Maintenance: Marinol—in clinical trials Antagonist: Rimonblat—in clinical trials Definitive: none at present Supportive: antidepressants, mood stabilizers (e.g., lithium)

Tobacco

Marijuana Cocaine

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Further Reading Aach RD, Girard DE, Humphrey H, et al: Alcohol and other substance abuse and impairment among physicians in residency training. Ann Intern Med 116:245-254, 1992. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed [DSM-IV]. Washington, DC, American Psychiatric Press, 1994. Bohigian GM, Croughan JL, Sanders K: Substance abuse and dependence in physicians: An overview of the effects of alcohol and drug abuse. Mo Med 91:233-238, 1994. Gold MS, Aronson MD: Screening and diagnosis of patients with alcohol problems, and treatment of alcohol abuse and dependence. Harvard University’s UpToDate Web site and CD-ROM Educational Program, 2005.

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Gold MS, Frost-Pineda K: Substance abuse and psychiatric dual disorders: Focus on tobacco. J Dual Diagnosis 1:15-36, 2005. Gold MS, Frost-Pineda K, Jacobs WS: In Galanter M, Klever HD (eds): Textbook of Substance Abuse Treatment, 3rd ed. New York, American Psychiatric Press, 2004, pp 167-188. Gold MS, Jacobs W: Cocaine (and crack): Clinical aspects. In Lowinson JH, Ruiz P, Millman RB (eds): Substance Abuse: A Clinical Textbook, 2nd ed. Baltimore, Williams & Wilkins, 2004, pp 218-251. Herridge P, Gold MS: Pharmacological adjuncts in the treatment of opioid and cocaine addicts. J Psychoactive Drugs 20:233-242, 1988. Jacobs WS, Hall JD, Pomm R, et al: Prognostic factors for physician addiction: Outcomes at five years. J Addict Dis 22:140, 2003. Jacobs WS, Repetto M, Vinson S: Random urine testing as an intervention for drug addiction. Psych Ann 34:781-785, 2004. Koob GF: Neuroadaptive mechanisms of addiction: Studies on the extended amygdala. Eur Neuropsychopharmacol 13:442-452, 2003. Miller NS, Mahler JC, Gold MS: Suicide risk associated with drug and alcohol dependence. J Addict Dis 10:49-61, 1991. Repetto M, Frost-Pineda K, Gold MS: Pharmacological therapeutics for alcohol, cocaine and opioid intoxication and detoxification. In Miller NS, Wadland WC (eds): Addictions in Medicine: Principles and Practice. Hoboken, NJ, John Wiley & Sons, 2004. Repetto M, Gold MS: Cocaine (and crack): Neurobiology In Lowinson JH, Ruiz P, Millman RB (eds): Substance Abuse: A Clinical Textbook, 2nd ed. Baltimore, Williams & Wilkins, 2004, pp 195-218. Robinson TE: Addicted rats. Science 305:951-953, 2004. Talbott GD, Richardson AC Jr, Mashburn JS, et al: The Medical Association of Georgia’s Disabled Doctors Program—a 5-year review. J Med Assoc Ga 70:545-549, 1981. Vaillant GE, Brighton JR, McArthur C: Physicians’ use of mood-altering drugs: A 20-year follow-up report. N Engl J Med 282:365-370, 1970.

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health care professional educational programs to minimize the risk of future chemical dependency problems. If primary prevention has failed, there is still the opportunity for early intervention. Even if dependence has developed, we know that treatment works, especially for physician addicts, who have remarkably positive 5-year outcomes. Treatment can prevent or reduce the incidence of a number of adverse health outcomes. Another method to detect and prevent drug use that is increasingly being used in training, workplace, and treatment settings is random drug testing. Some leading institutions, such as Massachusetts General Hospital, have incorporated random testing into their substance abuse policy and now routinely test residents and house staff.

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Juliana Barr Case Synopsis An otherwise healthy 65-year-old, 80-kg man with coronary artery disease is given fentanyl (2 mg), midazolam (20 mg), and vecuronium (15 mg) intravenously during a 3-hour coronary artery bypass grafting procedure. He remains intubated and mechanically ventilated after surgery and is transferred to the intensive care unit (ICU) in stable condition. The surgeons elect for early extubation, but the patient remains deeply sedated, does not respond to painful stimuli, and is not “fighting” the ventilator. He is given intravenous (IV) naloxone (2 mg) and flumazenil (1 mg) over 5 minutes. He becomes acutely hypoxemic, with increasing rales and frothy pulmonary secretions. A chest radiograph reveals acute pulmonary edema, and the electrocardiogram shows ventricular ectopy.

PROBLEM ANALYSIS Definition Naloxone. Naloxone (Narcan) is an opioid antagonist that competitively inhibits the sedative, analgesic, and cardiopulmonary depressant effects of opioids at various opioid receptors. Typically, it is used to reverse the sedative and respiratory depressant effects of opioids. Following a single IV bolus injection, the onset of naloxone is rapid, with a short duration of effect (Table 33-1). It is metabolized hepatically, with renal excretion of its inactive metabolites. Small IV doses of naloxone (e.g., 20 to 40 μg) may reverse the respiratory depressant and sedative effects of opioids, but with incomplete reversal of the analgesic effects (Table 33-2). Larger doses may cause acute cardiopulmonary instability, especially in critically ill patients. Hypertension, tachycardia, arrhythmias, or acute fulminant pulmonary edema may occur following the administration of naloxone, even with incomplete reversal of the opioid’s analgesic and sedative effects. Flumazenil. Flumazenil (Romazicon) is a benzodiazepine antagonist with weak agonist activity at the γ-aminobutyric

Table 33–1

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Clinical Parameters of Intravenous Reversal Agents

Drug

Onset (min)

Peak Effect (min)

Duration of Effect (min)

Elimination Half-life (min)

Naloxone∗ Flumazenil

1-2 1-2

5-15 2-10

60-240 45-90

40-60† 50‡

∗Can also be given intramuscularly, subcutaneously, or endotracheally, although time to onset, peak effect, and duration and magnitude of effect may vary considerably among patients. † Doubled in neonates. ‡ Halved in neonates and prolonged in patients with liver disease.

128

acid (GABA) receptor. It is given intravenously to reverse benzodiazepine-induced sedation, amnesia, disorientation, hypoventilation, or cardiovascular instability. After a single IV bolus dose, flumazenil’s onset of action and peak effect occur within minutes (see Table 33-1). Because of its rapid hepatic clearance, flumazenil is short acting. It has no active or toxic metabolites. Flumazenil’s duration of effect may be prolonged in patients with severe liver disease owing to reduced hepatic clearance. Unlike naloxone, flumazenil does not precipitate the acute onset of cardiopulmonary instability in critically ill patients, although it can cause signs of withdrawal or seizures in some patients.

Recognition Naloxone. The onset of naloxone’s cardiopulmonary side effects is rapid. Acute pulmonary edema results from increased hydrostatic pressure across the pulmonary capillary bed and increased pulmonary capillary permeability. This causes rapid extravasation of protein-rich fluid into the lung parenchyma. Hypertension is due to increased cardiac output, as well as increased systemic and pulmonary vascular resistance. The cardiovascular side effects of naloxone may resolve more quickly than the pulmonary edema and pulmonary hypertension. Flumazenil. Like naloxone, the onset of flumazenil action is rapid. Because of its short duration of action, flumazenil does not precipitate cardiopulmonary instability; however, resedation and respiratory depression may recur after its administration. The total dose of flumazenil needed to achieve a full and sustained reversal of the side effects of benzodiazepines may vary with the potency and residual plasma concentration of the benzodiazepine used. Respiratory depression may not be fully reversed, however, even with maximal doses of flumazenil. In patients with a history of chronic benzodiazepine use, those undergoing benzodiazepine withdrawal, or those with tricyclic antidepressant overdose, flumazenil can cause seizures or other

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Dosing Reversal Agents for Postoperative Sedation and Respiratory Depression

Drug

Intermittent IV Bolus Dosing*

Continuous IV Infusion*

Naloxone Flumazenil

20-40 μg q1-2 min (5-20 μg q1-2 min) 0.2 mg q2-5 min to ≤1 mg; may repeat q20 min; maximum dose 3 mg/hr (4-20 μg/kg)

4-8 μg/kg/hr (4-8 μg/kg/hr) 0.5-1 μg/kg/min to ≤3 mg/hr (0.5-1 μg/kg/min)

∗Pediatric doses are in parentheses.

signs of drug withdrawal. There are no reports of seizures following flumazenil administration to ICU patients who received benzodiazepines for chronic sedation.

Risk Assessment Naloxone. The incidence of cardiopulmonary instability after naloxone administration is not known. Although it appears to occur more commonly in patients with preexisting cardiopulmonary disease, it has also been reported in patients without such disorders. Cardiopulmonary instability is more likely in critically ill patients and after cardiac surgery, because much larger doses of highly potent opioids (e.g., alfentanil, fentanyl, sufentanil) are used in these patients. Patients with a history of opioid use and physical dependency also appear to be at increased risk for cardiopulmonary instability, as well as seizures and other symptoms of opioid withdrawal (e.g., nausea, vomiting, diaphoresis, agitation), after naloxone. The risk for cardiopulmonary instability is increased with rapid administration of high IV doses of naloxone (400 μg).1 Flumazenil. Flumazenil is an effective means of reversing the residual sedative or respiratory depressant effects of benzodiazepines following the small doses typically used for anesthesia or conscious sedation. However, owing to flumazenil’s short duration of action, ICU patients who receive chronic infusions or large doses of benzodiazepines may experience resedation and recurrent respiratory depression once flumazenil’s antagonistic effects wear off. Therefore, flumazenil should not be used to hasten the termination of benzodiazepine sedation in these patients. However, a trial of flumazenil may be diagnostically useful in critically ill patients who fail to awaken within a reasonable time after discontinuing benzodiazepines. If the patient fails to awaken after receiving the maximal dose of IV flumazenil (3 mg over 1 hour), other causes of the persistent sedation or respiratory depression should be considered. Patients who do respond to flumazenil should be carefully monitored for up to 2 hours after the last dose of flumazenil for signs of resedation or recurrent respiratory depression.

1 Over a period of 2 months, shortly after naloxone became available for the reversal of high-dose opioid effects, the editor saw three cases of acute fulminant pulmonary edema that developed within 15 to 20 minutes after IV bolus naloxone (400 μg) was given in the postanesthesia care unit to patients who had had lengthy, major noncardiac surgeries. ICU admissions were not planned.

Implications Acute-onset hypertension, tachycardia, arrhythmias, or pulmonary edema after naloxone, or seizures after flumazenil, may not be well tolerated, especially in critically ill patients with preexisting cardiopulmonary disease. Cardiac surgical patients appear to be at even greater risk for hemodynamic instability after naloxone due to compromised myocardial performance and postoperative arrhythmias. Also, hemodynamic profiles can fluctuate rapidly with rewarming or increased circulating catecholamines. Moreover, the pulmonary capillary bed becomes more permeable owing to systemic inflammatory mediators released during cardiopulmonary bypass. If so, early postoperative naloxone may trigger acute, life-threatening cardiopulmonary changes in cardiac surgical patients. In contrast, flumazenil does not precipitate acute anxiety, hypertension, tachycardia, myocardial ischemia, or ventricular dysfunction in postoperative cardiac surgical patients who do not take benzodiazepines chronically.

MANAGEMENT Avoid IV boluses and continuous naloxone infusions if cardiopulmonary instability occurs. Treat the patient symptomatically, as follows, until naloxone’s effects resolve: ●

● ● ●

●

● ●

Control blood pressure with short-acting IV antihypertensives (see Chapter 77). Treat myocardial ischemia with nitrates (see Chapter 76). Treat tachycardia with β-blockers (see Chapter 11). Treat arrhythmias with pacing, cardioversion, or defibrillation and antiarrhythmic drug therapy (see Chapters 10-13, 79-82, and 229). Minimize intravascular volume to minimize extravasation of fluid into lung tissues (see Chapter 16). Support oxygenation and ventilation. Provide treatment for exacerbating conditions or imbalances (e.g., acidosis, hypercarbia, hypoxia, hypokalemia, hypomagnesemia, agitation, pain).

Flumazenil can precipitate withdrawal symptoms (e.g., seizures, agitation, confusion) in patients with a physical dependence on benzodiazepines and can cause seizures in patients with tricyclic antidepressant overdose. Patients with any of these symptoms after flumazenil should be treated symptomatically, as follows: ●

Seizures: antiepileptics, including benzodiazepines, phenytoin, or barbiturates

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Table 33–2

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Acute agitation and delirium: short-acting anxiolytics, including benzodiazepines Observation: careful monitoring for resedation or recurrent respiratory depression for up to 2 hours after benzodiazepine reversal with flumazenil

PREVENTION Naloxone. Avoid high doses of naloxone, especially in critically ill patients. Small IV bolus doses (20 to 40 μg) or continuous infusions (4 to 8 μg/kg per hour) may reverse opioid-induced respiratory depression and sedation without reversing the analgesic effects of opioids or precipitating cardiopulmonary instability. The duration of naloxone’s effect is brief and variable. Resedation and respiratory depression may occur following a single dose of naloxone. Although naloxone can be given intramuscularly, subcutaneously, or endotracheally, IV dosing is preferred because of the variable uptake with other routes of administration. Further, the dose does not need to be adjusted in patients with hepatic or renal insufficiency, although the elimination half-life and duration of clinical effect may be prolonged in neonates. Naloxone readily crosses the placenta and may precipitate acute withdrawal symptoms or seizures in neonates or their opioid-dependent mothers. Flumazenil. Flumazenil is safe and effective for reversing short-term sedation and respiratory depression with benzodiazepines, but not for chronically dependent patients.

It should be given in small divided doses, and patients must be carefully observed for signs of resedation and respiratory depression for at least 2 hours. Small repeat IV boluses (0.2 mg) or a low-dose continuous IV infusion (0.5 to 1 μg/kg per minute, up to 3 mg/hour) can be titrated to the desired level of sedation and ventilation. This more reliably prevents resedation of postoperative patients and also avoids abrupt or complete reversal of anxiolysis. Finally, avoid flumazenil in patients with chronic dependence on benzodiazepines or suspected tricyclic antidepressant overdose.

Further Reading Bertaccini E, Geller E: Benzodiazepine antagonists and their role in anesthesia and critical care. Anaesth Pharmacol Rev 3:74-81, 1995. Murray MJ, DeRuyter ML, Harrison BA: Opioids and benzodiazepines. In Cheng EY (ed): Sedation of the critically ill patient. Crit Care Clin 11:849-874, 1995. Rudolph U, Crestani F, Möhler H, et al: Sedatives, anxiolytics, and amnestics. In Evers AS, Maze M (eds): Anesthetic Pharmacology: Physiologic Principles and Clinical Practice. Philadelphia, Churchill Livingstone, 2004, p 431. Sasada M, Smith S: Flumazenil. In Drugs in Anaesthesia and Intensive Care, 3rd ed. New York, Oxford University Press, 2003, pp 162-163. Sasada M, Smith S: Naloxone. In Drugs in Anaesthesia and Intensive Care, 3rd ed. New York, Oxford University Press, 2003, pp 266-267. Stoelting RK: Benzodiazepines. In Pharmacology and Physiology in Anesthetic Practice, 3rd ed. Philadelphia, JB Lippincott–Williams & Wilkins, 1999, p 138. Stoelting RK: Opioid agonists and antagonists. In Pharmacology and Physiology in Anesthetic Practice, 3rd ed. Philadelphia, JB Lippincott– Williams & Wilkins, 1999, pp 106-107. White PF, Shafer A, Boyle WA, et al: Benzodiazepine antagonism does not provoke a stress response. Anesthesiology 70:636-639, 1989.

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Bhiken Naik and Lisa Thannikary

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34

Steroids Case Synopsis A 55-year-old man with severe chronic obstructive airway disease and steroid dependence is taken to the operating room emergently for an acute abdomen due to a perforated colonic diverticulum. The patient has been maintained on this dose of steroids for 1 year. Intraoperatively, he demonstrates hemodynamic instability requiring largevolume fluid resuscitation and the use of vasopressors. Postoperatively, he is transferred to the intensive care unit, where he is intubated and ventilated and remains hemodynamically unstable.

PROBLEM ANALYSIS Definition Steroids are the mainstay of therapy for a variety of disorders, including autoimmune diseases, and for immune suppression following solid organ transplantation. With chronic steroid therapy, there is a risk of triggering an addisonian crisis if cortisol levels are insufficient to meet the increased physiologic, perioperative demands. Following surgery, peak plasma cortisol concentrations are achieved after 4 to 5 hours and may remain elevated for 48 to 72 hours, especially following major surgery. Minor surgery induces less than 50 mg of cortisol production during the first 24 hours, but after major surgery, 75 to 100 mg of cortisol is produced in the same period. With maximal stress (e.g., septic shock), the adrenals may produce as much as 300 to 500 mg of cortisol per day. Adrenal insufficiency is classified as primary, secondary, or tertiary, based on the anatomic level of impairment within the hypothalamic-pituitary-adrenal (HPA) axis. With primary adrenal insufficiency, the abnormality is in the adrenal gland. More than 90% of the adrenal gland must be destroyed before symptoms of glucocorticoid and mineralocorticoid deficiency are evident. The most common cause of primary adrenal insufficiency in the United States is autoimmune in nature. In secondary adrenal insufficiency, the abnormality is at the level of the pituitary gland. Such patients show symptoms of glucocorticoid deficiency but usually have intact mineralocorticoid function. Tertiary adrenal insufficiency is the most common type and is caused by suppression of the HPA axis by chronic exogenous steroids. However, there is a lack of prospective, randomized trials investigating perioperative steroid supplementation in patients receiving chronic steroids. Most available data are based on small case series and personal preference.

Recognition The clinical presentation of an addisonian crisis varies from mild, nonspecific constitutional symptoms to the presence of profound shock unresponsive to vasopressor therapy. Clinicians should maintain a high index of suspicion when caring for patients receiving chronic steroids during the perioperative period. Mild symptoms or signs of adrenal

insufficiency include nausea, vomiting, and abdominal pain. With associated hypoglycemia, there may be subtle neurologic symptoms (e.g., restlessness, lethargy). Mineralocorticoid deficiency occasionally accompanies an addisonian crisis and presents as hyponatremia and hyperkalemia with metabolic acidosis. With severe adrenal insufficiency, arterial hypotension with postural accentuation is common. Such hypotension may be refractory to fluid and vasopressor therapy.

Risk Assessment The following are important predictors of risk for the development of adrenal insufficiency during the perioperative period: ● ● ● ●

Total daily dose of steroids Duration of steroid therapy Type of surgery and degree of perioperative stress Response to short (rapid) adrenocorticotropic hormone (ACTH) stimulation test

It has been shown that the total daily dose of steroids determines the responsiveness of the HPA axis to stress. LaRochelle and colleagues demonstrated that when the total daily dose of prednisone was less than 5 mg, there was a normal response to the short ACTH test. With doses greater than 5 mg/day, however, responses to the short ACTH test varied widely. Although these authors reported that the duration of steroid therapy did not affect HPA axis recovery, there is evidence that HPA axis responsiveness may be impaired for up to 9 months after chronic steroid therapy. The nature of the surgery and the degree of perioperative stress are important determinants for steroid replacement therapy. Subjects undergoing major surgery have elevated glucocorticoid concentrations commensurate with the degree of stress and nature of the surgery. Finally, the response to the short ACTH test can help the clinician determine whether the HPA axis has returned to normal. It is sensitive for determining HPA axis impairment in subjects on chronic steroid therapy. Following measurement of baseline plasma cortisol concentrations, 250 μg of cosyntropin is administered intravenously (IV). Blood cortisol concentrations are then determined at 30 and 60 minutes. A normal response is a peak cortisol concentration greater than 18 μg/dL and a minimal increase of 7 μg/dL above baseline. 131

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Table 34–1

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Steroid Supplementation Guidelines

Dose and Duration of Steroid Therapy*

Perioperative Management

<5 mg/day >5 mg/day—minor surgery >5 mg/day—moderate surgery >5 mg/day—major surgery Steroids stopped <6 mo Steroids stopped >6 mo Septic shock with abnormal ACTH test Late fibroproliferative ARDS

Normal HPA axis; no supplemental steroids necessary Hydrocortisone 25 mg at anesthetic induction; resume oral steroids Hydrocortisone 75-100 mg/day; taper over 1-2 days to usual dose Hydrocortisone 100-150 mg/day; taper over 1-2 days to usual dose Assume HPA axis impaired; dose steroids according to type of surgery Assume HPA axis intact; no supplemental steroids necessary Hydrocortisone 100 mg q 8 h for 5-7 days Methylprednisolone 2 mg/kg/day tapered to 0.125 mg/kg/day over 32 days

*Based on dose of cortisol (hydrocortisone). For relative potencies of synthetic corticosteroids, see Table 34-2. ACTH, adrenocorticotropic hormone; ARDS, acute respiratory distress syndrome; HPA, hypothalamic-pituitary-adrenal.

Implications Although addisonian crisis secondary to inadequate steroid supplementation is rare, vigilance by the anesthesiologist for subtle signs of adrenal insufficiency is important. The cumulative daily dose, the duration of chronic steroid therapy, and the nature of surgery are important factors for determining the integrity and responsiveness of the HPA axis. Further, there is increasing evidence of the importance of physiologic replacement doses of steroids in patients with sepsis and septic shock. Although supraphysiologic steroid doses have not been shown to improve outcomes, studies by both Annane and Bollaert and their coworkers have shown the benefits of physiologic replacement doses of steroids in septic shock. There also appears to be a beneficial role for steroid therapy in the late fibroproliferative phase of acute respiratory distress syndrome (ARDS). Although this conclusion is based on a small study by Meduri and associates, a larger multicenter trial is being conducted by the ARDS Network.

MANAGEMENT As discussed earlier, the decision to supplement steroids in the perioperative period is based on the history of steroid intake and the severity of the planned surgery (Tables 34-1 and 34-2). A standard dose for all patients should be avoided. Supplemental doses should be individualized based on total

Table 34–2

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daily dose, duration of therapy, and severity of perioperative stressors. Although the short ACTH test is useful for determining the integrity of the HPA axis, it may be impractical to perform the test in all patients. When steroids have been stopped for at least 6 months, it can be assumed that the HPA axis has returned to normal. Although some data suggest that a minimum of 2 months is sufficient time for the resumption of normal cortisol production, it is prudent to assume that HPA axis function will be impaired for up to 6 months. Patients taking less than 5 mg/day of prednisone or its equivalent can be assumed to have an intact HPA axis and do not require supplemental doses of steroids; however, it is important to continue the daily dose of the steroid. With minor surgery, a supplemental dose of 25 mg of hydrocortisone should be given IV at induction of anesthesia; normal oral replacement therapy should be resumed postoperatively. With moderate surgical stress, the chronic daily steroid dose should be given IV preoperatively. Additional doses of hydrocortisone between 75 and 100 mg/day should be given IV. If there are no postoperative complications, the supplemental steroid should be weaned rapidly over 1 to 2 days, and the normal oral steroid dose should be restarted. With major surgery, the preoperative oral steroid dose should be followed by an additional 100 to 150 mg of intravenous hydrocortisone administered over 24 hours. In uncomplicated cases, this dose can be rapidly tapered within 24 to 48 hours. Patients with septic shock who are refractory to

Steroid Comparisons: Relative Glucocorticoid and Mineralocorticoid Potencies and Duration of Action

Steroid Cortisol* Prednisone Prednisolone Methylprednisolone Dexamethasone Fludrocortisone *Identical to hydrocortisone.

Glucocorticoid Potency 1 4 4 5 25-30 10

Mineralocorticoid Potency 1 0.8 0.8 0.5 0 120

Duration of Action (hr) 8-10 18-36 12-36 18-36 36-54 18-36

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PREVENTION The following steps are useful for preventing a steroidinduced crisis: ●

● ●

●

Identify patients who are at risk of developing adrenal insufficiency. Be vigilant for subtle signs of hypoadrenalism. Have a low threshold for treating patients with possible adrenal insufficiency. Use postoperative steroids in patients with septic shock, based on emerging evidence of their beneficial role in this patient subgroup.

●

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133

Consider the possible benefit of steroids for attenuating the late fibroproliferative phase of ARDS and reducing mortality.

Further Reading Annane D, Sebille V, Charpentier C, et al: Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862-871, 2002. Bollaert PE, Charpentier C, Levy B, et al: Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med 26:645-650, 1998. Friedman RJ, Schiff CF, Bromberg JS: Use of supplemental steroids in patients having orthopaedic operations. J Bone Joint Surg Am 77:1801-1806, 1995. LaRochelle GE Jr, LaRochelle AG, Ratner RE, et al: Recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients with rheumatic diseases receiving low-dose prednisone. Am J Med 95:258-264, 1993. Meduri GU, Headley AS, Golden E, et al: Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: A randomized controlled trial. JAMA 280:159-165, 1998. Salem M, Tainsh RE Jr, Bromberg J, et al: Perioperative glucocorticoid coverage: A reassessment 42 years after emergence of a problem. Ann Surg 219:416-425, 1994.

PHARMACOLOGY

fluid and vasopressor therapy can be treated with hydrocortisone 100 mg IV every 8 hours or with a continuous infusion of 10 mg/hour. Before initiating therapy, a short ACTH test should be performed to document adrenal insufficiency. When surgery is urgent or emergent and time constraints prevent the performance of a short ACTH test, dexamethasone can be given, because this will not interfere with future tests to determine normal blood cortisol concentrations in response to a short ACTH test.

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Antiemetic Drugs M. Pamela Fish Case Synopsis A 21-year-old woman (American Society of Anesthesiologists [ASA] status 1) presents with a suspected ectopic pregnancy for outpatient laparoscopy. She has no history of previous psychiatric illness or drug use. Metoclopramide 10 mg and glycopyrrolate 0.2 mg are administered intravenously as premedication. The patient becomes severely agitated and verbally abusive and refuses to proceed with surgery. She returns the following day and receives no premedication. Anesthesia and surgery proceed uneventfully.

PROBLEM ANALYSIS Definition Complications of antiemetic therapy are undesirable effects resulting from the administration of medications to prevent or treat nausea and vomiting. Untreated, up to 30% of surgical patients will suffer postoperative nausea and vomiting (PONV). For high-risk patients, the incidence can be as high as 80%. Thus, antiemetic drugs are commonly used in the perioperative period.

Recognition Conditions such as hypotension, hypoxemia, hypoglycemia, raised intracranial pressure, and bowel obstruction should be considered in the differential diagnosis of PONV. Currently available antiemetics produce their effect by antagonizing neurotransmitters in the brainstem. The major

Table 35–1

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receptor sites at which these drugs act are listed in Table 35-1. Except for antiserotonin (5-HT3) antagonists, most antiemetics antagonize more than one neurotransmitter. The antiemetic action of the corticosteroids is not well understood; some of the proposed mechanisms include prostaglandin antagonism, tryptophan depletion, and reduced 5-HT3 concentrations. Common side effects with antiemetic therapy are provided in Table 35-2.

Risk Assessment All patients who receive antiemetic therapy are at risk for related side effects. The following factors increase the likelihood that a patient will require treatment with antiemetic drugs: PATIENT FACTORS ● ●

Female sex and children under the age of puberty Nonsmoking history

Receptor Site Affinity of Antiemetic Drugs

Drug

Dopamine Receptor

Cholinergic (Muscarinic) Receptor

Histamine Receptor

Serotonin Receptor

Phenothiazine Chlorpromazine (Thorazine) Prochlorperazine (Compazine)

+++ +++

++ +

+++ ++

+ +

+ ++

++ +++

+++ ++++

– –

++++

–

+

+

++

–

+

++

– – –

– – –

– – –

++++ ++++ ++++

+

++++

–

–

Antihistamine Diphenhydramine (Benadryl) Promethazine (Phenergan)

Butyrophenone Droperidol (Inapsine)

Benzamide Metoclopramide (Reglan)

Antiserotonin Ondansetron (Zofran) Dolasetron (Anzemet) Granisetron (Kytril)

Anticholinergic Scopolamine (Hyoscine)

The number of plus signs indicates the relative degree of activity from least (+) to most (++++); a minus sign indicates no activity. Adapted from Watcha MF, White PF: Postoperative nausea and vomiting. Anesthesiology 77:162-184, 1992.

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+

+ +

+ +

+

+

+ +

+ +

+ +

+ +

+ +

+ +

+

+

+

+

+

+

+

+

+

+

ECG Changes

Visual Effects/ Diplopia

Cutaneous Flushing/ Perineal Itching

Dry Mouth

+

Tachycardia

+

Hypotension

Diphenhydramine + Promethazine +

Dizziness

+ +

Headache

+ +

Disturbed Coordination

Extrapyramidal Movements

+ +

Drug

Dysphoria

Restlessness/ Agitation

Side Effects of Antiemetic Drugs

Sedation

■

135

Antiemetic Drugs

PHARMACOLOGY

Table 35–2

■

Neuroleptic Malignant Syndrome

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Hallucinations

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Phenothiazine Chlorpromazine Prochlorperazine

Antihistamine + +

+

Anticholinergic Scopolamine

+

+

+

+

+

+

+

+

+

+

+

Benzamide Metoclopramide

+

+

+

+

+

+

+

Butyrophenone Droperidol

+

+

Antiserotonin Ondansetron Dolasetron Granisetron

+ + +

+ + +

+ + +

Corticosteroid Dexamethasone

+

+

ECG, electrocardiogram.

● ● ●

Prior history of motion sickness or PONV Preoperative anxiety or pain Any disease process that delays gastric emptying

●

Overly early or aggressive fluid intake, or requirement of oral fluid intake before discharge home

Implications SURGICAL FACTORS ● ● ● ●

Strabismus repair, head and neck surgery, or dental surgery Laparoscopic gynecologic procedures, shoulder surgery Plastic surgery (especially breast augmentation) Adenotonsillectomy, hernia repair, orchiopexy, and penile surgery in children

The following list describes some considerations and potential complications with antiemetic therapy: ●

●

ANESTHESIA FACTORS ● ● ● ●

● ● ●

Inadequate fluid replacement Duration of surgery (risk increases for length up to 3 hours) General anesthesia with volatile anesthetic agents Nitrous oxide use, due to gastrointestinal distention or increased middle ear (labyrinthine, vestibular apparatus) pressure Use of narcotic analgesics Use of certain hypnotic agents (etomidate, ketamine) Use of neostigmine (>2.5 mg)

●

●

POSTOPERATIVE FACTORS ● ●

Pain Sudden motion

Sedation ● This is the most common side effect with all antiemetic drugs. Metoclopramide ● Causes an increased risk of extrapyramidal reactions in children and the elderly ● Avoid in patients with hypertension or those taking monoamine oxidase inhibitors ● Painful stimulation may provoke supraventricular tachycardia after administration. ● Use is contraindicated in patients with epilepsy ● Because of its short half-life, not effective when administered at start of surgery Antihistamines ● Often cause dizziness, sedation, and hypotension in elderly patients Serotonin receptor antagonists ● Headache (dose dependent), dizziness, blurred vision, and abnormal liver enzymes have been reported. ● Blockage of cardiac sodium and potassium channels can cause transient electrocardiogram (ECG) changes.

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Cross-reactive hypersensitivity (anaphylactic, anaphylactoid) reactions among different 5-HT3 receptor antagonists have been reported. Droperidol ● A Food and Drug Administration (FDA) advisory was issued concerning potential Q-T prolongation and fatal arrhythmias with droperidol use (see Chapter 81). ● Contraindicated in patients with Parkinson’s disease Phenothiazines ● Drug ampules contain sodium bisulfite and sodium sulfite, which may cause an allergic-type reaction, especially in patients with a history of asthma. ● Perphenazine, the most potent antiemetic among the phenothiazines, is reserved for intractable vomiting. Scopolamine ● Use of the transdermal route is limited by long onset time and excessive drowsiness. ● Psychosis may be seen in the elderly and has also occurred in pediatric patients. Dexamethasone ● Wound infection and adrenal suppression have not been noted after a single bolus dose in otherwise healthy patients. ● Phosphate (injectable solution) is linked to perineal itching and cutaneous flushing. ●

●

●

●

●

PREVENTION The following list describes measures to avoid complications with drugs used to treat or prevent PONV: ●

●

●

MANAGEMENT Management of the complications of antiemetic drugs can range from simple observation after discontinuing the drug to treatment with specific agents. Sedation is a common side effect of antiemetc drug therapy, frequently resulting in delayed transfer from the recovery room or discharge home after ambulatory surgery. There is no specific therapy other than continued observation. Hypotension usually responds to increased intravenous fluids. However, parenteral phenothiazines may produce hypotension, requiring therapy with a vasoconstrictor such as phenylephrine. As noted earlier, ECG changes with antiserotonin antagonists are usually temporary. Although there have been reports of Q-T interval prolongation and fatal arrhythmias (torsades de pointes) with larger doses of droperidol, there have been no reports in any peer-reviewed journal of Q-T prolongation, arrhythmias, or cardiac arrest associated with the much smaller intravenous doses (0.125 mg) used for the management of PONV. Extrapyramidal disorders can present as dystonic reactions (especially in children), motor restlessness (akathisia), or signs and symptoms of parkinsonism (especially in the elderly). Treatment of extrapyramidal effects involves the administration of benztropine (a centrally acting anticholinergic) or diphenhydramine. For akathisia, antiparkinsonian drugs, benzodiazepines, or propranolol may be useful. Clinical manifestations of the neuroleptic malignant syndrome include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability. Management is discontinuation of nonessential drugs, intensive correction of fluid and electrolyte imbalance, and therapy with dopamine agonists such as bromocriptine or dantrolene.

●

Prophylaxis for PONV ● In general, there is no rationale for routine prophylactic antiemetic therapy. ● Prophylaxis in some high-risk patients may be appropriate, however (see “Risk Assessment”). ● Dexamethasone requires 4 to 5 hours for an optimal effect, so it is best administered before induction of anesthesia. ● Low-dose dexamethasone or droperidol and a 5-HT 3 receptor antagonist have been shown to be effective prophylaxis for patients at high risk for PONV. Appropriate preoperative antiemetic management ● Use premedication with oral clonidine or benzodiazepines. ● In females, avoid elective laparoscopic surgery around the time of their menses. ● Acupressure or acupuncture at the P-6 (Neiguan) point should be considered. Anesthetic technique ● Use regional anesthesia when possible. ● Choose appropriate anesthetic agents (e.g., total intravenous anesthesia with propofol). ● Avoid gastric distention from high positive-pressure facemask ventilation. ● Consider prophylactic gastric decompression (oroor nasogastric tube) before endotracheal extubation (especially for patients having emergency surgery, with a history of PONV, or at high risk for PONV). ● Avoid ingestion of blood with throat packs, or insert an oro- or nasogastric tube. ● Ensure adequate fluid replacement. ● Provide effective postoperative analgesia (consider epidural analgesia, peripheral nerve blocks, or local anesthetic wound infiltration). This will reduce opiate needs and the associated increased risk for PONV. ● Use analgesics that are less likely to cause PONV (e.g., ketorolac, COX-2 inhibitors). Antiemetic therapy ● Should PONV occur, select the antiemetic agent most appropriate for the patient. ● Serotonin receptor antagonists are more effective against vomiting than nausea. ● Repeated low doses of droperidol (0.125 mg) increase the drug’s antinausea efficacy, with reduced side effects. However, current FDA guidelines require that ECG monitoring be performed before and continued for 2 to 3 hours after droperidol use, thus limiting its use in outpatient settings. ● Antihistamines are the agents of choice following middle ear surgery. ● Ephedrine, an indirect-acting sympathomimetic, is effective for treating emesis due to hypotension associated with spinal anesthesia. ● A new class of drugs, the neurokinin-1 (NK ) receptor 1 antagonists, is currently under investigation for the prevention of PONV.

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Apfel CC, Laara E, Koivuranta M, et al: A simplified risk score for predicting postoperative nausea and vomiting. Anesthesiology 91:693-700, 1999. Caldwell C, Rains G, McKiterick K: An unusual reaction to preoperative metoclopramide. Anesthesiology 67:854-855, 1987.

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137

Gan TJ, Meyer T, Apfel CC, et al: Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 97:62-71, 2003. Sinclair DR, Chung F, Mezei G: Can postoperative nausea and vomiting be predicted? Anesthesiology 91:109-118, 1999. Watcha MF, White PF: Postoperative nausea and vomiting. Anesthesiology 77:162-184, 1992.

PHARMACOLOGY

Further Reading

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PREANESTHETIC ASSESSMENT

36

Preanesthetic Evaluation: False-Positive Tests

GENERAL ANESTHESIA

Michael P. Ford and Scott R. Springman Case Synopsis A 25-year-old male athlete presents for repair of the anterior cruciate ligament of his knee. He is taking no medications. He has a negative personal and family history of abnormal clotting or bleeding or easy bruising. Multiple tests, including prothrombin time and partial thromboplastin time (PTT), are ordered. The PTT results are reported as above normal. The surgery is postponed, and an extensive hematology workup is performed. The final report concludes, “normal variant, no coagulation defect.”

PROBLEM ANALYSIS Definition A test is useful only to the extent that clinicians can understand the implications of a positive or negative result. Few, if any, tests always correctly identify the presence or absence of disease in all patients. Clinicians can decide what to do with a “positive” test result only when they have a clear knowledge of the test’s characteristics and its statistical predictive value when applied to a specific patient population. Such “medical decision analysis” directly affects the clinical care of patients. Some tests provide a qualitative positive or negative result. Many test results, however, are quantitative and define a range of “normal” values around a mean. Therefore, a few members of any population will have an “abnormal” test result but not actually have a disease. This means that a test result may be misleading owing to variability in the patient population. The test itself can give an incorrect result due to (1) inaccuracy, (2) imprecision, or (3) incorrect performance. The accuracy of a test is the difference between the mean value of test results and the true result, as measured by a gold standard test. The precision of a test is the reproducibility of results between instruments or persons performing the test. An incorrectly performed test can invalidate any result. Test accuracy can be described in several ways. The sensitivity of a test measures the proportion of individuals who have a disease and are correctly identified as being positive for that disease, based on the test. Specificity measures the proportion of individuals who do not have a disease and are identified as being disease free, based on the test. False-positive results are more likely with tests that have a high sensitivity, low specificity, or both. Sensitivity and specificity are characteristics of the test and do not change with the prevalence (frequency) of disease in the population. Said another way: a test’s sensitivity and specificity do not affect the probability of a patient having a disease. The predictive value of tests, in contrast, depends on the prevalence of a disease in a population of patients.

The predictive value of a positive test indicates the proportion of those with a positive test who actually have the disease. Often, the predictive value of tests is expressed as the probability, or odds, that a condition is present. Likelihood ratios express the amount that the odds change when the results of the test are available (Table 36-1). In this respect, an important concept is Bayes’ theorem, which “relates the probability of an item (e.g., a patient) being a member of a particular group (e.g., clinical class), given the presence of an attribute (e.g., an abnormal test result), to the probability of known group members having the attribute and the probability of

Table 36–1

■

Accuracy and Predictive Value of Tests Target Disorder, Based on Gold Standard Test

Diagnostic Test Results Positive Negative Total

Present

Absent

a c a+c

b d b+d

Number of Patients with This Test Result a+b c+d

1. a/(a + c) = Sensitivity. 2. d/(b + d) = Specificity. 3. a/(a + b) = Positive predictive value, or post-test probability of having the target disorder among patients with positive test results. 4. d/(c + d) = Negative predictive value, or post-test probability of not having the target disorder among patients with negative test results. 5. c/(c + d) = Post-test probability of having the target disorder for patients with negative test results. 6. (a + c)/(a + b + c + d) = Prevalence or pretest probability of having the target disorder. 7. Sensitivity/(1 – Specificity) = Likelihood ratio (of having the target disorder) for a positive test result = [a/(a + c)]/[b/(b + d)]. 8. (1 – Sensitivity)/Specificity = Likelihood ratio (of having the target disorder) for a negative test result = [c/(a + c)]/[d/(b + d)]. 9. Post-test probability of the target disorder (expressed as odds) = Pretest probability of target disorder (expressed as odds) × Likelihood ratio for the test result. 10. Odds = Probability/[1 – Probability]. Adapted from Sackett DL: A primer on the precision and accuracy of the clinical examination. JAMA 267:2638-2644, 1992.

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obtaining a group member when picking at random an item from the universe of items.”1 It allows the calculation of changes in the probability of disease as new information (e.g., test results) becomes available. The post-test probability is calculated with the Fagan nomogram, similar to that shown in Figure 36-1. A Web-based interactive nomogram can be accessed at http://www.cebm.net/nomogram.asp.

Recognition A positive test result may turn out to be false if the test was performed incorrectly. Alternatively, a patient may not actually have a disease if the results of a gold standard test are normal. Other, non–gold standard tests may falsely indicate that a patient has a disease when he or she does not. Finally, because of population variability, a patient may truly test positive for a disease (be outside the “normal” range) yet be clinically normal.

Probability of at least one abnormal result

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1.0 0.8

PN = .90 P = .95 N PN = .98

0.6

PN = .99

0.4

PN = .995 0.2 0

10

20

30

40

50

60

70

80

No. of independent tests (Each with probability of normality = PN) Figure 36–2 ■ Probability of at least one falsely abnormal result for multiple tests, each with a probability of a normal result (PN), for selected values of PN. (From Berwick DM: Screening in health fairs. JAMA 254:1495, 1985.)

99

.1 .2

Risk Assessment .5 1 2

5 10 20

1000

95 90

500 200 100 50

80

20 10 5

60

2

30

Implications

20

In the preoperative setting, the most likely outcome of a false-positive test is the delay or cancellation of surgery. Physicians often repeat the test, hoping that the first result was due to an improperly performed test. Other tests to corroborate the diagnosis may be performed. However, both these options add to costs. Further, if the test is invasive, it adds to the risk of physical harm to the patient. Yet if elective surgery is not delayed and the test was not falsely positive, the providers run the risk of professional or medicolegal scrutiny. In addition, any unnecessary alteration in perioperative management may add cost and risk to the patient’s care. Finally, a false-positive result, such as for human immunodeficiency virus (HIV), may cause unnecessary psychological stress for the patient, as well as for providers.

70 50 40

1 30

.5

40

.2 .1 .05

50 60 70 80 90 95

.02 .01 .005 .002

.001

10 5

2 1 .5

.2 99 Pretest probability

If we assume that tests are being performed correctly and that their precision is high, then the accuracy of the test and the prevalence of the disease are the main factors that determine whether a test result will be “correct.” Patients who undergo multiple tests are likely to have at least one that is falsely positive. This is true especially if the tested patient population has a low prevalence of the condition. This scenario often occurs when asymptomatic patients undergo large numbers (a battery) of preoperative screening tests (Fig. 36-2).

Likelihood ratio

.1 Post-test probability

Figure 36–1 ■ Draw a line from the pretest probability through the likelihood ratio to determine the post-test probability. (Adapted from Fagan TJ: Nomogram for Bayes’s theorem. N Engl J Med 293:257, 1975.)

1 This definition is found in the 25th edition of Stedman’s Medical Dictionary, Baltimore, Williams & Wilkins, 1990.

MANAGEMENT The decision to accept a positive test result as “true” must depend on knowledge of the test’s characteristics and its performance pitfalls. The decision also depends on knowledge of the incidence of the tested condition in the patient population in question. Every test result should be examined to determine whether it fits the overall picture of the patient’s condition. If it does not, and if there are no corroborative

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findings, further investigation may be required before accepting the result as true. In many cases, a lone finding should be suspect unless it is known that the specificity of the test is high, the incidence of the condition is high, or both.

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Preanesthetic Evaluation: False-Positive Tests

143

analysis may help decide whether a test should be performed at all, in spite of the complexity of such evaluations and the need for subjective value judgments.

Further Reading

Clearly, the best way to minimize the chances of a false-positive test result is to avoid any unnecessary testing. Appropriate guidelines may take into account available scientific studies and local and national expert medical opinion. Selection of tests with a high specificity can also reduce the number of false-positive results. However, both physicians and patients abhor adverse outcomes, and the consequences of missing a true-positive result may be serious; therefore, testing and the acceptance of a certain incidence of false-positive results are commonplace. The use of cost-benefit and risk-benefit

Pasternak LR: Preoperative laboratory testing: General issues and considerations. Anesthesiol Clin North Am 22:13-25, 2004. Practice Advisory for Preanesthesia Evaluation: A Report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation. Anesthesiology 96:485-496, 2002. Roizen MF, Foss JF, Fischer SP: Preoperative evaluation. In Miller R (ed): Anesthesia. New York, Churchill Livingstone, 2000, pp 824-883. Ross AF, Tinker JH: Preoperative evaluation of the healthy patient. In Longnecker DE, Tinker JH, Morgan GE (eds): Principles and Practice of Anesthesiology. St. Louis, Mosby–Year Book, 1998, pp 3-51. Sackett DL: A primer on the precision and accuracy of the clinical examination. JAMA 267:2638-2644, 1992. Vitez TS: Principles of cost analysis. J Clin Anesth 6:357-363, 1994.

GENERAL ANESTHESIA

PREVENTION

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Preanesthetic Evaluation: Inadequate or Missing Test Result

37

Thomas P. Broderick and Scott R. Springman Case Synopsis A 44-year-old man with a history of hypertension, obesity, and episodes of epigastric pain is scheduled for elective laparoscopic cholecystectomy. No preoperative electrocardiogram is obtained. The patient subsequently sustains perioperative myocardial infarction secondary to undiagnosed coronary artery disease.

PROBLEM ANALYSIS Definition Effective preoperative test selection is best achieved by knowing how outcome is affected by the performance or omission of a test. The following are three important outcomes: 1. Adverse medical events 2. Cost of care 3. Litigation

However, if a patient has severe, unrecognized coronary disease and sustains a perioperative myocardial infarction, there will definitely be more medical care required, greater time spent in the hospital, increased costs, and possible long-term disability or risk of death. Further, emotional, professional, economic, and medicolegal risks for the providers will be increased.

MANAGEMENT

Patients are at risk for adverse outcomes when tests are not done owing to an oversight, inadequate history and physical examination, inadequate guidelines, or inappropriate emphasis on cost reduction. Process failures also occur when tests are done but the results are unavailable or lost or when providers fail to review the results before an anesthetic is administered.

If a test is found to be missing before an anesthetic is administered and the surgery is elective, the anesthesiologist and the surgeon must determine whether official internal or external policies absolutely mandate the test. If so, the test should be obtained, or the providers must justify in the medical record why they were willing to proceed with anesthesia or surgery without the test results. Of course, for emergent or urgent procedures, physicians should always weigh the expected benefits of a test against the risks of delay. If the test is discovered to be missing after anesthesia or surgery has commenced, the providers must determine whether obtaining the test result will make a real difference and whether the procedure should be terminated (fortunately, rare). Tests may, of course, be obtained during the provision of an anesthetic and serve the same purpose as a preoperative test. This is not true, however, if a preoperative test would have changed the decision to proceed with the procedure or if the test would have substantially affected the initial anesthetic plan. An example of this would be the finding of an elevated prothrombin time before the administration of a neuraxial anesthetic. If a test is discovered to be missing after surgery, is there a need to obtain the test? It may be wise to do so if postoperative or long-term medical management would be altered by the results.

Implications

PREVENTION

If a test is mandated by policy but is not done, the outcome may or may not be affected. For example, if a patient has a slightly elevated serum calcium level or is slightly anemic, for most operations, adverse perioperative outcomes are unlikely.

VALUE-BASED MEDICAL CARE

These may or may not be related. Simply knowing the result of a preoperative test cannot ensure a good outcome. Moreover, the accuracy and usefulness of a test depend greatly on its sensitivity and specificity, combined with the frequency of the condition in the patient population.

Recognition It is easy to determine whether a test was not done, not reviewed, or not available. A more difficult issue is whether a specific test was actually indicated. Hindsight may not be adequate to determine actual preoperative need. Only well-structured clinical studies and logical analysis can provide direction for clinicians who wish to provide evidenced-based care.

Risk Assessment

144

If the absence of a test leads to an adverse outcome, the system should be reexamined to prevent future problems.

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Preanesthetic Evaluation: Inadequate or Missing Test Result

EVIDENCE-BASED MEDICAL CARE Ideally, all tests should be ordered using the principle of evidence-based medical care. Many articles have been written about preoperative assessment, but few cite sufficient rigorous evidence to be of significant use. Recently, an American Society of Anesthesiologists task force found that there were insufficient scientific outcome studies to support a specific scheme for preoperative testing, other than sound medical practice based on a careful history and physical examination. The National Institute for Clinical Excellence (NICE) in the United Kingdom published a lengthy set of preoperative testing guidelines based on both patient disease and severity of surgery (www.nice.org.uk). The American College of Cardiology–American Heart Association guideline update (see also Chapter 38) can help determine the need for cardiac testing based on criteria that rely heavily on the history and physical examination. FOCUSED PREOPERATIVE TESTING The proper use of the history and physical examination is to focus further preoperative testing. However, it is important to note that many symptoms are sensitive but not highly specific indicators of problems. Interobserver variability also may be high. In addition, the value of the history depends on the adequacy of the past medical record and the patient’s reliability and communication skills.

Table 37–1

■

NONSELECTIVE

VERSUS

SELECTIVE TESTING

Pathology can exist without significant symptoms or signs. With that in mind, most schemes for preoperative testing distinguish between nonselective and selective testing. The former requires that every patient be tested or screened, even if asymptomatic. Although this approach was commonly used in the past, few recommend it today. Selective testing requires that certain groups of criteria be used to determine the need for testing. Patient Factors. The first group of criteria involves patient factors. These include, but are not limited to, symptoms, age, past medical history, gender, and physical findings. Other factors, such as the ability to obtain a reliable history or perform an adequate examination, should also be considered. Type of Surgery. The second group of criteria involves the type of surgery. Baseline values may be required because the surgery itself will alter these values or because of possible physiologic derangements caused by the surgery. Type of Anesthesia. The last group of criteria relates to the type of anesthesia. Although local or regional anesthesia may require a different testing scheme or perhaps fewer tests, there is always the possibility that local or regional anesthesia may be inadequate, and conversion to general anesthesia may be required. TESTING GUIDELINES Lacking rigorous outcome studies, criteria must be based on local and national experience. Policies or guidelines need to be constantly updated to be credible, and local consensus is an absolute necessity. Published guidelines may be simple (Table 37-1) or complex, such as the NICE guidelines. Others may simply recommend testing “as indicated by history and examination.” Experience has shown, however, that such nonspecific guidelines often result in many more or fewer tests than needed, especially when nonanesthesia providers are responsible for ordering the tests. Importantly, there are good reasons to omit nonindicated tests. Even if the tests cost nothing, they can do harm by leading to further testing, inappropriately altering case

Preanesthetic Testing and Type of Anesthesia

General or Major Conduction Anesthesia (Asymptomatic Individuals) Age

Men

Women

6 mo-<40 yr 40-<50 yr 50- <65 yr 65-74 yr

None ECG ECG HGB or HCT, ECG, BUN, GLU HGB or HCT, ECG, BUN, GLU, ± chest radiograph

HCT ± pregnancy test HCT ± pregnancy test HCT ± pregnancy test, ECG HGB or HCT, ECG, BUN, GLU HGB or HCT, ECG, BUN, GLU, ± chest radiograph

≥75 yr

Sedative-Hypnotics for IV Monitored Anesthesia

Peripheral Nerve Blocks

None None HCT (≤6 mo) HCT (≤6 mo), ECG (≤1 yr)

None None None HCT (≤6 mo)

HCT (≤6 mo), ECG (≤1 yr), BUN (≤6 mo), GLU (≤6 mo)

HCT (≤6 mo), ECG (≤1 yr)

BUN, blood urea nitrogen; ECG, electrocardiogram; GLU, glucose; HCT, hematocrit; HGB, hemoglobin; IV, intravenous. Adapted from Roizen MF, Fisher SP: Preoperative evaluation: Adults and children. In White PF (ed): Ambulatory Anesthesia and Surgery. Philadelphia, WB Saunders, 1997, p 164.

GENERAL ANESTHESIA

Caution should be used, however, in ascribing causality. Bad outcomes do not necessarily mean that more defensive testing is indicated. Consider whether testing really would have made a difference in the outcome. In addition, short-term and long-term benefits versus the potential harmful effects of testing must be considered. This is consistent with the concept of value-based anesthesia care. Complex cost-benefit analysis may be needed; time has actual value in medicine, and a seemingly more costly process may turn out to be less expensive in the long run than a less costly but lengthier process. A thoughtfully managed continuous quality improvement program may provide process and systems benefits, minimizing the pitfalls of arbitrarily assigning value based purely on cost to clinical decision making.

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management, giving the anesthesiologist and surgeon a false sense of security, and even distracting them from more important issues. Performing tests when there is no plan to review them before surgery is medically useless and legally dangerous. COMPUTERIZED PREOPERATIVE ASSESSMENT SYSTEMS PREANESTHETIC EVALUATION CLINICS

AND

A preanesthetic evaluation clinic can provide a systematic, logical, cost-effective, and streamlined approach to preoperative testing. Also, a well-structured computerized preoperative assessment system (which must comply with the Health Insurance Portability and Accountability Act) can both enhance the collection of patient data and reduce the volume of unnecessary or missed preoperative visits. Further, an electronic medical record employing integrated “decision support” may substantially improve both the quality and the availability of preoperative evaluation and testing. The anesthesiologist’s review of a patient’s workup is then more convenient, complete, and useful. Gaining consensus about the indications for testing, the timing of testing, who orders the tests, and who reviews the test results is the first step in optimizing a preoperative evaluation process.

Further Reading American Society of Anesthesiologists: Practice advisory for preanesthesia evaluation: A report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation. Anesthesiology 96:485-496, 2002. Eagle KA, Berger PB, Calkins H, et al: ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery— executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Anesth Analg 94:1052-1064, 2002. Ferrari LR: Preoperative evaluation of pediatric surgical patients with multisystem considerations. Anesth Analg 99:1058-1069, 2004. Fischer S: Development and effectiveness of an anesthesia preoperative evaluation clinic in a teaching hospital. Anesthesiology 85:196-206, 1996. Fisher S: Cost-effective preoperative evaluation and testing. Chest 115: 96S-100S, 1999. Gibby G: How preoperative assessment programs can be justified financially to hospital administrators. Int Anesthesiol Clin 40:17-30, 2002. Hildred W, Watkins L: The nearly good, the bad, and the ugly in cost effectiveness analysis of health care. J Econ Issues 30:755-775, 1996. Orkin FK: Moving toward value-based anesthesia care. J Clin Anesth 5: 91-98, 1993. Roizen MF, Fisher SP: Preoperative evaluation: Adults and children. In White PF (ed): Ambulatory Anesthesia and Surgery. Philadelphia, WB Saunders, 1997, pp 155-172.

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Cardiac Risk Assessment John L. Atlee

38

Case Synopsis GENERAL ANESTHESIA

A 70-year-old man with intermittent claudication, hypertension, non-insulin-dependent diabetes mellitus, and hyperlipidemia is admitted for same-day right axillary–bifemoral and right femoral–popliteal bypass surgery for arterial occlusive disease. His past medical history is significant for myocardial infarction (MI) 5 years ago and 50 pack-years of smoking before that. His left ventricular ejection fraction is 45%, but his exercise capacity is limited by claudication. The 12-lead electrocardiogram (ECG) shows sinus bradycardia (56 beats per minute), old anterior wall infarction, and occasional ventricular extrasystoles (VES). In the preoperative holding area, his blood pressure is 168/95 mm Hg, and the monitored ECG shows 4 to 6 VES/minute. His current medications include metoprolol, glyburide, atorvastatin, and a long-acting nitrate. His primary physician has cleared him for surgery.

PROBLEM ANALYSIS Definition Cardiovascular disease and all types of surgeries are increasing globally, both in prevalence and in number. Cardiovascular conditions that may affect the postoperative outcomes of cardiac and noncardiac surgery alike include hypertensive crisis,1 coronary artery disease, valvular heart disease, arrhythmias or conduction disturbances, and hypertrophic or dilated cardiomyopathy. Cardiomyopathies also increase the risk for perioperative congestive heart failure. Chronic pulmonary disease, hepatic or renal insufficiency, diabetes mellitus, and other severe systemic disease can also have an adverse impact on postoperative cardiovascular outcomes. The cardiovascular complication of most concern is perioperative acute MI. Others are acute heart failure, thromboembolism (e.g., stroke, pulmonary embolism), arrhythmias and conduction disturbances, and hypertensive crisis.

Recognition The initial history, physical examination, and ECG assessment should focus on identifying potentially serious cardiac disorders, including coronary artery disease (defined as previous MI or angina), heart failure, and symptomatic arrhythmias; the presence of an implanted cardiac rhythm management device, such as a pacemaker or internal cardioverter-defibrillator (see Chapter 97); or a history of orthostatic intolerance. The Framingham Heart Study identified major, predisposing, and conditional risk factors for coronary artery disease (Table 38-1). Although age per se is not a modifiable risk factor, it relates to the length of time a person is exposed to risk factors that increase the severity

1 Hypertensive crisis includes urgencies and emergencies. Both require severe (stage 2) blood pressure elevation above 160/100 mm Hg. For emergencies, end-organ damage is also evident.

of atherosclerosis; it is also an important index in the Framingham risk equation. Because obesity, family history of early coronary artery disease, and physical inactivity contribute to other risk factors, they too are considered major risk factors.

Risk Assessment Clinical predictors of increased risk for perioperative MI, heart failure, or death are listed in Table 38- 2. Major predictors

Table 38–1

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Risk Factors for Coronary Artery Disease

\

Major Cigarette smoking Elevated blood pressure Elevated serum total and LDL cholesterol Low serum HDL cholesterol Diabetes mellitus Advanced age

Other (Predisposing) Risk Factors Obesity Abdominal obesity Physical inactivity Family history of premature coronary heart disease Ethnic characteristics Psychosocial factors

Conditional Risk Factors Elevated serum triglycerides Small LDL particles Elevated serum homocysteine Elevated serum lipoproteins Prothrombogenic factors (e.g., fibrinogen) Inflammatory markers (e.g., C-reactive proteins) HDL, high-density lipoprotein; LDL, low-density lipoprotein. Adapted from Eagle KA, Brundage BH, Chaitman BR, et al: Guidelines for perioperative cardiovascular evaluation for noncardiac surgery. Circulation 93: 1278-1317, 1996; and Eagle KA, Berger PB, Calkins H, et al: ACC/AHA update for perioperative cardiovascular evaluation for noncardiac surgery. Circulation 105: 1257-1267, 2002.

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Clinical Predictors of Increased Risk for Perioperative Myocardial Infarction, Heart Failure, or Death

Major Unstable coronary syndromes Acute or recent MI* Unstable or severe angina† (Canadian class III or IV)‡ Evidence of large ischemic burden by clinical symptoms or noninvasive testing Decompensated heart failure Significant arrhythmias High-grade atrioventricular block Symptomatic ventricular arrhythmias in the presence of underlying heart disease Supraventricular arrhythmias with uncontrolled ventricular rate Severe valvular heart disease

Intermediate Mild angina pectoris Previous MI by history or pathologic Q waves Compensated or prior heart failure Diabetes (particularly insulin-dependent) Renal insufficiency

Minor Advanced age Abnormal ECG (left ventricular hypertrophy, left bundle branch block, ST-T abnormalities) Rhythm other than sinus (e.g., atrial fibrillation) Low functional capacity (e.g., inability to climb one flight of stairs with a bag of groceries) History of stroke Uncontrolled systemic hypertension *Acute MI is within 7 days; recent MI is >7 days but ≤30 days. † May include “stable” angina in patients who are unusually sedentary. ‡ See Campeau L: Grading of angina pectoris. Circulation 54:522-523, 1976. ECG, electrocardiogram; MI, myocardial infarction. Adapted from Eagle KA, Brundage BH, Chaitman BR, et al: Guidelines for perioperative cardiovascular evaluation for noncardiac surgery. Circulation 93: 1278-1317, 1996; and Eagle KA, Berger PB, Calkins H, et al: ACC/AHA update for perioperative cardiovascular evaluation for noncardiac surgery. Circulation 105: 1257-1267, 2002.

of increased risk are unstable coronary syndromes or evidence of large ischemic burden, decompensated heart failure, significant arrhythmias, or severe valvular heart disease. Evidence of such risk factors is found in clinical symptoms or results of noninvasive testing. Anemia also may increase the risk for perioperative cardiovascular events. Further, the patient’s underlying cardiac condition, which might be stable at present (e.g., angina, heart failure, valvular disease), may become manifest with perioperative stress (e.g., pain, high circulating catecholamines, hypoxia, hypercarbia, acute electrolyte imbalance). Also, one should identify serious comorbid conditions (e.g., diabetes, peripheral vascular disease, renal insufficiency, stroke, pulmonary disease), because these too may affect perioperative outcome. Intermediate predictors of increased risk for perioperative cardiovascular events are mild angina, more remote previous MI, compensated heart failure, creatinine 2.0 mg/dL or greater, and diabetes mellitus. Minor predictors are advanced age, abnormal ECG, low functional capacity, history of stroke, and uncontrolled systemic hypertension. Odds ratios for variables that

Table 38–3

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Factors that Increase the Risk for Perioperative Cardiac Events and Are Indications for β-Blocker Therapy

Risk Variables

Odds Ratio (95% CI)

β-Blocker Indicated

Clinical features Coronary artery disease (CAD)* Heart failure (HF) Diabetes melliltus†

2.4 (1.3-4.2)

Yes

1.9 (1.1-3.5) 3.0 (1.3-7.1)

Yes Yes

Renal insufficiency

3.0 (1.4-6.8)

Poor functional status‡

1.8 (0.9-3.5)

High-risk surgery§

2.8 (1.6-4.9)

Probably yes, if secondary to CAD or HF Probably yes, if secondary to CAD or HF Yes

∗Includes angina and prior myocardial infarction. † Especially if insulin required. ‡ Inability to walk four blocks or climb two flights of stairs. § See Table 38-4. CI, confidence interval. Adapted from Fleisher LA, Eagle KA: Clinical practice: Lowering cardiac risk in noncardiac surgery. N Engl J Med 345:1677-1682, 2001.

increase the risk of perioperative cardiac complications, as well as indications for perioperative β-blocker therapy, are listed in Table 38-3. Cardiac risk for various types of surgery is stratified in Table 38-4. Note that a remote history of MI or abnormal Q waves by ECG is an intermediate predictor of increased risk for perioperative cardiovascular events, whereas an acute MI (documented MI ≤7 days before preoperative evaluation) or recent MI (>7 but <30 days before preoperative evaluation),

Table 38–4

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Cardiac Risk Stratification for Various Types of Surgical Procedures

High risk (reported cardiac risk* ≥ 5%) Emergency major operations, especially in the elderly Aortic, major vascular, and peripheral vascular surgery Extensive operations with large volume shifts and/or blood loss

Intermediate risk (reported cardiac risk ≥ 1% but < 5%) Intraperitoneal surgery Intrathoracic surgery Carotid endarterectomy Head and neck surgery Orthopedic surgery Prostate surgery

Low risk (reported cardiac risk† < 1%) Endoscopic procedures Superficial biopsy Cataract surgery Breast surgery ∗Combined incidence of cardiac death and nonfatal MI † Does not generally require further preoperative cardiac testing Adapted from Eagle KA, Brundage BH, Chaitman BR, et al: Guidelines for perioperative cardiovascular evaluation for noncardiac surgery. Circulation 93:1278-1317, 1996.

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Implications Preoperative cardiac risk assessment is important for reducing perioperative morbidity and mortality, especially for patients having noncardiac surgery. Such risk is best evaluated by a multidisciplinary, integrated approach. This requires good communication among the patient, primary physician, consultant, anesthesiologist, and surgeon.

MANAGEMENT The goal of cardiac risk assessment and any remedial therapy is to improve intra- and postoperative and long-term outcomes. Optimization of associated medical conditions may include control of hypertension, coronary revascularization, treatment for congestive heart failure and other important systemic conditions (e.g., hepatic or renal insufficiency, pulmonary insufficiency), and management for coagulation or anticoagulation disorders.

PREVENTION Perioperative β-blockers are used to prevent postoperative atrial fibrillation and perioperative hypertension. Anticoagulation may be required to reduce the risk of thromboembolism and

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stroke in patients at increased risk (e.g., those with atrial fibrillation, hemoglobinopathies, coagulopathies, heart failure, prolonged bed rest). For patients with systemic anticoagulation or coagulopathies who are at increased risk for bleeding complications, special precautions must be taken if regional anesthesia will be used or is contemplated.

Further Reading Boersma E, Poldermans D, Bax JJ, et al: Predictors of cardiac events after major vascular surgery. JAMA 285:1865-1873, 2001. Dupuis J-Y, Wang F, Nathan H, et al: The cardiac anesthesia risk evaluation score. Anesthesiology 94:194-204, 2001. Eagle KA, Berger PB, Calkins H, et al: ACC/AHA update for perioperative cardiovascular evaluation for noncardiac surgery. Circulation 105:1257-1267, 2002. Eagle KA, Brundage BH, Chaitman BR, et al: Guidelines for perioperative cardiovascular evaluation for noncardiac surgery. Circulation 93:1278-1317, 1996. Fleisher LA, Eagle KA: Clinical practice: Lowering cardiac risk in noncardiac surgery. N Engl J Med 345:1677-1682, 2001. Grundy SM: Age as a risk factor: You are as old as your arteries. Am J Cardiol 83:1455-1457, 1999. Grundy SM, Pasternak R, Greenland P, et al: Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: A statement for healthcare professionals from the American Heart Association and the American College of Cardiology. Circulation 100:1481-1492, 1999. Lee TH, Marcantonio ER, Mangione CM, et al: Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 100:1043-1049, 1999. Mukherjee D, Eagle KA: Perioperative cardiac assessment for noncardiac surgery. Circulation 107:2771-2774, 2003. Nashef SA, Roques F, Michel P, et al: European system for cardiac operative risk evaluation (EuroScore). Eur J Cardiothorac Surg 16:9-13, 1999. Ouattara A, Niculescu M, Ghazouani S, et al: Predictive performance and variability of the cardiac anesthesia risk score. Anesthesiology 100:405-410, 2004. Park KW: Preoperative cardiology consultation. Anesthesiology 98:754-762, 2003. Tu JV, Jaglal SB, Naylor D: The Steering Committee of the Provincial Adult Cardiac Care Network of Ontario: Multicenter validation of a risk index for mortality, intensive care unit stay, and overall hospital length of stay after cardiac surgery. Circulation 91:677-684, 1995. Wilson PWF, D’Agostino RB, Levy D: Prediction of coronary heart disease using risk factor categories. Circulation 97:1837-1847, 1998.

GENERAL ANESTHESIA

with evidence of important ischemic burden by symptoms or noninvasive study, is a major predictor. This definition of acute and recent MI was a consensus recommendation and avoids the traditional division of MI into 3-month and 6-month intervals. Finally, current management of MI provides for risk stratification during convalescence. If a recent stress test does not indicate residual myocardium at risk (ischemic burden), the likelihood of perioperative reinfarction with noncardiac surgery is low. Although there are no adequate clinical trials on which to base firm recommendations, it appears reasonable to wait 4 to 6 weeks after acute MI to perform elective surgery.

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Christine M. Zainer Case Synopsis A 47-year-old female executive with breast cancer is scheduled to have a lumpectomy and sentinel node biopsy under general anesthesia. She has a history of mild depression and a 1-week history of an upper respiratory infection that is resolving. The patient denies allergies and medications. Upon further questioning, she admits to taking St. John’s wort, Ginkgo biloba, dong quai, multivitamin and calcium supplements, and vitamin E. She also admits to taking ginseng and echinacea for the past week to treat her upper respiratory symptoms, because she did not want to postpone her surgery.

PROBLEM ANALYSIS Definition Many complementary and alternative medicine (CAM) systems rely on herbs or dietary supplements or modifications. These substances are also called nutraceuticals—anything that can be considered a food or part of a food and provides medical or health benefits, including the prevention and treatment of disease. Such CAM systems include Ayurveda (India), traditional Chinese medicine, homeopathy, and naturopathy. Other CAM systems do not necessarily include nutraceuticals but may involve manipulative, body-based, or energy therapies. These include the following: ● ● ● ● ● ●

Chiropractic Acupuncture Bioelectromagnetic field therapies Qi gong Reiki Therapeutic touch

Under the 1994 Dietary Supplement Health and Education Act, herbals are considered dietary supplements, not drugs. According to the Food and Drug Administration (FDA), dietary supplements are nutrients (vitamins, minerals, amino acids), botanicals (herbs or extracts from plants, including flowers, trees, shrubs, algae, ferns, fungi, seaweeds, and grasses), and glandular extracts from animal or synthetic sources. Manufacturers are allowed to state that their products affect the “structure or function” of the body, provided that there is a disclaimer that the product has not been evaluated by the FDA. Manufacturers are responsible for their products’ quality and safety, but the FDA does not require proof of efficacy or purity or reporting of adverse effects. The FDA may withdraw products shown to be harmful (e.g., fen-phen, cholestin, contaminated L-tryptophan, ephedra). Also, since 1998, FDA regulations require that dietary supplements that claim to “diagnose, treat, prevent, or cure disease” are to be regarded as drugs and must meet safety and efficacy 150

standards; hence the disclaimers on so many product labels. Homeopathic and parenteral nutritional products are registered by the FDA but are not approved as drugs.

Recognition Herbal medicines have been used for many thousands of years and are still used by 80% of the world’s population. Herbal medicines are prescribed in Europe, and the German Commission E monographs for over 400 herbs are a resource for physicians. One third of conventional drugs are plant derived; aspirin (willow bark), digoxin (foxglove), ephedrine (ma huang), and atropine (belladonna alkaloids) are some common examples. More than 5000 suspected herb-related adverse effects were reported to the World Health Organization prior to 1996. Between 1993 and 1998, the FDA received 2621 reports of adverse events, with 101 deaths associated with dietary supplements. In contrast, in 1995 the FDA received reports of 7000 deaths related to adverse prescription drug effects. One meta-analysis estimated that 100,000 deaths per year are associated with adverse drug reactions in hospitalized patients. Given the widespread use of herbals and other dietary supplements, reported adverse effects are relatively few. However, lack of recognition and underreporting are possible reasons for this disparity. Many reports of adverse effects lack documentation of temporal effects, concomitant drug use, and positive identification of the herb in question, and they exclude the possible effects of contaminants or adulterants. For any substance that may have pharmacologic effects, vigilance is prudent, especially during anesthesia and surgery. Consumers consider nutraceuticals to be safe, effective, and natural; as a result, their use is often not reported to physicians. As many as 20% of adults in the United States may use nutraceuticals, including herbs, and these numbers are increasing. One survey of more than 1000 adults undergoing preanesthetic evaluation revealed that about 40% were using at least one supplement, and 32% of these patients took herbals. More than 70% of these patients failed to report this use during routine preanesthetic assessment. A survey of more

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Risk Assessment Although mechanical and infectious complications have been reported after some CAM therapy, an extensive review is beyond the scope of this chapter. Given that there are more than 20,000 herbal products in the United States, this chapter focuses on those substances most commonly used or most likely to have adverse pharmacologic effects in the perioperative period. Assessment of risk is difficult, given the relative paucity of reports, incomplete information, and multiple patient and product variables. Dietary supplements, including vitamins, may contain a variety of substances with herbal ingredients. Product labels may not accurately reflect the contents or amounts. Also, lot-to-lot potency may vary owing to many factors, such as growing conditions, part of the plant used, time of harvest, preparation and extraction methods, and storage techniques. Standardization of compounds extracted from herbs is sometimes attempted, but the pharmacologic effects may be due to the combined or synergistic effects of the many compounds present in the herb. Further, products may be misused or adulterated with contaminants, such as misidentified botanical species, pesticides, herbicides, heavy metals, and conventional drugs. Asian products have a high rate of contamination (about 30%). For example, contaminants in L-tryptophan resulted in eosinophilia-myalgia syndrome. Also, substitution of Aristolochia fangchi (fang-ji, a known nephrotoxin) for Stephania tetrandra (huang-fang ji) in a Chinese weight-loss preparation sold in Belgium caused more than 100 cases of renal failure and urothelial carcinoma. The safety of raw animal glandular products (e.g., melatonin) is not known, especially those originating from the brains of animal species capable of transmitting spongiform encephalopathies. Synthetic sources are available for some of these substances. Possible adverse effects are often based on in vitro studies of isolated compounds in animal models, isolated case reports, or small observational clinical trials. Often, any observed adverse effects are assumed to be related to the active ingredients. Randomized, controlled trials of the effects of herbs in the perioperative period are lacking. Future risk assessment must distinguish a “no observed effect level” and a “no observed adverse effect level” similar to that adopted for food additives and contaminants. More study is definitely needed.

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Dietary substances affect enzyme systems and have clinical effects. For example, foods in the nightshade family (e.g., tomato, potato, eggplant) decrease acetylcholinesterase and pseudocholinesterase activity. These foods may influence the levels of drugs metabolized by these routes, including the neuromuscular blocking agent succinycholine. Dietary regimens that lead to subclinical vitamin deficiency states may predispose patients to complications. Neurologic complications after nitrous oxide anesthesia have been reported in patients with vitamin B12 deficiency, including one patient on a restricted vegan diet.

Implications Common side effects include gastrointestinal upset, allergic reactions, and dermatitis. Direct, indirect, synergistic, antagonistic, and toxic pharmacologic effects are possible when herbs are taken alone or in combination with conventional drugs. Herbs and nutraceuticals associated with organ system toxicity or physiologic effects are listed in Table 39-1. Table 39-2 summarizes the common uses for these herbs, the perioperative concerns, and other pertinent information. The risk of toxicity with conventional medications is increased for patients at the extremes of age, as well as those who are pregnant, have a chronic illness or metabolic dysfunction, or are receiving chronic drug treatment. These patients may also be at increased risk for adverse effects or drug interactions with some nutraceuticals.

MANAGEMENT There are no formal guidelines for the perioperative management of patients who are taking herbals or nutraceuticals. It may be reasonable to postpone elective surgery in those who are using nutraceuticals that may affect coagulation or cardiovascular, central nervous system, or other major organ function. The American Society of Anesthesiologists has made no formal statement about the known therapeutic properties of herbal medications, and it has no formal policy or standards of care that apply specifically to phytopharmaceuticals. It does advise, however, that patients inform their physicians if they are using phytopharmaceuticals, that physicians specifically ask their patients about such use, and that patients discontinue these products 2 to 3 weeks before anesthesia and surgery. Just as discontinuing some conventional medications is associated with increased morbidity and mortality, the discontinuation of herbal preparations may have similar effects. Abruptly stopping the use of some herbs may produce withdrawal symptoms. Individual management based on available pharmacokinetic data is recommended by some authors and may be the most practical approach in some clinical scenarios (Table 39-3). As for neuraxial blocks, herbal medicines alone are not thought to create a risk that would mandate the cancellation of surgery. Concurrent use of oral anticoagulants or heparin may increase the risk for bleeding. There are no wholly accepted tests for hemostasis in patients using

GENERAL ANESTHESIA

than 1000 preoperative pediatric patients showed that 12% used herbal remedies. Supplement use is more prevalent among the following groups: females, nonsmokers, those with higher incomes, those who exercise regularly, those educated beyond high school, those in generally good health (albeit with one or more health problems), presurgical patients, and patients with cancer, liver disease, human immunodeficiency virus (HIV), asthma, and rheumatologic disorders. By sales, the 10 top-ranked herbs in 2001 were echinacea, garlic, Ginkgo biloba, saw palmetto, ginseng, grapeseed extract, green tea, St. John’s wort, bilberry, and aloe. Studies have shown statistically significant efficacy in the case of garlic, Ginkgo biloba, saw palmetto, and St. John’s wort.

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Organ System or Pharmacologic Effects of Herbals and Nutraceuticals

Effects

Herbal/Nutraceutical

Abortifacient effects

Devil’s claw Dong quai Goldenseal Aromatherapy Salicylate sources: willow bark, meadowsweet Feverfew (↓ migraines) Fish oils (ω-3 fatty acids)

Analgesic effects

Anti-inflammatory effects

Blood pressure effects

Carcinogen Cardiac effects

Cardiac glycoside–like effects

Cardiac effects— ischemic preconditioning CNS effects Cognitive function Seizures Sedative effects

Ginseng (↓ opioid effects) Blueberry Devil’s claw Ginkgo biloba Ginger Green tea Milk thistle Red grapes Stinging nettle Turmeric Willow bark Yarrow Black cohosh (↓) Celery (↓) Fenugreek (↓) Garlic (↓) Hawthorn (↓) Horseradish (↓) Capsicum (↑) Ephedra (↑) Goldenseal (↑) Licorice (↑) Ginger (↓ or ↑) Ginkgo (↑ or ↓) Ginseng (↓ or ↑) St. John’s wort (↓ or ↑) Calamus Sassafras Aconite Black cohosh Ephedra Fenugreek Fish oils GBL, BD, GHB Ginger Ginkgo biloba Goldenseal Hawthorn

Other Names

Oxytocic

Withdrawal possible Decreases pain associated with migraines, sickle cell, rheumatoid arthritis Vaccinium myrtillus Harpagophytum procumbens Ginkgo biloba Zingiber officinale Camellia sinensis Silybum marianum Vitus vinifera Urtica dioica Curcuma longa Salix alba Achillea millefolium

Jimsonweed Licorice Lobelia Foxglove (yellow, purple) Digitalis lanata; purpurea Kyushin Milkweed Apocynum androsaemifolium Lily of the valley Plantain (adulterated with foxglove) Siberian ginseng Eleutherococcus senticosus Hawthorn berries Uzara root Antioxidants (free radicals are involved in ischemic preconditioning in animals) Melatonin Ginkgo toxin in seed and leaf Celery Chamomile

Specific Effects/Comments

Arrhythmias ↓ HR, vasodilator Arrhythmias ↑ HR ↓ Sudden death, ↓ lipids ↓ HR, death ↓ HR, inotrope in vitro Vasodilator, but HTN noted Cardiac stimulant, ↓ coronary blood flow Arrhythmias; potentiation of digitalis; possible β-blocker, ACE inhibitor properties ↑ HR, anticholinergic effects HTN, hypokalemia ↑ HR

Vitamin C–attenuated beneficial effect of ischemic preconditioning in pigs Case report—used to treat/prevent postoperative delirium Neurotoxin; decreased seizure threshold Unconsciousness, slow respirations Table continued on following page

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Organ System or Pharmacologic Effects of Herbals and Nutraceuticals—cont’d

Effects

Herbal/Nutraceutical

Coagulation effects

Drug interactions Digoxin Digoxin assay: interference/ without toxicity Dilantin MAOIs SSRIs Warfarin ↓ INR ↑ INR Potentiation of effect Drug metabolism Hepatic enzyme inducers ↓ drug concentrations (subtherapeutic) Hepatic enzyme inhibitors ↑drug levels (toxicity) Esterase inhibitors (↓ metabolism of cocaine, heroin, esmolol, local ester anesthetics, cholinesterase inhibitors, neuromuscular blocking drugs) Electrolyte abnormalities

Valerian Chinese herbs (most P) Dan-shen (P) Dong quai (P) Vitamin E (P) (>800 mg = 1200 IU/day) Feverfew (P) Fish oils (P) Garlic (P) Ginger (P) (inhibits thromboxane synthetase) Ginkgo biloba (P) (inhibits plateletactivating factor) Ginseng—Panax (P, F) (prolongs PT, PTT; but ↓ INR on warfarin) Ginseng—American (↓ INR) Kava kava (P) Hawthorn Licorice St. John’s wort Kyushin (false ↑) Siberian ginseng (false ↑) Shankhapushpi (Ayurvedic) Ginseng (Panax) Licorice St. John’s wort St. John’s wort St. John’s wort Coenzyme Q10 Ginseng (Panax, American) Dan-shen Dong quai Garlic Ginger Ginkgo

Specific Effects/Comments

Serotonergic syndrome with SSRIs (tremor, headache, myalgias, restlessness, mental status changes) Withdrawal syndrome Coumarin-containing plants: alfalfa, capsicum, celery, chamomile, fenugreek, ginseng, horseradish, licorice, passsionflower, red clover

↑ Toxicity ↓ Digoxin levels Traditional Chinese medicine “to save the heart” ↓ Plasma concentration

Serotonergic syndrome with concomitant use

Vitamin K analogue

St. John’s wort

Echinacea Grapefruit juice Glycoalkyloids of Solanaceae (nightshades—potato, tomato, eggplant)

Aloe Artichoke Celery Dandelion

Cathartic, hypokalemia Diuretic Diuretic Diuretic Table continued on following page

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GBL, BD, GHB Ginseng Goldenseal Hops Kava kava Passionflower St. John’s wort

Other Names

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Organ System or Pharmacologic Effects of Herbals and Nutraceuticals—cont’d

Effects

Herbal/Nutraceutical

Other Names

Glossypol Goldenseal Licorice Glucose blood levels Increased

Decreased

Hepatic toxicity

Immune function

Devil’s claw Ephedra Ginseng Licorice Chromium Cinnamon Fenugreek Garlic Ginseng Karela Sage Chaparral Comfrey Germander Kava kava Pennyroyal Yohimbe Echinacea

Nausea and vomiting Neuromuscular blockade

Ginger (↓ motion sickness) Potato glycoalkaloids Solanaceae (nightshade—tomato, potato, eggplant)

Renal toxicity Skin effects

Aristolochia fangchi Kava kava Dong quai St. John’s wort Valerian (GABAergic)

Withdrawal syndromes

Specific Effects/Comments Hypokalemia Aquaretic (water, not Na+, excreted; ↑ HTN, edema) Hypokalemia, pseudoaldosteronism

Momordica charantia

Need for liver transplant or death Multicomponent product Not recommended for patients with autoimmune diseases Inhibits pseudocholinesterase (in vitro, human; in vivo, rabbit) Inhibits pseudocholinesterase and acetylcholinesterases Urothelial carcinoma, renal failure Kava dermopathy (yellow, dry, flaky skin) Photosensitizer Photosensitizer Consider tapering over 2 wk; give benzodiazepines for withdrawal

ACE, angiotensin-converting enzyme; BD, 1,4-butanediol; CNS, central nervous system; F, fibrin formation inhibitor; GABA, γ-aminobutyric acid; GBL, γ-butyrolactone; GHB, γ-hydroxybutyrate; HR, heart rate; HTN, hypertension; INR, international normalized ratio; MAOI, monoamine oxidase inhibitor; P, platelet aggregation inhibitor; PT, prothrombin time; PTT, partial thromboplastin time; SSRI, selective serotonin reuptake inhibitor.

herbal preparations, nor are there specific concerns or recommendations regarding the timing of neuraxial block placement or catheter removal. Information and vigilance are key to recognizing potentially adverse reactions and responding to them appropriately. Also, the recognition of potentially advantageous effects may come with further research.

PREVENTION Physicians should be informed about and familiar with the effects of commonly used herbals and nutraceuticals, whether positive and negative. They should ask patients about their use and be willing to act as resource for them.

Patients should consult with their physicians before using herbals or nutraceuticals and then report any beneficial or adverse side effects. Consumers who use these substances should be cautious about product quality, especially with foreign manufacturers or distributors. They may want to consider requesting independent laboratory test results for product content and the presence of contaminants. Information about herbals and nutraceuticals is available from many public and private resources (Table 39-4). Suspected adverse effects should be reported to the FDA’s Center for Food Safety and Applied Nutrition (http://vm.cfsan.fda.gov/~dms/supplmnt.html) or to the FDA MedWatch Program (www.fda.gov/medwatch; 1-800FDA-1088).

Ginseng American (Panax quinquefolius) Asian (Panax ginseng) Sanchi (Panax pseudoginseng var notoginseng) Siberian (Eleutherococcus senticosus) GBL, BD, GHB

Ginkgo (Ginkgo biloba)

Ginger (Zingiber officinale)

Garlic (Allium sativum)

Illegally distributed (not approved by FDA) for bodybuilding, weight loss, sleep aid

HTN; hyperlipidemia; respiratory, digestive, liver complaints Nausea, vomiting; vertigo; motion sickness; antispasmodic; digestive complaints Dementia; claudication; increased mental acuity; tinnitus; vertigo Adaptogen; immunomodulation; tonic for many conditions

Weight loss; antitussive; asthma Antioxidant; antiaging; cardiovascular health and cancer prophylaxis; fibrocystic breast syndrome Migraines; fever

Ephedra, ma huang (Ephedra sinica) Vitamin E

Feverfew (Tanacetum parthenium)

Upper respiratory infections, flu

Echinacea (E. angustifolia, E. pallida, E. purpurea)

Yes Yes

Inhibits platelet-activating factor; seed and leaf contain a neurotoxin HTN; tachycardia; bleeding; ↓ INR with warfarin; CNS stimulation; hypoglycemic effects in type 2 diabetes

Yes

Yes

Inhibits platelet aggregation; ↑ INR with warfarin Inhibits thromboxane synthetase

Yes

Yes

Yes

Inhibits platelets

HTN, arrhythmias, sympathomimetic effects

Possible inhibition of platelet aggregation and cyclooxygenase; ↑ INR on warfarin Immunostimulant; inhibits CYP3A4, so risk of toxicity for drugs metabolized by CYP3A4 (alprazolam, calcium channel blockers, protease inhibitors)

Continued

Death; seizures; unconsciousness; bradycardia; slowed respirations requiring intubation

Spontaneous hyphema, subdural hematoma; no known interaction with cardiac glycosides or hypoglycemics Stevens-Johnson syndrome; epistaxis; vaginal bleeding; mastalgia Siberian ginseng interferes with digoxin assay— false elevation of digoxin levels without toxicity

Abrupt withdrawal can cause headache, insomnia, nervousness, arthralgias, fatigue, stiffness; aphthous ulcers Case of elderly man who developed spontaneous epidural hematoma while gardening—4 raw cloves/day Possible mutagenesis

Tachyphylaxis; autoimmune disease exacerbation; potentially hepatotoxic, but lacks 1,2 unsaturated necrine ring associated with other hepatotoxic pyrrolizidine alkaloids Banned by FDA in 2004; interactions with cardiac glycosides Possible bleeding with doses >800 mg = 1200 IU/day

Photosensitivity

Structurally related to vitamin K

↓ INR on warfarin

Congestive heart failure, cardiovascular health; used with statins Menopausal symptoms

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Dong quai (Angelica sinensis)

Cross-allergenicity with ragweed

Hypokalemia Sedation

Digestion, cathartic Insomnia

Other Concerns

Aloe Chamomile (Matricaria chamomilla) Coenzyme Q10 (ubiquinone, ubidecarenone)

Potential Bleeding

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Potential Perioperative Concerns

Common Uses of and Potential Problems with Herbals and Nutraceuticals Common Uses

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Herbal/Nutraceutical

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156 Depression; anxiety; sleep disorders Insomnia; sedation; anxiety

St. John’s wort (Hypericum perforatum)

Valerian (Valeriana officinalis)

Kava dermopathy (red eyes; dry, flaky, yellow skin and nails); inhibits cyclooxygenase Cross-reacts with digoxin assays Glycyrrhizic acid inhibits 11-β-hydroxysteroid dehydrogenase resulting in mineralocorticoid effects; transient myopathy (2 wk) Inhibits dihydrotestosterone binding and 5α-reductase activity; possible interaction with other hormone therapies Photosensitivity; induction of hepatic cytochromes P-450, 3A4; decreased digoxin levels; decreased HIV protease inhibitors and NNRTIs Withdrawal possible; treat with benzodiazepines

Coma with alprazolam; GABA effects; potentiates barbiturates and benzodiazepines; hepatotoxicity False elevations of digoxin levels without toxicity HTN; K+ loss; edema; pseudoaldosteronism

Prolongs barbiturate-induced sleep

Possible weak MAOI; possible SSRI (mechanism uncertain); use caution with β-sympathomimetic amines, SSRIs, MAOs

None known

Oxytocic; aquaretic, not diuretic (no Na+ excreted, just free water)

Other Concerns

HTN; edema; paralysis with overdosage

Potential Bleeding

BD, 1,4-butanediol; CNS, central nervous system; FDA, Food and Drug Administration; GABA, γ-aminobutyric acid; GBL, γ-butyrolactone; GHB, γ-hydroxybutyrate; HIV, human immunodeficiency virus; HTN, hypertension; INR, international normalized ratio; MAOI, monoamine oxidase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; SSRI, selective serotonin reuptake inhibitor.

Benign prostatic hypertrophy

Saw palmetto (Serenoa repens)

Diuretic; antiinflammatory; laxative; hemostatic Insomnia; sedation; anxiety Chinese medicine “to save the heart” Licorice (Glycyrrhiza glabra) Digestion; ulcers

Goldenseal (Hydrastis canadensis)— turmeric root Kava kava (Piper methysticum) Kyushin

Potential Perioperative Concerns

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Common Uses of and Potential Problems with Herbals and Nutraceuticals—cont’d

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Herbals and Alternative Medicine

Recommended Preoperative Discontinuation of Herbs Preoperative Discontinuation

Aloe Echinacea Ephedra (banned) Garlic Ginkgo Ginseng Kava kava St. John’s wort Valerian

No data No data At least 24 hr At least 7 days At least 36 hr At least 7 days At least 24 hr At least 5 days No data (benzodiazepine-like acute withdrawal possible)

■

Herbal and Dietary Supplement Resources

Organization

Web Address/Phone

Information/Comments

Alternative Medicine Foundation

http://www.herbmed.org

American Botanical Council

www.herbalgram.org

Certificates of analysis

Various sources; available on request from manufacturers or distributors www.epocrates.com http://vm.cfsan.fda.gov/~dms/supplmnt.html 1-888-723-3366 www.fda.gov/medwatch 1-800-FDA-1088 www.cancer.gov

Research publication summaries; MEDLINE links News, information; German Commission E Monographs Amount of active ingredient in given lot; presence of contaminants Alternative medicine tables Report adverse events; safety, industry regulations Report adverse events Search “alternative medicine”

http://nccam.nih.gov 1-888-644-6226

Fact sheets, consensus reports, databases

Epocrates Rx Pro FDA, Center for Food Safety and Applied Nutrition FDA Medwatch NCI, Division of Cancer Prevention and Control, Chemoprevention Program NIH, National Center for Complementary and Alternative Medicine NIH, Office of Alternative Medicine and Office of Dietary Supplements NIH, Office of Dietary Supplements, International Bibliographic Information on Dietary Supplements (IBIDS) PDR for Herbal Medicines Quackwatch US Department of Health and Human Services US Pharmacopoeia

www.altmed.od.nih.gov www.ods.od.nih.gov

Abstracts of peer-reviewed literature

ISBN 1-56363-292-6; Medical Economics Co., Montvale, NJ http://www.quackwatch.com www.healthfinder.gov

General health care; CAM Search “alternative medicine”

www.usp.org

Private organization; quality standards

CAM, complementary and alternative medicine; FDA, Food and Drug Administration; NCI, National Cancer Institute; NIH, National Institutes of Health; PDR, Physicians’ Desk Reference.

Further Reading Abebe W: Herbal medication: Potential for adverse interactions with analgesic drugs. J Clin Pharm Ther 27:391-401, 2002. Adusumilli PS, Ben-Porat L, Pereira M, et al: The prevalence and predictors of herbal medicine use in surgical patients. J Am Coll Surg 198: 583-590, 2004. Anesthesiologists warn: If you’re taking herbal products, tell your doctor before surgery. Information for patients: http://www.asahq.org/ patientEducation/insiderherb.html. Information for doctors: http://www.asahq.org/patientEducation/herbal.html. Ang-Lee MK, Moss J, Yuan C: Herbal medicines and perioperative care. JAMA 286:208-216, 2001. Bent S, Ko R: Commonly used herbal medicines in the United States: A review. Am J Med 116:478-485, 2004.

Borins M: The dangers of using herbs—what your patient needs to know. Postgrad Med 104:91-100, 1998. Chagan L, Ioselovich A, Asherova L, Cheng JWM: Use of alternative pharmacotherapy in management of cardiovascular diseases. Am J Manag Care 8:270-285, 2002. Considerations for anesthesiologists—what you should know about your patients’ use of herbal medicines and other dietary supplements. American Society of Anesthesiologists brochure, 2003. Available at www.ASAhq.org. De Smet PAGM: Herbal remedies. N Engl J Med 347:2046-2056, 2002. Ernst E: The risk-benefit profile of commonly used herbal therapies: Ginkgo, St John’s wort, ginseng, echinacea, saw palmetto, and kava. Ann Intern Med 136:45-53, 2002. Ezzo J, Berman BM, Vickers AJ, et al: Complementary medicine and the Cochrane collaboration. JAMA 280:1628-1630, 1998.

GENERAL ANESTHESIA

Herb

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Fugh-Berman A: Herb-drug interactions. Lancet 355:134-138, 2000. Get the facts—what is complementary and alternative medicine (CAM). National Institutes of Health Center for Complementary and Alternative Medicine. Available at http://nccam.nih.gov/health/ whatiscam/index.htm. Hanania M, Kitain E: Melatonin for treatment and prevention of postoperative delirium. Anesth Analg 94:338-339, 2002. Horlocker TT, Wedel DJ, Benzon H, et al: Regional anesthesia in the anticoagulated patient: Defining the risks. Reg Anesth Pain Med 29:1-11, 2004. Izzo AA, Ernst E: Interactions between herbal medicines and prescribed drugs. Drugs 61:2163-2175, 2001. Kaye AD, Clarke RC, Sabar R, et al: Herbal medicines: Current trends in anesthesiology practice—a hospital survey. J Clin Anesth 12:468-471, 2000. Kaye AD, Kucera I, Sabar R: Perioperative anesthesia clinical considerations of alternative medicines. Anesthesiol Clin North Am 22:125-139, 2004. Kottke MK: Scientific and regulatory aspects of nutraceutical products in the United States. Drug Dev Indust Pharm 24:1177-1195, 1998. Lazarou J, Pomeranz BH, Corey PN: Incidence of adverse drug reactions in hospitalized patients. JAMA 279:1200-1205, 1998. Lee P, Smith I, Piesowicz A, Brenton D: Spastic paraparesis after anaesthesia. Lancet 353:554, 1999. Lin Y, Bioteau AB, Ferrari LR, Berde CB: The use of herbs and complementary and alternative medicine in pediatric preoperative patients. J Clin Anesth 16:4-6, 2004. McGehee DS, Krasowski MD, Fung DL, et al: Cholinesterase inhibition by potato glycoalkaloids slows mivacurium metabolism. Anesthesiology 93:510-519, 2000. Miller LG: Herbal medicinals—selected clinical consideration focusing on known or potential drug-herb interactions. Arch Intern Med 158:2200-2211, 1998. Murphy JM: Preoperative considerations with herbal medicines. AORN J 69:173-183, 1999.

Niggemann B, Gruber C: Side-effects of complementary and alternative medicine. Allergy 58:707-716, 2003. Norred CL: A follow-up survey of the use of complementary and alternative medicines by surgical patients. AANA J 70:119-125, 2002. Norred CL, Brinker F: Potential coagulation effects of preoperative complementary and alternative medicines. Altern Ther Health Med 7:58-67, 2001. Norred CL, Zamudio S, Palmer SK: Use of complementary and alternative medicines by surgical patients. AANA J 68:13-18, 2000. Pinn G: Adverse effects associated with herbal medicine. Aust Fam Physician 30:1070-1075, 2001. Pribitkin E, Boger G: Herbal therapy—what every plastic surgeon must know. Arch Facial Plast Surg 3:127-132, 2001. Rados C: Ephedra ban: No shortage of reasons. FDA Consumer Magazine, July 2004. Available at http//www.fda.gov/fdac/features/2004/ 204_ephedra.html. Rose KD, Croissant PD, Parliament CF, Levin MB: Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic ingestion: A case report. Neurosurgery 26:880-882, 1990. Rosener M, Dichgans J: Severe combined degeneration of the spinal cord after nitrous oxide anaesthesia in a vegetarian. J Neurol Neurosurg Psychiatry 60:354, 1996. Sabar R, Kaye AD, Frost EAM: Perioperative considerations for the patient on herbal medicines. Middle East J Anesthesiol 16:287-314, 2001. Skyschally A, Schulz R, Gres P, et al: Attenuation of ischemic preconditioning in pigs by scavenging of free oxyradicals with ascorbic acid. Am J Physiol Heart Circ Physiol 284:698-708, 2003. Walker R: Criteria for risk assessment of botanical food supplements. Toxicol Lett 149:187-195, 2004. Yuan CS, Wei G, Dey L, et al: Brief communication: American ginseng reduces warfarin’s effect in healthy patients: A randomized controlled trial. Ann Intern Med 141:23-27, 2004.

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Difficult Airway: Cannot Ventilate, Cannot Intubate

40 GENERAL ANESTHESIA

Michael P. Ford and George A. Arndt Case Synopsis A moderately obese man with lung contusions and a closed head injury requires endotracheal intubation on admission to the hospital. Two days later, after neurologic and respiratory recovery, his trachea is extubated. The patient immediately develops respiratory difficulty. Attempts to ventilate the lungs via facemask are unsuccessful. As the patient loses consciousness, laryngoscopy is performed, but the laryngeal structures cannot be visualized. The patient’s oxygen saturation decreases rapidly.

PROBLEM ANALYSIS Definition CANNOT VENTILATE, CANNOT INTUBATE The cannot ventilate, cannot intubate (CVCI) situation is defined as the inability to ventilate the patient’s lungs via facemask despite multiple attempts, and the inability to intubate the patient’s trachea via conventional direct laryngoscopy. In 2003 the American Society of Anesthesiologists (ASA) Task Force on Management of the Difficult Airway updated the applicable practice guidelines. It is hoped that use of the ASA difficult airway algorithm (Fig. 40-1) will reduce the likelihood of adverse outcomes. The CVCI situation can develop quickly but often occurs after repeated attempts at direct laryngoscopy or after a failed rapid-sequence induction or intubation. No more than two or three attempts should be made at direct laryngoscopy, because repeated attempts may worsen the patient’s outcome. The CVCI portion of the ASA algorithm entails the use of rescue options with varying degrees of invasiveness. Before resorting to invasive airway rescue techniques, it is crucial that every effort be made to achieve oxygenation and ventilation through noninvasive techniques, such as optimal facemask ventilation (two-person mask technique, ensuring adequate jaw thrust and facemask seal, with an oral or nasal airway [or both]) or supraglottic ventilation using a laryngeal mask airway. Although potentially lethal, the CVCI situation is, fortunately, a rare occurrence. El-Ganzouri and colleagues evaluated the airways of 10,507 consecutive patients and found that 107 (1%) had a poor laryngoscopic view (grade 4—neither laryngeal structures nor epiglottis visualized), 535 (5.3%) patients had a grade 3 laryngeal view, and only 8 patients (0.07%) could not be adequately ventilated using a facemask. DIFFICULT AIRWAY A difficult airway is defined as a clinical situation in which a conventionally trained anesthesiologist experiences difficulty

with facemask ventilation of the airway, difficulty with tracheal intubation, or both. Intubation is difficult when multiple attempts, maneuvers, blades, and endoscopies are required. Some patients with a difficult airway for mask ventilation may be relatively easy to intubate, and vice versa. Reasons for the majority of airway complications and management failures are listed in Table 40-1. DIFFICULT FACEMASK VENTILATION Difficult facemask ventilation occurs when positive-pressure ventilation, by an unassisted anesthesiologist, fails to maintain oxygen saturation above 90% (with an inspired oxygen concentration of 100%) or the ventilation effort fails to prevent or reverse signs of inadequate gas exchange. Inadequate facemask ventilation is secondary to inadequate facemask seal, excessive gas leak, or excessive resistance to the ingress or egress of gas. Signs of inadequate facemask ventilation are listed in Table 40-2. The incidence of difficult facemask ventilation is approximately 5%. The incidence of difficult ventilation, despite optimization of the mask airway using supraglottic adjuncts, is less than 0.5%. All patients should be oxygenated before the induction of general anesthesia; doing so decreases the incidence of and prolongs the time interval to oxygen desaturation when facemask ventilation is inadequate or not attempted (rapidsequence induction). In pediatric and uncooperative patients, however, the effectiveness of preoxygenation may be limited. In obese patients, preoxygenation using continuous positive airway pressure and the reverse Trendelenburg position lengthens the time to decreased oxygen saturation after the onset of apnea or inadequate ventilation. Patient factors associated with difficult facemask ventilation, as well as some suggestions for dealing with them, are listed in Table 40-3. Multiple factors indicate a high likelihood of difficult facemask ventilation. Placing a laryngeal mask airway permits adequate positive-pressure ventilation to occur in most patients and should be used early when difficulty with facemask ventilation (or difficult intubation) is encountered. 159

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1. Assess the likelihood and clinical impact of basic management problems: A. Difficult ventilation B. Difficult intubation C. Difficulty with patient cooperation or consent D. Difficult tracheostomy 2. Actively pursue opportunities to deliver supplemental oxygen throughout the process of difficult airway management 3. Consider the relative merits and feasibility of basic management choices: A.

Awake intubation

vs.

Intubation attempts after induction of general anesthesia

B.

Noninvasive technique for initial approach to intubation

vs.

Invasive technique for initial approach to intubation

C.

Preservation of spontaneous ventilation

vs.

Ablation of spontaneous ventilation

4. Develop primary and alternative strategies: A.

AWAKE INTUBATION

Airway approach by noninvasive intubation

Succeed*

Cancel case

Invasive airway access(b)*

B.

INTUBATION ATTEMPTS AFTER INDUCTION OF GENERAL ANESTHESIA

Initial intubation attempts successful*

From this point onward consider: 1. Calling for help 2. Returning to spontaneous ventilation 3. Awakening the patient

FAIL

Consider feasibility of other options(a)

Initial intubation attempts UNSUCCESSFUL

Invasive airway access(b)*

FACEMASK VENTILATION ADEQUATE

FACEMASK VENTILATION NOT ADEQUATE

Consider / Attempt LMA

NONEMERGENCY PATHWAY Ventilation adequate, intubation unsuccessful

LMA ADEQUATE*

LMA NOT ADEQUATE OR NOT FEASIBLE

EMERGENCY PATHWAY Ventilation not adequate, intubation unsuccessful Alternative approaches to intubation(c)

Successful intubation*

FAIL after multiple attempts

IF BOTH FACEMASK AND LMA VENTILATION BECOME INADEQUATE

Call for help

Emergency noninvasive airway ventilation(e)

Successful ventilation*

Invasive airway access(b)*

Consider feasibility of other options(a)

Awaken patient(d)

FAIL

Emergency invasive airway access(b)*

* Confirm ventilation, tracheal intubation, or LMA placement with exhaled CO2. a. Other options include (but are not limited to): surgery utilizing facemask or LMA anesthesia, local anesthesia infiltration or regional nerve blockade. Pursuit of these options usually implies that mask ventilation will not be problematic. Therefore, these options may be of limited value if this step in the algorithm has been reached via the Emergency Pathway. b. Invasive airway access includes surgical or percutaneous tracheostomy or cricothyrotomy. c. Alternative noninvasive approaches to difficult intubation include (but are not limited to) use of different laryngoscope blades, LMA as an intubation conduit (with or without fiberoptic guidance), fiberoptic intubation, intubating stylet or tube changer, light wand, retrograde intubation, and blind oral or nasal intubation. d. Consider repreparation of the patient for awake intubation or canceling surgery. e. Options for emergency noninvasive airway ventilation include (but are not limited to) rigid bronchoscope, esophageal-tracheal Combitube ventilation, or transtracheal jet ventilation.

Figure 40–1 ■ American Society of Anesthesiologists difficult airway algorithm. LMA, laryngeal mask airway. (From Practice guidelines for management of the difficult airway—an updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology 98:1269-1277, 2003.)

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Reasons for Airway Complications and Management Failures

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Patient Factors Associated with Difficult Facemask Ventilation and Suggested Solutions

Facial Hair Place adhesive plastic sheet, with mouth and naris openings, over facial hair to achieve better mask seal Place oral, nasal, or laryngeal mask airway early

Edentulous Consider leaving dentures in place until laryngoscopy to improve facemask seal Place laryngeal mask airway early

Body Mass Index >26

DIFFICULT INTUBATION Difficult intubation occurs when endotracheal intubation requires multiple attempts. The ASA Task Force defines difficult intubation as more than three attempts at conventional direct laryngoscopy or more than 10 minutes to achieve intubation. Difficult laryngoscopy is the inability to visualize any portion of the vocal cords after multiple attempts using conventional rigid laryngoscopy. The incidence of difficult direct laryngoscopy (more than two attempts) is between 0.5% and 2%. The first attempt must be optimized, including adequate depth of anesthesia and muscle relaxation, proper positioning of the head and neck, use of a styletted tube, and application of laryngeal manipulation. External laryngeal pressure or manipulation by the laryngoscopist’s right hand (or by an assistant) may convert a grade 3 visualization of the larynx to a grade 2 (Fig. 40-2). Straight laryngoscope blades can be efficacious with “anterior” anatomy. Alternative, specialized laryngoscopes should be employed only by those experienced with their use. No more than two or three attempts should be made at direct laryngoscopy, because repeated attempts may worsen the patient’s outcome (e.g., conversion of a can-ventilate to a cannot-ventilate situation, or laryngeal edema causing glottic airway obstruction after tracheal extubation). Facemask ventilation must occur between attempts, and direct laryngoscopy must be stopped if oxygen saturation falls below 90% to 92% (maintenance of oxygenation takes precedence). The most experienced anesthesiologist available should perform the final attempt at direct laryngoscopy.

Table 40–2

■

Signs of Inadequate Facemask Ventilation

Insufficient or absent chest movement Absent or inadequate breath sounds Audible signs of airway obstruction, gastric air insufflation, or gastric dilatation Inadequate or decreasing oxygen saturation Cyanosis Absent, inadequate, or elevated end-tidal carbon dioxide Absent or inadequate exhaled gas flow (spirometry) Hemodynamic consequences of hypercarbia or hypoxemia (e.g., tachycardia, hypertension, dysrhythmias)

Preoxygenate patient with continuous positive airway pressure and use 20- to 30-degree reverse Trendelenburg position Increases time interval to desaturation after onset of apnea or difficult mask ventilation Reverse Trendelenburg “unloads” diaphragm, improving pulmonary compliance Use laryngeal mask airway early for positive-pressure mask ventilation

Snoring and Obstructive Sleep Apnea Place oral, nasal, or laryngeal mask airway early

Age >55 yr History of Smoking Supraglottic, Glottic, and Subglottic Pathology or Stridor Consider prospective placement of translaryngeal jet ventilation catheter Strongly consider awake airway management Avoid sedation if stridor is present

Bronchospasm (active or at risk for) Nebulize with bronchodilator before induction

Recognition The cause of the majority of difficult endotracheal intubations is limited oropharyngeal space, decreased atlantooccipital extension, decreased pharyngeal space, or decreased submandibular compliance. Recognition of potentially difficult direct laryngoscopy and endotracheal intubation is facilitated by a systematic search for abnormalities during the preoperative airway examination (Table 40-4). Unfortunately, airway examination findings have low and variable sensitivity and marginal specificity; however, worrisome findings, particularly in combination, suggest a difficult intubation. A Mallampati class higher than II (Fig. 40-3) in association with other airway findings signifies potential difficulty during traditional direct laryngoscopy. Reviewing the patient’s prior anesthetic history and previous records of airway management (if available) is extremely helpful when formulating the airway management plan. Anesthesiologists must accurately document the ease or difficulty of facemask ventilation, laryngoscopy attempts and blades used, the laryngoscopic view obtained (see Fig. 40-2), how intubation was ultimately achieved, and any special maneuvers or devices used. Assume high reliability if the patient selfreports a difficult airway. Consider any systemic diseases or congenital abnormalities that require special attention during airway management.

GENERAL ANESTHESIA

Inaccurate or incomplete preoperative airway assessment Incorrect prediction of: Easy mask airway Routine direct laryngoscopy-guided intubation Uncomplicated extubation Unwillingness to abandon failed airway management plan Failure to call for help early, when difficult airway is first apparent Incomplete preparation of backup plan Deterioration of performance under stress Failure in judgment

Difficult Airway: Cannot Ventilate, Cannot Intubate

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Figure 40–2 ■ Laryngoscopic view grading systems. A, Cormack-Lehane system: grade 1, visualization of the entire laryngeal aperture; grade 2, visualization of only the posterior portion of the laryngeal aperture; grade 3, visualization of only the epiglottis; grade 4, visualization of only the soft palate. B, Modified grading system of view at direct laryngoscopy: grade 1, most of cords visible (direct intubation); grade 2A, posterior cord visible (direct intubation); grade 2B, only arytenoids visible (indirect intubation); grade 3A, epiglottis visible and liftable (indirect intubation); grade 3B, epiglottis adherent to pharynx (specialist required for intubation); grade 4, no laryngeal structures seen (specialist required for intubation). (A, From Cormack RS, Lehane J: Difficult tracheal intubation in obstetrics. Anaesthesia 39:1105, 1984. B, From Cook TM: A new practical classification of laryngeal view. Anaesthesia 55:274-279, 2000.)

Laryngoscope

Epiglottis

A

1

2

3

4

Grade 1

B

Grade 2A

Grade 2B

Easy

Grade 3A

Restricted

ENDOTRACHEAL INTUBATION INTRODUCERS AND INTUBATING CATHETERS A malleable tracheal tube introducer (gum-elastic bougie [GEB], length 60 cm) or an intubating catheter can be placed blindly and gently under the epiglottis (or directed through partially visible, posterior vocal cords) into the trachea during one of the laryngoscopic attempts. The anesthesiologist will not see the GEB entering the larynx with a grade 3 or 4 laryngoscopic view. Tactile “clicking” may be felt as the angled (about 60 degrees), anteriorly directed tip of the GEB passes over (hits against) the tracheal rings. If clicks are not perceived, the GEB should be gently advanced to a maximum depth of 45 cm (in an adult patient). If distal hold-up is sensed, such as slight resistance to further advancement, the GEB is likely “caught up” in the bronchial tree, and the patient may cough if not completely paralyzed. If neither clicks, hold-up, nor coughing is evoked, the GEB is probably in the esophagus and should be removed. A second attempt at passing the GEB blindly into the trachea can be considered, unless there is a grade 4 laryngeal view or the epiglottis

Grade 3B

Grade 4

Difficult

cannot be elevated (the epiglottis is “adherent” to the pharynx). If the GEB is believed to be in the trachea, an internally lubricated endotracheal tube (ETT) is advanced (“railroaded”) over the GEB. Leaving the laryngoscope blade in the mouth and rotating the ETT 90 degrees counterclockwise facilitates ETT advancement (orientation of the Murphy eye at the 12 o’clock position prevents the ETT tip from hanging up on the right vocal cord or arytenoids during passage). Tracheal location is confirmed by auscultation of equal bilateral breath sounds and sustained end-tidal carbon dioxide waveforms. The rule is, “if in doubt, take the ETT out,” unless immediate flexible bronchoscopy via the ETT confirms a tracheal location. Optimal results achieving intubation with the GEB are dependent on experience and regular use. DIFFICULT EXTUBATION The risks for difficult facemask ventilation and difficult intubation, as well as other events, herald difficult extubation. Patients with a difficult airway should meet the usual criteria for extubation and be fully awake. They also should cough

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Airway Examination Predictors of Difficult Direct Laryngoscopy and Endotracheal Intubation

Interincisor Gap

Length of Upper Incisors Long incisors impede alignment of oral and pharyngeal axes during direct laryngoscopy Relatively long, protruding upper incisors are worrisome Mallampati Oropharyngeal Classification (see Fig. 40-3) With Mallampati class I or II, tongue should be easily retracted from the line of site during direct laryngoscopy Mallampati class >II is worrisome

Mandibular Space With hyomental and thyromental distances (estimates of mandibular space) >6 and 7 cm, respectively, larynx should be sufficiently posterior for favorable line of sight with direct laryngoscopy Distance <3 ordinary fingerbreadths (5 cm) is worrisome

Length and Thickness of Neck Short, thick neck reduces ability to align upper airway axes during direct laryngoscopy In obese patients, large neck circumference and Mallampati class >II are worrisome

Head and Neck Range of Motion Atlanto-occipital (AO) extension or neck flexion on chest of <35 degrees predicts difficult direct laryngoscopy; this amount of AO extension and neck flexion is required for proper alignment of oral, pharyngeal, and laryngeal axes Obese body habitus may preclude optimal alignment of oral, pharyngeal, and laryngeal axes Direct laryngoscopy in obese patients is facilitated when head, neck, and shoulders are elevated (“stacked”), bringing chin level with sternum; fiberoptic bronchoscopy intubation is rarely necessary with proper positioning Higher Mallampati class and large neck circumference are reliable predictors of difficult intubation in obese patients Inability to touch chin to chest is worrisome

Maxillary-Mandibular Overbite (Buck Teeth) Buck teeth reduce the ability to align oral and pharyngeal axes during direct laryngoscopy

Mandibular Translation Ability to protrude lower jaw by more than 1 cm often predicts good direct laryngoscopic view Ability to touch bottom incisors to the upper lip–skin border is reassuring

Mandibular Space Compliance Worrisome findings include stiffness, induration, and presence of mass

Palate Configuration Narrow or highly arched palate reduces oropharyngeal volume and ability to visualize glottis with both laryngoscope blade and endotracheal tube in mouth

Class I

Class II

Class III

Class IV

Figure 40–3 ■ Mallampati classification. With the patient seated and the head in the neutral position, the patient is asked to open the mouth as wide as possible and to protrude the tongue out as far as possible (the patient should not phonate during this evaluation). Class I, soft palate, fauces, uvula, and anterior and posterior tonsillar pillars are visible; class II, soft palate, fauces, and uvula are visible; class III, soft palate and base of uvula are visible; class IV, only hard palate is visible. (Modified from Mallampati S, Gatt S, Gugino L, et al: A clinical sign to predict difficult tracheal intubation: A prospective study. Can J Anaesth 32:429, 1985; and Samsoon GLT, Young JRB: Difficult tracheal intubation: A retrospective study. Anaesthesia 42:487, 1987.)

GENERAL ANESTHESIA

If distance between upper and lower incisors is less than 3-4 cm, direct laryngoscopy may be difficult because of: Insufficient space for blade insertion and blade “traction” without dental injury Less room for endotracheal tube passage and direction Possible obscured line of sight to glottic opening

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Factors to Consider When Formulating an Extubation Strategy

Relative advantages of awake extubation vs tracheal extubation before return of consciousness Was intubation difficult? Was facemask ventilation difficult? Is risk for aspiration high? Upper airway edema or bleeding may have adverse impact on effective ventilation after extubation Bleeding, tissue edema, or nerve injury can cause airway obstruction after neck surgery Edema risk may be higher with recent neck infection or prior irradiation Direct or indirect trauma to peritracheal, laryngeal, and supraglottic structures Manipulation during surgery increases potential for airway obstruction Edema may occur after difficult or multiple laryngoscopies but not be apparent until after extubation Recurrent laryngeal nerve injury Predetermined plan for airway management if patient is unable to maintain adequate ventilation after removal of endotracheal tube Extubation over previously inserted endotracheal tube exchange catheter Functions as a guide for rapid reintubation Can facilitate ventilation if tube exchanger has a lumen Extubation over flexible fiberoptic bronchoscope Endotracheal tube can be readvanced into trachea if necessary Trachea and glottic and supraglottic structures can be examined for abnormalities as bronchoscope is slowly removed Bronchoscope removal can be stopped if significant airway concerns are identified Bronchoscope may be readvanced into trachea, with subsequent passage of “loaded” endotracheal tube Wire can be inserted through fiberoptic bronchoscope suction channel before bronchoscope’s gradual removal to serve as guide for reintroduction of bronchoscope or airway exchange catheter into trachea

and phonate during ETT cuff deflation. Patients at high risk should have the ETT removed over an intubating stylet (bougie or exchange catheter), guidewire, or fiberoptic bronchoscope, with an experienced surgeon (for cricothyrotomy and tracheostomy) at the bedside. Factors to consider in formulating an extubation strategy are listed in Table 40-5.

Risk Assessment Risk assessment for a potentially difficult airway is multifactorial (Table 40-6). Reduction of risk with the CVCI situation begins with a thorough assessment of the patient’s airway before induction, predicting which patients may be difficult or impossible to ventilate via facemask (see Table 40-2) or intubate (see Table 40-4).

Table 40–6

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Risk Assessment of the Difficult Airway

Physical examination predictors suggestive of difficult facemask or supraglottic ventilation Physical examination predictors suggestive of difficult intubation Preexisting medical conditions and congenital abnormalities Actual difficulties with mask ventilation or laryngoscopy-guided intubation How was effective ventilation achieved? How was intubation achieved? Preexisting or current airway pathology Airway infection Tumor; prior head or neck surgery or radiation treatment Supraglottic or subglottic edema Presenting injuries of the airway, facial bones, and cervical spine Postoperative effects on airway From prior surgery From just-completed surgical procedure From multiple laryngoscopic attempts or traumatic intubation

Implications The inability to provide adequate ventilation to a patient may rapidly result in disability or death. ASA closed claims analysis revealed that the most common mechanisms of adverse respiratory events were inadequate ventilation, difficult intubation, and esophageal intubation. The airway sites most frequently injured were the larynx (33%), pharynx (19%), and esophagus (18%). Injuries to the trachea and esophagus were more commonly associated with difficult endotracheal intubation. Injuries to temporomandibular joint and the larynx were more frequently associated with intubations that were classified as “nondifficult.” Injuries to the esophagus were more devastating and resulted in larger payments to the plaintiffs than did claims for injuries to other locations. Although the CVCI situation is rare, the consequences can be devastating.

MANAGEMENT Optimal airway management requires recognition of the causes of a difficult airway and familiarity with the methods to secure it. Goals include maintenance of adequate oxygenation, ventilation, and protection of the airway from aspiration. Many airway management devices and techniques are available. The ASA difficult airway algorithm (see Fig. 40-1) favors no single method. It is unlikely that an individual anesthesiologist will be adept at all techniques and devices; each anesthesiologist should use the airway techniques at which he or she is adept. All anesthesiologists must have clinical familiarity with a number of airway devices and techniques, however, including (but not limited to) fiberoptic intubation, a method for emergency nonsurgical ventilation that allows blind supraglottic placement (laryngeal mask airway or esophageal-tracheal Combitube), and a method for emergency nonsurgical ventilation that allows subglottic

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From Sanchez A, Trivedi NS, Morrison DE: Preparation of the patient for awake intubation. In Benumof JL (ed): Airway Management: Principles and Practice. St. Louis, Mosby, 1996, pp 159-182.

placement (transtracheal jet ventilation or percutaneous dilatational cricothyrotomy). If there is any reason to believe that conventional facemask or supraglottic ventilation may be unsuccessful, awake management of the airway is indicated (Table 40-7). Recently, Rosenblatt published a decision tree for organizing preoperative airway information (Fig. 40-4). This approach asks a series of questions regarding management of the airway. A positive answer leads the operator to the next question, and a negative answer directs the clinician to the appropriate location in the ASA algorithm (see Fig. 40-1). Predicting specific difficulties with airway management prospectively (preoperatively) and integrating this information into the airway approach strategy may avoid the need to use the emergency branches of the ASA algorithm (e.g., encourage the anesthesiologist to use awake intubation initially rather than intubation after induction of general anesthesia, apnea, and paralysis). The CVCI situation, once recognized, must be managed quickly and decisively. “Rapid” options for management include the following: ● ● ● ● ●

Laryngeal mask airway Esophageal-tracheal Combitube Laryngeal tube Transtracheal jet ventilation Cricothyrotomy

The first three methods of establishing ventilation are supraglottic ventilatory mechanisms, and the latter two are subglottic ventilatory mechanisms. Only the most invasive method, cricothyrotomy with insertion of a cuffed airway device, is capable of definitively securing the airway, allowing positive-pressure ventilation, and preventing aspiration

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1) Must the airway be managed? (Is airway control necessary?) • If NO, is regional anesthesia or monitored anesthesia care an acceptable alternative for the patient, surgeon, and anesthesiologist? If NOT, continue on to question 2. – Regional anesthesia doesn’t always preclude airway management. 2) Is there potential for a difficult laryngoscopy? • If NO, enter ASA-DAA @ Intubation Attempts After Induction of General Anesthesia. 3) Can supraglottic ventilation be utilized? (LMA or Combitube for rescuing the airway, if the cannot-ventilate, cannot-intubate scenario occurs). • If NO, enter ASA-DAA @ Awake Intubation. 4) Is the stomach empty? (Is there an aspiration risk?) • If NO, enter ASA-DAA @ Awake Intubation. 5) Will the patient tolerate an apneic period if unable to ventilate? • If NO, enter ASA-DAA @ Awake Intubation. • If YES, enter ASA-DAA @ Intubation Attempts After Induction of General Anesthesia with supraglottic airway/ventilation device present. A “NO” answer to any of the AAA questions directs the anesthesiologist to a “root point” of the American Society of Anesthesiologists−Difficult Airway Algorithm (ASA-DAA). A “YES” answer leads the anesthesiologist to the subsequent question. The AAA does not suggest particular procedures or specific pathways, but rather is meant to organize the anesthesiologist’s own beliefs and choices along the lines of the ASA-DAA. Figure 40–4 ■ Airway approach algorithm (AAA). LMA, laryngeal mask airway. (Modified from Rosenblatt W: The airway approach algorithm: A decision tree for organizing preoperative airway information. J Clin Anesth 16:312-316, 2004.)

of gastric material. Regardless of the temporary measures taken to ventilate a patient in the CVCI situation, efforts should be made to definitively secure the airway as soon as possible. The following techniques are commonly employed in managing the difficult airway.

Fiberoptic Bronchoscopy and Endotracheal Intubation Many anesthesiologists prefer to use fiberoptic bronchoscopy (FOB) to manage a known or suspected difficult airway and for an unrecognized difficult intubation when supraglottic ventilation is achieved and maintained. FOB can be performed in awake or anesthetized patients. Success requires careful patient selection and preparation, as well as sufficient operator skill and experience. The decision to perform the procedure in an awake or sedated patient versus after the induction of general anesthesia depends on the patient’s ability to cooperate and the ability to maintain ventilation and oxygenation. Fiberoptic intubation under general anesthesia should be considered only if the anesthesiologist believes that adequate ventilation and oxygenation can be readily maintained. It is often better to maintain spontaneous ventilation and consciousness, especially in a patient with a difficult airway. INDICATIONS

AND

CONTRAINDICATIONS

Tumors, abscesses, maxillofacial trauma, and suspected or actual cervical spine injuries are indications for FOB intubation, provided the airway can be safely navigated.

GENERAL ANESTHESIA

History of difficult intubation Anticipated difficult airway Prominent protruding teeth Small mouth opening Narrow mandible Micrognathia Macroglossia Short, muscular neck Very long neck Limited neck extension Congenital airway anomalies Obesity Known airway pathology Known airway malignancy Upper airway obstruction Trauma Facial Upper airway Cervical spine Anticipated difficult mask ventilation Severe risk of aspiration Respiratory failure Severe hemodynamic instability

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Other indications include the following situations: (1) neck extension for optimal alignment of the oral, pharyngeal, and laryngeal axes is difficult or ill advised; (2) difficult direct laryngoscopy is predicted on the basis of airway risk assessment; (3) risk of aspiration is high; (4) patient who cannot tolerate a period of apnea; and (5) patient with an injury to or near the airway. Absolute contraindications to FOB intubation include (1) high risk of dislodging friable tissue or rupturing an abscess, (2) bleeding or swelling that prevents visualization of airway structures or passage of the bronchoscope, and (3) life-threatening airway obstruction or hemodynamic instability (lack of time). Relative contraindications include (1) copious secretions despite an anticholinergic drying agent, (2) friable tissues that cannot be navigated despite careful manipulation, (3) edema of the pharynx or tongue, (4) hematoma, (5) tracking infections, and (6) infiltrating masses. PATIENT PREPARATION Nasal FOB intubation is generally easier to perform than oral FOB intubation because the angle of curvature of the inserted ETT naturally approximates that of the patient’s upper airway. The ETT serves as a channel for the bronchoscope, and the gag reflex is less pronounced with the nasal approach. The sitting position is preferred to the supine position because it facilitates passage of the bronchoscope and drainage of secretions. Extension of the cervical spine (if not contraindicated) provides the optimal position for the performance of fiberoptic laryngoscopy. For awake or sedated patients, nasal or oral oxygen is administered, monitors are applied, and an anticholinergic drying agent (to increase the effectiveness of topical anesthetics and decrease secretions) and sedation are administered, according to the anesthesiologist’s preferences. Good topical anesthesia (with adequate time allowed) is essential for awake techniques. The naris and nasopharynx are anesthetized with cocaine or lidocaine-phenylephrine, if vasoconstrictors are not contraindicated. The superior laryngeal nerve (innervates the epiglottis, aryepiglottic folds, and laryngeal mucosa) is blocked by the advancement of cotton-tipped applicators into the pyriform fossa. The oropharynx, base of tongue, and larynx are sprayed with a topical anesthetic, or the patient can gargle with a topical anesthetic. A lidocaine and phenylephrine mixture can be nebulized via a facemask; lidocaine can also be sprayed onto the vocal cords and into the tracheal lumen via the bronchoscope as they are encountered or viewed. The use of transtracheal lidocaine, superior laryngeal nerve blocks, and glossopharyngeal blocks is optional. Insufflation of oxygen through the suction port of the bronchoscope serves as a defogging mechanism, blows secretions away from the tip of the bronchoscope, and provides supplemental oxygen during the procedure. When performing FOB in apneic patients, transnasal jet ventilation, via a nasal airway, often effectively oxygenates the patient for a short time.

side of the nose has a larger “passage,” which can be determined with trials of nasal airways of progressively increasing diameters. “Softened” ETTs (warmed in warm water) usually pass more easily. The largest ETT possible should be used— 8 mm internal diameter in adults, if a 34 French soft nasal airway readily passes. The ETT is positioned proximally over the bronchoscope. The most patent naris is intubated first, preventing it from exiting the Murphy eye of the ETT during bronchoscope advancement. If the ETT is inserted through the naris first, the bronchoscope should be visualized following the stripe on the ETT to the beveled tip. This prevents passage of the bronchoscope through the Murphy eye. Lidocaine is sprayed via the bronchoscope on or in airway structures as they are identified. Inflating the cuff of the ETT can create more space in the pharynx and directs the FOB channel (ETT) anteriorly. The bronchoscope is advanced until the epiglottis or glottis is identified, maneuvered past the glottis into the trachea, and advanced to the carina. Subsequently, the ETT is advanced into the trachea. The ETT may hang up on supraglottic structures as it is advanced over the bronchoscope. Rotation of the ETT 90 degrees counterclockwise may facilitate passage. The appropriate depth of the ETT can be determined by visualizing the distance between the carina and the tip of the ETT as the bronchoscope is removed. If the ETT does not advance or the bronchoscope cannot easily be removed from the ETT, both must be removed together (to avoid bronchoscope damage), and FOB intubation should be reattempted, possibly with a smaller ETT. Factors affecting the success of FOB-guided intubation are summarized in Table 40-8. Oral Intubation. Oral FOB intubation is well suited for apneic or anesthetized patients, as well as for awake or sedated patients who are well anesthetized topically. Preparation of the nasal passageway is unnecessary, and the oral route can be used in patients when the nasal route is contraindicated. Neck extension, if not contraindicated, reduces the angle between the oropharynx and larynx, facilitating advancement of the bronchoscope into the trachea. The bronchoscope can be advanced through a fiberoptic-compatible oral airway (FCOA) or advanced above and around a “pulled-out” or protruded tongue. The FCOA serves as a channel for the bronchoscope, prevents “bite” damage to it, and facilitates midline positioning by mechanically guiding the bronchoscope (Fig. 40-5). An FCOA with an “anterior channel” may be better at directing the bronchoscope toward the glottic opening. Performing a jaw thrust or pulling the tongue forward can be helpful. Oral FOB intubation can readily be accomplished by using a laryngeal mask as the channel for the bronchoscope. Ventilation is continuous via the laryngeal mask airway (LMA), either spontaneously or by positive pressure, as the bronchoscope is passed through a bronchoscope port adapter, through the LMA ventilating tube, and into the trachea.

TECHNIQUES

Blind Nasal Intubation

Nasal Intubation. Care must be taken to minimize the risk of epistaxis. Nasal intubation is contraindicated in patients with coagulation disorders, who cannot tolerate vasoconstrictors, and with facial or basilar skull trauma. Often one

Blind nasal intubation is much less stimulating than direct laryngoscopy. The patient must breathe spontaneously and be adequately sedated and cooperative. Topical anesthesia and nasal vasoconstriction precede the insertion of a

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Factors Affecting Successful Fiberoptic Bronchoscopy and Intubation

Factor

Comments and Possible Solutions

Patient Selection Frequent suctioning and topical vasoconstrictor will help reduce small amounts of bleeding Rarely a problem with elective FOB but may be in trauma or emergency situations Titrate sedation as indicated Amount of sedation inversely proportional to degree of airway difficulty Inadequate time to safely anesthetize patient and intubate trachea Skill and experience can decrease FOB intubation time

Unstable patient

Patient Preparation Topical anesthesia

Reduce and remove secretions so topical agents are in contact with mucosa Allow sufficient contact time Spray lidocaine (via suction port of bronchoscope) onto structures as they are identified Nerve blocks are often unnecessary Administer anticholinergic drying agent and vasoconstrictor Suction oral pharynx with tonsil tip suction before starting Connect O2 source to suction port of bronchoscope to blow away secretions Use nasal prongs or mask O2 during FOB Maintain spontaneous ventilation Attach O2 source to suction port of bronchoscope Instruct patient to breathe during procedure Avoid excessive sedation Ventilate with LMA Use LMA as channel or conduit for bronchoscope Jet-ventilate via nasal airway

Secretions, blood Decreased O2 saturation

Endoscopist Experience Abnormal anatomy

Full knowledge of normal anatomy necessary to negotiate abnormal anatomy with difficult airway Maintain spontaneous ventilation Use nasal route; allow sufficient laryngeal space Use channel for bronchoscope (ETT, FCOA) Awake patient: instruct patient to pant, say “ahh,” or stick out tongue Unconscious or anesthetized patient: jaw thrust, pull out tongue, use FCOA, use nasal route Warm and wipe bronchoscope lens with dilute detergent before use Insufflation of O2 via suction port decreases fogging Lubricate bronchoscope If tube becomes hung up, try rotating it counterclockwise 90 degrees May exit Murphy eye of ETT Remove tube and bronchoscope as unit and try again

Large, floppy epiglottis Fogging of objective Inability to advance ETT Inability to remove bronchoscope

ETT, endotracheal tube; FCOA, fiberoptic-compatible oral airway; FOB, fiberoptic bronchoscopy; LMA, laryngeal mask airway; O2, oxygen.

A

B

Figure 40–5 ■ Fiberoptic-compatible oral airways (FCOAs). A, Two FCOAs, with anterior versus posterior channels compared. On the left is the Williams airway intubator, with an anterior channel; on the right is a Luomanen FCOA, with a posterior channel. Note that an anterior channel may offer more immediate entry into an anteriorly oriented glottis. B, Berman and Ovassapian oral intubating airways. (A, From Atlas GM: A comparison of fiberoptic-compatible oral airways. J Clin Anesth 16:66-73, 2004. B, From Stackhouse R: Fiberoptic airway management. Anesthesiol Clin North Am 20:933-951, 2002.)

GENERAL ANESTHESIA

Oropharyngeal bleeding Uncooperative patient

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Endotracheal Tube Malpositioning and Corrective Measures during Blind Nasal Intubation

Table 40–10

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Lighted Stylet–Assisted Oral Intubation

Indications Vocal cords outside larynx Obstructed tube passage despite good detection of breath sounds Can often be corrected by gentle rotation Vallecula Often causes midline supralaryngeal bulge in neck Retract tube a few centimeters, followed by gentle pressure just above larynx or slight flexion of head Left or right pyriform fossa Often results in corresponding lateral bulge in neck Gently use tongue depressor or laryngoscope blade to see if endotracheal tube is in midline Correct this problem by: Displacing patient’s larynx slightly in direction of bulge Rotating tube Moving head toward side of displacement Using lighted stylet to transilluminate endotracheal tube tip location Esophagus Pull back endotracheal tube and try again

“warmed” ETT. The ETT is gently passed and advanced. Breath sounds (or air movement) heard through the ETT become louder as the tube tip nears the glottis. Tracheal passage is facilitated during patient inspiration. Palpation bilaterally under the patient’s mandible may detect passage of the ETT off the midline and guide redirection by rotation of the ETT. Other ETT tip locations outside the trachea and corrective measures that may enable successful blind nasal intubation are listed in Table 40-9. Multiple blind passages must be avoided. Bleeding can compromise subsequent attempts at FOB intubation or direct laryngoscopy. Switch to FOBguided intubation if blind passage is not successful.

Lighted Stylet Oral Intubation The lighted stylet (LS) or light wand is sometimes used for routine elective and difficult endotracheal intubations. The LS is inserted into the lumen of the ETT until its tip is within 5 mm from the end of the ETT. The LS and distal ETT tip are bent or curved about 90 degrees and advanced during tongue retraction (the LS tip must point anteriorly). Light transilluminates through the anterior neck tissue (darken the room if necessary), facilitating redirection of the ETT-LS tip toward and into the trachea. Once past the glottis, the LS transilluminates brightly through the trachea, producing a distinct jack-o’-lantern effect (well-circumscribed glow through the anterior neck if in the trachea; diffuse glow if in the esophagus). The ETT is stabilized while the LS is removed. Transillumination may be inadequate in obese patients. Indications for LS intubation and contraindications to blind passage of the LS are listed in Table 40-10.

Elective, asleep, oral intubation Patients with the following: Restricted movement of cervical spine (e.g., cervical spine instability) Limited mouth opening Capped teeth Severe overbite Poor dentition Facial trauma Direct “blind” passage of endotracheal tube through intubating laryngeal mask airway To facilitate intubation using direct laryngoscopy Difficult airway alternative in experienced hands Situations in which a fiberoptic bronchoscope is unavailable Situations in which fiberoptic bronchoscopy is difficult to perform (e.g., secretions, blood)

Contraindications Airway pathology Foreign body Laryngeal fracture Pharyngeal mass Retropharyngeal abscess

useful for emergency airway management unless the cause of airway obstruction is glottic or subglottic in nature. The recently introduced laryngeal tube has also been used to manage the difficult airway. LARYNGEAL MASK AIRWAY The LMA plays an important role in the management of the difficult airway, serving as an airway ventilating device, a conduit for achieving endotracheal intubation, or both. The incidence of the cannot-ventilate situation decreased dramatically after the adoption and widespread use of the LMA, which is now an integral part of the ASA difficult airway algorithm (see Fig. 40-1). The LMA is blindly inserted into the hypopharynx until the leading edge of the mask is behind the arytenoids and cricoid cartilage and lies just above the upper esophageal sphincter. The LMA “mask” is inflated to form a low-pressure seal (20 cm H2O or less; about 30 cm H2O with a ProSeal LMA) around the laryngeal inlet. Spontaneous or controlled positive-pressure ventilation can be used. Disadvantages of the LMA include the following: ●

●

●

●

SUPRAGLOTTIC AIRWAY DEVICES Many supraglottic airway devices are available, and they have changed our approach to airway management. Most, if not all anesthesiologists commonly use the laryngeal mask. Both the LMA and the esophageal-tracheal Combitube are

It is a supraglottic device and may be ineffective in the presence of glottic or subglottic pathology. It does not protect the trachea against pulmonary aspiration of gastric contents. It may be placed over the esophageal inlet, resulting in gastric distention, especially when positive-pressure ventilation is employed. It may not be able to achieve adequate airway sealing pressures in patients with poor pulmonary compliance who require positive-pressure ventilation.

The aperture of a properly positioned classic LMA aligns itself anatomically with the glottis and can serve as a conduit to endotracheal intubation. An FOB wire-guided

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exchange technique for achieving endotracheal intubation via a classic laryngeal mask is as follows: ● ●

●

● ●

●

●

The intubating LMA (ILMA) was specially designed to facilitate endotracheal intubation, either blindly or by fiberoptic guidance. In a recent study by Combs and associates using a treatment algorithm (the gum-elastic bougie [GEB] and ILMA were proposed as the first and second steps in the case of impossible laryngoscope-assisted tracheal intubation, respectively), 100 cases of unexpected difficult airway were recorded among 11,257 intubations (0.9%), with no cases of impossible ventilation. Deviation from the algorithm was recorded in three cases, and two patients were wakened before any alternative intubation technique was attempted. All remaining patients were successfully ventilated with either the facemask (89 of 95) or the ILMA (6 of 95). Six difficult-to-ventilate patients required the ILMA before completion of the first intubation step. Eighty patients were intubated using the GEB, and 13 required a blind intubation through the ILMA. Two patients ventilated with the ILMA were never intubated. In emergency situations, the ProSeal LMA may prove especially useful when positive-pressure ventilation is required and gastric distention or regurgitation is a major concern (e.g., cannot intubate in the obstetric patient). The ProSeal is not useful as a channel for FOB (smaller lumen for the bronchoscope; channel off the midline). ESOPHAGEAL-TRACHEAL COMBITUBE The esophageal-tracheal Combitube (ETC, Sheridan Catheter, Argyle, NY) was developed for emergency airway management. The ETC is a double-lumen airway containing a “tracheoesophageal” lumen with an open distal end. The second “pharyngeal” lumen, resembling an esophageal obturator-type airway, contains a distally blocked end and perforations in the lumen through which ventilation occurs. Dual standard airway connectors allow ventilation in either the esophageal or the tracheal position. The ETC comes in 37 and 41 French sizes for patients 4 to 6 feet tall and greater than 6 feet tall, respectively. With the neck in a neutral position (the sniffing position may hinder insertion), the ETC is inserted through the mouth. It is advanced over and beyond the tongue using a gentle, downward-curved, dorsocaudal movement and then advanced parallel to the patient’s horizontal plane until the proximal marker rings are at the upper incisors (or the

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alveolar ridge in edentulous patients). When inflated, the proximal, 100-mL, latex oropharyngeal balloon essentially seals the patient’s mouth and nose (some titrate the oropharyngeal balloon volume to air leak). The distal tracheoesophageal 15-mL balloon (use 10 to 15 mL air) seals either the esophagus or the trachea after insertion and inflation. Insertion results in esophageal intubation more than 96% of the time. Ventilation is initiated via tube 1 (the longer blue tube), with ventilation occurring via perforations in the “pharyngeal lumen” between the two balloons. Air is forced past the epiglottis into the trachea because the two balloons seal off all other “escape routes” (nose, mouth, esophagus). If there are no breath sounds or expired carbon dioxide (<4% of the time), tube 2 (the shorter clear tube) is ventilated (via the tracheoesophageal lumen), because the ETC has presumably entered the trachea. The ETC is an important method of out-of-hospital emergency airway management and can be used as a rescue ventilation device in the management of the difficult airway. When properly positioned, the ETC allows higher airway sealing pressures than a classic LMA. The distal balloon may prevent gastric distention and protect from gastric regurgitation and pulmonary aspiration. The risk of aspiration should theoretically be less than that with an LMA because the esophagus is sealed by the distal cuff. The ETC is a useful device to facilitate airway control in trauma patients with possible cervical spine injury because it is placed with the neck in the neutral position. In addition, the ETC is useful in patients with massive airway bleeding or regurgitation or limited access to the airway. Laryngoscopy can also be performed to ease placement of the ETC and may decrease soft tissue trauma compared with blind passage. The ETC has a good safety record, with only rare reports of esophageal injury. LARYNGEAL TUBE The laryngeal tube (LT) is a new supraglottic ventilatory device consisting of an airway tube and two low-pressure balloons (cuffs). When inserted, the LT lies along the length of the tongue with the distal tip (blind end; no gastric access) positioned in the upper esophagus. The distal (esophageal) balloon seals the airway distally, protecting from regurgitation. The proximal (pharyngeal) balloon seals both the oral and nasal cavities. The two balloons are inflated sequentially. Openings in the airway tube are situated between the two balloons and allow ventilation to occur. Fiberoptic tracheal intubation through the LT using an “exchange technique” is also possible. Recently, the LT was fitted with a second lumen for suctioning and free gastric drainage, but not for ventilation, as with the Combitube.

Invasive Airway Techniques RETROGRADE TRACHEAL INTUBATION Retrograde tracheal intubation has been used with good success to manage difficult airways and is a useful alternative in difficult (or anticipated to be difficult) intubations. The entry site for transtracheal puncture is made midline through the cricothyroid membrane. The risk of significant bleeding is low because the cricothyroid membrane is relatively avascular. The patient is placed supine—ideally, in the sniffing

GENERAL ANESTHESIA

●

Place a classic LMA while adequate ventilation is occurring. Pass a fiberoptic bronchoscope through a bronchoscope port adapter attached to the classic LMA ventilating tube. Guide the bronchoscope visually through the LMA aperture into the trachea, without interrupting ventilation. Pass a wire through the working channel of the bronchoscope into the trachea. Remove the bronchoscope. Place an airway exchange catheter over the wire into the trachea. Subsequently, remove the LMA over the airway exchange catheter. Pass an ETT over the airway exchange catheter into the trachea.

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position, if it is not contraindicated. Under sterile technique, an epidural needle or intravenous needle-catheter (18 gauge), with a saline (or lidocaine) half-filled syringe attached, is advanced in a 30- to 40-degree cephalad direction through the cricothyroid membrane. Upon air aspiration, lidocaine can be injected into the trachea. The patient’s tongue is pulled or protruded anteriorly. An epidural catheter, or spring guidewire, is passed “retrograde” back through the glottis into the mouth or naris. The guidewire needs to be long enough to pass out of the mouth or naris (a 100-cm wire is recommended to allow the use of adjunct equipment or manipulation of the ETT). An ETT is advanced over the epidural catheter or guidewire past the glottis into the trachea. The guidewire or epidural catheter is removed via the mouth (or naris) in the retrograde direction to prevent contamination of the cervical soft tissues at the puncture site. Unfortunately, the ETT may fall back into the hypopharynx upon release of the guide. Tracheal location of the ETT is confirmed using standard techniques. A guidewire technique using a commercially available retrograde intubation kit (Cook Critical Care, Bloomington, Ind) is shown in Figure 40-6. Indications, contraindications, and alternative methods for retrograde tracheal intubation are summarized in Table 40-11.

A

B

C

D

E

F

SURGICAL AIRWAY The rapid development of severe hypoxemia, especially if associated with bradycardia, is an indication for immediate intervention with an invasive technique, because rapid reoxygenation is essential. Surgical methods to secure the airway include cricothyrotomy and surgical tracheostomy. The cricothyroid membrane is the most accessible portion of the trachea below the level of the glottis. Cricothyrotomy is easier and preferred for transtracheal jet ventilation (TTJV). Contraindications to cricothyrotomy are listed in Table 40-12. Tracheostomy. The classic emergency surgical tracheostomy involves incision through the skin and platysma, division of the isthmus of the thyroid gland, hemostasis, incision of the tracheal cartilage, and insertion of a cuffed tracheostomy tube. Emergency tracheostomy can be very difficult to perform and may result in serious complications. Although a few surgeons may be able to perform a tracheostomy in 3 minutes or less, most take longer. Delay in completing a tracheostomy during the CVCI scenario may result in serious morbidity or death of the patient. Some patients require awake tracheostomy as the initial airway management method. Cannula Cricothyrotomy with Percutaneous Transtracheal Jet Ventilation. Compared with emergency surgical cricothyrotomy or tracheostomy, establishment of percutaneous TTJV via needle-cannula cricothyrotomy is quicker and simpler. TTJV permits continuous, uninterrupted ventilation and oxygenation in patients without an anatomic impediment to passive exhalation through the upper airway. This allows time to secure the patient’s airway by alternative techniques. Some anesthesiologists place a “prophylactic” TTJV catheter before intubation attempts in patients with suspected difficult airways so that a ready conduit is available in the event of difficulty with ventilation. The cricothyroid membrane is identified, and a 12- to 16-gauge over-the-needle catheter, attached to a partially

Figure 40–6 ■ Retrograde intubation using the guidewire technique. A, The J-tip of the guidewire and the guiding catheter. B, After standard preparation of the access site, advance the 18-gauge sheath needle (attached to a 6-mL disposable syringe) in a cephalad direction through the cricothyroid membrane and into the trachea. Free flow of air aspirated into the syringe confirms correct positioning. Remove the needle and syringe, leaving the sheath in place. C, Advance the J end of the guidewire through the sheath and up the trachea in a cephalad direction, until the tip of the guidewire can be retrieved through the mouth or nose. Note: The black proximal positioning mark of the guidewire should be visible at the access site, ensuring that enough guidewire is exposed orally or nasally for control of subsequent catheter introduction. Remove the sheath, leaving the guidewire in place. D, Advance the catheter antegrade over the guidewire by way of the mouth or nose and into the trachea until tenting is noted at the cricothyroid access site. E, With the catheter is position, advance the endotracheal tube over the catheter and into position below the level of the vocal cords. Note: Always maintain control and position of the guidewire during advancement of the endotracheal tube. F, Remove the guidewire and catheter from the endotracheal tube and inflate the balloon cuff of the endotracheal tube. Verify the position, and secure in a standard fashion. (From Behringer ED: Approaches to managing the upper airway. Anesthesiol Clin North Am 20:813-832, 2004; courtesy of Cook Critical Care, Bloomington, Ind.)

saline-filled syringe, is inserted at a 30- to 45-degree angle caudally into the “air vessel.” Easy aspiration of air into the syringe confirms placement (Fig. 40-7). Kink-resistant catheters are recommended because standard intravenous catheters are readily bent. The catheter hub is connected (preferably by a Luer-Lok connector) to a TTJV system. An alternative technique is to use a Seldinger catheter introducer set (8.5 French introducer kit commonly used for

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Indications

Contraindications Unfavorable anatomy in area of cricoid cartilage and cricothyroid membranes Nonpalpable landmarks Pretracheal mass Severe flexion deformity of neck Laryngotracheal pathologic condition Malignancy Tracheal stenosis Severe trauma to larynx or laryngotracheal separation Infection Significant coagulopathy Patients requiring immediate intubation and ventilation (can take up to 5 min to complete) Complete upper airway obstruction

Alternative Techniques Needle placement through infracricoid membrane instead of cricothyroid membrane (may increase success rate because it facilitates passage of ETT through larynx) Introduction of guidewire or epidural catheter (previously passed retrograde into mouth or naris) through hollow airway exchange catheter; passage of tube exchanger down over guidewire into trachea; subsequent advancement of ETT down over tube exchanger into trachea; guide lessens chance of dislodgment or hang-up of ETT tip in vocal cords, arytenoid cartilage, vallecula, or pyriform sinus Insertion of guide (previously passed retrograde into mouth or naris) through distal lateral eye of ETT before passing ETT over guide into trachea; can prevent entrapment of ETT tip in arytenoids or epiglottis Use of pulling techniques, either by creating loop around side eye or simply knotting epidural catheter with Murphy’s eye; can increase success rate of retrograde tracheal intubation Insertion of bronchoscope with preloaded ETT over guidewire via bronchoscope’s suction channel; allows visualization of airway structures as bronchoscope is advanced; wire is removed while observing bronchoscope remaining in trachea, with subsequent advancement of ETT into trachea ETT, endotracheal tube.

pulmonary artery catheters). The needle is used to make the initial puncture, air is aspirated, the guidewire is inserted into the distal trachea, and the catheter is threaded over the guidewire using the dilator. These 8.5 French catheters may allow some exhalation to take place via the catheter if the system can be vented. The TTJV system should provide 50 pounds per square inch of pressure (using an adjustable high-pressure device, driven by gas pipeline pressure) for adequate inspiratory gas flow. The oxygen flush systems of most modern anesthesia machines do not provide

Table 40–12

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Contraindications to Cricothyrotomy

Preexisting laryngeal disease Acute inflammation Chronic inflammation Malignancy Translaryngeal intubation >3 days Increased incidence of subglottic stenosis Coagulopathy Distortion of normal airway anatomy Infants and children <6 yr Inexperience in cricothyrotomy procedure (experience decreases complications)

sufficient pressure. Jaw thrust facilitates exhalation. The catheter must be stabilized during ventilation, or else the jet pressure may force it out of the trachea. TTJV should be considered a temporary measure because it can maintain adequate oxygenation for only about 30 to 60 minutes. Progressive hypercapnia is likely to occur because overall minute ventilation is usually inadequate. When air entry exceeds air exit during TTJV, lung hyperinflation, tension pneumothorax, pneumomediastinum, and subcutaneous emphysema will inevitably occur. Strategies to minimize barotrauma are listed in Table 40-13. Major changes in cardiovascular parameters should be assumed to be related to TTJV and possible barotrauma. TTJV can sometimes facilitate endotracheal intubation using standard methods because the high intratracheal pressure from TTJV can lift up and open the glottis. The escape of gas under high pressure causes the edges of the glottis to flutter, which may facilitate the identification of the glottic opening. If TTJV fails or surgical emphysema or another complication occurs, convert immediately to surgical cricothyrotomy. Surgical Cricothyrotomy. Surgical cricothyrotomy may allow the rapid restoration of oxygenation and ventilation in the CVCI scenario. Surgical cricothyrotomy is also indicated in the setting of severe maxillofacial trauma preventing oral intubation, known unstable cervical spine fracture,

GENERAL ANESTHESIA

Multiple intubation attempts have caused bleeding or edema Patients with limited mouth opening or neck movement Facial trauma Failed endotracheal intubation Elective management of difficult airway

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Figure 40–7 ■ Needle insertion for cricothyrotomy and transtracheal jet ventilation (TTJV). A, A 14-gauge (or larger) angiocatheter is directed caudad, using an angle of approximately 30 degrees to the skin, and passed through the cricothyroid membrane. B, The free return of air on aspiration through the syringe confirms the position of the tip of the needle in the tracheal lumen. The catheter is advanced over the needle into the tracheal lumen, the needle is removed, and the hub of the catheter is connected to the TTJV tubing (Luer-Lok connector recommended). (From Patel RG, Norman JR: The technique of transtracheal ventilation. J Crit Illness 11:803-808, 1996.)

laryngotracheal trauma (except for tracheal transection), complete upper airway obstruction, oropharyngeal obstruction, or inability to secure the airway by other intubation techniques. It is contraindicated in patients younger than 12 years and in the case of laryngotracheal separation or tracheal transection (the transected airway may be tenuously held together by cervical fascia), tracheal foreign body, or penetrating trauma to the neck (in either high zone 2 or zone 3) associated with an expanding hematoma. The surgical cricothyrotomy technique uses low-pressure ventilation through a cuffed tube placed in the trachea. A simplified cricothyrotomy technique (consisting of palpation, incision, insertion, and intubation) can be performed in approximately 30 seconds in experienced hands (Table 40-14). Invasive airway access is a temporary measure to restore oxygenation. Definitive airway management follows, such as surgical tracheostomy; alternatively, because oxygenation and ventilation have been established, there may be time to achieve tracheal intubation. Guidewire techniques of cricothyrotomy have been developed, and some claim that these techniques can restore the airway as quickly as the

Table 40–13

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Minimizing Barotrauma during Transtracheal Jet Ventilation

Preset jet ventilator to 25-50 psi by using additional in-line regulator Use lowest effective psi Limit inspiratory time to <1 sec Keep natural airway maximally patent with bilateral jaw thrust and oropharyngeal or nasopharyngeal airway (or both) If laryngeal mask airway was used, leave in place to facilitate exhalation Confirm ventilation of lungs and exhalation through upper airway psi, pounds per square inch.

standard surgical technique. Percutaneous dilatational cricothyrotomy (PDC) kits are commercially available. PDC is a rapid, relatively straightforward procedure that is touted as having a decreased operative time and lower late complication rate compared with surgical cricothyrotomy.

PREVENTION Prevention of complications related to difficult airway management requires the following: ● ●

● ●

Ability to recognize a potentially difficult airway Well-thought-out plan with suitable alternatives for all patients Willingness to call for help at the first sign of difficulty Availability of all necessary equipment (i.e., difficult airway cart)

Table 40–14

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Technique of Rapid Cricothyrotomy

Identify cricothyroid membrane (CTM) Palpate and stabilize larynx by bracing laryngeal cartilage with thumb and middle finger Maintain position of CTM with index finger Make horizontal stab incision through skin and CTM, just above cricoid cartilage Immediately insert tracheal hook (preferred), hemostat, or blade handle into opening Do not lose control of opening Apply caudal traction on CTM (if tracheal hook used) Intubate trachea with appropriately sized, preferably cuffed, endotracheal tube Tube insertion can be facilitated by passage of introducer (bougie) through incision or use of tracheal retractor Avoid excessive insertion depth (endobronchial tube placement) Confirm breath sounds and expired carbon dioxide

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●

●

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Adequate technical assistance (i.e., knowledgeable staff, dedicated to the task) Immediate availability of another anesthesiologist experienced with difficult airway management

Further Reading Agro F, Frass M, Benumof JL, Krafft P: Current status of the Combitube: A review of the literature. J Clin Anesth 14:307-314, 2002. Atlas GM: A comparison of fiberoptic-compatible oral airways. J Clin Anesth 16:66-73, 2004. Behringer EC: Approaches to managing the upper airway. Anesthesiol Clin North Am 20:813-832, 2002. Blanda M, Gallo UE: Emergency airway management. Emerg Med Clin North Am 21:1-26, 2003. Bogetz M: Using the laryngeal mask to manage the difficult airway. Anesthesiol Clin North Am 20:863-870, 2002. Cheney FW, Posner KL, Caplan RA: Adverse respiratory events infrequently leading to malpractice suits: A closed claims analysis. Anesthesiology 75:932-939, 1991. Combes X, Le Roux B, Suen P, et al: Unanticipated difficult airway in anesthetized patients: Prospective validation of a management algorithm. Anesthesiology 100:1146-1150, 2004. Cook TM: A new practical classification of laryngeal view. Anaesthesia 55:274-279, 2000. Davis L, Cook-Sather SD, Schreiner MS: Lighted stylet tracheal intubation: A review. Anesth Analg 90:745-756, 2000. Domino KB, Posner KL, Caplan RA, Cheney FW: Airway injury during anesthesia: A closed claims analysis. Anesthesiology 91:1703-1711, 1999. Dorges V, Ocker H, Wenzel V, et al: The Laryngeal Tube S: A modified simple airway device. Anesth Analg 96:618-622, 2003. el-Ganzouri AR, McCarthy RJ, Tuman KJ, , et al: Preoperative airway assessment: Predictive value of a multivariate risk. Anesth Analg 82:1197-1204, 1996. Ezri T, Szmuk P, Warters RD, et al: Difficult airway management practice patterns among anesthesiologists practicing in the United States: Have we made any progress? J Clin Anesth 15:418-422, 2003.

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Gaitini LA: The esophageal-tracheal Combitube. Anesthesiol Clin North Am 20:893-906, 2002. Genzwuerker H, Vollmer T, Ellinger K: Fibreoptic tracheal intubation after placement of the laryngeal tube. Br J Anaesth 89:733-738, 2002. Hagberg CA: Special devices and techniques. Anesthesiol Clin North Am 20:907-932, 2002. Hagberg CA: Current concepts in the management of the difficult airway. ASA Refresher Course, 2004. Henderson JJ, Popat MT, Latto IP, et al: Difficult Airway Society guidelines for management of the unanticipated difficult intubation. Anaesthesia 59:675-694, 2004. Langeron O, Masso E, Huraux C, et al: Prediction of difficult mask ventilation. Anesthesiology 92:1229-1236, 2000. Levitan RM: Patient safety in emergency airway management and rapid sequence intubation: Metaphorical lessons from skydiving. Ann Emerg Med. 42:81-87, 2003. Melker RJ, Florete OG: Cricothyrotomy: Review and debate. Anesthesiol Clin North Am 13:565, 1995. Mort TC: Emergency tracheal intubation: Complications associated with repeated laryngoscopic attempts. Anesth Analg 99:607-613, 2004. Patel RG, Norman JR: The technique of transtracheal ventilation. J Crit Illness 11:803-808, 1996. Practice guidelines for management of the difficult airway—an updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology 98:1269-1277, 2003. Rosenblatt W: The airway approach algorithm: A decision tree for organizing preoperative airway information. J Clin Anesth 16:312-316, 2004. Stackhouse R: Fiberoptic airway management. Anesthesiol Clin North Am 20:933-951, 2002. Weksler N, Klein M, Weksler D, et al: Retrograde tracheal intubation: Beyond fiberoptic endotracheal intubation. Acta Anaesthesiol Scand 48:412-416, 2004. Wilson WC: Emergency airway management. In Brown D (ed): Cardiac Intensive Care. Philadelphia, WB Saunders, 1998, pp 705-734. Wong EK, Bradrick JP: Surgical approaches to airway management for anesthesia practitioners. In Hagberg CA (ed): Handbook of Difficult Airway Management. Philadelphia, Churchill Livingstone, 2000, pp 209-210.

GENERAL ANESTHESIA

It is also incumbent on any clinician who is confronted with a difficult airway to enroll the patient in the MedicAlert system (1-800-344-3226) to apprise other clinicians of the patient’s history.

Difficult Airway: Cannot Ventilate, Cannot Intubate

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Difficult Airway: Opiate-Induced Muscle Rigidity Narayan Baliga and Theodore J. Sanford, Jr. Case Synopsis Anesthetic induction is being performed in a 70-kg, 65-year-old man undergoing elective coronary artery bypass graft surgery. Following 3 minutes of preoxygenation, fentanyl (3000 μg) is administered intravenously over 5 minutes. The chest and abdominal wall become rigid, and it becomes very difficult to ventilate the patient’s lungs with a mask and bag. The oxygen saturation drops rapidly, and the anesthesiologist cannot maintain the airway. It is difficult to open the patient’s mouth to insert an oropharyngeal airway.

PROBLEM ANALYSIS Definition Opioid-induced muscle rigidity usually occurs with large doses of potent opioids given intravenously. These include drugs such as fentanyl, alfentanil, sufentanil, and remifentanil. Morphine and meperidine can also cause such reactions, but this is not common with the doses used during balanced anesthesia. There have been published reports of muscle rigidity occurring with relatively small doses of highly potent opiates such as sufentanil and alfentanil. The phenomenon of muscle rigidity is usually seen during induction of anesthesia when opioids are the sole or primary anesthetic agent. All the skeletal muscles are involved. The rigidity starts within 1 or 2 minutes of opioid administration and typically lasts 10 to 20 minutes. The mechanism is thought to originate in the central nervous system. Rigidity of the torso muscles leads to a fall in chest wall compliance, hypoventilation, respiratory acidosis, and systemic arterial hypotension.

Recognition MUSCLE RIGIDITY The rigidity is immediate and occurs in all skeletal muscles. Sometimes the rigidity is accompanied by explosive myoclonus and vertical nystagmus, resembling seizures. There is an increase in electromyographic activity, but the electroencephalogram does not indicate seizure activity. It has been shown that this increase in muscle tone is most likely central in origin.

opioid is the causative agent. Chest wall rigidity makes it difficult to ventilate the patient with a mask and bag. Inability to open the mouth may make it impossible to insert an oropharyngeal or laryngeal mask airway. Although a nasopharyngeal airway can be inserted, airway obstruction caused by glottic closure may make it difficult to ventilate the patient manually. Chest wall rigidity leads to a rise in intrathoracic pressure, which causes an immediate rise in right atrial pressure. If sustained, this leads to a reduction in venous return and cardiac output and, ultimately, systemic arterial blood pressure.

Risk Assessment The differential diagnosis for inability to maintain the airway and oxygen desaturation includes the following: ● ●

●

Muscle rigidity from rapid narcotic administration Laryngospasm from a noxious stimulus during light anesthesia Seizures, if there is a history of epilepsy or an intracranial lesion

The incidence of muscular rigidity is between 50% and 100% in unpremedicated patients given large doses of the contemporary synthetic opioids (e.g., fentanyl, alfentanil, sufentanil, remifentanil). The doses noted to cause rigidity from various studies are as follows: fentanyl, 12 to 15 μg/kg; alfentanil, 175 μg/kg; sufentanil, 2.6 μg/kg. Much smaller doses may cause rigidity when given rapidly as an IV bolus. Little time is available for making a diagnosis. Rapid muscular paralysis and control of the airway are imperative and must be done immediately to prevent cerebral hypoxia.

CARDIORESPIRATORY EFFECTS The sudden onset of muscle rigidity immediately following the intravenous (IV) administration of opioids, accompanied by apnea and rapid oxygen desaturation, suggests that the 174

Implications Chest wall rigidity and respiratory insufficiency can lead to cardiovascular collapse and cerebral hypoxia. Unlike thiopental,

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opioids do not sufficiently reduce cerebral oxygen consumption to protect the brain during a global hypoxic event. Prompt intervention is required to prevent cerebral hypoxia. Patient awareness does not seem to be a problem; patients have no recall of the event when questioned postoperatively.

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Difficult Airway: Opiate-Induced Muscle Rigidity

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MANAGEMENT Attempts to manually ventilate the patient’s lungs without muscle relaxants are usually inadequate. Management consists of IV administration of either a depolarizing or a rapidly acting nondepolarizing neuromuscular blocking agent in the usual intubating doses (succinylcholine 1 mg/kg, vecuronium 150 μg/kg, or rocuronium 100 μg/kg). Manual ventilation is performed easily within 60 seconds after the administration of succinylcholine, and the airway can then be secured with an endotracheal tube. Once the airway has been secured, IV or inhaled anesthetics are administered to continue the anesthesia. A 7.6% incidence of delayed postoperative muscle rigidity has been reported when large doses (100 μg/kg) of fentanyl are used for induction of anesthesia. If this is severe enough to cause failure of ventilation, either a muscle relaxant or naloxone can be administered to reverse muscle rigidity.

PREVENTION Opioid-induced rigidity is difficult to prevent. The incidence can be reduced by slow injection of the opioid agent and

Further Reading Bailey PL, Wilbrink J, Zwanikken P, et al: Anesthetic induction with fentanyl. Anesth Analg 64:48-53, 1985. Benthuysen JL, Smith NT, Sanford TJ, et al: Physiology of alfentanil-induced rigidity. Anesthesiology 64:440-446, 1986. Janis KM: Acute rigidity with small intravenous dose of Innovar: A case report. Anesth Analg 51:375-376, 1972. Lui PW, Tsen LY, Fu MJ, et al: Involvement of locus coeruleus and noradrenergic neurotransmission in fentanyl-induced muscular rigidity in the rat. Neurosci Lett 96:114-119, 1989. Muller P, Vogtmann C: Three cases with different presentation of fentanylinduced muscle rigidity—a rare problem in intensive care of neonates. Am J Perinatol 17:23-26, 2000. Sanford TJ, Weinger MB, Smith NT, et al: Pretreatment with sedativehypnotics, but not with nondepolarizing muscle relaxants, attenuates alfentanil-induced muscle rigidity. J Clin Anesth 6:473-480, 1994. Streisand JB, Bailey PL, LeMaire L, et al: Fentanyl-induced rigidity and unconsciousness in human volunteers: Incidence, duration, and plasma concentrations. Anesthesiology 78:629-634, 1993. Weinger MB, Segal IS, Maze M: Dexmedetomidine, acting through central alpha2-adrenoceptors, prevents opiate-induced muscle rigidity in the rat. Anesthesiology 71:242-249, 1989. Weinger MB, Smith NT, Blasco TA, et al: Brain sites mediating opiate-induced muscle rigidity in the rat: Methylnaloxonium mapping study. Brain Res 544:181-190, 1991.

GENERAL ANESTHESIA

pretreatment with midazolam (0.1 mg/kg) or α2-agonists, such as clonidine and dexmedetomidine. Rigidity cannot be prevented or significantly reduced by pretreatment with small doses of nondepolarizing muscle relaxants. Careful attention to the time frame over which the newer synthetic opioids are administered and pretreatment with midazolam are the most important measures for prevention.

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Unstable Cervical Spine, Atlantoaxial Subluxation Lois A. Connolly Case Synopsis A 79-year-old man presents with C1 and odontoid fractures sustained in a fall down stairs while he was intoxicated. He was found at the bottom of the stairs 2 days after the injury. In addition to alcoholism, the patient has a history of hypertension and smokes 1 to 2 packs of cigarettes per day. The patient is not oriented to time, place, or person and has inappropriate verbal responses, but there is no apparent neurologic deficit.

PROBLEM ANALYSIS Definition Cervical spine stability is defined as the ability of the spine to maintain relationships between vertebrae during physiologic loading, so as not to damage contained neural structures. Cervical spine instability occurs when physiologic loading causes patterns of vertebral displacement that jeopardize the cervical spinal cord. The muscles of the neck, along with ligamentous structures, intervertebral disks, and osseous articulations, all play a role in cervical spine stability. Upper cervical spine stability may be affected by trauma, congenital disorders, and inflammatory diseases, all of which may result in atlantoaxial instability (Table 42-1). TRAUMATIC ATLANTOAXIAL INSTABILITY The transverse ligament normally allows no more than 3 mm of anteroposterior translation between the odontoid and the anterior arch of the atlas. If disruption of this ligament

Table 42–1

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occurs, displacement of the odontoid reduces the space available for the spinal cord (Fig. 42-1). In the normal spine, the space available for the spinal cord is about 20 mm. Cord compression does not occur when the space is greater than 18 mm, but it does occur if it is less than 14 mm. CONGENITAL ATLANTOAXIAL INSTABILITY Congenital or chromosomal anomalies may contribute to atlantoaxial instability by means of either odontoid hypoplasia or laxity of the transverse ligaments. The stabilizing action of the odontoid during extension is lost with odontoid hypoplasia, and subluxation of the atlas occurs on the axis anteriorly, reducing the space available for the spinal cord. Laxity of the transverse ligament is present in 14% to 22% of patients with trisomy 21. Excessive laxity of other joints correlates with the presence of atlantoaxial instability. INFLAMMATORY ATLANTOAXIAL INSTABILITY Cervical spine involvement is common in inflammatory arthropathies such as rheumatoid arthritis (RA). The pathophysiology involves pannus formation, with subsequent destruction of cartilage and subchondral bone, along with

Conditions Associated with Atlantoaxial Subluxation Anterior arch of atlas

Congenital Down’s syndrome Odontoid anomalies Mucopolysaccharidoses

Odontoid process of axis

Transverse ligament

Acquired Rheumatoid arthritis Juvenile rheumatoid arthritis Ankylosing spondylitis Psoriatic arthritis Enteropathic arthritis Crohn’s disease Ulcerative colitis Reiter’s syndrome Trauma Odontoid fracture Ligamentous disruption From Crosby ET: The adult cervical spine: Implications for airway management. Can J Anaesth 37:77-93, 1990.

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Space available for cord

Posterior arch Figure 42–1 ■ Atlantoaxial articulation—view from above. (From Crosby ET: The adult cervical spine: Implications for airway management. Can J Anaesth 37:77-93, 1990.)

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EPIDEMIOLOGY ●

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●

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●

●

Cervical spine injuries occur in 1.5% to 7.7% of all major trauma cases. The peak distribution of injury is at the C2 and C5-C6 levels. The highest prevalence is in 15- to 24-year-old males, with a smaller peak occurring in persons older than 55 years. Most cervical spine injuries result from motor vehicle accidents (42% to 56%), falls (19% to 30%), or gunshots and sports-related activities (6% to 7%). Motor vehicle accidents and sports-related activities account for the majority of cervical spine injuries in younger patients, whereas falls account for most cervical spine injuries in older patients. Young children are less susceptible to cervical spine injury because they weigh less and have more cartilage than adults do; vulnerability increases with age. Cervical spine injuries in children younger than 2 years are exclusively C1-C2 injuries, because facet joints at this level are more horizontal and the ligaments more lax.

Unstable Cervical Spine, Atlantoaxial Subluxation

Vertebral injury can occur without cord damage because the spinal canal is widest in the cervical region. Neurologic deficits are present in 46% of patients and are more frequent with injuries involving C5-C7. A thorough neurologic examination should enable classification and identification of the level of the spinal cord lesion. Autonomic instability may occur acutely and is termed spinal shock. With spinal shock, loss of sympathetic tone leads to generalized hemodynamic instability characterized by bradycardia, peripheral arterial and venous vasodilatation, hypotension, and arrhythmia. Respiratory compromise may occur acutely due to loss of intercostal muscle innervation or, with high cervical lesions, due to phrenic nerve loss. In normal individuals, expansion of the rib cage accounts for 60% of resting tidal volume. Therefore, alveolar ventilation and the ability to cough are decreased with loss of intercostal muscle innervation, even if phrenic nerve function remains intact. Thus, acute cervical cord injury may cause hypoxia, atelectasis, and respiratory failure. The possibility of aspiration pneumonitis may compound the situation. In addition, neurogenic pulmonary edema may be associated with spinal cord injury due to massive sympathetic discharge associated with trauma. RADIOGRAPHIC EVALUATION Radiographic evaluation of the cervical spine is indicated for all of the following patients: ●

The cervical spinal cord is particularly prone to injury because of spinal flexibility and the mass of the head. The spinal cord is injured when the ligaments, muscles, and osseous structures fail to dissipate the energy of impact. Transmission of this energy results in microhemorrhage in the spinal cord central gray matter and loss of neurotransmission in the surrounding white matter. A biochemical cascade that destabilizes the neurologic axon membrane and promotes vasospasm creates a secondary injury pattern after the initial insult. Also, primary cervical spinal cord injury leads to altered autonomic tone, loss of autoregulation, depressed cardiovascular function, and hypotension. Current pharmacologic treatment is concerned with minimizing the deleterious effects of secondary injury.

Recognition HISTORY

AND

PHYSICAL EXAMINATION

Recognition of a cervical spine injury begins with the history. High-risk causes (e.g., motor vehicle accident, fall, long-standing RA) or known chromosomal abnormalities may alert the clinician to the presence of an unstable cervical spine. For example, a patient with RA may complain of clicking on neck flexion and pain and stiffness of the neck. An alert trauma patient may complain of neck pain or tenderness. An alert patient without neck pain or neurologic deficit does not require further cervical spine evaluation, immobilization, or special precautions during airway manipulation. If the patient is not fully alert, complains of neck pain, has neurologic deficits, or has other painful injuries, cervical spine precautions should be maintained.

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Alert, sober patients who complain of neck pain or tenderness Patients who have neurologic deficits or multiple traumatic injuries, including craniofacial injuries Inebriated or unconscious patients

A missed cervical spine injury can have devastating longterm consequences. Therefore, coexistent cervical spine injury should be assumed until the diagnosis is excluded. Patients with no significant mechanism of injury and who are fully alert and oriented, with no evidence of head trauma or a distracting injury, may be cleared clinically if they have no neck pain or tenderness and have a normal neurologic examination. The most appropriate method for clearing the cervical spine in patients with mental status changes is controversial. There is no national or international consensus for the optimal approach to this patient population. The Eastern Association for the Surgery of Trauma’s 1998 practice management guidelines state that “trauma patients with altered levels of consciousness who are unable to complain of neck pain or neurological deficits for 24 hours or more may be considered to have a stable cervical spine if adequate threeview radiography and thin-cut CT images through C1 and C2 are read as normal.” Others recommend a passive extension-flexion examination under fluoroscopy to assess ligamentous stability. Ligamentous injury is the type most often missed on other radiographic studies, even though unstable cervical spine ligamentous injury without fracture is rare (<0.5%). Others suggest indefinite cervical immobilization. However, collar complications such as rash, skin breakdown, and pressure-related injuries; difficult central venous access; and delay in tracheostomy are possible when collars are left on for more than 72 hours.

GENERAL ANESTHESIA

ligamentous laxity and instability. Atlantoaxial subluxation occurs in about 25% of patients with RA. It occurs more frequently in men, in those with disease of long duration, in patients with subcutaneous nodules or seropositive disease, and in those receiving steroid therapy. Vertical subluxation of the odontoid process through the foramen magnum may also occur in patients with RA.

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A lateral cervical spine radiograph is assessed first. All seven cervical vertebrae should be evaluated, because 20% of cervical spine injuries are at C7. A swimmer’s view may be used if necessary to view C7. Alignment of the vertebral bodies, transverse processes, and spinous processes is best assessed on the lateral view (Fig. 42-2). Each vertebra should be examined for bony integrity, intervertebral disk spaces, facet joints, and interspinous distance. Sensitivity of the cross-table lateral view alone is 80%; that is, 20% of patients with cervical spine injury have a normal lateral view. The sensitivity increases to 93% by adding the anteroposterior and odontoid views. The cervical spine cannot be considered cleared on the basis of the lateral view alone. A diagnostic algorithm for the evaluation of cervical spine fractures is shown in Figure 42-3. Computed tomography (CT) is considered the gold standard for diagnosis. It is superior to plain films in evaluating injuries to C1-C2. Fractures in the axial plane may be difficult to identify by CT scan, and ligamentous injury may not be appreciated. Magnetic resonance imaging (MRI) provides excellent visualization of spinal soft tissue structures and clear definition of canal compromise. In an emergent situation, however, MRI may be impractical. In conditions associated with the possibility of atlantoaxial subluxation (e.g., RA, Down’s syndrome), lateral cervical spine films are obtained in neutral, flexed, and extended positions. Evidence of both anterior and vertical subluxation should be sought, and the space available for the spinal cord

Anterior vertebral line Spinous process line

Spinolaminar line Figure 42–2

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Lateral cervical spine.

MRI scan if: - Indirect reduction of facet dislocation - Abnormal neurology

Clear C-spine clinically? No pain/tenderness Alert and oriented No alcohol or drugs Pain-free active movement No distracting injury

Thoracolumbar spine films if: - Evidence of thoracolumbar injury - Unconscious - Cervical spine injury

No

Unconscious? No

Yes

Lateral, AP, and odontoid plain films Normal

Remove immobilization and reassess

Lateral and AP plain films + CT scan C0-C2 abnormalities, areas not seen

Abnormal

CT scan abnormalities, areas not seen

Regain consciousness within 24 hours?

Abnormal exams

Flexion-extension views

Yes

Leave immobilization and reassess

No

Dynamic fluoroscopy or MRI scan

Figure 42–3 ■ Algorithm for evaluation of cervical spine injury. AP, anteroposterior; CT, computed tomography; MRI, magnetic resonance imaging. (From Brohi K, Wilson-Macdonald J: Evaluation of unstable cervical spine injury: A 6-year experience. J Trauma 49:76-80, 2000.)

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should be measured. In patients with RA, the anteroposterior view may be examined for the presence of laryngeal deviation.

Risk Assessment

● ●

●

●

●

●

●

Evaluation of the cervical spine radiographically Determination of the adequacy of respiration (blood gas analysis or spirometry) Examination for evidence of spinal shock (blood pressure, heart rate, arrhythmia, electrocardiographic changes, need for vasopressors) Evaluation of the injury’s effect on the central nervous system (neurologic evaluation, evidence of closed cranial trauma) Examination of associated injuries (chest radiograph or CT and electrocardiogram to rule out chest injuries) Determination of hemoglobin, electrolyte levels, coagulation status, and creatinine level Assessment of temperature balance

Implications As discussed, multiple organs are affected by acute spinal cord trauma. Spinal shock requires invasive arterial monitoring, central venous pressure monitoring, and titration of vasopressors to ensure adequate perfusion pressure. If neurogenic pulmonary edema exists, further monitoring with a pulmonary artery catheter may be warranted. Acute spinal cord injuries are treated with high-dose methylprednisolone. This is believed to reduce edema, have anti-inflammatory effects, and protect neuronal membranes by scavenging free radicals. However, complications of such therapy include an increased rate of wound infection and a greater risk of gastrointestinal hemorrhage. Initial immobilization, with supervised reduction and realignment, is achieved with skeletal traction. Cervical immobilization is paramount and must be maintained during airway manipulation.

MANAGEMENT Intraoperative Concerns The primary intraoperative concerns are as follows: ● ● ● ● ●

Monitoring Airway management Positioning Administration of anesthetic drugs (succinylcholine) Fluid management, glucose administration

Intraoperative management requires tracheal intubation. The urgency of airway intervention is probably the most important factor in planning for airway management. Other factors include patient cooperation, assessment of the airway, and risk to the cord with neck movement. Direct laryngoscopy requires atlanto-occipitoaxial extension and mild inferior rotation of C3-C5, although there is minimal movement below C3. Accordingly, unstable C1-C2 injuries

Unstable Cervical Spine, Atlantoaxial Subluxation

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are most likely to cause neurologic damage. Manual in-line traction reduces atlanto-occipital extension during intubation, and several published series detail the use of direct laryngoscopy with in-line traction without evidence of neurologic deterioration. The use of a Miller-type blade results in less movement (i.e., axial distraction) than the use of curved (e.g., Macintosh) blades. Preintubation techniques, such as jaw-thrust and chin-lift maneuvers, cause the most motion and narrowing of the space available for the cord; therefore, great care must be taken when performing these maneuvers. Failed intubation is a danger, however, and the laryngoscopist’s view may be hindered by the stabilization. Direct laryngoscopy with in-line stabilization is most useful when it is vital to gain rapid control of the airway (e.g., patients with respiratory failure, hemodynamic instability, increased intracranial pressure). Use of a laryngeal mask airway is not advised because it can exert a great deal of pressure against the cervical vertebrae. Indeed, it may produce posterior displacement of the cervical spine (C2-C6) and possible rupture of the posterior longitudinal ligament. Awake tracheal intubation is probably the ideal way to secure the airway in a patient with an unstable cervical spine, although it may be inappropriate if rapid intubation is necessary. Use of the fiberoptic scope allows intubation under direct vision, but it may be difficult if the patient has pharyngeal bleeding or is uncooperative. Other awake techniques include blind nasal intubation or retrograde intubation over a wire. Cricothyrotomy or tracheotomy may be considered if attempts at placing an endotracheal tube by other means are unsuccessful. Once tracheal intubation is achieved in a conscious patient, positioning for surgery requires that continuous cervical spine stability be maintained. Often, the patient is positioned awake, so that any neurologic deterioration can be identified immediately. In addition to securing the airway and correct patient positioning, choice of anesthetic agents is paramount. Beyond the first 24 hours after injury, succinylcholine may cause hyperkalemia. In denervated muscle, motor end plates proliferate, and succinylcholine produces an exaggerated depolarizing response with a large release of potassium. This acute increase in potassium may lead to arrhythmia, cardiac arrest, and death. Anesthetic drugs are chosen based on preserved spinal cord perfusion and autoregulation and neuroprotective effects. If somatosensory evoked potential monitoring is done intraoperatively, anesthetic drugs may affect the latency or amplitude of evoked potentials. Hypotension and hypothermia may also affect somatosensory evoked potential monitoring. A drug regimen based on nitrous oxide, opiates, and nondepolarizing muscle relaxants, with minimal use of potent inhalational agents, appears most advantageous. Fluid management should balance the need to maintain intravascular volume to ensure adequate perfusion with the avoidance of interstitial edema. Avoidance of glucosecontaining solutions is important. Worsening neurologic outcomes have been demonstrated with transient spinal cord ischemia and exposure to modest elevations in plasma glucose concentrations.

GENERAL ANESTHESIA

Preoperative assessment in a patient with a known unstable cervical spine should include the following:

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Postoperative Concerns Extubation relies on the level of the neurologic lesion and the absence of associated injuries to the head and chest. Weaning criteria used for other patients, which include a maximum inspiratory force of –20 cm H2O, a vital capacity of 1000 mL, and a PaO2/FiO2 ratio greater than 250, may not be appropriate for a quadriplegic patient. If the surgical approach includes the anterior neck, a leak test around the endotracheal tube is helpful to rule out edema or airway compression from a neck hematoma. Both the recurrent laryngeal nerve and branches of the vagus may be damaged during neck dissection (more common on the right side than the left), leading to vocal cord paralysis and stridor on extubation, as well as dysphagia.

PREVENTION Prevention of neurologic deterioration with an unstable cervical spine requires the following: ●

●

●

● ●

Recognition of cervical spine injury and stabilization of the cervical spine during airway maneuvers and positioning Preservation of spinal cord perfusion by optimizing mean arterial pressure Minimization of spinal cord edema by careful attention to fluid management Use of high-dose steroids Prompt treatment of respiratory compromise to prevent hypoxia and further neurologic deterioration

In summary, the unstable cervical spine requires prompt recognition, evaluation of neurologic deficits, and evaluation and treatment of systemic effects, as well as meticulous airway management to ensure optimal outcome from the cervical spine injury.

Further Reading Ajani AE, Cooper DJ, Scheinkestel CD, et al: Optimal assessment of cervical spine trauma in critically ill patients: A prospective evaluation. Anaesth Intensive Care 26:487-491, 1998. Brohi K, Wilson-Macdonald J: Evaluation of unstable cervical spine injury: A 6-year experience. J Trauma 49:76-80, 2000.

Chin WC, Haan JM, Cushing BM, et al: Ligamentous injuries of the cervical spine in unreliable blunt trauma patients: Incidence, evaluation, and outcome. J Trauma 50:457-464, 2001. Cornelius RS, Leach JL: Imaging evaluation of the cervical spine trauma. Neuroimaging Clin N Am 5:451-463, 1995. Crosby ET, Lui A: The adult cervical spine: Implications for airway management. Can J Anaesth 37:77-93, 1990. Davis JW, Kaups KL, Cunningham MA, et al: Routine evaluation of the cervical spine in head-injured patients with dynamic fluoroscopy: A reappraisal. J Trauma 50:1044-1047, 2001. Donaldson WF, Heil BV, Donaldson VP, et al: The effect of airway maneuvers on the unstable C1-C2 segment: A cadaver study. Spine 22: 1215-1218, 1997. Edge CJ, Hyman N, Addy V, et al: Posterior spinal ligament rupture associated with laryngeal mask insertion in a patient with undisclosed unstable cervical spine. Br J Anaesth 89:514-517, 2002. Gerling MC, Davis DP, Hamilton RS, et al: Effects of cervical spine immobilization technique and laryngoscope blade selection on an unstable cervical spine in a cadaver model of intubation. Ann Emerg Med 36:293-300, 2000. Hastings RH, Marks JD: Airway management for trauma patients with potential cervical spine injuries. Anesth Analg 73:471-482, 1991. http://www.dhfs.state.wi.us/Disabilities/Physical/SCI.htm Keller C, Brimacombe J, Keller K: Pressures exerted against the cervical vertebrae by the standard and intubating laryngeal mask airways: A randomized, controlled, cross-over study in fresh cadavers. Anesth Analg 89:1296-1300, 1999. Laine FJ, Smoker WRK: Neuroradiology. In Cottrell JE, Smith DS (eds): Anesthesia and Neurosurgery, 4th ed. St. Louis, Mosby–Year Book, 2001, pp 151-156. Mackenzie CF, Geisler FH: Management of acute cervical spinal cord injury. In Albin MS (ed): Textbook of Neuroanesthesia. New York, McGrawHill, 1997, pp 1083-1136. Marshall WK, Mostrom JL: Neurosurgical diseases of the spine and spinal cord: Anesthetic considerations. In Cottrell JE, Smith DS (eds): Anesthesia and Neurosurgery, 4th ed. St. Louis, Mosby–Year Book, 2001, pp 557-590. Netterville JL, Koriwchak MJ, Winkle M, et al: Vocal fold paralysis following the anterior approach to the cervical spine. Ann Otol Rhinol Laryngol 105:85-91, 1996. Pasquale M, Fabian T: Practice management guidelines for trauma from the Eastern Association for the Surgery of Trauma. J Trauma 44:941-957, 1998. Short DJ, El Masry WS: High dose methylprednisolone in the management of acute spinal cord injury—a systematic review from a clinical perspective. Spinal Cord 38:273-286, 2000. Slucky AV, Eismont FJ: Treatment of acute injury of the cervical spine. Instr Course Lect 44:67-80, 1995. Stewart M, Johnston RA, Stewart I, et al: Swallowing performance following anterior cervical spine surgery. Br J Neurosurg 9:605-609, 1995. Walker DAJ: Management of the patient with spinal cord injury. In Fleisher LA, Prough DS (eds): Problems in Anesthesia: Traumacare, vol 13. Philadelphia, JB Lippincott–Williams & Wilkins, 2001, pp 340-347.

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Dental Injuries Lee M. Radke Case Synopsis

PROBLEM ANALYSIS Definition Most anesthesia references identify damage to teeth and dental prostheses as the most common complication of endotracheal intubation. In fact, dental complications are the most common reason for complaints against anesthesiologists. The incidence of dental trauma during general anesthesia has been reported to be as high as 12% and as low as 0.04%. A large survey in which more than 1 million endotracheal intubations were examined reported an incidence of approximately 1 dental injury per 1000 intubations.

Recognition Modern dental materials and techniques make dental injury difficult to recognize and diagnose. Restorations are often quite natural appearing, and to the untrained eye, it may be difficult to differentiate whether damage has occurred to a natural tooth or a restored tooth. Intubation-related dental injuries include fractured teeth, displaced restorations, subluxation, and avulsion. Individual teeth are numbered according to a system (Fig. 43-1), and damage to a tooth is classified in the following manner: ● ● ● ● ● ●

Class I: fracture confined to enamel Class II: fracture involving dentin layer Class III: fracture resulting in exposure of dental pulp Class IV: fracture of tooth root Class V: subluxation of tooth Class VI: tooth avulsion

Risk Assessment The greatest risk of dental injury occurs during laryngoscopy and tracheal intubation. The anterior maxillary teeth are most commonly damaged, with the left incisors affected most often. Damage to oral hard and soft tissues can usually be attributed to use of the maxillary anterior teeth as a fulcrum or resting place for the proximal laryngoscope blade during tracheal intubation. However, dental injuries occur in other ways as well. During airway maintenance, a poorly positioned airway or bite block can damage the dentition. During recovery, especially when volatile anesthetic agents have been used, powerful masseter muscle spasms can occur. If an oropharyngeal airway device has been left in place, the spastic biting and grinding forces against the airway can be sufficient to cause dental injury.

Patients with preexisting dental problems are at greater risk for dental injury during general anesthesia. During the preanesthetic evaluation, the anesthesiologist should note the patient’s risk for dental injury, especially the condition of the number 9 and 10 incisors (see Fig. 43-1), which are the teeth at highest risk for injury. Any potential dental problems should be noted in the patient’s chart: ●

●

●

●

●

●

Teeth that are decayed and not restored are susceptible to chipping or fracture. Teeth with dental restorations (e.g., large fillings or crowns), although strong and functional, can fracture when subjected to impact stresses. Endodontically treated teeth (e.g., root canal therapy) are weaker and more brittle than healthy, vital teeth. Periodontal disease results in decreased bony support. In this situation, laryngoscopy, tracheal intubation, or insertion of a laryngeal mask airway makes subluxation or avulsion of affected teeth more likely. Elderly patients may experience thinning of the tooth enamel due to aging and attrition. Such enamel is more easily damaged during instrumentation of the airway. Loose, exfoliating deciduous teeth are at risk for displacement in young patients.

Although deciduous teeth often are considered expendable, premature loss can result in problems. Deciduous teeth maintain space in the dental arch and help guide the permanent teeth into the proper position. If deciduous teeth are lost prematurely, the dental arch could collapse, with a resultant crowding of the permanent teeth. Further, any damage to a deciduous tooth may harm the underlying permanent tooth. Difficulty of endotracheal intubation can be a contributing factor to dental injury. Emergent, hurried intubations are more likely to result in tooth damage. Unfavorable anatomic features, such as mandibulofacial abnormalities or a short neck, complicate intubation, as do conditions that cause decreased mobility of the mandible or the neck. Although not well studied, another factor contributing to dental injury during general anesthesia is the experience level of the person performing the intubation.

Implications As stated, patients with preexisting dental problems are at the greatest risk for dental injuries related to intubation. If the patient is aware of dental problems or is informed of such risk before general anesthesia, liability is greatly diminished, even if damage occurs. Affected teeth should be noted 181

GENERAL ANESTHESIA

A 55-year-old man is taken to the operating room for hernia repair. He has cervical ankylosis, and intubation proves to be difficult. Two maxillary incisors are fractured. Hernia repair is completed, and the dental service is contacted for consultation.

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Molars Bicuspids Canine Lateral incisor Central incisors Lateral incisor Canine Bicuspids

1

2

32

31

3

4 30

5 29

6 28

7 27

8

9

10

26 25 24 23

11 22

12 21

13 20

14 19

Molars

15

16

18

17

Molars Bicuspids Canine Lateral incisor Central incisors Lateral incisor Canine Bicuspids Molars Figure 43–1

■

Nomenclature and universal numbering system for permanent (adult) dentition.

by number (see Fig. 43-1) during the preanesthetic airway evaluation. The consequences of dental trauma during general anesthesia can range from minor to severe. Many dental injuries can be repaired easily with standard restorative dental procedures, such as replacement of a displaced filling or repair of chipped enamel. More severe damage, such as dentoalveolar injury,“healthy” tooth loss, or damaged crowns or bridgework, is costly to rectify, causes substantial patient dissatisfaction and upset, and may result in litigation. Endobronchial aspiration of a natural, restored, or prosthetic tooth is the most serious adverse outcome of dental injury.

MANAGEMENT Ideally, management of an intubation-related dental injury is undertaken by a dental consultant shortly after the injury occurs. Because this service is not always immediately available, the anesthesia staff usually provides early management of such injuries. If a fragment of a tooth or restoration is displaced, the pieces must be located and recovered. If it is apparent that not all pieces have been retrieved, radiographs should be

obtained to ensure that the object has not passed through the glottic opening. Anteroposterior and lateral chest radiographs and lateral head and neck views should be taken. If a tooth is loosened but not avulsed, it should be returned to its original position as soon as possible. The inner and outer alveolar bone should be compressed with digital pressure to realign bone fragments. Temporary splinting should be done with tape or suture, especially if the tooth is very loose and aspiration is a concern. If a tooth is avulsed, it should be replanted immediately into its original position. Care must be taken not to wipe or dry the root surface. Tooth roots attach to the alveolar socket through a network of collagenous fibers, which form the periodontal ligament. Wiping or drying the root disrupts the attachment fibers, making successful replantation less likely. In addition, the less time a tooth is out of its socket, the more likely it is that replantation will be successful. Teeth replanted within 30 minutes can usually be retained. Temporary splinting with tape or suture is indicated. Often, a tooth cannot be safely replanted until the patient awakens because of concern about aspiration. If this is the case, the tooth should be handled carefully by the crown and placed in a suitable medium. Saline is readily available and works well, but milk is better. Milk may be available

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PREVENTION Preoperative Evaluation Prevention of anesthesia-related dental injuries begins during the preoperative anesthetic evaluation. Clinicians should determine whether the patient has any difficulty opening his or her mouth and whether any fixed or removable prostheses are present. The patient should be asked whether he or she is aware of any carious teeth or teeth that have been loosened by periodontal disease, especially any anterior teeth (numbers 6 to 11 and 21 to 27; see Fig. 43-1). Many patients do not receive regular dental care and may be totally unaware of their dental and periodontal status. If any teeth have periodontal disease (e.g., gingival recession, gingivitis, stain, calculus deposits, exudate), an evaluation for hypermobility should be done. This can be done using a tongue depressor blade or wooden cotton-tipped applicator to apply pressure to the facial aspect of the tooth while bracing the lingual aspect with the index finger of the other hand. Subtle, almost imperceptible movement is normal. Do not attempt to evaluate mobility by wiggling a tooth with the fingertips alone, because the sponginess of the fleshy part of the fingertip could be perceived as tooth movement. Accurate documentation of preexisting conditions (e.g., loose teeth, decay, restorations) and honest discussion of the risk of dental injury with the patient and his or her family

Dental Injuries

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members or representatives will greatly reduce liability if damage to the teeth should occur during anesthesia. If time permits (i.e., elective surgery) and there are serious concerns related to poor dental health, a dental consultation may be requested to thoroughly evaluate and possibly treat dental problems before the planned surgery. Tooth protection devices should always be considered for patients undergoing laryngoscopy or endoscopy, especially those who have known risk factors for dental injury. Prefabricated rubber or plastic protectors are available but are not universally used or accepted. Concerns that tooth protectors may hinder visualization during direct laryngoscopy may account for their limited use. Custom-made protectors can be fabricated by a dentist before surgery if the need exists and time permits. Custom-made protectors are somewhat expensive, but they offer a high degree of protection with minimal hindrance to visualization of the larynx. It has been reported that some degree of tooth protection may be provided by applying several layers of surgical adhesive tape to the teeth or the back of opposing surface of the laryngoscope blade. In an attempt to minimize contact between the teeth and the laryngoscope, many modifications to the shape of the blade have been proposed. It is suggested that an angulated straight blade with a low heel offers greater visualization between the posterior end of the blade and the upper teeth. Regardless, it is apparent that most anesthesia-related dental injuries can be prevented with a knowledge of dental factors that predispose teeth to such injury and the use of devices or strategies to protect the teeth.

Further Reading Burton JF, Baker AB: Dental damage during anaesthesia and surgery. Anaesth Intensive Care 15:262-268, 1987. Chadwick RG, Lindsay SM: Dental injuries during general anesthesia. Br Dental J 180:255-258, 1996. Givol N, Gershtansky Y, Halamish-Shani T, et al: Perianesthetic dental injuries: Analysis of incident reports. J Clin Anesth 16:173-176, 2004. Lockhart PB, Feldbau EV, Gabel RA, et al: Dental complications during and after tracheal intubation. J Am Dent Assoc 112:483, 1986. Skeie A, Schwartz O: Traumatic injuries of the teeth in connection with general anaesthesia and the effect of use of mouthguards. Endodont Dental Traumatol 15:33-36, 1999. Warner ME, Benenfeld SM, Warner MA, et al: Perianesthetic dental injuries: Frequency, outcomes, and risk factors. Anesthesiology 90:1302-1325, 1999. Watanabe S, Suga A, Asakura N, et al: Determination of the distance between the laryngoscope blade and the upper incisors during direct laryngscopy. Anesth Analg 79:638-641, 1994.

GENERAL ANESTHESIA

from the lunch bag of an understanding employee or from a nearby cafeteria. In the case of significant dental injury, arrangements should be made for immediate referral to a dentist for further evaluation. Loosened or avulsed teeth usually require splinting, and root canal therapy is often necessary if the teeth are to be retained. The circumstances of a dental injury should be documented in the patient’s chart and discussed with the patient as soon as he or she is able to understand the situation. Hospital policy usually requires that an incident report be filed. Administrative personnel from risk management or an equivalent department should become involved to help prevent public-relations, legal, or economic problems for the hospital and physicians involved. Responsibility for reimbursement of the patient for anesthesia-related dental injury could rest with the hospital, anesthesia department, or physician, depending on the hospital’s policy.

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Laryngeal and Tracheal Injury William Hope Case Synopsis A 65-year-old man describes persistent hoarseness and stridor after prolonged tracheal intubation and mechanical ventilation for treatment of respiratory insufficiency after emergent abdominal aortic aneurysm repair.

PROBLEM ANALYSIS Definition Acute and chronic injuries associated with laryngoscopy and tracheal intubation include but are not limited to the following: ● ● ● ● ● ● ●

Tracheobronchial laceration and rupture Laryngeal and tracheal edema and scarring Tracheal ulceration and stricture Subglottic and posterior glottic stenosis Dislocation of the arytenoid cartilages Vocal cord paralysis Ductal retention cysts

These complications can result in vocal cord dysfunction and airway obstruction of variable severity. In addition, laryngoscopy and placement of a tracheal tube may cause acute problems related to excessive autonomic stimulation and device malposition or malfunction. An endotracheal tube always lies in and exerts pressure on the posterior larynx, with potential damage to the arytenoid cartilages and cricoarytenoid joints, posterior glottis, and subglottis involving the inner surface of the cricoid cartilage. The degree of damage from intubation differs among patients. Damage has been shown to occur within a few hours and increases with the duration of intubation. Changes such as edema and hyperemia are seen initially. Progression to mucosal ulcerations and granuloma formation can lead to scar tissue formation and strictures, with chronic airway obstruction. Depending on the site of the injury and the presence of granulation or scar tissue, there can be stenosis and adhesions at, above, or below the level of the vocal cords, possibly with vocal cord dysfunction. Ductal retention cysts form due to irritation and obstruction of subglottic mucous gland ducts. Tracheal erosion caused by tracheal tube trauma may ultimately lead to tracheoesophageal fistula or tracheomalacia and potential tracheal collapse.

Recognition Laryngeal and tracheal injuries can be divided into those occurring after short-term or prolonged intubation. 184

SHORT-TERM TRACHEAL INTUBATION Acute injury, including mucosal and vocal cord edema, usually manifests within hours after extubation and may produce a barking, brassy cough and varying degrees of respiratory obstruction. Dyspnea, stridor, tachypnea, tachycardia, and suprasternal retraction are common presenting signs. Vocal cord dysfunction from recurrent laryngeal nerve injury or arytenoid dislocation presents as partial airway obstruction, dysphonia, and dysphagia. Although usually unilateral, bilateral vocal cord paralysis can present as complete airway obstruction necessitating emergency airway management. Tracheobronchial rupture is suspected with subcutaneous emphysema, respiratory distress, pneumomediastinum, and pneumothorax. Radiography and fiberoptic bronchoscopy confirm the diagnosis. PROLONGED TRACHEAL INTUBATION Chronic disorders often present weeks to months after prolonged intubation. Patients present with persistent voice dysfunction, dysphagia, and symptoms of airway obstruction. The lesion can be diagnosed endoscopically or radiographically. In the case of arytenoid dislocation, direct laryngoscopy with the patient under general anesthesia allows testing of the mobility of the cricoarytenoid joint. Flow-volume loops can be used to detect airway obstruction and provide valuable information about its location and functional importance. For example, in patients with airway obstruction, flows are reduced over the full range of lung volume from total lung capacity to residual volume (Fig. 44-1).

Risk Assessment Because late complications of tracheal intubation present weeks to months after the injury, the acute care practitioner is often unaware of the true incidence of the problem. There is evidence that even with short-term intubation, laryngoscopy results in radiographic and endoscopic evidence of laryngeal damage in a high percentage of patients. As many as 4% of young children experience symptomatic tracheal or laryngeal edema after intubation. The incidence of granuloma formation in adults reportedly ranges from 1 in 800 to 1 in 20,000 tracheal intubations. Granuloma formation occurs more commonly in women than in men and is relatively rare in children.

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Normal

MANAGEENT

4

Obstruction 2

1

2

3

4

TLC

5

6

RV Expired volume (L)

Figure 44–1 Hypothetical expiratory flow-volume curve for a patient with severe airway obstruction due to tracheal stenosis compared with that for a normal person. Note that flows are reduced over the full range of lung volumes, from total lung capacity (TLC) to residual volume (RV). ■

The following factors have been identified as contributing to intubation trauma:

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●

185

Laryngeal abnormalities (external trauma, inflammatory conditions) Difficult, traumatic, or repeated attempts at tracheal intubation Endotracheal tube movement (during coughing, swallowing, mechanical ventilation) Impairment of mucociliary clearance mechanisms or stasis of secretions Bacterial superinfection (prolongs healing and increases scar formation) Gastroesophageal reflux with spillover of acid into the laryngeal and subglottic region Nasogastric tube (increases the likelihood of gastroesophageal reflux and can cause pressure necrosis in the posterior cricoid region) Acute or chronic disease states with altered consciousness, poor tissue perfusion, or hypoxemia Long duration of intubation (5 to 7 days in adults and 1 to 2 weeks in children) Endotracheal tube characteristics (larger size, highpressure cuff)

Implications Laryngeal and tracheal injuries after laryngoscopy and tracheal intubation can be a significant cause for perioperative morbidity and, possibly, mortality. Tracheal rupture can lead to mediastinitis and pneumothorax. Acute airway edema can result in significant obstruction; this is especially

For acute laryngeal edema, nebulized racemic epinephrine (0.5 mL of a 2% solution diluted in a volume of 2 to 4 mL, given every 4 hours) can improve the symptoms of stridor. This dose should not be repeated more frequently than every 2 hours, and the patient must be observed for at least 4 to 6 hours after the last dose for possible rebound effects. Although its efficacy has not been proved, dexamethasone (0.2 to 0.4 mg/kg; maximum dose, 10 mg) may be beneficial. With prolonged intubation (adults, 5 to 7 days; children, 1 to 2 weeks), consultation for endoscopic laryngeal assessment is advised. Minor injuries usually resolve spontaneously after removal of the endotracheal tube. However, the finding of deep ulcerations calls for immediate extubation or tracheotomy, in addition to precautions to reduce the risk of infection (antibiotic therapy). If extubation is attempted in a patient with laryngeal edema, steroids can be administered in addition to the interim placement of a smaller endotracheal tube for 24 to 48 hours. The removal of granulation tissue may be required for successful extubation. Chronic injury secondary to intubation trauma may require laser ablation of scar tissue; tracheal dilatation, resection, reconstruction, or stents; or even anterior cricoid arch resection. Tracheal rupture usually requires emergent thoracotomy for repair.

PREVENTION Attempt to treat modifiable risk factors as follows: ● ●

● ●

Judicious use of intubating stylet Use of smallest endotracheal/tracheostomy tube diameter possible Aggressive gastroesophageal reflux treatment Antibiotic treatment for tracheostomy site infection

Further Reading Benjamin B: Prolonged intubation injuries of the larynx: Endoscopic diagnosis, classification, and treatment. Ann Otol Rhinol Laryngol Suppl 160:1-15, 1993. Flemming DC, Orkin FK, Kirby RR: Hazards of tracheal intubation. In Gravenstein N, Kirby RR (eds): Complications in Anesthesiology, 2nd ed. Philadelphia, Lippincott-Raven, 1996, pp 229-239. Reidenbach MM, Schmidt HM: Membranous tracheal rupture after endotracheal intubation. Ann Thorac Surg 60:1367-1371, 1995.

GENERAL ANESTHESIA

Flow (L/sec)

8

●

Laryngeal and Tracheal Injury

true in young children because of their small airway diameter. Sedatives, anesthetics, and muscle relaxants oppose the necessary compensatory increased activity of the accessory muscles of breathing in patients with severe airway obstruction to cause respiratory embarrassment. Bilateral recurrent laryngeal nerve palsy and flaps of granulation tissue can cause sudden and complete airway obstruction, necessitating the immediate establishment of an artificial airway.

10

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Case Synopsis An obese, agitated, 43-year-old man presents for exploratory laparotomy following a gunshot wound to the abdomen. He is uncooperative for examination of the airway. Following rapid-sequence induction of anesthesia, laryngoscopy is unexpectedly difficult. As neuromuscular function returns, the patient vomits a massive quantity of semidigested food.

PROBLEM ANALYSIS Definition The pulmonary aspiration of gastric contents can produce a variety of hazardous sequelae, depending on the nature of the aspirate. Aspirations may include the following: ●

●

● ●

●

Large food fragments, which can obstruct the airway, rapidly causing asphyxia Small particles (e.g., particulate antacids), which can produce severe granulomatous inflammation Gastric acids, which can induce chemical pneumonitis Blood and digestive enzymes, which are relatively innocuous Feculent material, which can cause severe infectious pneumonia

Recognition Unwanted materials can enter the lungs in either a subtle or a dramatic manner. Signs and symptoms (Table 45-1) can appear immediately or after several hours. Rales and rhonchi may be audible in affected lung regions, whereas wheezing may be prominent in only one third of patients with pulmonary aspiration. Dyspnea and tachypnea may develop in an awake patient. Both bronchial obstruction and pulmonary edema can induce profound hypoxemia. Pulmonary edema may also be associated with pink, frothy sputum. Tachycardia can result from respiratory distress as well as from intravascular hypovolemia. The latter can be due to a massive leakage of fluid through damaged pulmonary capillaries. Radiographic infiltrates may appear promptly or after a variable delay, and they may continue to worsen even as the clinical picture begins to improve. No particular radiographic

Table 45–1

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Signs and Symptoms of Pulmonary Aspiration

Rales and rhonchi Wheezing Dyspnea and tachypnea Hypoxemia Tachycardia Pulmonary infiltrates or edema

186

pattern is specific to pulmonary aspiration; it depends on the volume of material inhaled and the patient’s position during aspiration. In supine adult patients, the bronchial anatomy most commonly directs foreign matter into the right lower lobe and, less frequently, into the left upper lobe.

Risk Assessment Several large surveys have found that the incidence of clinically significant aspiration ranges from 0.5 to 4.7 per 10,000 cases. In some studies, the likelihood of pulmonary aspiration is three to four times greater for emergency surgery than for elective surgery. Children and the elderly are more likely to aspirate than are patients of intermediate ages. It may be troubling to note that whereas one third to one half of manifest pulmonary aspirations occur during anesthetic induction or laryngoscopy, one fifth to one third occur during emergence from anesthesia and extubation, when vigilance for this complication is lessened. The preoperative factor most often associated with aspiration is gastrointestinal obstruction. When aspiration occurs in the absence of known predisposing factors, two thirds of such episodes are complications of unanticipated difficulties in airway management. Pulmonary aspiration has two basic components. First, gastric contents must either escape or be propelled from the stomach into the oropharynx. Second, they must enter the lungs. Active vomiting can be provoked by opioids, cricoid pressure, gastrointestinal obstruction, or hypotension (Table 45-2). Passive regurgitation is promoted by increased intragastric volume or pressure or reduced lower esophageal sphincter (LES) tone. Failure of protective laryngeal reflexes can result from neurologic or neuromuscular disorders, sedative or narcotic medications, or general medical debility. Among the factors that influence the risk of pulmonary aspiration and its sequelae are the volume and character of gastric contents (Table 45-3). Increased volume alone may overcome any protection afforded by the strength of LES tone. Although the normal stomach apparently passes clear liquids within 2 to 3 hours, clearance of solids may require 6 hours or longer. Gastric acid secretion is thought to be stimulated by ethanol, hypoglycemia, and anxiety. In contrast, antegrade gastric emptying may be inhibited by diabetic gastroparesis, opioids, and pain. LES tone is weakened by nicotine, caffeine, fats, and gastric acid. Although a nasogastric tube permits gastric decompression, it also prevents LES closure. Finally, it is important to seek a history of gastroesophageal reflux

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Table 45–2

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Risk Factors for Pulmonary Aspiration: Escape of Gastric Contents

Vomiting

Regurgitation Gastrointestinal obstruction Diabetic gastroparesis Gastroesophageal reflux Increased intragastric pressure Decreased lower esophageal sphincter tone

Other Factors Impaired laryngeal protective reflexes Difficult airway management

from all patients and to recognize that elderly individuals may have feeble gag or cough reflexes. Some large clinical studies have failed to confirm conventional notions regarding the risk for aspiration. In these studies, patient factors that did not reliably predict gastric fluid acidity or volume were outpatient status, reflux history, anxiety, obesity, duration of fasting, and pregnancy. Similarly, the intake of alcohol, nicotine, or opioids had limited predictive value.

Implications When pulmonary aspiration of gastric contents occurs, the possible consequences range from benign to lethal. In one series of more than 200,000 operations, nearly two thirds of obvious aspirations produced no signs or symptoms within 2 hours. In this fortunate majority, no related complications ensued. For those patients who developed coughing, wheezing, infiltrates, or hypoxemia within 2 hours of aspiration, more than half required mechanical ventilation for at least several hours. Half the patients who required mechanical ventilation for more than 24 hours never fully recovered. In this and other large series, overall mortality from pulmonary aspiration was less than 5%; however, others reported much higher mortality rates. In two major surveys, pulmonary aspiration was never fatal in healthy patients after elective surgery. Even in Mendelson’s historic 1946 report of peripartum aspiration, the only fatalities resulted from rapid asphyxiation caused by food solids.

■

Risk Factors for Pulmonary Aspiration: Volume and Character of Gastric Contents

Increased volume of gastric contents Increased acidity of gastric contents Particulate matter in stomach Feculent matter in aspirate

187

MANAGEMENT When gastric contents enter the pharynx, the first priority is to clear the upper airway and prevent asphyxia. Tracheal intubation should follow promptly, even if difficult intubation precipitated the aspiration. Bronchoscopic suctioning of the lower airways may be indicated for pulmonary toilet. It is utterly useless, at best, to attempt to neutralize or dilute inhaled acids with an alkaline or saline chaser. Gastric acids experimentally instilled into the bronchi appear at the surface of the lung in less than 20 seconds. Thus, pulmonary parenchymal damage occurs almost immediately. It had been hoped that corticosteroids might interrupt the pulmonary inflammatory response to acid aspiration and ameliorate the subsequent clinical course. Unfortunately, after 3 decades of investigation, no beneficial effect has been shown. Although corticosteroids may attenuate inflammatory pneumonitis, the immunosuppressant effect of glucocorticoids may exacerbate any secondary bacterial pneumonia or sepsis. Also, prophylactic antibiotics are now considered useless in cases of pulmonary aspiration and may promote rather than prevent secondary infection with resistant pathogens. However, when the aspirate is feculent, antibiotic coverage may be indicated. The most important therapeutic measure after any pulmonary aspiration is maintenance of pulmonary gas exchange. Often, mechanical ventilation is instituted immediately after any major pulmonary aspiration. Although the prophylactic benefits of positive-pressure ventilation and positive endexpiratory pressure on the development of subsequent lung injury have been debated, such measures are often required merely to provide adequate arterial oxygenation.

PREVENTION Prevention of pulmonary aspiration includes careful, skilled airway management, as well as pharmacologic alteration of gastric contents and emptying with the following agents: ● ●

●

Nonparticulate antacids H2-receptor antagonists (or other suppressants of gastric acid secretion) Gastroprokinetic drugs

Several classes of drugs are used as chemoprophylaxis to alter gastric fluid volume and pH and to reduce both the likelihood of pulmonary aspiration and any associated complications (Table 45-4). Nonparticulate citrate antacids can Table 45–4

Table 45–3

Pulmonary Aspiration

■

Prophylaxis for Pulmonary Aspiration

Safe airway management Cricoid pressure Gastric tube decompression Chemoprophylaxis Clear citrate antacids H2-receptor histamine antagonists Proton pump inhibitors Gastroprokinetic agents

GENERAL ANESTHESIA

Gastrointestinal obstruction Opioids Cricoid pressure Hypotension

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elevate gastric pH in most patients, although gastric acids do reaccumulate. Commonly, 15 or 30 mL of sodium citrate or Bicitra is given before cesarean section and has been shown to raise gastric fluid pH to a presumably safe level in the vast majority of parturients. When given before nonobstetric emergency surgery in nonfasting patients, citrates reportedly have less consistent effects. In nonobstetric patients, 30 mL of citrate appears to be more reliable than 15 mL. However, the effects of citrates can never be presumed to persist through emergence and extubation. Particulate antacids are hazardous to the lungs and are therefore contraindicated preoperatively. Various H2-receptor histamine antagonists (e.g., cimetidine, ranitidine, famotidine) have been evaluated in many oral and parenteral regimens. Such drugs effectively suppress gastric acid secretion in most patients for several hours. However, they exert no effect on secretions already present in the stomach. Thus, their clinical utility is limited in truly emergent surgical patients. Proton pump inhibitors (e.g., omeprazole) are similarly effective in reducing further gastric acid production, but they have no demonstrable advantage over the H2-receptor histamine antagonists for aspiration prophylaxis. Gastroprokinetics (e.g., metoclopramide) may both facilitate antegrade gastric emptying and strengthen LES barrier pressure. However, their efficacy is somewhat inconsistent. Diabetics and others with known or suspected gastroparesis are likely the best candidates for gastroprokinetic medications. When preparing a patient for emergency surgery, a 10- or 20-mg intravenous dose of metoclopramide can empty the stomach within 10 to 20 minutes, whereas an oral dose takes 30 to 60 minutes. Erythromycin is also known to accelerate gastric emptying. Of course, individual responses vary, and it is potentially dangerous (and contraindicated) to attempt to increase gastrointestinal motility in the presence of intestinal obstruction. Prevention of pulmonary aspiration rests primarily on proper airway management. Chemoprophylaxis is useful, but it is only an adjunct. Although a variety of drugs can safely reduce the pulmonary threat imposed by gastric contents, their routine use is generally not advocated in otherwise healthy, nongravid surgical patients without apparent risk factors for aspiration. Owing to the infrequency of aspiration

pneumonitis in such patients, it is unlikely that these drugs will ever be shown to have a statistically significant effect on clinical outcome. Whenever possible, a difficult airway should be identified preoperatively. Gastrointestinal obstruction and airway morphology may warrant tracheal intubation before protective laryngeal reflexes are pharmacologically ablated. Although a gastric tube may not completely empty the stomach, it can provide a vent for increased intragastric pressure. Cricoid pressure (Sellick’s maneuver), when properly applied, can help prevent the passage of gastric contents into the oropharynx. However, it may also provoke active vomiting in an unanesthetized patient. In recent years, more authors have questioned the primary benefits of this maneuver. It is physically difficult to maintain cricoid pressure at the recommended level or force for more than a few minutes. In addition, backward pressure on the cricoid cartilage facilitates laryngoscopy in some patients but interferes with it in others. In fact, in some patients, pushing the larynx posteriorly, cephalad, and to the right provides the best view of the vocal cords. Cricoid pressure can also impede mask or laryngeal mask airway ventilation. Although Sellick’s maneuver remains a standard component of aspiration prophylaxis, oxygenation, ventilation, and securing the airway must always take precedence.

Further Reading ASA Task Force: Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: Application to healthy patients undergoing elective procedures: A report by the American Society of Anesthesiologists Task Force on Preoperative Fasting. Anesthesiology 90:896-905, 1999. Ljungqvist O, Soreide E: Preoperative fasting. Br J Surg 90:400-406, 2003. LoCicero J: Bronchopulmonary aspiration. Surg Clin North Am 69:71-76, 1989. Marik PE: Primary care: Aspiration pneumonitis and aspiration pneumonia. N Engl J Med 344:665-671, 2001. Mendelson CL: The aspiration of stomach contents into the lungs during obstetric anesthesia. Am J Obstet Gynecol 52:191-205, 1946. Ng A, Smith G: Gastroesophageal reflux and aspiration of gastric contents in anesthetic practice. Anesth Analg 93:494-513, 2001. Sellick BA: Cricoid pressure to control regurgitation of stomach contents during induction of anaesthesia. Lancet 2:404-406, 1961. Warner MA, Warner ME, Weber JG: Clinical significance of pulmonary aspiration during the perioperative period. Anesthesiology 78:56-62, 1993.

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46

Bronchospasm Joan Benca Case Synopsis

GENERAL ANESTHESIA

A 4-year-old boy with cerebral palsy has general anesthesia for repair of an inguinal hernia. Following intubation, peak inspiratory pressure increases acutely from 18 to 35 cm H2O. This is accompanied by a decrease in oxygen (O2) saturation from 100% to 82%, a decrease in blood pressure from 98/64 to 68/34 mm Hg, and an increase in heart rate from 90 to 140 beats per minute. Chest auscultation reveals diffuse bilateral expiratory wheezes.

PROBLEM ANALYSIS Definition In asthmatics, bronchospasm is caused by the spasmodic contraction of the bronchial smooth muscle. However, it occurs rarely during general anesthesia. In one series, wheezing occurred in only 0.17% of nonasthmatic and 0.8% of asthmatic patients. However, following induction with thiopental, wheezing has been reported in 6.7% to 8.1% of normal patients and in up to 45% of asthmatics. One review of a large number of asthmatic patients who received general anesthesia concluded that bronchospasm was a rare event and that associated adverse outcomes were uncommon. Thus, the relationship between intraoperative wheezing due to bronchospasm and severe adverse outcomes is unclear. However, data from the American Society of Anesthesiologists (ASA) closed claims study indicate that severe bronchospasm can result in death or brain injury. Patients who have bronchial asthma or chronic bronchitis may exhibit exaggerated responses to mechanical or chemical irritants or toxins, such as severe bronchoconstriction. Other factors can contribute to increased airway resistance with bronchospasm, such as mucosal edema, excessive mucus production and plugging, and desquamation of bronchial epithelium. Likely, all these in combination (bronchoconstriction, mucosal edema, mucus production, and inflammation) constitute bronchospasm, not just bronchial smooth muscle contraction. Normal airways are slightly constricted in their baseline condition. Bronchial smooth muscle tone is controlled by the parasympathetic nervous system via efferent vagal activity. Histamine also directly stimulates afferent parasympathetic pathways and directly increases bronchial smooth muscle tone. Muscarinic receptors can be blocked with atropine or glycopyrrolate. The parasympathetic nervous system is an important pathway in bronchoconstriction caused by inhaled irritants. Asthmatics have a smaller baseline airway caliber and hypertrophied bronchial smooth muscle, giving irritants greater access to receptors mediating bronchoconstriction. The smaller baseline airway caliber of asthmatic patients is significant; any further decrease in diameter will have a major effect on airway resistance, because laminar flow is proportional to the fourth power of the radius (Poiseuille’s law).

Large airways account for 80% of airflow resistance. The remaining 20% is accounted for by small airways and peripheral bronchioles. These smaller airways are sometimes referred to as the silent zone because their resistance can increase before there is a significant change in total airway resistance. Different factors trigger bronchospsasm in pediatric patients versus adult patients with obstructive airway disease. In pediatric patients, environmental allergens and viral respiratory illnesses are the most common causes of acute bronchospasm, whereas in adults, mechanical and chemical irritants are probably the most common causes. Further, viral illnesses can exacerbate symptoms in patients with asthma and can cause normal patients to exhibit increased airway reactivity. Thus, it is important to consider these mechanisms when tailoring therapy for individual patients.

Recognition Symptoms and signs of acute bronchospasm include wheezing, prolonged expiration, reduced breath sounds, and increased airway pressure during positive-pressure ventilation. O2 saturation may decrease, and the patient may become hypotensive. Owing to ventilation-perfusion mismatch, end-tidal carbon dioxide (CO2) concentration may decrease, even with an increased arterial CO2 concentration. End-tidal CO2 monitoring shows an upsloping curve, but this alone is not specific for bronchospasm; it indicates only obstruction to exhalation somewhere along the expiration pathway (i.e., from the patient’s alveolus to where the end-tidal CO2 sensor is positioned in the breathing circuit). Further, bronchospasm is not the only cause of wheezing. Table 46-1 lists other causes of wheezing in anesthetized, ventilated patients, and Table 46-2

Table 46–1

■

Causes of Nonbronchospastic (Asthmatic) Wheezing in Anesthetized Patients

Mechanical obstruction of endotracheal tube Negative-pressure expiration Tension pneumothorax Pulmonary edema Pulmonary aspiration of gastric contents Pulmonary embolism

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Causes of Increased Peak Airway Pressure during Ventilation

Increased inspiratory flow rate Excessive tidal volume: “alveolar overdistention” Increased intrapleural pressure Coughing Pleural effusion, ascites Abdominal gas insufflation, abdominal packs Restraints, bandages Head-down position Tension pneumothorax Increased resistance of endotracheal tube Small caliber, kinks, secretions Increased resistance of patient’s airway Secretions, bronchospasm* *If confronted with wheezing and increased peak inspiratory pressure, other causes must be ruled out before making the diagnosis of acute bronchospasm.

lists causes of increased peak inspiratory pressure during ventilation. Table 46- 3 lists causes of acute bronchospasm in anesthetized patients.

Risk Assessment Many patients with bronchospasm do not have a history of obstructive pulmonary disease. Also, most patients with obstructive pulmonary disease do not have bronchospasm under anesthesia. Factors that increase the risk for intraoperative bronchospasm are the following: ● ● ● ●

Recent viral upper respiratory infection Recent exacerbation of pulmonary symptoms Recent hospital admission for treatment of asthma Exposure to tobacco smoke

Bronchospasm may be more common in patients with tracheal intubation. One study showed a reversible component of increased airway system resistance after placement of an endotracheal tube, but not after placement of a laryngeal mask airway.

Implications Acute bronchospasm requires early diagnosis and treatment. Untreated, it causes hypoxemia, hypotension, and possibly brain damage or death. In the 1991 ASA closed claims study, 2% of the claims involved bronchospasm, and in 90% of these, the result was brain injury or death. The majority of these cases occurred during induction of general anesthesia and airway instrumentation. Airway instrumentation may precipitate acute bronchospasm, likely due to mechanical irritation and parasympathetic stimulation.

MANAGEMENT AND PREVENTION Acute bronchospasm is not limited to patients with a history of bronchial hyperreactivity. It is helpful, however, to make sure that patients with such a history receive bronchodilators and possibly steroids before the induction of general anesthesia. Patients with a history of asthma or chronic bronchitis who

Table 46–3

■

Causes of Acute Bronchospasm in Anesthetized Patients

Nonspecific bronchial hyperresponsiveness Allergic or anaphylactic reaction to drugs or blood transfusion Allergic or anaphylactic reaction to other allergens (e.g., latex) Exacerbation of asthma Pharmacologic factors (e.g., β-blockers, prostaglandin inhibitors, anticholinesterases) Stimulation of parasympathetic fibers and M2 and M3 muscarinic receptors Tracheal irritation from intubation

are scheduled for elective surgery should continue all their medications, and the chest examination should be at their baseline. Preoperative physical examination on the day of surgery must include chest auscultation. Active wheezing, worsening cough, more than usual sputum production, shortness of breath, and fever are reasons to delay anesthesia and surgery. A review of any previous anesthesia records may help in planning anesthetic management. For severe asthmatics, preoperative investigation may include a chest radiograph, 1-second forced expiratory volume (FEV1), and arterial blood gas analysis. For patients who are asymptomatic, no laboratory tests are necessary. Guidelines for the treatment of asthmatic patients were described by the 1997 National Heart, Lung, and Blood Institute’s Expert Panel on Asthma and include the use of steroids as anti-inflammatory agents (Table 46-4). It is unnecessary to treat all patients with a history of wheezing with steroids and bronchodilators, however. There is about an 8% incidence of asthma in the United States, so checking the FEV1 and starting all patients with asthma on steroids before anesthesia would be excessively costly. Those at highest risk for postoperative pulmonary complications (e.g., those having cardiac surgery, thoracotomy or airway surgery, or abdominal surgery, and those with a history of significant pulmonary symptoms) should probably receive steroids and have a baseline pulmonary function assessment. Interventions that may attenuate bronchial hyperreactivity during induction of anesthesia and airway manipulation include pretreatment with a nebulized β-agonist (e.g., albuterol, salbutamol, ipratroprium); intravenous (IV), nebulized, or intratracheal lidocaine; IV propofol induction; and preoperative oral or inhaled steroids. It is difficult to compare studies of interventions to attenuate bronchial hyperreactivity because some report airway resistance changes in response to tracheal intubation, others report responses to a histamine challenge, and still others report the incidence of perioperative clinical wheezing. Clearly, patients with significant bronchial hyperreactivity will benefit from the administration of steroids before anesthesia and surgery. A combination of steroids and β-agonists is clearly superior to either agent alone. For patients requiring general anesthesia, potent inhalational agents (at least equal to or greater than one minimum alveolar concentration) are the mainstays of anesthetic technique. All potent inhalational agents effectively reduce airway resistance. Using propofol as an induction agent, instead of thiopental or etomidate, reduces the incidence of postintubation wheezing in both

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Table 46–4

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■

Bronchospasm

191

Approach to Asthma Management in Adults and Children Older than Five Years Daily Medications

Step 4 Severe, persistent Asthma

Anti-inflammatory: inhaled steroid (high dose) and long-acting inhaled β2-agonist; possibly systemic steroids Short-acting bronchodilator: inhaled β2-agonist as needed for symptoms Anti-inflammatory: inhaled steroid (medium dose) or inhaled steroid (low to medium dose) and inhaled long-acting β2-agonist Short-acting bronchodilator: inhaled β2-agonist as needed for symptoms Anti-inflammatory: inhaled steroid (low dose) or cromolyn or nedrocromil Short-acting bronchodilator: inhaled β2-agonist as needed for symptoms Anti-inflammatory: no daily medication needed Short-acting bronchodilator: inhaled β2-agonist as needed for symptoms

Step 3 Moderate, persistent Asthma Step 2 Mild, persistent Asthma Step 1 Mild, intermittent Asthma

Adapted from National Heart, Lung, and Blood Institute National Asthma Education and Prevention Program EPR-2, 1997.

asthmatic and nonasthmatic patients. Both inhaled and IV lidocaine attenuate histamine-induced bronchospasm; however, the use of inhaled lidocaine attenuates histamineinduced bronchospasm at lower serum levels of local anesthetic than does IV lidocaine. This effect appears to be independent of topical airway anesthesia, because inhaled dyclonine provides excellent topical anesthesia but does not attenuate bronchial hyperreactivity to histamine. Laryngeal mask airways do not provoke bronchospasm and should be used if endotracheal intubation is not necessary, especially for pediatric patients with upper respiratory infections. Regional anesthesia is another option that avoids the problems associated with tracheal intubation. However, a neuraxial block may adversely affect pulmonary function. For patients with primarily reactive airway disease but without increased mucus production, the reduced ability to cough with a high neuraxial block is not a problem. Further, there is some evidence that a high epidural block does not exacerbate symptoms of asthma, but it is unclear whether it is the lack of tracheal intubation, serum concentration of local anesthetic, or some other effect of epidural anesthesia that contributes to the lower incidence of bronchospasm. Bronchospasm may still occur despite careful patient preparation and choice of an appropriate anesthetic technique. Treating bronchospasm under anesthesia can be difficult. One should administer100% O2 and use a potent inhalational anesthetic, but these steps are not always effective. With bronchospasm, it can be difficult to deepen anesthesia with an inhalational agent if ventilation is severely compromised.

Table 46–5

■

Adjunctive measures to treat the bronchospasm include IV lidocaine, IV propofol, subcutaneous (SC) terbutaline, SC or IV epinephrine, and a nebulized β-agonist. With severely impaired ventilation due to bronchospsam, SC or IV epinephrine should be given, and anesthesia should be deepened with an IV agent until effective ventilation is possible. Table 46-5 lists therapeutic steps for acute bronchospasm. β-Agonists given via a breathing circuit elbow adapter and a metered-dose inhaler are not as effective as those administered via a nebulizer or aerosol-enhancing chamber. Much of the delivered dose is contained in large (>5 μm) particles that do not reach the distal airways (a particle size of 1 to 5 μm is required for deposition in the distal airways). Therefore, only 10% to 20% of a dose delivered by a metered-dose inhaler reaches the small airways under optimal conditions in nonintubated patients. Delivery systems for intubated patients are even less effective, with as little as 1% to 2% of the delivered dose reaching the distal airways. Corticosteroids do not have an immediate beneficial effect in acute bronchospasm. However, they should be given to patients with acute bronchospasm to help reduce ongoing inflammatory changes that contribute to the problem. Finally, the most important factor in preventing bronchospasm during general anesthesia is to provide an adequate depth of anesthesia before and during airway manipulation and tracheal intubation, as well as during the surgical procedure itself. It is important to use anesthetic adjuncts, such as lidocaine and narcotics, in addition to potent inhalational agents to achieve this goal.

Therapy for Acute Bronchospasm

Deepen anesthesia with potent inhalational anesthetics or IV anesthetics Administer β-agonist bronchodilators (albuterol, metoproterenol, salbutamol, ipratroprium) using a metered-dose inhaler through an aerosolization chamber or by solution in a nebulizer placed in the anesthesia circuit Epinephrine Adult dose: 0.1 to 0.5 mL of 0.1% epinephrine solution SC Pediatric dose: 0.01 mL/kg of 0.1% epinephrine solution SC (maximum, 0.3 mL); 0.10 to 0.01 μg/kg/min infusion Isoproterenol Pediatric dose: 0.01 μg/kg SC up to a maximum of 0.3 mg; 0.01 to 0.1 μg/kg/min infusion Corticosteroids Hydrocortisone Methylprednisolone Dexamethasone

GENERAL ANESTHESIA

Step and Asthma Type

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Further Reading Berry A, Brimacombe J, Keller C, Verghese C: Pulmonary airway resistance with the endotracheal tube versus laryngeal mask airway in paralyzed anesthetized adult patients. Anesthesiology 90:395-397, 1999. Bishop MJ: Preoperative corticosteroids for reactive airway? Anesthesiology 100:1047-1049, 2004. Bishop MJ, Cheney FW: Anesthesia for patients with asthma: Low risk but not no risk. Anesthesiology 85:455-456, 1996. Cheney FW, Posner KL, Caplan RA: Adverse respiratory events infrequently leading to malpractice suits. Anesthesiology 75:932-939, 1991. Eames WO, Rooke GA, Wu RS, Bishop MJ: Comparison of the effects of etomidate, propofol, and thiopental on respiratory resistance after tracheal intubation. Anesthesiology 84:1307-1310, 1996. Gold MI, Helrich M: A study of the complications related to anesthesia in asthmatic patients. Anesth Analg 42:283-293, 1963. Groeben H, Grosswendt T, Silvanus M-T, et al: Airway anesthesia alone does not explain attenuation of histamine-induced bronchospasm by local anesthetics: A comparison of lidocaine, ropivicaine, and cyclonine. Anesthesiology 94:423-426, 2001. Groeben H, Silvanus M-T, Beste M, Peters J: Combined intravenous lidocaine and inhaled salbutamol protect against bronchial hyperreactivity more effectively than lidocaine or salbutamol alone. Anesthesiology 89:862-865, 1998. Kil H-K, Rooke GA, Ryan-Dykes MA, Bishop M: Effect of prophylactic bronchodilator treatment on lung resistance after tracheal intubation. Anesthesiology 81:43-46, 1994. Kim ES, Bishop MJ: Endotracheal intubation, but not laryngeal mask airway insertion, produces reversible bronchoconstriction. Anesthesiology 90:391-393, 1999.

National Institutes of Health Guidelines for the Diagnosis and Management of Asthma: Clinical Practice Guidelines Expert Panel Report-2. Bethesda, Md, National Institutes of Health, 1997. Olsson GL: Bronchospasm during anaesthesia: A computer aided incidence study of 136,929 patients. Acta Anaesthesiol Scand 31:244-252, 1987. Pizov R, Brown RH, Weiss YS, et al: Wheezing during induction of general anesthesia in patients with and without asthma: A randomized, blinded trial. Anesthesiology 82:1111-1114, 1995. Rooke GA, Choi J-H, Bishop M: The effect of isoflurane, halothane, sevoflurane, and thiopental/nitrous oxide on respiratory system resistance after tracheal intubation. Anesthesiology 86:1294-1297, 1997. Scalfaro P, Sly PD, Sims C, et al: Salbutamol prevents the increase of respiratory resistance caused by tracheal intubation during sevoflurane anesthesia in asthmatic children. Anesth Analg 93:888-890, 2001. Shnider SM, Papper EM: Anesthesia for the asthmatic patient. Anesthesiology 22:886-892, 1961. Silvanus M-T, Groeben H, Peters J: Corticosteroids and inhaled salbutamol in patients with reversible airway obstruction markedly decrease the incidence of bronchospasm after tracheal intubation. Anesthesiology 100:1052-1057, 2004. Tait AR, Pandit U, Voepel-Lewis T, et al: Use of the laryngeal mask airway in children with upper respiratory tract infections: A comparison with endotracheal intubation. Anesth Analg 86:706-709, 1998. Warner DO, Warner MA, Barnes RD, et al: Perioperative respiratory complications in patients with asthma. Anesthesiology 85:460-464, 1996.

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Perioperative Hypoxia John C. Boncyk

47

Case Synopsis GENERAL ANESTHESIA

A 70-year-old, 63-inch, 110-kg woman has laparoscopic cholecystectomy. After satisfactory anesthesia (nitrous oxide-oxygen, isoflurane, and a muscle relaxant) and surgery, she is transported to the postanesthesia care unit (PACU). Upon arrival in the PACU, the oxygen saturation of her arterial blood by pulse oximetry (SpO2) is 85% with 40% oxygen by facemask. She does not appear to be in any distress, and her other vital signs are stable. Over the next few minutes, her SpO2 trends down to 70%, and she becomes dyspneic.

PROBLEM ANALYSIS Definition Hypoxia is reduced oxygen (O2) tension within or outside the body; however, it is usually construed as reduced O2 tension at the tissue level. The oxygen cascade (Fig. 47-1) depicts the movement of O2 down its partial-pressure gradient from that of dry ambient air to the mitochondria. There are four categories of hypoxia: hypoxemia, anemic hypoxia, circulatory hypoxia, and histiocytic hypoxia. HYPOXEMIA Hypoxemia is decreased blood O2 tension. The lungs play a central role in all causes of hypoxemia: ● ● ● ● ●

Low fraction of inspired O2 (FiO2) Hypoventilation . . Alveolar ventilation-perfusion (VA/Q) mismatch Increased shunt Diffusion limitations

How these affect the alveolar-arterial O2 partial-pressure difference [P(A-a)O2], the response to breathing 100% O2, and the arterial partial pressure of carbon dioxide (CO2) is shown in Table 47-1. Low Inspired Oxygen Concentration. In addition to altitude and incorrect flowmeter settings, low FiO2 may be caused by faulty tank or hose connections, central gas distribution, or excessive inspired concentrations of nitrous oxide or nitrogen. The inspired partial pressure of O2 (PiO2) is directly related to atmospheric minus saturated water (H2O) vapor pressure (47 mm Hg at 37°C, regardless of altitude) and FiO2. Hypoventilation. With hypoventilation, alveolar ventila. tion (VA) cannot remove all produced CO2, so arterial and alveolar CO2 concentrations increase. With constant O2 consumption, hypoxia inevitably results. However, even a small increase in FiO2 will increase the arterial partial pressure of O2 (PaO2), as predicted by the alveolar gas equation: PAO2 = FiO2 • (PB – PiH2O) – (PACO2/RQ) where PAO2 and PACO2 are alveolar partial pressures of O2 and CO2, respectively; FiO2 is the fraction of inspired O2;

PB is atmospheric (barometric) pressure; PiH2O is saturated H2O vapor pressure; and RQ is the respiratory quotient (0.8). Assuming an FiO2 of 0.21, sea-level PB (760 mm Hg) and PiH2O (47 mm Hg), and variable PACO2, PAO2 decreases from 100 to 50 mm Hg as PACO2 increases from 40 to 80 mm Hg. Simply increasing FiO2 to 0.3 (PACO2 80 mm Hg) will increase PAO2 to 114 mm Hg. Ventilation-Perfusion Mismatch. Matching alveolar venti. . lation (VA) and perfusion (Q) involves many factors: ● ● ● ● ● ● ● ●

Ventilation volume Alveolar pressure Lung compliance Chest wall compliance Airway resistance Gravity (posture) Pulmonary blood flow Mode of ventilation

. . When ventilation and perfusion are matched, VA/Q . is. equal to 1.0. However, the lung does not have uniform VA/Q (Fig. 47-2). Dead space refers to ventilation without perfusion, and perfusion without ventilation is called shunt. Note in Figure 47-2 that the top of the lung has more dead-space ventilation (and higher PAO2) than the bottom, and the bottom of the lung has relatively more shunt . .(and lower PAO2). The reason PaO2 is decreased with . V. A/Q mismatch is that capillary blood leaving the high-VA/Q regions has higherthan-normal PO2 but only minimally enhanced O2 content (owing to the shape of the dissociation curve). . oxyhemoglobin . Blood leaving the low-VA/Q regions has both low PO2 and low O2 content;.this.situation reduces O2 transfer to blood far more than high-VA/Q regions . .can increase it, thereby increasing the P(A-a)O2 gradient. VA/Q mismatch also interferes with the uptake and elimination of anesthetic gases. Denitrogenation and the uptake and elimination of inhalational . . anesthetic agents are slowed in patients with significant VA/Q mismatch. . . Increased Shunt. Anatomic right-to-left shunt (Qs /Qt) is not considered here (see Chapter 157). Right-to-left transpulmonary shunt (i.e., mixed venous blood traverses the pulmonary capillary bed without being oxygenated) is the primary mechanism for hypoxia in anesthetized patients and in those with pneumonia and pulmonary edema. Right-to-left shunt (either anatomic or transpulmonary) is the only mechanism 193

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Inspired oxygen concentration FiO2 Alveolar ventilation • VA

Scatter of • • V/Q ratios

0

Venous admixture • • Qs/Qt

Arterial blood PaO2

Hemoglobin concentration Hb

Cell PO2

Cytoplasm

c

0 Vol. (%)

Table 47–1

Oxygen consumption • VO2

Alveolar gas PaO2

Mitochondria

5

Arterial blood –

50

Inspired gas FiO2

a

Mean capillary blood –

10

A ‘Ideal’ alveolar gas –

100

E′ End-expiratory gas –

15

PO2

I

150

Air humidified at 37°C –

20

Blood flow • Q

mm Hg Dry atmospheric air –

kPa

Figure 47–1 ■ Oxygen partialpressure cascade from dry atmospheric air (160 mm Hg) to the mitochondria (3 to 20 mm Hg). (From Lumb AB: Nunn’s Applied Respiratory Physiology, 5th ed. London, Butterworth-Heinemann, 2000, p 250.)

Barometric pressure PB

■

Causes of Hypoxemia and Their Effects on Alveolar-Arterial Oxygen Partial Pressure Difference, Response to 100% Oxygen, and Arterial Partial Pressure of Carbon Dioxide

Cause

P(A-a)O2

100% O2

PaCO2

Low FiO2 Hypoventilation . . VA/Q mismatch . . Shunt (Q s/Q t ) Diffusion limitation

Normal Normal Increased Increased Increased

Increased PaO2 Increased PaO2 Increased PaO2 No change Increased PaO2

Normal Increased Normal Normal Normal

FiO2, fraction of inspired oxygen; PaO2, arterial partial pressure of oxygen; P(A-a)O2, alveolar-arterial oxygen . . partial pressure difference; PaCO2, arterial partial pressure of carbon dioxide; VA/Q , alveolar ventilation-perfusion.

•

•

VA

Q

•

•

VA/Q

PO2

(L/min)

PCO2

PN2

(mm Hg)

7

.24

.07

3.3

132

28

553

11

.52

.50

1.0

108

39

566

13

.82

1.29

0.63

89

42

582

. . Figure 47–2 ■ Regional lung alveolar ventilation-perfusion (VA/Q ) ratios and gas composition for three zones of the upright lung. (From West JB: Pulmonary Pathophysiology: The Essentials. Baltimore, Williams & Wilkins, 1980.)

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500

ANEMIC HYPOXIA

400

Anemic hypoxia is caused by a low hemoglobin concentration or abnormal hemoglobin function. The following considerations are relevant to the discussion of anemic hypoxia:

% Shunt 0

● ●

10

Breathing air

● ●

20

0

30 50

20 40 60 80 Inspired O2 concentration (%)

100

Figure 47–3 ■ Relationship between arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2) for shunts of various percentages (isoshunt diagram). Isoshunt lines hold for hemoglobin of 10 to 14 g/dL and arterial partial pressure of carbon dioxide (PaCO2) of 25 to 40 mm Hg. (Modified from Nunn JF: Applied Respiratory Physiology, 4th ed. London, Butterworth-Heinemann, 1993, p 184.)

for hypoxemia in which PaO2 stays well below PAO2, even with an FiO2 of 1.0 (Fig. 47-3). Diffusion Limitation. Alveolar-capillary gas exchange is limited by the diffusing capacity of a particular gas across the alveolar-capillary membrane (D). The normal resting diffusing capacity for O2 (DO2) is 21 mL/minute per mm Hg P(A-a)O2. During exercise, DO2 can increase to 65 mL/minute per mm Hg P(A-a) . O.2 owing to increased capillary exchange and improved VA/Q matching. Diffusion limitation is an unusual cause of clinical hypoxemia.

Oxygen-Hemoglobin Dissociation Curve. The O2-Hb dissociation curve is sigmoidal and describes the affinity of hemoglobin for O2. P50 is the value for PO2 when hemoglobin is 50% saturated with O2. For normal hemoglobin in adults, this is 26.6 mm Hg (see Fig. 47-4). A shift to the right means that hemoglobin unloads its O2 to tissues more easily, and a shift to the left means that hemoglobin unloads its O2 with more difficulty. Four factors regulate the affinity of hemoglobin for O2: 1. Hydrogen ion (Bohr effect) 2. 2,3-Diphosphoglycerate

Total 100 Hb ñ O2 80

20

15 60 10 Mixed venous

SaO2 (%)

Figure 47–4 ■ Oxyhemoglobin dissociation curve relates arterial oxygen saturation (SaO2; left ordinate) and content (CaO2 [mL/dL]; right ordinate) to tension (PaO2; abscissa). This assumes hemoglobin = 15 g/dL, CaO2 = 20 mL/dL, and arteriovenous CaO2 difference = 5 mL/dL. (From Luce JM, Pierson DJ, Tyler ML: Intensive Respiratory Care, 2nd ed. Philadelphia, WB Saunders, 1993, p 27.)

Hemoglobin Structure-Function Relationship. Hemoglobin is composed of four subunits to form a tetrameric molecule. There are several different subunits (denoted α through ε), but only two are contained in a single hemoglobin molecule. Normal adult hemoglobin has two α and two β subunits. Heme, the iron-containing moiety, fits into each hemoglobin subunit, allowing it to bind one molecule of O2 (oxygenation). Interactions between hemoglobin subunits (subunit cooperativity) are responsible for the increased O2 affinity that occurs as each successive O2 molecule is bound to hemoglobin. This property accounts for the sigmoid shape of the O2-Hb dissociation curve (Fig. 47-4).

40

20

5

Dissolved 0

0 0

20

40

60

80

PaO2 (mm Hg)

100

600

CaO2 (mL/dL)

100

Normal arterial

200

Hemoglobin structure-function relationship Oxygen-hemoglobin (O2-Hb) dissociation curve Oxygen content Other hemoglobin species Minimum hemoglobin concentration

●

300

GENERAL ANESTHESIA

Arterial PO2 (mm Hg)

Chapter 47

(a –v)O2 Difference

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3. CO2 (Haldane effect) 4. Temperature An increase in any of these factors decreases the affinity of hemoglobin for O2 and shifts the O2-Hb dissociation curve to the right (i.e., increases P50), with more O2 unloaded to tissues for a given PO2. A decrease shifts the O2Hb dissociation curve to the left, with less O2 unloaded to tissues at any given PO2. Oxygen Content. Four moles of O2 bind with each mole of hemoglobin. The O2 carrying capacity of hemoglobin is 1.39 mL O2/g; however, this is typically lower in patients (about 1.34 mL/g), owing to the small amounts of methemoglobin and carboxyhemoglobin that are normally present. In addition, there is physically dissolved O2 in plasma (0.003 mL/dL per mm Hg of PO2), so arterial O2 content (CaO2) is expressed as follows: CaO2 = SaO2 • [Hb] • 1.34 + PaO2 • 0.003 or 20 mL/dL (see Fig. 47-4). However, the amount of O2 given off to the tissues is dependent on O2 content and the P50 of the hemoglobin species. Other Hemoglobin Species. Myoglobin serves both as an O2 buffer and to store O2 in muscle. All known vertebrate

myoglobins and β-hemoglobin subunits are similar in structure, but myoglobin binds O2 more avidly at low PO2 (Fig. 47-5) because it is a monomer (i.e., it does not undergo a significant conformational change with oxygenation). Thus, myoglobin remains fully saturated at O2 tensions between 15 and 30 mm Hg and unloads its O2 to the muscle mitochondria only at very low O2 tensions. Note that fetal hemoglobin also functions at a lower PO2 than adult hemoglobin (see Fig. 47-5). Minimum Hemoglobin Concentration. The American Society of Anesthesiologists (ASA) addressed optimal hemoglobin concentrations in its Practice Guidelines for Blood Component Therapy. The ASA task force reviewed the pertinent literature and made the following recommendations: Transfusion is rarely indicated when hemoglobin values are greater than 10 g/dL and is almost always indicated when values are less than 6 g/dL. Determining whether a transfusion is indicated when the hemoglobin is between 6 and 10 g/dL is based on the risk of tissue hypoxia in the individual patient, as judged by the patient’s physician. The organ at highest risk during anemia is normally the heart, because it has a baseline O2 extraction ratio greater than 50%. In a study evaluating outcomes for critically ill patients transfused to hemoglobins of 7 to 9 g/dL versus greater than 10 g/dL, patients had better outcomes when maintained at the lower range, unless they had clinically significant cardiac disease.

Oxygen tension (mm Hg) 100

0

20

40

60

80

100

80

100

Carboxyhemoglobin Myoglobin A

Percentage saturation

80

Normal adult hemoglobin

60

Fetal blood 40

B

20

0 20

40

60

Oxygen tension (mm Hg)

Figure 47–5 ■ Oxyhemoglobin dissociation curves for adult and fetal hemoglobin and carboxyhemoglobin and myoglobin. Note that fetal hemoglobin and myoglobin function at much lower oxygen tension (PO2) levels than adult hemoglobin, and carboxyhemoglobin has a very left-shifted curve. (From Lumb AB: Nunn’s Applied Respiratory Physiology, 5th ed. London, Butterworth-Heinemann, 2000, p 266.)

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CIRCULATORY HYPOXIA

HISTIOCYTIC HYPOXIA Histiocytic hypoxia occurs if the cell is unable to use delivered O2. Cyanide (CN –) toxicity is a classic example and may occur with the administration of large amounts of sodium nitroprusside. CN – binds to mitochondrial cytochrome oxidase, disrupting aerobic metabolism and resulting in anaerobic metabolism. Early signs of CN – toxicity are tachycardia, increased mixed venous O2 saturation, bright red venous blood, and lactic acidosis. All are due to the inability of tissue to utilize O2. Carbon monoxide (CO), in addition to binding to hemoglobin and shifting the oxyhemoglobin curve to the left, binds to cytochrome c and interferes with oxidative metabolism at the mitochondrial level. The high affinity of CO for hemoglobin (200 times that of O2) requires a high concentration of O2 (100% at 1 to 3 atmospheres) to effectively treat CO poisoning. The subsequent regeneration of functional cytochrome c by the displacement of CO with O2 may be the mechanism by which neuronal death is prevented.

Recognition CYANOSIS Before the widespread use of pulse oximetry, the early recognition of hypoxemia (PaO2 <60 mm Hg) was difficult. The presence of cyanotic mucosal membranes or dark blood in the operative field often provided the earliest warning, because the anesthetic agents in use before the availability of SpO2 measurement tended to attenuate the physiologic (tachycardia, hypertension, tachypnea) and mental status (restlessness, somnolence) changes caused by hypoxia.

Table 47–2

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Perioperative Hypoxia

197

Even so, cyanosis is an imprecise monitor of O2 status, because hemoglobin saturation must be below 85% before cyanosis is clinically apparent. Anemia makes detection even more difficult. More than 50 years ago, Comroe and Botehlo used ear oximetry to assess whether hypoxia was invariably associated with clinical cyanosis. Of 1723 SpO2 measurements with values between 71% and 80%, 12% were said to be associated with a normal skin color. It is possible that anemia skewed the results in some patients, because 5 g of reduced hemoglobin must be present to allow the detection of cyanosis. ARTERIAL BLOOD GAS ANALYSIS The gold standard for the diagnosis of hypoxemia is direct PaO2 measurement with a Clark electrode; however, this is invasive and is rarely a continuous parameter. PULSE OXIMETRY Pulse oximetry provides an early warning of hypoxemia (for SpO2 from 70% to 100%), provided that reduced or oxyhemoglobin is the only hemoglobin present. Carboxyhemoglobin and methemoglobin have similar absorption spectra to oxyhemoglobin and may provide misinformation; in fact, carboxyhemoglobin and oxyhemoglobin are indistinguishable. Pulse oximetry readings are falsely high in the presence of carboxyhemoglobin. As methemoglobin concentrations increase, pulse oximetry readings tend to approach 85%. Fluorescent lighting can also cause a falsely elevated SpO2. Blue nail polish, tape adhesive, methylene blue, indigo carmine, and isosulfan blue may cause falsely low SpO2 measurements. A co-oximeter measures the amounts of deoxyhemoglobin, oxyhemoglobin, carboxyhemoglobin, and methemoglobin in a blood sample. Such testing is indicated if SpO2 readings are dubious (e.g., intravenous dyes have been injected or infiltrated for surgical mapping) or CO poisoning is suspected. One major manufacturer has developed a pulse co-oximeter using eight light wavelengths and capable of measuring deoxyhemoglobin, oxyhemoglobin, carboxyhemoglobin, and methemoglobin. SPECIFIC ORGANS Methods used to assess the adequacy of O2 delivery to organs and tissues are summarized in Table 47-2.

Methods to Assess the Adequacy of Organ and Tissue Oxygen Delivery

Organ/Tissue

Method

Brain

Cerebral perfusion pressure (CPP = MAP – ICP), transcranial Doppler monitoring, electroencephalography, jugular venous O2 saturation, near-infrared spectroscopy, SSEPs/MEPs Electrocardiography, transesophageal echocardiography, coronary sinus O2 saturation, pulmonary artery catheter PaO2/FiO2 ratio, lung injury score, pulmonary arterial pressures, airway pressures (lung compliance and resistance), bronchoalveolar lavage Lactate production, hepatic enzymes, urine output and specific gravity, blood urea nitrogen and creatinine, gastric tonometry

Heart Lungs Liver, kidneys, gut

CPP, cerebral perfusion pressure; FiO2, fraction of inspired oxygen; ICP, intracranial pressure; MAP, mean arterial pressure; MEP, motor evoked potential; PaO2, arterial partial pressure of oxygen; SSEP, somatosensory evoked potential.

GENERAL ANESTHESIA

Circulatory hypoxia results from insufficient cardiac output. All conditions that reduce heart rate or stroke volume also reduce cardiac output. However, cardiac output must increase with increased tissue O2 utilization (O2 demand). Basal O2 delivery (DO2) is about 200 mL O2 per liter of cardiac output per minute (or 1000 mL O2 for a cardiac output of 5 L/minute). But what is critical for survival? One study in conscious, resting volunteers reported a rate of 7.5 mL/kg per minute (525 mL/minute for a 70-kg adult). A case report of a Jehovah’s Witness patient found critical DO2 to be 184 mL/minute per square meter.

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Measures to Reduce the Risk of Perioperative Hypoxia Based on Cause

Cause

Measure

Hypoxemia

Verify O2 supply (check anesthesia machine), confirm fail-safe function; use in-line O2 analyzer; preoxygenate; increase FiO2 Confirm breath sounds and end-tidal CO2; increase FiO2; assess lung compliance; use bronchodilators; maintain bronchopulmonary toilet Increase FiO2; restrict volatile agents (inhibit hypoxic pulmonary vasoconstriction) Use larger tidal volumes (10-15 mL/kg), intermittent sighs, frequent suctioning; add PEEP in high-risk patients (low FRC, obesity, hypoalbuminemia) Increase FiO2 Evaluate hematocrit frequently; give transfusions; increase FiO2 Increase cardiac output (volume, inotropes, circulatory assist device); relieve surgical compression or traction; increase FiO2 Limit SNP to ≤1 mg/kg over 1-3 hr and 0.5 mg/kg/hr over 24 hr, use another vasodilator†, or combine another vasodilator or SNP with a β-blocker to reduce the need for SNP; increase FiO2 (especially with CO poisoning)

Hypoventilation . . VA/Q mismatch Shunt Diffusion limitation* Anemia Circulatory failure O2 utilization

*Uncommon cause in healthy patients; may contribute to hypoxia after lung resection in patients with a reduced alveolar capillary bed (emphysema) and high cardiac output (sepsis). † Nicardipine IV may be preferred to SNP owing to the possibility of cyanide toxicity with large doses of the latter (see Chapters 1 and 77). CO, carbon. monoxide; CO2, carbon dioxide; FiO2, fraction of inspired oxygen; FRC, functional residual capacity; PEEP, positive end-expiratory pressure; SNP, sodium . nitroprusside; VA/Q , alveolar ventilation-perfusion.

Risk Assessment Inhalational anesthetics reduce the slope of the CO2-ventilation response curve in direct proportion to dose. Intravenous anesthetics (except ketamine) have the same effect. Inhalational anesthetics and propofol have also been shown to depress the ventilatory response to hypoxia, even at low doses. Functional residual capacity decreases upon the induction of anesthesia and does not return to normal until hours after anesthesia has been.terminated. This contributes to atelectasis . in alveoli with low VA/Q ratios. Volatile (but not intravenous) anesthetic agents oppose hypoxic pulmonary . vasoconstric. tion and increase the risk of hypoxia due to VA/Q mismatch. During recovery, elimination of nitrous oxide lowers PAO2 for several minutes. Anesthetics also reduce the tone in muscles involved in maintaining pharyngeal patency, increasing the risk of partial or complete airway obstruction. For these reasons, any patient having an anesthetic is at risk for hypoxia. Patients at increased risk for hypoxia include those with significant cardiopulmonary disease, morbid obesity, major trauma, thromboembolism, sepsis, head injury, pulmonary aspiration, and drug overdose. Risk also increases when diagnostic or therapeutic procedures are performed with the patient under intravenous sedation and inattentive, untrained, or preoccupied personnel are responsible for patient monitoring (e.g., interventional radiology or cardiology, magnetic resonance imaging). The risk for postoperative hypoxia is increased with long-acting anesthetic agents or neuromuscular blockers and with hypothermia or impaired drug metabolism and elimination.

Implications Severe hypoxia leads to ischemia or death. The central nervous system is most vulnerable to hypoxia (tolerating ≤5 minutes of normothermic ischemia). With hypoxia, anaerobic metabolism replaces aerobic metabolism, with a consequent fall in intracellular high-energy compounds and acidosis.

Insufficient high-energy compounds leads to the failure of intracellular pumps and the release of calcium from intracellular stores, damaging the intracellular elements. Acidosis and consequent anaerobic metabolism of glucose (causing lactic acidosis) produce further cell damage. As noted, the brain is most vulnerable, followed by the heart, the liver, and the kidneys.

MANAGEMENT ● ● ● ●

●

●

Identify and correct the primary cause. Supply supplemental oxygen; increase FiO2. Increase . O.2 delivery (transfusion, inotropes, or both). Treat VA/Q mismatch (positive end-expiratory pressure, sighs, inhaled nitric oxide, patient posturing). Protect vital organs (hypothermia, drugs, spinal drainage, steroids). Administer amyl nitrate, sodium nitrite, or thiosulfate for CN – toxicity.

PREVENTION Measures to reduce the risk of perioperative hypoxia from the causes discussed herein are listed in Table 47-3.

Further Reading Comroe JH, Botehlo S: The unreliability of cyanosis in the recognition of arterial hypoxemia. Am J Med Sci 214:1, 1947. Comroe JH, Forster RE, Dubois AB, et al: Diffusion. In The Lung: Clinical Physiology and Pulmonary Function Tests, 2nd ed. Chicago, Year Book Medical Publishers, 1962, pp 111-139. Hall AH: Systemic asphyxiants. In Irwin RS, Rippe JM (eds): Intensive Care Medicine, 5th ed. Philadelphia, JB Lippincott–Williams & Wilkins, 2003, pp 1608-1616. Herbert PC, Wells G, Blajchman MA, et al: A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 340:409-417, 1999.

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Moon RE, Camporesi EM: Respiratory monitoring. In Miller RD (ed): Anesthesia, 5th ed. Philadelphia, Churchill Livingstone, 2000, pp 1255-1295. Stehling LC, Doherty DO, Faust RJ, et al: Practice guidelines for blood component therapy. Anesthesiology 84:732-747, 1996. van Woerkens ECSM, Trouwborst A, van Lanshot JJB: Profound hemodilution: What is the critical hemodilution at which oxygen deliverydependent oxygen consumption starts in an anesthetized human? Anesth Analg 75:818-821, 1992. Wilson WC, Shapiro B: Perioperative hypoxia: The clinical spectrum and current oxygen monitoring methodology. Anesth Clin North Am 19:769-812, 2001.

GENERAL ANESTHESIA

Kelly SD, Lieberman J, Feiner JR, et al: Critical oxygen delivery in resting conscious humans is less than 7.5 mL O2 /kg/min [abstract]. Anesthesiology 87:58, 1997. Lumb AB: Anaesthesia. In Nunn’s Applied Respiratory Physiology, 5th ed. London, Butterworth Heinemann, 2000, pp 420-459. Lundsgaard C, Van Slyke DD: Cyanosis. Medicine 2:1, 1923. Martin RL, Lloyd HGE, Cowan AI: The early events of oxygen and glucose deprivation: Setting the scene for neuronal death? Trends Neurosci 17:251-256, 1994. Moon RE, Camporesi EM: Clinical care at altered environmental pressure. In Miller RD (ed): Anesthesia, 5th ed. Philadelphia, Churchill Livingstone, 2000, pp 2271-2301.

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48

Robert E. Kettler Case Synopsis A 45-year-old man presents for repair of an inguinal hernia. Other than a history of epilepsy, his past medical history is unremarkable. Except for the inguinal hernia, his physical examination is also unremarkable.

PROBLEM ANALYSIS Definition Epilepsy presents clinically as sudden, usually spontaneous episodes of involuntary motor activity with an altered level of consciousness. Epilepsy is a chronic condition. It has an annual incidence of 30 to 55 per 100,000 persons and affects about 2 million people in the United States. In addition, many patients with chronic pain syndromes are treated with anticonvulsants. Thus, anesthesiologists have a high probability of managing patients receiving these drugs. Epilepsy is classified according to seizure type, which also determines which drug will be used to manage the epileptic syndrome. Partial seizures originate in part of one cerebral hemisphere, whereas more generalized seizures originate throughout the hemispheres. Partial seizures are further classified as follows: ●

●

●

Simple partial seizures (i.e., with no impairment of level of consciousness) Complex partial seizures (i.e., with impairment of level of consciousness) Partial seizures that progress to generalized seizures

Generalized seizures are associated with an altered level of consciousness and are further classified as follows: ● ● ● ●

Absence seizures Myoclonic seizures Tonic-clonic seizures Atonic seizures

Complex partial seizures are the most common type of seizures in both adult and pediatric epileptic populations, constituting 23% and 39% of seizures in these groups, respectively. Generalized tonic-clonic seizures are second in frequency; this seizure type accounts for 25% of adults and 19% of children with epilepsy. The pathologic mechanism of epilepsy is unknown; however, several mechanisms have been proposed. It is thought that absence seizures may result from disruption of normal thalamocortical activity. As a result, cortical activity typical of non–rapid eye movement sleep occurs during periods of wakefulness. Such activity may be due to the abnormal function of T-type calcium channel or γ-aminobutyric acid (GABA) receptors. Other more generalized seizures may be 200

caused by an abnormality of the sodium channel, resulting in frequent depolarization. Additional evidence suggests that there is a reduction in potassium channel activity, which also increases the frequency of depolarization. Partial seizures may be due to structural alterations that result in hyperexcitability and altered GABA receptor functioning. The result of these neuronal changes is a pool of neurons that have the following characteristics: ● ● ● ●

Increased excitability Increased excitatory input Increased effectiveness of excitatory input Decreased inhibition

Primary physicians caring for patients with epilepsy must evaluate such patients with the goals of (1) determining that the patient does indeed have a seizure disorder, (2) the cause of the disorder, and (3) the type of seizure disorder. Goals of pharmacotherapy are reduction in seizure frequency, maximization of overall function, and minimal adverse effects. Typically, patients who present with one seizure but have no family history of epilepsy, no history of brain injury or mass lesion, and a normal electroencephalogram (EEG) are not treated. Such patients have only a 24% rate of seizure recurrence in the subsequent 2 years. However, patients who have a second seizure should be treated because the risk of recurrence then rises to 80%. Patients presenting with a new seizure, a history of brain injury or lesion, and an abnormal EEG have a 65% chance of recurrence in 2 years; therefore, these patients receive treatment. Most patients can be adequately managed with one drug. The principles that guide therapy are (1) the slow titration of medications to attain satisfactory seizure control, or (2) increased doses of medication until, in the absence of any appreciable effect on seizures, unacceptable side effects occur. If one medication fails, the physician should try a drug with a different mechanism of action rather than one with the same mechanism. If several trials of monotherapy are ineffective, polydrug therapy is a reasonable option. The risk of congenital anomalies is apparently increased in offspring of epileptic women, but extant studies contain a number of methodologic flaws. The presumption that antiepileptic drugs cause such anomalies is based on the observations that (1) a dose-response relationship seems to exist, and (2) multidrug therapy seems to increase the frequency of seizures owing to decreased serum levels of

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anticonvulsant drugs caused by the physiologic changes of pregnancy. Therefore, it is prudent to monitor serum drug concentrations in pregnant women. Also, pregnant women taking antiepileptic medications appear to be at 1.5- to 3-fold greater risk for hemorrhage, preterm labor, toxemia, placental abruption, and stillbirth than normal parturients.

No data exist regarding the incidence of epilepsy that first presents in the perioperative period. It is likely that the vast majority of patients with seizure disorders (aside from those associated with local anesthetic systemic toxicity; see Chapter 56) have been diagnosed and placed on antiseizure medications before they present for elective surgery. The history should suffice for recognizing the presence of epilepsy and assessing the patient’s compliance with the prescribed therapy. However, it is useful to query these patients about seizure frequency, known triggers, compliance with medications and dosing, and side effects of antiseizure medications.

Risk Assessment Patients with epilepsy have a mortality rate about 20 times that of the general population. Causes of death include accidents, arrhythmias, pulmonary edema, and myocardial infarction. Perioperative risk of morbidity and mortality has not been quantified with rigorous methodology. Likely, the most important consideration is to maintain the best possible control of seizure activity by maintaining appropriate antiepileptic therapy during the perioperative period. Antiepileptic medications typically have sedative effects, which could affect the speed of the patient’s recovery from general anesthesia, opiates, or sedative-hypnotics. Many of the anticonvulsants interfere with the hepatic metabolism of other drugs, and anesthesiologists must be aware of this issue. The drugs gabapentin, levetiracetam, tiagabine, and topiramate are less likely to affect hepatic metabolism. Finally, anesthesiologists may be called on to assist with the management of patients in status epilepticus (especially those with airway and cardiovascular issues). Patients in status epilepticus can have a very high mortality (10% to 30%) when not properly managed.

Implications Because of the prevalence of epilepsy and the increased use of anticonvulsants to manage various pain syndromes, anesthesiologists are likely to care for patients receiving anticonvulsants. Though unquantified, the risk of adverse outcomes in these patients is likely low. Awareness of the potential problems and use of the measures outlined in the next section are probably sufficient. There are no data to support the notion that one anesthetic technique is preferable to another.

MANAGEMENT AND PREVENTION Anesthesiologists should evaluate patients’ compliance with antiepileptic therapy and its effectiveness with a careful history.

Patients with Seizure Disorders

201

A patient’s report of the success of therapy is more meaningful than serum concentrations of the drugs used; the latter are used to evaluate compliance with therapy. Patients should take their usual medications with a sip of water before surgery and resume their regimens as soon as possible after surgery. If patients are unable to take oral medications, tablets can be crushed and given via a gastric tube. Consultation with a pharmacist may be necessary. If the enteric route is inappropriate, consider administering a parenteral form or substituting a comparable parenteral agent. Consultation with a neurologist may be needed. Because pain and sleep deprivation may provoke seizures, adequate pain management, combined with sedatives and anxiolytics, may be beneficial during the perioperative period. Anesthesiologists may be called on to assist with the management of status epilepticus. They have the necessary expertise in airway management, ventilation, intravascular line placement, cardiopulmonary monitoring, assessment and management of acid-base derangements, and use of neuromuscular blockade. It is important to keep in mind that untreated electrical brain activity can be associated with morbidity, even without seizure-related motor activity. When standard anticonvulsants fail to control status epilepticus, the anesthesiologist may have to administer general anesthesia with either midazolam or propofol. Effective general anesthesia for status epilepticus is induced with intravenous midazolam in a dose of 0.2 mg/kg and an intravenous maintenance dose of 0.75 to 10 μg/kg per minute. If propofol is used, it is induced with 1 to 2 mg/kg intravenously and maintained at 10 mg/kg per hour intravenously. The EEG is used to monitor the therapeutic effectiveness of either drug. If midazolam and propofol are ineffective, continuous intravenous thiopental or pentobarbital may be necessary. Patients under general anesthesia may require aggressive intravenous fluid therapy and hemodynamic support with dopamine or dobutamine to maintain adequate vital organ perfusion.

Further Reading Brodie MJ, Dichter MA: Antiepileptic drugs. N Engl J Med 334:168-175, 1996. Broune TR, Holmes GR: Epilepsy. N Engl J Med 344:1145-1151, 2001. Chang BS, Lowenstein DH: Epilepsy. N Engl J Med 349:1257-1266, 2003. Dichter MA, Brodie MJ: New antiepileptic drugs. N Engl J Med 334: 1583-1590, 1996. Lowenstein DH, Alldredge BK: Status epilepticus. N Engl J Med 338: 970-976, 1998. McNamara JC: Drugs effective in the therapy of the epilepsies. In Hardman JG, Limbird LE (eds): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York, McGraw-Hill, 2001, pp 521-547. Pedley TA: The epilepsies. In Goldman L, Bennett JC (eds): Cecil Textbook of Medicine, 21st ed. Philadelphia, WB Saunders, 2000, pp 2151-2163. Rowbotham MC, Petersen KL: Anticonvulsants and local anesthetic drugs. In Loeser JD, Butler SH, Chapman CR, Turk DC (eds): Bonica’s Management of Pain, 3rd ed. Philadelphia, JB Lippincott–Williams & Wilkins, 2001, pp 1727-1735.

GENERAL ANESTHESIA

Recognition

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ANCILLARY TOPICS

Blood and Blood Products: Transfusion Reaction

49

Lester T. Proctor Case Synopsis A 40-year-old woman undergoing an abdominal hysterectomy receives a unit of blood for a hematocrit of 24. Shortly after the transfusion begins, the patient’s blood pressure decreases by 20 mm Hg. The urine is noted to be bloody.

PROBLEM ANALYSIS Definition Transfusion reactions are broadly defined as any unfavorable consequence of blood transfusion. This chapter addresses primarily transfusion reactions that are immune mediated (Table 49-1).

Recognition When the transfusion of blood or a blood product is associated with fever, chills, flank pain, hemodynamic instability, wheals, nausea, and symptoms of anaphylaxis, this suggests the occurrence of a transfusion reaction. Certain symptoms (fever, chills, dyspnea, urticaria) can be helpful in delineating the type of reaction involved (Table 49-2). The identification of a transfusion reaction may be more challenging in anesthetized patients, when the only obvious symptoms may be hypotension, hemoglobinuria, or a bleeding diathesis. The features of the major immune-mediated transfusion reactions are noted in Table 49-3 and discussed individually in the paragraphs that follow.

the fixing of complement to red cell membranes, resulting in hemolysis and the release of cellular debris, which may trigger the development of disseminated intravascular hemolysis. Immune complexes also induce the formation of cytokines, which results in hypotension, fever, and the mobilization and activation of leukocytes. The elaboration of sympathetic amines in response to hypotension contributes to renal failure by renal vasoconstriction. AHTRs usually involve antibodies to antigens from the ABO blood group. Because these antibodies are readily identifiable, most AHTRs are the result of clerical errors. Symptoms of an AHTR, especially those occurring while a patient is anesthetized, are limited to hemoglobinuria, hemodynamic instability, bleeding diathesis, and failure to achieve the expected rise in hematocrit. A positive direct antiglobulin (Coombs’) test confirms the diagnosis. In contrast, evidence of hemolysis (e.g., hemoglobinuria, high free serum hemoglobin, low serum haptoglobin) with a negative direct Coombs’ test suggests hemolysis from a nonimmune cause (Table 49-4). FEBRILE NONHEMOLYTIC TRANSFUSION REACTION Febrile nonhemolytic transfusion reactions (FNTRs) present as a temperature increase of at least 1°C associated with

ACUTE HEMOLYTIC TRANSFUSION REACTION Acute hemolytic transfusion reactions (AHTRs) result from the binding of donor red blood cell antigens with recipient antibodies to form immune complexes. Complexes trigger

Table 49–1

■

Immune-Mediated Transfusion Reactions

Acute Hemolytic Nonhemolytic Febrile Allergic: anaphylactoid (immediate generalized reaction) or anaphylactic Transfusion-related acute lung injury

Delayed Hemolytic

202

Table 49–2

■

Determination of Transfusion Reaction Type by Presenting Symptom

Fever or chills Hemolytic transfusion reaction: acute or delayed Bacterial contamination of blood product Febrile nonhemolytic reaction Hemolysis (may present as hemoglobinuria) Acute hemolytic transfusion reaction Bacterial contamination of blood product Dyspnea Anaphylactic reaction Transfusion-related acute lung injury Congestive heart failure or volume overload Urticaria Urticarial transfusion reaction Adapted from Welborn JL, Hersch J: Blood transfusion reactions: Which are lifethreatening and which are not? Postgrad Med 90:125-138, 1991.

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Table 49–3

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Blood and Blood Products: Transfusion Reaction

■

203

Nonimmune-Mediated Causes of Hemolysis Cause

Characteristics

Incidence per Unit

Mortality

Acute hemolytic transfusion reaction

Recipient Ab vs donor RBC Ag

1 in 25,000

10%

Febrile nonhemolytic transfusion reaction Allergic reaction

Recipient Ab vs donor granulocyte Ag Recipient Ab vs donor Ag

Hemolysis, hypotension, DIC, hypoperfusion, renal failure, fever Fever

1 in 200

None reported

Urticaria: 1 in 200 Anaphylaxis: 1 in 150,000

Rare

Transfusion-related acute lung injury

Donor Ab vs recipient leukocyte Ag

1 in 2400

5%

Delayed hemolytic transfusion reaction

Recipient Ab vs donor RBC Ag

1 in 2500

Rare

IGR: hives only Anaphylactic: potentially severe hypotension and bronchospasm Respiratory distress with noncardiogenic pulmonary edema Fever, jaundice, decreasing hemoglobin

Ab, antibody; Ag, antigen; DIC, disseminated intravascular coagulation; IGR, immediate generalized reaction; RBC, red blood cell.

a transfusion and without any other explanation. FNTRs are usually caused by binding of the recipient’s antibodies to antigens on donor granulocytes, lymphocytes, or platelets. An FNTR often presents with chills and rigor and is a diagnosis of exclusion once AHTR and bacterial contamination of transfused blood are ruled out. ALLERGIC REACTION Allergic reactions are either immunoglobulin E (IgE) mediated (anaphylactic) or not IgE mediated (anaphylactoid or immediate generalized reaction; see Chapter 27). Immediate generalized reactions are typically mild, involving reactions to transfused serum proteins, medications taken by

Table 49–4

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Nonimmune-Mediated Causes of Hemolysis

Mechanical trauma to red blood cells Thermal injury Overheating (>40°C) Freezing or partial freezing Osmotic injury Sterile water for bladder irrigation during cystoscopy Reconstitution of red blood cells with nonisotonic solutions Shearing injury High-pressure infusion or small catheter size Mechanical valves, vascular grafts, hematomas Extracorporeal circulation Bacterial contamination (gram-negative bacteremia) Drug-induced hemolysis: penicillin, quinidine, methyldopa Disease-mediated hemolysis Hemolytic anemias: glucose-6-phosphate dehydrogenase deficiency, autoimmune anemias Paroxysmal nocturnal hemoglobinuria; hemolytic uremic syndrome Thrombotic thrombocytopenic purpura; malaria; mononucleosis Sepsis with disseminated intravascular coagulation Modified from Cooper CL: Complications of transfusion therapy. In Lake CL, Moore RA (eds): Blood: Hemostasis, Transfusion, and Alternatives in the Perioperative Period. New York, Raven Press, 1995, p 320.

the donor (e.g., penicillin), or additives from blood product preparation. Diagnosis is based on the presence of only mild allergic symptoms that respond to an antihistamine. Anaphylactic reactions are typically more severe in presentation and usually manifest within minutes after the transfusion begins. Symptoms include shock, respiratory distress, dermatologic findings, and generalized enteritis, usually in the absence of fever. Although most such reactions commence immediately after the transfusion begins, the presentation may be delayed for up to an hour after the transfusion has been completed. Anaphylactic reactions are most commonly mounted by patients who lack immunoglobulin A (IgA) but have an anti-IgA antibody. IgA deficiency occurs in 1 in 700 patients in the general population, although only 20% of IgA-deficient patients develop antibodies to IgA. Of these, only 20% have clinically significant reactions. The diagnosis is usually based on the striking presentation and confirmed by finding anti-IgA antibody in the patient’s serum. TRANSFUSION-RELATED ACUTE LUNG INJURY Transfusion-related acute lung injury (TRALI) presents as a syndrome of respiratory distress, fever, hypoxia, hypotension, and noncardiogenic pulmonary edema that occurs 1 to 6 hours after the transfusion of plasma containing blood products. The proposed mechanism involves the reaction between the donor’s antibodies and the recipient’s leukocytes. Cytokines present in the donated unit may also augment this response. An aggressive search for cardiogenic or other noncardiogenic sources of pulmonary edema must be undertaken, because TRALI is relatively rare. The diagnosis may be confirmed by identifying an antileukocyte antibody in the donor blood unit that corresponds to the patient’s human leukocyte antigen type. DELAYED HEMOLYTIC TRANSFUSION REACTION Delayed hemolytic transfusion reactions (DHTRs) present with red blood cell hemolysis from 2 days to several months after a transfusion. Symptoms and signs include fever,

GENERAL ANESTHESIA

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mild jaundice, and an inexplicable decline in hemoglobin concentration. Other serious symptoms, more typical of an AHTR (e.g., renal failure, hemoglobinuria), are uncommon. DHTRs commonly result in postoperative jaundice and may significantly lower the patient’s hemoglobin level. The cause of DHTRs is the delayed generation of an antibody to a donor antigen to which the recipient has been previously exposed. The culprit antibody binds a non-ABO group such as the Rh, Kidd, Kell, or Duffy groups. The diagnosis of a DHTR may be difficult. A direct antiglobulin test is not positive until several days after the transfusion and then remains positive only while there are active symptoms.

Risk Assessment The risk of developing a transfusion reaction varies, depending on the type of reaction. An AHTR typically results from an antibody against an antigen of the ABO blood group. Because antibodies to the ABO group are readily identifiable, an AHTR is usually the result of a clerical error, typically involving the administration of a unit of blood to a patient without confirming the patient’s identification. Careful attention to paperwork, especially during multiple-unit transfusions, should reduce the incidence of AHTRs. FNTRs occur more frequently in multiparous women and in patients who have received multiple transfusions, because antibody production is induced by prior exposure to foreign antigens. It has been estimated that up to 55% of women develop leukoagglutinins after three pregnancies. Allergic reactions can occur in any patient, although certain groups of patients are at higher risk than others. The most severe reactions are noted in IgA-deficient patients. Most of these persons are genetically deficient in IgA, although some with common variable immune deficiency who receive multiple gamma globulin injections may also develop antiIgA antibodies. Less severe reactions are typical of non-IgAdeficient patients. Renal dialysis patients are particularly prone to allergic reactions because they may develop a sensitivity to sterilizers or plasticizers found in dialysis equipment and react to these substances in transfusion equipment. Atopic patients are more sensitive to vasoactive substances released during reactions, and they manifest more clinically significant reactions than do nonatopic individuals. TRALI does not appear to be any more common in one patient population than another. Screening of donor serum is discussed under the section on prevention. DHTRs occur almost exclusively in patients who have undergone multiple transfusions in the past or in multiparous women. In most cases, these individuals have become sensitized to non-ABO blood groups that are undetectable in the serum until after the patient has been re-exposed to the antigen via transfusion.

20 deaths per year due to AHTRs in the United States. TRALI is a rare complication but results in an estimated 5% mortality. FNTRs and allergic reactions rarely result in death.

MANAGEMENT Management of transfusion reactions varies with the type of reaction involved. Often the clinician must base therapy on only one or two symptoms. The management of any reaction begins by stopping the transfusion while maintaining intravenous access. Next, the type of reaction must be identified. This section outlines an appropriate diagnostic plan based on the presenting symptom. Once the type of transfusion reaction has been identified, more specific therapy can be applied. Therapies for immune-mediated transfusion reactions are given in Table 49-5.

Fever and Chills Fever and chills, the most common presenting symptoms of a transfusion reaction, are usually due to an FNTR, AHTR, or sepsis from bacterial contamination. The primary goal is to rule out an AHTR by (1) confirming that the patient is receiving the intended unit of blood and (2) drawing a sample of the patient’s blood for a free hemoglobin and direct antiglobulin (Coombs’) test. Ruling out septic contamination requires (1) examination of the unit for discoloration or gas and (2) stain and culture for bacteria in the transfused blood and the patient’s blood. In the absence of positive results, the diagnosis of exclusion is FNTR. The occurrence of hemoglobinuria, hypotension, or bleeding diathesis should prompt a second look for AHTR or septic contamination, because these findings are not characteristic of FNTR.

Hemoglobinuria Hemoglobinuria may be the sole indicator of a transfusion reaction, and its presence should prompt a search for evidence of hemolysis, which may be caused by an AHTR, bacterial contamination, or a nonimmune-mediated source (see Table 49-4). Hemolysis in the absence of other symptoms is characteristic of a nonimmune-mediated hemolytic cause.

Dyspnea Dyspnea may be caused by an anaphylactic reaction, cardiogenic pulmonary edema from fluid overload, or (more rarely) TRALI. The management of dyspnea relies less on making the diagnosis than on supportive care for the patient’s condition, which may require mechanical ventilation. Invasive monitoring or transesophageal echocardiography to determine whether the cause of the pulmonary edema is cardiogenic or noncardiogenic is often helpful.

Implications The risk of death associated with the major immunemediated transfusion reactions is given in Table 49-3. The majority of transfusion-related deaths are related to AHTRs. It is estimated that 1 out of 33,000 transfused units of blood are incompatible. This estimate predicts a mortality of

Urticaria Urticaria in the absence of other symptoms is characteristic of an immediate generalized reaction, although the patient should be reevaluated periodically for progression to a fullblown anaphylactic reaction.

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Table 49–5

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Blood and Blood Products: Transfusion Reaction

205

Treatment of Immune-Mediated Transfusion Reactions Treatment

Acute hemolytic transfusion reaction (AHTR) with positive direct antiglobulin test

1. 2. 3. 4. 5. 1. 2.

Febrile reaction secondary to bacterial contamination Febrile nonhemolytic transfusion reaction

1. 2. 3. 4.

Allergic: urticarial reaction

1. 2. 3. 4. 1. 2. 3. 4. 1. 2.

Allergic: anaphylaxis

Transfusion-related acute lung injury

Delayed hemolytic transfusion reaction

3. 1. 2. 3.

Stop the transfusion Maintain systolic blood pressure >100 mm Hg Maintain urine output (diuretics; fluids ≥100 mL/hr) Support blood pressure with pressors as needed Maintain vigilance for DIC and treat as needed Treat as for AHTR (above) After Gram stain and cultures, cover with broad-spectrum antibiotic for gram-positive and -negative organisms Stop the transfusion Rule out AHTR and bacterial contamination Administer an antipyretic Consider a leukocyte filter (blood products) or antipyretics before the next transfusion Stop the transfusion Administer diphenhydramine 20-50 mg IV Restart blood slowly after 30 min Consider giving an antihistamine before the next transfusion Stop the transfusion Administer epinephrine 400 μg SC Support ventilation; use bronchodilators or intubation if needed Support circulation; administer vasopressors if needed Stop the transfusion Rule out cardiogenic pulmonary edema and other sources of noncardiogenic pulmonary edema Support ventilation as needed Usually, no acute treatment required Maintain urine output with evidence of renal failure Maintain hemoglobin level with additional transfusions after identifying responsible antibody

DIC, disseminated intravascular coagulation. Data from Jenner PW, Holland PV: Diagnosis and management of transfusion reactions. In Petz LD, Swisher SN, Kleinman S, et al (eds): Clinical Practice of Transfusion Medicine. New York, Churchill Livingstone, 1996, p 908; and Welborn JL, Hersch J: Blood transfusion reactions: Which are life-threatening and which are not? Postgrad Med 90:125-138, 1991.

PREVENTION ●

Vigilance and a high index of suspicion lead to early recognition of transfusion reactions and may limit their severity. In addition, specific measures can be taken to reduce the risk of certain immune-mediated transfusion reactions: ●

●

●

●

●

AHTRs are usually the result of misidentification of the patient or the unit of blood. Because one third of all transfusion reactions occur in the operating room, the anesthesiologist should carefully match the patient with the blood unit to limit the risk of AHTR. FNTRs may be limited by the use of leukocyte filters to reduce the number of leukocytes in transfused blood. Prophylactic antipyretics may help limit the symptoms. Antihistamines can be used before transfusion to pretreat patients with a history of mild allergic reactions. The use of washed blood products is generally reserved for patients who do not benefit from antihistamines. Patients with known IgA deficiency should receive blood products from IgA-deficient donors. In an emergency situation, washing of red blood cells or platelets should limit the risk of a fatal reaction. TRALI can be prevented if the antibody responsible for the antileukocyte reaction can be determined. If so, the

administration of blood products containing this antibody can be avoided. DHTRs usually cannot be prevented before the first episode, because the antibody responsible for the reaction is present in undetectable titers. Once a DHTR has occurred, however, and the culprit antibody has been identified, blood with the corresponding antigen should be avoided.

Further Reading Brand A: Immunological aspects of blood transfusions. Transpl Immunol 10:183-190, 2002. Cooper CL: Complications of transfusion therapy. In Lake CL, Moore RA (eds): Blood: Hemostasis, Transfusion, and Alternatives in the Perioperative Period. New York, Raven Press, 1995, pp 319-334. Gilstad CW: Anaphylactic transfusion reactions. Curr Opin Hematol 10:419-423, 2003. Heddle NM: Universal leukoreduction and acute transfusion reactions: Putting the puzzle together. Transfusion 44:1-4, 2004. Janatpour K, Holland PV: Noninfectious serious hazards of transfusion. Curr Hematol Rpt 1:149-155, 2002. Jenner PW, Holland PV: Diagnosis and management of transfusion reactions. In Petz LD, Swisher SN, Kleinman S, et al (eds): Clinical Practice of Transfusion Medicine. New York, Churchill Livingstone, 1996, pp 905-929. Lozano M, Cid J: The clinical implications of platelet transfusions associated with ABO or Rh(D) incompatibility. Transfus Med Rev 17:57-68, 2003.

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Reaction Type

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Noninfectious Complications of Blood Transfusion. In Technical Manual of the American Association of Blood Banks. Bethesda, Md., American Association of Blood Banks, 543-562, 1996. Sharma AD, Grocott HP: Platelet transfusion reactions: febrile nonhemolytic reaction or bacterial contamination? Diagnosis, detection, and current preventive modalities. J Cardiothorac Vasc Anes 14:460-466, 2000.

Telen MJ: Principles and problems of transfusion in sickle cell disease. Sem Hematol 38:315-323, 2001. Welborn JL, Hersch J: Blood transfusion reactions: Which are life-threatening and which are not? Postgrad Med 90:125-138, 1991.

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Blood and Blood Products: Hepatitis and HIV

50

Jonathan M. Anagnostou GENERAL ANESTHESIA

Case Synopsis An otherwise healthy 40-year-old woman experiences 2000 mL blood loss while undergoing abdominal hysterectomy. She receives 2 units of packed red blood cells during the course of her resuscitation. Following surgery, the patient’s husband is very upset that his wife “probably caught something from the blood she received.”

PROBLEM ANALYSIS Definition Blood-borne infections are a concern of patients, family members, and health care providers alike. Individuals may be exposed to these infections through the transfusion of banked blood products or through blood-contaminated injuries (e.g., needle sticks). Although blood products (especially platelets) can transmit bacterial infections, viral infections are more common. Despite the modern screening of blood products, hepatitis C is a major cause of post-transfusion hepatitis, although hepatitis B remains a clinical concern. Hepatitis D is a blood-borne viral infection that affects only patients infected with hepatitis B, because it requires the hepatitis B virus for replication. Although the parenteral spread of hepatitis A has been reported, it is normally spread through the oral-fecal route. Human immunodeficiency virus (HIV) has become an increasing concern since its recognition in the early 1980s.

of suspicion and the development of viral symptoms weeks to months after exposure. Initial HIV infection is often asymptomatic, although roughly half of infected patients develop a viral syndrome (e.g., fever, pharyngitis, myalgia, lymphadenopathy) within 6 weeks of exposure. Similarly, initial infection with hepatitis B or C may be asymptomatic or may involve a flulike syndrome weeks or even months after exposure. Clinical jaundice develops in less than one third of patients. A chronic infection may result in 10% of those infected with hepatitis B and in up to 80% to 90% of patients with hepatitis C. The development of symptoms consistent with hepatitis (e.g., malaise, jaundice) several weeks after exposure to blood should prompt referral for appropriate hematologic studies, such as hepatic enzyme levels and antigen-antibody testing. Antibody testing for hepatitis B has been available for many years, and similar testing for hepatitis C is now available. Serologic evidence of anti-HIV antibodies by enzyme-linked immunosorbent assay (ELISA) testing confirms HIV infection.

Risk Assessment Recognition Given the emotional impact associated with the risk of bloodborne infections, this issue must be put in its proper perspective during the patient’s preoperative visit. In the case of any procedure that might involve significant blood loss, a discussion of the potential risks of transfusion should take place. Many hospitals include a separate consent form for blood products in their admission paperwork. Blood-contaminated injuries to health care providers are another important issue. Each health care facility should have defined infection-control procedures to deal with such events. Although painful needle-stick or scalpel injuries are obvious, practitioners should also recognize that blood seepage under torn or defective gloves onto a preexisting hand wound also constitutes a blood-contaminated injury. Clearly, risks from patient blood contact are significant. In the United States, approximately 0.2% to 0.4% of the population are carriers of the hepatitis B virus, and 0.5% carry hepatitis C. The incidence of HIV infection varies widely from near zero in some areas to well over 5% in certain urban populations. Following transfusion or other blood exposure, the diagnosis of hepatitis or HIV infection depends on an index

The risk of transfusion-related infection is estimated as follows (per unit of blood): ● ●

Hepatitis: 1 in 180,000 to 220,000 HIV: 1 in 900,000 to 1.4 million

The risk of needle-stick infection is estimated as follows (per incident): ● ●

HIV-positive: 1 in 250 to 300 Hepatitis C-positive: 1 in 20

Improved blood screening has reduced but not eliminated the risk of transfusion-associated infections. False-negative test results can occur, and in the case of antibody testing (e.g., for HIV), there is an interval between infection with the virus and the appearance of detectable antibodies in blood. It was estimated in 1996 that the risk of transfusionrelated hepatitis in the United States was approximately 0.3 per 10,000 units transfused, and the risk of HIV infection from a single transfused blood unit was roughly 1 in 493,000 transfusions. Blood-contaminated injuries are a significant occupational hazard for health care workers. The risk of infection 207

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via a hepatitis C–contaminated needle stick is estimated to be 0.5%, and that for anti-HIV antibody seroconversion after an HIV-contaminated needle stick is approximately 0.004%. The risk of infection may be greater under certain circumstances (e.g., hollow-core needles, large virus inoculum).

Implications Infections from blood-borne viruses can be benign or lethal, and the emotional impact of blood transfusion can represent a distinct psychological complication. The manifestations of hepatitis range from an asymptomatic infection to fulminant hepatic dysfunction and death. Chronic infection with hepatitis B or C can result in cirrhosis, hepatic failure, or hepatocellular carcinoma. Although HIV infection commonly leads to acquired immunodeficiency syndrome (AIDS), many otherwise healthy individuals remain asymptomatic for years after documented HIV seroconversion.

MANAGEMENT Management of transfusion-related hepatitis or AIDS is clearly beyond the typical anesthesia provider’s scope of practice. Recognition and appropriate referral are of the utmost importance, although transmission of these illnesses is only retrospectively linked with a patient’s history of blood product transfusion or a provider’s history of occupational exposure.

PREVENTION Avoiding contact with blood and blood products is the obvious key to prevention. Blood or banked blood products should not be administered as generic volume expanders but should be given only for specific indications, such as to increase oxygen carrying capacity or increase clotting factor levels. The predonation of autologous blood, the use of isovolumic hemodilution, or both may be useful in avoiding exposure to homologous blood products. For practitioners, strict

Table 50–1

■

adherence to universal precautions (Table 50-1) should minimize the risk of contact with potentially infectious blood and body fluids. Needle-stick injuries can be minimized by careful operating technique and by the use of alternative equipment when possible (e.g., needleless intravenous injection systems, “blunt” suture needles). Vaccination is an important preventive measure for many infectious diseases. Although no vaccines are currently available for HIV or hepatitis C, hepatitis B vaccination is strongly advised for high-risk health care providers, including anesthesia personnel. For those who have received the vaccination, no set schedule for booster doses has been established. With the recent recommendation of the U.S. Public Health Service for childhood hepatitis B vaccination, the overall incidence of hepatitis in the United States (including hepatitis D) should continue to decline. When a blood-contaminated injury occurs, the affected area should be washed immediately with soap and water. Involved mucous membranes are flushed with water or an appropriate salt solution. Injuries contaminated with blood should be reported to the institution’s infection-control office for documentation, counseling, and management. There is no accepted postexposure prophylaxis available for hepatitis C, but if the source patient is infected with hepatitis B and the provider has not been immunized, passive immunization with hepatitis immune globulin (0.06 mL/kg intramuscularly), followed by hepatitis B vaccination, is advised. If the source patient is HIV infected, the initiation of postexposure chemoprophylaxis within 24 to 36 hours may be appropriate to reduce the risk of HIV infection. Although data regarding efficacy are limited, chemoprophylaxis after percutaneous exposure normally includes the use of two or even three antiretroviral drugs (e.g., zidovudine, lamivudine, stavudine, didanosine). In practice, the timely institution of chemoprophylaxis may be complicated if the source patient’s HIV status is unknown and by the legal difficulties involved in obtaining informed consent for HIV testing. The National HIV/AIDS Clinician’s Consultation Center offers a 24-hour postexposure prophylaxis hotline (1-888-HIV-4911). The Centers for Disease Control and Prevention has current information on its Web site (http://www.cdc.gov/niosh/topics/bbp).

Highlights of Universal Precautions

Barrier precautions with all patients to prevent blood and body fluid contact Gloves when contacting blood or body fluids or nonintact skin (do not wash or disinfect gloves, because disinfectants can cause deterioration) Gown, mask, eyewear if splash or spray is likely Avoid sharps injuries Prompt disposal in appropriate container Avoid recapping needles Hand washing after glove removal or any blood or body fluid contact Artificial mouthpieces and airways for cardiopulmonary resuscitation Providers with exudative or weeping cutaneous lesions should refrain from direct patient contact until condition resolves From Centers for Disease Control and Prevention: Recommendations for prevention of HIV transmission in the health-care setting. MMWR Morb Mortal Wkly Rep 36:3-18, 1987; updated MMWR Morb Mortal Wkly Rep 37:377-388, 1988.

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209

Perillo RG, Regenstein FG: Viral and immune hepatitis. In Kelly WN (ed): Textbook of Internal Medicine. Philadelphia, Lippincott-Raven, 1997, pp 822-833. Petrovitch CT: Hemostasis and hemotherapy. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 3rd ed. Philadelphia, Lippincott-Raven, 1997, pp 189-217. Rehm SJ: Approach to the patient with human immunodeficiency virus exposure. In Kelly WN (ed): Textbook of Internal Medicine. Philadelphia, Lippincott-Raven, 1997, pp 1867-1868. Schreiber GB, Busch MP, Kleinman SH, et al: The risk of transfusiontransmitted viral infections. N Engl J Med 334:1685-1690, 1996.

GENERAL ANESTHESIA

Centers for Disease Control and Prevention: Updated US Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Morb Mortal Wkly Rep 50:1-54, 2001. Goodnough LT: Risks of blood transfusion. Crit Care Med 31:S678-S686, 2003. Murray DJ: Blood component therapy: Indications and risks. In Rogers MC, Tinker JH, Covino BG, et al (eds): Principles and Practice of Anesthesiology. St. Louis, Mosby–Year Book, 1993, pp 2482-2498. Ockner RK: Acute viral hepatitis. In Wyngaarden JB, Smith LH Jr, Bennett JC (eds): Cecil Textbook of Medicine. Philadelphia, WB Saunders, 1992, pp 763-771.

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Nosocomial Infections: Bacterial Pneumonia

51

Charles E. Edmiston, Jr. Case Synopsis A 78-year-old man is diagnosed with pneumonia 4 days after exploratory abdominal laparotomy. While the patient was mechanically ventilated, a fever and purulent tracheal secretions developed. Radiographic evidence was consistent with pneumonia involving both lower lobes.

PROBLEM ANALYSIS Definition Nosocomial, or hospital-acquired, pneumonia is defined as pneumonia occurring more than 48 hours after hospital admission. However, this definition excludes any infection that is incubating at the time of hospital admission. Pneumonia is the second most common nosocomial infection. The proportion of patients who acquire pneumonia in the intensive care unit (ICU) ranges from 10% to 65%. This is associated with significant morbidity and mortality. Data from the National Nosocomial Infection Surveillance program indicate that 75% of all cases of nosocomial bacterial pneumonia occur postoperatively. Patients having a thoracoabdominal procedure have a 38-fold higher risk than other patients do. Those with mechanically assisted ventilation constitute the population at highest risk for the development of nosocomial pneumonia. Ventilator-associated pneumonia occurs in 8% to 28% of mechanically ventilated patients. Rates of ventilator-associated pneumonia are dependent on the duration of mechanical ventilation; the incremental risk is 1% to 3% per day (5% at 5 days, and >68% for patients ventilated for ≥30 days). Along with causing significant morbidity and mortality, ventilator-associated pneumonia is an important determinant of excessive hospital length of stay and inpatient resource utilization. The most probable cause of nosocomial pneumonia is colonization of the aerodigestive tract by pathogenic microorganisms. Subsequently, these contaminated secretions are aspirated into the lower airways. Aerobic microorganisms are the predominant isolates recovered, including gram-negative bacilli such as Escherichia coli, Klebsiella species, Enterobacter species, and Pseudomonas aeruginosa. Staphylococcus aureus and Streptococcus pneumoniae are other important isolates and may express drug resistance (e.g., methicillin-resistant S. aureus [MRSA], penicillinresistant pneumococci). Late-onset infections (occurring >72 hours after admission) are most often associated with multidrug-resistant microorganisms such as Acinetobacter, Pseudomonas, and MRSA. Yeasts such as Candida albicans or other Candida species are an infrequent cause of nosocomial pneumonia (<4%). 210

Pneumonia-associated morbidity prolongs hospitalizations by 4 to 9 days and is associated with significant institutional costs. Death from nosocomial pneumonia accounts for 60% of all nosocomial-associated fatalities.

Recognition Nosocomial bacterial pneumonia is extremely difficult to diagnose, especially in intubated ICU patients with mechanically assisted ventilation. Generally accepted criteria include the following: fever, cough with productive or purulent sputum, and radiographic evidence of a pulmonary infiltrate. The diagnosis of pneumonia in these patients is especially difficult because traditional culture methods may be highly nonspecific or have low sensitivity. Endotracheal aspiration is the most common sampling technique used in mechanically ventilated patients. The accuracy of the method, however, is compromised by contamination with upper respiratory flora. A consensus recommendation proposed a standardized method for diagnosing pneumonia in this patient population. It is based on direct—rather than clinical—evidence and includes one of the following: ●

● ●

Bronchoscopically acquired protective specimen brush (PSB) with quantitative culture Bronchoalveolar lavage (BAL) Protected BAL

The sensitivity of these procedures is reported to vary from 70% to 100%, and their specificity varies from 60% to 100%. PSB is widely accepted as the reference method for pneumonia diagnosis in ventilator patients. False-positive findings have been reported, however, and may be related to prior antibiotic therapy.

Risk Assessment Tracheal intubation and mechanical ventilation alter the patient’s first-line barrier defenses and greatly enhance the risk of nosocomial pneumonia. This risk is 6 to 21 times greater than that for patients who do not receive ventilator support. In addition to a thoracoabdominal procedure or intubation, other risk factors include the following: ● ●

Mean age older than 70 years Reintubation or self-extubation

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● ● ● ● ● ●

●

In addition, manipulation of the ventilator circuit or endotracheal tube increases the potential for cross-contamination. Recent studies have shown that interdisciplinary educational initiatives coupled with appropriate infection-control practices can reduce the risk of cross-contamination.

Implications The high morbidity and mortality associated with pneumonia in ventilator-dependent patients encourage a more aggressive approach to diagnosis and treatment. Yet invasive bronchoscopic techniques (e.g., PSB, protected BAL) may be associated with complications, including hypoxemia, bleeding, or arrhythmia.

MANAGEMENT Once the diagnosis of nosocomial pneumonia has been made, the choice of therapeutic agent is based on which organisms are associated with hospital-acquired pneumonia in the specific ICU environment, as well as the sensitivity and resistance patterns of those organisms. Recent studies suggest that selecting an inappropriate antibiotic for the treatment of nosocomial pneumonia is an independent risk factor for mortality, especially with highly resistant gram-negative bacilli (e.g., Pseudomonas, Acinetobacter, MRSA). In addition, if the patient received prior antibiotic therapy, it is likely that an extended-spectrum agent will be needed. Selected empirical antimicrobial agents for the treatment of nosocomial pneumonia include the following: ●

●

Early-onset infections: third- or fourth-generation cephalosporin (ceftriaxone, ceftizoxime, cefepime), βlactam inhibitor combination (ampicillin-sulbactam or piperacillin-tazobactam), new extended-spectrum fluoroquinolone (moxifloxacin), or aztreonam plus clindamycin Late-onset infections: aminoglycoside or fluoroquinolone (ciprofloxacin) plus one of the following: imipenem, antipseudomonal broad-spectrum β-lactam, or aztreonam

A glycopeptide (vancomycin) or oxazolidinone (linezolid) should be added for the treatment of MRSA infection. Recent studies suggest that linezolid for documented MRSA nosocomial pneumonia reduces patient mortality compared with traditional glycopeptide therapy. Resistant gram-negative pathogens such as Enterobacter species have been successfully treated with either imipenem or ciprofloxacin. If P. aeruginosa is recovered or suspected, ceftazidime or ciprofloxacin is included. If anaerobic species involvement is suspected, especially in an aspirationprone patient, the addition of clindamycin is appropriate.

Nosocomial Infections: Bacterial Pneumonia

211

However, the emerging resistance among some anaerobic gram-negative bacteria suggests that a β-lactam inhibitor combination or fourth-generation fluoroquinolone (e.g., moxifloxacin) should be considered. The rate of MRSA infections in the ICU population continues to increase, and resistance among gram-negative microbial pathogens (e.g., Klebsiella, E. coli) to extendedspectrum third-generation cephalosporins is being reported with greater frequency. Therefore, prior knowledge of existing patterns of gram-positive and gram-negative resistance within the ICU is crucial for the development of an appropriate therapeutic strategy for nosocomial pneumonia. Once microbiologic results are available, broad-spectrum antimicrobial therapy should be de-escalated to a specific antimicrobial agent in an effort to minimize the emergence of resistance.

PREVENTION Prevention of nosocomial pneumonia is complex and requires attention to patient-, device-, and personnel-related factors. The use of antimicrobial prophylaxis to prevent nosocomial pneumonia is highly questionable and may lead to superinfection. An attempt should be made to prevent microbial colonization of the oropharynx, trachea, and stomach by gramnegative pathogens. For instance, the use of sucralfate rather than antacids or H2-blockers to prevent stress bleeding in critically ill, postoperative, or mechanically ventilated patients may prevent gastric bacterial overgrowth by preserving gastric acidity. Other interventions aimed at reducing the risk of postoperative pneumonia include earlier ambulation, deepbreathing exercises, chest physiotherapy, use of incentive spirometry, intermittent positive-pressure breathing, and continuous positive airway pressure by facemask. Simply placing a patient in a semirecumbent position may reduce the aspiration of oropharyngeal secretions with potential nosocomial pathogens. Studies have shown that the longer a patient remains supine, the greater the volume of secretions aspirated. Control of pain in the immediate postoperative period with intravenous or regional analgesia has also been shown to be beneficial in decreasing the incidence of pulmonary complications after surgery. Bacteria rapidly adhere to biomaterial surfaces. Over time, they can produce a biofilm that is effective at protecting them from antibiotic and host defense mechanisms. These organisms can be dislodged by mechanical ventilatory flow, tube manipulations, or suctioning. Therefore, gentle suctioning and barrier precautions by the caregiver can decrease the incidence of cross-contamination to patients from either contaminated respiratory therapy devices or the hands of health care professionals. Appropriate hand hygiene should be emphasized among health care workers. For intubated patients, chlorhexidine-based oral hygiene can reduce the risk of endotracheal tube colonization. It is difficult to prevent the pooling of secretions around the endotracheal cuff, but this situation can provide bacteria with direct access to the lower respiratory tract. The internal machinery of mechanical ventilators is rarely associated with bacterial contamination of inhaled gases.

GENERAL ANESTHESIA

●

Depressed level of consciousness (e.g., closed head trauma) Underlying chronic lung disease Supine head position Conditions favoring aspiration or reflux 24-hour ventilator circuit changes Stress-bleeding prophylaxis with cimetidine (with or without antacid) Antimicrobial administration Exposure to contaminated respiratory equipment

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However, bacterial contamination from the patient’s oropharynx or condensate in the inspiratory-limb tubing of the ventilator circuit may occur rapidly after the initiation of mechanical ventilation (33% at 2 hours, and 80% after 24 hours). Tracheobronchial tree spillage may occur when the endotracheal tube is manipulated. Therefore, less frequent ventilator circuit tube changing (every 24 to 48 hours versus 6 to 8 hours) has been suggested as a way to reduce such contamination.

Further Reading American Thoracic Society: Hospital-acquired pneumonia in adults: Diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies: A consensus statement, American Thoracic Society, November 1995. Am J Respir Crit Care 153:1711-1725, 1996. Babcock HM, Zack JE, Garrison T, et al: An educational intervention to reduce ventilator-associated pneumonia in an integrated health system. Chest 125:224-231, 2004.

Croce MA, Fabian TC, Stewart RM, et al: Empiric monotherapy versus combination therapy of nosocomial pneumonia in trauma patients. J Trauma 35:303-309, 1993. Eggimann P, Hugonnet S, Sax H, et al: Ventilator-associated pneumonia: Caveats for benchmarking. Intensive Care Med 29:2086-2089, 2003. Guidelines for prevention of nosocomial pneumonia. MMWR Morb Mortal Wkly Rep RR-I:1-79, 1997. Hoffken G, Niedermann MS: Nosocomial pneumonia: The importance of a de-escalating strategy for antibiotic treatment of pneumonia in the ICU. Chest 122:2183-2196, 2002. Leroy O, Soubrier S: Hospital-acquired pneumonia: Risk factors, clinical features, management and antibiotic resistance. Curr Opin Pulm Med 10:171-175, 2004. Pringleton SK, Fagon J-Y, Leeper KV: Patient selection for the clinical investigation of ventilator-associated pneumonia: Criteria for evaluating diagnostic technique. Chest 102(Suppl 5):553S-556S, 1992. Pugin J, Auckenthaler R, Lew DP, et al: Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. JAMA 265:2704-2710, 2001. Sanford JP, Gilbert DN, Sande M: The Sanford Guide to Antimicrobial Therapy, 25th ed. Dallas, Antimicrobial Therapy Inc, 1996, pp 26-28.

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52

Postobstruction Pulmonary Edema Kenneth W. Travis and John L. Atlee

GENERAL ANESTHESIA

Case Synopsis Progressive Respiratory Distress After 3 days of malaise and fever, a 5-year-old, 16-kg girl develops a barking cough, stridor, and progressive respiratory distress. Her respiratory rate is 32 breaths per minute. Lung auscultation reveals reduced breath sounds and coarse rales. Her room air oxygen (O2) saturation is 82%, and the chest radiograph shows bilateral infiltrates. Postextubation Stridor A 22-year-old, 90-kg triathlete has marked inspiratory stridor lasting about 1 minute after tracheal extubation in the operating room, after an otherwise uneventful general anesthetic for septorhinoplasty. Within 15 minutes, he has tachycardia and tachypnea, with forced exhalations. His O2 saturation is 88% while breathing O2 via facemask at 6 L/minute.

PROBLEM ANALYSIS Definition Acute pulmonary edema that develops during or shortly after relief of severe upper airway obstruction is called postobstruction or negative-pressure pulmonary edema. The precipitating event is the generation of extreme negative intrapleural pressure, which increases the pulmonary transvascular hydrostatic pressure gradient (Table 52-1). In addition, associated hypoxia, catecholamine excess, exaggerated hemodynamic changes, and increased pulmonary vascular permeability disrupt the dynamic fluid equilibrium in the lung (Figs. 52-1 and 52-2). The accelerated movement of fluid from the pulmonary vasculature to the interstitium eventually exceeds the clearing capacity of the pulmonary lymphatic system, and the alveolar epithelial barrier becomes compromised; alveolar flooding is the end result. Owing to the rapidity and the severe pathophysiology associated with postobstruction pulmonary edema (POPE), prompt recognition and management of the condition are mandatory.

Recognition PRESENTATION POPE is suspected in the following situations: ●

●

●

A child (see also Chapter 157) or adult has hypoxemia, prolonged expiration, wheezing, and rales, with or without signs of bilateral pulmonary infiltrates. Pink, frothy tracheal secretions accumulate suddenly after tracheal intubation for acute or chronic upper airway obstruction. Oxygenation deteriorates after resolution of acute laryngospsam or removal of a foreign body (see Table 52-1).

Usually, POPE develops immediately or within minutes after intubation or extubation of the trachea. Sometimes, however, symptoms and signs of POPE do not appear for several hours, prompting some physicians to advise up to 18 hours of close surveillance for patients who have had significant perioperative or out-of-hospital obstructive events. NOTABLE FINDINGS In the most severe cases, the voluminous pulmonary edema fluid is pink and frothy and high in protein content. The chest radiograph frequently reveals bilateral, perihilar, patchy infiltrates and edema around the major pulmonary arteries. These arteries are believed to have endothelial damage as a result of high intravascular volumes and pressures. TIME COURSE In general, the more rapid the onset of the obstruction, the more severe the associated acute pulmonary edema. It has been postulated that patients with fixed upper airway obstruction, in whom the negative inspiratory forces are largely compensated for by forced expiration (Valsalva’s maneuver) or the development of air trapping (which causes increased positive end-expiratory pressure—auto-PEEP), are more likely to develop pulmonary edema following relief of the obstruction. Patients with variable upper airway obstruction that is more severe during inspiration are more prone to develop pulmonary edema during the obstruction. DIFFERENTIAL DIAGNOSIS With prompt treatment, POPE usually resolves within 12 to 24 hours, but recovery may take as long as 96 hours. Many mild cases probably go undetected. Common differential diagnoses include aspiration pneumonitis and other causes of increased capillary permeability edema (e.g., fat or amniotic 213

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Mechanisms, Recognition, and Management of Postobstruction Pulmonary Edema

Mechanism

Recognition

Management

Severe upper airway obstruction: Airway-related causes: Ensure and maintain patent airway: Partial or complete laryngospasm Inspiratory stridor Insert naso- or oropharyngeal airway Upper airway tumor or foreign body Wheezing Insert laryngeal mask airway Relaxed tongue or other Barking cough Suction or remove upper airway secretions, blood, oropharyngeal soft tissue structure Emesis (aspiration pneumonitis) vomit, particulate matter, foreign body Hypertrophy of tonsils or adenoids Perform endotracheal intubation or reintubation Croup or epiglottitis Perform cricothyrotomy or tracheostomy Extremely negative intrapleural Pulmonary edema with airway Respiratory management: pressures: obstruction: Ensure adequate oxygenation and ventilation Increased pulmonary transvascular Variable obstruction (most severe Increase FiO2 hydrostatic pressure gradient with inspiration) Facial, endotracheal or tracheal CPAP Hypoxia, hypercarbia, acidosis: Hypoxia, rales, prolonged expiration, Mechanical ventilation with pressure support or PEEP associated vasoconstriction of wheezing the pulmonary bed leads to Chest radiograph—perihilar, myocardial depression and fluffy (patchy) infiltrates increased capillary permeability Hyperadrenergic state: peripheral arterial or venous constriction leads to increased preload or afterload, “forward heart failure,” increased capillary permeability Associated hemodynamic changes: Pulmonary edema after relief of Additional measures: Marked increase in venous return upper airway obstruction: IV sedation and muscle relaxants to RV Fixed obstruction compensated Diuretics; vasoactive medications Ventricular interdependence by Valsalva’s maneuver or Invasive cardiovascular monitoring Reduced LV compliance auto-PEEP Specific therapy directed at cause Increased RV and LV Florid, pink, frothy, proteinaceous Indicated therapy for complications preload and afterload (“cotton candy”) airway fluids Admission to an appropriate facility for postevent Reduced LV stroke volume Onset can be immediate, within observation and treatment Increased pulmonary vascular minutes after relief of obstruction, volume and pressure or delayed (hours) Increased alveolar interstitial fluid Progressive respiratory distress Chest radiograph—often shows bilateral infiltrates Other pathophysiologic mechanisms: Common differential diagnoses: Pulmonary lymphatic system Aspiration pneumonitis overwhelmed Iatrogenic fluid overload Alveolar epithelial barrier breached Cardiogenic fulminant heart failure Alveolar flooding CPAP, continuous positive airway pressure; FiO2, fraction of inspired oxygen; LV, left ventricle; PEEP, positive end-expiratory pressure; RV, right ventricle.

Figure 52–1 ■ The Starling equation describes fluid flux in pulmonary capillaries: Q = K [(Pmv – Ppmv) – ∑(πmv – πpmv)], where K is the hydraulic conductance, Pmv is the hydrostatic pressure in the microvasculature, Ppmv is the hydrostatic pressure in perivascular tissue (interstitium), ∑ is the reflection coefficient for albumin, πmv is the osmotic pressure within the microvasculature, and πpmv is the osmotic pressure in the perimicrovascular tissue. Extremely negative intrapleural pressure increases the pulmonary transvascular hydrostatic gradient. (Modified from Nunn JF: Nunn’s Applied Respiratory Physiology, 4th ed. Oxford, Butterworth-Heinemann, 1993, p 487.)

P = Hydrostatic pressure (kPa or cm H2O) – relative to atmosphere π = Protein osmotic pressure (kPa or cm H2O) Lumen of alveolus P = zero

Route for alveolar flooding Lymphatic π = 1.5 (15) P= –0.7 (–7)

P= –0.6 (–6)

Interstitium P = – 0.4 (–4) π = 1.5 (15) P = 1.7 (17)

Arterial end

P = 1.2 (12) π = 3 (30) Microcirculation

Venous end

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Right Heart

II) Hyperadrenergic response leads to central redistribution of blood volume due to • Anxiety • Hypoxia • Hypercarbia • Cerebral ischemia

Postobstruction Pulmonary Edema

Lungs

Left Heart

I) Factors promoting pulmonary edema 1) Negative interstitial pressure 2) Increased pulmonary blood volume 3) HPV and hyperadrenergic environment 4) Increased pulmonary venous pressure (LV dysfunction) 5) Increased pulmonary capillary permeability

I) LV dysfunction leading to decreased LVSV 1) ↑Afterload 2) Acidosis 3) Hypoxemia

II) Factors opposing pulmonary edema 1) Auto-PEEP 2) Lymphatics 3) Valsalva maneuver 4) Fixed vs. variable extrathoracic airway obstruction

215

II) Elevated left-sided pressures secondary to decreased compliance 1) Ventricular interdependence 2) Hypoxia 3) Acidosis

BLOOD FLOW OUT

BLOOD FLOW IN

Figure 52–2 ■ Hypoxia causes pulmonary vasoconstriction, increased capillary permeability, and myocardial depression. The hyperadrenergic state, which results from hypoxia, anxiety, hypercarbia, acidosis, and cerebral ischemia, favors a central redistribution of blood volume. This, combined with the markedly negative intrapleural pressure during inspiration, dramatically increases venous return to the right ventricle (RV) and afterload stress to both the RV and the left ventricle (LV). Increased right ventricular volumes and pressures also cause a leftward shift of the interventricular septum. This reduces left ventricular compliance (ventricular interdependence) and raises end-diastolic and pulmonary microvascular pressures. Hypoxia, hypercarbia, and acidosis contribute to left ventricular dysfunction. Reduced left ventricular stroke volume causes a further rise in pulmonary blood volume and vascular pressure, which mechanically increases the transudation of fluid into the alveolar interstitium. When the rate of interstitial fluid flux exceeds the capacity of lymphatic clearance mechanisms, discontinuities appear in the alveolar epithelial cells, accompanied by crescentic alveolar fluid filling, flooding, and atelectasis. (Modified from Lang SA, Duncan PG, Shephard DAE, et al: Pulmonary oedema associated with airway obstruction. Can J Anaesth 37:213, 1990.)

fluid embolism, sepsis, cardiogenic causes, iatrogenic fluid overload). Acute pulmonary edema has also been reported in patients with head injury, heroin or other narcotic overdose, overly abrupt reversal of intraoperative narcotics (e.g., using 400 μg of naloxone as opposed to 20- to 40-μg increments), venous air embolism, pulmonary embolectomy, and high-altitude exposure. Usually, careful review of the patient’s past medical history and temporal events points to a cause. However, if it is still unclear, echocardiography, invasive hemodynamic monitoring, or both may be needed to rule out other causes. Patients with POPE have shown normal hemodynamic measurements after relief of upper airway obstruction. Other causes of extremely negative pulmonary interstitial pressures and pulmonary edema are rapid expansion of a collapsed lung and overly aggressive pleural suctioning during chest tube thoracentesis.

Risk Assessment Anyone strong enough to generate significant sustained negative intrapleural pressure against a closed glottis (Müller’s maneuver) or severely restricted upper airway is at risk for the development of POPE. This condition more commonly occurs in younger, healthy patients. Although the exact incidence is unknown, it is estimated that 11% to 12% of adult or pediatric patients who require urgent tracheal intubation or tracheostomy due to upper airway obstruction of various causes have associated POPE. Laryngospasm during emergence from general anesthesia accounts for 50% of reported cases in adults. In children younger than 10 years old,

croup and epiglottitis are associated with more than half the reported cases of POPE.

Implications In most instances, establishment of a patent airway improves the clinical condition of patients with significant upper airway obstruction. The dramatic appearance of pulmonary edema before, during, or after the relief of upper airway obstruction in a previously healthy individual is, to say the least, disconcerting. Further, without prompt recognition and treatment, it can lead to severe morbidity. However, it is important to remember that when POPE occurs in such patients and is appropriately managed, it is usually self-limited. If so, staff, family, and friends can be reassured that there is likely to be a favorable outcome and that the problem is unlikely to recur.

MANAGEMENT After recognition, management includes maintenance of a patent airway and the provision of adequate arterial oxygenation. Supplemental O2 is required, with or without continuous positive airway pressure (CPAP) or mechanical ventilation with PEEP (see Table 52-1). Tracheal intubation or reintubation is necessary to sustain the airway in 85% of adults and children. Slightly more than 50% of adults and just under 50% of children require mechanical ventilation. It therefore seems prudent, after ensuring upper airway patency, to first administer 100% O2 and CPAP in some

GENERAL ANESTHESIA

I) Negative intrapleural pressure → ↑ venous return

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form (e.g., spontaneous breathing with CPAP, tracheal intubation and CPAP, mechanical ventilation with pressure support and PEEP) while assessing the severity of the POPE and ruling out other causes of acute pulmonary edema. Along with appropriate sedation, treatment includes titrating the fraction of inspired O2 (FiO2) into the range of 0.4 as the alveolar-arterial O2 difference improves and the patient no longer demonstrates respiratory distress. The ventilatory and airway pressure supports can then be reduced. If fluid overload or coexisting cardiogenic dysfunction compounds the problem, diuretics or vasoactive agents may be indicated. Often, however, no additional medication is needed. Patients with a mild case may require only supplemental O2. The decision of where to manage patients with POPE depends on local capabilities and the availability of experienced caregivers. The most severely affected patients and those in whom the diagnosis is less certain benefit from admission to a designated critical care facility. Well-staffed freestanding ambulatory surgery centers might retain less severe cases of POPE in the postanesthesia care unit, but others might choose to transfer patients to an affiliated institution with critical care facilities. Office-based practitioners are best advised to transfer such patients to an acute care facility.

PREVENTION Vaccination against invasive Haemophilus influenzae type B has effectively reduced the number of cases of severe epiglottitis and, by inference, the number of cases of severe POPE from that cause in children. Other measures to protect against POPE include the following: ●

Use of bite blocks to prevent patients from biting and obstructing the endotracheal tube while attempting to inhale at the same time

●

●

Avoidance of factors that cause laryngospsam: (1) repeated failed attempts at endotracheal intubation (“Woody Woodpecker” syndrome), (2) inadequate anesthetic depth or skeletal muscle relaxation for tracheal intubation, and (3) excessive oropharyngeal secretions Careful timing of tracheal extubation after general anesthesia to avoid stimulation during the excitement phase

The immediate, judicious use of CPAP after tracheal intubation or extubation in patients at high risk for POPE might mitigate the severity of the syndrome and minimize the need for reintubation and mechanical ventilation.

Further Reading Benumof JL: Anesthesia for Thoracic Surgery, 2nd ed. Philadelphia, WB Saunders, 1995, pp 43-56. Capatanio MK, Kirkpatrick JA: Obstruction of the upper airway in children as reflected by the chest radiograph. Pediatr Radiol 107:159-161, 1973. Lang SA, Duncan PG, Shephard DAE, et al.: Pulmonary oedema associated with airway obstruction. Can J Anaesth 37:210-218, 1990. Meissner HH, Robinson L, Dubinett SM, et al: Pulmonary edema as a result of chronic upper airway obstruction. Respir Med 92:1174-1176, 1998. Nunn JF: Nunn’s Applied Respiratory Physiology, 4th ed. Oxford, Butterworth-Heinemann, 1993, pp 484-493. Oswalt CE, Gates GA, Holmstrom FMG: Pulmonary edema as a complication of upper airway obstruction. JAMA 238:1833-1835, 1977. Ringold S, Klein EJ, Del Beccaro MA: Postobstructive pulmonary edema in children. Pediatr Emerg Care 20:391-395, 2004. Staub NA: Pathophysiology of pulmonary edema. In Staub NA, Taylor AE (eds): Edema. New York, Raven Press, 1984, pp 719-741. Travis KW, Todres ID, Shannon DC: Pulmonary edema associated with croup and epiglottitis. Pediatrics 59:695-698, 1977. Van Kooy MA, Gargiulo RF. Postobstructive pulmonary edema. Am Fam Physician 62:401-404, 2000. Wilson WC, Benumof JL: Respiratory physiology and respiratory function during anesthesia. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 679-722.

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53

Latex Reactions in Health Care Personnel Kevin J. Kelly and Robert E. Kettler

GENERAL ANESTHESIA

Case Synopsis A 44-year-old anesthesiologist notes a rash on his right middle finger that has recently progressed to urticaria. He has been in good general health all his life; however, he is allergic to fish and ragweed pollen, and he was treated for eczema as a child. The rash has been intermittently present for several years and is exacerbated by wearing gloves to perform medical procedures. In the past 2 weeks, he has experienced chest tightness and rhinoconjunctivitis on entering the operating room. His only medication is an antihistamine taken during autumn for hay fever.

PROBLEM ANALYSIS Definition Natural rubber latex allergy (see also Chapter 161) is an issue of clinical importance for health care workers in terms of both patient management and occupational health. Use of rubber gloves dates to the late 1800s, when Halsted apparently produced them to protect the hands of his scrub nurse from the disinfectant solution she used to wash her hands. Skin lesions on the hands caused by the wearing of rubber gloves were first described in the medical literature in the 1930s. The increasing prevalence of latex-induced reactions is due to a confluence in the late 1980s of a number of factors: the increasing prevalence of hepatitis and acquired immunodeficiency syndrome (AIDS) led to the need for universal precautions; this led to increased demand for and use of barrier devices, including gloves made from natural rubber latex. The rubber industry responded to meet this demand, but final product quality may have been compromised by new entrants into the field, new geographic locations for rubber production, political turmoil in rubber-producing countries, and changes in the manufacturing process to increase output while complying with environmental and occupational health concerns. This increase in demand was associated with a greater number of medical gloves imported into the United States. As the use of latex gloves increased, allergic reactions in patients and health care providers were reported, leading to greater awareness of the problem, which in turn led to efforts to recognize and report it. This growing medical awareness was reflected by an increase in MEDLINE citations of journal articles published with latex as a key word, as shown in Table 53-1. There was an increase in both the absolute number of these citations and the number of these citations relative to the entire database. By mid-2004, the number of latex citations had increased to 0.1% of the MEDLINE database. Natural latex contains several polypeptides that bind immunoglobulin E (IgE) and that may be altered during

denaturation, polymerization, or breakdown during the manufacturing process. Most latex gloves have a cornstarch powder to facilitate donning. This powder binds various latex antigens and can be dispersed in the atmosphere, readily facilitating exposure through the respiratory system.

Recognition Three types of untoward latex reactions are recognized (Table 53-2): irritant dermatitis, type I IgE-mediated reactions, and type IV delayed contact hypersensitivity reactions. IRRITANT DERMATITIS Irritant reactions occur because the glove creates a local environment that can cause physical or chemical irritation to the skin. Risk factors for irritant reactions include increased age, cold weather, and excessive sweating. The skin breaks down over several days, and erythema and fissures are noted on inspection of the affected area. These reactions are not immunologically mediated. However, by disrupting the cutaneous barrier to allergens, they may be risk factors for the development of immunologically mediated reactions.

Table 53–1

Year 1966-1974 1975-1979 1980-1984 1985-1989 1990-1993 1994-1997 1966-1997

■

Latex Citations in MEDLINE Database Number (%) of Latex Citations 445 241 286 348 472 679 2471

(0.02) (0.02) (0.02) (0.02) (0.03) (0.07) (0.03)

Total Literature Citations (Millions)* 2.0 1.3 1.4 1.7 1.5 1.0 8.8

*All entries are rounded to nearest 100,000. In August 2004 the MEDLINE database contained 14 million citations, of which 14,372 (10%) were about latex.

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Manifestations of Irritant, Immediate, and Delayed Reactions to Latex

Reaction Type

Time of Onset

Clinical Signs

Immune Mechanism

Irritant dermatitis

Often gradual (days)

None

IgE-mediated reaction (type I)

Within minutes; rarely >2 hr

Erythema; scalded or parched appearance; chapped, cracked, fissured, or scaling skin; possibly vesicles or blisters Swelling, pruritus, urticaria, rhinoconjunctivitis, asthma, hypotension, anaphylaxis

Delayed contact hypersensitivity reaction (type IV)

6-48 hr after contact

Acute: erythema, pruritus, vesicles, blisters, cracking, crusting, desquamation Chronic: dryness, scaling, fissures, thickening or darkening of skin

IgE release of mast cell mediators; antigens are natural latex proteins Delayed or cell-mediated immunity; T-cell response to small rubber chemicals acting as haptens

From Ownby DR: Manifestations of latex allergy. Immunol Allergy Clin North Am 15:34, 1995.

TYPE I IGE-MEDIATED REACTION Type I reactions are mediated by IgE and usually occur within minutes of contact with latex proteins. The allergen binds to IgE, resulting in the release of vasoactive substances from mast cells (i.e., histamine, bradykinin, leukotrienes, prostanoids). There are several potential manifestations of IgE-mediated reactions, including urticaria, pruritus, bronchospasm, rhinoconjunctivitis, flushing, hypotension, angioedema, and anaphylaxis. TYPE IV DELAYED HYPERSENSITIVITY REACTION Type IV reactions to latex gloves are cell-mediated reactions to chemicals retained in the glove. The symptoms are apparent within several days and include erythema, pruritus, vesicles, fissuring, scaling, and thickening. The rash usually extends beyond the site of contact. Natural rubber latex is usually not the cause of type IV reactions; additives from the manufacturing process, such as thiuram and mercaptobenzathiazole, are more likely causes.

Risk Assessment There are few studies on the natural history and clinical course of natural rubber latex reactions; in addition, owing

Table 53–3

■

to differences in their methodology, there is variation in the reported prevalence. Even so, the prevalence of latex allergy in the general population has been consistently reported as less than 1%. Although a study of blood donors revealed detectable antibody in 6.5% of subjects, this does not indicate the presence of clinical allergy. The pediatric spina bifida population has been estimated to have a prevalence of 28% to 67%. The prevalence of latex allergy in health care workers is 5% to 17%, but its prevalence in health care workers with a history of atopy is 24% to 36%. Latex reaction risk factors include a history of environmental allergy, food allergy (especially to banana, kiwi, or avocado), hay fever, eczema, asthma, and chronic latex exposure (either occupational or as a result of repeated therapeutic procedures, with both frequency and exposure intensity being factors). The skin is relatively impermeable to latex proteins. However, disruption of the skin by irritant or contact reactions may predispose subjects to the development of IgE-mediated disease and subsequent systemic reactions. Cornstarch powder lubricant, which binds latex protein, and any activity that disperses these particles in the atmosphere can increase the quantity of respiratory exposure. If a patient’s history indicates a risk of latex allergy, a serum level of IgE reactive to latex allergens or skin testing from an allergist may be obtained. Further workup can be performed as outlined in Table 53-3.

Manifestations of Irritant, Immediate, and Delayed Reactions to Latex

Negative

Positive

Patient at Risk of Latex Allergy* No symptoms; no latex allergy; no testing needed

Symptomatic; possible latex allergy; perform diagnostic tests

Serum Test Negative; do further testing

Positive; no further testing needed (latex allergy confirmed)

Latex Use Test Negative; do further testing

Positive; no further testing needed (latex allergy confirmed)

Skin Test Negative; no latex allergy

Positive; no further testing needed (latex allergy confirmed)

*Some investigators have advocated latex testing in all patients with spina bifida. This approach would identify asymptomatic patients who have positive serum test results. Until further studies are performed, this patient group should be considered to be allergic to latex. From Kelly KJ, Kurup VP, Reijula KE, et al: The diagnosis of natural rubber latex allergy. J Allergy Clin Immunol 93:814, 1994.

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Implications

MANAGEMENT The mainstays of management are as follows: ● ● ●

Avoidance of allergens Topical therapy Systemic therapy (see Chapter 27)

Antigen avoidance can be difficult because of the ubiquitous presence of natural rubber products, especially in the health care environment. However, steps can be taken, such as wearing nonlatex gloves or using some type of barrier between the latex gloves and the skin (e.g., vinyl gloves). Using gloves only when necessary can also reduce exposure. Individuals who suffer severe reactions and cannot avoid allergens may have to change their specialty or profession. Airborne exposure can be eliminated or reduced to levels that are clinically insignificant by the exclusive use of powder-free, low-allergen latex gloves or synthetic gloves. Topical therapy with steroids and moisturizers can relieve the symptoms of irritant and type IV reactions. Therapy for systemic IgEmediated reactions includes airway management, ventilatory and circulatory support if necessary (including the use of epinephrine), antihistamines, and bronchodilators.

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PREVENTION Susceptible individuals should be advised to avoid latex products, but as already noted, this can be difficult. They should wear allergy-alert identification and carry an autoinjectable device for the emergency administration of epinephrine. Institutions should consider managing prevention through a multidisciplinary committee that develops guidelines for patients, health care workers, and other employees. This committee should provide guidelines for the identification of latex-containing medical products, the identification and purchase of latex-free substitutes, the establishment of latex-free treatment areas for susceptible individuals, and the use of powder-free gloves.

Further Reading Garabrant DH, Schweitzer S: Epidemiology of latex sensitization and allergies in health care workers. J Allergy Clin Immunol 110:S82-S95, 2002. Kelly KJ: Management of the latex-allergic patient. Immunol Allergy Clin North Am 15:139-157, 1995. Kelly KJ, Kurup VP, Reijula KE, et al: The diagnosis of natural rubber latex allergy. J Allergy Clin Immunol 93:813-816, 1994. Landwehr LP, Boguniewicz M: Current perspectives on latex allergy. J Pediatr 128:305-312, 1996. Ownby DR: Manifestations of latex allergy. Immunol Allergy Clin North Am 15:31-43, 1995. Ranta PM, Owenby DR: A review of natural-rubber latex allergy in health care workers. Clin Infect Dis 38:252-256, 2004. Sussman GL, Beezhold DH: Allergy to latex rubber. Ann Intern Med 122: 43-46, 1995. Truscott W: The industry perspective on latex. Immunol Allergy Clin North Am 15:89-121, 1995.

GENERAL ANESTHESIA

The severity of a latex reaction can range from a minor annoyance to life-threatening anaphylaxis and can include disabling symptoms (e.g., asthma). In addition to these medical complications, there are social implications, such as the need to change responsibilities or careers and the cost of disability payments. Institutions and individuals may have to change aspects of their medical practice to reduce the risk of latex reactions in others.

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Spinal Anesthesia: Post–Dural Puncture Headache

54

Matthew P. Feuer and Spencer S. Liu REGIONAL ANESTHESIA & PAIN MANAGEMENT

Case Synopsis A 25-year-old woman undergoes spinal anesthesia with a 25-gauge Quincke needle for outpatient knee arthroscopy. The following day, she complains of a severe frontaloccipital headache in the upright position that resolves when she is supine.

PROBLEM ANALYSIS Definition

●

●

Presence of less common associated symptoms: shoulder pain, cranial nerve dysfunction, auditory complaints Spontaneous resolution between 1 and 6 weeks after dural puncture

Post–dural puncture headache (PDPH) is a well-known complication of spinal anesthesia. It commonly occurs 24 to 48 hr after dural puncture (in 92% of affected patients), but the presentation can be delayed for as long as 5 days. Current evidence from laboratory and clinical imaging studies strongly supports the theory that loss of cerebrospinal fluid (CSF) from the puncture site is the key initiating factor (Fig. 54-1). Reduction in CSF fluid and pressure allows sagging of the brain and supporting structures when the patient assumes the upright position. Sagging of the brain places direct traction on pain-sensitive structures and can also cause painful reflex vasodilatation of cerebral blood vessels. This theory is also supported by PDPH’s pathognomonic feature of occurrence or exacerbation in the upright position and resolution in the supine position. Typically, 70% of PDPHs resolve spontaneously by 1 week after dural puncture, and 95% resolve by 6 weeks.

Recognition PDPH should be considered a diagnosis of exclusion. Medical conditions that have been misdiagnosed as PDPH include hypothalamic tumors, eclampsia, spinal meningitis, and superior sagittal sinus thrombosis. Clinical features of PDPH include the following: ● ●

●

● ●

History of dural puncture Delayed presentation of headache (usually 24 to 48 hours after dural puncture) Positional nature of headache (exacerbated when upright and resolved when supine) Headache that is typically frontal or occipital in nature Presence of common associated symptoms: neck ache (57%), backache (35%), nausea (22%)

Figure 54–1 ■ Lumbar spine magnetic resonance image in a patient with post–dural puncture headache before the administration of an epidural blood patch. The static collection of fluid at L2-L3 (arrows) corresponds to leakage of cerebrospinal fluid from the dural puncture site. (From Vakharia SB, et al: Magnetic resonance imaging of cerebrospinal fluid leak and tamponade effect of blood patch in postdural puncture headache. Anesth Analg 84:585, 1997.)

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Risk Assessment With current anesthetic practice, the incidence of PDPH typically ranges from 1% to 7% after spinal anesthesia. Both patient characteristics and anesthetic technique have been implicated as risk factors for the subsequent development of PDPH. Patient factors that increase the risk include the following: ●

● ●

Younger age, probably owing to changes in the elastic properties of the dura with aging Female gender Previous history of PDPH

Anesthetic factors that reduce the risk of PDPH are the following: ●

●

●

Smaller-diameter spinal needles, probably owing to smaller dural punctures (Figs. 54-2 and 54-3) Use of pencil-point rather than cutting-tip spinal needles— the former result in less CSF leakage in vitro (see Figs. 54-2 and 54-3) Orientation of the bevel of cutting-tip needles parallel to the long axis of the dura, which may produce a smaller rent in the dura because of the longitudinal splitting of fibers, as opposed to direct transection (cutting)

Figure 54–2 ■ From the left: Atraucan, Quincke, Gertie Marx, Sprotte, and Whitacre needles. Note the cutting points on the Atraucan and Quincke needles. Also, note the differences in the configuration of the lateral eyes of the pencil-point needles. The eye of the Gertie Marx needle is the smallest and situated closest to the needle tip. The left horizontal markings are in 2-mm increments. (From Vallejo MC, et al: Postdural puncture headache: A randomized comparison of five spinal needles in obstetric patients. Anesth Analg 91:916, 2000.)

MANAGEMENT Implications PDPH can result in significant discomfort and limitation of activity owing to its positional nature. Approximately 60% of affected patients can be treated with mild analgesics until spontaneous resolution occurs. Of these patients, approximately 18% will have slight restriction of physical activity, 31% will be partially bedridden with restricted physical activity, and 51% will be entirely bedridden.

Both systemic and invasive therapies have been advocated for the treatment of PDPH. It is reasonable to try systemic treatments before instituting more invasive therapies (Fig. 54-4).

Systemic Therapy Because the proposed pathophysiology of PDPH includes reflex vasodilatation of cerebral blood vessels, systemic

mL/5 hr 140

120 116 100

80

60 54.6 40 40.3 31.2 25.5

20

22.5 17.2

16.2

11.8

9.4

27 W

26 A

0 22 Q

25 Q

24 S

27 Q

25 W

25 S

26 W

29 Q

Needle type

Figure 54–3 Relationship between needle size and bevel type and leakage of cerebrospinal fluid after dural puncture in a laboratory model. (From Holst D, et al: In vitro investigation of cerebrospinal fluid leakage after dural puncture with various spinal needles. Anesth Analg 87:1331, 1998.) ■

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Signs and symptoms of PDPH

12–24 hr PO fluids Mild analgesics Caffeine 300 mg PO Caffeine 500 mg IV 12–24 hr

Figure 54–4 headache.

■

12–24 hr

Epidural blood patch 20 mL blood

Suggested treatment algorithm for post–dural puncture

therapies generally focus on the administration of vasoconstrictive agents or adrenocorticotropic hormone (ACTH). Caffeine. The intravenous administration of caffeine (500 mg) has been observed to decrease cerebral blood flow by 22% in patients suffering from PDPH. Success rates with intravenous caffeine therapy range from 40% to 80%, with mild side effects (dizziness, flushing). Oral caffeine can also be an effective therapy, with an approximately 50% success rate after 300 mg of oral caffeine.

Spinal Anesthesia: Post–Dural Puncture Headache

225

after “bloody” dural punctures. Epidural blood patch (EBP) is currently the gold standard for PDPH treatment, with a success rate ranging from 90% to 99%. Its mechanisms of action are thought to involve increased intracranial CSF pressure due to mass effect and sealing of the dural puncture site with fibrin clot (Fig. 54-5). Injection of blood into the epidural space results in an immediate mass effect persisting for at least 3 hours. Mature clot formation and sealing of the dural rent occurs by 7 hours after injection. Initial reports of EBP used small volumes of blood (2 to 3 mL), but recent recommendations are for larger volumes (15 to 20 mL). These larger volumes provide greater spread of clot (five to nine spinal segments), greater mass effect, and a higher incidence of successful treatment. Although safe and effective, the use of EBP is not risk free. Contraindications to EBP include systemic infection, localized infection of the back, and active neurologic disease. Reported complications of EBP include transient backache (35% to 100% incidence), mild temperature elevation (5%), sudden bradycardia, and radicular pain. Prolonged sequelae from EBP may also occur. Less successful epidural analgesia after prior EBP has been reported. Epidural Injection of Other Solutions. Both saline and dextran have been injected into the epidural space for the treatment of PDPH. Highly variable success rates have been reported, ranging from no effect to 90% success. The variable and often temporary nature of relief from saline or dextran,

Sumatriptan. This serotonin type 1d receptor agonist is a potent cerebral vasoconstrictor that is an effective treatment for migraine and cluster headaches. Sumatriptan can be administered intranasally, orally, or by subcutaneous injection. Case reports on the use of sumatriptan to treat PDPH are conflicting, and the sole available small randomized trial showed no benefit. Adrenocorticotropic Hormone. ACTH and its synthetic analogues have been administered intravenously for the treatment of PDPH. Proposed mechanisms of action include increased CSF production, dural edema secondary to aldosterone production, and increased β-endorphin production. Anecdotal evidence suggests a success rate of 70% to 95%, but the sole randomized controlled trial to date showed no benefit. There have been case reports of seizures in obstetric patients treated with ACTH analogues.

Invasive Therapy Loss of CSF pressure due to leakage of CSF from the dural puncture site has prompted investigators to inject substances into the epidural space to try to return CSF pressure to normal: Epidural Blood Patch. Epidural injection of autologous blood was first proposed as a treatment for PDPH in 1960, after anecdotal observations of a reduced incidence of PDPH

Figure 54–5 ■ Magnetic resonance image of 20-mL epidural blood patch demonstrating sealing of the dural leak and spread from L4 to T12 (arrowheads). (From Vakharia SB, et al: Magnetic resonance imaging of cerebrospinal fluid leak and tamponade effect of blood patch in postdural puncture headache. Anesth Analg 84:585, 1997.)

REGIONAL ANESTHESIA & PAIN MANAGEMENT

Sumatriptan 6 mg SQ? Cosyntropin 0.5 mg IV?

12–24 hr

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coupled with the inherent risk of an epidural injection, makes their use questionable. A recent case report documented the successful use of 3 mL of fibrin glue to treat a PDPH resistant to three EPBs.

PREVENTION The cornerstone of preventing PDPH is the selection of small, non-cutting-tipped needles for dural puncture. The prophylactic administration of systemic therapies has not been well studied, and results are disappointing. The prophylactic administration of EBP is controversial. Because not all patients undergoing dural puncture will develop PDPH, many experts recommend EBP only after the development of symptoms. Another argument against the prophylactic use of EBP is its questionable efficacy when administered early (<24 hours after dural puncture). Several studies of the early administration of relatively small volumes of blood (7 to 10 mL) via an epidural catheter after dural puncture with a large-gauge Tuohy needle reported virtually no effects on the subsequent development of PDPH. However, these studies have been criticized for using small volumes of blood. A recent study administering a larger volume of blood (15 mL) via an epidural catheter after dural puncture with a large-gauge Tuohy needle reported

a marked reduction in the incidence of PDPH in obstetric patients (5% in treated versus 88% in untreated patients). Another recent controlled trial demonstrated the efficacy of the immediate injection of 10 mL of saline after inadvertent dural puncture (32% of treated patients developed PDPH, versus 62% of those untreated). Thus, if patient and anesthetic risk factors are considered great enough to warrant prophylactic therapy, a large-volume EBP or immediate saline injection may be a reasonable and effective therapy.

Further Reading Canovas L, Barros C, Gomez A, et al: Use of intravenous tetracosactin in the treatment of postdural puncture headache: Our experience in forty cases. Anesth Analg 94:1369, 2002. Connelly NR, Parker RK, Rahimi A, Gibson CS: Sumatriptan in patients with postdural puncture headache. Headache 40:316-319, 2000. Halpern S, Preston R: Postdural puncture headache and spinal needle design: Metaanalyses. Anesthesiology 81:1376-1383, 1994. Harrington BE: Postdural puncture headache and the development of the epidural blood patch. Reg Anesth Pain Med 29:136-163, 2004. Kroin JS, Nagalla SK, Buvanendran A, et al: The mechanisms of intracranial pressure modulation by epidural blood and other injectates in a postdural puncture rat model. Anesth Analg 95:423-429, 2002. Lybecker H, Djernes M, Schmidt J: Postdural puncture headache (PDPH): Onset, duration, severity, and associated symptoms. Acta Anaesthesiol Scand 39:605-612, 1995.

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Local Anesthetic Neurotoxicity: Cauda Equina Syndrome

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Kenneth Drasner Case Synopsis

PROBLEM ANALYSIS Definition As the term cauda equina syndrome (CES) implies, clinical manifestations are related to injury to the nerve roots below the conus medullaris. Consequently, CES results in varying degrees of bowel and bladder dysfunction, perineal sensory loss, and lower extremity motor weakness. Although there are multiple potential causes, two are of most concern to anesthesiologists: (1) compressive injuries (e.g., epidural hematoma or epidural abscess), and (2) direct toxicity of substances administered into the intrathecal space. Recent clinical experience and experimental data suggest that, under certain circumstances, local anesthetics in current clinical use have the potential to induce neurotoxic damage. That is the focus of this chapter.

Recognition Throughout the last century of clinical use, sporadic reports of neurologic injury associated with spinal and epidural anesthesia raised the concern that local anesthetics might be neurotoxic. Clinical and experimental evidence accumulated over the last decade, beginning with reports of CES associated with continuous spinal anesthesia (CSA), has substantiated this concern. All the CSA-related cases shared certain common elements: there was evidence of a restricted sacral block that required repetitive doses of local anesthetic to achieve adequate surgical anesthesia, and the cumulative dose far exceeded that commonly used with single-injection spinal anesthesia. It was suggested that the combination of maldistribution and high dose of anesthetic led to neurotoxic concentrations

REGIONAL ANESTHESIA & PAIN MANAGEMENT

A 48-year-old man underwent right inguinal hernia repair under spinal anesthesia. With the patient in a sitting position, a 24-gauge pencil-point needle was inserted at the L4-L5 level, and 75 mg of 5% lidocaine hydrochloride with 7.5% glucose, 0.1 mg of epinephrine, and 25 μg of fentanyl was administered, resulting in an L3 block after 5 minutes. The patient was then placed in the right lateral decubitus position, and an additional 50 mg of 5% lidocaine with glucose was administered intrathecally. A T10 block was achieved, and surgery proceeded uneventfully. Twelve hours postoperatively, perineal numbness persisted, and the patient was unable to void. Anal sphincter tone was diminished, and anal reflexes were absent. Lumbosacral spine films and lumbosacral magnetic resonance imaging results were within normal limits. Six months postoperatively, the patient had to strain to urinate, was unable to have a spontaneous bowel movement, and continued to have diminished sensation in the S3-S5 region bilaterally.

in a restricted area of the subarachnoid space, a mechanism supported by subsequent in vitro and in vivo experimental data. Although most of the injuries involved the administration of 5% lidocaine through small-bore microcatheters, not all were associated with lidocaine, and some involved intrathecal delivery of anesthetic through an epidural catheter. Therefore, withdrawal of microcatheters from clinical practice has not eliminated the risk of injury, as practitioners remain at liberty to use epidural equipment for CSA. Further, some clinicians routinely convert to a continuous spinal technique if dural puncture accidentally occurs during attempted epidural placement. Factors that lead to neurotoxic injury with CSA are not unique to this technique; they also apply to single-injection spinal anesthesia. Specifically, inadequate sensory block with single-injection spinal anesthesia is often the result of maldistribution. Under such circumstances, there is the potential for repeat injections to distribute in the same pattern, resulting in neurotoxic concentrations of local anesthetic within a restricted area of the subarachnoid space. Case reports and review of the closed claims database appear to support this concern. There is a third mechanism by which high doses of anesthetic may be administered into the subarachnoid space. If a practitioner is administering an epidural anesthetic and fails to appreciate that the needle or catheter has traversed the dura or arachnoid, the doses administered may achieve neurotoxic concentrations in the subarachnoid space. Such doses may be sufficient to induce injury even in the absence of maldistribution, as evidenced by case reports. Reports of neurologic injury with CSA, repetitive injection after failed spinal anesthesia, and inadvertent intrathecal injection of anesthetic intended for the epidural space established the potential toxicity of anesthetics administered at a dose 227

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exceeding the usual clinical range for spinal anesthesia. More surprising, two fairly recent reports raised the suspicion that neurologic deficits might occur with the administration of lidocaine at doses recommended for single-injection spinal anesthesia. One was a case report of CES following the intrathecal injection of 100 mg of lidocaine with epinephrine. The second was a prospective study of regional anesthesia from France. In both reports there were persistent deficits following single injections of lidocaine that could not be otherwise explained. In all cases, relatively high doses (≥75 mg) were used, and cases of permanent injury occurred only after injection of the maximum recommended clinical dose (100 mg).

Risk Assessment In prospective studies, retrospective reviews, and epidemiologic studies, the incidence of CES resulting from neurotoxic reactions to local anesthetic varies. Such information is potentially misleading, however, because the incidence depends on practice patterns. For example, the very high incidence associated with the repetitive administration of high doses of anesthetic through continuous spinal catheters has little relevance to current anesthetic practice. Similarly, the roughly 1 in 5000 incidence of permanent deficits with single-injection lidocaine spinal anesthesia in the aforementioned report from France may overestimate the risk, because modifications have been made to reduce the risk of injury (see “Prevention”). Nonetheless, when assessing the likelihood that postoperative CES is the result of a neurotoxic reaction, one should consider the circumstances of the case relative to factors known to be associated with clinical toxicity (e.g., inadvertent intrathecal injection of an intended epidural dose of anesthetic). In addition to the rare occurrence of CES following spinal or epidural anesthesia, transient neurologic symptoms— defined as pain or dysesthesia in the buttocks and lower extremities—may occur in up to a third of individuals receiving lidocaine for spinal anesthesia. Known risk factors include outpatient status and surgical positioning (e.g., patients undergoing knee arthroscopy or placed in the lithotomy position). However, transient neurologic symptoms can be readily distinguished from CES because the former is not associated with sensory or motor deficits or disturbance of bladder and bowel function. Although there has been considerable speculation that these transient symptoms and CES may represent opposite ends of a spectrum of toxicity, recent evidence suggests that these two entities are not mediated by the same mechanism.

Implications CES is a rare but disastrous complication that may result from neurotoxic injury to the nerve roots below the conus medullaris. Because of its seriousness and lack of effective treatment, attention must be focused on the adoption of clinical strategies that minimize risk (see “Prevention”).

MANAGEMENT Although some advocate the use of high-dose steroids, these agents have no proven benefit for nerve root injuries resulting

from local anesthetic toxicity. As mentioned earlier, there are many potential causes of CES. It is critical to consider the possibility that clinical manifestations may be due to a compressive lesion (e.g., hematoma, abscess). Unlike neurotoxic damage, injury from compression is readily reversible, and the extent of recovery is related to the degree of functional loss and the time from the onset of deficits to surgical decompression. The clinical circumstances, such as coagulation status, may provide guidance as to the likelihood of this alternative. Also, local anesthetic neurotoxicity presents with a block that does not recede, whereas a period of normal postoperative function followed by progressive loss in the absence of ongoing administration of local anesthetic is strongly suggestive of a compressive lesion. Because time is of the essence, any suspicion should be investigated by emergent magnetic resonance imaging.

PREVENTION Analysis of the clinical reports of CES occurring with spinal and epidural anesthesia and data generated in experimental studies of neurotoxicity has led to the identification of factors that appear to potentiate risk. This information forms the basis of practice modifications.

Continuous Spinal Anesthesia Injuries occurred with CSA because high doses of anesthetic were administered intrathecally to compensate for a restricted sensory block. Guidelines have been proposed that emphasize reliance on a test dose, adjustment of technique, and abandonment of the technique if adequate block is not achieved within the normal clinical dose range for singleinjection spinal anesthesia (Table 55-1).

Repeat Injection after Failed Spinal Anesthesia Similar to CSA, guidelines for the management of failed spinal anesthesia have been proposed. These include an assessment of the likelihood of technical error (e.g., failure to inject the drug intrathecally) and appropriate adjustment of the dosage for the repeat injection. However, a more efficient

Table 55–1

■

Continuous Spinal Anesthesia: Guidelines for Administration

Insert the catheter just far enough to confirm and maintain placement. Use the lowest effective anesthetic concentration. Place a limit on the amount of anesthetic to be used. Administer a test dose, and assess the extent of block. If maldistribution is suspected, use maneuvers to increase the spread of local anesthetic (e.g., change the patient’s position, alter the lumbosacral curvature, switch to a solution with a different baricity). If well-distributed sensory anesthesia is not achieved before the dose limit is reached, abandon the technique. Adapted from Rigler ML, Drasner K, Krejcie TC, et al: Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg 72:275-281, 1991.

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Local Anesthetic Neurotoxicity: Cauda Equina Syndrome

(and perhaps safer) strategy is to simply limit the combined anesthetic dosage to the maximum amount a clinician would consider reasonable to administer as a single intrathecal injection.

Epidural Anesthesia

Lidocaine Spinal Anesthesia Most of the recent injuries associated with spinal and epidural anesthesia have been associated with the use of lidocaine. Experimental investigations have reinforced concerns about this anesthetic, suggesting that its inherent toxicity exceeds that of bupivacaine. Modified guidelines for the use of this agent are summarized in Table 55-2 and detailed in the following paragraphs (although lidocaine is the focus, most of these considerations apply to any intrathecal anesthetic agent). Dose. Most studies indicate that the potency ratio of lidocaine to bupivacaine is approximately 1:4. Yet the maximum recommended doses of 100 mg and 20 mg, respectively, or the administration of whole ampules of these agents (100 mg and 15 mg), result in ratios of 5:1 or 6.7:1. The issue of relative toxicity aside, 100 mg exceeds the dose of lidocaine required for reliable spinal anesthesia. This, combined with case reports of probable neurotoxicity at the upper end of the dose range, leaves little justification for the continued use of a 100-mg ceiling. The data are inadequate to make a firm recommendation regarding the maximum safe dose, but it is my personal practice not to exceed 60 mg. Concentration. Abundant data suggest that anesthetic neurotoxicity is, to some extent, concentration dependent. It is therefore hard to justify the continued use of concentrations that far exceed that required for adequate blockade.

Table 55–2

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Lidocaine Spinal Anesthesia: General Guidelines

Dosage should be limited to 60 mg. Concentration should not exceed 2%. Epinephrine should not be used to enhance anesthesia or prolong the duration of block. Modified from Drasner K: Lidocaine spinal anesthesia: A vanishing therapeutic index? Anesthesiology 87:469-472, 1995.

With respect to lidocaine, the injected concentration should not exceed 2% lidocaine because it will produce sensory anesthesia that is clinically equivalent to a 5% solution. Glucose. A feature common to most recent cases of clinical injury is the use of an anesthetic solution with a high concentration of glucose and a tonicity far exceeding the normal physiologic range. Despite this association, 7.5% glucose does not affect the compound action potential in vitro or potentiate anesthetic-induced conduction failure. Moreover, dose-dependent loss of sensory function produced by intrathecal lidocaine in vivo is unaffected by the presence of 7.5% glucose, and the administration of 10% glucose does not induce impairment or morphologic damage. These findings suggest that it is appropriate to continue to use glucose to increase baricity. Vasoconstrictors. Vasoconstrictors might contribute to toxicity by promoting ischemia, decreasing anesthetic uptake, or directly affecting neural elements. Recent data indicate that epinephrine potentiates sensory impairment induced by intrathecal lidocaine. Combined with the clinical report of a deficit following the intrathecal injection of 100 mg lidocaine with epinephrine, these data argue against using a vasoconstrictor with lidocaine for spinal anesthesia. Moreover, if the goal is to provide a longer duration of surgical anesthesia, this can be readily achieved with bupivacaine. Thus, there is no cogent argument for the continued use of epinephrine with lidocaine.

Further Reading Auroy Y, Narchi P, Messiah A, et al: Serious complications related to regional anesthesia: Results of a prospective survey in France. Anesthesiology 87:479-486, 1997. Drasner K: Lidocaine spinal anesthesia: A vanishing therapeutic index? Anesthesiology 87:469-472, 1997. Drasner K, Rigler M: Repeat injection after a “failed spinal”—at times, a potentially unsafe practice. Anesthesiology 75:713-714, 1991. Drasner K, Rigler M, Sessler D, Stoller M: Cauda equina syndrome following intended epidural anesthesia. Anesthesiology 77:582-585, 1992. Freedman J, Li D, Drasner K, et al: Transient neurologic symptoms after spinal anesthesia: An epidemiologic study of 1863 patients. Anesthesiology 89:633-694, 1998. Hampl KF, Schneider MC, Ummenhofer W, Drewe J: Transient neurologic symptoms after spinal anesthesia. Anesth Analg 81:1148-1153, 1995. Hashimoto K, Bollen A, Ciriales R, Drasner R: Comparative toxicity of glucose and lidocaine administered intrathecally in the rat. Reg Anesth Pain Med 23:444-450, 1998. Hashimoto K, Hampl K, Nakamura Y, et al: Epinephrine increases the neurotoxic potential of intrathecally administered local anesthetic in the rat. Anesthesiology 94:876-883, 2001. Lambert L, Lambert D, Strichartz G: Irreversible conduction block in isolated nerve by high concentrations of local anesthetics. Anesthesiology 80:1082-1093, 1994. Pollock JE, Neal JM, Stephenson CA, Wiley CE: Prospective study of the incidence of transient radicular irritation in patients undergoing spinal anesthesia. Anesthesiology 84:1361-1367, 1996. Rigler M, Drasner K: Distribution of catheter-injected local anesthetic in a model of the subarachnoid space. Anesthesiology 75:684-692, 1991. Rigler M, Drasner K, Krejcie T, et al: Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg 72:275-281, 1991.

REGIONAL ANESTHESIA & PAIN MANAGEMENT

The potential for toxicity with inadvertent intrathecal injection of an epidural dose of anesthetic underscores the importance of a test dose and the fractional administration of anesthetic. Additionally, should high doses of anesthetic be administered through a misplaced catheter, repetitive withdrawal of small volumes of cerebrospinal fluid and replacement with saline should be considered, regardless of the anesthetic agent.

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Francis V. Salinas Case Synopsis A 65-year-old man (183 cm, 87 kg, American Society of Anesthesiologists [ASA] status 1) was scheduled for a left total knee arthroplasty revision. His only medical problem was hypertension that was well controlled with atenolol 50 mg/day. After resolution of an uneventful 15-mg isobaric bupivacaine subarachnoid block, a continuous femoral nerve block was planned for postoperative analgesia. The patient was positioned supine for the femoral nerve block, and a brisk quadriceps response was obtained at a minimal current of 0.4 mA. A perineural catheter was advanced 10 cm beyond the needle tip, and the stimulating needle was removed. After a negative catheter aspiration test, ropivacaine 0.5% with epinephrine 2.5 μg/mL (30 mL) was injected slowly over 60 seconds. Near the end of the injection, the patient complained of unfocused vision and suddenly developed a generalized tonic-clonic seizure.

PROBLEM ANALYSIS Definition Local anesthetics are used to block the generation and propagation of electrical impulses (action potentials) in electrically excitable tissues. They bind to voltage-gated sodium channels and prevent conformational changes within those channels that allow the movement of ions for the propagation of action potentials. Clinically, local anesthetics are usually injected directly into perineural tissues (central neuraxis, major plexus, or peripheral nerves), joint spaces, and subcutaneous tissues. Additionally, they can be applied topically to mucosal surfaces to provide anesthesia of the airway or interpleural and intraperitoneal spaces. They may also be administered intravenously to provide regional anesthesia or treat arrhythmias. Adverse reactions to local anesthetics are either systemic or localized (e.g., direct neurotoxicity; see Chapter 55). Systemic toxicity involves primarily the central nervous system (CNS) and the cardiovascular system (CVS). In practice, systemic toxicity occurs as a result of the inadvertent intravascular injection or systemic absorption of excessive doses of local anesthetics from the injection site. Less commonly, systemic toxic reactions are due to methemoglobinemia, allergic reactions, or direct myo- or neurotoxicity. For example, ortho-toluidine (a metabolite of benzocaine and prilocaine) may oxidize deoxyhemoglobin to methemoglobin; deoxyhemoglobin does not bind oxygen or carbon dioxide.

Recognition CENTRAL NERVOUS SYSTEM TOXICITY Based on studies of unsedated human volunteers receiving intravenous infusions of local anesthetics, the early symptoms of local anesthetic-induced CNS toxicity include perioral numbness, lightheadedness or dizziness, tinnitus, difficulty 230

focusing visually, paresthesia, disorientation, and drowsiness. As the local anesthetic’s plasma concentration increases, common signs include dysarthria, skeletal muscle twitching, and tremors; these can progress to generalized tonic-clonic seizures. With still higher plasma concentrations, CNS toxicity may cause unconsciousness, respiratory arrest, and coma. Symptoms of CNS excitation are thought to be related to an initial blockade of inhibitory neurons in the cerebral cortex, thereby allowing facilitative neurons to function in an unopposed manner. This may ultimately lead to generalized seizures. With further increases in plasma and CNS concentrations of local anesthetics, both inhibitory and facilitative neurons are blocked, leading to more global CNS depression. This stereotypical pattern of initial CNS excitation relates primarily to slow intravenous injection or absorption of local anesthetics. Because the most common cause of clinical systemic toxicity is inadvertent intravenous injection of large amounts of local anesthetics, symptoms and signs of toxicity may progress much more rapidly, and generalized seizures may be the initial presentation of CNS toxicity. Also, the use of intravenous sedatives during the performance of an epidural or peripheral nerve block can attenuate early signs and symptoms of CNS toxicity. If so, skeletal muscle twitching and tremors or loss of consciousness may be the initial presentation. CARDIOVASCULAR SYSTEM TOXICITY Local anesthetics’ inhibition of cardiac sodium channels reduces the action potential duration, the effective refractory period, and the maximal depolarization rate of Purkinje fibers and ventricular muscle. Electrophysiologic studies in animal models have shown that local anesthetics produce dosedependent depression of cardiac conduction, leading to a prolonged P-R interval and QRS duration and depression of sinoatrial and atrioventricular activity. Local anesthetics also exert direct dose-dependent negative inotropic effects

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on the ventricular myocardium, which may be related to the blockage of calcium channels and mitochondrial energy metabolism. Further, local anesthetics are peripheral vasodilators and exert potent inhibitory effects on sympathetic smooth muscle vasoconstriction. CVS toxicity from local anesthetics’ direct actions on both myocardium and the peripheral vasculature may present as arrhythmias (refractory ventricular arrhythmias, sinus bradycardia or arrest), profound hypotension (due to negative inotropic effects or vasodilatation), or cardiovascular collapse.

Risk Assessment Multiple factors determine the risk of developing local anesthetic–induced systemic toxicity and its severity: ● ● ●

●

Regional anesthetic technique Pharmacokinetic factors Physiochemical and stereoselective properties of individual local anesthetics Individual patient characteristics

Based on several large series from the mid-1980s to the late 1990s, the reported overall incidence of seizures and cardiac arrest is relatively low (Table 56-1). Because premonitory signs precede the vast majority of seizures, they are most likely the result of acutely increased plasma levels of local anesthetic secondary to inadvertent intravascular injection. Seizures are five times more frequent after peripheral nerve block than after epidural anesthesia; this difference may be explained by the fact that the former usually requires larger

Table 56–1

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Reported Incidence of Seizures and Cardiac Arrest after Regional Anesthesia

Technique

Seizures

Cardiac Arrest

Peripheral nerve block

36/72,746 (4.9/10,000) 9/52,844 (1.3/10,000) 3/11,229 2.6/10,000

4/72,746 (0.54/10,000) 3/52,844 (0.57/10,00) 0/11,229 0

Epidural Intravenous regional

231

●

● ●

●

Amount of administered drug Physiochemical properties (e.g., lipid solubility, protein binding) of the individual local anesthetic Regional blood flow Presence of perineural tissue and fat that can bind local anesthetics Concomitant use of vasoconstrictors with local anesthetics

In general, perineural tissue with greater regional blood flow has a more rapid and complete uptake of local anesthetic, regardless of its type. Based on technique, the rates of systemic absorption generally decrease, in the following order: interpleural, intercostal, epidural, brachial plexus, sciatic-femoral (Table 56-2). The greater the total dose administered, the greater the systemic absorption and peak plasma levels. Within clinically recommended doses, and with the exception of speed of injection, this relationship is nearly linear. The addition of epinephrine causes a 20% to 30% reduction in peak plasma levels during epidural anesthesia and peripheral nerve blocks. After systemic absorption, local anesthetics are rapidly distributed throughout different tissues in the body, based on organ perfusion. Because the CNS and CVS are highly perfused, initial tissue levels of local anesthetics may not correlate with systemic blood levels. Thus, regional pharmacokinetics play an important role in the subsequent systemic pharmacodynamic effects of these anesthetics. The severity of local anesthetic–induced toxicity can also be influenced by the patient’s acid-base status. With increased arterial carbon dioxide tension or decreased pH, the seizure threshold is reduced. Increased hydrogen ion concentrations enhance cerebral blood flow, so that more local anesthetic is delivered to the CNS. Also, hypercapnia or acidosis reduces plasma protein binding of local anesthetics, which increases the amount of free drug available to diffuse across cell membranes. Patients with advanced liver disease may be particularly susceptible to local anesthetic–induced toxicity with the amide class of drugs, owing to the combination of reduced protein synthesis and hepatic degradation.

Implications In general, more potent local anesthetics produce seizures at lower plasma concentrations and doses than do less potent local anesthetics. The relative CNS toxicity of bupivacaine and lidocaine is approximately 4:1, which mirrors their relative anesthetic potency. The cardiovascular manifestations during the excitatory phase of CNS toxicity can include increased heart rate, blood pressure, and cardiac output. The CVS is much more resistant to the toxic effects of local anesthetics than the CNS is. Severe CVS toxicity is rare with the less potent amide local anesthetics, and severe direct myocardial

REGIONAL ANESTHESIA & PAIN MANAGEMENT

Methemoglobinemia is characterized by central cyanosis that is refractory to supplemental oxygen. Central cyanosis usually develops with methemoglobin levels greater than 15%. Higher concentrations may result in anxiety, dyspnea, headache, weakness, nausea, and vomiting. Severe methemoglobinemia (>50% to 60% methemoglobin) may cause confusion, seizures, arrhythmias, hemodynamic instability, and death. The diagnosis is suggested by the presence of “chocolate-colored” blood that does not change color when exposed to air and an arterial percentage of oxygen saturation gap when analyzed by pulse oximetry and arterial blood gases. The diagnosis is confirmed by qualitative measures of methemoglobin concentrations by co-oximetry.

Local Anesthetic Systemic Toxicity

doses of local anesthetics than the latter does. In contrast, the frequency of cardiac arrest is low with either technique. Although the systemic toxic effects of local anesthetics are dose dependent, the rate of change in plasma levels is also an important factor. In the absence of intravascular injection, local anesthetics are absorbed into the systemic circulation by uptake and distribution from the surrounding perineural tissue. Subsequent plasma levels are governed by the following factors: ●

METHEMOGLOBINEMIA

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Table 56–2

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Lidocaine

Mepivacaine

Ropivacaine

Levobupivacaine

Regional Anesthesia and Pain Management

Typical Maximal Plasma Concentrations of Common Local Anesthetics, by Regional Technique

Local Anesthetic Bupivacaine

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Technique Brachial plexus Epidural Intercostal Sciatic/femoral Brachial plexus Epidural Intercostal Sciatic/femoral* Brachial plexus Epidural Intercostal Sciatic/femoral Brachial plexus Epidural Intercostal Femoral† Psoas compartment† Brachial plexus‡ Epidural

Dose (mg) 150 50 140 400 400 400 400 650 500 500 500 500 190 150 140 150 150 250 150

Cmax (μg/mL) 1.00 1.50 1.26 1.89 4.00 4.27 6.80 2.39 3.68 4.95 8.06 3.59 1.30 1.07 1.10 0.65 1.19 1.20 1.02

Tmax (min) 20 1.7 20 15 25 20 15 30 24 16 9 31 53 40 21 30 15 55 2

Toxic Plasma Concentration (μg/mL) 3 3 3 3 5 5 5 5 5 5 5 5 4 4 4 4 4 >4 >4

*Data from Elmas C, Atanassoff PG: Combined inguinal paravascular (3-in-1) and sciatic nerve blocks for lower limb surgery. Reg Anesth 18:88-92, 1993. † Data from Kaloul I, Guay J, Cote C, et al: Ropivacaine plasma concentrations are similar during continuous lumbar plexus block using the anterior three-in-one and the posterior psoas compartment techniques. Can J Anaesth 51:52-56, 2004. ‡ Data from Crews JC, Weller RS, Moss J, James RL: Levobupivacaine for axillary brachial plexus block: A pharmacokinetic and clinical comparison in patients with normal renal function or renal disease. Anesth Analg 95:219-223, 2002. Cmax, maximal plasma concentration; Tmax, maximal time. From Salinas FV: Ion channel ligands/sodium channel blockers/local anesthetics. In Evers AS, Maze M (eds): Anesthetic Pharmacology: Physiologic Principles and Clinical Practice, 1st edition. Philadelphia, Churchill Livingstone, 2004, pp 507-537.

depression and peripheral vasodilatation occur only with extremely high levels of either lidocaine or mepivacaine. Conversely, more potent amide local anesthetics, such as bupivacaine, have a significantly narrower margin of CVS safety, expressed as the ratio of the dosage or plasma concentration required to produce irreversible cardiovascular collapse (CC) to that required to produce CNS toxicity (generalized seizures). In contrast to lidocaine, the CC/CNS ratio for bupivacaine can result in nearly simultaneous progression from CNS toxicity to cardiovascular collapse, in large part owing to bupivacaine’s ability to cause malignant ventricular arrhythmias. Bupivacaine’s enhanced ability to precipitate ventricular arrhythmias is thought to be related primarily to differences in the recovery of sodium channel block between bupivacaine and lidocaine. Both drugs rapidly block sodium channels during systole; however, bupivacaine dissociates from the sodium channel receptor much more slowly than lidocaine during diastole. Thus, within the physiologic range of heart rate, lidocaine dissociates rapidly (fast on–fast off) from the sodium channel, whereas bupivacaine remains avidly bound to it during diastole (fast on–slow off). The net electrophysiologic effect is slowed ventricular conduction and prolonged refractoriness, both of which are conducive to reentry ventricular arrhythmias. Although bupivacaine has the advantage of prolonged duration of block, with enhanced sensory-motor dissociation, concerns about its potent cardiotoxicity led to the development of alternative long-acting amide local anesthetics with the same beneficial properties but an enhanced margin of safety.

Ropivacaine is the propyl homologue of mepivacaine and bupivacaine. In contrast to older amide local anesthetics, which exist as racemic mixtures, ropivacaine is an enantiomerically pure (levorotatory isomer) local anesthetic. In general, the levorotatory isomer has less potential for systemic toxicity than the dextrorotatory isomer of the same local anesthetic. Animal and human volunteer studies have confirmed that ropivacaine is approximately 30% to 40% less cardiotoxic than racemic bupivacaine. Ropivacaine causes less prolongation of cardiac conduction and less direct negative inotropic effects than equivalent doses of bupivacaine. During cardiac resuscitation after incremental overdosage in anesthetized dogs, free plasma concentrations of ropivacaine causing cardiac arrest were more than twice those of bupivacaine. Further, the inability to resuscitate dogs with bupivacaine was higher than with ropivacaine (50% versus 10%). Recent case reports attest to ropivacaine’s lower cardiotoxicity, even after the injection of large doses sufficient to cause cardiac arrest. Although the incidence of severe systemic toxicity from local anesthetics appears to be decreasing, the potential catastrophic outcomes from cardiotoxicity cannot be underestimated. In the most recent ASA closed claims analysis of injuries associated with regional anesthesia, unintentional intravascular injections were the second largest category of neuraxial anesthesia claims that were block related and resulted in high-severity outcome (death or brain damage). Of 12 such cases, 11 occurred in the 1980s and only 1 in the 1990s; 75% of these were associated with cardiac arrest. Clinically significant methemoglobinemia can occur when large doses of prilocaine (>600 mg) are administered.

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MANAGEMENT Management of systemic toxicity depends on the severity of the event. Because plasma levels of local anesthetics associated with minor reactions fall rapidly, as long as normal metabolic processes are functional, such events can be allowed to terminate spontaneously, provided attention is paid to maintaining airway patency and providing supplemental oxygen and hemodynamic support. Seizures can be terminated with small doses of intravenous midazolam (0.05 to 0.1 mg/kg), sodium thiopental (1 to 2 mg/kg), or propofol (0.5 to 1.5 mg/kg). If generalized tonic-clonic seizures are not aborted with these doses of intravenous anesthetics, administration of succinylcholine followed by endotracheal intubation is indicated. Prompt termination of seizure activity is important to prevent the rapid development of severe metabolic acidosis associated with tonic-clonic muscular contractions.

Table 56–3

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Local Anesthetic Systemic Toxicity

233

Cardiovascular depression should be treated by fluid resuscitation and vasopressors, if required. Because hypotension is usually due to a combination of direct myocardial depression and peripheral vasodilatation, agents with both β1 and α1 activity are recommended: ephedrine or phenylephrine or both (even epinephrine or norepinephrine) in incremental doses until the desired response is obtained. With cardiovascular collapse refractory to these drugs, vasopressin should be considered. Malignant ventricular arrhythmias should be managed with direct-current cardioversion and amiodarone if needed to prevent recurrences. If CVS toxicity is not responsive to any of these measures, intravenous lipid infusion or cardiopulmonary bypass should be considered. Recent animal models have demonstrated that intravenous lipid emulsion can facilitate resuscitation from acute bupivacaine overdose.

PREVENTION Because the vast majority of systemic toxic reactions to local anesthetics are the result of either inadvertent intravascular injection or systemic absorption of excessive doses, efforts should be made to minimize that potential. The anesthesiologist must be aware of the risk factors associated with both the regional technique and physiologic status of the patient that predispose to clinically significant systemic toxic reactions. Proper patient preparation includes appropriate monitoring of heart rate, blood pressure, and oxygenation; recent data indicate the added value of continuous electrocardiography. Resuscitative drugs and equipment should be immediately available. Sedatives may increase the seizure threshold but also attenuate the patient’s ability to report subjective symptoms of CNS toxicity, as well as reducing the heart rate’s response to the traditional 15-μg epinephrine “test dose.” Techniques that reduce the likelihood of direct intravascular injection should be used. Although no single measure is 100% reliable in preventing severe systemic toxicity, the following measures are recommended: ●

●

●

Inject local anesthetics in small, fractionated doses, with frequent aspiration of the syringe to assess for intravascular placement of either the needle or catheter. In the absence of contraindications, add epinephrine to local anesthetic solutions to aid in the identification of intravascular injections (“test dose”) and to decrease systemic absorption from the injection site. Be aware of the different criteria for a positive epinephrine test dose during different clinical scenarios (Table 56-3).

Criteria for Positive Epinephrine (15 μg) Test Dose in Adults

Clinical Scenario

Heart Rate Increase (bpm)

Systolic Blood Pressure Increase (mm Hg)

>20

>15

Decrease ≥25%

NA >9 >8

>15 >15 >15

NA Decrease ≥25% Decrease ≥25%

Age <60 yr (not on β-blockers) β-blockers Age >60 yr General anesthesia bpm, beats per minute; NA, not applicable.

T-Wave Amplitude

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After several cases reports of methemoglobinemia after intravenous prilocaine was used for regional anesthesia, it was withdrawn for such use. However, it is still available as a eutectic mixture of prilocaine 2.5% and lidocaine 2.5% (EMLA cream), commonly used as a topical anesthetic. Neonatal patients have immature reductase enzyme pathways that may predispose them to methemoglobinemia with the application of EMLA cream. Benzocaine is an ester-type local anesthetic commonly used for topical anesthesia before fiberoptic intubation, bronchoscopy, transesophageal echocardiography, and upper gastrointestinal endoscopy procedures. The Food and Drug Administration’s adverse event reporting system described 132 cases of methemoglobinemia secondary to benzocaine between 1997 and 2002. These resulted in two deaths (1.5%) and 55 (42%) life-threatening complications. Potential risk factors include concomitant use of other oxidizing agents and excessive absorption from either breaks in the mucosal barrier or delivery of excessive dosages. Clinically significant toxicity is effectively treated with intravenous methylene blue (1 mg/kg). Immunologic-mediated (allergic) reactions to preservative-free amide local anesthetics are extremely rare. However, ester local anesthetics may produce allergic reactions due to their metabolism to para-aminobenzoic acid (PABA), a known allergen. Amide local anesthetics are not metabolized to PABA unless preservatives (e.g., methylparaben) are used in their formulation; methylparaben is metabolized to PABA. Patients with true allergic reactions to ester local anesthetics should be treated with preservative-free local anesthetics.

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Although the scientific basis for maximum recommended doses is tenuous, and actual plasma levels vary with the site of injection, always administer the minimum effective dose. For blocks with a higher risk of intravascular injection or systemic absorption, consider using ropivacaine. During the administration of the local anesthetics, be vigilant for symptoms and signs of toxicity. Early intervention can reduce the complications of local anesthetic–induced toxicity.

Further Reading Albright GA: Cardiac arrest following regional anesthesia with etidocaine or bupivacaine [editorial]. Anesthesiology 51:285-287, 1979. Auroy Y, Benhamou D, Barguues L, et al: Major complications of regional anesthesia in France: The SOS regional anesthesia hotline service. Anesthesiology 97:1274-1280, 2002. Auroy Y, Narchi P, Messiah A, et al: Serious complications related to regional anesthesia: Results of a prospective survey in France. Anesthesiology 87:479-486, 1997. Berkum Y, Ben-Zvi A, Levy Y, et al: Evaluation of adverse reactions to local anesthetics: Experience with 236 patients. Ann Allergy Asthma Immunol 91:342-345, 2003. Bernards CM, Carpenter RL, Rupp SM, et al: Effects of midazolam and diazepam premedication on the central nervous system and cardiovascular toxicity of bupivacaine in pigs. Anesthesiology 70:318-323, 1989. Braid DP, Scott DB: The effect of adrenaline on the systemic absorption of local anaesthetic drugs. Acta Anaesthesiol Scand Suppl 23:334-346, 1996. Brown DL, Ransom DM, Hall JA, et al: Regional anesthesia and local anesthetic-induced systemic toxicity: Seizure frequency and accompanying cardiovascular changes. Anesth Analg 81:321-328, 1995. Butterworth JF, Brownlow RC, Leith JP, et al: Bupivacaine inhibits cyclic-3′, 5′-adenosine monophosphate production: A possible contributing factor to cardiovascular toxicity. Anesthesiology 79:88-95, 1993. Butterworth JF, Strichartz GR: Molecular mechanisms of local anesthesia: A review. Anesthesiology 72:711-734, 1990. Chazalon P, Tourtier JP, Villevielle T, et al: Ropivacaine-induced cardiac arrest after peripheral nerve block: Successful resuscitation. Anesthesiology 99:1449-1451, 2003. Clarkson CW, Hondeghem LM: Mechanism for bupivacaine depression of cardiac conduction: Fast block sodium channels during the action potential with slow recovery during diastole. Anesthesiology 62: 396-405, 1985. Dernedde M, Furlan D, Verbesselt R, et al: Grand mal convulsions after accidental intravenous injection of ropivacaine. Anesth Analg 98:521-523, 2004. Gall H, Kaufmann R, Kalveram CM: Adverse reactions to local anesthetics: Analysis of 197 cases. J Allergy Clin Immunol 97:933-937, 1996. Groban L: Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model. Reg Anesth Pain Med 28:3-11, 2003. Groban L, Butterworth J: Lipid reversal of bupivacaine toxicity: Has the silver bullet been identified? [editorial] Reg Anesth Pain Med 28:167-169, 2003.

Groban L, Deal DD, Vernon JC, et al: Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs. Anesth Analg 92:37-43, 2001. Heavner JE: Cardiac toxicity of local anesthetics in the intact isolated heart model: A review. Reg Anesth Pain Med 27:545-555, 2002. Huet O, Eyrolle LJ, Mazoit JX, Ozier YM: Cardiac arrest after injection of ropivacaine for posterior lumbar plexus blockade. Anesthesiology 99:1451-1453, 2003. Knudsen K, Suurkula MB, Blomberg S, et al: Central nervous and cardiovascular effects of IV infusions of ropivacaine, bupivacaine, and placebo in volunteers. Br J Anaesth 78:507-514, 1997. Lee LA, Posner KL, Domino KB, et al: Injuries associated with regional anesthesia in the 1980s and 1990s: A closed claims analysis. Anesthesiology 101:143-152, 2004. Liu PL, Feldman HS, Giasi R, et al: Comparative CNS toxicity of lidocaine, etidocaine, bupivacaine, and tetracaine in awake dogs following rapid intravenous administration. Anesth Analg 62:375-379, 1983. Lofstrom JB: 1991 Labat lecture: The effects of local anesthetics on the peripheral vasculature. Reg Anesth 17:1-11, 1992. Moore JM, Liu SS, Neal JM: Premedication with fentanyl and midazolam decreases the reliability of intravenous lidocaine test dose. Anesth Analg 86:1015-1017, 1998. Moore TJ, Walsh CS, Cohen MR: Reported adverse event cases of methemoglobinemia associated with benzocaine products. Arch Intern Med 164:1192-1196, 2004. Mulroy MF: Systemic toxicity and cardiotoxicity from local anesthetics: Incidence and preventative measures. Reg Anesth Pain Med 27:556-561, 2002. Orringer CE, Eustace JC, Wunsch CD, Gardner LB: Natural history of lactic acidosis after grand-mal seizures. N Engl J Med 297:796-799, 1977. Salinas FV: Ion channel ligands/sodium channel blockers/local anesthetics. In Evers AS, Maze M (eds): Anesthetic Pharmacology: Physiologic Principles and Clinical Practice, 1st ed. Philadelphia, Churchill Livingstone, 2004, pp 507-537. Scott DB: Evaluation of the toxicity of local anesthetic agents in man. Br J Anaesth 47:56-59, 1975. Soltesz EG, van Pelt F, Byrne JG: Emergent cardiopulmonary bypass for bupivacaine cardiotoxicity. J Cardiothorac Vasc Anesth 17:357-358, 2003. Stewart J, Kellett N, Castro D: The central nervous system and cardiovascular effects of levobupivacaine and ropivacaine in healthy volunteers. Anesth Analg 97:412-416, 2003. Szocik JF, Gardener CA, Webb RC: Inhibitory effects of bupivacaine and lidocaine on adrenergic neuroeffector junctions in rat-tail artery. Anesthesiology 78:911-917, 1993. Tanaka M, Nishikawa T: T-wave amplitude as in indicator for detecting intravascular injection of epinephrine test dose in awake and anesthetized elderly patients. Anesth Analg 93:1332-1337, 2001. Tanaka M, Sato M, Nishikawa T: The efficacy of simulated intravascular test dose in sedated patients. Anesth Analg 93:1612-1617, 2001. Weinberg GL: Current concepts in resuscitation of patients with local anesthetic cardiac toxicity. Reg Anesth Pain Med 27:568-575, 2002. Weinberg GL, Ripper R, Feinstein DL, Hoffman W: Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med 28:198-202, 2003. Xuecheng J, Xiaobin W, Bo G, et al: The plasma concentration of lidocaine after slow versus rapid administration of an initial dose of epidural anesthesia. Anesth Analg 84:570-573, 1997.

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Spinal Hematoma Terese T. Horlocker Case Synopsis A 75-year-old man undergoes total knee replacement under continuous epidural anesthesia. The epidural catheter is left indwelling to provide postoperative analgesia with 0.125% bupivacaine. Thromboprophylaxis with low-molecular-weight heparin (LMWH), 30 mg twice daily, is initiated 24 hours after surgery. Forty-eight hours later, the epidural catheter is removed 1 hour after a dose of LMWH. The patient’s sensory and motor block progresses, however, despite discontinuation of the local anesthetic infusion. A magnetic resonance image reveals an epidural hematoma at T12. Immediate surgical decompression results in complete neurologic recovery.

Definition The actual incidence of neurologic dysfunction resulting from hemorrhagic complications associated with neuraxial blockade is unknown; however, estimates in the literature are less than 1 in 150,000 for epidural anesthesia and less than 1 in 220,000 for spinal anesthesia. In a review of the literature between 1906 and 1994, Vandermeulen and colleagues reported 61 cases of spinal hematoma associated with epidural or spinal anesthesia. In 42 of the 61 patients (69%) with spinal hematomas associated with central neural blockade, there was evidence of hemostatic abnormality. Twenty-five of the patients had received intravenous or subcutaneous (unfractionated or low-molecular-weight) heparin, and an additional five patients were presumably administered heparin during vascular surgical procedures. In addition, 12 patients had evidence of coagulopathy or thrombocytopenia or were treated with antiplatelet drugs (aspirin, indomethacin, ticlopidine), oral anticoagulants (phenprocoumon), thrombolytics (urokinase), or dextran 70 immediately before or after the spinal or epidural anesthetic. Needle and catheter placement

Table 57–1

■

was difficult in 15 patients (25%) and bloody in 15 patients (25%). Overall, in 53 of 61 cases (87%), either a clotting abnormality or difficult needle placement was noted. A spinal anesthetic was administered in 15 patients. The remaining 46 patients received an epidural anesthetic, including 32 patients with indwelling catheters. In 15 of the latter, spinal hematoma occurred immediately after removal of the epidural catheter. These results suggest that catheter removal is not entirely atraumatic and that the patient’s coagulation status should be optimized at the time of both catheter placement and removal.

Recognition In Vandermeulen’s series, neurologic compromise presented as progression of sensory or motor block (68% of patients) or bowel or bladder dysfunction (8% of patients), rather than severe radicular back pain. Spinal hematoma should be ruled out in patients exhibiting early signs of cord compression in the postoperative period. The differential diagnosis includes cauda equina syndrome, epidural abscess, and anterior spinal artery syndrome (Table 57-1). If spinal hematoma is suspected, radiographic confirmation must be sought immediately,

Differential Diagnosis of Epidural Abscess, Epidural Hemorrhage, and Anterior Spinal Artery Syndrome

Finding

Epidural Abscess

Epidural Hemorrhage

Anterior Spinal Artery Syndrome

Age of patient Previous history Onset Generalized symptoms

Any age Infection* 1-3 days Fever, malaise, back pain

Elderly Arteriosclerosis, hypotension Sudden None

Sensory involvement Motor involvement Segmental reflexes Myelogram/CT scan Cerebrospinal fluid Blood data

None or paresthesias Flaccid paralysis, later spastic Exacerbated*; later obtunded Signs of extradural compression Increased cell count Rise in sedimentation rate

50% >50 yr Anticoagulants Sudden Sharp, transient back and leg pain Variable, late Flaccid paralysis Abolished Signs of extradural compression Normal Prolonged coagulation time*

Minor, patchy Flaccid paralysis Abolished Normal Normal Normal

*Infrequent findings. CT, computed tomography. From Wedel DJ, Horlocker TT: Risks of regional anesthesia—infectious, septic. Reg Anesth 21:57-61, 1996.

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PROBLEM ANALYSIS

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because delay can lead to irreversible cord ischemia. Although spontaneous recovery has been reported, the treatment of choice is decompressive laminectomy. Complete neurologic recovery is unlikely if surgery is postponed for more than 8 hours.

Risk Assessment The risk of spinal hematoma depends on the timing of needle or catheter placement and removal and the degree of anticoagulation with the following drugs: ● ● ● ●

Standard heparin (intravenous and subcutaneous) Low-molecular-weight heparin (LMWH) Oral anticoagulants Antiplatelet medications

STANDARD HEPARIN Ruff and Dougherty reported spinal hematomas in 7 of 342 patients (2%) who underwent diagnostic lumbar puncture with subsequent heparinization. Three factors were associated with increased risk: less than 60 minutes between the administration of heparin and the lumbar puncture, traumatic needle placement, and concomitant use of other anticoagulants (aspirin). These findings have been used to define safe practice protocols for patients undergoing neuraxial blockade during systemic heparinization, particularly in the case of vascular surgery. Intrathecal and epidural anesthesia and analgesia, along with complete heparinization and cardiopulmonary bypass, have been reported without neurologic sequelae. However, at this time, there are insufficient data and experience to quantify the risk of spinal hematoma among this patient population. Low-dose subcutaneous, unfractionated heparin is administered for thromboprophylaxis in patients undergoing major thoracoabdominal surgery and in those at increased risk for hemorrhage with oral anticoagulant or LMWH therapy. A review by Schwander and Bachmann noted no spinal hematomas in more than 5000 patients who received subcutaneous heparin with spinal or epidural anesthesia. There were five cases of spinal hematoma associated with neuraxial blockade in patients receiving low-dose heparin. This confirms the limited risk associated with the use of epidural and spinal anesthesia in the presence of subcutaneous heparin treatment. LOW-MOLECULAR-WEIGHT HEPARIN Despite a notable safety record in Europe, in the first 5 years after the release of LMWH in North America, there were 40 cases of spinal hematoma associated with LMWH and neuraxial anesthesia. The risk of spinal hematoma, based on LMWH sales, prevalence of neuraxial techniques, and reported cases, was estimated to be approximately 1 in 3000 continuous epidural anesthetics, compared with 1 in 40,000 spinal anesthetics. However, this risk was later found to be much higher. Similar to the Vandermeulen series, severe radicular back pain was not the presenting symptom. Most patients complained of new-onset numbness, weakness, or bowel and

bladder dysfunction. About half of patients undergoing a continuous technique reported neurologic deficits 12 hours or more after catheter removal. The median interval between initiation of LMWH therapy and neurologic dysfunction was 3 days, and the median time to onset of symptoms and laminectomy was more than 24 hours. Less than one third of patients reported fair or good neurologic recovery. Over the past 5 years, the number of reported cases of spinal hematoma associated with LMWH therapy has declined markedly. This may be a result of decreased reporting, improved management, or simple avoidance of all neuraxial techniques in patients receiving LMWH. Continued monitoring is necessary. Indications and labeled uses for LMWH continue to evolve, including for thromboprophylaxis and the treatment of deep venous thrombosis. In addition, several off-label applications of LMWH are of special interest to the anesthesiologist and warrant discussion. LMWH has been shown to be efficacious as “bridge therapy” for patients chronically anticoagulated with warfarin, including parturients and patients with prosthetic cardiac valves, a history of atrial fibrillation, or preexisting hypercoagulable conditions. The patient is therapeutically anticoagulated with LMWH while the warfarin effect is allowed to resolve before surgery. Doses of LMWH are two- to threefold higher than those used for thromboprophylaxis. At least 24 hours is required for normal hemostais following this level of LMWH anticoagulation. ORAL ANTICOAGULANTS Few data exist regarding the risk of spinal hematoma in patients with indwelling epidural catheters who are anticoagulated with warfarin. The optimal duration of an indwelling catheter and the timing of its removal in an anticoagulated patient are also controversial. A combined series of 651 patients reported no spinal hematomas in those receiving neuraxial block in conjunction with low-dose warfarin therapy. The mean international normalized ratio (INR) at the time of catheter removal was 1.4. However, marked variability in patient response to warfarin was noted. ANTIPLATELET MEDICATIONS Several large studies have demonstrated the relative safety of neuraxial blockade in obstetric, surgical, and ambulatory pain clinic patients receiving antiplatelet medications. In a prospective study involving 1000 patients, Horlocker and colleagues reported that preoperative antiplatelet therapy did not increase the incidence of blood present at the time of needle or catheter placement or removal, suggesting that trauma during needle or catheter placement is neither increased nor sustained by these medications. The paucity of case reports among these patients is notable, given the prevalence of aspirin and other nonsteroidal anti-inflammatory drug (NSAID) use among patients with acute, chronic, or cancer pain who receive interventional therapy. No series involving the performance of neuraxial blockade in the presence of thienopyridine derivatives (clopidogrel and ticlopidine) or platelet glycoprotein IIb/IIIa receptor antagonists has been reported. Although case reports are inconsistent, increased perioperative bleeding has been noted in patients undergoing cardiac and vascular surgery after

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receiving ticlopidine, clopidogrel, and glycoprotein IIb/IIIa antagonists. This suggests that these medications may increase the risk of regional anesthesia–related hemorrhagic complications.

●

Low-molecular-weight heparin ● Proceed cautiously. ● For preoperative LMWH, administer spinal anesthesia 12 to 24 hours after the administration of LMWH, depending on dose (i.e., treatment versus thromboprophylaxis). ● Epidural catheters may remain indwelling with oncedaily dosing of LMWH. Place or remove catheters in the morning; administer LMWH in the evening. ● Epidural catheters should not remain indwelling with twice-daily dosing of LMWH. Remove the epidural catheter 2 hours before the initiation of twice-daily LMWH therapy.

●

Oral anticoagulants ● Preoperative administration does not preclude regional technique. ● Monitor the prothrombin time postoperatively; there is marked variability in patient response. ● Remove the catheter when the INR is less than 1.5.

●

Antiplatelet agents ● NSAIDs do not represent significant risk. ● Allow the antiplatelet effects of clopidogrel, ticlopidine, and glycoprotein IIb/IIIa inhibitors to resolve before neuraxial block.

Intravenous heparin ● Administer heparin 60 minutes after needle placement. ● Monitor the effect of the heparin. ● Remove the catheter when heparin activity is low or completely reversed.

Table 57–2

■

PREVENTION The patient’s coagulation status should be optimized at the time of spinal or epidural needle or catheter placement, and

Pharmacologic Activities of Anticoagulants, Antiplatelet Agents, and Thrombolytics Effect on Coagulation Variables

Time to Normal Hemostasis after Discontinuation

Agent

PT

aPTT

Time to Peak Effect

Intravenous heparin Subcutaneous heparin Low-molecular-weight heparin Warfarin

↑ — — ↑↑↑

↑↑↑ ↑ — ↑

Minutes 40-50 min 3-5 hr 4-6 days (less with loading dose)

4-6 hr 4-6 hr 12-24 hr 4-6 days

Antiplatelet agents Aspirin Other NSAIDs Ticlopidine, clopidogrel Platelet glycoprotein IIb/IIIa receptor inhibitors Fibrinolytics

—

— Hours Hours Hours Minutes

5-8 days 1-3 days 1-2 wk 8-48 hr

Minutes

24-36 hr

↑

↑↑

aPTT, activated partial thromboplastin time; NSAID, nonsteroidal anti-inflammatory drug; PT, prothrombin time; —, no effect; ↑, clinically insignificant increase; ↑↑, possibly clinically significant increase; ↑↑↑, clinically significant increase.

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Subcutaneous heparin ● Consider delaying administration until after needle or catheter placement in patients with anticipated technical difficulties. ● Monitor platelet count in patients receiving heparin for more than 4 days.

MANAGEMENT Before surgery, the patient’s history should be reviewed for medical conditions associated with bleeding tendencies, and the patient should be questioned about previous episodes of sustained bleeding after trauma or surgery. Because patients respond to anticoagulants with varying sensitivities, it may be helpful to verify the reversal of heparin’s or warfarin’s effects before the performance of epidural or spinal blockade (Table 57-2). The following guidelines will assist in the management of patients with altered hemostasis undergoing regional anesthetic techniques. Except in the most extraordinary circumstances, spinal and epidural blockade should be avoided in fully anticoagulated patients or those who have received thrombolytic therapy.

Spinal Hematoma

●

Implications Whether to perform spinal or epidural anesthesia or analgesia and the timing of catheter removal in a patient receiving thromboprophylaxis should be decided on an individual basis, weighing the small but definite risk of spinal hematoma against the benefits of regional anesthesia for the particular patient. Alternative anesthetic and analgesic techniques exist for patients considered to be at an unacceptably high risk.

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the level of anticoagulation must be carefully monitored during the period of epidural catheterization. It is important to note that patients respond with variable sensitivities to anticoagulant medications. Indwelling catheters should not be removed in the presence of therapeutic anticoagulation, because this appears to significantly increase the risk of spinal hematoma. In addition, communication among clinicians involved in the perioperative management of patients receiving anticoagulants for thromboprophylaxis is essential to decrease the risk of serious hemorrhagic complications.

Further Reading Bergqvist D, Lindblad B, Matzsch T: Low molecular weight heparin for thromboprophylaxis and epidural/spinal anaesthesia: Is there a risk? Acta Anaesthesiol Scand 36:605-609, 1992. Chaney MA: Intrathecal and epidural anesthesia and analgesia for cardiac surgery. Anesth Analg 84:1211-1221, 1997. CLASP (Collaborative Low-Dose Aspirin Study in Pregnancy): A randomized trial of low-dose aspirin for the prevention and treatment of preeclampsia among 9364 pregnant women. Lancet 343:619-629, 1994. Ho AM, Chung DC, Joynt GM: Neuraxial blockade and hematoma in cardiac surgery: Estimating the risk of a rare adverse event that has not (yet) occurred. Chest 117:551-555, 2000. Horlocker TT, Bajwa ZH, Ashraft Z, et al: Risk assessment of hemorrhagic complications associated with nonsteroidal antiiflammatory

medications in ambulatory pain clinic patients undergoing epidural steroid injection. Anesth Analg 95:1691-1697, 2002. Horlocker TT, Wedel DJ, Benzon H, et al: Regional anesthesia and anticoagulation—defining the risk. The Second ASRA consensus conference on neuraxial anesthesia and anticoagulation. Reg Anesth Pain Med 28:172-197, 2003. Horlocker TT, Wedel DJ, Offord KP, et al: Preoperative antiplatelet therapy does not increase the risk of spinal hematoma associated with regional anesthesia. Anesth Analg 80:303-309, 1995. Odoom JA, Sih IL: Epidural analgesia and anticoagulant therapy. Anaesthesia 38:254-259, 1983. Rao TLK, El-Etr AA: Anticoagulation following placement of epidural and subarachnoid catheters: An evaluation of neurologic sequelae. Anesthesiology 55:618-620, 1981. Ruff RL, Dougherty JH: Complications of lumbar puncture followed by anticoagulation. Stroke 12:879-881, 1981. Schroeder DR: Statistics: Detecting a rare adverse drug reaction using spontaneous reports. Reg Anesth Pain Med 23:183-189, 1998. Schwander D, Bachmann F: Heparin and spinal or epidural anesthesia: Decision analysis [review]. Ann Fr Anesth Reanim 10:284-296, 1991. Tryba M: Epidural regional anesthesia and low molecular heparin: Pro [German]. Anasth Intensivmed Notfallmed Schmerzther 28:179-181, 1993. Vandermeulen EP, Van Aken H, Vermylen J: Anticoagulants and spinalepidural anesthesia. Anesth Analg 79:1165-1177, 1994. Wu CL, Perkins FM: Oral anticoagulant prophylaxis and epidural catheter removal. Reg Anesth 21:517-524, 1996.

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James C. Crews Case Synopsis

PROBLEM ANALYSIS Definition Infectious complications of central neuraxial anesthetic and analgesic procedures occur rarely but may be associated with significant patient morbidity, including sepsis, epidural or paravertebral abscess formation, meningitis, and paraplegia. A high index of suspicion, early diagnosis, and prompt intervention with appropriate therapy are important for achieving optimal outcomes. Infectious complications of central neuraxial block techniques may range from superficial infection at the percutaneous puncture site to more consequential infections, such as epidural abscess or meningitis. Most consequential infectious complications are associated with percutaneous catheter techniques, although epidural abscess and meningitis have been reported after single-injection epidural anesthesia or corticosteroid injections. Potential mechanisms for infection associated with central neuraxial block include (1) direct inoculation during needle or catheter placement; (2) infection at the catheter exit site, with spread along the catheter track; (3) contamination of the injectate; and (4) hematogenous spread (“bacteremic seeding”) from a distant site of infection. Progressive neurologic impairment of bowel and bladder function or lower extremity sensory and motor function may result from epidural or paravertebral abscess with spinal cord or nerve root compression. The specific pathogenesis underlying spinal cord dysfunction with spinal epidural abscess is thought to be related to direct mechanical

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A 63-year-old woman with a history of diabetes mellitus, hypertension, and chronic low back pain underwent a small bowel resection for obstruction secondary to metastatic colon cancer. A thoracic epidural catheter was placed for perioperative analgesia, and the patient received an epidural infusion of bupivacaine and morphine for 3 days postoperatively. At the time of epidural catheter removal, the insertion site was surrounded by a small area of erythema, with a scant amount of serosanguineous drainage. The patient was followed by the Acute Pain Service for an additional 2 days, at which time she reported severe thoracolumbar back pain, low-grade fever, and heaviness in her legs. Examination of the back revealed a small erythematous area at the previous epidural catheter insertion site with a small amount of purulent drainage. The neurologic examination was unremarkable. Laboratory studies demonstrated leukocytosis. Owing to the patient’s history and complaints, a magnetic resonance imaging (MRI) scan with and without gadolinium contrast was obtained of the thoracic, lumbar, and sacral spine. MRI demonstrated an extensive posterior spinal epidural abscess from T10 to L2. The patient underwent a laminotomy drainage procedure and culture-directed antibiotic therapy for Staphylococcus aureus. The remainder of her hospital recovery was uneventful, and she was discharged home without neurologic sequelae.

compression or vascular damage, with resultant spinal cord hypoxia.

Recognition Superficial infectious complications usually present with localized erythema and drainage at the needle or catheter insertion site. Deep infections may present with local symptoms at the needle or catheter insertion site in addition to the following: ● ● ● ●

Back pain Fever Localized tenderness Leukocytosis

Neurologic impairment due to deep tissue abscess and spinal cord or nerve root compression may present with the following: ● ● ●

Radicular irritation Progressive sensory or motor neurologic deficit Bowel and bladder incontinence The clinical features of meningitis include the following:

● ● ● ●

Nuchal rigidity Headache Leukocytosis and fever Photophobia

Patients with evidence of superficial infection should be evaluated and monitored for the development of symptoms associated with deep infection. Culture of purulent drainage at the site of infection or epidural catheter tip may 239

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be important to direct appropriate antibiotic therapy. Before hospital discharge, patients must be instructed to notify appropriate health care personnel or to seek emergency medical evaluation in the event of any of the following: ● ● ● ●

New onset of back pain Fever Redness or soreness at the needle or catheter insertion site Subtle signs or symptoms of neurologic impairment

Patients with signs or symptoms suggestive of spinal or epidural abscess should be urgently evaluated for fever and leukocytosis and have a thorough neurologic evaluation. Radiographic diagnosis of spinal epidural abscess is best made by gadolinium-enhanced MRI scan of the spine (Figs. 58-1 and 58-2). Diagnosis and treatment of epidural abscess should not be delayed until neurologic deficits become apparent.

Risk Assessment In a meta-analysis of 915 patients with spinal epidural abscess reported in the world literature between 1954 and 1997, neuraxial anesthesia or analgesia had been performed in 5.5% of them; other invasive procedures as diverse as vascular access and spinal surgery accounted for 16.5%. Estimates of the incidence of spinal epidural abscess after central neuraxial block range from 1 in1930 for continuous epidural catheter techniques to 1 in 100,000 for single-injection and short-term techniques. For patients with chronically implanted epidural catheter systems, infectious risk has been reported as 1 per 1702 catheter-days. Although the specific incidence is unclear, the presence of any of the following factors suggests a higher risk for infection following central neuraxial block: ●

● ●

Immunocompromised state (e.g., acquired immunodeficiency syndrome [AIDS], cancer chemotherapy, organ transplantation, chronic dialysis, intravenous drug abuse, chronic alcoholism) Diabetes mellitus Concomitant steroid treatment

Figure 58–2 ■ Sagittal T1-weighted magnetic resonance image of the spine following intravenous administration of gadolinium. There is a large gadolinium-enhanced mass (arrow) in the posterior epidural space extending from T9 to L3. The area of low signal density within the abscess represents a poorly perfused area of liquefaction. (From Rathmell JP, Garahan MB, Alsofrom GF: Epidural abscess following epidural analgesia. Reg Anesth Pain Med 25:79-82, 2000.)

● ● ● ●

Localized infection at insertion site Sepsis Long-term catheter use Bacteremia

Implications Both meningitis and epidural abscess can be life threatening or result in permanent neurologic sequelae if not treated immediately. A high index of clinical suspicion, early diagnosis, and prompt treatment before massive neurologic symptoms occur are key to optimizing patient outcomes.

MANAGEMENT

Figure 58–1 ■ Axial T2-weighted magnetic resonance image of the spine at the level of L1. There is a large, high-signal fluid collection in the posterior epidural space. The abscess is causing anterior displacement of the dural sac (arrowheads), producing approximately 30% reduction in the anteroposterior diameter of the spinal canal. (From Rathmell JP, Garahan MB, Alsofrom GF: Epidural abscess following epidural analgesia. Reg Anesth Pain Med 25:79-82, 2000.)

Patients with superficial infectious complications can be managed by local drainage and antibiotic therapy. However, even these patients, especially those at increased risk for more serious infectious complications, should be carefully instructed and monitored for the development of any signs or symptoms of epidural or spinal abscess or meningitis. They should also be advised to seek immediate medical attention for progressive back pain, fever, or the development of subtle neurologic changes. This will facilitate timely detection, diagnosis, and therapy. Patients with a history of central neuraxial block who present with back pain and fever should undergo a thorough evaluation for serious infectious complications as part of the differential diagnosis. Epidural abscess following

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PREVENTION As with any invasive procedure, the risks associated with a planned central neuraxial block must be weighed against its potential benefits. Although infectious complications are rare, patients who might benefit most from such blocks are often those with associated morbidities or other factors that increase the risk for serious infectious complications. If central neuraxial blocks are used in patients at increased risk for complications, especially if the extended use of indwelling catheters is anticipated for postoperative or post-traumatic injury pain relief, a higher index of suspicion is required when evaluating these patients for potential infectious complications. Meticulous attention to sterile technique is vital for reducing infectious complications associated with central neuraxial blocks or catheters. Thorough hand washing, sterile gloves, surgical caps or hoods and masks, and sterile block techniques are all important considerations. A wide area of skin should be prepared with povidone-iodine, iodophor-inisopropyl alcohol, or chlorhexidine. Adequate time must be given for the solution to dry before the central neuraxial block is performed. Also, use of a “no-touch” technique (i.e., landmarks identified and marked, if necessary, before skin preparation) helps reduce the risk of central neuraxial infectious complications. Chlorhexidine and iodophor-in-isopropyl alcohol reportedly provide better antimicrobial skin disinfection and prevention of bacterial regrowth compared with povidone-iodine. Use of clear plastic surgical drapes offers the advantage of being able to visualize landmarks during the block procedure. Further, covering epidural catheters with clear sterile dressings allows daily assessment of the insertion site. Sterile technique should be maintained for dosing catheters and when changing infusion connections for continuous epidural infusions. Maintaining a tightly closed infusion system throughout therapy should help reduce catheter contamination during line or infusate changes. Infusion solutions should be prepared by pharmacy personnel with sterile technique and under a laminar flow hood. Central neuraxial block in patients with bacteremia remains controversial. If such blocks are deemed necessary or appropriate in patients with bacteremia, one should consider performing the block only after appropriate antibiotic

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coverage has been provided. For patients with indwelling epidural catheters who become bacteremic, it is my practice to remove the catheter, provide indicated antibiotic therapy, and then replace the catheter at a different level if continuous epidural therapy is still desired. Both for cost considerations and because of its low predictive value in identifying contamination and infection, routine culture of epidural catheter tips is not advised. However, if the epidural catheter insertion site is surrounded by an area of localized inflammation or drainage, bacteriologic examination of the epidural catheter tip may suggest appropriate antibiotic therapy. Although preventive measures are important, they cannot entirely eliminate the risk of infectious complications of central neuraxial block. A high index of suspicion for the development of infectious complications, prompt diagnosis, and immediate therapy are paramount for reducing patient morbidity and permanent neurologic injury.

Further Reading Aota Y, Onari K, Suga Y: Iliopsoas abscess and persistent radiculopathy: A rare complication of continuous infusion techniques of epidural anesthesia. Anesthesiology 96:1023-1025, 2002. Birnbach DJ, Meadows W, Stein DJ, et al: Comparison of povidone iodine and DuraPrep, an iodophor-in-isopropyl alcohol solution, for skin disinfection prior to epidural catheter insertion in parturients. Anesthesiology 98:164-169, 2003. Dawson S: Epidural catheter infections. J Hosp Infect 47:3-8, 2001. Du Pen SL, Peterson DG, Williams A, Bogosian AJ: Infection during chronic epidural catheterization: Diagnosis and treatment. Anesthesiology 73:905-909, 1990. Hooten WM, Kinney MO, Huntoon MA: Epidural abscess and meningitis after epidural corticosteroid injection. Mayo Clin Proc 79:682-686, 2004. Huang RC, Shapiro GS, Lim M, et al: Cervical epidural abscess after epidural steroid injection. Spine 29:E7-E9, 2004. Kindler CH, Seeberger MD, Staender SE: Epidural abscess complicating epidural anesthesia and analgesia: An analysis of the literature. Acta Anaesthesiol Scand 42:614-620, 1998. Kinirons B, Mimoz O, Lafendi L, et al: Chlorhexidine versus povidone iodine in preventing colonization of continuous epidural catheters in children: A randomized, controlled trial. Anesthesiology 94:239-244, 2001. Koka VK, Potti A: Spinal epidural abscess after corticosteroid injections. South Med J 95:772-774, 2002. Lee BB, Kee WD, Griffith JF: Vertebral osteomyelitis and psoas abscess occurring after obstetric epidural anesthesia. Reg Anesth Pain Med 27: 220-224, 2002. Leys D, Lesoin F, Viaud C, et al: Decreased morbidity from acute bacterial spinal epidural abscesses using computed tomography and nonsurgical treatment in selected patients. Ann Neurol 17:350-355, 1985. Rathmell JP, Garahan MB, Alsofrom GF: Epidural abscess following epidural analgesia. Reg Anesth Pain Med 25:79-82, 2000. Reihsaus E, Waldbaur H, Seeling W: Spinal epidural abscess: A meta-analysis of 915 patients. Neurosurg Rev 23:175-204, 2000. Sorensen P: Spinal epidural abscesses: Conservative treatment for selected subgroups of patients. Br J Neurosurg 17:513-518, 2003. Steffen P, Seeling W, Essig A, et al: Bacterial contamination of epidural catheters: Microbiological examination of 502 epidural catheters used for postoperative analgesia. J Clin Anesth 16:92-97, 2004. Trautmann M, Lepper PM, Schmitz FJ: Three cases of bacterial meningitis after spinal and epidural anesthesia. Eur J Clin Microbiol Infect Dis 21:43-45, 2002. Wang LP, Hauerberg J, Schmidt JF: Incidence of spinal epidural abscess after epidural analgesia: A national 1-year survey. Anesthesiology 91: 1928-1936, 1999. Wittum S, Hofer CK, Rolli U, et al: Sacral osteomyelitis after single-shot epidural anesthesia via the caudal approach in a child. Anesthesiology 99:503-505, 2003.

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central neuraxial block has been diagnosed days, weeks, and even months after the intervention. Although more conservative treatment approaches have been reported, surgical drainage and antibiotic therapy for epidural abscess are still the definitive treatment of choice. Epidural abscess with neurologic signs or symptoms requires urgent surgical intervention to prevent progressive and possibly permanent neurologic injury. Antibiotic therapy should be initiated promptly. The initial agent used should be effective against Staphylococcus aureus and able to penetrate bone. Ultimately, antibiotic therapy should be directed by specific culture and sensitivity determinations, as well as by clinical or institutional considerations. Depending on the nature and severity of the infection, antibiotic therapy may be required for 4 to 6 weeks or longer.

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Thomas McCutchen and J. C. Gerancher Case Synopsis A frail, 55-kg, 79-year-old woman is admitted for elective hip replacement as the first surgery of the day in a busy ambulatory surgery center. An epidural catheter is placed for surgical anesthesia and postoperative analgesia. With the patient sitting on the operating room table, catheter placement is uneventful. Fifteen milliliters of a slightly hypobaric solution (2% lidocaine with 5 μg/mL of both fentanyl and epinephrine) is administered via the catheter in three 5-mL doses over 3 minutes. Pain in the arthritic hip is immediately relieved, and the patient’s lower extremities become insensate. Five minutes later, she complains of weakness and experiences difficulty breathing. She then becomes apneic and unconscious, with subsequent oxygen desaturation and hypotension. She is ventilated with a mask and then intubated. Blood pressure is maintained with ephedrine and intravenous fluid.

PROBLEM ANALYSIS Definition When local anesthetic in volumes typically used for epidural analgesia or anesthesia is unintentionally administered into the subarachnoid (intrathecal) space, morbidity and mortality may result due to high spinal anesthesia. Such injection may occur if local anesthetic is delivered through a needle or catheter that has fully or partially penetrated the dura and arachnoid membranes.

Recognition The clinical consequences of unintended intrathecal injection depend on the amount of local anesthetic introduced into the cerebrospinal fluid (CSF). Small amounts result in numbness of the lower extremities; larger amounts result in extensive spread and possibly unconsciousness and respiratory arrest secondary to brainstem anesthesia.

Risk Assessment: Anatomic Considerations The epidural space lies outside the dura mater. This tough outer layer of the meninges fuses with periosteum at the foramen magnum. The epidural space extends laterally to the spinal nerve roots, where it fuses with epineurium in the intervertebral foramina, caudad to the sacrococcygeal ligament and anterior to the posterior longitudinal ligament, ligamentum flavum, and laminae. It communicates with the paravertebral space via intervertebral foramina. The contents of the epidural space consist of fat, which is found predominantly posteriorly and laterally. Valveless veins are found predominantly in the lateral and anterior epidural space. 242

The arachnoid membrane is a delicate membrane that abuts the inner surface of the dura mater. It consists of layers of flattened cells with connective tissue fibers running between these layers. The cells are interconnected by tight junctions, which likely accounts for the fact that the arachnoid is the principal physiologic barrier for drugs diffusing from the epidural space to the intrathecal space. In the region of the foramina, where spinal nerve roots traverse both the arachnoid and the dura mater, the arachnoid membrane herniates through the dura to form granulations. Both spinal and intracranial arachnoid granulations serve as portals for CSF and its constituents to exit the central nervous system. The pia mater is an even more delicate layer of the meninges that is adherent to the spinal cord. The intrathecal space lies between the arachnoid membrane and the pia mater and contains CSF. Spinal CSF directly communicates with intracranial CSF.

Implications The epidural space is a potential space, as the majority of the dura is in contact with the walls of the vertebral canal. It is also a discontinuous series of compartments that become continuous only when liquid or air is injected. Thus, a larger dose of local anesthetic is required for epidural anesthesia or analgesia compared with spinal anesthesia. This anatomy also explains the bandlike block that develops in dermatomes just above and below the level of epidural local anesthetic injection, with further spread directly related to the volume of local anesthetic injected. In contrast, when local anesthetic is introduced into and diffuses throughout CSF within the intrathecal space to produce spinal anesthesia, it can produce block well above and below the level of injection. In addition to the volume of drug delivered and its concentration, spread

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MANAGEMENT Early recognition of unintentional spinal injection is paramount to prevent further injections and limit the potential for morbidity. If the patient is in pain as the epidural is being dosed (e.g., an obstetric patient in active labor), the first sign of an unintended intrathecal injection may be almost immediate, total cessation of all pain after injection of a small test dose. This may be followed by motor and sensory block that develops more rapidly and extensively than expected with epidural injection. Treatment for unintended spinal injection is supportive and consists of ensuring a patent airway, oxygenating and ventilating the patient, and supporting blood pressure with fluids (volume) and vasopressors (if needed) until the high block resolves. In any setting where neuraxial anesthesia is used, basic airway equipment must be readily available, along with a wellthought-out plan for managing unconscious and apneic patients with possible complete cardiovascular collapse.

PREVENTION Prevention requires a high index of suspicion during epidural needle and catheter placement, with careful aspiration and appropriate test dosing of the needle and catheter before the administration of the planned epidural volume of local anesthetic. With obvious free flow of CSF via the epidural needle or catheter during attempts to locate the epidural space, epidural-strength doses and volumes of local anesthetic should not be administered. Often, inadvertent intrathecal needle or catheter placement is not obvious. For example, a dural rent or small tear may be made by the tip of the needle intended for epidural placement. This rent or tear may be large enough to admit an epidural catheter, but there would be no CSF return from the needle because its tip resides mostly in the epidural space. In this case, slow, deliberate aspiration of the catheter before injection might identify CSF.

If saline is used for the loss-of-resistance technique or an epidural catheter is being replaced after recent dosing via a previously placed epidural catheter, it may be difficult to determine whether the clear fluid aspirated from the supposed epidural space is previously injected saline or local anesthetic or CSF. Several maneuvers have been suggested to distinguish CSF from other fluids, including measurement of pH, temperature, glucose, and turbidity when mixed with thiopental. Unfortunately, none of these methods has broad clinical utility. If bubbles are aspirated along with the clear fluid and the total amount of clear fluid that can be aspirated is less than 3 to 5 mL, the catheter is not likely to be in the intrathecal space. However, the catheter should not be used until it has been adequately tested. Epidural test doses consist of a small amount of local anesthetic. The rationale is that such small amounts injected into the intrathecal space would produce an easily recognizable motor and sensory spinal block without producing unacceptably high spinal anesthesia; if the same test dose were injected epidurally, it should produce minimal or no obvious effects. A typical test dose might be 40 to 60 mg of lidocaine, which would quickly produce signs and symptoms of relatively low-level spinal block if injected intrathecally. One must also keep in mind that if combined spinal-epidural anesthesia is performed and the patient has received sufficient spinal local anesthetic for high- or low-level surgical anesthesia, any subsequent epidural test dose might result in an unacceptably high level of spinal anesthesia. In all instances, repeat dosing of an in situ epidural catheter should be incremental. Case reports have noted catheter migration into the intrathecal space. Providing an appropriate time interval between incremental dosing to assess for intrathecal injection should allow for the detection of migrated catheters. Finally, intrathecal catheters left in place intentionally should be clearly labeled as such, to prevent accidental dosing with epidural volumes of local anesthetic.

Further Reading Bernards CM: Epidural and spinal anesthesia. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 4th ed. Philadelphia, Lippincott Williams & Wilkins, 2001, pp 689-713. Bernards CM, Hill H: The spinal nerve root sleeve is not a preferred route for redistribution of drugs from the epidural space to the spinal cord. Anesthesiology 75:827, 1991. Calimaran AL, Strauss-Hoder TP, Wang WY, et al: The effect of epidural test dose on motor function after a combined spinal-epidural technique for labor analgesia. Anesth Analg 96:167-172, 1996. Hogan Q: Epidural catheter tip position and distribution of injectate evaluated by computed tomography. Anesthesiology 90:964-970, 1994. Poblete B, Van Gessel EF, Gaggero G, Gamulin Z: Efficacy of three test doses to detect epidural catheter misplacement. Can J Anaesth 46:34-39, 1999. Reisner LS: Epidural test solution or spinal fluid? Anesthesiology 44:451, 1976. Tessler MJ, Wiesel S, Wahba RM, Quance DR: A comparison of simple identification tests to distinguish cerebrospinal fluid from local anaesthetic solution. Anaesthesia 49:821-822, 1994. Visser WA: Delayed subarachnoid migration of an epidural catheter. Anesthesiology 88:1414-1415, 1998. Waters JH, Rizzo VL, Ramanathan S: A re-evaluation of the ability of thiopental to identify cerebrospinal fluid in epidural catheter aspirate. J Clin Anesth 7:224-227, 1995.

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of an intrathecally administered local anesthetic is related to the patient’s position, depending on whether a hypotonic or hypertonic local anesthetic solution is injected. If the solution is isotonic, spread of the block is more dependent on the volume and concentration of the local anesthetic injected intrathecally, regardless of whether vasoconstrictors are used to prolong the block. The C3-C5 spinal nerve roots, which contribute to the phrenic nerves, may be anesthetized with “high” epidural blocks. Thus, phrenic nerve paralysis may result from high epidural anesthesia. This can lead to respiratory paralysis with complete awareness. However, because intracranial and vertebral spinal fluid are continuous, spinal anesthetics can reach and anesthetize the brainstem. Finally, direct communication between the epidural and paravertebral spaces may result in a one-sided epidural block, especially if the epidural catheter is placed near, or the majority of local anesthetic is deposited into, a nerve root foramen laterally or the posterior longitudinal ligament anteriorly.

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Thomas McCutchen and J. C. Gerancher Case Synopsis A healthy, 80-kg primigravida (38 weeks’ gestation) is admitted in active labor, with a cesarean section (C-section) planned for breech presentation. Because of an anticipated 1-hour delay before the C-section can begin, a lumbar epidural block is requested for analgesia and anesthesia. This is placed without incident. The patient experiences a significant amount of pain with injection of the 3-mL test dose (1.5% lidocaine with 1:200,000 epinephrine). There are no signs of intrathecal or intravenous administration. The catheter is pulled back 1 cm, and 10 mL of 2% lidocaine is injected in 5-mL increments, with less pain. Her contraction pain resolves completely, and she develops a T6-level block to temperature. Fifteen minutes before the C-section, an additional 15 mL of 2% lidocaine is administered through the epidural catheter, with total loss of sensation below T6 5 minutes after arrival in the operating room. Fifteen minutes later, the patient complains of difficulty breathing; her hand grip and biceps strength are weak. The patient becomes lethargic, followed by a loss of consciousness and finally apnea. She is successfully intubated, and the case proceeds under general anesthesia. She is mechanically ventilated in the operating room and postanesthesia care unit for 3 hours after the initial epidural dosing. She then begins to awaken, gains strength, and is successfully extubated. Later that day, radiopaque contrast material is injected through the epidural catheter and reveals cephalad, parallel, “train-tracking” of the contrast medium.

PROBLEM ANALYSIS Definition If local anesthetic in volumes typically used for epidural analgesia or anesthesia are unintentionally administered into the subdural space, considerable morbidity and mortality may result. Also, such injections may result in inadequate blockade.

Recognition Classically, subdural injection has been described as an unexpectedly high block 15 to 35 minutes after intended lumbar epidural injection. When investigated with radiographic contrast material, a stereotypical cephalad “railroad tracking” of contrast material (outlining the subdural space circumferentially around the thecal sac) has been seen (Figs. 60-1 to 60-3). Since 1975, there have been 30 reports of unusually extensive blocks with subdural injection that were confirmed by radiocontrast radiography. Because the subdural space extends above the foramen magnum, some cases presented as unconsciousness with centrally mediated apnea. Recent work, mainly by Collier, suggests that cases with the latter presentation are merely one subset of the possible clinical manifestations of subdural injection. Other presentations, including low block, unilateral block, and dermatomal block, are usually not investigated with radiographic contrast 244

material and thus are not recognized as attributable to local anesthetic subdural injection. The myriad possible presentations of subdural injection have not been identified owing to the dearth of investigation. Collier recently used radiography to investigate 35 cases of atypical or inadequate epidural blocks for cesarean delivery and found four instances (11.4%) of subdural radiocontrast injection. Each patient had severe pain with injection of less than 5 mL of “epidural” local anesthetic. Three had low blocks, and one had a one-sided block. With time (25 to 50 minutes), and after the injection of 10 to 20 mL of additional local anesthetic, all patients eventually achieved surgical anesthesia. Depending on the volume injected and the force and direction of injection, local anesthetic may track cephalad, caudad, or laterally toward a nerve root or form a well-localized “pocket” of local anesthetic. Further, use of multiple orifice catheters may facilitate multicompartment (e.g., subduralepidural or subdural-intrathecal) injections. Collier further speculates that several potential tissue planes exist within the arachnoid membrane and the arachnoid-dura interface,“with each plane having its own radiographic findings and clinical significance.”

Risk Assessment Subdural injections are not injections into a potential space, as epidural injections are. Rather, the injectate produces

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A

B

Figure 60–1 ■ Anteroposterior (A) and lateral (B) views of the lumbar spine after radiocontrast injection through a lumbar catheter (dotted line) reveal a focal collection of contrast material in the subdural space anterior to the thecal sac. (From Collier CB: Accidental subdural injection during attempted lumbar epidural block may present as failed or inadequate block: Radiographic evidence. Reg Anesth Pain Med 29:45-51, 2004.)

A

B

Figure 60–2 ■ Anteroposterior (A) and lateral (B) views of the lumbar spine after contrast injection through a lumbar catheter (dotted line) reveal multicompartment spread of radiocontrast around the thecal sac in the subdural space of L3-L5 (S), and anterior-caudad spread of radiocontrast into the sacral canal (E). (From Collier CB: Accidental subdural injection during attempted lumbar epidural block may present as failed or inadequate block: Radiographic evidence. Reg Anesth Pain Med 29:45-51, 2004.)

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A

B

Figure 60–3 ■ Anteroposterior (A) and lateral (B) views of the lumbar spine after radiocontrast injection through a lumbar catheter reveal multicompartment subdural spread of radiocontrast (S), including localized extension along the L4 nerve root (visible in A) and into the epidural space (E) of L3. (From Collier CB: Accidental subdural injection during attempted lumbar epidural block may present as failed or inadequate block: Radiographic evidence. Reg Anesth Pain Med 29:45-51, 2004.)

a disruptive dissection between two tissue planes. Both Collier and Reina and colleagues describe the subdural space as the dura-arachnoid interface formed by a cellular junction between the two membranes. This junction is composed of neuroepithelial cells surrounded by an amorphous substance. There is no subdural space in nontraumatized tissues. Both groups hypothesize that a subdural space may appear if the neuroepithelial cells break up as a result of pressure exerted by mechanical shear forces, air, or injected fluids. Any of these have the potential to create fissures within the amorphous substance of the dura-arachnoid interface. Such fissures could readily expand toward weaker areas, especially laterally, where the amorphous substance is more prolific. Unintended subdural injection occurs when local anesthetic is injected through a needle or catheter that has created a disruption in the subdural space large enough to accommodate local anesthetic. Subdural injections are unpredictable. Given the flimsy nature of the arachnoid and its intimate relationship with the dura, it is remarkable that subdural injections are even possible. Indeed, the most skilled neurosurgeons have difficulty incising the dura under direct vision without disrupting the arachnoid membrane. The reported rate of unintended subdural injection during epidural anesthesia is about 0.8%. However, it is now believed that subdural injections are more common than previously thought. Indeed, the radiology literature reports a 10% rate of subdural injection during attempted spinal myelography. A likely explanation for this discrepancy is that radiologists have readily available radiocontrast materials for detecting subdural injections. Thus, unusual blocks following

epidural injection that are not investigated radiographically may be the result of subdural injection.

Implications Patients may have transient pain with the injection of small volumes of local anesthetic. This is uncommon with epidural or intrathecal injection of similar volumes. This pain is thought to be caused by either cleaving of meningeal tissues or nerve root compression due to the mass effect of subdural injectates. Pain is short-lived and without sequelae. Additional doses cause little if any pain. Subdural local anesthetic injection can present in multiple ways, depending on the spread and direction of the dissecting injectate and the amount that enters the epidural, subdural, or intrathecal compartment. Subdural and multicompartment injections may present as a high block, low block, radicular block, “patchy” block, or one-sided block. High blocks caused by subdural injections have a clinical presentation similar to that of high spinal blockade (unconsciousness, centrally mediated apnea, hypotension). High subdurals may be difficult to distinguish from high epidurals, because both blocks mature over a relatively long period (15 to 30 minutes). With additional local anesthetic and time, inadequate blocks may eventually resemble a normal epidural block, or they may require catheter manipulation and replacement. Attempted intrathecal block after subdural injection may be difficult, because the needle and injectate tend to reenter the newly created subdural space. This may occur even several months after suspected subdural injection, suggesting

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that a permanent defect may be formed that predisposes the patient to subsequent subdural injections. Indeed, two of Collier’s most recent cases involved one patient who experienced subdural injection during what appeared to be uncomplicated epidural catheter placements for two cesarean deliveries.

MANAGEMENT Treatment of extensive blockade is supportive, as for unintended high intrathecal injection. Inadequate subdural blockade may be overcome with additional doses of local anesthetic, but there is the associated risk of more extensive block.

Unlike the situation with intrathecal needle or catheter placement, aspiration and incremental dosing do not prevent

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subdural injection. However, removing a needle or catheter through which small injections of local anesthetic produced pain may prevent subdural blockade.

Further Reading Bernards CM: Epidural and spinal anesthesia. In Barash PG, Cullen BF, Stoelting RK (eds):Clinical Anesthesia, 4th ed. Philadelphia, Lippincott Williams & Wilkins, 2001, pp 689-713. Collier CB: Accidental subdural block: Four more cases and a radiographic review. Anesth Intensive Care 20:215-232, 1992. Collier CB: Accidental subdural injection during attempted lumbar epidural block may present as a failed or inadequate block: Radiographic evidence. Reg Anesth Pain Med 29:45-51, 2004. Jones M, Newton T: Inadvertent extra-arachnoid injections in myelography. Radiology 80:818, 1963. Lubenow T, Keh-Wong E, Kristof K, et al: Inadvertent subdural injection: A complication of epidural block. Anesth Analg 67:175, 1988. Reina MA, De Leon Casasola O, Lopez A, et al: The origin of the spinal subdural space: Ultrastructure findings. Anesth Analg 94:991-995, 2002. Schultz GH, Brogden BG: The problem of subdural placement in myelography. Radiology 79:91-95, 1962.

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PREVENTION

Epidural Anesthesia: Unintended Subdural Injection

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Alain Borgeat and Steffan Blumenthal Case Synopsis A 25-year-old man presents for rotator cuff repair and has an interscalene block and catheter placed. The block is performed using Winnie’s landmarks and with the aid of a nerve stimulator. A triceps response is obtained at a depth of 2.5 cm. The catheter is threaded 6 cm past the tip of the stimulating needle. The procedure is uneventful, except for transient resistance encountered during catheter placement. After negative aspiration for blood and cerebrospinal fluid, 0.5% bupivacaine is slowly injected through the catheter. After 10 mL is injected, the patient becomes drowsy, then unresponsive and apneic, with loss of muscle tone in all extremities; his pupils are widely dilated. The patient is given oxygen with manual assisted ventilation, followed by tracheal intubation.

PROBLEM ANALYSIS Definition Total spinal anesthesia is one of the most severe complications that can occur during the performance of an interscalene block. Other severe complications include injection of the local anesthetic into the vertebral artery, high epidural anesthesia, subdural injection, pneumothorax, and neuropathy.

Recognition The signs and symptoms of total spinal anesthesia result from blockade of the cervicothoracic segments of the central neuraxis. Symptoms of central nervous system involvement are virtually always present and range from the inability to phonate to unconsciousness and the rapid development of bilateral flaccid paralysis. Bilateral dilated, nonreactive pupils are frequently observed, consistent with a block of parasympathetic efferent activity from the Edinger-Westphal nucleus. The latter sign demonstrates that some amount of local anesthetic entered the cranium. Apnea is usually (but not always) present, due to the close proximity of the phrenic nerve roots (C3-C5) to the site of interscalene injection (C6-C7). The development of bradycardia and hypotension is explained by either cervicothoracic spinal block of the cardiac accelerator fiber (T1-T4) or penetration of local anesthetic into the medullary region of the central nervous system. The application of local anesthetic in this structure results in hypotension, bradycardia, and ventricular arrhythmias. The differential diagnosis includes injection of local anesthetic into the vertebral artery. When this occurs, seizures and unconsciousness are almost immediate. Hypotension and bradycardia may also be due to the cardiotoxic effects of local anesthetics. After epidural injection, such signs and symptoms develop more slowly. Moreover, the epidural 248

space does not extend intracranially. Therefore, signs and symptoms related to intracranial spread of local anesthetic are unlikely. Subdural injection is also part of the differential diagnosis. In this case, the development of clinical block is even slower and usually asymmetrical and incomplete. Intravascular injection or rapid reabsorption of the local anesthetic should always be considered with both central nervous system toxicity and hemodynamic instability. However, the presence of bilateral flaccid paralysis makes this diagnosis very unlikely. Different mechanisms may be implicated in the occurrence of total spinal anesthesia following interscalene block (Table 61-1). Direct injection into the subdural or epidural space may be the consequence of incorrect needle placement through an intervertebral foramen. A perineural or intraneural injection may lead to secondary migration of the drug into the subdural space. Finally, long dural sleeves have been shown in autopsy studies, extending as far as 3 to 5 cm beyond the intervertebral foramen. Placement of a needle into an abnormally long dural root sleeve may explain the spread of local anesthetic into the intrathecal space.

Risk Assessment Total spinal anesthesia following interscalene block, either with or without a perineural catheter, is a rare but serious complication. Such events are often documented as case

Table 61–1

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Proposed Mechanisms of Intrathecal Migration of Local Anesthetics

Injection through intervertebral foramen Direct intraneural injection Injection into dural root sleeve

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Advantages/ Disadvantages Spinal injection Epidural injection Vertebral artery injection Intravenous injection Pneumothorax Discomfort Ease of catheter placement

Winnie ++ ++ + + + +/− −

Posterior ++ ++ +/– + + ++ +

Modified Lateral – – − + + +/− ++

reports. Thus, there is no way to estimate the specific risk for this complication. The only identifiable factor that increases risk is the approach used to perform the block. Three main techniques are used: the Winnie approach, the posterior approach, and the modified lateral approach. The relative advantages and disadvantages of each technique are given in Table 61-2.

Implications Total spinal anesthesia is a rare complication following interscalene block. However, its diagnosis should be prompt. The differential diagnoses of vertebral artery or intravenous injection should be rapidly ruled out so that the appropriate remedial measures can be instituted. Spontaneous breathing often ceases promptly, so assisted manual or mechanical ventilation will be necessary. Bradycardia and hypotension may occur as a result of vasodilatation and block of the cardiac accelerator fibers, which may lead to cardiac arrest if not treated urgently.

Figure 61–1 ■ Winnie’s technique. The needle is directed medially, caudad, and slightly posteriorly toward the transverse process of C6. The needle is close to the spinal structures. C, clavicle; MC, cricothyroid membrane; MS, clavicular head of sternocleidomastoid muscle; dotted line, interscalene groove.

intra-arterial, or intrathecal drug administration is still possible. The choice of approach for performing the interscalene block has implications in the occurrence of complications. Winnie’s approach (Fig. 61-1) directs the needle more toward the spine and therefore increases the risk of injection through an intervertebral foramen, especially if the needle is directed too horizontally. The posterior approach is a paravertebral block. All paravertebral blocks carry at least some risk of puncturing the dural cuff (whether abnormally long or not) that accompanies spinal nerves distal to the intervertebral foramina. The modified lateral approach (Fig. 61-2) directs the needle away from spinal structures and is likely the safest technique for avoiding intervertebral or inadvertent dural puncture Advancing the catheter more than 2 to 3 cm past the tip of the stimulating needle carries no advantage. In fact, by threading it

MANAGEMENT The first step is to immediately cease the local anesthetic injection. Further management includes the following: ●

●

●

●

●

Provide assisted manual or mechanical ventilation with 100% oxygen. Tracheal intubation is often necessary but not always mandatory. Consider the patient’s mental status, drugs administered, and surgical procedure. Volume expansion may be required to treat or prevent hemodynamic instability. Vasopressors, positive chronotropic drugs, or temporary pacing may be required to treat bradycardia or hypotension. Monitor the patient in the intensive care unit or recovery room until the block wears off.

PREVENTION The most important precaution is to administer the drug slowly, with repeated aspiration; however, intravenous,

Figure 61–2 ■ Modified lateral approach. The needle is inserted toward the plane of the interscalene space at an angle of between 45 and 60 degrees. The needle avoids the spinal structures. C, clavicle; MC, cricothyroid membrane; MS, clavicular head of sternocleidomastoid muscle; dotted line, interscalene groove.

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++, most likely/easiest; +, less likely/easy; +/−, possible; − unlikely/difficult.

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farther, the anesthesiologist loses control over its position (e.g., interscalene catheters have been placed within the pleura). Last, an important precaution is to perform the interscalene block only in awake or lightly sedated patients. This allows the patient to report paresthesia (needle encounters a nerve root) or pain due to intraneural injection, and it allows the operator to more promptly recognize early signs of central nervous system toxicity.

Further Reading Borgeat A, Dullenkopf A, Ekatodramis G, Nagy L: Evaluation of the lateral modified approach for continuous interscalene block after shoulder surgery. Anesthesiology 99:436-442, 2003.

Borgeat A, Ekatodramis G, Kalberer F, Benz C: Acute and nonacute complications associated with interscalene block and shoulder surgery: A prospective study. Anesthesiology 95:875-880, 2001. Brown AR: Regional anesthesia for shoulder surgery. Tech Reg Anesth Pain Manage 3:64-78, 1999. Iocolano CF: Total spinal anesthesia after an interscalene block. J Perianesth Nurs 12:163-170, 1997. Long TR, Wass CT, Burkle CM: Perioperative interscalene blockade: An overview of its history and current clinical use. J Clin Anesth 14:546-556, 2002. Norris D, Klahsen A, Milne B: Delayed bilateral spinal anaesthesia following interscalene brachial plexus block. Can J Anaesth 43:303-305, 1996.

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Supraclavicular and Infraclavicular Block: Pneumothorax Sandra L. Kopp Case Synopsis

PROBLEM ANALYSIS Definition Pneumothorax is an accumulation of air or gas in the space between the lung and the chest wall (pleural space). With the supraclavicular approach, the brachial plexus is blocked at the level of its three trunks, where it is most compactly arranged (Fig. 62-1). There are several advantages to the supraclavicular brachial plexus technique, including neutral position of the arm, quick onset of blockade, and a very homogeneous block. Limitations of this approach include difficulty describing or teaching the technique and the risk of pneumothorax. This block is best avoided in uncooperative patients or those with unclear landmarks. Special consideration must be given to patients who could not tolerate the respiratory distress that may accompany a pneumothorax or phrenic nerve block, such as those with severe respiratory disease. The infraclavicular approach to brachial plexus block allows local anesthetic injection above the level where the musculocutaneous and axillary nerves branch off the plexus. This approach is more proximal than the axillary technique and more distal than the supraclavicular approach, thus leading to blockade of all the nerves derived from the plexus, but with a lower incidence of pneumothorax (Fig. 62-2). As with the supraclavicular approach, the arm can remain in a neutral position. This approach has recently gained favor for use in patients requiring a continuous catheter technique, because maintaining an aseptic dressing at this site is much more practical than in the axilla.

Recognition Recognition of a pneumothorax is based largely on the clinical presentation. A pneumothorax may occur immediately during block placement, or it may present hours later. The diagnosis of pneumothorax should be suspected if air is aspirated through the needle during performance of the block, or if a patient becomes acutely dyspneic after block placement.

Unilateral phrenic nerve paralysis and concomitant elevation of the hemidiaphragm must be ruled out, as this is very common after proximal brachial plexus blocks (e.g., interscalene blocks). Although the incidence of hemidiaphragmatic paresis is significantly lower in patients having supraclavicular block compared with interscalene block, it is still estimated to occur in approximately 50% of all patients. Infraclavicular block is rarely associated with changes in pulmonary function. If a patient’s clinical condition suddenly deteriorates during mechanical ventilation, pneumothorax must be considered.

Middle and anterior scalene muscles

Brachial plexus

A

First rib

Brachial plexus

B

Subclavian artery

Figure 62–1 ■ A, Supraclavicular block. The needle is systematically walked anteriorly and posteriorly along the rib until the brachial plexus is located. B, Trunks of the brachial plexus are compactly arranged at the level of the first rib. (From Miller RD [ed]: Anesthesia, 5th ed. Philadelphia, Churchill Livingstone, 2000, p 1524.)

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A 42-year-old man complains of shortness of breath and mild right-sided chest pain in the outpatient recovery area, shortly after a right wrist fusion. A preoperative brachial plexus block was placed using the supraclavicular approach. Upon examination, the patient’s respiratory rate is 20 breaths per minute, and his room-air saturation is 94%. His blood pressure and heart rate are normal. A chest radiograph is positive for a small, right-sided pneumothorax.

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Chassaignac's tubercle C6

B 2.5 cm Insertion site

A Figure 62–2 ■ A, Surface markings for the infraclavicular approach to brachial plexus block. B, Cephalocaudad arc of needle redirection. (From Brown DL: Atlas of Regional Anesthesia, 2nd ed. Philadelphia, WB Saunders, 1999, p 47.)

Patients who are being ventilated with volume-controlled ventilators present with increased peak and plateau pressures; those ventilated with pressure-controlled ventilators have reduced tidal volumes with a new pneumothorax. The chest may have a hyperresonant or tympanitic sound during percussion. There may also be absent breath sounds on the affected side. These signs are most notable when there is at least a 25% reduction in lung volume. Although a computed tomography (CT) scan is the most sensitive study, a chest radiograph is usually diagnostic. Radiographs obtained at the end of expiration allow easier visualization because the pneumothorax takes up a greater proportion of the hemithorax during this part of the respiratory cycle. The main radiographic feature of a pneumothorax is a white visceral pleural line, separated from the parietal pleura by an avascular collection of gas. In most cases, no pulmonary vessels are visible beyond the visceral pleural edge (Fig. 62-3).

Implications Normally, the pressure in the pleural space is negative with respect to the alveolar pressure during the entire respiratory cycle. If the needle punctures the chest wall during block placement, it creates a communication between the atmosphere and the pleural space. Air begins to enter the pleural space until

Risk Assessment The incidence of pneumothorax during supraclavicular block ranges from 0.5% to 6.1%. There is an inverse relationship between the incidence of pneumothorax and the experience of the anesthesiologist performing the block. Relatively new techniques, such as the “plumb-bob” approach, have been used to reduce the risk of pneumothorax. Routine chest radiography following a supraclavicular block is not justified because of the low incidence of pneumothorax and the fact that the onset of symptoms may take up to 24 hours.

Figure 62–3 ■ Right-sided 40% pneumothorax. Arrows mark the visceral pleural line.

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MANAGEMENT If the patient has minimal symptoms and the pneumothorax is less than 15% of the lung volume, simple observation is advised. It is also necessary to provide the patient with supplemental oxygen, which will increase the rate of absorption of the pneumothorax. Because nitrogen is the primary gas in the pleural space, the gradient for nitrogen absorption into the blood is the main factor in determining the rate of reabsorption of a pneumothorax. Reabsorption can be accelerated by breathing 100% oxygen, which lowers the partial pressure of nitrogen in the blood, thereby increasing the gradient for nitrogen absorption from the pleural space. If the patient has more than minimal symptoms or if the pneumothorax occupies more than 15% of the hemithorax, aspiration with a plastic catheter is the treatment of choice. If aspiration does not prevent expansion of the pneumothorax, tube thoracostomy should be performed. Treatment of patients who are undergoing positivepressure mechanical ventilation should include tube thoracostomy to prevent the development of a tension pneumothorax.

Most often, the chest tube is inserted via an incision at the fourth or fifth intercostal space in the anterior axillary or midaxillary line and directed apically. A tension pneumothorax is a medical emergency. When it is suspected, the patient should immediately receive 100% oxygen to alleviate hypoxia. A large-bore angiocatheter should be inserted into the pleural space through the second intercostal space, along the midclavicular line. If the diagnosis is confirmed by the aspiration of air through the catheter, the patient should undergo immediate tube thoracostomy.

PREVENTION Many modifications have been made to supraclavicular and infraclavicular blocks to decrease the complication rate. In 1949 Bonica and colleagues first recommended a careful, gentle technique; thorough familiarity with anatomic relationships; use of the first rib as a protective shield over the lung; and use of a short, fine needle to help prevent complications, including pneumothorax. Although many years have passed, and several reviews have been published since then, this careful approach is still the best advice for any anesthesiologist planning to perform these techniques.

Further Reading Bonica JJ, Moore DC, Orlov M: Brachial plexus block anesthesia. Am J Surg 65, 1949. Brown DL, Bridenbaugh LD: The upper extremity: Somatic block. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in Clinical Anesthesia and Management of Pain, 3rd ed. Philadelphia, Lippincott-Raven, 1998, pp 345-371. Brown DL, Cahill DR, Bridenbaugh LD: Supraclavicular nerve block: Anatomic analysis of a method to prevent pneumothorax. Anesth Analg 76:530-534, 1993. Light RW, Broaddus VC: Pneumothorax, chylothorax, hemothorax, and fibrothorax. In Murray JF, Nadel JA (eds): Textbook of Respiratory Medicine, 3rd ed. Philadelphia, WB Saunders, 2000, pp 2043-2066. Neal JM, Moore JM, Kopacz DJ, et al: Quantitative analysis of respiratory, motor, and sensory function after supraclavicular block. Anesth Analg 86:1239-1244, 1998. Rodriquez J, Barcena M, Rodriguez V, et al: Infraclavicular brachial plexus block effects on respiratory function and extent of the block. Reg Anesth Pain Med 23:564-568, 1998.

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the pressure gradient is eliminated or the communication is repaired. The main physiologic changes associated with a pneumothorax are decreased arterial partial pressure of oxygen (PO2) and decreased vital capacity. The consequences are much more pronounced in patients with poor lung function, because a decrease in vital capacity can lead to respiratory insufficiency, which manifests as hypoventilation and ultimately respiratory acidosis. Although a tension pneumothorax is unlikely in a spontaneously breathing patient, those who have positive-pressure mechanical ventilation are at significantly increased risk. A tension pneumothorax occurs when the positive pressure of inspiration forces more air into the pleural space than exits during expiration. A sudden decline in the patient’s cardiopulmonary status should raise suspicions of the presence of a tension pneumothorax. The deterioration in cardiopulmonary status is likely due to the combination of decreased cardiac output secondary to decreased venous return and extreme hypoxia due to ventilation-perfusion mismatching.

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Gilbert Y. Wong and David L. Brown Case Synopsis A 55-year-old woman presents with epigastric abdominal pain of several months’ duration and a recent diagnosis of pancreatic cancer. To manage her pain, a neurolytic celiac plexus block is performed using the classic posterior percutaneous approach. Soon after injection of the neurolytic solution, she notices sensory loss and impaired motor control of her lower extremities.

PROBLEM ANALYSIS Definition Neurolytic celiac plexus block (CPB) is an effective analgesic technique used primarily for pain management in patients with intra-abdominal malignancies, especially pancreatic cancer. Neurolytic solutions are injected in the area of the celiac plexus or splanchnic nerves, which are the neural structures transmitting the majority of visceral pain from the abdomen. Because the targeted area of neurolysis is in close proximity to vascular and other neurologic structures (Fig. 63-1), neurologic side effects and complications are the primary concerns associated with CPB. Neurologic side effects such as orthostatic hypotension or bowel hypermotility often occur after an effective neurolytic CPB. The celiac plexus and splanchnic nerves are primarily sympathetic nervous system structures. Neurolysis of these structures results in sympatholysis and a relative increase in parasympathetic tone in the splanchnic region. As a result, vasodilatation of the splanchnic vasculature, especially the venous capacitance bed (which effectively reduces venous return and cardiac preload), can result in orthostatic hypotension. In addition, the relative increase in parasympathetic outflow to the viscera can result in increased peristalsis and bowel hypermotility. Neurologic complications are the most serious concerns associated with neurolytic CPB. Although they are rare, these complications can include sensory and motor deficits of the lower trunk and lower extremities, loss of bladder or bowel control or both, and impotence in males. Neurolysis of sensory or motor nerves can occur from direct contact of the neurolytic solution, such as alcohol or phenol, spreading to the intrathecal or epidural space or thoracic or lumbar nerve roots (see Fig. 63-1). In a separate mechanism, alcohol has been shown to cause arterial spasm of feeding arteries to the spinal cord, which can result in ischemia and permanent neurologic deficits (Fig. 63-2).

Recognition Neurologic side effects, such as orthostatic hypotension and bowel hypermotility, are not appreciated until after the 254

neurolytic procedure is completed. Patients with intraabdominal malignancies often have decreased oral intake owing to pain or nausea. Decreased intravascular volume can potentiate the hypotensive effects of neurolytic CPB. Symptoms associated with orthostatic hypotension include syncope or dizziness in the upright position, which may be exacerbated during a rapid shift from the supine position. These symptoms may occur immediately after the CPB. Orthostatic hypotension can be diagnosed based on blood pressure measurements performed before and after the neurolytic CPB with the patient in the supine and upright positions. Bowel hypermotility effects may not be noticed until hours after the neurolytic CPB. Because patients experiencing pain associated with intra-abdominal malignancies are frequently treated with opioid medications, and because constipation is a common side effect of opioid medications, such patients often consider increased bowel motility to be beneficial. Neurologic complications, such as sensory and motor changes of the lower trunk and extremities, must be carefully evaluated both during and after the CPB procedure. Although not completely reliable, needle aspiration for cerebrospinal fluid or blood should occur both before and during the incremental injections of neurolytic solution. If cerebrospinal fluid or blood is aspirated, no additional injections should occur until the needle position is reevaluated. Before the injection of a neurolytic agent, a functional test consisting of local anesthetic injection is important to rule out incorrect needle placement. Neurologic deficits occurring as a result of local anesthetic injection into the intrathecal or epidural space or in contact with the thoracolumbar nerve roots confirm incorrect needle positioning. Radiographic guidance, such as fluoroscopy or CT, can also be used to recognize grossly inaccurate needle placement.

Risk Assessment The risks of neurologic side effects and complications must be carefully considered and weighed against the benefits of neurolytic CPB in patients with intra-abdominal malignancies and limited life expectancy. Meta-analysis of the literature regarding patients undergoing neurolytic CPB found that hypotension occurred in

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Aorta Retrocrural spread

L1

Splanchnic nerves Celiac plexus

REGIONAL ANESTHESIA AND PAIN MANAGEMENT

Ao

Anterocrural spread

Diaphragmatic crura Figure 63–1 ■ The spread of neurolytic solution in a celiac plexus block occurs in anterocrural or retrocrural regions. The neurolytic solution is in close proximity to vital structures associated with the spine, including the intrathecal and epidural spaces, thoracic and lumbar nerve roots, and major feeding arteries of the spinal cord.

Ant. sulcal a.

Ant. radicular a. A. of Adamkiewicz Ant. spinal a. T – 12

L–1

L–2

Lumbar a. Aorta

Figure 63–2 ■ Arterial supply of the spinal cord at low thoracic and high lumbar vertebral levels. The largest feeding artery to the spinal cord is the artery of Adamkiewicz (anterior radicular artery), which branches from the lumbar artery (in this case).

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38% of cases and bowel hypermotility occurred in 31% to 44% of cases. A case series of 136 patients who had neurolytic CPB reported that 8 patients (6%) with symptomatic orthostatic hypotension required treatment. Another study (61 patients) that prospectively compared different CPB techniques reported a 38% incidence of transient decreases in systolic blood pressure greater than 33% compared with baseline measurements. Bowel hypermotility also occurred in 31% of these patients. In the largest series (2730 patients) evaluating neurologic complications associated with neurolytic CPB, four cases (0.15%) of permanent paraplegia were identified. In three of these cases, there was also loss of anal and bladder sphincter function. Radiographic guidance with radiocontrast dye was used for CPB in all four cases. In a case series by Brown and coworkers, there were no cases of permanent paraplegia in 136 patients undergoing neurolytic CPB. Meta-analysis of the literature revealed a 1% incidence of neurologic complications, including lower extremity weakness, paresthesia, epidural anesthesia, and lumbar puncture, after neurolytic CPB.

Implications Benign neurologic side effects can occur in patients receiving neurolytic CPB. These side effects can usually be treated in a symptomatic manner with no significant impact on the patient. Orthostatic hypotension typically improves shortly after equilibration of the intravascular volume. Bowel hypermotility is usually transient and may actually be desirable in many patients. The potential for neurologic side effects should be discussed with the patient and family before the procedure. Neurologic complications are very uncommon but can have a significant impact. In patients with intra-abdominal malignancies, these neurologic deficits are likely to continue for the remainder of their lives.

MANAGEMENT The management of neurologic side effects is directed toward symptomatic relief. Orthostatic hypotension, if symptomatic, can be treated by increasing oral fluid intake or intravenous fluids. Leg wrappings with elastic bandages or support stockings can also decrease venous capacitance and improve hypotension. Antihypertensive medications, if any, should be discontinued until equilibration of intravascular volume is reached. If symptoms are sustained and not responsive to conservative therapy, pharmacologic treatment with an α1-agonist, such as midodrine, can be considered. Bowel hypermotility can be treated symptomatically with antihypermotility medications such as diphenoxylate with atropine.

The management of neurologic complications is more complicated. If neurologic deficits occur during neurolytic CPB, the procedure should be terminated immediately. Aspiration of the injectate can be attempted but is unlikely to be effective. Emergency consultation with a neurologist is recommended. If ischemia of the spinal cord is suspected as a result of spasm of a lumbar radicular artery, the immediate involvement of an interventional radiologist for arterial vasodilatation should be considered.

PREVENTION The neurologic side effects of orthostatic hypotension and bowel hypermotility are not preventable; they are merely the result of a successful CPB. The ability to prevent neurologic complications with the use of radiographic guidance is controversial. Traditionally, the CPB procedure relies on anatomic landmarks rather than radiographic guidance. Needle position is confirmed with a functional test of injected local anesthetic. If the patient notes an appropriate improvement in preexisting pain with no neurologic deficits, the needle position is considered to be correct. This approach requires that the patient not be oversedated, so that he or she can provide reliable responses. The large case series of 2730 patients undergoing neurolytic CPB revealed four cases of permanent paraplegia, all of which involved the use of radiography and radiocontrast dye to confirm final needle placement. Thus, radiographic guidance cannot ensure the prevention of neurologic complications. Despite these observations, the use of radiographic guidance provides the advantage of confirming needle position and the spread of injectate, as traced by the radiocontrast dye, before the injection of neurolytic solution.

Further Reading Brown DL, Bulley CK, Quiel EL: Neurolytic celiac plexus block for pancreatic cancer pain. Anesth Analg 66:869-873, 1987. Davies DD: Incidence of major complications of neurolytic coeliac plexus block. J R Soc Med 86:264-266, 1993. Eisenberg E, Carr DB, Chalmers TC: Neurolytic celiac plexus block for treatment of cancer pain: A meta-analysis. Anesth Analg 80:290-295, 1995. Goudas L, Carr DB, Bloch R, et al: Management of Cancer Pain: Evidence Report/Technology Assessment No. 35 (AHCPR Publication No. 02E002). Rockville, Md, Agency for Healthcare Research and Quality, 2001. (Prepared by the New England Medical Center Evidence-Based Practice Center under Contract No. 290-97-0019.) Ischia S, Ischia A, Polati E, et al: Three posterior percutaneous celiac plexus block techniques. Anesthesiology 76:534-540, 1992. Wong GY, Brown DL: Transient paraplegia following celiac plexus block. Reg Anesth 20:352-355, 1995. Wong GY, Schroeder DR, Carns PE, et al: Effect of neurolytic celiac plexus block on pain relief, quality of life, and survival in patients with unresectable pancreatic cancer—a randomized controlled trial. JAMA 291:1092-1099, 2004.

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Robert S. Weller Case Synopsis

PROBLEM ANALYSIS Definition Retroperitoneal hemorrhage after psoas compartment block (PCB) results from arterial bleeding into the retroperitoneal space. Signs and symptoms of PCB depend on the rate and extent of bleeding and whether the hematoma compresses adjacent structures. The most rapid and dramatic bleeding occurs with aortic rupture, which is often fatal. However, bleeding from smaller arteries after PCB can also cause morbidity or mortality. Numerous cases of retroperitoneal hemorrhage have been reported following interventional radiology procedures requiring femoral artery cannulation, especially if the artery is injured proximal to the inguinal ligament. The incidence following cardiac catheterization is reportedly 0.12%. Only a few cases of retroperitoneal hemorrhage have been reported after PCB or lumbar sympathetic block; anticoagulant therapy at the time of or after the block was involved in each of those cases. Spontaneous retroperitoneal hematoma may also occur in patients on chronic anticoagulant therapy. The risk of this complication increases as the degree of anticoagulation increases. Finally, spontaneous iliopsoas hemorrhage with femoral nerve palsy is the most common nerve palsy caused by spontaneous bleeding in hemophiliacs.

Recognition Retroperitoneal bleeding is deep, concealed, and rarely obvious until significant blood loss has occurred. The most common signs of retroperitoneal hemorrhage are hypotension and tachycardia due to intravascular volume depletion, and

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A 76-year-old man with a mechanical aortic valve was scheduled for left above-knee amputation. Chronic warfarin (Coumadin) was stopped, and a heparin infusion was begun on admission but stopped 4 hours before surgery. On arrival in the preoperative area, his prothrombin time, international normalized ratio, and activated partial thromboplastin time were normal; hemoglobin was 13 g/dL. A posterior approach to the lumbar plexus block (psoas compartment block) was performed, in combination with a subgluteal sciatic block. His vital signs remained stable, and the surgery and recovery room stay were uneventful. The estimated blood loss was 300 mL. The patient was returned to the floor, and heparin was restarted 8 hours postoperatively at 1200 units/hour. His blood pressure gradually declined overnight from his usual 140/90 to 95/55 mm Hg, and he became confused and oliguric. He received several 500-mL normal saline fluid challenges. The blood pressure improved, but urine output remained low. The next morning, his hemoglobin was 7.3 g/dL. Two units of packed red blood cells were given. Hemoglobin was 7.7 g/dL. He was moved to the intensive care unit, heparin was discontinued, and a computed tomography (CT) scan of the abdomen showed a large left retroperitoneal hematoma.

anemia (Table 64-1). In one series, 64% of patients had hypotension (systolic blood pressure <90 mm Hg), and 73% showed progressive anemia. Ultimately, there is hemorrhagic shock, with oliguria and mental status changes. Oliguria can also result from ureteral obstruction, although retroperitoneal hematoma usually does not extend across the midline. Therefore, oliguria is more commonly due to hypovolemia. Symptoms of retroperitoneal hematoma include abdominal, flank, groin, or leg pain, as well as lumbar plexus irritation or dysfunction. In the series noted earlier, 45% of patients complained of pain in the lower extremity, and 55% had femoral nerve palsy. Over time, patients may also develop flank ecchymoses (Grey Turner’s sign; Fig. 64-1). In addition to the complications of PCB itself, the differential diagnosis for hypotension and anemia hours after PCB includes inadequate surgical blood replacement or continued surgical bleeding, which is usually obvious after lower extremity surgery. Perioperative hypotension may also be due to sepsis, with anemia absent and fever usually present. Abdominal CT should be performed if retroperitoneal bleeding is suspected; it readily demonstrates retroperitoneal hematoma (Fig. 64-2).

Table 64–1

■

Signs and Symptoms of Retroperitoneal Hemorrhage

Hypotension Anemia Shock Abdominal, flank, groin, or leg pain Femoral neuropathy Flank ecchymoses (Grey Turner’s sign)

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Figure 64–1 ■ Patient in the left lateral decubitus position showing widespread flank ecchymoses (Grey Turner’s sign) due to retroperitoneal hematoma after psoas compartment block.

Risk Assessment The translumbar, posterior approach to lumbar plexus block or PCB was described in 1974. The approach and landmarks have since been modified. The most popular contemporary approach for PCB requires the use of a nerve stimulator to identify the femoral nerve component of the lumbar plexus. Local anesthetic injection through a PCB needle or catheter has a much higher rate of success in blocking the femoral, lateral femoral cutaneous, and obturator branches (especially the last) of the lumbar plexus, compared with about a 25% success rate with the inguinal perivascular (three-inone) block of these branches. PCB has also been used to provide analgesia following hip replacement. Some have found that PCB provides equivalent analgesia to epidural local anesthetic, with fewer side effects; others have found it inferior to intrathecal morphine. Continuous PCB has been used for patients with femoral neck fracture, and although it is inadequate for surgical anesthesia, PCB produces analgesia that is superior to systemic

meperidine analgesia. When used alone for analgesia following knee replacement surgery, continuous PCB is equivalent to a continuous femoral block; both blocks are superior to intravenous patient-controlled morphine. The incidence of epidural spread of local anesthetic after PCB ranges from 2% to 25% and must be considered a side effect of this approach. Epidural and even intrathecal catheter placement has occurred during attempted continuous PCB. This is not unexpected, given the anatomic proximity of the intervertebral foramen to the intended site of needle or catheter placement. Although PCB is usually safe and successful, a number of serious complications have been reported in addition to retroperitoneal hematoma (Table 64-2). In a survey of major complications associated with regional anesthesia, Auroy and colleagues cautioned that PCB may be associated with a higher rate of life-threatening complications (8:1000) than other peripheral nerve block procedures. However, this survey included only 394 PCBs, a small percentage of the total number of peripheral nerve blocks performed. The retroperitoneal space contains a rich network of arteries and veins. Segmental lumbar arteries arise from the aorta, run along the vertebral bodies, and then course behind the psoas major and lumbar plexus between the lumbar transverse processes. The iliolumbar arteries ascend from their origin at the hypogastric arteries and anastomose with the fourth lumbar artery at the medial border of the psoas major. Segmental lumbar veins connect to each other by the ascending lumbar vein (Fig. 64-3), which feeds into the inferior vena cava. With this abundant vascular supply in the vicinity of the lumbar plexus, it is not surprising that needles or catheters may occasionally enter or injure these vessels during PCB, producing hemorrhage or systemic local anesthetic toxicity. The potential for concealed, significant hemorrhage must be taken into account when calculating the risk-benefit ratio of PCB for each patient. Alternative techniques, the use of anticoagulant or antiplatelet drugs, and the degree of anticoagulation must be included in this analysis. The American Society of Regional Anesthesia and Pain Medicine (ASRAPM) has developed consensus guidelines for the performance of central neuraxial blocks in the setting of anticoagulant therapy (see Chapter 67), but no such guidelines exist for the performance of peripheral nerve and plexus blocks. The incidence of clinically significant retroperitoneal bleeding following single-injection or continuous PCB with the typical dose of drugs used for perioperative thromboprophylaxis or anticoagulation therapy is not known.

Table 64–2

Figure 64–2 ■ Abdominal computed tomography scan showing a large retroperitoneal hematoma after psoas compartment block.

■

Complications following Psoas Block

Retroperitoneal hematoma Renal injury and hematoma Intrathecal, epidural, and intra-abdominal catheter placement Development of severe phantom limb pain Femoral neuropathy Total spinal anesthesia with cardiac arrest Systemic toxicity with cardiac arrest Death

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In contrast to retroperitoneal hematoma following PCB, epidural hematoma with spinal cord compression after epidural block requires urgent diagnosis and surgical decompression to reduce the risk of catastrophic injury to the patient (i.e., paraplegia). However, retroperitoneal bleeding after PCB, if diagnosed early and treated with transfusion and supportive care, typically results in complete recovery and usually does not require surgical intervention. For this reason, some believe that it is not necessary to apply the ASRAPM guidelines to PCB. Others argue that, at a minimum, significant retroperitoneal hemorrhage requires substantial transfusion, an extended hospital stay, and the reversal of anticoagulation, with its attendant risks. Even worse, retroperitoneal hemorrhage after PCB can cause persistent femoral neuropathy, life-threatening hemorrhagic complications, and even death. Therefore, the more conservative approach is to avoid PCB in patients with coagulation abnormalities that preclude epidural or spinal anesthesia.

Implications Consideration of PCB as a component of surgical anesthesia or postoperative analgesia must take into account its success rate and benefits compared with those of alternative techniques, as well as the potential for severe complications, including life-threatening bleeding. This is especially true for patients with significant bleeding abnormalities, including those who are fully anticoagulated or on high-dose antithrombolytic therapy. The risk is less well established for those receiving antiplatelet drugs or perioperative thromboprophylaxis. Because the signs and symptoms of retroperitoneal hemorrhage are well known, one must maintain a strong index of suspicion for bleeding-related complications in any patient receiving PCB, especially those with seemingly less consequential acquired or intrinsic coagulation abnormalities (e.g., patients taking nonsteroidal anti-inflammatory drugs).

MANAGEMENT The most common presentation of retroperitoneal hematoma is hypovolemia and anemia. In this case, intravascular volume repletion is the first priority (Table 64-3). Hemoglobin concentration, platelet count, and coagulation parameters should be measured to guide transfusion and other therapy. Discontinuation or reversal of anticoagulation may be necessary, although this must be weighed against the risk of venous thrombosis and embolism that such therapy was intended to prevent. It might be necessary to transfer the patient to a high-observation unit until cardiovascular stability has been achieved. Once the patient has stabilized, a CT scan can confirm the diagnosis and demonstrate the extent of bleeding. If active bleeding continues, technetium 99 scanning can help identify its source and guide embolization of the bleeding vessel. Many authorities believe that patients with continued or progressive nerve dysfunction from compression of branches

Table 64–3

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Management of Retroperitoneal Hemorrhage following Psoas Block

Restore intravascular volume Measure blood count and coagulation activity Transfuse blood and coagulation factors as indicated Reverse anticoagulation pharmacologically Transfer to high-acuity unit until cardiovascular stability achieved Perform abdominal computed tomography scan to confirm diagnosis when stable Consider interventional radiology for continued hemorrhage Consider surgical exploration for continued hemorrhage or femoral palsy

REGIONAL ANESTHESIA & PAIN MANAGEMENT

Figure 64–3 ■ Anatomic cross section through the L4 vertebral body. The enlarged image shows the lumbar artery and much larger ascending lumbar vein close to the lumbar plexus.

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of the lumbar plexus should undergo urgent decompressive surgery. Others believe that surgical intervention is a last resort and recommend that evolving femoral neuropathies be managed more expectantly, especially in patients with congenital coagulopathies.

PREVENTION The vascularity of the tissues through which the needle passes for PCB makes it impossible to completely avoid arterial or venous trauma. Because the larger needles and catheters used for continuous epidural anesthesia carry a higher risk for epidural hematoma than does single-injection spinal anesthesia, it seems logical that this would also be true for peripheral nerve blocks, including PCB. If an insulated needle and nerve stimulator are used to locate the lumbar plexus for PCB, vascular puncture might go unrecognized. Even with hollow-core needles, vascular injury might not be obvious. Regardless of the type of needle used, retroperitoneal hematoma following PCB has been reported. Thus, the following precautions are prudent: ●

●

●

●

●

Avoid PCB in fully anticoagulated patients or if thrombolytic therapy is likely. Maintain an index of suspicion for concealed bleeding in patients who have undergone PCB and are anticoagulated postoperatively. If known vascular puncture has occurred during PCB, communicate this to the surgical team and delay potent thromboprophylactic therapy postoperatively. Also, careful patient follow-up and monitoring of serial hematocrits are advised. Avoid PCB catheter removal during therapeutic anticoagulation, and maintain a high index of suspicion for bleeding after catheter removal in patients on more modest prophylactic anticoagulation postoperatively. Communicate the potential for concealed bleeding with members of the primary surgical service so that they too have the appropriate index of suspicion for bleeding complications after PCB, especially when unanticipated anemia or hypovolemia occurs in the postoperative period.

Further Reading Auroy Y, Benhamou D, Bargues L, et al: Major complications of regional anesthesia in France: The SOS Regional Anesthesia Hotline Service. Anesthesiology 97:1274-1280, 2002.

Capdevila X, Biboulet P, Morau D, et al: Continuous three-in-one block for postoperative pain after lower limb orthopedic surgery: Where do the catheters go? Anesth Analg 94:1001-1006, 2002. Capdevila X, Marcaire P, Dadure C, et al: Continuous psoas compartment block for postoperative analgesia after total hip arthroplasty: New landmarks, technical guidelines, and clinical evaluation. Anesth Analg 94:1606-1613, 2002. Chudinov A, Berkenstadt H, Salai M, et al: Continuous psoas compartment block for anesthesia and perioperative analgesia in patients with hip fractures. Reg Anesth Pain Med 24:563-568, 1999. Kaloul I, Guay J, Cote C, Fallaha M: The posterior lumbar plexus (psoas compartment) block and the three-in-one femoral nerve block provide similar postoperative analgesia after total knee replacement. Can J Anaesth 51:45-51, 2004. Klein SM, D’Ercole F, Greengrass RA, Warner DS: Enoxaparin associated with psoas hematoma and lumbar plexopathy after lumbar plexus block. Anesthesiology 87:1576-1579, 1997. Levine MN, Raskob G, Landefeld S, Kearon C: Hemorrhagic complications of anticoagulant treatment. Chest 119(1 Suppl):109S-121S, 2001. Maier C, Gleim M, Weiss T, et al: Severe bleeding following lumbar sympathetic blockade in two patients under medication with irreversible platelet aggregation inhibitors. Anesthesiology 97:740-743, 2002. Souron V, Delaunay L, Schifrine P: Intrathecal morphine provides better postoperative analgesia than psoas compartment block after primary hip arthroplasty. Can J Anaesth 50:574-579, 2003. Sreeram S, Lumsden AB, Miller JS, et al: Retroperitoneal hematoma following femoral artery catheterization: A serious and often fatal complication. Am Surg 59:94-98, 1993. Tokarz VA, McGrory JE, Stewart JD, Croslin AR: Femoral neuropathy and iliopsoas hematoma as a result of postpartum factor-VIII inhibitor syndrome. J Bone Joint Surg Am 85:1812-1815, 2003. Turker G, Uckunkaya N, Yavascaoglu B: Comparison of the cathetertechnique psoas compartment block and the epidural block for analgesia in partial hip replacement surgery. Acta Anaesthesiol Scand 47:30-36, 2003. Weller R, Gerancher JC, Crews JC, Wade KL: Extensive retroperitoneal hematoma without neurologic deficit in two patients who underwent lumbar plexus block and were later anticoagulated. Anesthesiology 98:581-585, 2003. Williams P: Gray’s Anatomy: The Anatomical Basis of Medicine and Surgery, 38th ed. New York, Churchill Livingstone, 1995, pp 1562, 1558, 1600. Wilson MW, Fidelman N, Lull RJ, et al: Evaluation of active bleeding into hematomas by technetium-99m red blood cell scintigraphy before angiography. Clin Nucl Med 27:763-766, 2002. Winnie A, Ramamurthy S, Durrani Z, Radonjic R: Plexus blocks for lower extremity surgery: New answers to old problems. Anesthesiol Rev 1:11-16, 1974. Witz M, Cohen Y, Lehmann JM: Retroperitoneal haematoma—a serious vascular complication of cardiac catheterisation. Eur J Vasc Endovasc Surg 18:364-365, 1999.

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ACUTE AND CHRONIC PAIN MANAGEMENT

Side Effects of Neuraxial Opioids

65

Susan B. McDonald Case Synopsis

PROBLEM ANALYSIS

Risk Assessment RESPIRATORY DEPRESSION

Definition Epidural and intrathecal administration of opioids in humans was first described in 1979. It was termed “selective spinal analgesia” because it offered profound segmental analgesia without the motor, sensory, and autonomic blockade of local anesthetics. Since then, neuraxial opioids have been widely accepted as a means of providing prolonged analgesia in acute postoperative, obstetric, and chronic pain scenarios. There is evidence that patients may have better postoperative outcomes with neuraxial opioid analgesia than with conventional opioid use. The addition of intrathecal fentanyl to spinal anesthesia prolongs the duration of sensory blockade without increasing the time to discharge, making it a popular choice in the ambulatory surgery setting. Intrathecal narcotics for labor analgesia, or “walking epidurals,” are a desirable option for parturients.

Recognition The most common side effects associated with neuraxial opioids are the following: ● ● ● ● ●

Respiratory depression Sedation Pruritus Nausea and vomiting Urinary retention

In general, the adverse effects associated with neuraxial opioids are similar to those seen with intravenous, intramuscular, or oral opioids. However, the severity, incidence, and timing differ owing to the interaction of receptors in the spinal cord and the brain. The most serious complication is respiratory depression, which can be early or delayed.

The degree and rate of the opioid’s rostral spread in the cerebrospinal fluid (CSF) determine the side effect profile for respiratory depression. The natural circulation of CSF brings residual drug into direct contact with the brain’s respiratory center, which lies on the floor of the fourth ventricle. Typically, lumbar CSF reaches the brain in about 4 to 6 hours. Thus, factors that determine the amount of drug reaching the rostral CSF include where the drug was placed (intrathecally versus epidurally; thoracic versus lumbar area), its dose, and its lipid solubility. When a highly lipophilic drug such as fentanyl or sufentanil is placed intrathecally, it rapidly penetrates the spinal cord tissues to directly act on the dorsal horn neurons. Low residual concentrations of the drug remain in the CSF; therefore, such drugs have a more segmental analgesic effect. In contrast, morphine is not highly lipophilic and has a slower uptake into the spinal cord and efflux from the CSF (via arachnoid granulations). Therefore, higher concentrations of drug remain in the CSF for longer periods. As a result, morphine is much more likely to reach the brain’s respiratory center and cause delayed respiratory depression than is fentanyl or sufentanil. If an opioid is placed epidurally, it can have spinal or supraspinal (systemic) effects, imparting a biphasic nature to respiratory depression. This may manifest early (<2 hours) due to vascular uptake and redistribution, similar to what occurs after intramuscular dosing, or late (6 to 12 hours) due to rostral migration of the drug in the CSF. The ratio of spinal to supraspinal effects depends on how much of the drug is absorbed into the epidural venous plexus, how much is deposited in epidural fat, and how much penetrates the meninges and passes into the CSF. The drug’s lipid solubility and molecular weight and shape in large part determine dural penetration and the amount that remains in the CSF long enough to spread rostrally. This explains why hydrophilic morphine or hydromorphone has more dural 261

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A 55-year-old obese woman undergoes a total vaginal hysterectomy under spinal anesthesia comprising local anesthetic and 100 μg of morphine. Later that evening, her oxygen saturation is normal with oxygen supplementation by nasal cannula, but she appears excessively somnolent.

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penetration (and therefore spinal activity) than highly lipophilic drugs such as fentanyl or sufentanil. For the same reason, there is a much greater risk of respiratory depression when morphine or hydromorphone is placed in the high thoracic or cervical epidural space. Patients considered at increased risk for respiratory depression include the elderly and debilitated, those with significant pulmonary disease (including sleep apnea), and those receiving concomitant opioids or central nervous system depressants. Patients receiving chronic opioid therapy are drug tolerant and thus much less likely to experience centrally mediated, neuraxial opioid respiratory depression. Postpartum patients also demonstrate less respiratory depression, possibly because of their younger age and increased ventilatory drive due to pregnancy. Finally, the overall reported incidence of significant respiratory depression (i.e., that requiring treatment) from neuraxial opioids is 0.2% to 2%, which is not much different from that associated with more conventional use (about 1%). Table 65-1 lists risk factors for respiratory depression. SEDATION Sedation correlates with respiratory depression for two reasons. First, the opioid may have a direct effect on the thalamus, limbic system, or cerebral cortex from rostral spread in the CSF. Second, if significant respiratory depression does occur, resultant hypercapnia may create carbon dioxide narcosis. Therefore, when a patient becomes increasingly somnolent after neuraxial opioids, episodic hypoventilation and respiratory depression should be carefully considered, even when respiratory rate and oxygenation are within acceptable limits. PRURITUS The incidence of pruritus with neuraxial opioids ranges from 30% to 100%, but it is severe in only about 1% of patients. Larger doses and intrathecal administration carry a higher risk for pruritus, as does pregnancy (possibly owing to high plasma estrogen). Fentanyl and morphine are more likely to cause itching, but all opioids have been implicated. The exact mechanism is unclear. Neuraxial opioids appear to interact with medullary inhibitory pathways in the spinal cord. The time course for itching correlates with the analgesic effect. Opioids may also

Table 65–1

■

Factors That Increase the Risk of Respiratory Depression

Opioid Characteristics Larger doses Intrathecal administration Hydrophilic morphine or hydromorphone Repeated boluses versus continuous infusion

Patient Characteristics Elderly Debilitated Significant pulmonary disease Sleep apnea Opioid naïve Concomitant opioids or central nervous system depressants

act on an “itch center” in the medulla, which is associated with the trigeminal nucleus; this may explain why facial itching is most common. Histamine release is not a cause of neuraxial opioid-induced pruritus. NAUSEA

AND

VOMITING

Nausea is less likely with neuraxial administration than with more conventional dosing. The incidence is about 30%. The risk is higher in female patients and with morphine and intrathecal use, probably due to the drug’s direct interaction with the vomiting center and chemoreceptor trigger zone located in the fourth ventricle. URINARY RETENTION The incidence of urinary retention with neuraxial opioids varies widely but is higher than that seen after parenteral or oral administration. The opioid’s effect on the sacral spinal cord receptors likely interferes with parasympathetic outflow and causes detrusor muscle relaxation and decreased sensation of the urge to void. It occurs more often in males and is dose dependent in duration. Time to complete recovery can be more than 5 hours after intrathecal sufentanil and more than 15 hours after intrathecal morphine.

Implications Proper patient selection and careful vigilance can reduce serious adverse effects from neuraxial opioid use, especially central respiratory depression. Appropriate postoperative care requires the recognition that hydrophilic drugs (morphine, hydromorphone) can lead to a delayed onset and longer duration of respiratory depression. Monitoring is necessary for at least 24 hours after the administration of neuraxial morphine or hydromorphone. Excessive somnolence may be the first sign, which is why mental status checks should be performed during postoperative observation. Most hospitals provide thorough nurse education and have precise written protocols for monitoring and treatment in the case of significant respiratory depression. An example is given in Table 65-2. Also, concomitant administration of other narcotics or central nervous system depressants should be avoided, especially in opioid-naïve patients. Small doses of lipophilic drugs such as fentanyl can be safely used in ambulatory surgery settings. Studies have shown that the risk of respiratory depression is minimal with intrathecal doses of less than 25 μg of fentanyl, even in elderly patients. For patients receiving postoperative epidural analgesia, no special monitoring is necessary if fentanyl is used in reasonable doses, even with thoracic epidural catheters. Side effects such as pruritus, nausea and vomiting, and urinary retention may be viewed as nuisance or minor complications, but even so, there can be undesirable consequences. If they are severe enough, there may be an unanticipated hospital admission or a delay in discharge, unpleasant side effects from the treatment medications, or unwanted procedures such as an indwelling bladder catheter for inability to void. Use of intrathecal narcotics for labor and delivery has become increasingly popular. Complications such as prolonged early labor and severe fetal bradycardia have been reported,

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Table 65–2

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Example of Postoperative Orders for Patients Receiving Neuraxial Morphine

Table 65–3

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Side Effects of Neuraxial Opioids

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263

Common Treatment Modalities for Neuraxial Opioid Side Effects

Respiratory Depression Postoperative Orders for Intrathecal or Epidural Morphine

but a causal relationship is still debated in the obstetric literature. The incidence of fetal heart rate abnormalities, especially bradycardia, may be dose dependent. The presumed cause is uterine hyperactivity due to an imbalance in circulating catecholamines after the rapid onset of analgesia. It should be emphasized that such heart rate abnormalities respond to conservative measures and are not associated with poor neonatal outcomes.

MANAGEMENT For serious adverse effects, including respiratory depression, the best reversal agent is a pure opioid antagonist such as naloxone. Although intravenous naloxone has a rapid onset, the duration of a single bolus may be insufficient, and infusions are often warranted. For less critical side effects (e.g., pruritus), naloxone may be hard to titrate to effect without the reversal of at least some analgesia. If so, a mixed agonistantagonist such as nalbuphine may be more suitable. Studies have shown that nalbuphine can effectively treat pruritus, nausea, or vomiting without altering the level of pain control. Other agents have been used to treat the side effects of neuraxial opioids (Table 65-3). Serotonin 5-HT3 antagonists (e.g., ondansetron) are effective for the treatment of both pruritus and nausea. Droperidol, with its weak serotonin antagonist activity, may help treat pruritus but is more useful against nausea and vomiting, whether administered intravenously or epidurally. Propofol inhibits dorsal horn signal transmission and can effectively treat nausea and pruritus; however, the management and cost of a propofol infusion

Pruritus Nalbuphine Diphenhydramine Propofol Ondansetron

Nausea or Vomiting Droperidol Ondansetron Propofol Nalbuphine

Urinary Retention Naloxone Bladder catheterization

for this purpose probably outweigh the benefits. Although histamine release is not the mechanism for opioid-induced pruritus, the sedating effect of antihistamines such as diphenhydramine may be beneficial by breaking the itchscratch cycle, but they do not directly reduce the itch. Future directions include the development of peripheral opioid antagonists. These may reduce side effects such as pruritus and postoperative nausea and vomiting without affecting analgesia. Respiratory depression, however, is less likely to be treated with such agents, as it is a centrally mediated effect.

PREVENTION Limiting the dose of a neuraxial opioid can reduce the incidence of side effects. Thus, a multimodal approach to postoperative analgesia may be the best prophylactic regimen. Nonsteroidal anti-inflammatory drugs, for example, reduce opioid requirements, provide analgesia, and perhaps even prevent pruritus by inhibiting prostaglandin synthesis. Dexamethasone is also an effective prophylaxis against nausea and vomiting and, in higher doses, may enhance analgesia. Droperidol may help reduce postoperative nausea and vomiting. Prophylactic ondansetron has been shown to reduce nausea, vomiting, and pruritus. Nalbuphine, however, may be a better drug for treatment than for prophylaxis. Intraoperative propofol infusions do not prevent either pruritus or nausea in the postoperative period. For continuous epidural analgesia, adding a low concentration of local anesthetic to the infusion reduces the opioid dose via a synergistic effect.

Further Reading Bates JJ, Foss JF, Murphy DB: Are peripheral opioid antagonists the solution to opioid side effects? Anesth Analg 98:116-122, 2004. Chaney MA: Side effects of intrathecal and epidural opioids. Can J Anaesth 42:891-903, 1995.

REGIONAL ANESTHESIA & PAIN MANAGEMENT

Pain Service beeper no: _______________ Patient received morphine ____________mg (dose) Intrathecal Epidural (circle correct route) at ___________(time) Epidural morphine __________mg bolus every ___________hours DO NOT administer any narcotic until patient reports discomfort No other opioids or sedative-hypnotics are to be given without notifying the Pain Service  Vitals: check respiratory rate and level of sedation q1hr × 12 hr, q2hr × 12 hr, and q4hr thereafter NOTIFY the Pain Service in case of the following: • Respiratory depression: respiratory rate <8 and patient unarousable • Inadequate analgesia  Activity: assisted ambulation only  IV fluids: maintain IV access for 12 hours following intrathecal or epidural morphine dose Medications (medication management of side effects to be discontinued 12 hours after epidural discontinued): Naloxone 0.1mg IV STAT (may repeat ×3) for respiratory rate <8 and patient unarousable Droperidol 0.5 mg IV q4hr PRN for nausea or vomiting Diphenhydramine 25 to 50 mg IV or PO q4hr PRN for itching Nalbuphine 2.5 mg IV q4hr PRN for itching Other: ____________________________

Naloxone Close observation and frequent monitoring Supplemental oxygen Avoid concomitant opioids and central nervous system depressants

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Cousins MJ, Mather LE: Intrathecal and epidural administration of opioids. Anesthesiology 61:276-310, 1984. de Leon-Casasola OA, Lema MJ: Postoperative epidural opioid analgesia: What are the choices? Anesth Analg 83:867-875, 1996. Etches RC, Sandler AN, Daley MD: Respiratory depression and spinal opioids. Can J Anaesth 36:165-185, 1989. Kuipers PW, Kamphuis ET, van Venrooij GE, et al: Intrathecal opioids and lower urinary tract function: A urodynamic evaluation. Anesthesiology 100:1497-1503, 2004.

Szarvas S, Harmon D, Murphy D: Neuraxial opioid-induced pruritus: A review. J Clin Anesth 15:234-239, 2003. Van de Velde M, Teunkens A, Hanssens M, et al: Intrathecal sufentanil and fetal heart rate abnormalities: A double-blind, double placebocontrolled trial comparing two forms of combined spinal epidural analgesia with epidural analgesia in labor. Anesth Analg 98:1153-1159, 2004.

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Brian A. Williams and Tetsuro Sakai REGIONAL ANESTHESIA & PAIN MANAGEMENT

Case Synopsis An otherwise healthy 30-year-old man underwent outpatient high tibial osteotomy. The uncomplicated procedure was performed with the patient under general anesthesia with endotracheal intubation. After emergence, the patient experienced severe, uncontrolled pain and then postoperative nausea and vomiting (PONV) after opioids were used in the postanesthesia care unit for pain control. He later required unplanned hospital admission for intractable pain, PONV, and somnolence. The patient was discharged after 2 days, when he was finally able to tolerate oral intake. However, he was readmitted to the emergency room 5 days later with constipation, episodic nausea, and wound dehiscence. The wound cultured positive for methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis.

PROBLEM ANALYSIS Definition The development of anesthesia techniques for outpatient surgery has led to great improvements in the management of PONV and postoperative pain. A growing demand for ambulatory surgery and anesthesia has resulted, because these adverse sequelae are the most common causes of unplanned hospital admissions. Multimodal analgesic techniques are especially recommended in ambulatory surgery patients to reduce many of the complications associated with high-dose opioid analgesia. Successful same-day discharge also protects patients from nosocomial and iatrogenic complications inherent to hospitalization. Currently, many complex procedures are performed on an outpatient basis. This trend will continue in order to meet patients’ desire for a more rapid return of cognitive and social function, as well as the public desire to reduce health care expenditures. The evolving subspecialties of outpatient orthopedic anesthesia and acute postoperative pain management are increasingly recognized for their positive effect on reducing hospital length of stay and improving functional recovery and patient satisfaction. Complications in the setting of outpatient orthopedic anesthesia and surgery require a multidisciplinary approach by anesthesiologists, nursing staff, surgeons, and hospital administrators. The goals of ambulatory surgery are as follows: ● ●

To maintain or improve quality and safety of care To schedule cases efficiently

●

● ●

To minimize complications, such as poorly controlled pain and PONV To avoid unplanned postoperative hospital admissions To minimize readmissions after initial hospital discharge

The choice of anesthetic technique has paramount importance in achieving these goals, particularly in orthopedic surgery.

Recognition Traditional belief in the safety and efficacy of general endotracheal anesthesia (GETA) in the inpatient setting should be reexamined in the context of outpatient surgery. In the setting of same-day surgery, a postoperative in-hospital care “buffer” is not necessarily available to manage such common problems as uncontrolled pain and PONV. For orthopedic outpatients, problems associated with GETA include the following: ● ● ●

●

●

Dental or oral mucosal injury from airway instrumentation Respiratory complications from mechanical ventilation Complications from volatile anesthetics (e.g., PONV, malignant hyperthermia) Prolonged or adverse effects from induction agents and systemic muscle relaxants Side effects from opioids (e.g., PONV, somnolence, delayed awakening, pruritus, respiratory depression, urinary retention, constipation)

Prolonged recovery from GETA often requires laborintensive admission to a postanesthesia care unit for prolonged surveillance with physican-directed/interpreted monitoring and intervention. Significant cardiopulmonary 265

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changes caused by GETA are to be expected among elderly patients or those with predisposing medical risk factors. Unplanned admissions to an intensive care unit may also be necessary if prolonged mechanical ventilation or other patient support measures are required for cardiorespiratory or other complications. Regional anesthesia, including peripheral nerve block (PNB), has traditionally been reserved for patients with contraindications to GETA. In outpatient orthopedic surgery, however, there is a shift toward the preferential use of PNB among progressive practitioners, whereas GETA (with volatile agents and no PNB) is reserved for outpatients in whom PNB is contraindicated. PNB for orthopedic outpatients can help avoid the risks associated with GETA mentioned earlier. Williams and colleagues recently reviewed 1200 consecutive cases of outpatient knee surgery and reported that general anesthesia with a volatile agent was associated with a 200% increase in nursing interventions for pain control in the same-day recovery unit and a 300% increase in unplanned hospital admissions compared with anesthesia consisting of sedation and femoralsciatic nerve block techniques. In addition, continuous PNB using indwelling catheters and portable infusion pumps can offer excellent postoperative pain control for 2 to 3 days at home.

Risk Assessment Absolute contraindications to PNB for outpatient surgery include the following: ●

●

● ●

Patient refusal (with appropriate patient education by the anesthesiologist, which may take 10 to 15 minutes, many patients who initially refuse PNB ultimately will accept it) Coagulopathies (systemic anticoagulants such as warfarin should be converted to intravenous heparin preoperatively, if PNB is indicated) Infection at the site of needle placement Systemic bacteremia or sepsis

In practice, these contraindications are highly unlikely in outpatients presenting for same-day orthopedic surgery. Preexisting neurologic conditions are relative contraindications to PNB. Careful documentation of any preexisting neurologic deficit is mandatory if PNB will be performed in such patients. To perform successful ambulatory surgery with PNB, the environment and resources must be coordinated. Good communication between the anesthesiologist and the surgical team is mandatory. To select the appropriate PNB modality, the anesthesiologist must be familiar with the surgical procedure, its invasiveness, and the dermatomes that must be covered. Also, the anesthesiologist must be comfortable performing the indicated PNB. All precautions for conversion to general anesthesia must be immediately available. This includes proper preoperative airway assessment and preparation of the required airway equipment before any regional procedure is performed. Ideally, an induction room or separate facility where PNB can be performed is preferable, to reduce time in the operating room. Anesthesiologists and nursing staff need to be aware of PNB-associated risks. These include central nervous system

and cardiovascular toxicity of local anesthetics and potential peripheral nerve damage with the PNB procedure; the incidence of the latter ranges from 4 in 1000 to 2 in 10,000. The centerpiece of anesthesia care in outpatient orthopedic surgery is multimodal analgesia, including the use of PNB, the prevention of PONV with routine multimodal antiemetic prophylaxis, and the avoidance of general anesthesia with volatile agents whenever possible. A propofol-based intravenous anesthesia technique should be considered as an adjunct to PNB if sedation is required.

Implications Preferential (but careful) use of PNB in orthopedic outpatients is beneficial in terms of reducing hospital costs and improving patient satisfaction. The use of PNB for anesthesia has been associated with earlier discharge (fewer nursing interventions for pain or PONV and fewer unplanned hospital admissions) when compared with GETA in patients undergoing ambulatory orthopedic surgery.

MANAGEMENT There are two methods of PNB: single-injection PNB and continuous PNB with an indwelling catheter. Although single-injection techniques are effective, they offer postoperative analgesia for only a few hours—certainly no more than 12 to 24 hours—depending on the local anesthetic and adjuncts used. Consequently, the duration of the block may be too brief to provide adequate postoperative analgesia or sufficient analgesia to initiate physical therapy. Early physical therapy is essential to optimize functional recovery after orthopedic surgery. Continuous PNB catheter techniques have the following advantages over single-injection or neuraxial techniques: ● ● ●

●

Longer duration of postoperative analgesia Titratable dosage Preferential sensory block, when active physical therapy is required Avoidance of the neuraxis and associated complications (especially in the context of systemic anticoagulation)

Once it is established that PNB is indicated, one must select the correct PNB modality according to the invasiveness of the planned orthopedic procedure. An example of a PNB algorithm for the care of outpatients undergoing knee surgery is given in Table 66-1. Use of a peripheral nerve stimulator facilitates PNB and catheter placement (Fig. 66-1). The patient can later be discharged with the PNB catheter in place and a portable infusion pump. Written instructions for catheter and pump management should be provided and explained to the patient at the time of discharge. Further, the anesthesia care team should make daily contact with the patient by telephone and be available by pager if the patient has questions. PNB can be used safely in patients who require postoperative anticoagulation with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin to prevent deep venous thrombosis and pulmonary embolism. Systemic anticoagulation is seldom used in surgical outpatients.

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Table 66–1

■

■

Complications in Orthopedic Outpatients Not Receiving Peripheral Nerve Blocks

267

Recommended Peripheral Nerve Blocks for Outpatient Knee Surgery

Category I (Mild) No blocks unless unanticipated postoperative pain occurs

Category II (Moderate) Single-injection femoral nerve block recommended: arthrotomy, deep hardware removal, microfracture, mosaicplasty or chondroplasty, ACL allograft Femoral bolus: 30 mL of preferred long-duration local anesthetic No sciatic block unless unanticipated pain refractory to femoral block Continuous catheter recommended: ACL patellar tendon autograft, femoral osteotomy Femoral catheter initial bolus: 20 to 30 mL of preferred long-duration local anesthetic Femoral catheter infusion: 5 mL/hr of low-concentration, long-duration local anesthetic No sciatic block unless unanticipated pain refractory to femoral block

Category III (Severe) Femoral Nerve Block

Sciatic Nerve Block

Continuous femoral catheter−initial bolus: 20-30 mL of intermediate-concentration, long-duration local anesthetic Catheter dose: 5 mL/hr of low-concentration, long-duration local anesthetic

Continuous sciatic catheter−initial bolus: 5-10 mL of low-concentration, longduration local anesthetic Catheter dose (postoperatively): 5-20 mL bolus as needed, followed by 3 mL/hr of low-concentration, long-duration local anesthetic

Continuous femoral catheter−initial bolus: 20 mL of low- concentration, long-duration local anesthetic Catheter dose: 5 mL/hr of low-concentration, long-duration local anesthetic

Single-injection sciatic: 20 mL of intermediate-concentration, long-duration local anesthetic

Most Invasive Category III* Total knee replacement High tibial osteotomy Multiligament reconstruction (including PCL, LCL, MCL, POL) Posterolateral corner reconstruction

Moderately Invasive Category III ACL hamstring autograft Meniscal reconstruction Unicompartmental knee arthroplasty

Less Invasive Category III Distal patella realignment

Single-injection femoral: 30 mL of Single-injection sciatic: 20 mL of intermediate-concentration, long-duration low- to intermediate-concentration, local anesthetic long-duration local anesthetic Algorithm for the use of nerve block additives: −If a catheter is used, clonidine is not routinely added. −If no catheter is used, clonidine is routinely recommended if ropivacaine is the local anesthetic used. −Regardless of catheter status, buprenorphine may be a useful analgesic adjunct (as part of the catheter bolus dose or single-injection dose). The buprenorphine dose should be restricted to a total of 150 μg for an adult patient to prevent nausea, vomiting, and pruritus associated with higher doses. *Test for dorsiflexion postoperatively before ablating sciatic nerve motor response. ACL, anterior cruciate ligament; LCL, lateral collateral ligament; MCL, medial collateral ligament; PCL, posterior cruciate ligament; POL, posterior oblique ligament.

Figure 66–1 ■ Patient receiving a continuous sciatic nerve block catheter after already having received a femoral nerve block catheter (not shown). Note that the catheter is a stimulating catheter (StimCath, Arrow International, Reading, Pa) and that its proper placement can be confirmed with nerve stimulation before the nerve block catheter is dosed with local anesthetic. The operator’s hand is highlighting the attachment of a nerve stimulator adapter clip to the catheter’s Luer-Lok connection device. This catheter can later be attached to an infusion pump containing low-dose local anesthetic that can be infused for up to 72 hours after surgery.

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Procedure

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Finally, use of a continuous propofol infusion as an adjunct to PNB is beneficial for ambulatory surgery patients to reduce the risk of PONV, especially if intraoperative sedation or total intravenous anesthesia is indicated.

PREVENTION One should avoid the underutilization of PNB techniques in outpatient orthopedic surgery, assuming the availability of anesthesiologists who are skilled in such techniques. Anesthesiologists must be proactive and educate patients and surgeons about the benefits of PNB techniques. Using PNB, either as the main anesthetic or as an adjunct to total intravenous anesthesia with propofol, facilitates rapid emergence and perioperative analgesia. Finally, to prevent nosocomial wound infections and unplanned hospital admissions, it is important to discharge patients home the same day. This requires a comprehensive plan for symptom management as part of the total anesthesia and analgesia care plan.

Further Reading Chelly JE, Ben-David B, Williams BA, Kentor ML: Anesthesia and postoperative analgesia: Outcomes following orthopedic surgery. Orthopedics 26(8 Suppl):S865-S871, 2003.

Gupta A, Wu CL, Elkassabany N, et al: Does the routine prophylactic use of antiemetics affect the incidence of postdischarge nausea and vomiting following ambulatory surgery? A systematic review of randomized controlled trials. Anesthesiology 99:488-495, 2003. Ilfeld BM, Morey TE, Enneking FK: Continuous infraclavicular brachial plexus block for postoperative pain control at home: A randomized, double-blinded, placebo-controlled study. Anesthesiology 96:1297-1304, 2002. Ilfeld BM, Morey TE, Wright TW, et al: Continuous interscalene brachial plexus block for postoperative pain control at home: A randomized, double-blinded, placebo-controlled study. Anesth Analg 96:1089-1095, 2003. Klein SM, Nielsen KC, Greengrass RA, et al: Ambulatory discharge after long-acting peripheral nerve blockade: 2382 blocks with ropivacaine. Anesth Analg 94:65-70, 2001. Williams BA, Kentor ML, Vogt MT, et al: Femoral-sciatic nerve blocks for complex outpatient knee surgery are associated with less postoperative pain before same-day discharge: A review of 1200 consecutive cases from the period 1996-1999. Anesthesiology 98:1206-1213, 2003. Williams BA, Kentor ML, Vogt MT, et al: The economics of nerve block pain management after anterior cruciate ligament reconstruction: Significant hospital cost savings via associated PACU bypass and same-day discharge. Anesthesiology 100:697-706, 2004. Williams BA, Vogt MT, Kentor ML, et al: Nausea and vomiting after outpatient ACL reconstruction with regional anesthesia: Are lumbar plexus blocks a risk factor? J Clin Anesth 16:276-281, 2004.

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67

James R. Hebl Case Synopsis

PROBLEM ANALYSIS Definition The use of peripheral nerve blocks (PNBs) for perioperative anesthesia and analgesia has increased dramatically over the past several years. Importantly, this shift in practice does not appear to be a transient phenomenon. For example, more than 40% of clinicians surveyed in 1998 in the United States estimated that their use of PNB techniques would increase over the next several years. Further, use of PNB in France increased approximately 18-fold between 1980 and 1996. Reasons for the increased use of PNB include not only its potential benefits (Table 67-1) but also the avoidance of complications that may accompany central neuraxial techniques, including concerns about perioperative anticoagulation, hemodynamic instability due to sympathetic block, and delayed discharge after outpatient surgery. However, the use of PNB is associated with its own unique set of concerns and complications. In particular, hemorrhagic complications have been reported with greater frequency as changes in clinical practice occur (e.g., more aggressive perioperative anticoagulation, new regional techniques, continuous perineural catheters) and the popularity of PNB continues to increase. Although hemorrhagic complications are quite rare, they can be among the most devastating complications

Table 67–1

■

Potential Benefits of Peripheral Nerve Block

Superior postoperative analgesia Improved rehabilitative efforts (owing to analgesia) Decreased perioperative nausea and vomiting Faster emergence and recovery Earlier mobilization (unilateral blockade) Faster outpatient discharge Improved blood flow to affected extremity Benefits extended with continuous catheter techniques

of PNB. Such injury has been reported with a variety of PNBs, including interscalene, axillary, intercostal, paravertebral, femoral, ilioinguinal, posterior lumbar plexus, and lumbar sympathetic blocks. Patients at greatest risk include those receiving unfractionated heparin, LMWH, warfarin, antiplatelet aggregation medications, or antithrombolytic therapy.

Recognition In general, localized bruising and tenderness are very common following PNB, with reported frequencies ranging from 8% to 23%. True hemorrhagic complications appear to be much less common. For example, the reported frequency of hematoma formation after brachial plexus block ranges from 0.2% to 3%. Most hematomas are small, unrecognized, and clinically inconsequential. However, there have been reports of more severe hemorrhagic complications, as well as significant neurologic impairment after hematoma formation. Recognition of bleeding complications relies on astute clinical vigilance throughout the perioperative period; this is especially important in patients receiving perioperative anticoagulation with intravenous heparin, warfarin, LMWH, or antiplatelet drugs. Significant hypotension, localized pain or tenderness, severe ecchymosis, unexplained anemia, or the development of neurologic deficits may signal underlying hemorrhage or a compressive hematoma. Computed tomography (CT), magnetic resonance imaging, or ultrasonography may be required for confirmation and to determine the location and extent of injury.

Risk Assessment There are no reports on the frequency or severity of hemorrhagic complications with PNB in patients receiving anticoagulants. However, there are reports of serious complications following neurovascular sheath cannulation for central vascular access. Although this intervention is not the same as PNB, it may predict what can occur after PNB 269

REGIONAL ANESTHESIA & PAIN MANAGMENT

A 73-year-old man with a history of ischemic heart disease and diabetes mellitus is scheduled to undergo an elective total hip arthroplasty. The patient has been receiving daily anticoagulation with warfarin since his aortic valve replacement 3 years ago. Five days before surgery, the patient’s warfarin was discontinued by his primary care physician, at which time he began therapeutic anticoagulation bridging therapy with low-molecularweight heparin (LMWH). The patient’s last injection of LMWH was about 24 hours ago. The orthopedic surgeon intends to reinitiate anticoagulation with LMWH 12 hours after surgery. During the preanesthetic interview, the patient requests spinal anesthesia and a peripheral nerve catheter for extended postoperative analgesia.

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needle- or catheter-caused vascular injury in patients receiving anticoagulants or antiplatelet drugs. Fransson and Nylander reported vascular complications in 0.26% of 4879 patients having cardiac catheterization, coronary angiography, or angioplasty at one university hospital. These included pseudoaneurysm (12 cases), thromboembolism (4 cases), and excessive bleeding (3 cases). There was no neurologic impairment in any patient. Among those with vascular complications, 58% were receiving anticoagulation, compared with 10% of those with no complications. Reports of vascular injury after PNB are limited to case reports. Such complications have occurred in patients with normal hemostasis and in those receiving anticoagulation therapy. Complications include anemia with profound hypotension and the need for transfusion, myocardial ischemia, acute renal insufficiency, localized pain and tenderness, neurologic injury, and even death. Of note, all reported adverse neurologic sequelae were transient and self-limited, with full recovery by 12 months. Thus, in contrast to central neuraxial bleeding, bleeding into a more compliant peripheral nerve site seems unlikely to be associated with irreversible, permanent nerve injury. The majority of severe hemorrhagic complications after PNB have been associated with either posterior lumbar plexus (i.e., psoas compartment; see Chapter 64) or lumbar sympathetic blocks. In all instances, patients received anticoagulants before, during, or after PNB. Klein and associates reported one case of psoas compartment hematoma with transient neuropathy after lumbar plexus block for belowknee amputation. That patient received 30 mg of enoxaparin 20 hours before the attempted PNB and also 4 hours afterward. After several attempts at posterior lumbar plexus block, an anterior three-in-one block (lumbar plexus and sciatic nerves) was performed. On postoperative day 1, the patient had right hip pain, which progressed to complete paralysis by day 9. A CT scan revealed a large retroperitoneal hematoma in the psoas compartment, displacing the kidney anteriorly. Her coagulation profile and platelet count were normal. She was treated conservatively, enoxaparin was stopped, and motor function gradually returned over the next 5 days, with complete return by 4 months. Also, Weller and coworkers reported extensive retroperitoneal hemorrhage in two patients, both of whom were anticoagulated after three-inone blocks. Neither had new neurologic deficits, and both had normal coagulation profiles at the time of the block. One received enoxaparin (30 mg) 90 minutes after removal of a catheter within the neurovascular sheath (postoperative day 2) and later developed severe right paravertebral low back pain, hypotension (hemoglobin 7.1 g/dL), and transient renal insufficiency. A CT scan revealed a large retroperitoneal hematoma with renal displacement. The other patient had previously undergone aortic valve replacement and was taking warfarin (Coumadin); this drug was stopped, and the coagulation profile was normal before single-injection three-inone block for knee arthroscopy. Heparin was started 8 hours after the block, and Coumadin was restarted the evening of postoperative day 1. On day 3, the patient had back pain at the block site, with a slow decline in hemoglobin from 12.8 to 8.5 g/dL. The CT scan revealed moderate retroperitoneal hematoma, which was treated conservatively, without residual neurologic impairment.

Irreversible platelet aggregation inhibitors (e.g., ticlopidine, clopidogrel) are implicated as contributing to hemorrhagic complications in patients with PNB. Maier and colleagues reported two cases of severe bleeding after lumbar sympathetic block (LSB). The first patient had peripheral vascular disease, and his medications included ticlopidine (500 mg/day) for stroke prevention. After his first LSB, hemoglobin decreased from 13.5 to 10.3 g/dL, and he complained of groin pain and medial thigh numbness. Inadvertent vascular puncture occurred during a second LSB performed 6 days later. The next night, the patient experienced severe groin pain, with a simultaneous drop in blood pressure and hemoglobin to 8.9 g/dL. A large retroperitoneal hematoma was diagnosed. He was transfused and discharged 5 days later, with no permanent neurologic deficits. The second patient was referred for diagnostic LSB and was receiving clopidogrel (75 mg/day). This drug was discontinued 3 days before the LSB, which was uneventful. Nine hours later, the patient complained of burning groin and medial thigh pain, which was treated with intravenous opioids. Twelve hours after LSB, she was found pulseless. Attempted resuscitation was unsuccessful. At autopsy, there was a massive, congealed retroperitoneal hematoma. As these cases show, severe hemorrhage, but not permanent neurologic injury, may be the most serious complication of PNB in anticoagulated patients. It appears to be most likely if PNB is performed at concealed, noncompliant sites (e.g., psoas compartment). Further, such occult bleeding may go unrecognized for several hours to days.

Implications Perioperative anticoagulation for the prevention of venous thromboembolism can result in significant morbidity, mortality, and resource allocation. Knowledge of specific clinical risk factors for thromboembolism (Table 67-2) is the basis for the proper use of perioperative anticoagulation treatment or prophylaxis. These risk factors are present alone or in combination

Table 67–2

■

Clinical Risk Factors for Venous Thromboembolism

Increased age Prolonged immobility Prior stroke or paralysis Previous venous thromboembolism Cancer Major surgery Abdominal surgery Pelvic surgery Lower extremity surgery Trauma Obesity Varicose veins Cardiac dysfunction Indwelling central venous catheter Inflammatory bowel disease Nephrotic syndrome Pregnancy or estrogen use From American College of Chest Physicians: Sixth ACCP Consensus Conference on Antithrombotic Therapy. Chest 119(Suppl), 2001.

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in a high proportion of hospitalized patients. Consequently, many patients who present for elective or emergency surgery are, or will be, receiving medications that alter normal hemostasis. All clinicians should be aware of this, especially when performing regional anesthesia.

MANAGEMENT Patients receiving anticoagulants may be at the greatest risk of hemorrhagic complications after PNB. Therefore, astute clinical vigilance is mandatory. If such a complication is suspected, immediate clinical evaluation should occur, including the following:

●

Focused review of the patient’s perioperative history ● Past medical history ● Preoperative coagulation status ● Pre- and perioperative medications (e.g., hemostasisaltering drugs, herbals) ● Surgical course, including intra- and postoperative blood loss ● Immediate postoperative course Consideration of the patient’s chief complaint ● Pain (location, duration, nature) ● Neurologic deficits (sensory or motor, onset, duration, fluctuation) ● Orthostatic symptoms ● Fatigue, syncope, lightheadedness, postural hypotension

Table 67–3

■

●

●

Anticoagulants and Peripheral Nerve Block

Physical examination (including a detailed neurologic assessment) Laboratory investigation (complete blood count, coagulation profile, electrolytes) Radiographic imaging for definitive diagnosis (CT, magnetic resonance imaging, ultrasonography)

Surgical decompression with hematoma evacuation may be necessary if (1) the hematoma continues to expand, (2) there is progressive neurologic deterioration, (3) neural dysfunction does not improve despite hematoma resolution, or (4) there is evidence of airway, vascular, or lymphatic obstruction. In select cases, when these criteria are not satisfied, observation and conservative management may be appropriate. However, prompt assessment and appropriate intervention are critical in all patients to prevent hemorrhagic catastrophes and irreversible neurologic impairment.

PREVENTION Development of a central neuraxial hematoma due to bleeding into a fixed and noncompressible site is clearly the most significant and potentially devastating hemorrhagic complication of regional anesthesia. In an effort to reduce this risk, the American Society of Regional Anesthesia and Pain Medicine (ASRAPM) developed consensus guidelines for central neuraxial anesthesia and analgesia in anticoagulated patients (Table 67-3). Because the risk of such complications

American Society of Regional Anesthesia and Pain Medicine Guidelines for Central Neuraxial Anesthesia in Patients Receiving Thromboprophylaxis

Anticoagulant

Recommendation

Antiplatelet medications

No contraindication with NSAIDs Discontinue ticlopidine for 14 days Discontinue clopidogrel for 7 days Discontinue glycoprotein IIb/IIIa inhibitors 8-48 hr in advance

Unfractionated heparin Subcutaneous Intravenous Low-molecular-weight heparin (LMWH)

Warfarin Thrombolytics Herbal therapy

271

No contraindication; consider delaying heparin until after block if technical difficulty is anticipated Heparinize 1 hr after neuraxial technique Remove catheter(s) 2-4 hr after last heparin dose No mandatory delay if traumatic needle placement Preoperative dosing: Needle placement should occur at least 10-12 hr after last LMWH dose (prophylactic dosages) or at least 24 hr after higher doses (treatment dosages) Postoperative twice-daily dosing: LMWH 24 hr after surgery, regardless of technique Remove neuraxial catheter(s) 2 hr before first LMWH dose Postoperative once-daily dosing: LMWH 6-8 hr after surgery Give second postoperative dose no sooner than 24 hr after first dose Indwelling catheter(s) can be safely maintained Remove catheter(s) 10-12 hr after last dose of LMWH and 2 hr before subsequent dosing Document normal INR after discontinuation (before neuraxial technique) Remove catheter(s) when INR ≤1.5 (within initiation of therapy) No data on safe performance of neuraxial techniques or catheter removal No evidence of mandatory discontinuation before neuraxial techniques Be mindful of potential drug interactions (see Chapter 39)

INR, international normalized ratio; NSAID, nonsteroidal anti-inflammatory drug. Adapted from Horlocker TT, Wedel DJ, Benzon H, et al: Regional anesthesia in the anticoagulated patient: Defining the risks (the Second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Reg Anesth Pain Med 28:172-197, 2003.

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●

●

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in anticoagulated patients undergoing PNB is not clearly defined, one approach might be to apply these guidelines to all patients receiving regional anesthesia, including PNB. However, this might be overly cautious. Instead, it might be more prudent to consider the compressibility of the PNB needle insertion site and the vascular structures at risk. Also, it is strongly advised that, in patients with inherent or drug-induced coagulopathies, PNB be used only after a careful risk-benefit analysis, and that it be performed with extra caution. This is especially true if the PNB will be performed in a region where an expanding hematoma could compress the airway (e.g., deep cervical plexus, interscalene, or “plumb-bob” supraclavicular block) or might not become apparent for several hours to days in a noncompressible site (e.g., psoas compartment with a lumbar plexus block). Regardless, good communication among all clinicians involved in the perioperative care of any patient receiving drugs that affect hemostasis is critical to provide optimal patient care and to reduce the risk of serious hemorrhagic complications.

Further Reading Aida S, Takahashi H, Shimoji K: Renal subcapsular hematoma after lumbar plexus block. Anesthesiology 84:452-455, 1996. American College of Chest Physicians: Sixth ACCP Consensus Conference on Antithrombotic Therapy. Chest 119(Suppl), 2001. Ben-David B, Stahl S: Axillary block complicated by hematoma and radial nerve injury. Reg Anesth Pain Med 24:264-266, 1999. Bergman BD, Hebl JR, Kent J, Horlocker TT: Neurologic complications of 405 consecutive continuous axillary catheters. Anesth Analg 96: 247-252, 2003. Clergue F, Auroy Y, Perquignot F, et al: French survey of anesthesia in 1996. Anesthesiology 91:1509-1520, 1999.

Ekatodramis G, Macaire P, Borgeat A: Prolonged Horner syndrome due to neck hematoma after continuous interscalene block. Anesthesiology 95:801-803, 2001. Fransson SG, Nylander E: Vascular injury following cardiac catheterization, coronary angiography, and coronary angioplasty. Eur Heart J 15: 232-235, 1994. Hadzic A, Vloka JD, Kuroda MM, et al: The practice of peripheral nerve blocks in the United States: A national survey. Reg Anesth Pain Med 23:241-246, 1998. Horlocker TT: Peripheral nerve blocks: Regional anesthesia for the new millennium. Reg Anesth Pain Med 23:237-240, 1998. Horlocker TT, Wedel DJ, Benzon H, et al: Regional anesthesia in the anticoagulated patient: Defining the risks (the Second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Reg Anesth Pain Med 28:172-197, 2003. Johr M: A complication of continuous blockade of the femoral nerve [German]. Reg Anaesthesie 10:37-38, 1987. Klein SM, D’Ercole F, Greengrass RA, Warner DS: Enoxaparin associated with psoas hematoma and lumbar plexopathy after lumbar plexus block. Anesthesiology 87:1576-1579, 1997. Maier C, Gleim M, Weiss T, et al: Severe bleeding following lumbar sympathetic blockade in two patients under medication with irreversible platelet aggregation inhibitors. Anesthesiology 97:740-743, 2002. Neal JM, Hebl JR, Gerancher JC, Hogan QH: Brachial plexus anesthesia: Essentials of our current understanding. Reg Anesth Pain Med 27: 402-428, 2002. Nielsen CH: Bleeding after intercostal nerve block in a patient anticoagulated with heparin. Anesthesiology 71:162-164, 1989. Sada T, Kobayashi T, Murakami S: Continuous axillary brachial plexus block. Can Anaesth Soc J 30:201-205, 1983. Thomas PW, Sanders DJ, Berrisford RG: Pulmonary haemorrhage after percutaneous paravertebral block. Br J Anaesth 83:668-669, 1999. Vaisman J: Pelvic hematoma after an ilioinguinal nerve block for orchialgia. Anesth Analg 92:1048-1049, 2001. Weller RS, Gerancher JC, Crews JC, Wade KL: Extensive retroperitoneal hematoma without neurologic deficit in two patients who underwent lumbar plexus block and were later anticoagulated. Anesthesiology 98:581-585, 2003.

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Chronic Nonsteroidal Anti-inflammatory Drug Use Celeste M. Lombardi Case Synopsis

REGIONAL ANESTHESIA & PAIN MANAGMENT

A 60-year-old man with a history of osteoarthritis has been taking naproxen for the past 3 years without complications or side effects. He experienced sudden severe nausea and vomited frank blood. He was taken to the emergency room and underwent an urgent upper gastrointestinal (GI) endoscopy, which revealed a bleeding gastric ulcer.

PROBLEM ANALYSIS Definition Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used drugs that act by inhibiting cyclooxygenase and the formation of prostaglandins. Prostaglandins are derived from arachidonic acid, formed by phospholipase A2 acting on cell membrane phospholipids (Fig. 68-1). NSAIDs are among the most commonly used drugs worldwide and are usually well tolerated. However, like all medications, NSAIDs are not without side effects. They are known to cause the following: ● ●

●

●

●

GI toxicity, leading to the formation of peptic ulcers Unwanted antiplatelet effects (nonselective inhibitors of cyclooxygenase) Potential for increased thrombogenicity (selective cyclooxygenase-2 [COX-2] inhibitors) Renal toxicity, with potential alterations of potassium and fluid balance, decreased renal function, nephrotic syndrome with interstitial nephritis, papillary necrosis, and rhabdomyolysis Anaphylactic and anaphylactoid reactions in select patients

Recognition GASTROINTESTINAL EFFECTS NSAID use is the second most important cause of peptic ulcers after Helicobacter pylori infection. The primary mechanism of ulcer formation is from suppression of gastric prostaglandins, although decreases in nitric oxide and calcitonin gene-related peptide may also be involved. This leads to decreases in epithelial mucus, bicarbonate secretion, and mucosal resistance to injury. NSAIDs also reduce gastric mucosal blood flow, with subsequent damage to the vascular endothelium (an early effect of NSAID administration) in conjunction with an enhanced adherence of neutrophils to the vascular endothelium. The neutrophil adherence causes endothelial injury by release of oxygen-derived free radicals.

Arachidonic acid

COX-1 +

Lipoxygenase

COX-2 + Prostaglandins

Thromboxane

Gastric PGE Pain, inflammation, fever

Platelet aggregation

Mucosal blood flow Mucus secretion HCO3 secretion Cell restitution Scavenging of free radicals

+

Gastric mucosal protection

Figure 68–1 ■ Biosynthesis of prostaglandins from arachidonic acid via the cyclooxygenase (COX-1 and COX-2) pathways. Arachidonic acid, the immediate precursor of prostaglandins, is derived from membrane phospholipids in reactions catalyzed by the two COX isoenzymes. The gene for COX-1 (the “housekeeping” enzyme) is expressed constitutively and maintains organ homeostasis, including integrity of the gastric mucosa. The gene for COX-2 (the “inflammatory” enzyme) is inducible. Thromboxane derived via COX-1 causes platelet aggregation or the listed gastric mucosal protective effects. In contrast, prostaglandins such as prostacyclin (PGI2) derived via COX-2 are mediators of pain, inflammation, and fever. PGE, prostaglandin E. (Adapted from Wolfe MM: Therapy and prevention of NSAID-related gastrointestinal disorders. In Wolfe MM [ed]: Therapy of Digestive Disorders: A Companion to Sleisenger and Fordtran Gastrointestinal Diseases. Philadelphia, WB Saunders, 2000, pp 96-112.)

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THROMBOGENIC EFFECTS Thromboxane A2 is a major product of COX-1 metabolism in platelets (see Fig. 68-1). It causes platelet aggregration, vasoconstriction, and smooth muscle proliferation. In patients with peripheral vascular disease, increased thromboxane production is associated with increased risk of major vascular events. Aspirin is a potent inhibitor of platelet cyclooxygenase (COX-1), which blocks thromboxane production for the life of the platelet. With other NSAIDs, this process lasts 24 hours or less. This effect underlies aspirin’s ability to reduce the incidence of cardiovascular death, myocardial infarction, and stroke in high-risk patients. However, high doses or toxic doses of aspirin can inhibit vitamin K–dependent coagulation factors, leading to an increase in prothrombin time and international normalized ratio. In contrast, prostacyclin is a product of COX-2 metabolism in vascular endothelium. This is postulated from the finding that pharmacologic inhibition of COX-2 leads to the inhibition of prostacyclin formation. Prostacyclin inhibits platelet aggregation and smooth muscle proliferation and causes vasodilatation. Nabumetone, etodolac, and nonacetylated salicylates (relatively COX-2–selective NSAIDs) inhibit COX-2–mediated prostacyclin biosynthesis and seem to have little or no effect on platelet aggregation. Other NSAIDs block COX-1 thromboxane biosynthesis and COX-2 prostacyclin production with less selectivity (Table 68-1; Fig. 68-2).

Aspirin

3.12

Naproxen

1.79

Indomethacin

1.78

Ibuprofen

1.69

Nabumetone

0.64

Etodolac

0.11

Celecoxib

0.11

Meloxicam

0.09

Rofecoxib

0.05

0.00

0.50

1.00

1.50

2.00

2.50

3.00

3.50

IC50 for COX-2/IC50 for COX-1

Figure 68–2 ■ Selectivity of COX-2 inhibitors. Comparison of in vivo inhibitory concentration (IC50) ratios (COX-2/COX-1) of selective and nonselective nonsteroidal anti-inflammatory drugs. A lower ratio indicates an increased degree of selectivity for COX-2. (Adapted from Feldman M, McMahon AT: Do cyclooxygenase-2 inhibitors provide benefits similar to those of traditional anti-inflammatory drugs, with less gastrointestinal toxicity? Ann Intern Med 132:134-143, 2000.)

RENAL EFFECTS Up to 5% of patients on regular NSAID therapy develop one or more nephrotoxic side effects, including fluid and electrolyte abnormalities, acute renal failure, and nephrotic syndrome (Table 68-2). The mechanism of action of these side effects is inhibition of the production of prostaglandins I2, E2, and D2 by blocking of the COX-1 isoenzyme. This reduces renal perfusion by causing acute renal artery vasoconstriction, medullary ischemia, and, in some cases, acute renal failure. NSAIDs also decrease the efficacy of antihypertensive medications because they require intact renal prostaglandin function. The exceptions are calcium channel blockers and angiotensin II receptor antagonists, which are not influenced by renal prostaglandins. Various NSAIDs have different effects on blood pressure, depending on their capacity to inhibit renal

vasodilatory prostaglandins. Sulindac, for instance, may be a weaker inhibitor of renal prostaglandins and thus exert less effect on blood pressure in hypertensive individuals. Blood pressure needs to be closely monitored in patients who are started on NSAID therapy and take antihypertensive medication, especially those 55 years and older. Fluid and electrolyte disturbances are common NSAIDassociated renal side effects. They occur as a result of inhibition of prostaglandin formation in the thick ascending limb of the loop of Henle and the distal renal tubule, leading to hypotonic sodium and water retention. With the inhibition

Table 68–2

Table 68–1

■

Inhibition of Prostacyclin and Thromboxane Biosynthesis and Risk of Thrombosis

Drug Low-dose aspirin Conventional COX-2 specific inhibitors

Prostacyclin

Thromboxane

Thrombosis Risk

+/− ⇓ ⇓

⇓⇓ ⇓ +/–

⇓ Unclear Unclear

COX, cyclooxygenase; NSAID, nonsteroidal anti-inflammatory drug. From Catella-Lawson F, Crofford LJ: Cyclooxygenase inhibition and thrombogenicity. Am J Med 110:28-32, 2001.

■

Renal Syndromes Related to Therapy with Conventional Nonsteroidal Anti-inflammatory Drugs

Fluid and electrolyte abnormalities Acute renal failure Hemodynamic compromise Nephrotic syndrome (minimal-change glomerulopathy, interstitial nephritis) Acute papillary necrosis (typically, single drug cause) Other systemic interactions Hypernatremia Water retention Hyperkalemia Membranous glomerulopathy Chronic papillary necrosis (typically, multidrug causes) Chronic heart failure Hypertension (treated)

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ANAPHYLACTIC

AND

ANAPHYLACTOID REACTIONS

A small number of patient experience allergic and pseudoallergic reactions to aspirin and NSAIDs. Some reactions are caused by the similar pharmacologic properties of traditional NSAIDs, which inhibit both COX-1 and COX-2. Prostaglandin E2 formation is blocked by the inhibition of COX-1, leading to a relative increase in leukotriene formation and histamine release from mast cells. Such a pseudoallergic reaction occurs after the first exposure to the NSAID, which makes prior sensitization impossible. Aspirin and other NSAIDs that are more specific for COX-1 than COX-2 (see Fig. 68-2) can induce rhinorrhea, bronchospasm, and laryngospasm in patients with a prior history of sinusitis and asthma. Cross-sensitivity of aspirin and other relatively COX-1–specific NSAIDs with newer COX-2–selective antagonists does not occur. This is further evidence that COX-1 inhibition is the inciting event in aspirin-induced respiratory symptoms. Some patients display a true allergy to a specific NSAID, with prior exposure leading to the formation of immunoglobulin E (IgE) antibodies. On subsequent exposure, they experience symptoms, including urticaria, angioedema, and anaphylaxis. Assays for specific drug haptens have not been developed, and IgE antibodies are rarely found in the blood of these patients. Therefore, the term anaphylactoid has been used to describe such reactions. These reactions are caused by a specific NSAID, and patients are able to take other NSAIDs without difficulty.

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age (older than 65 years), renal or hepatic impairment, prior history of ulcers, smoking, alcohol use, concomitant use of oral corticosteroids or anticoagulants, high doses of NSAIDs, and prolonged duration of therapy. Since recognition of the two isoforms of cyclooxygenase, the COX-1 enzyme has been identified as the one responsible for the formation of gastric prostaglandin E1, and nonselective NSAIDs have been implicated in a higher risk of GI complications. It is important to understand the relative selectivity of the NSAIDs for COX isoforms, because this may influence the decision of which drug to choose for a patient. For example, etodolac, meloxicam, and nabumetone have a relatively higher affinity for COX-2 than for COX-1 (see Fig. 68-2) and have a safer profile with respect to GI toxicity. The Celecoxib Long-Term Arthritis Safety Study (CLASS) was a 6-month randomized, double-blind, controlled trial comparing the GI toxicity of celecoxib (400 mg twice a day) with that of more traditional NSAIDs (diclofenac 75 mg twice a day; ibuprofen 800 mg three times a day). The primary end point was ulcer-related complications (gastric perforation, gastric outlet syndrome, GI bleeding), and the secondary end point was symptomatic ulcers. Although there appeared to be a difference in symptomatic and complicated ulcers, this was not statistically significant. Two confounding factors in the study were the supratherapeutic doses of celecoxib used and the inclusion of 21% of patients on low-dose aspirin for cardiovascular prophylaxis. Aspirin is known to increase the risk of upper GI hemorrhage. The ulcer complication rate among the nonaspirin users who took celecoxib was similar to that of the general population, but because there was no placebo group, it was difficult to assess the risk of ulcers with celecoxib. However, we were able to ascertain that patients tolerate celecoxib better than diclofenac and ibuprofen, with less decline in hematocrit, a reduced incidence of dyspepsia, and fewer required endoscopies. The Vioxx Gastrointestinal Outcomes Research (VIGOR) was a 12-month trial performed to compare the GI toxicity of rofecoxib (Vioxx)1 50 mg daily to the more traditional NSAID naproxen 500 mg twice a day. The primary end point was confirmed clinical upper GI events, including symptomatic gastroduodenal ulcers, perforation, or obstruction or upper GI bleeding. The secondary end point was complicated GI events causing severe patient compromise. Results showed a statistically significant reduction in GI events with rofecoxib compared with naproxen. The reduced incidence of GI toxicity with rofecoxib was even present in patients with risk factors for GI events, including advanced age, corticosteroid use, prior history of GI perforation or obstruction, and H. pylori infection. This was the first study to demonstrate a definitive benefit with the use of a selective COX-2 inhibitor.

Risk Assessment and Implications

THROMBOGENICITY

GASTROINTESTINAL INJURY

COX-2–selective antagonists preferentially block the formation of prostacyclin, with little effect on thromboxane production. Thus, there is a theoretical concern about an increased risk

Dyspepsia is not a reliable means of assessing GI mucosal damage. Ten percent to 20% of patients on NSAID therapy complain of dyspepsia, yet 50% of endoscopic findings show normal GI mucosa. Most patients do not complain of GI symptoms until they develop a life-threatening upper GI bleed. Risk factors for the development of ulcers include advanced

1 Rofecoxib (Vioxx) was voluntarily withdrawn from the market by its manufacturer (Merck) on September 30, 2004, owing to an increased risk of coronary events.

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of the cyclooxygenase pathway, there is a theoretical increase in leukotriene formation via the 5-lipoxygenase pathway, leading to increased capillary permeability and edema formation. This is often seen in patients who develop congestive heart failure. Hyperkalemia is a rare but serious complication of chronic NSAID therapy. This can occur as a result of inhibition of prostaglandin-mediated renin release. This, in turn, leads to decreased aldosterone formation and decreased secretion of potassium in the distal renal tubules. The development of nephrotic syndrome with interstitial nephritis is rare and is not clearly understood. It is theorized that the preferential formation of leukotrienes and inhibition of prostaglandins increase vascular permeability, leading to nephrotic-range proteinuria and interstitial nephritis. Renal papillary necrosis is also rare and is thought to occur in cases of NSAID overdose in severely dehydrated patients. The combination of prostaglandin inhibition and high intrapapillary doses of NSAIDs, which may be cytotoxic themselves, leads to papillary necrosis. This is unlikely to occur with conventional doses of NSAIDs.

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of thrombosis.2 This may be especially true among elderly patients, who are at higher risk of atherosclerotic disease. In the CLASS study, there was no notable difference in cardiovascular events among patients taking celecoxib compared with diclofenac or ibuprofen. In the VIGOR study, there was a statistically significant increase in major cardiovascular events among patients taking rofecoxib versus naproxen. However, in my view, this is not necessarily indicative of a higher cardiovascular risk for patients taking rofecoxib: 27% of patients from the celecoxib study group and 100% of patients from the rofecoxib study group had rheumatoid arthritis, which increases the risk of cardiovascular events. Further, 21% of patients in the celecoxib study were on lowdose aspirin for cardiovascular prophylaxis; low-dose aspirin was an exclusion criterion in the rofecoxib study. RENAL INJURY Patients with the greatest risk of developing renal insufficiency due to the inhibition of renal prostaglandins are the elderly and those with renal or liver disease, hypertension, some degree of cardiovascular compromise, congestive heart failure, or hypovolemia. It has been noted that COX-2 is also produced in the kidney, so both nonselective and selective inhibition of COX-2 can lead to edema formation. Celecoxib has been evaluated for its ability to impair renal function—specifically, nephrotic syndrome, interstitial nephritis, increased serum creatinine levels, and papillary necrosis. Celecoxib seems to cause less renal impairment compared with nonselective COX inhibitors, but this has not been tested rigorously. Therefore, at least for now, selective COX-2 inhibitors must be used with caution in patients with preexisting renal disease, just as with traditional NSAIDs. ALLERGIC REACTIONS There have been rare reported cases of aseptic meningitis in patients with arthritis who were treated for months with specific NSAIDs. In these cases, the aseptic meningitis is thought to be an immune reaction to the NSAID. IgG and immune complexes have been found in the cerebrospinal fluid of patients with aseptic meningitis. This has not been reported with aspirin. There have also been rare reports of cough, fever, pulmonary infiltrates, and eosinophilia after exposure to multiple NSAIDs, except aspirin. Such allergic alveolitis or hypersensitivity pneumonitis is also thought to be mediated by an immune reaction, because interstitial lymphocytes and eosinophils were found in lung biopsies taken from these patients. This could be either an IgE-mediated reaction or delayed hypersensitivity.

MANAGEMENT Gastrointestinal Toxicity About 15,000 people die each year as a result of major GI complications from NSAIDs, including hemorrhage, perforation, 2 See footnote 1 and Topol EJ: Failing the public health—rofecoxib, Merck, and the FDA. N Engl J Med 351:1707-1709, 2004; and Fitzgerald GA: Coxibs and cardiovascular disease. N Engl J Med 351:1709-1711, 2004.

and obstruction. NSAID-induced ulcers heal spontaneously, but slowly, once the NSAID is discontinued; antisecretory therapy accelerates ulcer healing. Althoughe H2-antagonists are inexpensive, proton pump inhibitors are generally preferred. They cause more rapid ulcer healing and early symptomatic relief. If patients continue to take NSAIDs while on ulcer therapy with an H2-antagonist (e.g., ranitidine 150 mg twice a day) or proton pump inhibitor (e.g., omeprazole 20 mg daily), there is a high rate of ulcer recurrence. Surgery is reserved for patients who present with severe GI hemorrhage or perforation.

Allergic Reactions Aspirin desensitization has been successfully undertaken, with patients receiving aspirin 650 mg twice a day for up to 2 weeks. Urine leukotrienes have been followed, with a significant decrease noted after desensitization. Such desensitization may be especially beneficial for older patients with cardiovascular disease who need to be on long-term aspirin therapy.

PREVENTION Peptic Ulcers Misoprostol, a prostaglandin E1 analogue, decreases the risk of gastric and duodenal ulcers. H2-antagonists and proton pump inhibitors are used to reduce the incidence of duodenal ulcers and gastric ulcers, respectively. For patients at high risk of developing GI complications, a selective COX-2 antagonist is preferred.

Thrombogenicity If patients are taking traditional NSAIDs and COX-2–selective antagonists, those at risk for cardiovascular events should be on low-dose aspirin. Because the traditional NSAIDs and aspirin inhibit COX-1, there may be competitive antagonism. There is also the added risk of upper GI bleeding. Thus, for patients taking aspirin, an H2-antagonist may be the better choice for GI prophylaxis. Omeprazole increases aspirin’s rate of absorption. It may rapidly increase salicylate levels, with potential toxic effects.

Renal Toxicity In general, patients with a serum creatinine level of 2.5 mg/dL or higher should not be started on conventional NSAID therapy. Those on antihypertensive therapy need to have their blood pressure closely monitored during the initiation of NSAID therapy. Patients at risk of developing congestive heart failure should also be closely monitored while on NSAID therapy.

Further Reading Boyce EG, Takiya L: Nonsteroidal anti-inflammatory drugs: Review of factors guiding formulary selection. Formulary 35:142-168, 2000. Buttgereit F, Burmester GR, Lee LS: Gastrointestinal toxic side effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2-specific inhibitors. Am J Med 110(Suppl 3A):13S-19S, 2001.

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Catella-Lawson F, Crofford LJ: Cyclooxgenase inhibition and thrombogenicity. Am J Med 110(Suppl 3A):28S-32S, 2001. Frishman WH: Effects of nonsteroidal anti-inflammatory drug therapy on blood pressure and peripheral edema. Am J Card 89:18D-25D, 2002. Oviedo JA, Wolfe MM: Gastroprotection by coxibs: What do the Celecoxib Long-Term Arthritis Safety Study and the Vioxx Gastrointestinal Outcomes Research Trial tell us? Rheum Dis Clin North Am 29: 769-788, 2003. Shiotani A, Graham DY: Pathogenesis and therapy of gastric and duodenal ulcer disease. Med Clin North Am 86:1447-1466, 2002.

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Stevenson DD: Anaphylactic and anaphylactoid reactions to aspirin and other nonsteroidal anti-inflammatory drugs. Immunol Allergy Clin North Am 21:745-768, 2001. Stevenson DD: Aspirin and NSAID sensitivity. Immunol Allergy Clin North Am 24:491-503, 2004. Whelton A: Renal aspects of treatment with conventional nonsteroidal anti-inflammatory drugs versus cyclooxygenase-2-specific inhibitors. Am J Med 110(Suppl 3A):33S-42S, 2001.

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Opioid Tolerance William S. Blau Case Synopsis A 32-year-old woman with ovarian carcinoma, chronic cancer-related pain, and a previous history of intravenous drug abuse presents with small bowel obstruction and is posted for an emergency laparotomy. Her current medications include continuousrelease morphine and an oxycodone-acetaminophen preparation that she takes for breakthrough pain (8 to 12 pills daily).

PROBLEM ANALYSIS Definition Tolerance occurs when increasing doses of a substance are required to sustain a given effect. It may develop within 1 to 2 weeks after initiating opioid therapy, although recent evidence suggests that its onset may be faster, especially with potent, ultra-short-acting opioids such as remifentanil. The degree of tolerance depends on the magnitude and duration of exposure. Variable degrees of cross-tolerance occur between different opioids and different routes of administration (e.g., systemic versus epidural). It is important to distinguish tolerance (a predictable, involuntary physiologic response to drug exposure) from the related phenomena of physical dependence, addiction, and pseudoaddiction (Table 69-1).

Recognition Tolerance should be suspected when a patient requires greater than the usual dose of analgesic or fails to obtain appropriate relief at the usual dose. Any patient receiving opioid medications for 2 weeks or more can be presumed to have some degree of tolerance, related to the dose of opioid medication. Some patients who present for surgery may have developed opioid tolerance from prolonged therapy for chronic or cancer-related pain or from prior substance abuse. Tolerance is often not readily detectable from the preoperative history in drug abusers. Suspicion should be raised in patients who report multiple “allergies” to opioid medications, express a

Table 69–1

■

preference for specific medications, or are known to abuse alcohol or other substances. Prior medical records or history from family members may provide further evidence. In some cases, an unexpectedly high intraoperative or postoperative opioid requirement may be the first indication of prior exposure; however, it is important to recognize that there is a wide range of interindividual variability in opioid requirements, even among patients who are opioid naïve.

Risk Assessment Any patient with prolonged hospitalization, multiple surgeries, or history of chronic or cancer pain is at risk and should be carefully assessed for the possibility of tolerance. The lifetime prevalence of nonalcohol drug addiction ranges from 5% to 6%. There is probably a higher prevalence of chemical dependency among hospitalized individuals with acute pain problems caused by medical illnesses, trauma, or surgical procedures than among the general population. As many as half of acute trauma victims use drugs or alcohol before injury and may be habitual users. Patients receiving daily methadone or buprenorphine for chemical dependency should be assumed to have significant tolerance and crosstolerance to other opioids as well.

Implications Patients with opioid tolerance are difficult to assess and are at risk for inadequate postoperative pain control. These patients require higher than customary doses of opioids,

Definition of Terms

Term

Definition

Tolerance

Phenomenon whereby exposure to a drug results in diminution of effect or the need for a higher dose to maintain that effect Physiologic phenomenon characterized by the development of an abstinence syndrome following abrupt discontinuation of therapy, substantial dose reduction, or administration of an antagonist drug Psychological and behavioral syndrome characterized by (1) intense desire for a drug and overwhelming concern about its continued availability; (2) evidence of compulsive drug use; or (3) evidence of one or more associated behaviors, including manipulation of the treating physician or medical system for the purpose of obtaining additional drugs, acquisition of drugs from other medical or nonmedical sources, drug hoarding or sale, or unapproved use of other drugs during opioid therapy Iatrogenic syndrome of abnormal behavioral symptoms, mimicking those of addiction, that is a direct consequence of inadequate pain management

Physical dependence Addiction

Pseudoaddiction

278

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yet many physicians are inclined to undermedicate. As patients become more vocal about their needs, hospital staff may react negatively or even punitively, ultimately leading to the syndrome of pseudoaddiction. The risk of side effects from pain therapy, such as oversedation or respiratory depression, is also increased in patients with opioid tolerance. Many opioid-tolerant patients also exhibit physical dependence and are at risk of experiencing withdrawal during the postoperative period, especially when surgery eliminates the source of chronic pain and opioids are rapidly tapered or discontinued. Symptoms generally begin 8 to 12 hours after the last dose of an intermediate-acting opioid and may be difficult to distinguish from those of undertreated pain (e.g., hypertension, tachycardia, abdominal pain).

General Considerations Effective management of a patient with opioid tolerance begins with the preoperative assessment. The possibility of tolerance should be identified and anticipated, based on the patient’s history. Particular attention should be paid to preexisting sites and intensity of pain, baseline functional limitations, and the success of previous pain therapies. It is essential to establish a good therapeutic relationship with the patient as early as possible. Make the patient a partner in developing the analgesic plan, provide reassurance that every effort will be made to provide adequate pain control, but be direct and honest about the limitations of therapy. Patients can help establish realistic goals for pain and activity; for example, obtaining a score of 3 out of 10 after surgery may be unrealistic if the baseline score at home is 7 out of 10. Reassure the patient that his or her reporting of postoperative pain will be taken seriously but will also be corroborated by objective data whenever possible (e.g., quality of sleep; ability to cough, move, and participate in therapy). Involvement of family members may be helpful. Seek preoperative consultation from a pain specialist, as necessary. The patient’s preferences and requests for particular analgesics should be honored to the extent allowable by institutional policy and principles of safe pharmacologic practice. Plans and goals should be clearly communicated to the anesthesia team, postanesthesia care unit staff, and postoperative ward. The overriding principle of acute pain management for patients with opioid tolerance is to titrate analgesic therapy to effect, while anticipating the need for higher than usual doses. Frequent assessment, intervention, and reassessment are required. These patients are at increased risk for anxiety or sedation, and special arrangements may be necessary for postoperative monitoring of respiration and level of consciousness. Whenever possible, the cause or mechanism of pain should be identified and treated primarily. A multimodal approach should be taken, and the pain management plan should be initiated as early as possible. In some cases, preoperative intervention may have preemptive effects. Pharmacologic therapy for symptom control should be based on sound pharmacologic principles. Trials of alternative opioids or routes of delivery should be considered, owing to the possibility of incomplete cross-tolerance. Additional alternative

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therapies include nonopioid analgesics or adjuncts, regional analgesia, and nonpharmacologic interventions (e.g., transcutaneous electrical nerve stimulation, relaxation, heat or cold, massage, distraction). Every effort should be made to avoid the discontinuation of routine daily psychotropic medications that may promote psychological coping mechanisms.

Medications For patients receiving chronic opioids preoperatively, the daily baseline medication dose or analgesic equivalent should be continued throughout the perioperative period. In many cases, this may need to be administered parenterally and can often be incorporated into a basal infusion as part of a patient-controlled analgesia (PCA) prescription. For patients in substance abuse maintenance programs, continuation of the baseline methadone or buprenorphine dose is equally important. Also, avoid substituting medications if at all possible. On the day of surgery, the usual oral dose can be administered in the morning, with the remainder of the daily requirement titrated intravenously intraoperatively and after surgery. Additional intraoperative dosing above baseline requirements should be expected; double doses or greater of morphine, methadone, hydromorphone, or fentanyl may be required. It may be helpful to allow muscle relaxation to wear off near the end of general anesthesia and titrate additional opioid to a mild slowing of the spontaneous respiratory rate. Postoperatively, avoid administering analgesic medications solely on an as-needed basis. Intravenous PCA therapy is often appropriate and effective, even in a patient with a history of drug abuse. A loading dose should be provided and titrated to the level of pain so that the patient starts from a position of adequate pain control. If the patient is able to continue oral medications, PCA bolus dosing can be added, in combination with the baseline oral opioid dose. Otherwise, the total daily opioid dose can be converted to the intravenous morphine, hydromorphone, or fentanyl equivalent using standard conversion tables (Table 69-2) and provided as a basal infusion over 24 hours. Bolus dosing requirements

Table 69–2

■

Equianalgesic Opioid Conversion*

Drug

Oral Equivalent (mg)

Parenteral Equivalent (mg)

Morphine

60 (acute) 30 (chronic)

10 10

Methadone (Dolophine) Fentanyl (Duragesic) Hydromorphone (Dilaudid) Codeine Hydrocodone (Lorcet, Vicodin) Oxycodone (Percocet, Tylox)

†

†

— 7.5

0.125 1.5

180-200 15

130 —

15

—

*Based on single-dose studies only. † Conversions to and from methadone are unpredictable; they vary among patients and with the overall magnitude of opioid dose. However, acutely, the parenteral equivalent for methadone is the same as morphine (10 mg).

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MANAGEMENT

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1.5 to 3 times greater than those of opioid-naïve patients should be anticipated, correlating with the magnitude of the preoperative dose, intraoperative opioid requirements, and titrated loading dose. It should also be anticipated that the duration of therapy for acute or postoperative pain will be longer than for opioid-naïve patients. Most opioids have no specific toxicity, so there is no upper limit to dose titration. However, the agonist-antagonists and partial agonists, such as butorphanol and buprenorphine, exhibit an analgesic ceiling that limits dose titration and may precipitate withdrawal in patients with physical dependence. Meperidine and propoxyphene have active metabolites that may cause central nervous system toxicity, especially in the setting of impaired renal function. Combination drugs (e.g., oxycodone with acetaminophen) are relatively contraindicated because of the risk of acetaminophen or aspirin toxicity. Morphine alone and at extremely high doses, especially when delivered intrathecally, can rarely produce a state of paradoxical pain, which may be related to metabolite accumulation. Morphine and other opioid agonists are more or less equivalent in terms of clinical efficacy. Nevertheless, converting to an alternative opioid can improve analgesia in some cases, owing to incomplete cross-tolerance. In particular, methadone sometimes provides effective analgesia even at modest doses in the setting of inadequate pain control with high and rapidly escalating doses of morphine. Methadone can be administered at a dose of 20 to 40 mg orally (or half as much parenterally) over 24 hours, with additional breakthrough doses of 1 to 2.5 mg intravenously as often as every 5 to 10 minutes. However, care must be taken to avoid rapid dose escalation with methadone because of its prolonged half-life and variable pharmacokinetics. In addition to opioids, adjunctive medications should be used for pain. These include nonsteroidal anti-inflammatory drugs, tricyclic antidepressants and anticonvulsants for neuropathic sources of pain, muscle relaxants, and anxiolytics. There is accumulating evidence that some other medications, when administered perioperatively, may have novel analgesic applications that enhance the chance of successful pain modulation. These include gabapentin, clonidine, adenosine, lidocaine, and ketamine. Of these, ketamine has the most evidence supporting an analgesic benefit. It is my practice to infuse ketamine at 0.1 mg/kg per hour intraoperatively, along with the administration of 1 to 2 g magnesium intravenously, to suppress NMDA receptor activation in patients with opioid tolerance. The pain management plan continues through the hospital discharge process. The 24-hour parenteral opioid dose should be converted to an oral equivalent, with two thirds as the standing dose and one third administered on an as-needed basis. Depending on the severity and persistence of postoperative pain, the patient may be discharged on his or her baseline preoperative analgesic with a provision for breakthrough pain; often, however, upward adjustment of the baseline dose is required, at least temporarily. It is essential to have a clear postdischarge plan, with a responsible physician willing to manage and taper pain medications on an outpatient basis.

Regional Anesthesia Continuous regional anesthesia techniques can be invaluable in enhancing pain control and avoiding the escalation

of opioid doses, but they do not eliminate the need for ongoing administration of baseline analgesic medications in tolerant or dependent patients. Epidural analgesia is an acceptable and useful adjunct. For drug abusers or patients at high risk for opioid withdrawal, it may be advantageous to infuse only local anesthetic through the epidural catheter (e.g., bupivacaine 0.1% to 0.25%) and give the patient systemic analgesics to cover baseline needs.

Drug Abusers In patients with opioid tolerance due to active drug abuse or addiction, all the previously discussed principles of pain management apply; however, there are some special considerations. The first and foremost goal is satisfactory control of pain. This is not an appropriate time to attempt detoxification or assume a punitive role. It is essential to engage in a frank discussion with the patient preoperatively to (1) reassure him or her that all reasonable efforts will be made to provide satisfactory pain control and (2) set reasonable expectations and clear limits to avoid excessive negotiation about drug choices or doses. Avoid multiple pain managers, and aim for consistency of response rather than negotiation. Drug abuse–related behaviors should not be tolerated; ignore negative behaviors and reward cooperation with therapy. Consider the use of urine toxicologic screens, especially with the occurrence of oversedation or respiratory depression or the suspicion of unsanctioned drug use. Intravenous PCA is an acceptable technique for pain management. Offering the patient some degree of control, within specified limits, helps reduce negotiation and confrontation with hospital staff. Care must be taken, however, to monitor closely for evidence of tampering with the PCA device. Tapering and discontinuation of pain therapy should proceed according to a predetermined schedule, usually over 3 to 4 weeks. At discharge, clear instructions should be provided, along with a limited supply of pain medication, and only one physician should be responsible for any refills. Aberrant drug-related behaviors should not be tolerated. Some patients may require transfer to a detoxification center rather than discharge to home. Patients with a remote history of substance abuse do not necessarily require special treatment and can be managed with standard techniques. If the risk of relapse is deemed high, however, efforts should be made to rely minimally on systemic opioid analgesics in favor of other modalities, including single or continuous peripheral nerve blocks or epidural analgesia. Consultation with an addiction specialist should be obtained, and intensification of a formal relapse prevention program should be considered.

PREVENTION Tolerance is a predictable neurophysiologic response to continued opioid exposure. The possibility of tolerance is not a reason to avoid analgesic therapy if it is indicated. Propensity toward addiction is more a characteristic of the person using the drug than of the drug itself. The risk of creating a drug addiction problem when opioids are part of an analgesia plan for acute pain control is extremely low and is no reason to withhold therapy or to underdose.

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Care must be taken to prevent withdrawal after the transition to epidural therapy or during the tapering of therapy as pain resolves. A daily 10% to 50% dose reduction is usually well tolerated. Conversion to methadone before weaning can be helpful because of methadone’s longer half-life. The addition of clonidine 6 μg/kg per day, divided in four to six doses, can help prevent many autonomic features of withdrawal; this dose can be increased to 17 μg/kg per day as necessary and tolerated. Once symptoms are suppressed, clonidine can be weaned over several days.

Further Reading

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Fukunaga AF, Alexander GE, Stark CW: Characterization of the analgesia actions of adenosine: Comparison of adenosine and remifentanil infusions in patients undergoing major surgical procedures. Pain 101:129-138, 2003. Goyagi T, Tanaka M, Nishikawa T: Oral clonidine premedication enhances postoperative analgesia by epidural morphine. Anesth Analg 89: 1487-1497, 1999. Groudine SB, Fisher HAG, Kaufman RP Jr, et al: Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy. Anesth Analg 86:235-259, 1998. Guignard B, Bossard AE, Coste C, et al: Acute opioid tolerance: Intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology 93:409-417, 2000. Mitra S, Sinatra RS: Perioperative management of acute pain in the opioiddependent patient. Anesthesiology 101:212-227, 2004. Rapp SE, Ready LB, Nessly ML: Acute pain management in patients with prior opioid consumption: A case-controlled retrospective review. Pain 61:195-201, 1995. Steindler EM: ASAM addiction terminology. In Graham AW, Schultz TK (eds): Principles of Addiction Medicine, 2nd ed. Chevy Chase, Md, American Society of Addiction Medicine, 1998, pp 1301-1304. Weissman DE, Haddox JD: Opioid pseudoaddiction: An iatrogenic syndrome. Pain 36:363-366, 1989.

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De Kock M, Lavand’homme P, Waterloos H: “Balanced analgesia” in the perioperative period: Is there a place for ketamine? Pain 92:373-380, 2001. Dirks J, Fredensborg BB, Christensen D, et al: A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy. Anesthesiology 97:560-564, 2002. Doverty M, Somogyii AA, White JM, et al: Methadone maintenance patients are cross-tolerant to the antinociceptive effects of morphine. Pain 93:155-163, 2001.

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Stuart Grant Case Synopsis A 62-year-old man undergoing unilateral total knee arthroplasty has lumbar plexus and sciatic nerve perineural catheters placed for surgical anesthesia and postoperative analgesia. He receives ropivacaine 0.2% by patient-controlled infusion through the lumbar plexus catheter and ropivacaine 0.2% as a continuous infusion via the sciatic nerve catheter. In the recovery room he is pain free, but during the first postoperative night he complains of pain. This is managed using bolus 0.5% ropivacaine, but the next day, the physical therapist and surgeon complain because of the profound motor block.

PROBLEM ANALYSIS Definition Numerous studies have shown that perineural local anesthetic infusions provide profound analgesia. These techniques have been used to provide both intraoperative anesthesia and postoperative analgesia. Certain complications are block specific, such as a pneumothorax with classic (non-“plumbbob”) supraclavicular or infraclavicular blocks or epidural spread with a lumbar plexus block. This chapter does not discuss block-specific complications; rather, the focus is on those complications that can occur using continuous perineural local anesthetic infusions at any insertion site. A variety of complications have been reported, including the following: ●

● ● ● ● ● ● ●

Insertion difficulty or inability to insert a catheter, leading to block failure Local anesthetic toxicity Catheter migration into a vessel Retained catheter fragments Infectious complications Neurologic complications Prolonged motor block Pain during injection or infusion via the perineural catheter

Recognition The clinical features of local anesthetic toxicity are discussed in Chapter 56. The clinical features of infectious complications include the following: ●

● ● ●

Late onset of symptoms, 2 to 3 days after peripheral nerve catheter placement Tissue erythema and swelling at catheter insertion site Leukocytosis and fever Pain and tenderness at catheter insertion site

282

The clinical features of neurologic complications include the following: ●

●

●

Prolonged motor block long after cessation of local anesthetic infusion Reduced touch or paresthesias that persist or worsen after cessation of infusion Pain that is neuropathic in nature

The clinical features of motor block and inadequate analgesia include the following: ● ● ● ●

Numbness and perception of a heavy or weak extremity Loss of proprioception Increasing or high patient-reported pain score Increased opioid-related side effects

Risk Assessment The incidence of complications following peripheral nerve block is low and must be balanced against the risks of general anesthesia and central neuraxial techniques. Auroy and coworkers reported the incidence of serious complications related to regional anesthesia in a prospective study using data from 103,730 cases. The incidence of cardiac arrest and neurologic injury related to regional anesthesia was low, but both complications were more than three standard deviations greater after spinal anesthesia than after other regional procedures. These data did not discriminate between singleinjection and continuous peripheral nerve block techniques, but peripheral nerve blocks in general were associated with fewer neurologic injuries and cardiac arrests than were central neuraxial techniques. Bergman and coworkers retrospectively examined the neurologic complications after 405 consecutive continuous axillary nerve block catheter procedures. They found no greater incidence of neurologic complications using continuous catheter techniques than using single injections for axillary nerve block. Borgeat and colleagues prospectively examined complications associated with interscalene block

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Continuous Nerve Blocks: Perineural Local Anesthetic Infusion

Implications Infection can result in discomfort and limitation of activity. Neurologic complications can result in weakness and chronic pain, with reduced functional capacity after surgery. Careful technique and patient selection are important factors in reducing these complications. Prolonged motor block produced by high local anesthetic concentrations may delay early ambulation but has not been shown to affect long-term functional outcomes following arthroplasty. In fact, patients given either epidural or peripheral nerve catheters after knee arthroplasty have increased rates of recovery for the first 6 weeks after surgery compared with those on opioid analgesia regimens. Failed blocks result in pain and reduced patient satisfaction. This can lead to increased use of opioid analgesics and opioid-related side effects such as respiratory depression, pruritus, nausea, vomiting, and constipation.

MANAGEMENT Infection ● ● ● ●

Remove the infected catheter. Culture the catheter tip and obtain antibiotic sensitivities. Commence treatment with a broad-spectrum antibiotic. Convert to an appropriate multimodal analgesic regimen.

Neurologic Complications ●

Obtain a careful history and complete neurologic examination.

● ●

●

●

Refer the patient to a neurologist. Consider computed tomography to exclude hematoma (e.g., in the psoas compartment around the lumbar plexus; see Chapter 64). Perform early electromyography (EMG) to document any preexisting neurologic deficit, followed by late EMG to identify any perioperative nerve injury. Consider commencing gabapentin (Neurontin), especially in patients with symptoms of neuropathic pain.

Pain Pain should be assessed using the patient-reported analog scale. Peripheral nerve catheter techniques should be part of any balanced analgesic regimen. Use of nonsteroidal antiinflammatory agents and COX-2 enzyme inhibitors should be considered in all cases, unless contraindicated. The postoperative management of peripheral nerve catheters for pain control includes the following: ● Postoperative pain assessment ● Clinical examination for evidence of nerve block

PREVENTION Infectious complications can be reduced by the use of appropriate skin preparations. Chlorhexidine is more effective than iodine-based preparations in this regard. Care must be taken to ensure that the chlorhexidine has dried before needle insertion, because of the potential for neurotoxicity. Additionally, the choice of catheter insertion site is important. For example, a femoral nerve catheter placed in an obese patient with a large pannus is more likely to become infected. Surgeons fully appreciate that best medical practice supports the use of prophylactic antibiotics whenever foreign material is being inserted. The perineural nerve catheter is a foreign material, and if the surgical team prescribes prophylactic antibiotics, it makes sense to start these before peripheral nerve catheter insertion. If the surgeon does not prescribe antibiotics for the patient, the anesthesiologist may want to consider prescribing them for prophylaxis of perineural catheter infection. Evidence regarding the prevention of neurologic perineural catheter complications is scant, but by performing blocks in lightly sedated patients, minimizing pressure when injecting local anesthetics, and stopping injections immediately when pain is experienced, a practitioner may be able to reduce the likelihood of nerve injury. The use of blunt versus sharp needles is often debated in the literature, as is the technique of eliciting paresthesia versus the use of a nerve stimulator. The likelihood of motor block can be reduced by using lower concentrations of drug in perineural local anesthetic infusions. There is also evidence of better sensory versus differential motor blockade with ropivacaine than bupivacaine. Careful attention to the details of catheter fixation at the time of insertion, use of bolus local anesthetic via the catheter for breakthrough pain, and use of a patient-controlled regional anesthesia catheter can help reduce the likelihood of postoperative pain.

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and shoulder surgery and found no differences between catheter techniques and single-injection blocks. Leaving a catheter in situ entails the potential risk of infection and catheter migration into a vessel. This risk must be balanced against the improved analgesia. Although Cuvillon and coworkers were able to isolate bacterial colonization in 57% of 208 femoral nerve catheters, no clinically relevant infectious complications occurred. There was one case (0.1% incidence) of a serious infection (abscess), and superficial erythema was observed in 0.7% of the patients in Borgeat’s series (cited earlier). Only superficial skin infections (5% incidence) were reported in the recent series by Boezaart and associates. Only one case report of migration into a vessel has been reported in the literature, so the incidence of that complication is unknown. After resolution of the primary block with long-acting amide local anesthetics, inadvertent catheter dislodgment or incorrect initial catheter positioning is the most common cause of pain 12 hours or more after the initial block. This can occur in up to 10% to 20% of patients and is by far the most common complication of continuous perinural nerve blocks. Some patients with infusions of low concentrations of local anesthetics in a functional perineural catheter suffer breakthrough pain. Use of a patient-controlled bolus, in addition to the background basal infusion, can reduce the severity of breakthrough pain. As the case synopsis illustrates, the challenge for the clinician is to balance the risk of motor block or even local anesthetic toxicity against the patient’s discomfort from inadequately controlled pain.

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Further Reading Auroy Y, Narchi P, Messiah A, et al: Serious complications related to regional anesthesia: Results of a prospective survey in France. Anesthesiology 87:479-486, 1997. Bergman BD, Hebl JR, Kent J, Horlocker TT: Neurologic complications of 405 consecutive continuous axillary catheters. Anesth Analg 96: 247-252, 2003. Boezaart AP, De Beer JF, Nell ML: Early experience with continuous cervical paravertebral block using a stimulating catheter. Reg Anesth Pain Med 28:406-413, 2003. Borgeat A, Dullenkopf A, Ekatodramis G, Nagy L: Evaluation of the lateral modified approach for continuous interscalene block after shoulder surgery. Anesthesiology 99:436-442, 2003. Borgeat A, Kalberer F, Jacob H, et al: Patient-controlled interscalene analgesia with ropivacaine 0.2% versus bupivacaine 0.15% after major open shoulder surgery: The effects on hand motor function. Anesth Analg 92:218-223, 2001.

Capdevila X, Barthelet Y, Biboulet P, et al: Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology 91:8-15, 1999. Cuvillon P, Ripart J, Lalourcey L, et al: The continuous femoral nerve block catheter for postoperative analgesia: Bacterial colonization, infectious rate and adverse effects. Anesth Analg 93:1045-1049, 2001. Gillespie WJ, Walenkamp G: Antibiotic prophylaxis for surgery for proximal femoral and other closed long bone fractures. Cochrane Database Syst Rev 2000(2):CD000244, 2000. Grant SA, Nielsen KC, Greengrass RA, et al: Continuous peripheral nerve block for ambulatory surgery. Reg Anesth Pain Med 26:209-214, 2001. Tuominen MK, Pere P, Rosenberg PH: Unintentional arterial catheterization and bupivacaine toxicity associated with continuous interscalene brachial plexus block. Anesthesiology 75:356-358, 1991. Yentur EA, Luleci N, Topcu I, et al: Is skin disinfection with 10% povidone iodine sufficient to prevent epidural needle and catheter contamination? Reg Anesth Pain Med 28:389-393, 2003.

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Persistent Paresthesia Terese T. Horlocker

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Case Synopsis A 58-year-old woman with insulin-dependent diabetes mellitus is scheduled to undergo total wrist arthroplasty. An axillary block is performed with the transaxillary technique using 45 mL of 1.5% mepivacaine containing 5 μg/mL of epinephrine. Total tourniquet time is 130 minutes. After surgery, the patient has residual numbness in her fourth and fifth fingers. Electromyography performed at 8 weeks demonstrates a diffuse sensorimotor neuropathy and an ulnar neuropathy at the level of the axilla. The symptoms slowly and completely resolve over a period of 10 weeks.

Definition Perioperative nerve injuries have long been recognized as a complication of regional anesthesia. Fortunately, severe or disabling neurologic complications rarely occur. Cheney and coworkers examined the American Society of Anesthesiologists’ closed claims database to determine the role of nerve damage in malpractice claims filed against anesthesia care providers. Of the 4183 claims reviewed, 670 (16%) were for anesthesiarelated nerve injury. The most frequent sites of injury were the ulnar nerve (190 claims), brachial plexus (137 claims), lumbosacral roots (105 claims), and spinal cord (84 claims). Upper extremity nerve injuries were more often associated with general anesthesia. However, spinal cord and lumbosacral nerve root injuries having identifiable causes were associated predominantly with regional anesthetic techniques and were related to paresthesias during needle or catheter placement or pain during injection of local anesthetic. It is also notable that despite intensive medicolegal investigation, a definite mechanism of injury is rarely determined. The lack of an apparent mechanism often leads the patient (and consulting specialists) to assume that something must have been done incorrectly during the perioperative period to cause the nerve injury. This review demonstrates that although perioperative nerve injury is a significant source of anesthesia-related claims, the exact mechanism of injury is often unclear. The potential risk of nerve injury due to needle trauma, local anesthetic toxicity, or neural ischemia during regional anesthetic techniques increases the probability that neurologic deficits will be attributed to anesthetic agents. However, several series have demonstrated that neurologic deficits are more likely to be associated with a cause that is unrelated to regional anesthesia. For example, Horlocker and colleagues reported 61 nerve injuries after 1614 upper extremity surgical procedures performed under axillary block, for a 3.8% overall frequency of neural dysfunction. Only 7 of the 61 injuries (11%) were the result of the anesthetic; the remaining 54 (89%) were related to surgical factors. The anesthesiologist must therefore be aware of the surgical, medical, and anesthetic risk factors associated with perioperative nerve injuries to reduce the incidence of neurologic complications.

Recognition Neurologic complications associated with regional anesthesia can be divided into two broad categories: those that are unrelated to the regional anesthetic but coincide temporally, and those that are the direct result of the regional anesthetic agent or technique. Causes of nerve injury unrelated to the regional anesthetic agent or technique include the following: ● ● ● ● ● ●

Surgical trauma Surgical retractor Patient positioning Tourniquet ischemia Improperly placed dressings or casts Preexisting neurologic diseases

Causes of nerve injury directly related to the regional anesthetic agent or technique include the following: ● ● ● ●

Direct or indirect needle or catheter trauma Neural ischemia Local anesthetic neurotoxicity Infection

Risk Assessment Trauma, ischemia, infection, and local anesthetic neurotoxicity contribute to the development of neurologic complications after peripheral neural block. Patient and anesthetic factors that may be associated with an increased risk of neurologic complications after regional anesthetic agents or techniques include the following: ● ● ● ●

Preexisting neurologic disorder or diagnosis Needle bevel and configuration Local anesthetic (drug and concentration) Use of vasoconstrictors

The elicitation of a paresthesia while performing an axillary block may represent direct needle-induced trauma and increased risk of persistent paresthesia associated with regional anesthesia. Selander and coworkers reported a 2.8% incidence of postoperative nerve injury in patients in whom paresthesia was sought during axillary block, compared with a 0.8% incidence in those undergoing a perivascular technique (the difference was not statistically significant, however). 285

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The neurologic deficits ranged from slight hypersensitivity to severe paresis and persisted from 2 weeks to more than 1 year. Theoretically, using a nerve stimulator to localize neural structures should allow a high success rate without increasing the risk of neurologic complications, but this hypothesis has not been formally tested. Fanelli and colleagues prospectively evaluated 3996 patients undergoing sciatic-femoral, axillary, and interscalene blocks using multiple-injection and nerve stimulator techniques. During the first month after surgery, 69 patients (1.7%) developed neurologic dysfunction; recovery was complete in all but 1 patient by 4 to 12 weeks. (This frequency and outcome are similar to those reported using a paresthesia technique.) Direct needle trauma also may cause disturbances in nerve conduction without clinical evidence of a neuropathy. After sciatic nerve impalement with an axillary block needle in rats, histologic changes consistent with axonal injury persisted for 28 days. However, clinical evidence of hind leg hyposensitivity was present for only 2 weeks. Similar findings have been reported after sciatic nerve penetration with a microneurographic electrode in rats. These data suggest that a subclinical neuropathy may occur with greater frequency and longer duration than anticipated. Needle gauge, type (short versus long bevel), and bevel configuration may also influence the degree of nerve injury, although evidence from animal models is unclear, and there are no relevant human studies. The passage into and presence of an indwelling catheter in a peripheral nerve sheath represent an additional source of direct trauma. Although difficulty during catheter insertion may lead to vessel puncture, tissue trauma, and bleeding, significant complications are uncommon, and permanent sequelae are rare. The largest series of continuous brachial plexus blocks with indwelling catheters included only 405 patients. Bergman and coworkers reported nine complications in eight patients, for an overall frequency of 2.2%, including one each of the following: localized infection (treated with catheter removal and antibiotics), axillary hematoma, and retained catheter fragment requiring surgical excision. Two patients reported signs and symptoms of systemic local anesthetic toxicity manifesting as preseizure activity. Four patients (1%) reported new neurologic deficits postoperatively, only two of which were anesthesia related. Peripheral nerves have a dual blood supply consisting of intrinsic endoneural vessels and extrinsic epineural vessels. A reduction in or disruption of nerve blood flow may result in neural ischemia. Intraneuronal injection of volumes as small as 50 to 100 μL may generate intraneuronal pressures that exceed capillary perfusion pressure for as long as 10 minutes, thus causing neural ischemia. Endoneural hematomas have also been reported after intraneuronal injection. Epineural blood flow is responsive to adrenergic stimuli. Theoretically, the use of local anesthetic solutions containing epinephrine can produce local nerve ischemia, especially in patients with microvascular disease; however, the actual risk of significant neurologic ischemia in patients given local anesthetic solutions containing vasoconstrictors is unknown. Neurologic complications after regional block may be a direct result of local anesthetic toxicity. There is both laboratory and clinical evidence that local anesthetic solutions are potentially neurotoxic. Differences in neurotoxicity are dependent on pKa, lipid solubility, protein binding, and potency.

In histopathologic, electrophysiologic, and neuronal cell models, lidocaine and tetracaine appear to have a greater potential for neurotoxicity than does bupivacaine at clinically relevant concentrations. Additives such as epinephrine and bicarbonate may also affect neurotoxicity. Patients with microangiopathic processes, such as diabetes, demonstrate a reduction in neural blood flow and local anesthetic uptake. Concurrently, the presence of a peripheral neuropathy reduces the amount of local anesthetic required to produce neural block and toxicity. Therefore, these patients are more sensitive to the clinical effects of local anesthetic solutions. The concentration of local anesthetic selected, as well as the use of vasoconstrictors, must be carefully evaluated in patients with peripheral neuropathies, because prolonged exposure to or high concentrations of local anesthetic solutions within the neurovascular compartment may result in permanent neurologic deficits. The presence of a preexisting neurologic condition may predispose a nerve to injury by the neurotoxic effects of local anesthetics. The presumed mechanism is a “double crush” of the nerve at two locations, resulting in a nerve injury of clinical significance. The double-crush concept suggests that nerve damage caused by traumatic needle placement, local anesthetic toxicity, or neural ischemia during the performance of regional anesthesia may worsen neurologic outcome in the presence of an additional patient factor or surgical injury.

Implications Neurologic deficits that arise within the first 24 hours most likely represent extraneural or intraneural hematoma, intraneural edema, or a lesion involving a sufficient number of nerve fibers to permit immediate diagnosis. However, in many cases of persistent paresthesias after regional anesthesia, the symptoms of nerve injury do not develop until days to weeks later. The presentation of late disturbances in nerve function suggests an alternative cause, such as tissue reaction or scar formation, although it is unknown whether this reaction is due to mechanical trauma, chemical toxicity, or both.

MANAGEMENT Major complications after regional anesthetic techniques are rare but can be devastating to the patient and the anesthesiologist. Prevention and management begin during the preoperative visit with a careful evaluation of the patient’s medical history and a discussion of the risks and benefits of the available anesthetic techniques. Patients with preexisting neurologic disorders such as multiple sclerosis, poliomyelitis, or amyotrophic lateral sclerosis may develop new neurologic deficits perioperatively, and it is often difficult to differentiate between surgical and anesthetic causes. In these patients, if a regional anesthetic is indicated (or requested), the patient’s preoperative neurologic examination should be formally documented, and the patient must be made aware of the possible progression of the underlying disease process. Stable preexisting neurologic conditions (e.g., documented peripheral neuropathy, inactive lumbosacral radiculopathy, hemiparesis due to an old cerebrovascular accident) are not contraindications to the use of regional anesthesia. However, the

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timely evaluation with a multidisciplinary approach involving neurology, radiology, internal medicine, and surgery will allow appropriate treatment.

PREVENTION Further Reading Preventive measure include all of the following: ● ● ●

● ● ●

Appropriate patient selection Meticulous regional anesthetic technique Avoidance of direct needle trauma and intraneuronal injection Weighing of the risks and benefits of vasoconstrictors Use of appropriate local anesthetic concentrations Prompt evaluation of perioperative neuropathies

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Meticulous technique must be used during any central neuraxial or peripheral nerve block. Paresthesias elicited during needle or catheter placement or injection of local anesthetic should be documented. Painful paresthesias are associated with nerve injury and should be avoided. The total local anesthetic dose and concentration, as well as the addition of vasoconstrictors, must be carefully considered. Hadzic and associates recently evaluated the use of peripheral nerve stimulators to identify the nerves to be blocked to achieve regional anesthesia. They found that the nerve stimulators in common use in the United States vary greatly in terms of accuracy of current output and manufacturer-selected electrical characteristics (e.g., current duration, stimulating frequency, maximum voltage output). They also noted that most authors recommend obtaining a motor response with a current of 0.5 mA or less before injecting a local anesthetic, and they suggested that stimulation at currents higher than 0.5 mA may result in failure of the block; this was attributed to the needle being too far from the nerve to be blocked. In contrast, injection after nerve stimulation thresholds of 0.1 mA or less may increase the risk of nerve injury because of the possibility of intraneuronal local anesthetic injection. Finally, although postoperative neurologic complications may present immediately after surgery, some require days to weeks to emerge. Should such neurologic dysfunction occur,

Auroy Y, Narchi P, Messiah A, et al: Serious complications related to regional anesthesia: Results of a prospective survey in France. Anesthesiology 87:479-486, 1997. Bergman BD, Hebl JR, Kent J, Horlocker TT: Neurologic complications of 405 consecutive continuous axillary catheters. Anesth Analg 96: 247-252, 2003. Cheney FW, Domino KB, Caplan RA, Posner K: Nerve injury associated with anesthesia: A closed claims analysis. Anesthesiology 90: 1062-1069, 1999. Fanelli G, Casati A, Garancini P, et al: Nerve stimulator and multiple injection technique for upper and lower limb blockade: Failure rate, patient acceptance, and neurologic complications. Anesth Analg 88:847-852, 1999. Hadzic A, Vloka J, Hadzic N, et al: Nerve stimulators used for peripheral nerve blocks vary in their electrical characteristics. Anesthesiology 98:969-974, 2003. Horlocker TT, Kufner RP, Bishop AT, et al: The risk of persistent paresthesia is not increased with repeated axillary block. Anesth Analg 88:382-387, 1999. Kalichman MW, Calcutt NA: Local anesthetic-induced conduction block and nerve fiber injury in streptozotocin-diabetic rats. Anesthesiology 77:941-947, 1992. Neal JM: Effects of epinephrine in local anesthetics on the central and peripheral nervous systems: Neurotoxicity and neural blood flow. Reg Anesth Pain Med 28:124-134, 2003. Neal JM, Hebl JR, Gerancher JC, Hogan QH: Brachial plexus anesthesia: Essentials of our current understanding. Reg Anesth Pain Med 27: 402-428, 2002. Rice ASC, McMahon SB: Peripheral nerve injury caused by injection needles used in regional anaesthesia: Influence of bevel configuration, studied in a rat model. Br J Anaesth 69:433-438, 1992. Selander D, Dhuner KG, Lundborg G: Peripheral nerve injury due to injection needles used for regional anesthesia. Acta Anaesthesiol Scand 21: 182-188, 1977. Selander D, Edshage S, Wolff T: Paresthesiae or no paresthesiae? Acta Anaesthesiol Scand 23:27-33, 1979. Selander D, Sjostrang J: Longitudinal spread of intraneurally injected local anesthetics. Acta Anaesthesiol Scand 22:622-634, 1978. Stan TC, Krantz MA, Solomon DL, et al: The incidence of neurovascular complications following axillary brachial plexus block using a transarterial approach: A prospective study of 1000 consecutive patients. Reg Anesth 20:486-492, 1995.

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Anticoagulation Initiation and Reversal for Cardiac Surgery

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Peter Tassani-Prell Case Synopsis

PROBLEM ANALYSIS Definition Unfractionated heparin is a heterogeneous mixture of sulfated oligosaccharides with molecular weights ranging from 5000 to 50,000 daltons. The anticoagulant activity of heparin is initiated via binding to AT-III, which results in a conformational change that increases its inactivation of thrombin and factors Xa and IXa. Thus, in the setting of low AT-III activity, the clinical effect of heparin is reduced.

Recognition, Risk Assessment, and Implications There is wide individual variability in the clinical anticoagulant response to a single dose of heparin. This necessitates evaluation with on-site or laboratory coagulation testing. Owing to the extreme importance of ensuring sufficient anticoagulation before initiating CPB, on-site testing is preferred. A number of options are available to clinically assess heparininduced anticoagulation. The activated partial thromboplastin time is sensitive to low plasma heparin concentrations (0.1 to 1.0 units/mL). However, with the high doses of heparin required for the initiation of CPB, values exceed this method’s detection limit. The ACT assesses the clinical anticoagulation effect of the large doses of heparin (200 to 400 units/kg) required for the initiation of CPB. Though somewhat controversial, ACT values between 400 and 600 seconds are generally considered safe for anticoagulation during routine CPB, based on the observation of a lack of fibrin deposits on extracorporeal circuits. Even so, ACT values may be misleading because they

can be prolonged by factors other than heparin, such as hypothermia, hemodilution, and thrombocytopenia. Further, clinical investigations have shown that ACT values correlate poorly with plasma heparin concentrations in patients during mild hypothermic CPB. Commercially available ACT measurement devices use two different activators. Celiteactivated clotting time is prolonged by aprotinin, which may lead to inadequate heparinization during CPB. Kaolinactivated clotting time is unaffected by aprotinin. If aprotinin is used and only celite ACT testing is available, most clinicians prefer to maintain the ACT at greater than 800 seconds during CPB to ensure adequate heparinization. Heparin-protamine titration has been proposed as an alternative and more specific method for ensuring adequate heparin levels or protamine reversal in patients during CPB. However, the advantages of heparin-protamine titration (if any) over traditional methods have yet to be proved. Heparin resistance results in an unanticipated small increase in ACT values after initial and subsequent heparin dosing. Approximately 1 in 2000 patients has a heterozygotic deficiency (40% to 70% activity) of AT-III and is thus predisposed to developing deep vein thrombosis and pulmonary embolism. Significant reductions in AT-III levels may also occur secondary to AT-III consumption during heparin therapy. Other causes of heparin resistance include left ventricular clot, use of oral contraceptives, and thrombocytosis. These entities may be due to reduced plasma concentrations of heparin caused by its increased binding to plasma proteins and endothelium. Heparin may cause thrombocytopenia via immune- and nonimmune-mediated mechanisms. There are two types of heparin-induced thrombocytopenia (HIT) that can result from heparin use. Type I is nonimmune mediated, and 291

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An 81-year-old woman with dyspnea at rest due to aortic stenosis (valve area 0.4 cm2, mean gradient 50 mm Hg) presents for aortic valve replacement. Past medical history is significant for a recent pulmonary embolism, for which she received intravenous heparin therapy. At the time of operation, antithrombin III (AT-III) levels are low, and the activated partial thromboplastin time is elevated. After heparinization (375 units/kg), the activated clotting time (ACT) increases to 325 seconds. An additional 125 units/kg heparin and 2000 units of AT-III concentrate are given. Thereafter, the ACT increases to 866 seconds, and cardiopulmonary bypass (CPB) is commenced without further complications.

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type II is immune mediated. For standardization, the term non-heparin immune-associated thrombocytopenia is recommended for type I HIT. This is a benign condition, with no heparin-dependent antibodies present. The term heparininduced thrombocytopenia is recommended for type II HIT, in which heparin-dependent antibodies are detectable and produce thrombocytopenia.

MANAGEMENT Three different aspects of anticoagulation during cardiac surgery with CPB are discussed: routine management using anticoagulation with heparin and neutralization with protamine, management of AT-III deficiency (as in the case synopsis), and HIT. For the initiation of CPB, the heparin dose is based on body weight (300 to 400 units/kg, or 3 mg/kg). It is essential to obtain an ACT of about 480 seconds before initiating CPB. Determining the ACT before initiating CPB allows one to detect inadequate heparin dosing or AT-III deficiency. It is also recommended that the heparin injection be given via a central venous line after aspirating blood to ensure central vascular delivery. Patient-specific heparin dosing can be automatically extrapolated by several commercially available heparin monitoring systems. Subsequent heparin can be dosed empirically during CPB (e.g., 5000 to 10,000 units/hour, one third the initial dose every hour) if the ACT is less than 400 to 480 seconds or if plasma heparin concentration values are appropriate. Some commercial systems also calculate a heparin concentration corresponding to an ACT greater than 480 seconds. Hypothermia and hemodilution prolong ACT values independent of heparin concentration. Thus, basing subsequent heparin doses on ACT values may lead to inadequate inhibition of thrombin activity and subclinical thrombosis, fibrinolysis, and depletion of coagulation factors and platelets. Maintenance of patient-specific heparin concentrations during CPB may result in more accurate heparin dosing, more complete thrombin inhibition, and reduced postoperative bleeding and blood product use. With suspected heparin resistance, one must first confirm that the heparin was indeed given intravenously, followed by the administration of additional heparin from another vial or lot to exclude lot-specific reduced heparin activity. If the ACT values still remain below those expected, despite large doses of heparin, AT-III concentrates should be given, with an initial dose of at least 2000 units. Because of the danger of AT-III deficiency (thrombosis during CPB), the routine clinical practice in some centers is to confirm adequate AT-III levels in patients before any operation is performed requiring extracorporeal circulation. Non-heparin immune-associated thrombocytopenia (type I HIT) implies absent heparin-dependent antibodies. This entity is probably caused by direct nonimmune platelet activation by heparin. Type I HIT is usually associated with larger doses of heparin. In contrast, type II HIT can occur with any heparin dose. Further, type I HIT occurs earlier in the clinical treatment course (usually within 4 days) in 30% of patients receiving intravenous heparin therapy. The induced platelet abnormality is usually mild and reversible, even with

continued heparin administration. Type I HIT is self-limited and usually causes no important complications (e.g., thrombosis). Heparin therapy is continued despite low platelet counts. The clinical importance of type I HIT lies in the necessity to differentiate it from the more serious type II HIT. Type II HIT (or heparin-induced thrombocytopenia with thrombosis [HITT] syndrome) is an immune-mediated reaction to heparin that is often underdiagnosed and may lead to venous and arterial thrombosis. Type II HIT exists as three distinct entities: (1) latent (antibodies without thrombocytopenia), (2) HIT (antibodies with thrombocytopenia), and (3) HITT (antibodies with thrombocytopenia and thrombosis). Type II HIT is potentially more dangerous than type I HIT because it can be associated with thromboembolic complications (absent in type I). About 0.5% to 3% of patients given heparin develop type II HIT and moderate thrombocytopenia. In some, this leads to venous or arterial thrombosis. Thrombosis frequently leads to disastrous clinical sequelae, including loss of limbs and even death. The basis for this severe adverse drug reaction is production of an immunoglobulin G antibody that reacts with heparin and platelet factor 4 antigenic complexes. The diagnosis of type II HIT is made with the heparin-induced platelet aggregation (HIPA) assay. Alternatively, an enzyme-linked immunosorbent assay (ELISA) can detect the binding of antibodies to immobilized heparin–platelet factor 4 antigenic complexes. For patients with type II HIT who will be exposed to CPB, treatment generally includes either the use of alternative anticoagulants or combined treatment with platelet function inhibitors and heparin. Examples include the following: ●

●

●

●

●

Danaproid sodium. This is a low-molecular-weight heparinoid (i.e., a mixture of dermatan, glycosaminoglycans, and chondroitin sulfates) that does not contain heparin. Ancrod. This is an inhibitor of fibrin derived from Malayan pit viper venom. It provides a treatment option for patients with type II HIT who require anticoagulation. Hirudin and lepirudin. This combination is also used for anticoagulation in type II HIT patients. Hirudin is a direct inhibitor of thrombin, acting independently of cofactors such as antithrombin. Lepirudin (a form of recombinant hirudin derived from yeast cells) is a highly specific, direct, irreversible inhibitor of thrombin (one molecule of lepirudin binds with one of thrombin). Typically, patients given hirudin have more perioperative bleeding, require multiple allogeneic blood product transfusions, and have higher rates of mediastinal re-exploration for bleeding after CPB. Bivalirudin. This is a direct thrombin inhibitor and an analogue of the peptide fragment hirugen derived from hirudin. Bivalirudin is approved by the U.S. Food and Drug Administration for patients with unstable angina undergoing coronary angioplasty who are also receiving aspirin. Randomized clinical trials in cardiac surgery are currently in progress. Argatroban. This is a synthetic, competitive thrombin inhibitor derived from L-arginine. It reversibly binds to thrombin’s catalytic site. One recent case report described the successful use of argatroban as an alternative to heparin during CPB in a patient with type II HIT, end-stage renal failure, and ischemic cardiomyopathy with ventricular fibrillation.

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●

Type I is the most common, consisting of hypotension from too rapid administration of protamine. It is likely related to the release of histamine, and hypotension can be associated with a marked decrease in systemic vascular resistance. Type II is anaphylaxis and can be mediated by immunoglobulins. It occurs more frequently in patients with a history

●

of fish allergy. Subsequent release of histamine and leukotrienes results in systemic and pulmonary capillary leakage. Type III is associated with the formation of heparinprotamine complexes. Pulmonary macrophages activate complement and leukocyte aggregation, causing the release of free radicals and activation of the arachidonic acid pathway, which leads to the formation of thromboxane. This causes intense pulmonary vasoconstriction, pulmonary hypertension, and reduced left atrial pressure. The net result is right heart chamber dilatation and heart failure. Fortunately, type III responses are very uncommon.

PREVENTION The appearance of heparin resistance can delay surgery and disrupt the operating room schedule. Consequently, some clinicians advise preoperative AT-III level screening for all patients having cardiac surgery requiring CPB. Determination of the heparin dose-response curve can also alert clinicians to heparin resistance before CPB. This allows advance planning for subsequent heparin dosing. If possible, surgery is delayed in patients with type II HIT until antibody titers are absent. New drugs, such as bivalirudin, may be useful alternatives to heparin in such patients. To eliminate protamine reactions, antihistamines can be used. Also, protamine should be given slowly, preferably via a peripheral vein after substantial dilution. Some surgeons inject it into the aortic root to bypass the lungs during its initial distribution. Although heparin-bonded CPB circuitry may allow lower doses of intravenous heparin, this technology remains unproved.

Further Reading Anderson EF: Heparin resistance prior to cardiopulmonary bypass. Anesthesiology 64:504-507, 1986. Bull BS, Huse WM, Brauer FS, et al: Heparin therapy during extracorporeal circulation. II. The use of a dose-response curve to individualize heparin and protamine dosage. J Thorac Cardiovasc Surg 69:685-689, 1975. DeBois WJ, Liu J, Lee LY, Girardi LN: Diagnosis and treatment of heparininduced thrombocytopenia. Perfusion 18:47-53, 2003. Despotis GJ, Joist JH, Hogue CW Jr, et al: The impact of heparin concentration and activated clotting time monitoring on blood conservation. J Thorac Cardiovasc Surg 110:46-54, 1995. Despotis GJ, Joist JH, Hogue CW Jr, et al: More effective suppression of hemostatic system activation in patients undergoing cardiac surgery by heparin dosing based on heparin blood concentrations rather than ACT. Thromb Haemost 76:902-908, 1996. Despotis GJ, Levine V, Joist JH, et al: Antithrombin III during cardiac surgery: Effect on response of activated clotting time to heparin and relationship to markers of hemostatic activation. Anesth Analg 85:498-506, 1997. Edwards JT, Hamby JK, Worrall NK: Successful use of argatroban as a heparin substitute during cardiopulmonary bypass: Heparin-induced thrombocytopenia in a high-risk cardiac surgical patient. Ann Thorac Surg 75:1622-1624, 2003. Greinacher A: The use of direct thrombin inhibitors in cardiovascular surgery in patients with heparin-induced thrombocytopenia. Semin Thromb Hemost 30:315-327, 2004. Koster A, Spiess B, Chew DP: Effectiveness of bivalirudin as a replacement for heparin during cardiopulmonary bypass in patients undergoing coronary artery bypass grafting. Am J Cardiol 93:356-359, 2004.

CARDIOTHORACIC & VASCULAR SURGERY

The management of patients with HIT antibodies who require heart surgery is challenging, because heparin anticoagulation is an integral part of cardiac operations, with or without extracorporeal circulation. A standard approach to patients with HIT has not been established, although several options have been proposed for using the previously listed nonheparinoid anticoagulants. However, there is little experience with approved alternative anticoagulants, specific antidotes are not available, and special tests (which are not readily available) are needed to ascertain their effectiveness. In patients with a history of HIT but no detectable antibodies, heparin is currently the safest approach to the highdose anticoagulation required for CPB. However, before and after surgery, alternative anticoagulants should be used. The risk of clinical HIT after cardiac surgery may be reduced by substituting low-molecular-weight heparin for postoperative anticoagulation in patients with type II HIT antibodies found immediately before surgery. Alternatively, hirudin can be used as the anticoagulant for CPB in these patients. If hirudin is used, the ecarin clotting time (instead of ACT) can be used to guide anticoagulation therapy during CPB. A more recent approach in patients with a history of HIT is to selectively block platelet aggregation using monoclonal antibodies directed toward glycoprotein IIb/IIIa (GP IIb/IIIa) or to use a specific GP IIb/IIIa inhibitor (e.g., tirofiban). An 80% block of GP IIb/IIIa receptors and suppressed platelet aggregation (<20%) permit the use of unfractionated heparin and CPB in the usual way. After CPB, as usual, unfractionated heparin is neutralized with protamine. After approximately 2 to 12 months, most patients with a history of type II HIT no longer have laboratory evidence of heparin-induced platelet aggregation. If so, heparin use is likely acceptable. However, caution is advised with regard to further heparin exposure during the postoperative period (e.g., heparin flushes, cardiac catheterization). Use of aspirin or dipyridamole for anticoagulation in patients with type II HIT has been successful. Heparin reversal after CPB is usually accomplished with protamine, a protein derived from salmon sperm. The appropriate dosage is controversial. Most cardiac anesthesiologists use 1.0 to 1.3 mg/100 units of previously administered heparin. Commercial systems for whole blood, circulating heparin assays may allow exact titration of the required amount of protamine; however, despite their theoretical advantage, a fixed dose based on the amount of heparin used is more conventional. Additional protamine may be given about 30 minutes after heparin reversal. Protamine has a high number of positively charged arginine residues that form stable complexes with negatively charged heparin and are eliminated via the reticuloendothelial system. Protamine has been associated with significant clinical complications, consisting of three major types of adverse responses:

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Levy JH: New concepts in anticoagulation and reversal. In Stanley TH, Bailey PL (eds): Anesthesiology and the Cardiovascular Patient. Norwell, Mass, Kluwer Academic Publishers, 1996. Makhoul RG, McCann RL, Austin EH, et al: Management of patients with heparin-associated thrombocytopenia and thrombosis requiring cardiac surgery. Ann Thorac Surg 43:617-621, 1987. Messerli FH (ed): Cardiovascular Drug Therapy, 2nd ed. Philadelphia, WB Saunders, 1996. Nuttall GA, Oliver WC Jr, Santrach PJ: Patients with a history of type II heparin-induced thrombocytopenia with thrombosis requiring cardiac surgery with cardiopulmonary bypass: A prospective observational case series. Anesth Analg 96:344-350, 2003. Pravinkumar E, Webster NR: HIT/HITT and alternative anticoagulation: Current concepts. Br J Anaesth 90:676-685, 2003.

Sabbagh AH, Chung GKT, Shuttleworth P, et al: Fresh frozen plasma: A solution to heparin resistance during cardiopulmonary bypass. Ann Thorac Surg 37:466-468, 1984. Sane DC, Califf RM, Topol EJ, et al: Bleeding during thrombolytic therapy for acute myocardial infarction: Mechanisms and management. Ann Intern Med 111:1010-1022, 1989. Visentin GP, Ford SE, Scott JP, et al: Antibodies from patients with heparininduced thrombocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells. J Clin Invest 93:81-88, 1994. Walenga JM, Jeske WP, Prechel MM: Newer insights on the mechanism of heparin-induced thrombocytopenia. Semin Thromb Hemost 30(Suppl 1):57-67, 2004.

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73

Hemodilution and Blood Conservation Glenn P. Gravlee Case Synopsis A 61-year-old, 80-kg man is scheduled for removal and replacement of a total hip prosthesis. He is concerned about blood transfusion and the transmission of infectious diseases, particularly human immunodeficiency virus (HIV). He requests that transfusion of homologous blood be avoided, if possible. He predonated 2 units of autologous blood. During surgery, blood loss is more than 2000 mL, and the hemoglobin level is 7.5 g/dL after both units of autologous blood are given. Vital signs and urine output remain within normal limits. An additional 500 mL of intraoperative blood loss is expected.

PROBLEM ANALYSIS

Complications arising from the transfusion of homologous (also called allogeneic) blood products have been recognized since the beginning of modern transfusion therapy. Bacterial blood contamination was fairly common before the introduction of refrigerated storage and sterile plastic bags. Subsequently, contamination with viruses (e.g., cytomegalovirus, hepatitis B and C, HIV, and human T-cell lymphotropic virus) became a source of greater morbidity. Now, West Nile virus and possibly variant Creutzfeldt-Jakob disease have been added to the list of viral diseases transmissible by blood transfusion. Fortunately, improvements in donor screening and blood component testing have reduced the risk of both HIV and hepatitis C transmission to less than 1 per 1 million units, and that for hepatitis B to about 1 per 137,000 units. Cytomegalovirus remains prevalent in the blood pool, but its transmission is generally not a problem in the absence of clinical immunosuppression. Nevertheless, many blood banks now routinely apply leukoreduction techniques to all cellular blood components before dispensing them, which has greatly reduced the risk of cytomegalovirus transmission. Thus, viral transmission by blood transfusion is now so rare that bacterial contamination once again poses the highest risk for infectious complications, which is 1 in 30,000 red blood cell (RBC) units and 1 in 2000 to 3000 platelet units. Blood group incompatibility and anaphylactic reactions remain rare.

Implications Considerable evidence supports immunosuppression as a significant consequence of blood transfusion. This increases the risk of cancer recurrence and of bacterial infection among transfusion recipients. Large blood loss and hemodilution also raise the question of what constitutes a reasonable minimum hemoglobin level in an anesthetized patient with acceptable intravascular

MANAGEMENT This section focuses on available techniques (Table 73-1) and a cost-benefit analysis of autotransfusion techniques that may reduce or avoid the need for homologous RBC or blood component therapy.

Autologous Predonation Patients can donate blood up to 42 days before operation, which constitutes the maximum storage period for modern

Table 73–1

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Autotransfusion Techniques

Technique

Cost

Risk

Advisability*

Autologous predonation Acute normovolemic hemodilution Intraoperative salvage Postoperative salvage, unwashed Postoperative salvage, washed

Moderate Low

Low Low

Yes No

High Low

Low Moderate

Yes No

Moderate

Low

Yes

*For the patient described in the case synopsis.

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Definition, Recognition, and Risk Assessment

volume and vital signs. This is a surprisingly complex issue, but in general, healthy patients safely tolerate hemoglobin concentrations as low as 6 g/dL. Sicker patients may require hemoglobin concentrations as high as 10 g/dL. Assuming that the hypothetical patient described in the case synopsis is otherwise healthy, the limiting factor may be the rate and predictability of blood loss, because some margin of safety is desirable if sudden additional blood loss should occur. Also, one must consider the possibility of significant postoperative bleeding. Consequently, the patient’s hemoglobin concentration of 7.5 g/dL signals the possible need for homologous transfusion, unless shed blood is being effectively salvaged.

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anticoagulant and storage solutions. The frequency and amount of donation depend on the patient’s ability to tolerate serial phlebotomy while maintaining an adequate hemoglobin level. Typically, a patient donates 2 units of blood per week starting 2 to 4 weeks before surgery. The minimum recommended hemoglobin level for donation is 11 g/dL. To maintain this level, patients are routinely given iron supplementation. Erythropoietin can be used to increase hemoglobin levels during predonation, which enables patients to donate more units; this is quite expensive, however, costing approximately $800 per unit of erythropoietin “manufactured.” Erythropoietin augmentation of autologous predonation may be justified if some combination of the following factors exists: ● ●

● ●

The preoperative timeline is short (e.g., cancer resection). Homologous transfusion is not possible (e.g., Jehovah’s Witness). The patient is anemic. The anticipated surgical blood loss is large (>2000 mL).

Autologous predonation is most effective at avoiding homologous transfusion when used in combination with other autotransfusion techniques, such as intraoperative blood salvage. The cost-effectiveness of autologous donation varies widely, but it often fails to meet the usual standards of efficacy. For this reason, its popularity has dropped substantially over the past several years. The donation itself carries a hospitalization risk of approximately 1 in 17,000, which is 12 times that for community donations by healthy individuals. Even though the blood is autologous, its use still incurs some of the usual homologous transfusion risks, including bacterial contamination or clerical errors leading to incompatible blood transfusions. Compared with allogeneic blood units, autologous units typically require the same testing procedures but more complex storage and identification procedures, so the cost for each unit is higher.

drop in hemoglobin concentration could induce unanticipated end-organ ischemia if there is an undiagnosed condition such as critical stenosis of a coronary artery or carotid artery. Mathematical analyses strongly suggests that the blood loss savings are fairly minor unless this technique is used quite aggressively—for example, hemodilution from a starting hematocrit of 40% to one of 20% or lower. Typically, this would require withdrawing 6 to 10 500-mL bags of blood. One study found no difference in allogeneic transfusion exposure when 3 units of acute normovolemic hemodilution were compared with a similar volume of autologous predonation in patients undergoing total hip arthroplasty.

Postoperative Blood Salvage This technique involves the collection and reinfusion of blood shed postoperatively. The blood is collected through a relatively large filter and reinfused through a small-pore filter. This blood can be reinfused unmodified (“unwashed”), or it can be washed and concentrated in the same way as for intraoperative blood salvage. Reinfused blood typically contains very low concentrations of plasma coagulation factors and platelets. It also contains elevated levels of fibrin degradation products, free hemoglobin, and inflammatory products such as cytokines. With total hip arthroplasty, it might also contain fat and bone spicules. As a result, many clinicians elect to administer salvaged blood only after it has been washed. This somewhat controversial technique reduces the need for allogeneic blood only when postoperative blood losses are large (e.g., >1000 mL), because the hematocrit of blood shed postoperatively is typically in the 15% to 20% range.

Intraoperative Blood Salvage Acute Normovolemic Hemodilution Acute normovolemic hemodilution involves the removal of blood just before or after the induction of anesthesia, combined with volume replacement using crystalloid or colloid. The technique requires standard anesthesia monitors (electrocardiogram, blood pressure, pulse oximetry, and temperature) and large-bore intravenous access with a 14- or 16-gauge peripheral or central venous catheter. Blood is collected into standard citrate-phosphate-dextrose bags. Removed blood is then stored in anticoagulated sterile bags and returned to the patient intraoperatively or postoperatively. The rationale is that the patient will be losing fewer RBCs into the surgical field because shed blood has a lower hematocrit due to hemodilution. Assuming that the lowest hematocrit remains acceptable (>20%) and that intravascular volume also remains intact, tissue perfusion will be maintained (and perhaps enhanced). Also, oxygen delivery will be sufficient owing to reduced blood viscosity. Additional clinical advantages include low cost, simple storage, and ease of transportation and record keeping. Acute normovolemic hemodilution risks hypovolemia if volume replacement is inadequate. Further, the obligatory

This method involves using a suction apparatus to collect the patient’s blood as it is shed intraoperatively into the surgical field. An anticoagulant solution is added to the shed blood, and it is then stored in a filtered reservoir. Once an adequate amount of blood has been collected (typically >700 mL), it is washed and concentrated so that the final product usually has a hematocrit between 55% and 70%. Because intraoperative blood salvage conserves RBCs but not plasma or platelets, a dilutional coagulopathy should be anticipated if blood losses approach or exceed one blood volume. Otherwise, the risks of this technique are low if appropriate procedures and standards are followed and the blood is not contaminated with bacteria. The ability to conserve RBCs with this technique depends largely on the surgeon’s ability to capture shed blood using suction. In this regard, total hip arthroplasty is in an intermediate category between laparotomy for aortic aneurysm repair, where blood pools in a body cavity and is easily captured, and a more superficial procedure such as reduction mammaplasty, where blood typically runs off the surgical field onto the drapes or is absorbed by sponges.

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Table 73–2

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Other Potential Blood-Conservation Techniques

Technique

Cost

Risk

Advisability*

Induced hypotension Prophylactic aprotinin Spinal or epidural anesthesia

Varies Expensive Low

Varies Low Low

Questionable; patient’s age is cause for some concern Unclear; reduces blood loss, but expensive Facilitates blood pressure control; reduces deep vein thrombosis

*For the patient described in the case synopsis.

PREVENTION Often, clinicians fail to appreciate how much blood loss can be safely tolerated by patients before the need for transfusion. This can be estimated using the following formula: ABL = V × (Hi – Hd)/Hm,

Autologous Predonation In retrospect, if one could have predicted the amount of blood loss experienced by the patient in the case synopsis based on the surgeon’s track record with reoperative hip arthroplasties, the patient should have been given supplemental iron therapy and predonated 3 or 4 units of autologous blood over 3 to 4 weeks before surgery. If the patient’s original hematocrit was less than 40%, supplementation with erythropoietin would have been reasonable, although health insurance policies often do not cover the cost of erythropoietin used for this purpose.

Acute Normovolemic Hemodilution Arguably, the most common application of this procedure is to withdraw 2 units in smaller patients (e.g., those <70 kg) and 3 units in larger ones. This saves 1 to 2 units of allogeneic packed RBCs if the intraoperative blood loss is between 3000 and 6000 mL, which crudely approximates one half to one normal blood volume. As blood losses exceed 6000 mL, the number of units saved gradually diminishes (to 0.5 to 1 unit) with this technique. Initially, one bag containing approximately 450 mL of blood is collected. As this is occurring, either 500 mL of colloid solution or about 1500 mL of crystalloid solution is infused into the patient to maintain intravascular volume. Hypotension or tachycardia suggests inadequate volume replacement. The exchange continues to the desired end point, as long as the patient tolerates the procedure. Checking the hematocrit or hemoglobin concentration periodically is

Intraoperative Blood Salvage In the case presented here, intraoperative blood salvage may offer the best chance of respecting the patient’s wish to avoid homologous blood. Further, effective use of this technique tends to override any theoretical benefits of acute normovolemic hemodilution. Alternatively, if the patient is otherwise completely healthy, one might “tough it out” to a hematocrit as low as 20%. Considering this patient’s age, however, reducing the hematocrit below that level is probably ill advised.

Postoperative Blood Salvage Because the cost of this technique is low and the likelihood of substantial postoperative bleeding is high in the patient described in the case synopsis, postoperative salvage is appropriate. Wound drainage contains various undesirable elements, however, so washing the product before reinfusion is advisable. Bacterial contamination can also occur, so this strategy should be avoided unless the drainage exceeds 500 mL over an 8-hour period. After this time, the collection device should be replaced if reinfusion is planned.

Alternative Blood Conservation Techniques Other potential blood-conserving options are listed in Table 73-2. Moderate deliberate hypotension is reasonable if the patient is otherwise healthy; for a patient in his 60s, however, setting a relatively conservative lower mean arterial pressure limit, in the range of 70 mm Hg for 1 to 2 hours, might be prudent.1 Another reasonable approach for deliberate hypotension might be to reduce the mean arterial pressure

1 Because our hypothetical patient is male and older than 60 years, and assuming no coronary artery disease or risk factors for it (hyperlipidemia, hypertension, or smoking history; see Chapter 38), another way to estimate the minimal acceptable pressure for deliberate hypotension (i.e., that required to maintain coronary perfusion pressure) is diastolic blood pressure – left ventricular end-diastolic pressure = 50 mm Hg. The value for adequate coronary perfusion pressure may be higher in patients with advanced age, diastolic heart failure, or a strong family history of coronary artery disease, hypertension, or other heart disease (all associated with some amount of elevated left ventricular end-diastolic pressure).

CARDIOTHORACIC & VASCULAR SURGERY

where ABL is allowable blood loss; V is blood volume; Hi and Hd are the initial and lowest desired hematocrit values, respectively; and Hm is the hematocrit average of Hi and Hd. Assuming a blood volume of 5600 mL (80 kg × 70 mL/kg), an Hi of 40%, and an Hd of 25%, the patient in the case synopsis can tolerate a blood loss of almost 2600 mL without transfusion therapy. Intraoperative RBC salvage increases this figure in direct proportion to the efficacy of salvage.

advisable to reassess the appropriateness of the calculated end point. The blood is then stored at room temperature if it will be used within 8 hours; otherwise, refrigerated storage is required.

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by about 20% below the patient’s preoperative baseline level, which could probably be safely sustained for several hours if necessary. Aprotinin and its lysine analogues (e.g., tranexamic acid) can also reduce blood loss in hip replacement surgery with a low risk of complications, but the high cost of aprotinin must be considered.

Further Reading American Association of Blood Banks: All about blood (2004). Available at www.aabb.org/All_About_Blood. American Society of Anesthesiologists Task Force on Blood Component Therapy: Practice guidelines for blood component therapy. Anesthesiology 84:732-747, 1996. Birkmeyer JD, Goodnough LT, AuBuchon JP, et al: The cost effectiveness of preoperative autologous blood donation for total hip and knee replacement. Transfusion 33:544-551, 1993.

Goodnough LT: Red blood cell support in the perioperative setting. In Simon TL, Dzik WH, Snyder EL, et al (eds): Rossi’s Principles of Transfusion Medicine, 3rd ed. Philadelphia, JB Lippincott–Williams & Wilkins, 2002, pp 590-601. Goodnough LT, Despotis GJ, Merkel K, Monk TG: A randomized trial comparing acute normovolemic hemodilution and preoperative autologous blood donation in total hip arthroplasty. Transfusion 40:1054-1057, 2000. Goodnough LT, Monk TG, Brecher ME: Autologous blood procurement in the surgical setting: Lessons learned in the last 10 years. Vox Sang 71:133-141, 1996. Jacobs MR, Palavecino E, Yomtovian R: Don’t bug me: The problem of bacterial contamination of blood components—challenges and solutions. Transfusion 41:1331-1334, 2001. Wu W-C, Rathore SS, Wang Y, et al: Blood transfusion in elderly patients with acute myocardial infarction. N Engl J Med 345:1230-1236, 2001.

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74

Prashant Lotlikar and John R. Cooper, Jr.

COMPLICATIONS OF AORTIC ROOT CANNULATION: ACUTE AORTIC ROOT DISSECTION Case Synopsis

PROBLEM ANALYSIS Definition Acute aortic dissection following aortic cannulation is an infrequent but serious complication of cardiac surgery. The diagnosis must be made early and thus requires a high index of suspicion. Dissection may also occur during CPB or after decannulation. In this case, the cannula orifice was situated within the media of the arterial wall rather than the true lumen, owing to a dissection created during cannulation. For aortic dissection to occur, blood under pressure must gain access to the media of the aortic wall. In this case, access was obtained via cannula insertion and initiation of perfusion. Additional manipulation of the ascending aorta (e.g., aortic cross-clamp, antegrade cardioplegia line, proximal bypass grafts) may increase the risk of dissection. Predisposing factors that increase the risk for acute aortic dissection include conditions that weaken the aortic wall, such as the following: ● ● ● ●

elevation in arterial line pressure and bluish discoloration and enlargement of the aortic root. Myocardial ischemia, aortic insufficiency, or both may develop, and signs of organ hypoperfusion (including oliguria and pupil asymmetry) may be present if the dissection extends to other major arterial vessels. If transesophageal echocardiography is used, dissection may be evident on examination of the thoracic aorta (Fig. 74-1).

Cystic medial necrosis Elastic or medial degeneration associated with aging Poststenotic dilatation (aortic stenosis) Atheromatous disease

Dissection may occur spontaneously in the operating room or during the postoperative period in the intensive care unit.

Recognition A sudden, unexplained decrease in mean arterial pressure and venous return is usually seen, associated with an acute

Figure 74–1 ■ Transesophageal echocardiography of the ascending aorta just distal to the aortic valve, with an intraoperative aortic dissection evident showing true and false lumens. This dissection propagated from the antegrade cardioplegia administration site.

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A 75-year-old man with a history of calcific aortic stenosis was scheduled for valve replacement. Induction of anesthesia, sternotomy, and placement of cannulas were uneventful. The aortic tissue, however, appeared thin and calcified. The aortic purse strings and cannula appeared well placed, but on beginning cardiopulmonary bypass (CPB), the pump arterial line pressure increased, and systemic blood pressure (radial artery) decreased. The aorta appeared acutely dilated.

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MANAGEMENT

●

CPB must be discontinued immediately. The surgeon must then either reposition or replace the arterial cannula into the true lumen at a more distal site on the aortic arch or initiate femoral artery cannulation. Surgical repair of the aortic dissection is almost always necessary, including coronary artery reimplantation if patency of the coronary arteries is threatened.

●

●

●

●

PREVENTION

Blood pressure control (to avoid hypertension) at the time of cannulation Insertion of the cannula at a right angle to the aorta to prevent dissection into tissue planes Special care in locating the tip in the true lumen of the aorta Blood pressure reduction when the aortic cross-clamp is applied or removed Use of atraumatic clamps, with as few applications to the aorta as possible Continuous monitoring of arterial cannula pressure by the perfusionist

Measures that may be effective in reducing the incidence of aortic dissection during cannulation include the following:

CAROTID OR INNOMINATE ARTERY HYPERPERFUSION Case Synopsis A 58-year-old woman underwent CPB for coronary artery bypass grafting. After successful aortic and venous cannulation by the surgeon, the anesthesiologist noted right-sided facial blanching. Further examination showed the presence of a right carotid thrill.

Cannula too long

A

Cannula misdirected

B

Cannula too small Jet effect

D

Correct

C Figure 74–2 ■ Carotid or innominate artery hyperperfusion. A, The cannula is too long, causing it to enter the left carotid artery. B, The cannula angulation is incorrect, directing the majority of flow to the innominate artery. C, Correct position. D, The cannula is too small, resulting in a high-velocity jet. See Definition (next page) for further discussion. (From Moores WY: Cardiopulmonary bypass strategies in patients with severe aortic disease. In Utley JR [ed]: Pathophysiology and Techniques of Cardiopulmonary Bypass, vol 2. Baltimore, Williams & Wilkins, 1983, p 190.)

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PROBLEM ANALYSIS

MANAGEMENT

Definition

Repositioning of the cannula is necessary. Measures to reduce cerebral edema, including diuretics or head-up position, may be indicated.

Pump flow can be directed primarily into the carotid or innominate artery instead of the aorta. This can result in cerebral edema or arterial rupture due to high perfusion pressure or the creation of an intimal flap that obstructs arterial flow (Fig. 74-2).

Recognition Signs of innominate artery cannulation include ipsilateral facial blanching, pupillary dilatation, and conjunctival chemosis. Hypotension measured via a left radial or femoral artery catheter may be observed, but a right radial artery catheter may show hypertension.

PREVENTION Use of a short aortic cannula with a flange to prevent insertion too far into the aorta is usually effective. The anesthesiologist can check for bilateral carotid pulses without thrills after cannulation and initiation of CPB, but this may not reliably detect problems caused by carotid or innominate artery hyperperfusion.

OBSTRUCTION TO VENOUS RETURN Case Synopsis

PROBLEM ANALYSIS Definition Obstruction of venous return to the pump-oxygenator may have several causes: ●

● ● ● ● ●

An “air lock” created by the presence of large air bubbles within the venous cannula or tubing Failure to remove a venous line clamp Lifting of the heart within the chest by the surgeon Use of venous cannulas too small for the patient Presence of thrombus or tumor Kinked or malpositioned cannula (most common)

When two cannulas are used, the superior vena cava cannula may be placed into the azygos vein or, if advanced too far cephalad, into the innominate vein. The inferior vena cava cannula may be placed into the hepatic vein. In this case synopsis, the single cannula was placed so far into the inferior vena cava that there could be no venous return from the superior vena cava.

Recognition Decreasing venous reservoir volume in the pump-oxygenator is the first sign. Failure to reduce pump flow immediately can result in emptying of the venous reservoir, with a risk of massive arterial air embolism. Increased central venous

pressure occurs, along with obvious venous engorgement in the face and neck and later conjunctival chemosis. Also, lack of drainage from the right side of the heart may result in compression of the left ventricle, detected by direct visualization or by an increase in pulmonary artery or left atrial pressure.

MANAGEMENT Pump flow should be reduced until the cause of obstruction to venous return is found. The surgeon can propel an air lock through the venous tubing by progressively raising and tapping the tubing downstream from the bubble. Venous cannulas will probably have to be repositioned. Only after adequate venous return is established, with recovery of volume in the venous reservoir, should full-flow CPB be continued.

PREVENTION The surgeon should inspect the venous cannula for large bubbles and ensure proper venous cannula position. The anesthesiologist should routinely check the patient’s face, neck, and conjunctiva for signs of high venous pressures. Monitoring central venous pressures may not detect a superior vena cava obstruction because the catheter tip may be below the obstruction point.

CARDIOTHORACIC & VASCULAR SURGERY

A 60-year-old man was placed on CPB after uneventful aortic cannulation and use of a single venous cannula in the right atrium. There was an immediate decrease in both arterial pressure and pump-oxygenator venous reservoir volume. Obvious venous engorgement in the patient’s face and neck was noted immediately.

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MASSIVE GAS EMBOLISM Case Synopsis A 65-year-old woman undergoing mitral valve replacement was placed on CPB after uneventful insertion of aortic and venous cannulas. Before application of the aortic cross-clamp, the surgeon inserted a vent cannula into the left atrium via the left superior pulmonary vein. Blood initially began to drain normally toward the venous reservoir but then reversed direction, and a large quantity of air entered the heart and was ejected systemically.

●

PROBLEM ANALYSIS ●

Definition Systemic gas embolism is the most common serious adverse event associated with CPB and is largely preventable. Principal causes include the following: ●

Vortexing—air being pumped out of an empty or near empty oxygenator reservoir

●

●

●

Reversed roller-pump tubing in the vent line or arterial cannula Disconnection, leak, oxygenator disruption, or line occlusion proximal to the arterial pump, with air entrainment or cavitation Development of positive pressure in the cardiotomy reservoir, producing retrograde airflow into the heart or aorta Injection of air into the aortic root from the cardioplegia delivery system Clotted oxygenator or runaway pump head

Retrograde SVC pumping

A

B

Figure 74–3 ■ A, Massive air embolus through the aortic cannula. (circles represent the aortic root) B, The aortic cannula is removed, purged of air (circles), and inserted into the divided superior vena cava (SVC) cannula. Retrograde perfusion at 1200 mL/minute at 20∞C is carried out for 1 to 2 minutes. Air exits the aortic cannulation site. (From Mills NL, Ochsner JL: Massive air embolism during CPB: Causes, prevention and management. J Thorac Cardiovasc Surg 80:713, 1980.)

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Ejection of blood before the removal of air from the heart, or opening a beating heart Disconnection or rupture of the oxygenator or lines during CPB Failure to clamp the aortic line at the end of CPB, resulting in air infusion if the pump head is accidentally restarted

Recognition Air in the arterial cannula is usually visually apparent, but signs of myocardial or other organ ischemia may also occur. Rarely, withdrawal of air from an arterial pressure monitoring line indicates air embolism.

MANAGEMENT After recognition, if the embolus is massive, CPB must be discontinued. The patient is then placed in a steep Trendelenburg position, the aortic cannula is removed, and the CPB circuit is reprimed. Retrograde perfusion of the superior vena cava is initiated (Fig. 74-3). CPB is then restarted with hypothermia, increasing perfusion pressure, and

303

100% oxygen. Consideration can then be given to pharmacologic interventions to reduce cerebral injury, including mannitol, steroids, and barbiturates. Postoperative interventions may include initiation of hyperbaric oxygen treatment, reverse Trendelenburg position, initiation of slight hyperventilation, and avoidance of hyperglycemia and hyponatremia.

PREVENTION Special attention must be paid to maintaining a safe volume of blood in the oxygenator reservoir. Low-level alarms and bubble detectors should be used. The surgical team must protect the venous lines and communicate with the perfusionist when venous return is likely to be compromised. Other measures include the use of the following: ● ● ●

● ●

Centrifugal pumps Arterial line filters Bubble traps with an open air purge line guarded by a one-way valve Collapsible reservoirs One-way valves placed in the left heart vent line

Case Synopsis A 68-year-old man underwent CPB for combined mitral valve replacement and coronary bypass grafting. Five minutes after initiation of CPB, dark blood was observed by the anesthesiologist in the aortic cannula. An immediate blood gas sampling revealed a low arterial oxygen tension (PaO2).

PROBLEM ANALYSIS

MANAGEMENT

Definition

If oxygenator failure is suspected, a blood gas measurement from the arterial inflow line should be obtained, and the perfusionist should increase oxygen gas flows and determine the adequacy of mechanical pump flow. Additionally, the following actions should be taken:

This situation can be caused by oxygenator failure, with three possible causes of arterial inflow desaturation: (1) the gas supply system, (2) the oxygenator itself, or (3) specific patient characteristics or pathophysiology. Low PaO2 can also be caused by pump failure. This can occur by means of electrical or mechanical failure, tubing rupture or disconnection, or automatic shutoff by the bubble or reservoir level detector. A runaway pump head may inappropriately raise the pump flow rate to maximum. If the occlusion of a roller pump is improperly set, excessive regurgitation can cause reduced forward blood flow, hypotension, and metabolic acidosis.

Recognition Oxygenator failure results in dark blood in the arterial cannula and severe vasodilatation. Blood leaking into the heater-cooler water may also be seen with oxygenator rupture. With pump failure and low PaO2, one observes hypotension, metabolic acidosis, and perhaps hemolysis.

●

●

●

●

Careful inspection of the gas circuit, including gas sources, all connections, tubing, gas line filter, and vaporizer Inspection of the oxygenator for appropriate blood levels and adequacy of foaming (bubble oxygenator), and examination of the shell for leaks or cracks Inspection of the venous and arterial cannulas for appropriate patient connections Assurance of adequate muscle relaxation, appropriate patient temperature, and depth of anesthesia

If the heart is still beating, one should consider allowing it to eject blood into the pulmonary circulation for additional oxygenation and continue ventilation of the lungs until apparent arterialization of blood is observed in the aortic cannula. If there is pump failure, a hand crank can be used until a replacement is obtained or tubing is replaced. In the case

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PUMP OR OXYGENATOR FAILURE

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of a runaway pump head, the machine must be unplugged, and the tubing must be switched to a different roller head. If flow will be low or absent for more than a few minutes, and if the patient cannot be weaned immediately from CPB, hypothermia should be induced. One should then consider packing the head and heart in ice for additional protection.

PREVENTION Vigilance is paramount. Use of a pump arterial line oxygen saturation monitor and/or a partial pressure of oxygen analyzer may be beneficial. Backup equipment should always be available.

CLOTTED OXYGENATOR OR CIRCUIT Case Synopsis A 60-year-old man underwent aortocoronary bypass and concurrent abdominal aortic aneurysm repair. After weaning from CPB, while the aneurysm was being repaired, the CPB circuit was used for blood salvage and reinfusion. After 1 hour, as blood was given through the aortic cannula, a large clot was discovered in the oxygenator. The activated clotting time was greater than 400 seconds.

PROBLEM ANALYSIS

PREVENTION

Definition

The surgical team should ensure adequate heparin administration and monitoring in prolonged cases, plus visual inspection of the circuit and arterial line filter for clots. Heparinizing any blood products added to the circuit should be considered, and stagnant blood pooling in the CPB circuit should be avoided, even if heparinization is “adequate” by laboratory measurements.

This adverse event can prevent CPB flow, cause massive gas embolus, and interfere with gas exchange. Causes include inadequate heparinization, stagnation in the bypass circuit (no flow in the circuit during circulatory arrest), and, occasionally, addition of unheparinized blood products during CPB.

Recognition Visual inspection of the circuit for clots is most reliable, but the observation of air exiting from a bubble oxygenator or high arterial cannula pressure may also indicate a large clot.

MANAGEMENT Stop CPB and reheparinize the patient using a different lot of heparin, if possible. Hypothermia should be initiated, and open cardiac massage should be performed if the patient cannot be acutely weaned from CPB. The oxygenator may need to be replaced. The protocol for massive air embolism should be followed, if appropriate.

Further Reading Gravlee GP, Davis RF, Krusz M, Utley JR: Cardiopulmonary Bypass: Principles and Practice. Philadelphia, JB Lippincott–Williams & Wilkins, 2000, pp 69-97, 578-612. Hensley FA Jr, Martin DE, Gravlee GP: A Practical Approach to Cardiac Anesthesia, 3rd ed. Philadelphia, JB Lippincott–Williams & Wilkins 2003, pp 513-556. Mills NL, Ochsner JL: Massive air embolism during cardiopulmonary bypass: Causes, prevention, and management. J Thorac Cardiovasc Surg 80:708-717, 1980. Mora CT: Cardiopulmonary Bypass: Principles and Techniques of Extracorporeal Circulation. New York, Springer-Verlag, 1995, pp 302-307. Reed CC, Kurusz M, Lawrence AE Jr: Safety and Techniques in Perfusion. Stafford, Tex, Qualimed, 1988, pp 123-133.

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Bleeding after Cardiac Surgery Peter Tassani-Prell Case Synopsis A 73-year-old man presents with a history of aortic stenosis, coronary artery disease, peripheral vascular disease, dyspnea at rest, and chronic renal failure (creatinine level 1.6 mg/dL). Myocardial function is reduced (left ventricular ejection fraction is 35%). Combined aortic valve replacement and coronary artery bypass graft surgery is performed. Total cardiopulmonary bypass (CPB) time is 142 minutes. Increased bleeding is noted via the mediastinal tubes after surgery. Blood loss via these tubes is 2200 mL in the first 24 hours postoperatively.

PROBLEM ANALYSIS Definition

Risk Assessment Risk factors for postoperative bleeding include the following: ● ● ●

● ● ● ● ● ●

Recognition Surgical exploration for bleeding begins in the operating room (OR) following heparin neutralization with protamine after separation from CPB or completion of “off-pump” cardiac surgery. There are great individual differences in the amount of bleeding that can be detected by direct observation of the operative field. The multifactorial nature of coagulation disorders often makes the distinction between surgical and nonsurgical bleeding difficult. The typical delay in obtaining laboratory test results further complicates the decision as to what therapeutic treatment is needed (e.g., platelets, fresh frozen plasma, cryoprecipitate). Postoperatively, mediastinal chest tube drainage is monitored hourly. As a rule, drainage should not exceed 100 to 125 mL/hour for the first 4 postoperative hours, 250 mL for any hour during this period, or 50 to 75 mL/hour for the subsequent 24 hours. Life-threatening hypotension from postoperative bleeding can result from cardiac tamponade or hypovolemia. It is essential to initiate diagnostic efforts long before the patient’s arrival in the postoperative intensive care unit. Nonsurgical bleeding may be detected in the OR by the surgical team. Appropriate laboratory analysis should be initiated early to obtain results in the OR. Early detection of specific hemostatic deficiencies leads to specific therapy instead of nonspecific

● ●

Prolonged duration of CPB Repeat cardiac procedures Combined procedures (e.g., bypass grafting and valve surgery) Low body temperature after surgery Increased cell salvage usage Advanced age Chronic steroid use Intra-aortic balloon counterpulsation Internal mammary artery harvesting Female sex Preoperative use of anticoagulant drugs

Individual screening in the preoperative period is essential to identify patients at increased risk for postoperative bleeding. Clinical observation and the patient’s medical history are extremely important. Drugs that alter the coagulation system or platelet function are commonly used in patients scheduled for cardiac surgery. Glycoprotein IIb/IIIa inhibitors, including abciximab, eptifibatide, and tirofiban, are used extensively as short-term adjuncts to heparin or aspirin therapy in patients with acute coronary syndromes or in those having preoperative percutaneous coronary interventions. It is also likely that many patients requiring emergency cardiac surgery will have received anticoagulation therapy before arriving in the OR. When in doubt, additional laboratory analysis for specific coagulation disorders may be indicated.

Implications Use of CPB during cardiac surgery disrupts the normal hemostatic system in several ways. Combined effects of hypothermia, hemodilution, blood loss, and transient activation of platelets are often seen. Activated platelets following exposure to CPB are “exhausted” and have lost their function. 305

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Excessive bleeding after cardiac surgery is broadly categorized as surgical or nonsurgical. Surgical bleeding can originate from multiple locations, including bypass graft anastomoses, cannulation sites, mammary beds, sternal wires, or wherever blood vessel integrity has been interrupted. Nonsurgical or microvascular bleeding can result from hemostatic abnormalities involving the endothelium, platelets, coagulation factors, or fibrinolysis. The combined effects of large heparin and protamine doses required for cardiac surgery, CPB circuitry, blood scavenging systems, hypothermia, and, occasionally, massive transfusion can contribute to postoperative bleeding.

transfusion (“shotgun therapy”) of multiple types of blood products and coagulation therapies.

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However, with normal CPB duration, detrimental quantitative and qualitative platelet defects are usually short-lived. Hemodilution. Crystalloid CPB priming and cardioplegia solutions dilute platelets and coagulation factors. The significance of this depends on their baseline concentrations, as well as the volume used relative to the patient’s circulating blood volume. Recent efforts to reduce the volume of CPB priming solutions by using different CPB circuits for adults with lower body weight or using blood versus crystalloid cardioplegia may significantly reduce the amount of clinical hemodilution. Even so, hemodilution is rarely the sole cause of postoperative bleeding, because coagulation factor concentrations of 25% to 30% and platelet counts of 50,000 to 100,000/mm3 can be tolerated without excessive bleeding if platelet function is normal. Cardiopulmonary Bypass Circuitry. The exposure of blood to nonendothelial surfaces of the CPB circuit activates platelets and the coagulation and fibrinolytic pathways. Platelet dysfunction is the single most important cause of bleeding after cardiac surgery. Use of pericardial suction devices during surgery traumatizes blood cells and returns activated coagulation factors to the circulation via the venous reservoir. The use of closed reservoirs, coated CPB circuits, and retransfusion of the suctioned blood after preparation in an autotransfusion device have all been proposed to reduce the detrimental effects of CPB on coagulation. Hypothermia. Hypothermia may result in impaired platelet function and reduced function of temperature-dependent coagulation factors. Also, laboratory coagulation system assessment is uniformly done at 37°C. Therefore, misleading results might be obtained when analyzing cold blood samples obtained during hypothermic CPB. Cooling to more tepid temperatures (mild hypothermia) has been proposed by some to reduce the activation of inflammatory cascades and lessen coagulation abnormalities. Cell Salvage Systems. Because coagulation factors and platelets are removed during routine red cell salvage, reinfused products from cell salvage devices are deficient in these components. Thus, red cell salvage may contribute to abnormalities of coagulation. Heparin. Despite initial neutralization with protamine, heparin rebound can occur 2 to 6 hours afterward, leading to inhibition of platelet function. Antibody-mediated, heparininduced thrombocytopenia and thrombosis (type II HIT; see Chapter 72) is a distinct, severe, and rare entity that involves accelerated clearance or activation of platelets. The target antigen is generated in the presence of platelet factor 4 and heparin at a concentration that allows the formation of heparin–platelet factor 4 complexes. Such interaction then exposes neoepitopes, which bind to the heparin-dependent antibodies. These antibodies are generated in a minority of heparin-treated patients, and occasionally one subgroup develops thrombocytopenia associated with thrombosis.

MANAGEMENT Treatment of postoperative bleeding can be challenging because of its complex and multifactorial causes. Excessive mediastinal

tube drainage, especially when accompanied by hemodynamic instability, indicates a probable surgical source of bleeding and requires surgical re-exploration in the OR. However, the amount of mediastinal drainage does not allow one to differentiate between surgical and nonsurgical causes of bleeding—a distinction that is of the utmost importance. Therefore, a scientifically based algorithm (based on laboratory values) should be used for the precise diagnosis of specific hemostatic abnormalities. When the activated clotting time (ACT) returns to baseline values, this is often interpreted as meaning that heparin neutralization is complete. However, the ACT is insensitive to low circulating heparin concentrations. Even when the ACT has returned to baseline, heparin plasma concentrations can be as high as 0.2 unit/mL, which corresponds to an activated partial thromboplastin time (aPTT) of 1.5 times control. More sensitive tests for residual heparin following surgery include whole blood or plasma aPTT, thrombin time, whole blood heparin concentration measurements, or heparinase ACT values. Continued bleeding in the absence of detectable heparin concentrations warrants further evaluation of the coagulation system. Results of laboratory-based coagulation studies (e.g., prothrombin time, aPTT, platelet count) may take an hour or more to obtain. Commercially available onsite or point-of-care testing methods can provide clinically relevant coagulation test results in about 5 minutes. Such testing can provide a whole blood determination of prothrombin time and aPTT (i.e., plasma separation is not required). Because of the relative importance of quantitative and qualitative platelet defects following CPB, it is important to evaluate and correct such defects as soon as possible. It is difficult to obtain adequate surgical hemostasis without at least 50,000 to 100,000/mm3 of fully functional platelets. Therefore, use of an OR-based hemocytometer can provide rapid information about platelet concentrations. Normal counts, however, do not guarantee adequate platelet function. Modified computerized thromboelastography provides more rapid results than conventional thromboelastography and may be useful. This system allows rapid whole blood coagulation testing with different activators and additives, typically reaching the maximal amplitude after about 15 minutes. It is also possible to see this process in the OR while the test is still running in the laboratory. It is important to initiate diagnostic evaluation early, when microvascular bleeding (“oozing”) in the surgical field is first observed. Timely point-of-care, laboratory-assisted assessment of coagulation leads to reduced and more appropriate use of blood products in the OR.

Platelet Dysfunction Once the determination of thrombocytopenia or qualitative platelet dysfunction has been made, treatment includes the administration of desmopressin acetate (DDAVP), platelet transfusions, or both. DDAVP, a synthetic analogue of antidiuretic hormone, is thought to augment platelet function by the release of factor VIII and von Willebrand’s factor from endothelial cells. Other studies, however, indicate that DDAVP may have direct beneficial effects on platelets, such as increased expression of the adhesive receptor (glycoprotein Ib). The usual dose of DDAVP is 0.3 μg/kg, given intravenously over

Broad-spectrum serine protease inhibitor Interacts with trypsin, kallikrein, chymotrypsin Blood-sparing effects likely related to plasmin inhibition, with platelet function preserved Reduced activation of the hemostatic system via inhibition of contact (kallikrein inhibitor) and tissue factor (binding of VIIa-TF) pathways, with resultant reductions in thrombin and anti-inflammatory properties See above

Aprotinin (full-dose regimen)

Binds to plasmin, inhibiting fibrinolysis

Tranexamic acid

Comments

Loading dose: 10 mg/kg Maintenance dose: 1 mg/kg/hr

Test dose: 1 mL (10,000 units) to test for anaphylaxis Loading dose: 100 mL (1 million units) over 30 min before starting CPB Maintenance dose: 25 mL/hr (0.25 million units/hr); 100 mL in CPB prime solution Loading dose: 100-150 mg/kg or 5-10 g (adults) over 30 min Maintenance dose: 10-20 mg/kg/hr or 1 g/hr (adults)

Renal excretion; dose must be reduced in patients with renal failure Contraindicated with DIC or in presence of hematuria, because ureteral obstruction may result Risks include thrombotic complications Not approved by FDA for prophylaxis of cardiac surgical bleeding Renal excretion; dose must be reduced in patients with renal failure Contraindicated with DIC or in presence of hematuria, because ureteral obstruction may result Risks include thrombotic complications Not approved by FDA for prophylaxis of cardiac surgical bleeding

Half-dose regimen is effective for reducing blood loss for complex or repeat CABG surgery Anti-inflammatory effects with the full-dose regimen may affect other outcomes

Test dose: 1 mL (10,000 units) to test for Aprotinin prolongs the celite ACT, which may lead to anaphylaxis inadequate heparinization during CPB; kaolin ACT Loading dose: 200 mL (2 million units) is unaffected by aprotinin over 30 min before starting CPB Whole blood heparin concentrations (>3 units/mL) Maintenance dose: 50 mL/hr (0.5 million units/hr); can also be maintained with the heparin-protamine 200 mL in CPB prime solution titration method If only celite ACT is available, ACT should be kept >800 sec during CPB, or fixed heparin dosing should be used

Dose

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ACT, activated clotting time; CABG, coronary artery bypass graft; CPB, cardiopulmonary bypass; DIC, disseminated intravascular coagulation; FDA, Food and Drug Administration; TF, tissue factor.

Binds to plasmin, inhibiting fibrinolysis

∈-aminocaproic acid (EACA)

Aprotinin (half-dose regimen)

Mechanism of Action

Antifibrinolytic Drugs to Reduce Blood Loss and Requirements for Blood Transfusion after Cardiac Surgery

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30 minutes. The principal adverse side effect is hypotension. A similar beneficial effect, but without hypotension, can be achieved by giving 4 μg/kg of DDAVP intranasally. Platelet transfusion should consist of an appropriate number of units, preferably obtained by apheresis from a single donor. During cardiac transplantation, blood from the organ donor can be acquired during cardiac explantation, from which platelet-rich plasma is derived by separation plasmapheresis. Such platelet-rich plasma is then transfused into the organ recipient. This can substantially reduce the need for perioperative blood transfusion in cardiac transplant recipients.

Coagulation Factor Deficiencies When the prothrombin time is greater than 16 seconds or the aPTT is greater than 57 seconds, coagulation factor deficiencies are treated with fresh frozen plasma. Although the amount needed varies, depending on initial factor concentrations and circulating blood volume, 1 mL/kg of fresh frozen plasma usually increases coagulation factor concentrations by 1% to 2%. Cryoprecipitate provides a concentrated source of fibrinogen, which is beneficial when deficiencies of this coagulation factor are documented. A prothrombin complex concentrate may be useful when liver function is compromised or liver-generated coagulation factors have been chemically reduced by warfarin. Substitution or supplementation of native antithrombin III leads to higher ACT values and reduced concentrations of fibrin monomer and D-dimer. Substitution of antithrombin III is essential when its activity is less than 60%, because the heparin effect is dependent on it. Several case reports have described using recombinant activated factor VII in cases of life-threatening hemorrhage after cardiac surgery. Randomized, controlled trials to assess the efficacy and safety of such therapy are under way.

PREVENTION Measures to prevent bleeding after cardiac surgery include the following: ● ●

● ●

Minimal CPB duration Autologous blood procurement before CPB to provide a source of fresh whole blood with functioning platelets and coagulation factors for use after heparin neutralization Maintenance of normothermia Judicious postoperative blood pressure control

The fibrinolytic system is known to be up-regulated during CPB owing to the activation of multiple physiologic systems. This results in clot dissolution, coagulation factor

consumption, and platelet dysfunction. Multiple clinical studies indicate that the prophylactic administration of antifibrinolytic drugs reduces blood loss and the number of transfusions in patients after cardiac surgery, particularly reoperations (Table 75-1).

Further Reading Cammerer U, Dietrich W, Rampf T, et al: The predictive value of modified computerized thromboelastography and platelet function analysis for postoperative blood loss in routine cardiac surgery. Anesth Analg 96:51-57, 2003. Caputo M, Bryan AJ, Calafiore AM, et al: Intermittent antegrade hyperkalaemic warm blood cardioplegia supplemented with magnesium prevents myocardial substrate derangement in patients undergoing coronary artery bypass surgery. Eur J Cardiothorac Surg 14:596-601, 1998. Despotis GJ, Filos KS, Zoys TN, et al: Factors associated with excessive postoperative blood loss and hemostatic transfusion requirements: A multivariate analysis in cardiac surgical patients. Anesth Analg 82:13-21, 1996. Hekmat K, Zimmermann T, Kampe S, et al: Impact of tranexamic acid vs aprotinin on blood loss and transfusion requirements after cardiopulmonary bypass: A prospective, randomized, double-blind trial. Curr Med Res Opin 20:121-126, 2004. Herbertson M: Recombinant activated factor VII in cardiac surgery. Blood Coagul Fibrinolysis 15(Suppl 1):S31-S32. 2004. Levi M, Cromheecke ME, de Jonge E: Pharmacological strategies to decrease excessive blood loss in cardiac surgery: A meta-analysis of clinically relevant endpoints. Lancet 354:1940-1947, 1999. Levy JH, Despotis GJ, Szlam F, et al: Recombinant human transgenic antithrombin in cardiac surgery: A dose-finding study. Anesthesiology 96:1095-1102, 2002. Mongan PD, Hosking MP: The role of desmopressin acetate in patients undergoing coronary artery bypass surgery: A controlled clinical trial with thromboelastographic risk stratification. Anesthesiology 77:38-46, 1992. Nuttall GA, Fass DN, Oyen LJ, et al: A study of a weight-adjusted aprotinin schedule during cardiac surgery. Anesth Analg 94:283-289, 2002. Nuttall GA, Oliver WC, Santrach PJ, et al: Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary bypass. Anesthesiology 94:773-781, 2001. Ohata T, Sawa Y, Kadoba K, et al: Effect of cardiopulmonary bypass under tepid temperature on inflammatory reactions. Ann Thorac Surg 64:124-128, 1997. Remadi JP, Marticho P, Butoi I, et al: Clinical experience with the miniextracorporeal circulation system: An evolution or a revolution? Ann Thorac Surg 77:2172-2175, 2004. Richter JA, Meisner H, Tassani P, et al: Drew-Anderson technique attenuates systemic inflammatory response syndrome and improves respiratory function after coronary artery bypass grafting. Ann Thorac Surg 69:77-83, 2000. Spiess BD, Gillies BS, Chandler W, et al: Changes in transfusion therapy and reexploration after institution of a blood management program in cardiac surgical patients. J Cardiothorac Vasc Anesth 9:168-173, 1995. Tassani P, Otto D, Szekely A, et al: Transfusion of platelet-rich plasma from the organ donor during cardiac transplantation. J Clin Anesth 9:409-414, 1997. Woodman RC, Harker LA: Bleeding complications associated with cardiopulmonary bypass. Blood 76:1680-1697, 1990.

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Mark A. Chaney Case Synopsis A 62-year-old man is scheduled for elective coronary artery bypass grafting. Immediately after uneventful induction of general anesthesia and tracheal intubation, new ST segment depression is observed on the electrocardiogram (ECG) tracing.

PROBLEM ANALYSIS Definition

Recognition Ischemia Anginal symptoms and hemodynamic alterations are not necessarily reliable indicators of myocardial ischemia. Reliance on increased pulmonary artery wedge pressure for the detection of ischemia is controversial at best. In fact, acutely increased pulmonary artery wedge pressure probably signifies only global ischemia. Detection of regional wall motion abnormalities with transesophageal echocardiography is the most sensitive of the currently available, clinically useful techniques for detecting myocardial ischemia. In addition to wall motion abnormalities, decreased systolic wall thickening or abnormal diastolic filling patterns, detected by Doppler interrogation across the left ventricular

INFARCTION The ECG is the most commonly used modality to detect myocardial ischemia and acute MI. Transmural MI presents initially with prominent T waves, hyperacute ST segment elevation, or both. This evolves over minutes, hours, or even days to a pattern of significant Q waves (i.e., >40 msec duration, >30% of QRS amplitude) or persistent ST-T wave changes. Subendocardial (non-Q-wave) MI is less clearly defined because it may present only as subtle ST-wave or T-wave changes. Detection of non-Q-wave MI often relies on other modalities (e.g., CK, cardiac-specific troponins, transesophageal echocardiographic radionuclide imaging) to confirm the diagnosis. Most perioperative MIs are subendocardial in nature. Serum CK exceeds the normal range within 4 to 8 hours following acute MI and declines to normal by 2 to 3 days. Three isoenzymes of CK (BB, MM, MB) have been identified. Brain and kidney contain predominantly BB, skeletal muscle MM (with 1% to 3% MB), and myocardium both MM and MB (isoforms MB1 and MB2). One study found 59% and 92% sensitivity for the diagnosis of acute MI at 2 to 4 and 4 to 6 hours, respectively, for CKMB2 greater than 1 unit/L or CKMB2/CKMB1 ratio greater than 1.5. Cardiac troponins are highly sensitive and specific chemical markers for myocardial necrosis and predict increased risk of mortality and reinfarction in patients presenting with acute coronary syndrome. The troponin (Tn) complex consists of three subunits (TnC, TnI, TnT) that regulate calciummediated contraction in striated muscle. TnC binds to calcium, TnI binds to actin, and TnT binds to tropomyosin. Both TnI and TnT are present in skeletal and cardiac muscle, but they are encoded by different genes and have different amino acid sequences. This permits the production of specific antibodies for cardiac Tn (cTn) and the development of 309

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Myocardial ischemia results from an imbalance between myocardial oxygen supply and demand. If this persists, ischemia eventually leads to myocardial infarction (MI). Patients in whom perioperative ischemia develops are at increased risk for subsequent cardiac morbidity and mortality. Postoperative MI and major cardiac complications occur in more than 4% of patients who have either an established diagnosis of coronary artery disease or risk factors for it and who undergo major noncardiac surgery. In the United States alone, 1.5 to 2 million patients are at such risk for postoperative MI each year. There is marked variability in the reported short-term mortality (<10% to 70%), but few data exist for long-term prognosis after postoperative MI. Well over 50,000 patients a year sustain perioperative MI, adding substantial cost to postoperative care. Unlike nonsurgical MI, the clinical diagnosis of perioperative MI is often difficult or impossible, especially if it is based on the classic triad of (1) cardiac symptoms, (2) typical ECG findings, and (3) biochemical markers. The silent nature of perioperative MI, the subtle and transient ST depression changes on ECG (resulting in non-Q-wave MI), and the low specificity of the creatine kinase (CK) MB isoenzyme all lead to inconsistencies in the diagnosis of MI and uncertainty about the longterm significance of perioperative markers of MI.

inflow region at the tips of the mitral valve, may also contribute to the recognition of myocardial ischemia. However, transient systolic wall motion abnormalities without accompanying hemodynamic or ECG changes indicative of ischemia are not always related to ischemia. Nevertehless, patients who demonstrate new, persistent wall motion abnormalities perioperatively are more likely to experience a postoperative adverse cardiac outcome than are those with normal wall motion.

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quantitative assays for cTnI and cTnT. In patients with acute MI, cTnT and cTnI levels first begin to rise above their normal reference limits by 3 hours after the onset of chest pain. Elevations of cTnI may persist for 7 to 10 days, and cTnT for 10 to 14 days, following acute MI. The kinetics of release are similar in those with Q-wave or non-Q-wave acute MI. The assay for cTnI is currently the most sensitive and specific marker of myocardial injury. In surgical patients, cardiac troponins have been shown to identify postoperative MI better than CKMB isoenzymes. Finally, the cTnT assay is probably capable of detecting episodes of myocardial necrosis below the detection limit of current CKMB assays. Hence the terms minor myocardial damage and microinfarction have been coined to describe myocardial changes in patients with chest pain and elevated TnT but normal CKMB levels. Regardless, it is well established that such patients are at increased risk for an adverse clinical outcome (e.g., recurrent MI, need for revascularization, death).

Risk Assessment Most studies have focused on historical predictors of cardiac risk discovered during preoperative assessment. Of these, only recent MI (<6 months) and congestive heart failure are significant predictors of perioperative cardiac morbidity. New data show that postoperative ischemia is also a significant predictor of subsequent cardiac morbidity. All cardiac surgical patients are considered at risk for the development of perioperative ischemia, which may occur preoperatively (up to 20% of patients), intraoperatively (up to 50% of patients), and postoperatively (up to 30% of patients). A smaller proportion of noncardiac surgical patients are at risk for perioperative ischemia, depending on their underlying disease. In such patients, most ischemic episodes occur postoperatively. Contributing factors to perioperative myocardial ischemia are listed in Table 76-1. Traditionally, increases in myocardial oxygen demand were thought to be the most important causes of perioperative ischemia; however, recent data reveal that decreases in supply may also be a significant cause.

Table 76–1

■

Factors that Contribute to Myocardial Ischemia

Coronary artery vasoconstriction or vasospasm and thrombosis likely account for a large percentage of episodes of perioperative ischemia that occur without hemodynamic aberrations. Also, because oxygen extraction is near maximum in working myocardium, maintenance of normal blood oxygen content is critical in the presence of restrictions to coronary flow.

Implications Myocardial ischemia may initiate both systolic and diastolic myocardial dysfunction, lead to arrhythmias, or progress to MI. There is a proven association between the occurrence of perioperative ischemia and increased cardiac morbidity and mortality. Moreover, studies suggest a causal relationship between perioperative ischemia and MI. In cardiac surgical patients, intraoperative ischemia exhibits the strongest correlation with perioperative MI. In noncardiac surgical patients, postoperative ischemia exhibits the strongest correlation with perioperative MI. Perioperative MI increases mortality in both cardiac and noncardiac surgical patients. Development of acute MI is often preceded by a period of myocardial ischemia. Thus, early detection of perioperative myocardial ischemia should prompt therapeutic measures to relieve the ischemia, thereby reducing the incidence or size of any subsequent MI.

MANAGEMENT Management of perioperative myocardial ischemia is based on interventions that decrease myocardial oxygen demand or increase its oxygen supply (Table 76-2). Nitroglycerin. Nitroglycerin reduces myocardial oxygen demand by lowering left ventricular end-diastolic volume and afterload. It increases oxygen delivery by coronary artery vasodilatation and a reduction in left ventricular enddiastolic volume. Nitroglycerin is often the initial drug of choice for the management of perioperative myocardial ischemia. However, if such ischemia is associated with tachycardia, β-blockers are also indicated.

Table 76–2

■

Management of Myocardial Ischemia

Increased Myocardial Oxygen Demand

Reduce Myocardial Oxygen Demand

Increased Increased Increased Increased

Decrease heart rate Decrease contractility Decrease left ventricular end-diastolic volume Reduce afterload

heart rate contractility left ventricular end-diastolic volume wall tension (afterload)

Decreased Myocardial Oxygen Supply

Increase Myocardial Oxygen Supply

Decreased coronary blood flow Vasoconstriction Thrombosis Decreased diastolic time Decreased aortic diastolic pressure Increased ventricular end-diastolic pressure Decreased blood oxygen content Decreased hematocrit Decreased oxygen saturation

Increase coronary blood flow Decrease vasoconstriction Decrease thrombosis Increase diastolic time Increase aortic diastolic pressure Reduce ventricular end-diastolic pressure Increase blood oxygen content Optimize hematocrit Increase oxygen saturation

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β-Blockers. β-Blockers decrease myocardial oxygen demand by reducing heart rate and contractility. They increase oxygen supply by increasing diastolic time and reducing ventricular wall stress, especially in patients with left ventricular hypertrophy. Recent data indicate that β-adrenergic antagonists may decrease morbidity and mortality associated with myocardial ischemia and MI. Calcium Channel Blockers. The calcium channel blockers diltiazem and verapamil, but not the dihydropyridine calcium channel blockers (e.g., nicardipine), decrease myocardial oxygen demand by reducing heart rate and contractility and may increase oxygen supply via coronary artery vasodilatation,1 an increase in diastolic time, or a reduction in wall stress. Although still somewhat controversial, dihydropyridines such as sublingual nifedipine or intravenous nicardipine may be specifically indicated when coronary artery vasospasm is suspected.

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In summary, if myocardial ischemia occurs in association with tachycardia or hypertension, initially one must ensure adequate anesthesia, oxygenation, and ventilation. If all of these are present, nitroglycerin or β-blockers (or both) should be used. If myocardial ischemia is associated with tachycardia and hypotension, judicious volume expansion or careful use of α1-receptor agonists is instituted. If ischemia is associated with a normal heart rate and hypotension, therapy should be directed toward the suspected cause of hypotension (e.g., left ventricular pump failure, hypovolemia, reduced systemic vascular resistance). Intra-aortic balloon counterpulsation, via afterload reduction and diastolic augmentation, may also be beneficial and should be considered. When ischemia is not associated with hemodynamic aberrations, coronary vasodilator drugs (e.g., nitroglycerin) or those that both dilate coronary arteries and relieve coronary vasospasm (e.g., nifedipine,4 nicardipine) are used.

PREVENTION

Phosphodiesterase Inhibitors. The physiologic benefits are similar to those of β-adrenergic agonists. However, systemic and pulmonary vasodilatation, along with little effect on heart rate, makes these drugs more appealing than the traditional β-adrenergic agonists.

Perioperative myocardial ischemia and infarction result from a complex interaction among hemodynamic parameters, vascular tone, neural influences, and the coagulation system. Most attempts to prevent perioperative ischemia and infarction (especially with a single drug) have failed. Patients receiving cardiac medications should continue taking them until the time of operation. Preoperative antiischemic therapy should be directed at optimizing the cause of ischemia (myocardial oxygen supply and demand imbalance) and treating its consequences (e.g., congestive heart failure, arrhythmias). Anesthesia should be administered to maintain stable perioperative hemodynamic parameters. No evidence exists that the type of anesthesia (general versus regional, inhalation versus intravenous) affects the incidence of perioperative ischemia or MI in patients at risk. However, prophylactic use of β-blockers may significantly decrease the incidence of perioperative ischemia and subsequent cardiac morbidity. Prophylactic perioperative nitroglycerin is controversial, and the role of drugs that reduce the risk of coronary thrombosis remains to be determined. Aggressive control of postoperative pain with regional anesthesia and analgesia to attenuate associated stress may decrease cardiac morbidity and mortality in both cardiac and noncardiac surgical patients. Perioperative use of thoracic epidural anesthesia with local anesthetics may benefit all patients by blocking cardiac sympathetic efferent activity and improving the balance between myocardial oxygen demand and supply. Finally, studies have revealed that maintenance of normothermia may decrease perioperative myocardial ischemia and subsequent cardiac morbidity.

1 It is likely that diltiazem and verapamil also relieve coronary vasospasm. 2 Many believe that α1-mediated venoconstriction of the splanchnic venous capacitance bed (increasing venous return and preload) is mechanistically more important for any noted blood pressure increase than increased systemic vascular resistance per se. 3 Sodium nitroprusside also dilates the venous capacitance bed to reduce venous return and left ventricular preload. This enhances the effect of systemic arterial vasodilatation to reduce blood pressure.

4 Caution: Nifedipine is not available in intravenous form. It is available in capsule form for oral or sublingual use. However, owing to variable absorption after sublingual dosing and potentially adverse hemodynamic actions due to the drug’s polysorbate vehicle (direct depression of myocardial contractility, systemic venous and arterial dilatation), in 1985 the Food and Drug Administration advised against using nifedipine in hypertensive emergencies. Among the adverse effects reported with sublingual nifedipine in this setting were fatalities due to acute MI.

Sodium Nitroprusside. The physiologic benefits of sodium nitroprusside are similar to those of nitroglycerin, with the added benefit of afterload reduction. However, the precise role of sodium nitroprusside in the management of myocardial ischemia is controversial because of the possibility of coronary artery steal (from vasodilatation of coronary artery resistance vessels).3 β-Receptor Agonists. The physiologic effects of β-agonists may be beneficial (decreased left ventricular diastolic volume, increased aortic diastolic pressure) or detrimental (increased heart rate, reduced diastolic time, increased contractility). Their precise role, if any, in the management of myocardial ischemia is determined by the specific clinical hemodynamic aberration present.

CARDIOTHORACIC & VASCULAR SURGERY

α-Adrenergic Agonists. α1-Receptor agonists can increase myocardial oxygen supply by increasing aortic diastolic blood pressure, but they may also increase myocardial oxygen demand by increasing left ventricular end-diastolic volume and wall stress. α1-Agonists also have the potential to cause coronary artery vasoconstriction or vasospasm. These drugs should be used cautiously, and only in patients who would clearly benefit from systemic vasoconstriction and increased aortic diastolic pressure.2 α2-Receptor agonists reduce central nervous system sympathetic efferent tone. This leads to decreased myocardial oxygen demand secondary to reduced heart rate, blood pressure, and left ventricular end-diastolic volume and wall stress (i.e., dilatation of splanchnic venous capacitance bed).

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Further Reading Antman EM, Braunwald E: Acute myocardial infarction. In Braunwald E (ed): Heart Disease, 5th ed. Philadelphia, WB Saunders, 1997, pp 1184-1188. Apple FS, Wu AHB: Myocardial infarction redefined: Role of cardiac troponin testing. Clin Chem 47:337-339, 2001. Badner NH, Knill RL, Brown JE, et al: Myocardial infarction after noncardiac surgery. Anesthesiology 88:572-578, 1998. Beattie C, Fleisher LA: Perioperative myocardial ischemia and infarction: Preface. Int Anesthesiol Clin 30:xix-xxii, 1992. Brown CS, Bertolet BD: Cardiac troponin: See ya later, CK! Chest 111:2-4, 1997. Carrier M, Pellerin M, Perrault LP, et al: Troponin levels in patients with myocardial infarction after coronary artery bypass grafting. Ann Thorac Surg 69:435-440, 2000.

Chaney MA: Intrathecal and epidural anesthesia and analgesia for cardiac surgery. Anesth Analg 84:1211-1221, 1997. Duke PC (ed): Myocardial ischemia and performance. Anesthesiol Clin North Am 9:455-730, 1991. Fleisher LA, Barash PG: Preoperative cardiac evaluation for noncardiac surgery: A functional approach. Anesth Analg 74:586-598, 1992. Keats AS: Adventures in perioperative myocardial ischemia. Texas Heart Inst J 20:5-11, 1993. Leslie JB: Prevention and treatment of intraoperative myocardial ischemia Anesth Analg 84(Suppl):79-89, 1997. Mangano DT: Perioperative cardiac morbidity. Anesthesiology 72:153-184, 1990. Mangano DT, Goldman L: Preoperative assessment of patients with known or suspected coronary disease. N Engl J Med 333:1750-1756, 1995. Perez-Carceles MD, Osuna E, Vieira DN, et al: Biochemical assessment of acute myocardial ischaemia. J Clin Pathol 48:124-128, 1995.

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Perioperative Hypertension Jerrold H. Levy and Kenichi A. Tanaka

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Case Synopsis A 58-year-old man has just had abdominal aortic aneurysm repair. He is noted to be hypertensive, with a blood pressure of 160/110 mm Hg. His heart rate is 72 beats per minute in sinus rhythm, pulmonary artery pressure is 45/25 mm Hg, pulmonary artery occlusion pressure is 6 mm Hg, and central venous pressure is 5 mm Hg. The patient also has ST segment depression in the anterior precordial electrocardiogram (ECG) leads. Preoperative evaluation revealed no prior history of hypertension, but a history of peripheral vascular disease.

PROBLEM ANALYSIS Definition

Recognition Because BP monitoring is an essential part of perioperative management, either invasive or noninvasive methods may be acceptable for diagnosis and institution of therapy. In cardiac surgical patients, BP is usually kept at lower levels to avoid graft or suture line disruption. Based on data collected from an international survey, hypertension following cardiac surgery is defined as a sustained BP greater than 140/90 mm Hg. When pressures exceed this, most anesthesiologists institute therapy. Recently, new BP guidelines in medical patients were formulated following the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Implications When to treat perioperative hypertension and how rapidly to decrease the BP are not well-resolved issues. Management goals to maintain hemodynamic stability depend on many factors, especially preoperative BP—that is, the patient’s “normal” pressure. There are few data to guide management, and in selected patients (e.g., neurosurgical and cardiac surgical patients), BP may be kept at even lower values immediately following surgery to avoid complications such as hemorrhage, rupture of suture lines, cerebrovascular accidents, myocardial ischemia, and arrhythmias.

MANAGEMENT Therapeutic approaches to perioperative hypertension include the following: ●

● ●

Intravenous vasodilators, dihydropyridine (DHP) calcium channel blockers such as nicardipine,1 dopamine receptor agonists (fenoldopam), hydralazine, or, potentially, angiotensin-converting enzyme (ACE) inhibitors (enalaprilat) Intravenous β-adrenergic blockers Deepening anesthesia

Risk Assessment

Vasodilators

Reported risk factors for hypertension in the postanesthesia care unit include increasing age, smoking, and renal disease. Patients with a preoperative history of angina and those with inadequate ventilation during the postoperative period are also at increased risk for hypertension. Hypertension and tachycardia are associated with increased long-term morbidity and mortality. Preexisting hypertension is also a risk factor.

Nitroprusside and nitroglycerin release nitric oxide to produce arterial vasodilatation and venodilatation, which

1 Clevidepine, another rapid-acting DHP calcium channel blocker, is similar to nicardipine and has a similar hemodynamic profile. It, too, is suitable for intravenous administration and was set to enter phase III clinical trials in 2005.

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The definition of perioperative hypertension differs from that of chronic hypertension. Perioperatively, patients may have acute changes in blood pressure (BP) because of multiple factors, including rapid intravenous volume shifts and changes in sympathetic tone secondary to surgical stimulation, stress responses, or pain. Patients with otherwise normal BP may develop hypertension perioperatively because of these factors. Also, because oral antihypertensive therapy is not possible at this time, patients require parenteral treatment. Hypertension is a major problem after both cardiac and noncardiac surgery. The incidence of postoperative hypertension ranges from 6% to 20% in various noncardiac surgical studies, occurring more commonly in patients with preoperative hypertension, irrespective of anesthetic regimen.

Hypertension following surgery for coronary artery bypass grafting has been reported in 30% to 80% of patients. Augmentation of the stress response because of cardiopulmonary bypass has been suggested as the pathophysiologic basis of increased vascular resistance. Other factors to consider are rapid weaning from mechanical ventilation following cardiac surgery and coronary graft spasm. Ventricular dysfunction is common even in patients with normal preoperative function.

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contribute significantly to the labile hemodynamic state. In a hypertensive patient, intravenous volume administration is often used to allow nitroprusside to be infused when the patient is hypovolemic.2 Although nitroprusside is often used to control postoperative hypertension in other surgical interventions, it may contribute to myocardial ischemia by producing nonspecific coronary vasodilatation and coronary steal. Hydralazine, a more arterioselective vasodilator, is also used in obstetric patients and in perioperative settings, often concomitantly with a β-blocker.

Calcium Channel Blockers There are three types of calcium channel blockers: verapamil, diltiazem, and the DHPs (e.g., nicardipine). Vasodilatation can be produced by any of these drugs, which reduce calcium entry into vascular smooth muscle. DHP calcium channel blockers act by binding with high affinity to the L-type calcium channels, which modulates their voltage-dependent calcium conductivity. DHPs are mainly dilators of the peripheral resistance arteries. In doses that effectively reduce BP, the DHPs have little or no direct negative effect on cardiac contractility or conduction. Their lack of negative chronotropic effect allows an initial reflex increase in heart rate, which decreases during prolonged antihypertensive treatment. Calcium channel blockers do not affect venous smooth muscle; therefore, unlike nitrodilators, they are not venodilators and have little influence on filling pressure and preload. As a result, cardiac output is well maintained or increased when calcium channel blockers are given to reduce arterial pressure. Nicardipine also is a potent coronary and cerebral vasodilator, with important applications in neurosurgical and cardiac surgical patients.

Other Agents Although ACE inhibitors are widely used to treat heart failure, the only intravenous form available is enalaprilat, an indirect-acting agent that is used on occasion to treat perioperative hypertension. ACE inhibitors are complex drugs that interfere with angiotensin II synthesis and may increase nitric oxide release from blood vessels by increasing bradykinin levels. Specific dopamine (DA) receptor agonists are a new class of agents that are under clinical investigation. Fenoldopam, a selective agonist to peripheral DA1-receptors, produces vasodilatation, increases renal perfusion, and enhances natriuresis but may have variable effects on BP and heart rate.

2 Nitroprusside has prominent vasodilatory effects on the venous capacitance bed (i.e., is a potent venodilator) in addition to its arteriodilator effect. Venodilatation reduces venous return and cardiac preload. Because patients with chronic hypertension are often preload restricted—an adaptive response to chronic increased systemic vascular resistance and ventricular wall stress (i.e., afterload)—they may become relatively hypovolemic when given antihypertensive drugs with prominent venodilator effects.

β-Adrenergic Blockers β-Adrenergic blockers reduce heart rate and myocardial contractility, decreasing cardiac output and thus reducing both diastolic and systolic BP. Therefore, β-blockers should be considered in treating perioperative hypertension in patients with tachycardia. Because heart rate is a major determinant of myocardial blood supply, tachycardia must be treated aggressively in patients with ischemic heart disease, and β-blockers should be used as first-line therapeutic agents. Several β-blockers can be administered intravenously and are used as antihypertensive agents in the perioperative period: propranolol, metoprolol, atenolol, esmolol, and labetalol. Distinct advantages of esmolol are its short elimination half-life (<10 minutes) and β1-selectivity.

Deepening Anesthesia Increasing anesthetic depth is always a potential means of treating increased BP during surgery, but it may not always be possible or effective. Regional anesthetic techniques may also be effective at preventing perioperative hypertension. Not to be overlooked is the effect of positive-pressure ventilation or continuous positive airway pressure to impede venous return, effectively reducing preload and systemic BP.

PREVENTION Perioperative hypertension commonly occurs as part of the normal response to induction, surgery, emergence, and pain. Continuing treatment for chronic hypertension is important in the perioperative management of hemodynamic stability. Increasing use of regional anesthetic techniques to better control perioperative pain may also have important effects in preventing perioperative hypertension. Although increasing anesthetic depth can be effective in maintaining hemodynamic control, this technique may not always be feasible; thus, use of the specific antihypertensive agents reviewed here may be required.

Further Reading Aronson S, Boisvert D, Lapp W: Isolated systolic hypertension is associated with adverse outcomes from coronary artery bypass grafting surgery. Anesth Analg 94:1079-1084, 2002. Bailey JM, Tanaka KA, Levy JH: Cardiac surgical pharmacology. In Cohn LH, Edmunds H (eds): Adult Cardiac Surgery, 2nd ed. New York, McGraw-Hill, 2003, pp 85-118. Rose DK, Cohen MM, DeBoer, et al: Cardiovascular events in the postanesthesia care unit: Contribution of risk factors. Anesthesiology 84: 772-781, 1996. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Available at www.nhlbi.nih.gov/guidelines/hypertension/. Tanaka KA, Tsuda A, Yamaguchi K, et al: In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)-induced vasoconstriction in human internal mammary artery. Br J Anaesth 93:257-262, 2004. Vuylsteke A, Feneck RO, Jolin-Mellgard A, et al: Perioperative blood pressure control: A prospective survey of patient management in cardiac surgery. J Cardiothorac Vasc Anesth 14:269-273, 2000.

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Isobel Muhiudeen-Russell and James E. Baker Case Synopsis A 46-year-old woman with primary pulmonary hypertension requires assessment in the postanesthesia care unit. She underwent laparoscopy for acute cholecystitis but required conversion to an open procedure (via a right subcostal incision) to remove the gallbladder. She was mechanically ventilated for 2 hours postoperatively but has since been extubated. Her blood pressure is 78/50 mm Hg, with a heart rate of 110 beats per minute (sinus rhythm). Oxygen saturation is 93% despite receiving oxygen via a facemask with a reservoir bag. A pulmonary artery catheter was placed in the operating room, and her pulmonary artery pressure is 75/45 mm Hg. Temperature is 35.5∞C. The patient is dyspneic, complains of moderate abdominal pain, and appears to be splinting, with rapid, shallow tidal volumes. Her blood pressure has not improved despite a volume challenge with 250 mL of intravenous colloid solution.

Definition Pulmonary artery pressure (PAP) is normally substantially lower than systemic arterial blood pressure. Mean PAP greater than 25 mm Hg, or peak pressure greater than 40 mm Hg, is usually interpreted as pulmonary hypertension. Degrees of pulmonary hypertension are inconsistently defined and may be classified as mild (systolic PAP 40 to 49 mm Hg), moderate (systolic PAP 50 to 59 mm Hg), or severe (systolic PAP 60 mm Hg or above). In keeping with its low-pressure workload, the right ventricle (RV) is a low-pressure, thin-walled structure, but it is able to transmit all its blood to the left atrium owing to the large cross-sectional area and high compliance of the pulmonary vascular bed. Indeed, whereas systemic vascular resistance (SVR) is normally 900 to 1500 dynes •sec•cm–5, pulmonary vascular resistance (PVR) is usually 90 to 120 dynes•sec•cm–5 (1.1 to 1.5 Wood’s units).

Table 78–1

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Thus, pulmonary hypertension is due to either increased PVR, which requires a commensurate increase in the pressure generated by the RV, or a hyperdynamic cardiac state that increases PAP despite a normal PVR. Many disease entities that elevate PVR are chronic processes that, in addition to damaging pulmonary parenchyma, damage or destroy pulmonary blood vessels at both the arteriolar and capillary levels. Notable causes of pulmonary hypertension are listed in Table 78-1 and include chronic obstructive pulmonary disease and interstitial lung disease. Less commonly, pulmonary hypertension due to increased PVR may be congenital (persistent pulmonary hypertension of the newborn) or acquired as an idiopathic entity (primary pulmonary hypertension), as exemplified by the case synopsis. Also, systemic or extrathoracic disease processes may act on previously normal lungs to increase PVR (see Table 78-1). Abnormal cardiac physiology may cause secondary pulmonary hypertension in the absence of elevated PVR.

Causes of and Risk Factors for Pulmonary Hypertension

Idiopathic (primary pulmonary hypertension) Congenital heart disease with increased pulmonary artery blood flow or pressure Cardiac disease with elevated left atrial pressure (e.g., left-sided valvular disease or left ventricular failure) Respiratory system disorders with pulmonary parenchymal or vascular damage Chronic obstructive pulmonary disease Interstitial lung disease (idiopathic or secondary to rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis) Alveolar hypoxemia (e.g., obstructive sleep apnea, chronic high-altitude exposure) Chronic pulmonary thrombosis or thromboembolism (also, sickle cell disease) Congenital (e.g., persistent pulmonary hypertension of the newborn) Portal hypertension Compression of pulmonary veins (e.g., by tumor, lymphadenopathy, anastomotic stricture after lung transplantation) Miscellaneous causes Drugs or toxins Infections, including schistosomiasis and opportunistic infections with human immunodeficiency virus

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PROBLEM ANALYSIS

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Congenital heart disease with left-to-right intracardiac shunting may cause pulmonary hypertension by subjecting the lungs to increased blood flow (e.g., atrial septal defect) or backpressure from the left ventricle (LV; e.g., ventricular septal defect). Also, any cardiac disease that leads to increased left atrial pressure (e.g., dilated cardiomyopathy, ischemic heart disease, mitral stenosis) can also result in pulmonary hypertension, because mean PAP must be sufficiently higher than left atrial pressure to allow blood to flow through the pulmonary vasculature. Unfortunately, many sustained processes that begin as pulmonary hypertension with a normal PVR eventually lead to pulmonary arterial and arteriolar remodeling. This compounds the problem by causing a secondary increase in PVR. Such pulmonary remodeling includes increased muscularity of the medial layer, thickening of the connective tissue within the adventitial layer, and abnormal pulmonary endothelial regulatory function. These changes are usually at least partially irreversible and may perpetuate pulmonary hypertension, even when the underlying hemodynamic problem is corrected.

Recognition and Risk Assessment The ability to recognize pulmonary hypertension has important perioperative implications. It begins with being able to recognize which patients are at risk. When reviewing the patient’s preoperative history, special note should be made of congenital heart disease (whether corrected or not) and chronic pulmonary disease. Such patients constitute the majority of those at risk for significant perioperative pulmonary hypertension, but the other predisposing factors (see Table 78-1) should also be kept in mind. In some of these patients, pulmonary hypertension may have been diagnosed already, and they may have undergone an evaluation to define or quantify the problem. Cardiac catheterization is the gold standard for diagnosing pulmonary hypertension, although noninvasive echocardiography can also be used. In the absence of preoperative information that specifically confirms the diagnosis of pulmonary hypertension, a chest radiograph may show evidence of right-sided cardiac enlargement, and the electrocardiogram may show right axis deviation, right atrial enlargement, or an RV strain pattern. In the case synopsis, a pulmonary artery catheter was inserted preoperatively, prompted by the prior diagnosis of primary pulmonary hypertension. In such instances, the pulmonary artery catheter can confirm any significant elevation in PAP. Generally, mean PAP greater than 40 mm Hg or greater than two thirds of systemic arterial pressure can be interpreted as severe pulmonary hypertension. Although no degree of pulmonary hypertension is necessarily associated with adverse consequences, no degree is necessarily safe either. Indeed, many patients with pulmonary hypertension may tolerate PAP levels that appear quite alarming. Others may suffer adverse consequences even with relatively minor elevations, especially when the increase is acute. The difference is probably related to the RV’s ability to adapt to chronically elevated afterload by concentric hypertrophy, as does the LV in patients with systemic hypertension. Finally, many stresses related to surgery or the conduct of anesthesia influence the degree of perioperative pulmonary hypertension and patient tolerance.

Implications It must be remembered that the real significance of perioperative pulmonary hypertension is not its presence or any particular degree of hypertension but rather the RV’s ability to tolerate any increased afterload. Although pulmonary hypertension is an important cause of hemodynamic instability, the pattern depends on the RV’s inability to eject against increased afterload and to provide adequate LV filling to maintain cardiac output. As the RV fails, both its diastolic and systolic dimensions increase, displacing the ventricular septum to the left. LV function is subsequently impaired due to inadequate diastolic filling and its inability to adequately contract during systole. RV coronary perfusion is also reduced due to RV wall stretching and intracavitary hypertension (recall that unlike the LV, the RV normally receives significant coronary perfusion during systole and is therefore vulnerable to increased systolic and diastolic intracavitary pressures). If systemic hypotension develops from reduced LV stroke volume, RV coronary perfusion pressure is further reduced, and the problem becomes selfpropagating. Severe shock and cardiovascular collapse may be the ultimate expression of postoperative pulmonary hypertension.

MANAGEMENT Although pulmonary hypertension can be difficult to manage, especially when it is chronic and associated with pulmonary vascular remodeling, treatment is based on evidence that elevated PVR may be at least partly reversible. In any event, some factors may actually aggravate PVR, and care must be taken to avoid them to the extent possible. Table 78-2 summarizes the current approach to management.

Ventilatory Management Ventilation has an important impact on PVR and may worsen or improve pulmonary hypertension. Either a very high fraction of inspired oxygen (FiO2 1.0) or severely reduced arterial carbon dioxide tension (PaCO2 <30 mm Hg; significant respiratory alkalosis) may appreciably improve PVR. To reduce PVR, especially with respiratory acidosis, one can increase minute ventilation to lower PaCO2 (keeping it >20 mm Hg) or increase pH (keeping it <7.6). It is likely that pH mediates changes in pulmonary arteriolar tone, not PaCO2 itself. Therefore, if pulmonary parenchymal disease precludes this degree of hyperventilation, systemic alkalinization (sodium bicarbonate) might be considered. Ventilatory management must be conducted to avoid significant increases in lung volume and airway pressure. As lung volumes increase above functional residual capacity, the alveolar capillaries are stretched. This can lead to progressive collapse and reduction in the total cross-sectional area of the pulmonary capillary bed. Conversely, low lung volumes may contribute to the collapse of extra-alveolar vessels and alveolar atelectasis. The former directly increases PVR, whereas the latter increases it through hypoxic pulmonary vasoconstriction.

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Table 78–2

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Management of Severe Pulmonary Hypertension with Right Ventricular Heart Failure

Type of Treatment

Features of Therapy

Conservative and remedial measures to lower PVR Pharmacologic therapy to lower PVR Inotropic support for right ventricle Maintenance of coronary perfusion

High FiO2; avoid hypercarbia and acidosis; correct respiratory alkalosis (pH <7.6); avoid hypothermia or shivering; prevent both alveolar collapse and overdistention; optimize pain control Nitrates; PGE1; inhaled NO; prostacyclin

Optimization of RV preload Mechanical support

Milrinone, dobutamine, or isoproterenol for adequate SAP; norepinephrine or epinephrine if SAP is marginal or inadequate Add α-adrenergic agonist (e.g., phenylephrine) to a combined inotrope-vasodilator (e.g., milrinone); consider norepinephrine for combined inotropic support and elevation of SAP; avoid RV distention Avoid RV distention and underfilling; consider invasive (RAP or PAP) monitoring or transesophageal echocardiography where appropriate RV assist device; intra-aortic balloon pump

FiO2, fraction of inspired oxygen; NO, nitric oxide; PAP, pulmonary artery pressure; PGE1, prostaglandin E1; PVR, pulmonary vascular resistance; RAP, right atrial pressure; RV, right ventricular; SAP, systemic systolic arterial blood pressure.

Other Nonpharmacologic Management

Pharmacologic Management Pharmacologic management of pulmonary hypertension is undertaken to (1) lower PVR directly, (2) support RV inotropic function, and (3) maintain sufficient systemic arterial blood pressure for adequate RV coronary perfusion. Many drugs reduce PVR and have been used in patients with pulmonary hypertension. Nitroglycerin, nitroprusside, calcium channel antagonists, and especially prostaglandin E1 may be effective in reducing PVR and PAP. However, all these drugs have the same limitation: lack of specificity for the pulmonary vasculature. To whatever extent PVR is lowered by these agents, SVR may be similarly decreased. Given the importance of maintaining adequate RV coronary perfusion pressure, any significant reduction in SVR may be poorly tolerated and precipitate acute RV failure. Similarly, some inotropes, such as dobutamine, isoproterenol, and milrinone, are well known for their ability to lower PVR while also increasing inotropy, but use of these drugs is limited by their potential to reduce SVR and cause systemic hypotension when coronary perfusion pressure must be maintained. Use of α-agonists (e.g., phenylephrine) to reduce systemic hypotension may negate any salutary effects of other drugs given to reduce PVR. Thus, inotropes or systemic vasodilators that are also pulmonary vasodilators may be used with caution in patients with preserved systemic blood pressure, but the possibility of an overall deleterious effect

CARDIOTHORACIC & VASCULAR SURGERY

Other factors that may promote acutely elevated PVR and PAP include hypothermia, excess circulating catecholamines due to light anesthesia or uncontrolled postoperative pain, and sepsis. Patients having cardiac surgery are vulnerable to increased PVR due to an increase in circulating inflammatory mediators associated with cardiopulmonary bypass. Although not all of these factors can be controlled, it is important to maintain or reestablish normothermia postoperatively and to treat or prevent postoperative pain as effectively as possible.

and the need to support systemic blood pressure should be kept in mind. Although intravenous drugs that selectively reduce PVR are lacking, inhaled nitric oxide (NO) directly dilates the pulmonary vasculature. By virtue of its rapid degradation by circulating hemoglobin, its vasodilating action is effectively confined to the pulmonary vasculature; SVR is not significantly altered. NO dosages range from 10 parts per million (ppm) to a maximum of 80 ppm. These doses reduce RV afterload without compromising systemic blood pressure or coronary perfusion. Beneficial effects are achieved with NO in many perioperative and critical care settings, including lung or heart transplantation and surgery for congenital heart disease. Improved ventilation-perfusion matching and arterial oxygen tension (PaO2) may also be achieved because inhaled NO increases blood flow to those lung units that are best ventilated. Inhaled prostacyclin also selectively lowers PVR in patients with pulmonary hypertension. Although norepinephrine has the potential to increase PVR, it has been used successfully in many patients with critical pulmonary hypertension. In fact, it is preferred when systemic blood pressure is low or marginal. Owing to wellbalanced α- and β-adrenergic effects, coronary perfusion pressure is well maintained or improved, while RV contractility is enhanced. To the extent that high left-sided heart pressures contribute to pulmonary hypertension (e.g., severe mitral valve disease, ischemic LV failure), inotropic support for the LV may also reduce RV afterload by lowering left atrial pressure. Judicious volume therapy is important in patients with impaired RV function. An excessively low RV preload reduces cardiac output. However, RV overload increases RV wall stress, reduces coronary perfusion (via increased RV intracavitary pressure), and worsens tricuspid insufficiency. Most patients with severely elevated PAP, especially with RV failure or tricuspid insufficiency, do not require more RV preload unless volume or blood loss is significant. If so, any volume loading should be done with caution. For example, patients without improved hemodynamics after a 250-mL colloid or blood product challenge are unlikely to benefit from more volume.

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Also, invasive monitoring may be of some help. A central venous or right atrial pressure greater than 15 mm Hg suggests that more volume is unlikely to be beneficial. If available, transesophageal echocardiography provides the best assessment of left- or right-sided intracardiac volume status.

PREVENTION Unfortunately, pulmonary hypertension severe enough to cause perioperative RV failure is likely the result of a chronic or preexisting condition. Although it cannot be prevented, it may be mitigated or optimized by careful anesthetic management. An exception is new-onset or aggravated pulmonary hypertension caused by intraoperative protamine. This can be prevented by giving the drug more slowly or not giving it at all in patients with a history of protamineassociated pulmonary hypertension. Most other pulmonary hypertension cases, and any attendant cardiac dysfunction, should be diagnosed and quantified during preoperative assessment. Then perioperative management can be adjusted to prevent the development of further PAP increases in at-risk patients. This may require PAP monitoring, transesophageal echocardiography, or both to assess the effects of surgical stress and anesthetic drugs and techniques on PVR, cardiac output, and RV function.

Most nonpharmacologic strategies for treating pulmonary hypertension are also used in preventive intraoperative management for high-risk patients. Ventilator and overall blood gas management should aim to promote appropriate alveolar expansion, oxygenation, and respiratory alkalosis. If possible, agents that might increase PVR (e.g., histamine-releasing muscle relaxants, opioids) should be avoided. If necessary, systemic arterial blood pressure should be supported to maintain RV coronary perfusion. Also, as the case synopsis illustrates, the anesthetic plan must address the need for optimal postoperative pain control, especially when pain impairs ventilatory mechanics. Consider the use of regional analgesia when appropriate, use patient warming devices, and provide an appropriate duration of postoperative mechanical ventilation. Tracheal extubation should be attempted only when the patient is likely to have adequate respiratory mechanics and gas exchange without mechanical assistance.

Further Reading Fischer LG, Van Aken H, Burkle H: Management of pulmonary hypertension: Physiological and pharmacological considerations for anesthesiologists. Anesth Analg 96:1603-1616, 2003. Meyer KC, Love RB, Zimmerman JJ: The therapeutic potential of nitric oxide in lung transplantation. Chest 113:1360-1371, 1998. Stobierska-Dzierzek B, Awad H, Michler RE: The evolving management of acute right-sided heart failure in cardiac transplant recipients. J Am Coll Cardiol 38:923-931, 2001.

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Perioperative Tachyarrhythmias John L. Atlee Case Synopsis A 62-year-old man sustains sudden-onset monomorphic ventricular tachycardia (Fig. 79-1) after separation from cardiopulmonary bypass (CPB) for aortic valve replacement and coronary artery bypass grafting. The tachycardia terminates with internal cardioversion. The patient is returned to CPB for revision of a vein graft. Subsequent separation from CPB and the early postoperative course are uneventful. However, 16 hours after arrival in the intensive care unit, the patient has atrial fibrillation (Fig. 79-2), which is terminated by cardioversion. Antiarrhythmic drug therapy with intravenous amiodarone is begun. However, atrial fibrillation recurs two times over the next 12 hours. On each occasion, it is terminated by cardioversion. After this, the patient stabilizes. He is continued on intravenous amiodarone, with transition to the oral form during his hospitalization and after discharge home. At 1-year follow-up, there has been no recurrence of atrial fibrillation.

Definition Ventricular tachycardia, ventricular flutter or fibrillation, and atrial flutter or fibrillation commonly complicate cardiovascular and thoracic surgery in the early postoperative course. Indeed, without prophylaxis, the incidence of postoperative atrial flutter or fibrillation approaches 50%, especially after valve repair or replacement. Other tachyarrhythmias that may complicate the perioperative course of patients undergoing cardiothoracic or vascular surgery (or other high-risk surgery in high-risk patients) include paroxysmal supraventricular tachycardia, ectopic (uniform or multiform) atrial tachycardia, and junctional or idioventricular tachycardia. Tachyarrhythmias with ventricular preexcitation (i.e., WolffParkinson-White syndrome) or long QT syndromes are discussed in Chapters 80 and 81, respectively.

electrocardiogram (ECG) rhythm strip and place a copy in the patient’s chart. Other attributes that aid in arrhythmia diagnosis are (1) the presence or absence of cannon a waves (indicative of atrioventricualr dissociation), (2) the suddenness of onset and termination (paroxysmal tachycardias), and (3) a gradual rate increase at onset (“warm-up”) and slowing at termination (“fade”), which are characteristic of automatic or ectopic, in contrast to reentrant, tachycardias. The latter usually have a more abrupt onset (often following a supraventricular or ventricular extrasystole) and termination. Also, the onset of tachyarrhythmias can often be recognized by a sudden change in the patient’s hemodynamic status, which should prompt a look at the ECG monitor.

Risk Assessment Predisposing factors for perioperative tachyarrhythmias include (1) advanced age; (2) a history of tachyarrhythmias,

Recognition Electrocardiographic and other features of tachyarrhythmias are provided in Table 79-1. When confronted with a sustained tachyarrhythmia, it is useful (time permitting), for purposes of diagnosis and patient follow-up, to record an

Figure 79–1

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Onset of monomorphic ventricular tachycardia.

Figure 79–2

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Atrial fibrillation.

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Characteristic Electrocardiographic Rates and Rhythms of Perioperative Tachyarrhythmias

Arrhythmia

Rate (bpm)

Rhythm

Comments

Accelerated idioventricular rhythm Atrial fibrillation

A: 50-100* V: 50-110

A: regular V: fairly regular; may be irregular A: highly irregular V: highly irregular A: regular V: regular (with fixed AVHB) or “regularly” irregular (with varying AVHB) A: regular or irregular (with AVHB) V: fairly regular

Hemodynamic insufficiency; intermittent cannon a waves; not amenable to cardioversion

Atrial flutter

AV junctional tachycardia†

A: 400-600 V: 100-160 A: 250-360 V: 75-180 A: 70-130* V: 70-130

Ectopic atrial tachycardia

A: 100-250 V: ≥100‡

Paroxysmal supraventricular tachycardia

A: 150-250§ V: 150-250

Sinus tachycardia

A: 100-180 V: 100-180

Ventricular fibrillation

A: 60-100 V: 400-600

Ventricular flutter

A: 60-100*

Ventricular tachycardia

V: 150-300 A: 60-100*

V: 110-250

No a waves; ventricular rate slows with CSM but remains highly irregular Flutter waves; ventricular rate slows with CSM but remains “regularly” irregular; type 1 flutter (atrial rate ≤340 bpm) may be converted by rapid atrial pacing Hemodynamic insufficiency; intermittent cannon a waves; may slow slightly with vagal maneuvers or β-blocker; not amenable to cardioversion; can be overdriven by atrial pacing More a waves than c- -v waves; possible slowing with vagal maneuvers or CSM, followed by return to usual rate; not amenable to cardioversion

A: abnormal P waves (uniform or multiform); may be irregular V: normal appearance; may be irregular with AVHB A: very regular (if apparent), Constant cannon a waves; CSM or vagal maneuvers may except at onset and cause abrupt slowing and termination of tachycardia or termination have no effect V: very regular, except at onset and termination; normal QRS contour A: regular Rate may gradually slow with CSM or vagal maneuvers, then V: regular unless patient has gradually return to former rate ≥ second degree AVHB A: normal, but difficult Cannon a waves; imminently lethal unless early termination by to see on surface leads DC defibrillation V: grossly irregular and multiform appearance A: normal, but difficult Cannon a waves; imminently lethal unless terminated by DC to see on surface leads cardioversion V: regular, sine waves A: normal, but often not Intermittent cannon a waves; “slow” VT may be tolerated seen on surface leads hemodynamically; prompt DC cardioversion recommended unless capture beats are for most VT present (confirming VT) V: regular (R-R interval may vary by ≥20 msec in 20% of patients, unless interrupted by capture beats from higher pacemakers

*Constant and same as ventricular rate (AV junctional tachycardia, accelerated idioventricular rhythm, or ventricular flutter or tachycardia with retrograde atrial activation). † Also known as accelerated AV junctional rhythm or nonparoxysmal AV junctional tachycardia. ‡ Usually <250 bpm or limited by AV block. § P waves often nonapparent or may be inverted, depending on mechanism for reentry, which could be the AV node or the AV node with retrograde atrial activation via an electrically silent accessory pathway (i.e., the accessory pathway does not conduct from atria to ventricles during sinus rhythm to produce a δ wave associated with ventricular preexcitation). A, atrial; AV, atrioventricular; AVHB, AV heart block; bpm, beats per minute; CSM, carotid sinus massage; DC, direct current; V, ventricular; VT, ventricular tachycardia.

even if the patient is receiving adequate treatment and is now asymptomatic; (3) cardiovascular or chronic pulmonary disease; (4) the presence of an implanted cardiac rhythm management device (e.g., pacemaker, defibrillator, cardiac resynchronization device); (5) hepatic or renal insufficiency; (6) central nervous system disease or space-occupying lesion; (7) dysautonomias; and (8) metabolic or physiologic imbalance (e.g., circulatory or hemorrhagic shock, sepsis, hypercarbia, hypoxia, acid-base imbalance, adverse drug effects or interactions, stress, pain, anxiety, hyperthyroidism, other hyperadrenergic states). Also, some surgical procedures are more likely to be associated with tachyarrhythmias. Aside from cardiothoracic and vascular surgery, neurosurgery for

aneurysms and posterior fossa tumors is not uncommonly associated with bradycardia or tachyarrhythmias. Among the causes of perioperative tachyarrhythmias are ischemia-reperfusion injury, CPB, high circulating catecholamines secondary to physiologic stress (pain, anxiety), and physiologic or metabolic imbalance. Generally, it is uncommon for a patient with a structurally normal heart to develop sustained ventricular tachyarrhythmias. The most common cardiac disorder associated with sustained ventricular tachycardia is coronary artery disease with an acute coronary syndrome (e.g., myocardial ischemia or infarction) or healed myocardial infarction with scar (the substrate) and a superimposed trigger (e.g., ischemia, proarrhythmia, stress).

Ischemia; myocardial reperfusion injury; acute MI; digitalis toxicity Clinical or subclinical cardiovascular disease; cardiac surgery, especially valve surgery; history of treated hypertension, left atrial enlargement, stroke, valvular heart disease, or CHF; COPD; occult or manifest thyrotoxicosis See AFB; also, may occur after congenital heart disease surgery

Inferior wall MI; open heart surgery; acute rheumatic fever; myocarditis; digitalis toxicity*

EAT: possibly digitalis toxicity; more likely, significant structural heart disease

Accelerated idioventricular rhythm

Atrial fibrillation (AFB)

Atrial flutter (AFT)

AV junctional tachycardia (AVJT)

Ectopic atrial tachycardia: uniform (EAT) or multiform (MAT) MAT: commonly COPD or CHF; digitalis is an unlikely cause; theophylline has been implicated

Cause

Arrhythmia

Optimize treatment for COPD or CHF; stop digitalis and give potassium if not elevated; consider magnesium if hypomagnesemia is present

Possibly β-blockers; indicated treatment for predisposing factors; possibly magnesium supplementation in pediatric congenital heart surgery

Amiodarone; left or biatrial pacing or β-blockers for primary prevention in cardiac surgery; sotolol (class II and III activity) may also be effective; in thoracic surgery, primary prophylaxis with a β-blocker; indicated therapy for predisposing disease or conditions to facilitate more specific measures See AFB

Measures to correct cause; usually transient (seconds to minutes), so little or no effect on outcome

Prevention

Causes, Prevention, and Treatment of Tachyarrhythmias

Table continued on following page

MAT: possibly a β-blocker (nonasthmatics); give potassium or magnesium if low; antiarrhythmics include verapamil, diltiazem, or amiodarone; does not respond to DC cardioversion

DC cardioversion is preferred initial therapy (promptly restores sinus rhythm in most cases); IV ibutilide converts 60%-90% of episodes (but 8%-10% risk of proarrhythmia); rapid atrial pacing (AFT ≤340 bpm) converts some AFT (also, see AFB) If digitalis is the cause, stop it; potassium, β- blockers, lidocaine, or phenytoin may also be used; atrial or AV overdrive pacing (slowly reduce rate to wean from pacing); DC cardioversion should not be used if digitalis could be the cause; otherwise, it might be effective if AVJT is not caused by enhanced automaticity (e.g., if AVJT occurs with myocardial reperfusion injury) EAT: digitalis; consider β-blocker or CCB to slow ventricular rate; possibly add class IA, IC, or III antiarrhythmic; does not respond to DC cardioversion

Often transient (after establishing coronary reperfusion); overdrive atrial pacing preferred to drugs (atropine or other positive chronotropes) to increase atrial rate; easily overdriven by atrial pacing If hemodynamically destabilizing and acute, DC cardioversion; drugs for chemical conversion of acute AFB include class IA, IC, and III antiarrhythmics, but consider proarrhythmia risk (up to 8%-10% with ibutilide and dofetilide)

Treatment

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322 Stress, anxiety, or pain; sepsis; hypovolemia, hypercarbia, or hypoxia; light anesthesia; MH; sympathomimetic, anticholinergic, and some illicit drugs Myocardial ischemia, MI, reperfusion injury; cardiomyopathy (end stage) due to any cause; idiopathic Myocardial ischemia, MI, reperfusion injury; cardiomyopathy (end stage) due to any cause; specific types of VT†; severe imbalance due to physiologic or metabolic imbalance or drug related (e.g., proarrhythmia)

Sinus tachycardia

Indicated treatment for primary heart disease; removal of offending drugs(s); correction of physiologic or metabolic imbalance

Indicated treatment for primary heart disease

Treat, remove, or avoid the underlying cause

Rest, reassurance, or sedation may abort attacks; provide adequate pain control and avoid triggers; RF ablation of APs or AVN pathways is definitive for prevention

Immediate DF followed by IV amiodarone or procainamide to prevent recurrences; search for and correct causative conditions If destabilizing (some slow VT is not), immediate DC followed by IV amiodarone or procainamide to prevent recurrences; search for and correct identifiable causative or contributing conditions

After vagal maneuvers, adenosine, edrophonium, or CCB; if patient is unstable, immediate DC cardioversion; class IA antiarrhythmics increase AP conduction time and refractory periods; class II antiarrhythmics, adenosine, and digitalis increase AVN conduction time and refractory periods; class IC and III antiarrhythmics increase conduction time and refractory periods in both APs and AVN None unless symptomatic or causes myocardial ischemia; β-blockers

Treatment

*Recognized by regularization of rate in patients with AFB receiving digitalis, and signs of digitalis toxicity. † Idiopathic VT or that associated with arrhythmogenic right ventricular dysplasia, a surgical scar involving the right ventricular outflow tract (e.g., after correction of tetralogy of Fallot), bundle branch reentry, or mitral valve prolapse. AP, accessory pathway; AV, atrioventricular; AVN, AV node; bpm, beats per minute; CCB, calcium channel blocker; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; DC, direct current; DF, defibrillation; IV, intravenous; MH, malignant hyperthermia; MI, myocardial infarction; RF, radiofrequency; WPW, Wolff-Parkinson-White syndrome.

Ventricular tachycardia

Ventricular flutter or fibrillation

Anxiety; panic attacks; caffeine; theophylline; catecholamines; WPW

Paroxysmal supraventricular tachycardia

Prevention

Causes, Prevention, and Treatment of Tachyarrhythmias—cont’d

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Idiopathic left ventricular tachycardia and right ventricular outflow tract tachycardia are two uncommon but specific types of ventricular tachycardia that occur in patients without demonstrable heart disease. In addition, idiopathic ventricular fibrillation is a potentially lethal tachyarrhythmia that occurs in otherwise healthy individuals and requires aggressive management.

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of inducing a proarrhythmic event (ventricular tachycardia or fibrillation); this risk is greatest for patients with structural heart disease. Among the antiarrhythmic drugs approved for intravenous use, amiodarone carries the least risk of proarrhythmia (1% to 2%). The risk of proarrhythmia can be as high as 8% to 10% with some class IA or IC drugs and with ibutilide or dofetilide, especially in patients with structural heart disease.

Implications

MANAGEMENT Prompt direct-current cardioversion or defibrillation is the preferred initial treatment for all hemodynamically disadvantageous tachyarrhythmias that can be terminated by such shocks. Those that cannot be terminated by these methods are ectopic atrial tachycardias (uniform or multiform), accelerated atrioventricular junctional rhythm or idioventricular tachycardia, and tachyarrhythmias due to digitalis toxicity. For all tachyarrhythmias with distinct QRS complexes, synchronized shocks (direct current) are used. This applies to most non-sinus-origin supraventricular tachycardia and ventricular tachycardia. Defibrillation is used for ventricular fibrillation and polymorphic ventricular tachycardia if QRS complexes and T waves are indistinguishable. Antiarrhythmic drugs can be used for cardioversion if the arrhythmia does not pose an imminent threat to life. Examples are intravenous ibutilide or amiodarone for “chemical” conversion of atrial flutter or fibrillation. However, the use of drugs for cardioversion carries the risk

PREVENTION The old adage “an ounce of prevention is worth a pound of cure” is especially applicable to perioperative tachyarrhythmias. Meticulous attention to the preservation of optimal physiologic and metabolic balance is fundamental to the prevention of adverse arrhythmic events. Also, multiple antiarrhythmic drug therapy may have an adverse impact on cardiac arrhythmia “substrates” (any diseased myocardium). Further, one must be mindful of drug interactions that might promote arrhythmias or have other untoward circulatory or neuroregulatory consequences. Causes, prevention, and treatment of specific tachyarrhythmias (aside from those associated with ventricular preexcitation or long QT syndromes) are outlined in Table 79-2.

Further Reading Atlee J: Perioperative cardiac dysrhythmias. Anesthesiology 86:1397-1424, 1997. Crystal E, Connolly SJ, Sleik K, et al: Interventions on prevention of postoperative atrial fibrillation in patients undergoing heart surgery. Circulation 106:75-80, 2002. Dorman BH, Sade RM, Burnette JS, et al: Magnesium supplementation in the prevention of arrhythmias in pediatric patients undergoing surgery for congenital heart defects. Am Heart J 139:522-528, 2000. Ho RT, Cullans DJ: Malignant ventricular arrhythmias. In Antman EM (ed): Cardiovascular Therapeutics. Philadelphia, WB Saunders, 2002, pp 477-501. Hollenberg SM, Dellinger RP: Noncardiac surgery: Postoperative arrhythmias. Crit Care Med 28:145-150, 2000. Mangrum JM, DiMarco JP: Acute and chronic pharmacologic management of supraventricular tachyarrhythmias. In Antman EM (ed): Cardiovascular Therapeutics. Philadelphia, WB Saunders, 2002, pp 423-444. Olgin JE, Zipes DP: Specific arrhythmias: Diagnosis and management. In Braunwald E, Zipes DP, Libby P (eds): Heart Disease, 6th ed. Philadelphia, WB Saunders, 2001, pp 815-889. Thomas RG: Supraventricular tachycardia: Implications for the intensivist. Crit Care Med 28:129-135, 2000. Waktare JEP, Camm AJ: Atrial fibrillation: A comprehensive approach. In Antman EM (ed): Cardiovascular Therapeutics. Philadelphia, WB Saunders, 2002, pp 458-476.

CARDIOTHORACIC & VASCULAR SURGERY

Hemodynamic tolerance of tachycardia depends on the inherent stability of the rhythm, its rate and duration, and the status of atrial transport function, ventricular compliance, and ventricular function. Ventricular fibrillation, polymorphic ventricular tachycardia, and fast ventricular tachycardia are inherently unstable and pose an immediate threat to life. Tachyarrhythmias with sustained high ventricular rates impair ventricular filling, reduce diastolic time and coronary perfusion, and increase myocardial oxygen demand. Atrial transport function loss (which occurs with atrial fibrillation, junctional tachycardia, and all ventricular tachyarrhythmias) reduces ventricular filling and is especially disadvantageous for patients with reduced ventricular compliance. Finally, patients with marginally compensated heart failure may rely on sinus rhythm or a paced equivalent to meet their basic metabolic needs. Otherwise, they may develop overt heart failure.

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80

John L. Atlee Case Synopsis A 61-year-old woman has paroxysmal, irregular, wide QRS tachycardia in the recovery room following general anesthesia for left thoracotomy and upper lobe lung resection (Fig. 80-1). The ventricular rate exceeds 220 beats per minute for some beats, and the rhythm disturbance is poorly tolerated. Her preoperative electrocardiogram (ECG) during sinus rhythm revealed δ waves consistent with ventricular preexcitation.

PROBLEM ANALYSIS Definition The association of paroxysmal tachycardia with ECG evidence of ventricular preexcitation during sinus rhythm (δ waves) is known as Wolff-Parkinson-White (WPW) syndrome. Ventricular preexcitation requires functional accessory atrioventricular (AV) pathways that bypass normal AV conduction via the AV node during sinus rhythm to cause ventricular preexcitation. The fast conduction and refractory periods of accessory pathways (APs) are similar to those of atrial muscle. APs may also conduct from the ventricles to the atria (retrograde or ventriculoatrial conduction) to participate in AV reciprocating tachycardia (AVRT) (Fig. 80-2). Further, they may conduct atrial impulses more rapidly during atrial flutter or fibrillation than would otherwise be the case with conduction via the

Figure 80–1 ■ Electrocardiogram from the recovery room (leads V1-V3). Note the highly irregular, wide QRS tachycardia, with ventricular rates ranging from 150 to 300 beats per minute.

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AV node. Usually, the ventricular rate during atrial flutter or fibrillation is limited by the AV node refractory period (300 msec) to less than 200 beats per minute. In contrast, the AP refractory period is shorter (240 msec), which allows ventricular rates greater than 250 beats per minute. If such rates are sustained, rapid deterioration to ventricular fibrillation is possible.

Figure 80–2 ■ Atrioventricular reciprocating tachycardia (AVRT) in a patient with ventricular preexcitation (δ waves) during sinus rhythm. During AVRT, conduction to the ventricles (i.e., orthodromic conduction) is via the AV node, giving rise to a narrow QRS complex tachycardia. The propagating impulse returns to the atria via the accessory pathway (i.e., antidromic conduction) to complete the reentry circuit. The rate of tachycardia is about 210 beats per minute and is associated with evidence of myocardial ischemia (elevated or depressed ST segments, depending on which lead is viewed). Although retrograde P waves often accompany antidromic AVRT, in this example, the P waves are not apparent, possibly due to the ST segment changes related to ischemia.

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Recognition Features of WPW syndrome and ventricular preexcitation include the following: ● ●

● ●

Short P-R interval (<0.12 second) Wide QRS complex (>0.12 second) with slurred initial QRS (δ wave) in some leads Usually, normal terminal QRS ST-T changes commonly directed opposite to the major δ wave and QRS vectors

●

●

●

During orthodromic AVRT, inverted P waves (leads II, III, aVF) usually follow a narrow QRS complex. This contrasts with AV nodal reentry PSVT (the other >40% of all PSVTs), where P waves are usually nonapparent. With antidromic AVRT (<5% of PSVTs), retrograde P waves (if apparent) are upright in the inferior leads, and the QRS complex is widened (i.e., maximal preexcitation). Antidromic AVRT may be difficult to distinguish from monomorphic or polymorphic ventricular tachycardia. The appearance depends on whether single or multiple APs participate in ventricular activation during tachycardia. During atrial flutter or fibrillation in patients with WPW syndrome, antegrade conduction may occur via the AV node or APs. In this case, there might be no, incomplete, or maximal preexcitation. With maximal preexcitation, atrial flutter or fibrillation may be difficult to distinguish from polymorphic ventricular tachycardia; however, it may be better tolerated, and the R-R intervals are more irregular. Irregular R-R intervals with wide QRS tachycardia, with minimally or maximally preexcited beats (see Fig. 80-1), suggest atrial flutter or fibrillation as the mechanism for tachycardia.

Tachyarrhythmias with Ventricular Preexcitation

●

325

Primary ventricular tachycardia or fibrillation is rare in WPW syndrome (<1% of tachycardias).

The incidence of WPW syndrome is 1 to 3 per 1000 persons (60% to 70% male preponderance). However, the incidence is difficult to estimate, because the presence of ventricular preexcitation can be highly variable on the same day in the same individual. Indeed, APs may manifest (i.e., antegrade conduction over the AP during sinus rhythm) only at certain times in one’s lifetime. For example, the incidence of orthodromic AVRT in patients with WPW syndrome increases from 10% in adults younger than 40 years to 35% or more in those older than 60 years. The most common paroxysmal tachycardia with WPW syndrome is AVRT (70% to 80%), with orthodromic AVRT accounting for 90% to 95% of AVRT. Atrial fibrillation accounts for 15% to 30%, and atrial flutter for 5% of paroxysmal tachycardias in WPW syndrome. In the absence of coronary artery disease, heart failure, or other causes for arrhythmias, primary ventricular tachycardia is uncommon (<1% of tachyarrhythmias in patients with WPW syndrome). This is important to remember when confronted with a paroxysmal wide QRS tachycardia in a patient with WPW syndrome. For example, lidocaine to treat "presumed" ventricular tachycardia (see Fig. 80-1) might further reduce AP refractoriness and accelerate AP conduction, thereby increasing the rate of preexited tachycardia and possibly causing ventricular fibrillation. Any event that temporarily dissociates conduction via the AV node and APs can initiate paroxysmal AVRT. This could be an atrial, junctional, or ventricular extrasystole, asynchronous atrial or ventricular pacing, sinus tachycardia with rate-dependent AV block, or the use of certain drugs (e.g., theophylline, catecholamines, caffeine, illicit stimulants). Also, the risk of tachyarrhythmia is increased by stress, anxiety, fatigue, exercise, and alcohol abuse. No studies have shown that anesthetic drugs (except ketamine) facilitate the induction of tachyarrhythmias in patients with WPW syndrome. Indeed, many anesthetic drugs act directly or indirectly to increase AV node and AP refractoriness, so that AVRT is uncommon during anesthesia and surgery. However, orthodromic AVRT or preexcited tachyarrhythmias may occur in preoperative holding areas or postanesthesia care units in patients with WPW syndrome in response to stress, pain, anxiety, or some imbalance. Except for patients at increased risk for postoperative atrial tachyarrhythmias (e.g., cardiac surgery), anesthesia and surgery should have little effect on the incidence of perioperative atrial flutter or fibrillation in patients with WPW syndrome.

Implications Risk Assessment ●

●

●

●

Preexcitation can be highly variable (present or absent) over one’s lifetime. The most common paroxysmal tachycardia in WPW syndrome is orthodromic AVRT (70% to 80%); this is a narrow QRS tachycardia. Atrial flutter or fibrillation accounts for most other (20% to 25%) tachycardias in WPW syndrome. Ninety percent to 95% of AVRT in WPW syndrome is orthodromic tachycardia (narrow QRS), and 5% to 10% is antidromic tachycardia (wide QRS, preexcited tachycardia).

Due to the fast rates with orthodromic or antidromic AVRT (180 to 250 beats per minute—faster than AV node reentry PSVT) and the fact that the rate of atrial flutter or fibrillation may exceed 300 beats per minute, ischemia with early hemodynamic collapse and rapid deterioration to ventricular fibrillation is possible. Prompt intervention is thus required for most paroxysmal tachycardias in patients with WPW syndrome. Patients with WPW syndrome require a different approach to management, because AV conduction may occur exclusively or preferentially over the APs rather than over the AV node. A paradoxical acceleration of rate after the administration of

CARDIOTHORACIC & VASCULAR SURGERY

The QRS appearance with ventricular preexcitation may be confused with bundle branch block, ventricular hypertrophy, or even myocardial infarction. It varies, depending on the location of APs (left or right anterior, posterior septal, or free walls) and coexisting ECG abnormalities. APs may conduct antegradely (atria to ventricles) to cause δ waves or preexcited tachycardia, or retrogradely (ventricles to atria) to cause orthodromic AVRT, the mechanism for more than 40% of paroxysmal supraventricular tachycardias (PSVTs) in all patients, with or without WPW syndrome. Preexcited tachycardias include wide QRS antidromic AVRT and preexcited atrial flutter or fibrillation (see Fig. 80-1). Finally, APs may “manifest” (cause δ waves or preexcited tachycardia) at any time during one’s lifetime, but not at others. The ECG appearance with supraventricular tachyarrhythmias in WPW syndrome is as follows:

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cardiac glycosides, calcium channel blockers, or adenosine is due to both direct and indirect effects of these drugs, and they should generally be avoided in patients known to have WPW syndrome.

MANAGEMENT ●

●

Narrow QRS AVRT ● Vagal maneuvers ● Drugs that increase AV node or AP refractoriness, such as β-blockers, amiodarone, class IA or IC antiarrhythmics, or sotalol (a β-blocker possessing class III activity) ● Cardioversion, if hemodynamically unstable Wide QRS tachycardias: antidromic AVRT and preexcited atrial flutter or fibrillation ● Cardioversion with hemodynamic instability (equipment should be available at bedside when treating any wide QRS tachycardia with drugs in a patient with WPW syndrome) ● Intravenous amiodarone to terminate and prevent recurrences if not hemodynamically unstable ● A drug that increases AV node refractoriness (β-blocker) along with one that increases AP refractoriness (class IA or IC antiarrhythmic, amiodarone, sotalol)

For narrow QRS (orthodromic) AVRT, vagal maneuvers (e.g., carotid sinus massage) are attempted first, followed by drugs that increase AV node refractoriness (e.g., β-blockers, adenosine, and possibly verapamil if adenosine is ineffective). Verapamil will compound any hypotension that may ensue if AVRT fails to terminate, mandating immediate cardioversion. Early cardioversion is required for any AVRT that causes hemodynamic compromise (angina, heart failure, or hypotension). β-Blockers, diltiazem, or verapamil may help prevent recurrences. As a rule, however, patients with recurrent AVRT are best treated with catheter or surgical AP ablation. Although digitalis prolongs conduction time and refractoriness in the AV node, it has been reported to shorten refractoriness in the APs and speed the ventricular response in some patients with WPW syndrome and atrial fibrillation. Therefore, digitalis should not be used as a single drug in patients with WPW syndrome who are prone to or have atrial flutter or fibrillation. Further, because atrial fibrillation can develop during AVRT in many patients with WPW syndrome, this caveat probably applies to all patients with tachycardia and WPW syndrome. Instead, drugs that prolong refractoriness in the APs should be used, such as class IA and IC drugs. For preexcited (wide QRS) tachycardia with hemodynamic compromise, early cardioversion is required. Procainamide or flecainide (both increase AP refractoriness and reduce conduction over the APs) can be used if supine systolic blood pressure is >90 mm Hg. Either may reduce the ventricular rate and terminate preexcited tachycardia. Amiodarone increases AP and AV node refractoriness and may be effective. After direct-current cardioversion for hemodynamically unstable preexcited tachycardia, the previously mentioned drugs that increase AP refractoriness are used to prevent recurrences. Amiodarone increases AV node, atrial, and AP refractoriness and can be used when other drugs fail to prevent recurrences. However, AP ablation is definitive therapy.

With atrial flutter or fibrillation in a WPW patient, dangerous ventricular rates and rapid deterioration into ventricular fibrillation are of paramount concern. If cardioversion is not readily available, the immediate goal is to slow the ventricular rate. Drugs that increase refractoriness and conduction time in the AV node (β-blockers, verapamil, diltiazem), along with those that increase AP refractoriness (sotalol, procainamide, amiodarone), may temporarily reduce the ventricular rate while awaiting direct-current cardioversion.

PREVENTION ●

● ●

●

Provide stress-free circumstances (e.g., reassurance, sedation). Regional or general anesthesia (except ketamine) is safe. Risk of paroxysmal tachycardia is greatest during emergence from anesthesia and during the first few days following major or stressful surgery. Continue any antiarrhythmic drugs the patient may be taking.

For WPW patients with a history of tachyarrhythmias and facing surgery with a high risk of postoperative atrial fibrillation or flutter (e.g., cardiac surgery), consideration should be given to AP ablation before elective surgery. For all other surgery, the circumstances should be as stress free as possible. Reassurance, adequate preoperative sedation and analgesia, and local anesthesia for vascular access will help prevent attacks of paroxysmal tachycardia before surgery. Except for ketamine, it makes little difference which anesthetic agents or techniques are chosen, provided that the patient is adequately anesthetized for periods of maximal stress (e.g., airway or surgical manipulation). There is no literature suggesting that regional or general anesthesia is preferable for procedures that can be performed with either. The risk of paroxysmal tachyarrhythmias is likely highest during emergence and recovery from anesthesia due to sudden awareness and pain, and possibly during the first few postoperative days due to physiologic imbalance and increased stress (e.g., uncontrolled pain). Attention to minimizing these factors should help reduce the risk of paroxysmal tachycardias. Finally, as for any systemic condition requiring chronic medication, it is important that patients receiving antiarrhythmic drugs to prevent recurrences be given these medications up to and throughout the perioperative period. When there is any doubt, a cardiologist should be consulted.

Further Reading Atlee J: Perioperative cardiac dysrhythmias. Anesthesiology 86:1397-1424, 1997. Kastor J: Arrhythmias. Philadelphia, WB Saunders, 2000. Mangrum JM, DiMarco JP: Acute and chronic pharmacologic management of supraventricular tachyarrhythmias. In, Antman EM (ed): Cardiovascular Therapeutics. Philadelphia, WB Saunders, 2002, pp 423-444. Olgin JE, Zipes D: Specific arrhythmias: Diagnosis and treatment. In Braunwald E, Zipes DP, Libby P (eds): Heart Disease, 7th ed. Philadelphia, WB Saunders, 2005, pp 803-863. Thomas RG: Supraventricular tachycardia: Implications for the intensivist. Crit Care Med 28:129-135, 2000.

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John L. Atlee Case Synopsis A 48-year-old woman takes amitriptyline for depression and combined hydrochlorothiazide and triamterene for hypertension. In the recovery room following general anesthesia for abdominal hysterectomy, she has sudden-onset polymorphic ventricular tachycardia. This is poorly tolerated, does not respond to intravenous bolus lidocaine, and recurs following direct-current cardioversion. The corrected Q-T interval on her preoperative electrocardiogram (ECG) was 0.48 second, and her serum potassium concentration was 3.2 mEq/L.

PROBLEM ANALYSIS Definition and Causes

Recognition Figure 81–1 ■ Wide QRS, polymorphic tachycardia (PMVT) in lead II (contiguous tracings). The rate of tachycardia is about 250 beats per minute. Note that normal sinus beats preceding tachycardia in the upper tracing are associated with prolonged Q-T intervals. Therefore, this PMVT qualifies as torsades de pointes, which begins with an extrasystole during inscription of the T wave.

The upper limit of normal for the Q-Tc interval (Q-T interval corrected for heart rate using Bazett’s formula: Q-Tc = Q-T/[R - R1/2]) is 0.46 second for men and 0.47 second for women. In patients with either form of LQTS, there may be U-wave or T-wave abnormalities, such as notched or biphasic T waves or T-wave alternans. These reflect the heterogeneity 327

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The long QT syndrome (LQTS) is the association of polymorphic ventricular tachycardia (PMVT) with Q-T interval prolongation on the ECG (Fig. 81-1). Such PMVT is known as torsades de pointes (TdP). Without Q-T interval prolongation, often in association with an acute coronary syndrome, it is just termed PMVT. This distinction is important, because causes, management, and prevention differ. PMVT is discussed in Chapter 79, along with other perioperative tachyarrhythmias. LQTS has two forms: congenital and acquired. Although congenital LQTS was once thought to be caused by left-sided sympathetic imbalance, it is now known that LQTS is due to intrinsic (congenital) or acquired abnormalities of ionic currents that underlie cardiac repolarization. Prolongation of cardiac repolarization is critical to the generation of early afterdepolarizations (EADs), which in turn can generate spontaneous or triggered action potential upstrokes. If these propagate throughout the heart, ventricular extrasystoles preceded by normal sinus beats with long Q-T intervals are recorded on the surface ECG (see Fig. 81-1). Available evidence implicates EADs and triggered activity in the genesis of TdP. Notably, conditions that elicit EADs experimentally

(e.g., slow heart rate, hypokalemia, drugs that prolong the Q-T interval) are known to be associated with clinical TdP. Also, certain populations of cells within the ventricles (Purkinje fibers, midmyocardium or M cells) are more likely to develop EADs on drug challenge. EADs with heterogeneity in the development of prolonged cardiac action potentials result in a myocardial substrate vulnerable to reentry of excitation, the probable proximate cause for TdP. Genetic studies have now identified at least six separate genes that, if mutated, may cause congenital LQTS. Study of one of these genes (HERG), which encodes a potassium channel protein that regulates a major repolarizing current in cardiac fibers (IKr), has been especially informative with regard to drug-associated TdP. Mutations in HERG reduce IKr and thus prolong action potentials in individual cells, causing congenital LQTS. Further, virtually all drugs that prolong the Q-T interval and cause TdP also block IKr. Unfortunately, this finding is nonspecific, because many drugs that do not cause TdP also block IKr. It is also known that congenital LQTS can show incomplete penetrance; that is, family members with near-normal Q-T intervals may carry the same genetic mutations associated with LQTS that increase the risk of sudden death in their relatives. Available evidence also suggests that 5% to 10% of persons in whom TdP develops on exposure to drugs or other factors that prolong the Q-T interval harbor mutations associated with congenital LQTS and therefore can be viewed as having a subclinical form of the syndrome. This observation is consistent with the clinical concept of reduced repolarization reserve arising from an ion channel gene mutation that predisposes the carrier to drug or other forms of stress-induced TdP.

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of ventricular repolarization. ECG features of TdP with either form of LQTS are as follows (see Fig. 81-1): ●

●

●

QRS complexes that vary in amplitude and appear to twist around the isoelectric baseline Rate of tachycardia usually between 200 and 250 beats per minute Often associated with bradycardia or heart block (especially acquired LQTS)

Risk Assessment There are two forms of congenital LQTS. One (Jervell and Lange-Nielsen syndrome) is accompanied by deafness, and the other (Romano-Ward syndrome) is not. With either, there may be a history of syncope or sudden death due to TdP. With congenital LQTS, TdP is often precipitated by stress, sudden noise, or adrenergic stimulation. Adrenergic dependence may be explained as follows: (1) Mutant cardiac ion channels respond abnormally to adrenergic stimulation in a manner conducive to prolongation of repolarization; and (2) prolonged repolarization increases intracellular Ca2+ accumulation and the likelihood of EAD-triggered activity and TdP. In contrast, TdP with acquired LQTS is facilitated by bradycardia or sinus pauses (i.e., bradycardia- or pausedependent TdP). Syncope with congenital LQTS may initially be misdiagnosed as a seizure disorder, and ECGs may not be obtained. About 30% of patients are diagnosed during clinical evaluation for unexplained syncope or aborted sudden death. Another 60% are identified when family members of an individual with syncope or cardiac arrest (the proband) undergo ECG screening. The remaining 10% are identified by Q-T prolongation on routine ECG testing. What is the risk for syncope or cardiac arrest in individuals with congenital LQTS? Among 328 families with at least one affected family member, 50% of probands, 8% of affected family members, and 2% of unaffected family members experienced one or more cardiac events by 12 years of age. During 10 years of follow-up, 37% of probands, 5% of affected family members, and less than 1% of unaffected family members experienced a cardiac event. Among probands, event rates for syncope and sudden death were 5% and 0.9% per year, respectively. Risk factors for these included length of Q-T interval, history of cardiac event, and heart rate.

Implications Factors that predispose to Q-T interval prolongation and increase risk for TdP include baseline Q-T interval prolongation, high concentrations or rapid infusions of Q-T intervalprolonging drugs, older age, female sex, low left ventricular ejection fraction, congestive heart failure, left ventricular hypertrophy, digitalis, ischemia, bradycardia, hypokalemia or hypomagnesemia, and recent conversion from atrial flutter or fibrillation, especially with drugs that prolong the Q-T interval (e.g., dofetilide, ibutilide). Drugs that may prolong the Q-T interval and cause TdP are listed in Table 81-1. A more extensive list of such drugs can be found at http.//www.torsades.org.

Table 81–1

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Drugs that May Prolong the Q-T Interval and Cause Torsades de Pointes*

Antiarrhythmics

Anti-infectives

Amiodarone† Bepridil Disopyramide Dofetilide Ibutilide Procainamide Quinidine Sotalol

Azithromycin Ciprofloxacin Clarithromycin Clindamycin Erythromycin Fluconazole Gatifloxacin Halofantrine Levofloxacin Pentamidine Sparfloxacin Trimethoprim-sulfamethoxazole

Antidepressants Amitriptyline Desipramine Fluoxetine Imipramine Paroxetine Sertraline Venlafaxine

Antipsychotics Chlorpromazine Haloperidol Mesoridazine Olanzapine Pimozide Risperidone Thioridazine Ziprasidone

Antiemetics Domperidone Droperidol

Migraine Drugs Sumatriptan Zolmitriptan

Miscellaneous Arsenic trioxide Cisapride Isradipine Lidoflazine‡ Methadone Nicardipine

*For relative risk, consult http.//www.torsades.org. † Least likely of listed antiarrhythmic drugs to cause acquired long QT syndrome and torsades de pointes (<2%). ‡ Calcium channel blocker not marketed in the United States.

When an antiarrhythmic drug promotes arrhythmias, these are termed proarrhythmic events. For example, in patients with structural heart disease (especially ischemic cardiomyopathy), the class IC drugs flecainide or propafenone may cause proarrhythmia but not TdP; the proarrhythmia in this setting is incessant monomorphic ventricular tachycardia. Potent inhalational anesthetics also prolong the Q-T interval, but this prolongation is small and is not known to be associated with TdP. Bupivacaine and etidocaine, both of which avidly bind to cardiac sodium channels and have very slow offset kinetics, may be associated with malignant ventricular arrhythmias and severe myocardial depression (cardiotoxicity), but they are not listed as associated with Q-T interval prolongation or TdP (see http.//www. torsades.org). However, in an older study in pentobarbitalanesthetized dogs, both bupivacaine and etidocaine were associated with PMVT resembling TdP following ventricular burst pacing.1 In my view, it is prudent to avoid either local anesthetic in patients with congenital LQTS.

1 Burst pacing is a series of rapidly paced beats (often 10 to 15) intended to initiate or reproduce clinical atrial or ventricular tachyarrhythmias.

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MANAGEMENT Torsades de Pointes with Congenital Long QT Syndrome ●

●

●

●

Torsades de Pointes with Acquired Long QT Syndrome ●

●

●

●

If known, correct or remove the cause of Q-T interval prolongation. Intravenous magnesium sulfate is the initial drug of choice for TdP from an acquired cause. Also, consider administering intravenous potassium if the serum potassium concentration is low. Institute prophylactic atrial, dual-chamber, or ventricular pacing at 75 to 100 beats per minute for bradycardia or pause-dependent TdP. If pacing is not feasible or practical, cautious use of isoproterenol can achieve the same rates. If antiarrhythmic drugs are used to suppress TdP, they must be ones that do not prolong the Q-T interval (see Table 81-1).

2 A task force was commissioned by the American Society of Anesthesiologists (ASA) in 2003 to prepare a practice advisory for the management of patients with CRMD. This was approved by the ASA House of Delegates during the 2004 annual ASA meeting. See Further Reading.

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Polymorphic Ventricular Tachycardia Resembling Torsades de Pointes With PMVT resembling TdP and a normal Q-T interval, antiarrhythmic drugs used for ventricular tachycardia in the absence of Q-T interval prolongation (see Chapter 79) are used for treatment and to prevent recurrences. These include antiarrhythmic drugs that prolong the Q-T interval. With instability or tachycardia intolerance, immediate direct-current cardioversion is advised.

PREVENTION ●

●

●

●

●

With any Q-T interval prolongation, avoid drugs that might further prolong it. Provide stress-free perioperative circumstances, to the extent possible. Continue effective antiarrhythmic drugs (i.e., ones that do not cause Q-T interval prolongation). Consider prophylactic temporary pacing for bradycardia or pause-dependent tachycardia. If the patient is not receiving β-blockers (congenital LQTS), perioperative β-blockade is advised.

For patients with congenital LQTS facing anesthesia and surgery, it is important to provide circumstances that are as stress free as possible. Reassurance, adequate preoperative sedation and analgesia, and local anesthesia for vascular access can help prevent attacks of paroxysmal tachycardia before surgery. Except for ketamine and “sensitizing” inhalational anesthetics (halothane or enflurane, especially if preceded by thiopental induction), it makes little difference which anesthetic agents or techniques are used, provided the patient is adequately anesthetized during periods of maximal stress. There is no literature suggesting that either regional or general anesthesia is preferable for procedures that can be performed with either type. Risk for TdP may be increased during emergence and recovery from anesthesia and possibly for the first few days after major or stressful surgery. If a patient with congenital LQTS is receiving β-blockers, these should be continued throughout the perioperative period. Finally, consideration should be given to temporary perioperative pacing if the patient does not already have a functioning CRMD, and an external cardioverter-defibrillator should be available on site. For patients having elective surgery with ECG evidence of acquired LQTS (i.e., receiving drugs known to cause Q-T interval prolongation) and with a history of syncope, it is prudent to postpone surgery until the cause of syncope is explored thoroughly, and TdP should be high on the list of suspects. If TdP is identified as the cause of syncope, elective surgery should be delayed until the Q-T interval is normalized by withdrawal of the offending drugs. It is almost always possible to substitute another drug (or drugs) less likely to cause Q-T interval prolongation and TdP. Similar precautions apply when physiologic or nutritional imbalance causes acquired LQTS and TdP.

CARDIOTHORACIC & VASCULAR SURGERY

●

Patients with congenital LQTS and a history of syncope or aborted sudden death will likely have an implanted cardiac rhythm management device (CRMD2; see Chapter 97). The CRMD provides rate support (pacing) for bradycardia and internal cardioversion or defibrillation for TdP or ventricular fibrillation. For patients without CRMDs, institute maximally tolerated doses of β-blockers in those with a history of syncope, aborted sudden death, or complex ventricular tachyarrhythmias. If, despite maximally tolerated doses of β-blockers, the patient continues to experience complex ventricular arrhythmias or syncope and does not have a CRMD, consider left stellate ganglion block for patients requiring urgent or emergent surgery. If surgery is elective or can be postponed until after CRMD implantation, consider doing so. Treat TdP with class IB antiarrhythmics (e.g., lidocaine, mexiletine, diphenylhydantoin) and magnesium sulfate. Temporary pacing is advised for patients with bradycardia or pause-dependent TdP to reduce heterogeneity of repolarization with slow rates. Even in patients without profound bradycardia, temporary pacing at 75 to 100 beats per minute may provide rhythm stabilization. If temporary pacing is not feasible or practical, cautious use of isoproterenol to increase heart rate to 75 to 100 beats per minute may prevent recurrences of TdP.

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Further Reading Al-Khatib SM, LaPointe NMA, Califf RM: What clinicians should know about the QT interval. JAMA 289:2120-2127, 2003. American Society of Anesthesiologists Task Force on Perioperative Management of Patients with Cardiac Rhythm Management Devices: Practice advisory for the perioperative management of patients with cardiac rhythm management devices: pacemakers and implantable cardioverter-defibrillators: A report by the American Society of Anesthesiologists Task Force on Perioperative Management of Patients with Cardiac Rhythm Management Devices. Anesthesiology 103:186-198, 2005. Atlee JL: Management of perioperative dysrhythmias. Anesthesiology 86:1397-1424, 1997. Chaudhry G, Muqtada G, Haffagee CI: Antiarrhythmic agents and proarrhythmia. Crit Care Med 28:158-164, 2000.

El-Sherif N, Turitto G: The long QT syndrome and torsade de pointes. Pacing Clin Electrophysiol 22:91-110, 1999. Ho RT, Cullans DJ: Malignant ventricular arrhythmias. In Antman EM (ed): Cardiovascular Therapeutics. Philadelphia, WB Saunders, 2002, pp 477-501. Kasten GW: Amide local anesthetic alterations of effective refractory period temporal dispersion: Relationship to ventricular arrhythmias. Anesthesiology 65:61-66, 1986. Keating MT, Sanguinetti MC: Molecular and cellular mechanisms of cardiac arrhythmias. Cell 104:569-580, 2001. Olgin JE, Zipes DP: Specific arrhythmias: Diagnosis and treatment. In Braunwald E, Zipes DP, Libby P (eds): Heart Disease, 7th ed. Philadelphia, WB Saunders, 2001, pp 815-889. Roden DM: Drug-induced prolongation of the QT interval. N Engl J Med 350:1013-1022, 2004.

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Bradyarrhythmias Paul B. Zanaboni and Charles B. Hantler Case Synopsis During an open abdominal aortic aneurysm repair, a 71-year-old man suddenly becomes profoundly hypotensive following acute blood loss. The mean arterial blood pressure is 40 mm Hg, and the electrocardiogram (ECG) shows a wide complex rhythm of 35 beats per minute. The patient’s preoperative ECG showed a first degree heart block with a bifascicular bundle branch block pattern.

PROBLEM ANALYSIS Definition

Table 82–1

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Causes of Bradyarrhythmias

Failure of Impulse Formation Sinus bradycardia Slow sinus node automatic rate Sinoatrial conduction block Carotid sinus hypersensitivity Neurocardiogenic syncope (with decrease in sympathetic outflow)

Subsidiary Atrial Pacemakers. These pacemakers are found along the sulcus (crista) terminalis and around the coronary sinus orifice. Subsidiary atrial pacemaker rhythms are identified by flattened, biphasic, or negative P waves (e.g., wandering atrial pacemaker) in leads with normally upright P waves (leads II, III, and aVF). Both lower and upper rate cutoffs for subsidiary atrial pacemakers appear to be similar to those for the SA node. The P-R interval may be the same or slightly less than that of the SA node (<0.10 second).

Failure of Impulse Conduction Atrioventricular node heart block First degree Second degree Type I Type II Third degree

1 Fast-response fibers have higher action potential maximum amplitudes and overshoots and faster rates of conduction than do SA or AV node cells. They also have more prominent early rapid (phase 1) repolarization. 2 Advanced second degree AV heart block is defined as two or more successive, blocked P waves, but with some that are conducted. With third degree (complete) AV heart block, no P waves are conducted to the ventricles.

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Bradyarrhythmias include cardiac rhythm abnormalities associated with a slow ventricular depolarization rate (<60 beats per minute). Such rhythm disturbances are clinically significant when associated with abnormalities of vital organ function, such as central nervous system impairment (syncope, altered mental status), postural hypotension, heart failure, or other major organ system dysfunction (especially renal, hepatic, or gastrointestinal). Bradyarrhythmias are caused by failure of impulse formation, failure of impulse conduction, or both (Table 82-1). Anatomic structures involved in the generation and propagation of electrical impulses within the heart (i.e., its specialized conduction system) are depicted in Figure 82-1. The maximum diastolic potential of the sinoatrial (SA) node is between −50 and −60 mV. When maximum diastolic potential is reached, SA node cells immediately begin to depolarize. Spontaneous phase 4 depolarization is due to an imbalance between slowly decaying delayed rectifier (an outward potassium current) and slowly recovering inward calcium currents. The latter cause the cell interior to become progressively less negative with respect to the exterior. A pacemaker current is involved only when the cell interior is less negative than –50 mV. In SA node cells, this current is probably subserved by L-type calcium channels. However, T-type current may be activated during the latter half of spontaneous

phase 4 depolarization (i.e., normal automaticity). Cells of the SA node depolarize to +10 mV, their maximum action potential overshoot. Thus, maximum amplitudes are 60 to 70 mV. Once these are reached, SA node cells repolarize. During early repolarization, especially in atrial or ventricular muscle or Purkinje fibers (i.e.,“fast-response” fibers),1 sodium “window” and calcium currents contribute, along with several different potassium repolarizing (outward) currents. Regardless, in all fiber types, net ionic movements during repolarization favor net outward movement of positive charges (mainly potassium), in addition to a variable contribution of reduced inward calcium and sodium current. During the action potential upstroke (depolarization), net ionic movements favor the net inward movement of positive charges. These are carried mainly by sodium and calcium, but there is also reduced outward movement of potassium. The normal SA firing rate is 60 to 100 beats per minute. Drugs, neural input (both sympathetic and parasympathetic), temperature, and hormones influence the rate of sinus node depolarization by affecting either the rate of spontaneous (phase 4) depolarization or the threshold for a regenerative (self-sufficient) action potential upstroke. In addition to sinus bradycardia (sinus rhythm with a rate <60 beats per minute; Fig. 82-2), there may be bradycardic (slow) escape rhythms arising in lower pacemakers. Such escape pacemaker rhythms (i.e., originating below the atrioventricular [AV] junction) are often associated with advanced second and third degree AV heart block.2

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LA

Sinoatrial (SA) node Subsidiary atrial pacemakers AV junction

Figure 82–1 ■ Anatomic structures involved in the generation and propagation of electrical impulses within the heart (i.e., its specialized conduction system). LA, left atrium, LV, left ventricle; RA, right atrium; RV, right ventricle.

RA

Atrioventricular (AV) node His bundle

Interventricular septum RV

LV

Purkinje fibers

Right bundle branch

Left bundle branch

Atrioventricular Junctional Pacemakers. With AV junctional bradycardia, there may be no apparent P waves, or they may be inverted in ECG leads with normally upright P waves during sinus rhythm. Associated, inverted P (retrograde) waves may occur just before the QRS complex (P-R interval <0.10 second) or, less commonly, after the QRS complex. Purkinje Fibers. Typically (e.g., during escape rhythms associated with advanced second degree or complete [third degree] AV heart block), escape rates are less than 50 beats per minute (may be lower in adults). Commonly, there are no associated P waves; however, there may be dissociated, upright P waves. These originate in the SA node or subsidiary atrial pacemakers but are blocked and bear no relationship to QRS complexes. However, even with advanced second or third degree AV heart block, retrograde (ventriculoatrial) conduction may be intact, so that associated P waves may be possible. If so, these will be inverted in leads with normally positive P waves.3 Ventricular Muscle Fibers. Rarely, ventricular fibers exhibit automaticity. When this occurs, it is due to loss of resting membrane potential. The partial depolarization of these fibers may be the result of disease, usually in association with myocardial ischemia or infarction. Ventricular rates are generally less than 40 beats per minute, and retrograde

3 During advanced second or third degree AV heart block, the sinus node beats independently of the ventricles, and its rate is faster than that of the pacemaker controlling the ventricles. This is because sinus nodes are under autonomic control, blood pressure is lower with ventricular escape rhythm, and there is a baroreflex-mediated increase in sympathetic efferent activity.

P waves are uncommon. Not uncommonly, the atria beat independently of the ventricles (AV dissociation). Following SA node depolarization, the impulse is conducted via specialized atrial conducting tissue. SA conduction block is failure of conduction within the atrial tissue; it is characterized by the absence of P waves on the ECG. When this occurs (or the SA node fails to depolarize), lower pacemaker fibers must assume control of the ventricles. Finally, as alluded to earlier, the SA node is most influenced by altered parasympathetic or sympathetic (autonomic) control. Often, this is mediated by baroreceptors and cardiac mechanoreceptors.

Recognition ECG features of sinus bradycardia and lower pacemaker escape rhythms were already discussed. In addition, bradycardia may also be due to AV conduction delay or block. First degree AV block is simply delayed AV impulse transmission (P-R interval >0.12 second), with no dropped ventricular beats (QRS complexes). Second degree AV block is block of

Figure 82–2 ■ In sinus bradycardia, there is a regular relationship between the P waves and QRS complexes. The rate is less than 60 beats per minute.

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Figure 82–3 ■ With Mobitz type I (Wenckebach) second degree atrioventricular (AV) block, there is progressive P-R interval prolongation before blocked P waves (i.e., the fourth P wave). As with first degree AV block, the P-R interval is greater than 0.12 second, but there are no dropped ventricular beats. In this example, block would be variable (not shown) if the ratio of conducted to nonconducted atrial beats varied (e.g., 3:2, 4:3), as commonly occurs with Mobitz type I second degree AV block. Block usually occurs within the AV node or at its margins.

Risk Assessment Bradyarrhythmias can arise from either intrinsic myocardial causes or external influences, such as increased vagal tone or electrolyte imbalance. Implanted artificial pacemakers (see Chapter 97) are indicated for patients with symptomatic bradyarrhythmias (e.g., easy fatigability, near or true syncope) without reversible causes. GENERAL ANESTHESIA

AND

SURGERY

Bradyarrhythmias that occur during general anesthesia can have many causes. Deep inhalation anesthesia (especially with older volatile agents) and opiates are well-known

Figure 82–4 ■ With Mobitz type II second degree atrioventricular (AV) block, there may be no P-R interval variability (fixed block), or block may be variable (as shown) or intermittent. If fixed, block is constant at some fixed ratio of atrial to conducted beats (e.g., 2:1, 3:1, 4:1). If variable, block varies on a recurring basis (e.g., 2:1 and 3:1). If block is intermittent, periods of normal AV conduction are interrupted by occasional dropped beats, but not on a recurring basis. Type II second degree AV block most commonly occurs at or below the bundle of His.

Bradyarrhythmias

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Figure 82–5 ■ With third degree atrioventricular (AV) heart block (almost always at or below the bundle of His), P waves are independent of the QRS complexes (i.e., complete AV dissociation, as with ventricularorigin brady- or tachyarrhythmias). With third degree AV heart block, the QRS complexes can be narrow (as shown) if the pacemaker that controls the ventricles is within or above the bifurcation of the bundle of His, or widened if the pacemaker controlling the ventricles is more distal.

causes of significant bradycardia during anesthesia. Surgical stimulation may be associated with a relative increase in vagal tone, leading to slowing of SA node automaticity, AV node conduction, or both. Well-known examples are the oculocardiac reflex, peritoneal stimulation, and stimulation of the carotid body; such responses terminate when the stimulation is discontinued. Although both drug- and surgery-induced bradyarrhythmias usually respond to drugs—either anticholinergics (atropine, glycopyrrolate) or sympathomimetics (epinephrine, isoproterenol)—if temporary transvenous or pacing wires are available (e.g., during cardiac surgery), pacing is always preferable to drugs. Drugs have the potential to cause excessive tachycardia, are not easily reversed, and may cause arrhythmias. If AV conduction is intact and transesophageal pacing is available, it is preferred over drugs as treatment for sinus bradycardia and AV junctional rhythms. Drug-resistant, clinically significant bradyarrhythmias should always be treated with external (transesophageal or transcutaneous) or internal (transvenous or epicardial) pacing to improve hemodynamics. NEURAXIAL BLOCKADE Neuraxial blockade, involving the high thoracic level, may lead to vagal dominance (bradycardia) by blocking sympathetic outflow from the cardiac accelerator fibers that originate in the upper thoracic spinal cord. This bradycardia usually responds well to treatment with anticholinergic agents. DRUG-INDUCED BRADYCARDIA Many patients undergoing surgery are taking medications that slow the sinus heart rate or AV node conduction (e.g., β-blockers, nondihydropyridine calcium channel blockers). The combination of these medications, anesthesia, and surgery may result in significant bradyarrhythmias. Again, bradycardia is usually reversed with either anticholinergic or sympathomimetic agents. However, caution is advised, because excess tachycardia can put patients with ischemic heart disease or arrhythmias at further risk. In the case of elective surgery, one should consider a preoperative dose reduction of any drugs that may cause untoward bradycardia due to reduced heart rate or AV conduction block. METABOLIC CAUSES Metabolic conditions may cause significant preoperative or intraoperative bradyarrhythmias. These include hypothermia (now rare with the widespread use of forced air warming blankets), endocrine disorders, and electrolyte abnormalities.

CARDIOTHORACIC & VASCULAR SURGERY

some impulses between the atria and ventricles. It is further subdivided into Mobitz type I, Mobitz type II, and advanced second degree AV block. With Mobitz type I (Wenckebach) AV block (Fig. 82-3), some but not all atrial beats are blocked in a recurring pattern, with progressively prolonged P-R intervals before dropped beats. The ratio of conducted to dropped beats may be fixed (e.g., 3:2, 4:3) or variable (e.g., 4:3 and 3:2). With Mobitz type II block, there are no progressively prolonged P-R intervals before dropped beats, but the block may also be variable (Fig. 82-4). With advanced second degree AV block, there are two or more dropped beats between conducted beats; again, the ratio between the two can vary. Finally, with third degree (complete) AV block, there are no conducted atrial beats (Fig. 82-5). The atria and ventricles are controlled by different pacemakers, and the QRS complexes may be narrow (if the pacemaker that controls the ventricles is above the bifurcation of the bundle of His) or widened (if below the bifurcation). Thus, in third degree AV heart block, there is complete AV dissociation (independent beating of the atria and ventricles).

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With severe hypothermia, there may be sinus bradycardia or escape rhythms, with or without associated Osborne or J waves.4 Patients with hypothyroidism and Addison’s disease often have preoperative bradycardia that may become more clinically significant during surgery and anesthesia due to effects of anesthetic drugs. Hyperkalemia (which hyperpolarizes cells of the SA and AV nodes) can also cause significant sinus bradycardia or slow AV node conduction. The ECG may show a slow, wide-complex rhythm. Severe hyperkalemia can result in AV heart block or asystole. Hypermagnesemia may also cause sinus bradycardia by reducing the slow, inward, depolarizing calcium current. Both hyperkalemia and hypermagnesemia should be corrected before elective surgery to prevent bradyarrhythmias.

Implications Because cardiac output is often reduced with bradyarrhythmias, especially with impaired or loss of atrial transport function (e.g., slow atrial fibrillation or escape rhythms), bradyarrhythmias may be poorly tolerated during anesthesia. Moreover, any vasodilatation, hypovolemia, or myocardial depression is even more poorly tolerated with significant bradycardia. For example, the normal physiologic response to acute hypotension is impaired if there can be no increase in heart rate or cardiac output to maintain tissue perfusion. It is important to remember that cardiac output is the product of both heart rate and stroke volume. Whereas stroke volume is altered by contractility and preload, in addition to the effects of increased heart rate,5 cardiac output is reduced by bradycardia and bradyarrhythmias, especially if the latter are associated with loss of atrial transport function. Properly timed atrial contractions are critical for left ventricular filling in patients with impaired ventricular relaxation (diastolic dysfunction). These include aged patients and those with chronic hypertension, aortic stenosis, or hypertrophic cardiomyopathy. Patients with impaired ventricular systolic function may also tolerate slow heart rates poorly. In this case, stroke volume is reduced by increased end-systolic volume; forward flow must be increased by higher heart rates. Valvular regurgitation, such as mitral regurgitation, is more severe at slower heart rates, possibly due to an increase in mitral annular size.

(e.g., ephedrine, epinephrine, isoproterenol) is considered. If this is ineffective, or if sinus bradycardia results in severe hemodynamic compromise or collapse, artificial pacing (transcutaneous, transvenous, or transesophageal) should be instituted. ATRIOVENTRICULAR JUNCTIONAL ESCAPE RHYTHM AV junctional rhythms, whether bradycardia or tachycardia (rate >100 beats per minute), abolish any atrial transport function and may also be associated with tricuspid or mitral regurgitation. In patients dependent on atrial transport function (those with severe diastolic dysfunction), restoration of sinus rhythm is highly desirable. Anticholinergic or sympathomimetics are often ineffective or only increase the rate of AV junctional rhythm. Use of a β-adrenergic blocker (e.g., esmolol) may restore dominance of the SA node during general anesthesia. However, use of a drug that may exacerbate bradycardia is risky and should be attempted only when the AV junctional rhythm is greater than 60 beats per minute. Other measures include changing to an intravenous anesthetic that may have less impact on the SA node compared with volatile anesthetics. Transesophageal atrial pacing restores atrial transport function and improve preload. SICK SINUS SYNDROME Sick sinus syndrome includes sinus bradycardia, sinus arrest, and chronotropic incompetence; it also may be associated with supraventricular tachyarrhythmias (bradycardiatachycardia, or “brady-tachy” syndrome), the most common of which is atrial flutter or fibrillation. Regardless, treatment for bradycardia is as described earlier for sinus bradycardia. Management of associated tachycardia is discussed in Chapter 79. Always keep in mind, especially in patients with sick sinus syndrome and a history of tachyarrhythmias, that excessive tachycardia or tachyarrhythmias are a distinct possibility with any positive chronotropic treatment. Often, patients with symptomatic sick sinus syndrome have had dual-chamber pacemakers implanted, as well as drug treatment to prevent tachyarrhythmias and to slow AV node conduction.

Failure of Impulse Propagation FIRST DEGREE ATRIOVENTRICULAR BLOCK

MANAGEMENT Failure of Impulse Formation SINUS BRADYCARDIA Clinically significant sinus bradycardia is treated according to the severity of any physiologic impairment. Conservative management includes removing or reducing the dose of drugs known to inhibit the SA node or removing the surgical stimulus (e.g., oculocardiac reflex). If this is not effective or possible, use of anticholinergics (e.g., atropine) or sympathomimetics 4 Osborne or J waves consist of prominent notching of the terminal QRS complex with ST segment elevation. 5 Except for the treppe or Bowditch effect, whereby an increase in heart rate increases cardiac contractile force.

No treatment is indicated for first degree AV block, unless it is associated with symptomatic or hemodynamically significant bradycardia or escape rhythms. There are, however, rare exceptions. For example, after cardiac surgery, shorter P-R intervals may improve diastolic filling (preload), especially after hypertrophic cardiomyopathy repair. Thus, dual-chamber sequential (AV) pacing with surgically placed temporary pacing wires to shorten the P-R interval may result in improved ventricular filling. Also, if hemodynamic insufficiency is due to P-R interval prolongation, both perioperative and long-term (if symptomatic) dual-chamber pacing should be considered. SECOND DEGREE ATRIOVENTRICULAR BLOCK Mobitz type I AV block is usually due to impaired AV node conduction. It rarely progresses to complete heart block.

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have published guidelines for the implantation of permanent pacemakers (see “Further Reading”). Indications for temporary perioperative pacing are less well established. However, temporary pacing should be strongly considered for patients without an implanted cardiac rhythm management device and with debilitating symptoms or documented disadvantageous bradycardia, escape rhythms, or AV heart block and facing intermediate- or high-risk surgery.

THIRD DEGREE ATRIOVENTRICULAR BLOCK

Further Reading

Some children with congenital complete AV heart block are asymptomatic, and permanent pacemaker implantation can be postponed until adolescence. However, pacing is indicated for all adult patients with third degree block unless it has a reversible cause (e.g., digoxin intoxication, β-blocker overdose).

Atlee JL: Perioperative cardiac arrhythmias: Diagnosis and management. Anesthesiology 86:1397-1423, 1997. Atlee JL, Pattison CZ, Mathews EL, et al: Transesophageal atrial pacing for intraoperative sinus bradycardia or AV junctional rhythm: Feasibility as prophylaxis in 200 anesthetized adults and hemodynamic effects of treatment. J Cardiothorac Vasc Anesth 7:436-441, 1993. De Costa D, Brady WJ, Edhouse J: Bradycardias and atrioventricular conduction block. BMJ 324:535-538, 2002. Goodacre S, McLeod K: ABC of clinical electrocardiography. BMJ 324: 1382-1385, 2002. Gregoratos G, Abrams J, Epstein AE, et al: ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee on Pacemaker Implantation). Circulation 106:2145-2161, 2002. Zimetbaum PJ, Josephson ME: Use of the electrocardiogram in acute myocardial infarction. N Engl J Med 348:933-940, 2003.

PREVENTION Patients undergoing surgery have similar indications for permanent pacemaker placement as the general population. The American Heart Association, American College of Cardiology, and North American Society for Pacing and Cardiac Electrophysiology (now the Heart Rhythm Society)

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Pacing (temporary or permanent) is indicated only when any associated bradycardia is hemodynamically significant or severely symptomatic. Mobitz type II AV block can be treated conservatively in the absence of preoperative symptoms. It is likely due to intra- or infra-Hisian disease and frequently progresses to advanced second or third degree heart block. Symptomatic, hemodynamically disadvantageous bradycardia is an indication for temporary pacing (surgery) and, if persistent, permanent pacing.

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Mohammed Minhaj Case Synopsis A 62-year-old man underwent coronary artery bypass graft surgery via a median sternotomy, with harvesting of the internal mammary artery. During a routine postoperative visit, the patient complains of a “tingling” sensation in the fourth and fifth fingers of his left hand. On physical examination, he has decreased sensation over those fingers, with minimally reduced muscular function in the ulnar distribution. A neurologic consultation is obtained, and the patient is diagnosed with a brachial plexus injury.

PROBLEM ANALYSIS Definition Nerve injuries are a well-recognized complication of anesthesia, causing substantial morbidity for patients and liability for anesthesiologists. Despite their prominence in closed claims analyses (16% of injuries in the most recent American Society of Anesthesiologists [ASA] Closed Claims Project database), no single cause has been clearly delineated. Although the proportion of nerve injuries has remained relatively constant over the last two closed claims surveys, there has been a relative decrease in the proportion of ulnar nerve-related injuries. The reason for this decrease is probably more stringent attention to proper positioning, but given the multifactorial nature of this complication, it is unlikely that simple improvements in positioning can entirely eradicate this problem in the future. The ASA closed claims study found that anesthesia care was appropriate in 66% of all nerve injury claims, reinforcing the notion that multiple factors likely contribute to such complications. These factors include the following: ● ●

●

Ischemia to the brachial plexus Direct trauma (e.g., during central venous cannulation of the internal jugular vein via the needle or postprocedural hematoma) Needle injury, metabolic insults, and idiopathic injuries

The clinical syndrome of idiopathic brachial neuritis has been reported in a wide range of patient populations, including obstetric, arthritic, and noncardiac surgical patients. However, injuries to the ulnar nerve and brachial plexus occur more frequently during cardiac than noncardiac surgery. For example, the incidence of nerve injury in noncardiac surgery ranged from 0.02% to 0.06%, whereas that in cardiac surgery ranged from 2% to 38%. 336

Recognition Most often, nerve injuries that occur during cardiac surgery are identified postoperatively. Intraoperative identification of injury is limited, given that most patients are under general anesthesia (85% of all ulnar nerve injuries in ASA closed claims analyses were associated with general anesthesia). Further, there is no intraoperative monitoring that reliably detects nerve injury. Although some investigators have attempted to identify intraoperative signs that may predict postoperative dysfunction, these have not proved very reliable. Somatosensory evoked potentials (SEPs) reportedly allow the early identification of nerve injury, especially when harvesting of the internal mammary artery is involved. Such harvesting is typically associated with greater chest retraction, potentially producing excessive stretch on the brachial plexus. Transient intraoperative changes in SEPs obtained during venous cannulation have not reliably predicted postoperative sequelae, although SEPs obtained at the conclusion of surgery may do so. In general, nerve injury in cardiac surgical patients differs from that in noncardiac patients. As mentioned earlier, such injuries are more common in the former. Cardiac patients also typically demonstrate sensory deficits in the lower roots of the brachial plexus (C8-T1), compared with more upper and middle nerve root distributions in noncardiac surgical patients. Further, sensory deficits are typically more prominent than motor deficits in cardiac surgical patients; the opposite is true in noncardiac patients. Finally, symptoms are usually present in the early postoperative period in both groups of patients.

Risk Assessment Most peripheral nerve injuries are attributed to ischemia of the intraneural vasculature. The interruption of adequate oxygen and nutrient delivery leads to injury and postoperative deficits. Such ischemia is generally thought to be a result

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Table 83–1

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Risk Factors for Perioperative Nerve Injury during Cardiac Surgery

Sternal retraction Positioning of sternal retractors Asymmetrical sternal retraction Internal mammary artery harvesting Duration of surgery Duration of cardiopulmonary bypass Hypothermia Penetration injury due to first rib fracture during sternotomy Injury during cannulation of internal jugular vein Direct, needle-related injury Hematoma formation resulting in compression of brachial plexus

Table 83–2

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Preexisting Anatomic and Pathophysiologic Risk Factors for Perioperative Nerve Injury

Diabetes Neuropathy Alcoholism Herpes zoster Polyarteritis nodosa Peripheral vascular disease Coagulopathies Hypertension Hypothyroidism Cervical rib Deformities in shoulder or derivation of brachial plexus

Implications Most cardiac patients with postoperative brachial plexus injury recover quickly. It has been estimated that more than 90% of such patients recover substantially within 1 month of surgery. In one study, 94% of patients were asymptomatic by the time of hospital discharge. Subsequent referral to a hand clinic for continued symptoms has been reported in only 0.2% of all cardiac surgical patients. Even when recovery is prolonged, most patients recover fully within a year, and it is rare to have a patient with incomplete recovery. Coexisting diseases such as diabetes have been implicated in more prolonged or incomplete recoveries.

MANAGEMENT Because most cases resolve quickly and spontaneously, supportive management is often sufficient. Splints and physical therapy have been reported to be beneficial, even immediately postoperatively. These measures help prevent muscle atrophy and provide support until symptoms resolve. Only if symptoms are prolonged (>3 months) should more comprehensive interventions be considered. Electrophysiologic studies are usually performed only if symptoms persist and spontaneous recovery is prolonged. Electromyography may be performed to evaluate signs and symptoms of denervation during rest, reinnervation of motor units during weak effort, and loss of motor units during maximal effort. In one clinical study in which bilateral nerve conduction studies were performed in patients who experienced perioperative ulnar neuropathy, 12 of 14 patients with unilateral symptoms had abnormal nerve conduction studies on the contralateral side. These findings suggest that preexisting neuropathies may manifest during the perioperative period. Surgical intervention is usually limited to conditions that involve anatomic abnormalities, such as thoracic outlet syndrome, fracture of the first rib resulting in penetration of the brachial plexus, or compression by bony prominences.

PREVENTION Prevention of perioperative nerve injuries is difficult, given that the mechanisms of injury are incompletely understood.

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of stretching or compression of the plexus caused by patient malpositioning. There is, however, some debate regarding “appropriate” positioning during cardiac surgery. One study reported a higher rate of nerve injury in patients whose arms were at their sides compared with those whose arms were abducted (23.5% versus 14.5%), although this difference was not statistically significant. Some authorities advocate a “hands-up” position, with the arms abducted 90 degrees but flexed at the shoulder by 15 to 20 degrees, and the forearm flexed at the elbow by 90 to 110 degrees to reduce stretch on the brachial plexus and the associated risk of nerve injury. However, no data exist to show that this significantly reduces brachial plexus injuries when compared with the more traditional practice of tucking patients’ arms at their sides and padding the elbows. Because patient positioning is a concern in all surgeries, there has been considerable debate about ideal positioning. Also, because the incidence of postoperative nerve injury is higher with cardiac surgery than noncardiac surgery, investigators have searched for mechanisms (other than ischemia) specific to cardiac surgery. Multiple mechanisms have been postulated by various authors (Table 83-1); however, excessive sternal retraction is the most commonly accepted risk factor for brachial plexus injury. Understanding the anatomy of the brachial plexus and the effects of sternal retraction on it may help determine causative factors for perioperative injury. The nerve roots of the brachial plexus are fixed at their points of exit from the vertebral canal and are distally anchored to the axillary fascia. Moreover, the plexus lies close to many bony structures, such as the head of the humerus, first rib, clavicle, and coracoid process, making it vulnerable to compression at these sites. Autopsy studies have shown that excessive spread of the sternal retractor pushes the clavicles into the retroclavicular space and rotates the first rib upward. These movements may result in stretch of the brachial plexus. Finally, some investigators have postulated that fracture of the first rib during sternal retraction may cause direct penetration injury to the plexus. In addition, preexisting anatomic and pathophysiologic disease processes have been reported as risk factors not only for brachial plexus injury but also for delayed postoperative recovery (Table 83-2).

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Although proper patient positioning, along with adequate padding of pressure points and avoidance of brachial plexus stretch, may not prevent all nerve injuries, the importance of such measures cannot be overemphasized. A thorough understanding of the anatomy involved and the potential mechanisms of injury enables anesthesiologists to reduce such postoperative complications. In addition to awareness of the specific risk factors postulated to contribute to postoperative nerve injury in cardiac surgery, most clinicians advocate the following: ●

●

●

●

Proper vigilance with regard to patient positioning and position changes Minimal sternal retraction, especially during harvesting of the internal mammary artery, and placement of sternal retractors as caudally as possible Maintenance of a neutral (midline) head position to minimize tension on the brachial plexus produced by head rotation Avoidance of asymmetrical retraction when possible (perform true median sternotomy)

Further Reading Alvine FG, Schurrer ME: Postoperative ulnar-nerve palsy: Are there predisposing factors? J Bone Joint Surg Am 69:255-259, 1987. Ben-David B, Stahl S: Prognosis of intraoperative brachial plexus injury: A review of 22 cases. Br J Anaesth 79:440-445, 1997.

Cheney FW, Domino KB, Caplan RA, Posner KL: Nerve injury associated with anesthesia: A closed claims analysis. Anesthesiology 90:1062-1069, 1999. Dumitru D, Liles RA: Postpartum idiopathic brachial neuritis. Obstet Gynecol 73:473-475, 1989. Eggers KA, Asai T: Postoperative brachial plexus neuropathy after total knee replacement under spinal anaesthesia. Br J Anaesth 75:642-644, 1995. Hanson MR, Breuer AC, Furlan AJ, et al: Mechanism and frequency of brachial plexus injury in open-heart surgery: A prospective analysis. Ann Thorac Surg 36:675-679, 1983. Hickey C, Gugino LD, Aglio LS, et al: Intraoperative somatosensory evoked potential monitoring predicts peripheral nerve injury during cardiac surgery. Anesthesiology 78:29-35, 1993. Jellish WS, Martucci J, Blakeman B, Hudson E: Somatosensory evoked potential monitoring of the brachial plexus to predict nerve injury during internal mammary artery harvest: Intraoperative comparisons of the Rultract and Pittman sternal retractors. J Cardiothorac Vasc Anesth 8:398-403, 1994. Kroll DA, Caplan RA, Posner K, et al: Nerve injury associated with anesthesia. Anesthesiology 73:202-207, 1990. Lederman RJ, Breuer AC, Hanson MR, et al: Peripheral nervous system complications of coronary artery bypass graft surgery. Ann Neurol 12:297-301, 1982. Tomlinson DL, Hirsch IA, Kodali SV, Slogoff S: Protecting the brachial plexus during median sternotomy. J Thorac Cardiovasc Surg 94: 297-301, 1987. Vahl CF, Carl I, Muller-Vahl H, Struck E: Brachial plexus injury after cardiac surgery: The role of internal mammary artery preparation: A prospective study on 1000 consecutive patients. J Thorac Cardiovasc Surg 102:724-729, 1991. Vander Salm TJ, Cereda JM, Cutler BS: Brachial plexus injury following median sternotomy. J Thorac Cardiovasc Surg 80:447-452, 1980. Vander Salm TJ, Cutler BS, Okike ON: Brachial plexus injury following median sternotomy. Part II. J Thorac Cardiovasc Surg 83:914-917, 1982.

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David Muzic and Mark A. Chaney Case Synopsis A 68-year-old man with a history of non-insulin-dependent diabetes mellitus, hypertension, alcohol abuse, and heavy smoking is scheduled for four-vessel off-pump coronary artery bypass grafting (CABG). After uneventful induction of anesthesia, severe aortic atheromatous disease is observed via transesophageal echocardiography (TEE) in the descending aorta, and the aortic root is not well visualized. Epiaortic ultrasound scanning is performed to ascertain the best location for a planned radial artery graft anastomosis. The patient’s biventricular function is adequate, and the CABG is performed successfully. The postoperative course is complicated, however, by significant short-term memory loss, and the patient is discharged first to a skilled nursing facility and eventually to an assisted-living home.

Definition Central neurologic injury following CABG is much more common than was previously recognized. Such impairment was formerly observed primarily as stroke, which currently has a perioperative incidence of 1% to 5% for CABG surgery. However, studies of postoperative neuropsychological function using rigorous testing strategies have shown neurocognitive dysfunction in 50% to 90% of patients at discharge and in 20% to 40% throughout the first year after CABG. Accordingly, postoperative central nervous system (CNS) impairment is often divided into two types of adverse outcomes, along these same lines: ●

●

Type I outcomes due to macroembolic focal injury, associated with stupor and coma Type II outcomes due to macroembolic global injury, associated with deterioration of intellectual function or memory

The focal neurologic deficits representing overt stroke (type I outcomes) are caused mainly by macroemboli of atheroma debris, thrombus, and air. Current data suggest that microemboli of similar materials and debris such as bone wax, marrow, and lipid particles from retransfused cardiotomy suction blood are major contributors to the more diffuse (and much more common) injuries associated with type II outcomes. The systemic inflammatory response of surgical stress and blood contact with the cardiopulmonary bypass (CPB) circuit are believed to contribute importantly to type II injury. Other causes of both type I and type II CNS injury include cerebral hyperthermia during rewarming, arterial hypotension, and neurohormonal derangements.

A recent randomized, controlled trial comparing type II neurocognitive outcomes in patients undergoing conventional CABG with and without CPB showed a nonsignificant trend toward a benefit of off-pump CABG at 3 and 12 months postoperatively. The incidence of type II outcomes was 29% versus 21% at 3 months (P = 0.15) and 33% versus 31% at 12 months (P = 0.69) for conventional CABG versus off-pump CABG, respectively. Importantly, these findings suggest that type II neurologic outcomes are more common than previously thought and that rigorous neurocognitive testing is necessary for detection. For example, an earlier multicenter study demonstrated only a 3% incidence of type II outcomes at discharge for patients undergoing conventional CABG, whereas a more recent study with more thorough neurocognitive testing revealed incidences of 53%, 36%, 24%, and 42% at discharge, 6 weeks, 6 months, and 5 years after discharge following CABG, respectively.

Recognition The presence of type I CNS injury is often apparent in the immediate postoperative recovery period. This type of injury commonly presents with failure to awaken from anesthesia, obtundation, generalized or localized hypertonicity, aphasia, visual field deficits, hemineglect, or seizures and is thought to be caused by intraoperative embolic phenomena or global or regional cerebral hypoperfusion. Progressive deficits or signs of elevated intracranial pressure, especially in the presence of anticoagulation, suggest intracranial hemorrhage and require immediate evaluation. Computed tomography (CT) is often used in the first 24 hours to evaluate for hemorrhage and then again after 48 hours to detect evidence of infarction (infarcted brain tissue often appears normal on CT imaging before 48 hours). Magnetic resonance imaging is sometimes used in the first 24 hours owing to its higher 339

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sensitivity for diagnosing hemorrhage and brain ischemia; however, it cannot be used in the presence of implanted cardiac rhythm management devices. Worsened or new deficits postoperatively also warrant echocardiography for detection of a cardiac embolic source. Recognition of type II CNS injury is much more difficult. The first sign is often the patient’s report of “not feeling right” or the patient’s family members noting that their loved one has “slowed down” or become more forgetful. Studies to measure intellectual deterioration and memory deficits related to type II injury rely on changes in neurocognitive test scores compared with a preoperative baseline; in practice, however, such a baseline test is almost never performed. Therefore, any neurocognitive decline noted after CABG is rarely quantifiable.

Risk Assessment Perioperative neurologic risk can be divided into patientrelated preoperative risk factors and intraoperative procedurerelated factors. Recognized independent patient-related risk factors for type I injury include the following: ● ● ● ● ● ● ● ● ●

Advanced age Proximal aortic atherosclerosis Previous CABG Peripheral vascular disease Preexisting neurologic disease Diabetes mellitus Hypertension Pulmonary disease Unstable angina

Patient-related risk factors for type II injury include the following: ● ● ● ● ● ●

Advanced age Systolic hypertension greater than 180 mm Hg on admission Excessive alcohol consumption Previous CABG Arrhythmia on day of surgery Antihypertensive therapy

Whether the presence of the apoE ε-4 allele, which is associated with late-onset Alzheimer’s disease and poorer outcome after stroke or subarachnoid hemorrhage, is a risk factor for type I or type II injury remains controversial. Intraoperative procedure-related factors also play a major role in type I and type II injury after cardiac surgery, perhaps owing to increased microembolic and macroembolic load to the brain, cerebral hypoperfusion, or normal or increased cerebral metabolic rate. Manipulation of the aorta by CPB cannulation, cross-clamping, side-clamping, unclamping, or lifting of the heart and the use of an intraaortic balloon pump are also believed to increase the risk of CNS injury. Microembolic load to the brain, as measured by transcranial Doppler, has been shown to correlate with the severity of neurocognitive decline, and an association between microembolization and such aortic manipulations has been demonstrated. Similarly, manipulation of the CPB circuit itself and prolonged CPB time have been implicated as risk factors for CNS injury by increasing the embolic load of air and microthrombi. Open-heart procedures, such as

valve surgery or septal defect repair, also appear to be associated with a greater risk of CNS injury. Possibly the most important intraoperative risk factor is the surgeon’s choice of aortic cannulation site for CPB. Approximately 20% of patients undergoing CABG have moderate to severe ascending aortic atherosclerotic disease. If so, it is critical that the anesthesiologist be involved in the decision making to determine the optimal cannulation site. It has been shown that TEE is more accurate than direct palpation for locating aortic plaques. Therefore, TEE-guided aortic cannulation has become standard in most centers. More recent data show that detecting these plaques is best accomplished with direct epiaortic scanning using a sterilesheathed surface ultrasound probe applied directly to the aorta. Additionally, TEE is helpful in diagnosing other procedure-related risk factors for type I and II adverse neurologic outcomes, including intracardiac thrombi and air, septal defects, and iatrogenic aortic dissection. Maintaining a somewhat depressed cerebral metabolic rate intraoperatively is thought to help prevent CNS injury. Procedures performed under normothermic conditions, or those allowing rapid rewarming after CPB, increase the risk of type I and II injury. Rapid rewarming has been shown to cause a desaturation of jugular venous hemoglobin and is believed to correlate with poorer CNS outcomes. Similarly, avoiding glucose-containing CPB priming fluids and maintaining normoglycemia are believed to reduce risk. One might think that avoiding CPB altogether, by performing off-pump CABG whenever possible, would greatly reduce the risk of CNS injury. However, as mentioned earlier, a recent randomized, controlled trial failed to show any significant difference in type I or II CNS injuries for off-pump versus conventional CABG. Whether off-pump CABG involving bilateral internal mammary artery grafting and the avoidance of aortic manipulation could reduce CNS injury has yet to be shown.

Implications Perioperative CNS injury, whether overt type I or more subtle type II, can be devastating in terms of quality of life and resource utilization. In-hospital mortality is about 10-fold and 5-fold higher for type I and type II injuries, respectively. The need for skilled nursing facilities on hospital discharge also increases approximately 6-fold for type I and 4-fold for type II injury. The economic burden for CNS injury after cardiac surgery reaches well above the billion dollar mark annually.

MANAGEMENT AND PREVENTION Preventing or reducing the risk of neurologic injury during cardiac surgery is of the utmost importance. Even more subtle and common type II injuries have a great impact on postoperative autonomy and patient lifestyle and undermine the primary goal of surgery, which is to improve longevity and quality of life. Therefore, all patients should be considered at risk, and certain steps should be taken to identify and reduce specific risks for neurologic injury. Aortic Imaging. Intraoperative TEE or direct epiaortic scanning allows informed aortic cannulation. Without such

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imaging, an unacceptably large fraction of patients is unnecessarily exposed to large cerebral embolic loads from cannulation and clamping through or near aortic atheromas. Moderate Hypothermia. Cooling during CPB to approximately 32°C reduces the cerebral metabolic rate and provides cerebral protection. Careful rewarming is equally important in preventing unnecessary increases in cerebral metabolism. Avoidance of Arterial Hypotension. Some data suggest that higher mean arterial pressure during CPB is associated with better neurologic outcomes in higher-risk patients as identified by TEE evaluation or direct epiaortic scanning, but this is controversial. It is hypothesized that in these patients, optimizing collateral cerebral flow minimizes the risk of embolic neurologic injury. However, there is little evidence that maintaining a specific mean or cerebral perfusion pressure range improves outcome.

Avoidance of Retransfusion of Unprocessed Blood. Retransfusion of unprocessed cardiotomy suction blood delivers particulate microemboli consisting of cell aggregates, bone wax, lipids, and surgical debris to the circulation. This has been implicated in neurologic injury. Antifibrinolytic Therapy. Aprotinin, a serine protease inhibitor, reduces the inflammatory response to CPB and has the potential to reduce the incidence of stroke in CABG patients. Pharmacotherapy. Many drugs have been evaluated for their ability to reduce neurologic injury after cardiac surgery, but with conflicting results. Thiopental, propofol, etomidate, glucocorticoids, nimodipine, inhalational anesthetics, and others have been studied for their ability to reduce cerebral

metabolic rate, inhibit inflammation and brain edema, and limit the embolic load through cerebral vasoconstriction. However, none has yet been shown to improve neurologic outcome. Devices. Newly developed sutureless and clampless grafting devices allow surgeons to perform aortic proximal anastomoses without the need for aortic side-clamping. This may reduce the embolic load and improve neurologic outcome. Other Surgical Techniques. Minimizing CPB time or performing off-pump CABG may improve neurologic outcomes, but so far, the data have been inconsistent. Also, left and right internal mammary artery grafts (which avoid aortic manipulation), nontraditional aortic cannulation sites, and deep hypothermia have been advocated. However, further study is required to determine whether any of these techniques is truly effective.

Further Reading Arrowsmith JE, Grocott HP, Newman MF: Neurologic risk assessment, monitoring, and outcome in cardiac surgery. J Cardiothorac Vasc Anesth 13:736-743, 1999. Gringore AM, Grocott HP, Mathew JP, et al: The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery. Anesth Analg 94:4-10, 2002. Mackensen GB, Ti LK, Phillips-Bute BG, et al: Cerebral embolization during cardiac surgery: Impact of aortic atheroma burden. Br J Anaesth 91:656-661, 2003. Mark DB, Newman MF: Protecting the brain in coronary artery bypass graft surgery. JAMA 287:1448-1450, 2002. Mora CT, Henson MB, Weintraub WS, et al: The effect of temperature management during cardiopulmonary bypass on neurologic and neuropsychologic outcomes in patients undergoing coronary revascularization. J Thorac Cardiovasc Surg 112:514-522, 1996. Murkin JM: Attenuation of neurologic injury during cardiac surgery. Ann Thorac Surg 72:S1838-S1844, 2001. Newman MF, Wolman R, Kanchuger M, et al: Multicenter preoperative stroke risk index for patients undergoing coronary artery bypass graft surgery. Circulation 94:II74-II80, 1996. Roach GW, Kanchuger M, Mangano CM, et al: Adverse central nervous system outcomes following coronary artery bypass graft surgery in a multicenter study: Incidence, predictors and resource utilization. N Engl J Med 335:1857-1863, 1996. Scarborough JE, White W, Derilus FE, et al: Combined use of off-pump techniques and a sutureless proximal aortic anastomotic device reduces cerebral microemboli generation during coronary artery bypass grafting. J Thorac Cardiovasc Surg 126:1561-1567, 2003. Van Dijk D, Jansen EW, Hijman R, et al: Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: A randomized trial. JAMA 287:1405-1412, 2002.

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Alpha-Stat pH Management. During cooling, targeting a pH of 7.4 corrected to 37°C (i.e., alpha-stat pH management) and maintaining cerebral autoregulation may provide improved neurologic outcomes when compared with pH-stat management. The latter requires the addition of carbon dioxide to the CPB circuit in order to maintain the pH at 7.4 measured at the hypothermic patient’s actual body temperature. However, pH-stat may be beneficial during procedures requiring deep hypothermia, because it may provide better cerebral protection by decoupling cerebral autoregulation and enhancing cerebral blood flow. Even so, the relative importance of these techniques remains unclear.

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Mark Nunnally and Robert N. Sladen Case Synopsis A 75-year-old man with long-standing hypertension and type 2 diabetes mellitus underwent open repair of an infrarenal aortic aneurysm. His baseline creatinine was 1.6 mg/dL and rose to 2.0 mg/dL on the second postoperative day. On the fifth postoperative day, he developed progressive hypoxemia, fever, and hypotension. A contrastenhanced scan of the pulmonary vessels was not suggestive of pulmonary embolism. He was started on a β-lactam and an aminoglycoside for probable pneumonia. Over the next 12 hours, he became hypotensive and anuric. Renal replacement therapy was started, and antibiotic therapy was shifted to a quinolone. The patient’s renal function returned after several weeks, and he was eventually discharged.

PROBLEM ANALYSIS Definition Postoperative acute renal failure (ARF) describes a spectrum of renal dysfunction that occurs after surgery. Unfortunately, multiple definitions of this complication exist, including those based on intervention (dialysis required or not), relative or absolute decline in glomerular filtration rate (GFR), or relative or absolute increase in serum creatinine (SCr) level. It can include new-onset renal failure as well as acute worsening of chronic renal failure. The fractional change in SCr has emerged as a practical and consistent index of the severity of perioperative renal injury; however, the need for dialysis is a potent predictor of outcome. In one study of patients undergoing coronary artery bypass grafting (CABG), mortality associated with ARF was 14%, but this doubled to 28% when dialysis was required. The cause of ARF has traditionally been classified as prerenal (decreased perfusion), renal (parenchymal injury), or postrenal (urinary obstruction). Although these distinctions remain useful for directing diagnostic strategy, they frequently overlap. In about 90% of cases, postoperative ARF is a consequence of sustained prerenal injury that culminates in ischemic acute tubular necrosis (ATN). ATN can also be caused by nephrotoxic insults, which may themselves exacerbate ischemic injury. In animal models, transient low perfusion creates a prerenal state characterized by oliguria and low urine sodium, with salt and water retention. This is the normal renal tubular response to hypovolemia. With increased perfusion, urine flow returns to normal. This is a hemodynamically mediated event with preserved tubular function; it is reversed by restoration of normal hemodynamic function. More prolonged perfusion deficits result in oliguria (with high urine sodium) that does not reverse when perfusion increases. In this scenario, ATN occurs, characterized by tubular obstruction and “backleak.” The latter is a hemodynamically mediated event with loss of tubular function; it is not 342

reversed by restoration of normal hemodynamic function. Even so, intrinsic renal architecture is preserved, and the kidney may ultimately recover. The pathogenesis of ARF reflects the kidney’s unique sensitivity to insult. Figure 85-1 demonstrates several sensitive areas of the nephron. The medulla and inner cortex have marginal blood flow and are therefore at risk for ischemic ATN from alterations in renal oxygen delivery. This could result from intravascular volume depletion, hypotension, diminished cardiac output, or anemia. In nephrotoxic ATN, damage to the tubules is the result of inflammatory signaling, free radical damage, disturbances in cellular metabolism, and disruption of intrinsic renal vasodilators such as prostaglandins and nitric oxide. Tubular cell necrosis and apoptosis lead to loss of function, disruption of architecture, and nephron obstruction by cellular debris. Once this has occurred, restoration of renal blood flow can no longer reestablish GFR.

Recognition Perioperative oliguria is an unreliable index of renal function because it is almost inevitably prerenal in nature. It reflects absolute or relative hypovolemia, with vasoconstriction and sodium retention as a consequence of activation of the sympathoadrenal, renin-angiotensin-aldosterone, and antidiuretic hormone systems. With two very important exceptions (sepsis and liver failure), it is reversed by restoration of normal renal hemodynamics. In contrast, when postoperative ATN occurs, it is often a culmination of multiple lesser insults in a protected milieu, resulting in nonoliguric renal failure, defined as ARF with urine flow 15 to 80 mL/hour. In summary, oliguria is common but seldom implies ARF, but the presence of a normal urine flow rate does not exclude it. When ARF does ensue, loss of renal solute clearance begins to result in the buildup of serum concentrations of electrolytes, urea, water, and other osmotic elements (azotemia). Blood urea nitrogen and SCr are the most commonly used indicators of renal function. Urea depends on

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High levels of catecholamines and angiotensin II constrict the afferent arteriole and worsen GFR. Endothelin is involved in pathologic vasoconstriction. Afferent arteriole Glomerulus Efferent arteriole

Catecholamines Angiotensin II Vasopressin

Low levels of catecholamines and angiotensin II constrict the efferent arteriole and maintain GFR. Vasopressin constricts the efferent arteriole only.

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NO, PGE2, urodilatin

Distal proximal convoluted tubule: High risk for ischemic injury. Alpha receptor predominance makes blood flow sensitive to catecholamines in the setting of hypovolemia. Necrotic tubular cells slough and obstruct the pars recta and sustain low GFR despite restoration of RBF.

Medullary thick ascending loop of Henle: Receives <10% of RBF and is at constant risk of ischemia. Blood flow is maintained by endogenous vasodilators (prostaglandins, nitric oxide). Impaired vasodilation induces ischemicnephrotoxic injury (e.g., NSAIDs, intravenous contrast).

Figure 85–1 ■ The proximal tubule and medullary thick ascending loop of Henle are potential sites of ischemic and nephrotoxic tubular injury. Both segments have high oxygen consumption and are at risk owing to supply-demand imbalance. GFR, glomerular filtration rate; NO, nitric oxide; NSAIDs, nonsteroidal anti-inflammatory drugs; PGE2, prostaglandin E2; RBF, renal blood flow.

tubular excretion but may be a misleading surrogate for tubular function because its blood level is affected by nonrenal pathology, such as gastrointestinal hemorrhage and protein catabolism (abnormally increased) or malnutrition and end-stage liver disease (abnormally decreased). SCr reflects the balance between creatinine production and excretion. These come into equilibrium when renal function is in a steady state. Therefore, SCr is a reliable surrogate for GFR.

However, the relationship between SCr and GFR is not direct; it is exponentially inverse. That is, a doubling of SCr implies a halving of GFR. Thus, a “trivial” increase in SCr from 0.6 to 1.2 mg/dL implies a 50% decrease in GFR. Moreover, SCr does not increase above normal limits until GFR has decreased below 50 mL/minute. In cachectic patients with low creatinine production, SCr may be “normal” with a GFR as low as 30 mL/minute.

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Creatinine clearance provides a real-time estimate of GFR because its calculation (UV/SCr, where U is urine creatinine and V is urine flow rate) incorporates the creatinine excretion rate (UV), which is directly proportional to GFR. If a patient has a urinary catheter and the urine flow rate is carefully measured, reliable estimates of GFR can be obtained with urine collection times of 2 hours or less. A shortcut that is often used in perioperative studies of renal function is to forgo the necessity of urine collection by calculating creatinine clearance from a nomogram—the Cockroft-Gault formula: Creatinine clearance = [(140 – Age [years]) × Weight [kg] × 1.73 m2 × 0.85∗] 72 × SCr [mg/dL] × Body surface area [m2] In the presence of oliguria, evaluation of tubular function may help distinguish a prerenal syndrome from established ARF. The prerenal state is characterized by avid tubular sodium and water retention, leading to small quantities of concentrated urine with low urinary sodium (<10 mEq/L) and a fractional excretion of sodium (FENa) less than 1%. Prerenal states leading to elevated sodium excretion with intact tubular function (e.g., metabolic alkalosis, diuretic use) may spuriously elevate the FENa to greater than 3%. In this setting, a high FENa is unreliable, but persistence of FENa less than 1% is highly suggestive of a prerenal state. Fractional excretion of urea nitrogen has recently been proposed as a more sensitive and specific method to differentiate prerenal azotemia from ATN, especially when diuretics are used. In established ARF, tubular function is lost. The kidney is unable to concentrate urine and retain sodium, leading to small quantities of dilute urine with high urinary sodium (>80 mEq/L) and high FENa (>3%). Additional objective data may be derived from electrolyte disturbances and hemodynamic monitoring. Ultrasonography of the renal vasculature, kidneys, and urinary drainage system can help rule out obstructive uropathy and confirm the diagnosis of ATN (normal renal blood flow) or ischemic injury (regional or global deficits). Risk assessment serves to clarify suspicion and evaluate for treatable risk factors.

Risk Assessment Identification of patients at risk permits more accurate prediction of postoperative ARF and offers the opportunity for intervention. Risk assessment is achieved by integrating patient factors, the surgical procedure, and the perioperative milieu. The potential for acute renal injury increases exponentially as risk factors accumulate. For example, exposure to a single nephrotoxin (e.g., ketorolac) seldom causes a problem, but if combined with other nephrotoxins (e.g., gentamicin) and decreased perfusion (hypovolemia), the risk for ARF becomes extremely high. Of all preoperative risk factors, the most predictive is preexisting renal dysfunction. Renal risk increases exponentially when the preoperative SCr exceeds 2.0 mg/dL. Other important risk factors include advancing age and markers ∗0.85 conversion factor is used for females only.

for vascular disease and end-organ damage, such as diabetes, abnormal cholesterol metabolism, and hypertension. Severe obstructive jaundice and the hepatorenal syndrome are associated with abnormal portal absorption of endotoxin, which induces renal vasoconstriction and a refractory prerenal state characterized by low urine sodium. Sepsis induces a similar milieu, along with the insults of hypotension and sympathetic renal vasoconstriction. Finally, there may be a genetic predisposition to renal injury, as suggested by the finding of a decreased risk associated with a specific apolipoprotein genotype. Intraoperative risk factors are related to the type of surgery (potential for complications such as bleeding, hypotension, or low cardiac output states) and specific interventions that may cause renal injury (e.g., aortic cross-clamping, cardiopulmonary bypass). Suprarenal aortic cross-clamping leads to a complete cessation of GFR, and full recovery may take 24 to 48 hours. Infrarenal cross-clamping also induces a decrease in GFR through reflex vasoconstriction. In either event, the duration of cross-clamping correlates with the risk for ARF. The risk of postoperative renal dysfunction and ARF requiring dialysis is 12% to 25% and 3% to 8%, respectively, for thoracoabdominal aneurysm repair; the risk is 2% to 30% and 0.6% to 1%, respectively, for abdominal aortic aneurysm repair. Cardiopulmonary bypass also increases the risk of ARF, but this is remarkably well tolerated by patients with normal preexisting renal function who have an uncomplicated course. Despite early optimism, off-pump CABG does not consistently decrease the incidence of perioperative renal injury. The most important risk factors in cardiac surgery remain preoperative renal insufficiency, the complexity of the procedure, and postoperative cardiac dysfunction. For all types of surgery, the most important postoperative risk factor is circulatory instability. Sepsis alone may induce renal injury through local vasoconstriction and nephrotoxicity without substantial hemodynamic perturbations. The risk is markedly exacerbated by the concomitant occurrence of nephrotoxic insults. These include pigment nephropathy due to rhabdomyolysis, intravascular hemolysis, severe obstructive jaundice, contrast nephropathy, and drugs. In the case synopsis, the patient had preoperative renal dysfunction (i.e., high SCr), underwent a high-risk procedure (aortic aneurysm repair, even though infrarenal), and was later exposed to several other renal insults (sepsis, contrast exposure, and an aminoglycoside antibiotic).

Implications Overall outcome is substantially determined by the severity of renal injury, but it is adversely affected even when renal dysfunction is moderate. For example, ARF requiring dialysis is uncommon after CABG but is associated with high mortality. Renal dysfunction (SCr increased >1 mg/dL above baseline) is considerably more common and is associated with significantly greater mortality compared with patients with no renal dysfunction. This may be explained by concomitant cardiac dysfunction, or it may be related to an independent adverse effect of renal failure on global organ function. For high-risk surgeries, in-hospital mortality can exceed 60% with ARF; this also leads to a substantial increase in resource utilization.

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This forbidding mortality rate has been little altered despite the development of improved renal replacement therapies (RRTs), including continuous venovenous hemodialysis. Although RRT consistently controls electrolyte and acid-base abnormalities, circulatory overload, and acute uremia, it does not eliminate the risk of sepsis, multiorgan system dysfunction, or impaired wound healing, which also contribute substantially to postoperative morbidity and mortality. Isolated ATN is inherently reversible, but additional ischemic or nephrotoxic insults may convert it into protracted ARF or even established chronic renal failure. In particular, there is compelling evidence that autoregulation is lost in ARF, so when dialysis causes hypotension, it injures the tubular cells and paradoxically delays renal recovery.

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PREVENTION The simplest approach to preventing ARF is the maintenance of hemodynamic stability. This is predicated on the fact that 25% of the cardiac output normally goes to the kidneys. Ultimately, it is wiser to err on the side of hypervolemia rather than to restrict fluids and precipitate ARF. Hemodynamic stability implies the maintenance of both renal blood flow and renal perfusion pressure, especially in states in which autoregulation is lost (ARF) or impaired (vasodilatory shock). Nephrotoxic insults should be minimized or avoided, keeping in mind that the risk of nephrotoxic ATN is exponentially related to the number of insults, which are far more damaging in the presence of shock or sepsis. There are no pharmacologic “magic bullets” for the prevention of ARF. Osmotic diuresis with mannitol can prevent or even reverse tubular obstruction by cellular debris. This is of particular benefit in pigment nephropathy and is routinely used for renal protection during suprarenal aortic cross-clamping. However, although mannitol increases urine flow in infrarenal cross-clamping, it is no better than saline hydration in preserving GFR. Furosemide may decrease oxygen consumption in the thick ascending loop of Henle by diminished ion transport. To obtain its protective effects, however, furosemide must be administered before the insult occurs, and adequate intravascular volume must be maintained. “Renal dose” dopamine has become an increasingly controversial intervention because a number of studies have shown either no effect or possibly harm associated with prophylactic low-dose dopamine. In part, this may be due to the almost 30-fold variability in intersubject plasma dopamine levels, such that patients on low-dose dopamine may have plasma dopamine levels akin to high-level infusions, and vice versa. Nevertheless, we should not discount dopamine’s potential therapeutic role as an inotropic agent to restore normal renal perfusion in patients who are putatively normovolemic but have impaired cardiac function. Fenoldopam is a selective DA-1 receptor agonist and pure vasodilator that increases renal blood flow and blocks tubular sodium reabsorption. Unlike dopamine, it has predictable dose-related effects and is not arrhythmogenic. However, it may cause reflex tachycardia. It may prove to be useful for the prevention of ARF, but human outcome data are lacking, and a recent prospective study failed to show any benefit for reducing radiocontrast nephropathy. Human recombinant B-type natriuretic peptide (nesiritide) is approved by the Food and Drug Administration for the management of decompensated cardiac failure. It is a balanced venous and arterial vasodilator with natriuretic properties that can relieve pulmonary congestion and promote diuresis. Its role in perioperative renal protection is currently being investigated. Early results showing a decrease in radiocontrast renal injury with the prophylactic administration of oral N-acetylcysteine, a free radical scavenger, prompted considerable interest. However, subsequent studies were more equivocal and suggested that the benefit is no greater than that offered by hydration with saline. Most recently,

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A coherent strategic approach is predicated on vigilance for worsening renal function and its associated complications, judicious diuresis, and timely institution of RRT. Hyponatremia, acidosis, azotemia, and elevations in serum potassium, magnesium, and phosphate should be anticipated and treated promptly. Above all, maintenance of adequate renal blood flow and perfusion pressure helps avoid further damage. Diuretics may be helpful for the management of pulmonary congestion and electrolyte disorders, thereby delaying or even avoiding the need for RRT. With aggressive hydration, diuretics form an essential component of “tubular washout” therapy for pigment nephropathy (intravascular hemolysis, rhabdomyolysis). However, tubular delivery of loop diuretics is impaired because of the accumulation of organic acids that compete for active transport in the proximal tubule. Double or triple the normal doses may be required. Continuous infusion of furosemide (1 to 10 mg/hour) is a pharmacokinetically rational means of enhancing the drug’s tubular concentration at lower doses and is effective even in states of low GFR. Another effective strategy is dual segment blockade of sodium reabsorption, at the medullary thick ascending loop of Henle and the distal tubule, by combined administration of a loop diuretic (furosemide, ethacrynic acid, torsemide) and a thiazide diuretic (metolazone, hydrochlorothiazide). Initiation of RRT is required when pulmonary edema, acidosis, or hyperkalemia threaten life or when manifestations of acute uremia (encephalopathy, enteropathy, serositis, thrombocytopathy) are profound. There is limited evidence that early elective RRT may be favorable in ARF, but there is no established threshold for intervention on the basis of blood urea nitrogen or SCr values. Continuous venovenous hemodialysis provides both hemodialysis and ultrafiltration with minimal hemodynamic perturbation, allowing its use in much sicker patients. Nonetheless, because autoregulation is impaired, it is imperative to avoid episodic hypotension. Animal data suggest that intrarenal vascular responsiveness to norepinephrine is markedly decreased in ARF. If this applies to human patients, the use of this drug for the treatment of hypotension is unlikely to compromise renal blood flow.

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sodium bicarbonate appeared to prevent contrast nephropathy in a small randomized, controlled trial, but corroboration by larger clinical trials is needed. The low acquisition costs of these interventions make them particularly appealing. Other novel agents being investigated are prostaglandin analogues, human growth factors, and selective adenosine agonists and antagonists. All have theoretical advantages in ARF, but outcome data are preliminary.

Further Reading Bellomo R, Champman M, Finfer S, et al: Low-dose dopamine in patients with early renal dysfunction: A placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 356:2139-2143, 2000. Birck R, Krzossok S, Markowetz F, et al: Acetylcysteine for prevention of contrast nephropathy: Meta-analysis. Lancet 362:598-603, 2003. Braams R, Vossen V, Lisman BAM, et al: Outcome in patients requiring renal replacement therapy after surgery for ruptured and nonruptured aneurysm of the abdominal aorta. Eur J Vasc Endovasc Surg 18:323-327, 1999. Brezis M, Rosen S: Hypoxia of the renal medulla—its implications for disease. N Engl J Med 332:647-655, 1995. Carvounis CP, Nisar S, Guro-Razuman S: Significance of the fractional excretion of urea in the differential diagnosis of acute renal failure. Kidney Int 62:2223-2229, 2002. Chen G, Paka L, Kako Y, et al: A protective role for kidney apolipoprotein E: Regulation of mesangial cell proliferation and matrix expansion. J Biol Chem 276:49142-49147, 2001. Chertow GM, Lazarus JM, Christiansen CL, et al: Preoperative renal risk stratification. Circulation 95:878-884, 1997. Cockcroft DW, Gault MH: Prediction of creatinine clearance from serum creatinine. Nephron 16:31-41, 1976. Conlon PJ, Stafford-Smith M, White WD, et al: Acute renal failure following cardiac surgery. Nephrol Dial Transplant 14:1158-1162, 1999.

Forni LG, Hilton PJ: Continuous hemofiltration in the treatment of acute renal failure. N Engl J Med 336:1303-1309, 1997. Gines P, Guevara M, Arroyo V, et al: Hepatorenal syndrome. Lancet 362:1819-1827, 2003. Huynh TTT, Miller CC III, Estrera AL, et al: Determinants of hospital length of stay after thoracoabdominal aortic aneurysm repair. J Vasc Surg 35:648-653, 2002. Kelleher S, Robinette J, Miller F, et al: Effect of hemorrhagic reduction in blood pressure on recovery from acute renal failure. Kidney Int 31:725-730, 1987. MacGregor DA, Smith TE, Prielipp RC, et al: Pharmacokinetics of dopamine in healthy male subjects. Anesthesiology 92:338-346, 2000. Marik PE: Low-dose dopamine: A systematic review. Intensive Care Med 28:877-883, 2002. Merten GJ, Burgess WP, Gray LV, et al: Prevention of contrast-induced nephropathy with sodium bicarbonate. JAMA 291:2328-2334, 2004. Modi KS, Rao VK: Atheroembolic renal disease. J Am Soc Nephrol 12: 1781-1787, 2001. Novis BK, Roizen MF, Aronson S, et al: Association of preoperative risk factors with postoperative acute renal failure. Anesth Analg 78: 143-149, 1994. Ryckwaert F, Boccara G, Frappier J-M, et al: Incidence, risk factors, and prognosis of a moderate increase in plasma creatinine early after cardiac surgery. Crit Care Med 30:1495-1498, 2002. Singri N, Ahya SN, Levin ML: Acute renal failure. JAMA 289:747-751, 2003. Stone GW, McCullough PA, Tumlin JA, et al: Fenoldopam mesylate for the prevention of contrast-induced nephropathy. JAMA 290:2284-2291, 2003. Tang ATM, El-Gamel A, Keevil B, et al: The effect of “renal-dose” dopamine on renal tubular function following cardiac surgery: Assessed by measuring retinol binding protein (RBP). Eur J Cardiothorac Surg 15:717-722, 1999. Wahlberg E, DiMuzio PJ, Stoney RJ: Aortic clamping during elective operations for infrarenal disease: The influence of clamping time on renal function. J Vasc Surg 36:13-18, 2002.

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Postoperative Respiratory Failure David Porembka Case Synopsis

PROBLEM ANALYSIS Definition Numerous issues are involved in the trauma situation described in the case synopsis. The patient arrived at the hospital in hypovolemic shock with end-organ ischemia due to several life-threatening injuries (splenic rupture, liver injury, severe pelvic injury). Significant occult blood loss can occur with pelvic fractures alone, especially those involving vertical shear injury. Often, severe lactic acidosis accompanies such traumatic injuries and the associated hypovolemia and hypotension. Because the patient also sustained chest wall trauma with multiple rib fractures and pulmonary contusion, hypoxemia is inevitable. Indeed, with multiple trauma and associated lung injury, the potential for significant acute respiratory failure is high. In this case, aggressive blood and fluid resuscitation and immediate corrective surgery are required. However, these may compound the risk for acute respiratory failure. Fortunately, after surgery, the need for blood products and fluid replacement will be reduced. In the case described, however, the patient’s oxygenation worsened, suggesting associated severe lung injury or early acute respiratory distress syndrome (ARDS) and associated cellular, humoral, and oxidative pathophysiologic processes (Table 86-1).

Recognition Diagnostic criteria for ARDS are listed in Table 86-2. Early diagnosis and corrective measures are key to a successful

outcome. Initially, the work of breathing is greatly increased. Therefore, patients become tachypneic, tachycardic, and agitated. Typically, arterial blood gas measurement reveals respiratory alkalosis with hypoxemia or relative hypoxemia with supplemental oxygen. Subsequently, this progresses to an increase in the alveolar-arterial oxygen gradient. Without intervention (i.e., airway control and mechanical ventilatory support with positive end-expiratory pressure [PEEP]), the

Table 86–1

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Cellular

Oxidative

Endothelial cells Eosinophils Epithelial cells Fibroblasts Neutrophils Monocytes and macrophages

Antioxidant depletion Hypoxia-reoxygenation phenomena Oxygen toxicity Reactive oxygen species Superoxide radical Hydrogen peroxide Singlet oxygen Hypochlorous acid Reactive nitrogen species Nitric oxide Peroxynitrite Transition metal ion catalysts Xanthine oxidase

Humoral Arachidonic acid metabolites Thromboxane A2 Leukotrienes Complement C5a, C3a Cytokines TNF-α, IL-1β, IL-6, IL-8 Endotoxin Platelet-activating factor Prostaglandins

IL, interleukin, TNF, tumor necrosis factor.

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A 25-year-old person involved in a high-speed motor vehicle accident required prolonged extrication and underwent an emergency laparotomy for a positive diagnostic abdominal ultrasonogram. Injuries included a ruptured spleen, a grade III liver laceration, multiple right-sided rib fractures with an ipsilateral pulmonary contusion, and a vertical shear pelvic fracture. The initial vital signs were heart rate 120 beats per minute, respiratory rate 35, and systolic arterial blood pressure 80 mm Hg. Resuscitation required multiple transfusions (approximately 5 L). Following corrective surgery, the patient underwent embolization for the pelvic fracture. In the surgical intensive care unit, a continuous right ventricular ejection catheter with mixed venous saturation capabilities was placed. Also, transesophageal echocardiography (TEE) was used for initial diagnostic interrogation (ventricular function and volume, ventricular interaction, aortic interrogation) and for continuous postoperative hemodynamic assessment. During subsequent aggressive hemodynamic resuscitation, the patient’s hemodynamic instability improved, but oxygenation saturation status deteriorated (arterial oxygen tension [PaO2] 60 mm Hg with fraction of inspired oxygen [FiO2] of 1.0). After sedation and an appropriate level of analgesia (with continuous infusions of lorazepam and fentanyl) to a modified Ramsey score of 3 to 4, initial ventilator adjustments to improve static compliance did not improve PaO2.

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Diagnostic Criteria for Acute Respiratory Distress Syndrome

Clinical Criteria Appropriate risk factors or precipitating causes Respiratory distress with severe hypoxemia Radiographic evidence of noncardiac pulmonary edema Loss of lung compliance No obvious cardiac failure

NHLBI Criteria Widespread, bilateral infiltrates on chest radiograph <7 days duration Hypoxemia with PaO2/FiO2 <150 off PEEP or <200 on PEEP Pulmonary artery occlusion pressure <18 mm Hg *0, no lung injury; 0.1 to 2.5, mild to moderate lung injury; >2.5, severe lung injury (acute respiratory distress syndrome). FiO2, fraction of inspired oxygen; NHLBI, National Heart, Lung, and Blood Institute; PaO2, arterial oxygen tension; PEEP, positive end-expiratory pressure.

Figure 86–2 ■ Chest radiograph with bilateral fluffy infiltrates (panacinar pattern), consistent with severe acute respiratory distress syndrome.

work of breathing is so great that severe hypoxemia occurs. This is compounded by increased alveolar fluid, a significant decrease in the functional residual capacity, atelectasis, and loss of lung compliance. Metabolic acidosis may ensue if the hypoxemia is not reversed or becomes refractory, leading to end-organ and cellular damage. In addition to hypoxemia, the chest radiograph may reveal a pattern consistent with early ARDS, including bilateral patchy interstitial infiltrates (Fig. 86-1). Later, with severe ARDS, this pattern progresses to bilateral, fluffy infiltrates with a panacinar pattern (Fig. 86-2). These findings may worsen or even appear to dissipate with positive-pressure ventilation, especially if plateau pressures and PEEP are significantly elevated. Although patients were once considered to have ARDS if the pulmonary artery occlusion (wedge) pressure was

less than 18 mm Hg, today, with the greater use of echocardiography, this criterion may not apply to acidotic, underresuscitated patients. Because the left ventricle may be noncompliant, even if relatively empty, the pulmonary artery occlusion pressure may be falsely elevated. Even in the static phase of resuscitation, ongoing cellular injury occurs, and the phenomena of reperfusion injury proceed and continue to impair left ventricular function, which is inadequately measured by information derived from a pulmonary artery catheter. Even with correction of the medical or surgical pathology associated with ARDS, the pathophysiologic processes initiated by severe acute lung injury are unabated, leading to pulmonary microcirculation compromise.

Risk Assessment

Figure 86–1 ■ Chest radiograph consistent with the pattern of early acute respiratory distress syndrome following right-sided pulmonary contusion with multiple rib fractures. In addition to diffuse patchy infiltrates, note diffuse subcutaneous emphysema from either the traumatic insult or pulmonary barotrauma.

Conceptually, there are several categories of pulmonary edema, depending on cause and associated factors. Hydrostatic pulmonary edema results from volume overload, left ventricular failure, valvular heart disease, and lymphatic insufficiency. Permeability pulmonary edema (alveolar capillary leak) is associated with the systemic inflammatory response syndrome (SIRS; see Chapter 119) due to shock (e.g., traumatic, septic, cardiogenic, anaphylactic), pulmonary contusion, thermal injury, fat embolism, closed head injury, infectious agents, near-drowning, inhaled toxins, pancreatitis, drug ingestion, multiple transfusions, and so forth. Mixed pulmonary edema combines elements of both and often occurs in patients with subtle heart failure (due to systolic or diastolic dysfunction) with superimposed SIRS. The presence of mixed pulmonary edema in the intensive care unit is not well documented. However, it is a definite entity in gravely ill surgical and trauma patients, and it perplexes physicians with regard to the modulation of intravascular volume. Again, echocardiography (especially TEE) can help clinicians diagnose pathologic entities that might be involved and assess the patient’s hemodynamic

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apoptosis in pulmonary vascular endothelial cells. Also, the impaired coagulation observed in patients with septic shock may improve with activated protein C. It is unknown whether the use of such pharmacotherapy may benefit ARDS patients with impaired fibrinolysis and enhance platelet-fibrin thrombus formation. Although intensive glucose control is considered standard in critically ill patients, there are no prospective randomized trials of this practice in patients with severe ARDS. However, conventional wisdom dictates that such a course may be prudent. Ventilation-induced lung injury is a well-known entity, but it has only recently gained attention because of the unexpected results from the ARDS Network multicenter study. Patient enrollment was halted in that study because patients who received standard ventilatory support (12 mL/kg tidal volume) with a maximal plateau pressure of 50 cm H2O had a mortality rate of 39.8%, compared with 31.0% for those with 6 mL/kg and a maximal plateau pressure of 30 cm H2O (P =.007). However, in clinical practice, there is varying compliance with the lowered ventilatory settings promulgated by the ARDS Network. This is disconcerting, and clinicians must be encouraged to use more protective ventilatory strategies. What is also clear from the ARDS Network study is that ARDS is not a homogeneous process. Some alveoli will be overdistended by high pressure and volumes; others will never be opened, even with higher pressures and volumes. The latter include dependent regions of the lung. More recent studies show that simple alterations in mechanical ventilation can have deleterious effects. It is now known that systemic cytokine up-regulation is possible with high-pressure, high-volume ventilation. Another benefit of protective lung strategies is that systemic cytokine levels are significantly lower with lower-pressure, lower-volume ventilation. These levels decrease significantly over time owing to reduced lung injury (overdistention), while lung recruitment is maintained throughout the ventilatory cycle by more modest maximal plateau pressure. Other investigators have examined plasma chemokines (MCP-1, IL-8, and GRO) in patients with conventional (high volume, high plateau pressure) and protective (lower volume, lower plateau pressure) ventilation strategies. Plasma cytokines were increased in patients with conventional ventilation. Thus, there may be an associated risk of end-organ damage and the development of multiple organ failure. Circulating pro-apoptotic soluble factors (e.g., soluble Fas ligand) may contribute. Finally, studies in a rat model of ischemic gut suggest that patients with acute lung injury and ischemic gut may be at even higher risk for ARDS. This might be due to more pronounced release of inflammatory cytokines from ischemic gut.

Implications In the past, mortality from ARDS was significant, ranging from 53% to 69%. Recently, mortality from isolated ARDS has declined to 26% to 47%. This has been attributed to the following factors: ● Better ventilator management: pressure-controlled ventilation, reduced tidal volumes, permissive hypercapnia, and measures to recruit alveoli and avoid derecruitment

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status, particularly biventricular performance and interactions. Until clinicians have the capability to construct rightleft heart pressure-volume loops, clinical interventions are optimized with the appropriate use of pulmonary artery catheters and TEE. The pathogenesis of ARDS is complex. Our understanding of initiating factors in ARDS, as well as disease progression, resolution, and healing, is ever-changing. Recent strides in both basic and clinical research have increased our understanding of ARDS. Also, since the establishment of the ARDS Network, we have finally reduced earlier stagnant mortality rates (40% to 60%) by such simple interventions as reducing mechanical ventilatory tidal volumes and plateau pressures. The incidence of ARDS in the United States approaches 150,000 patients per year (75 per 100,000 population per year). The incidence depends on the primary cause of ARDS and associated pathophysiology: SIRS (41%), multiple transfusions (36%), near-drowning (33%), pulmonary aspiration (21%), multiple fractures (11%), drug overdose (8.5%). In patients with two risk factors, the incidence increases to 42%; in those with three risk factors, it is 85%. The 1-year outcome for ARDS survivors is not necessarily benign. Rapid resolution of lung injury, even without associated multiorgan system dysfunction, is more often observed in previously healthy patients. Even so, muscle wasting and weakness may occur, possibly related to critical myopathic illness that may accompany prolonged stays in the intensive care unit. By 6 months, pulmonary function generally improves in ARDS patients. However, most have a persistent reduction in carbon monoxide diffusing capacity. Only about half of ARDS survivors return to work in their prior capacity. There are many pathogenic processes involved in ARDS. However, because ARDS is a continuum, these are not easily subdivided. Nonetheless, in the acute phase of lung injury, there is an influx of protein-enriched fluid into the alveolar spaces. Transmigration of gases across the alveolar membrane is impaired owing to a breakdown of the alveolar-capillary barrier. This sets the stage for problematic management of ARDS patients. The alveolar epithelium (90% type I cells; 10% type II [cuboidal] cells) is also injured in early ARDS, and the extent of such injury is a predictor of ARDS mortality. Type I cells produce surfactant and are involved in ion transport. They also proliferate and differentiate into type II cells following lung injury. The loss of vital type I cell functions reduces the integrity of the barrier, leading to (1) pneumonia, sepsis, and septic shock and (2) cellular disorganization that interferes with epithelial repair and fibrosis. Neutrophil transmigration and consequent injury are well known in ARDS and contribute to continued injury and interference with healing. Extrapulmonary and pulmonary proinflammatory substances and cytokines are also implicated in the aggressive pathophysiology of ARDS involving alveolar epithelial cells, neutrophils, and fibroblasts. With such overwhelming inflammation and the production of interleukin-8 (IL-8) and tumor necrosis factor-α, any glucocorticoid-mediated inhibition is ineffective. Thus, the balance between pro- and anti-inflammatory cytokines and mediators is altered, but this is not yet well understood. ARDS also increases alveolar epithelial cell apoptosis and dysfunction. This process is enhanced by a kinase-1 signaling pathway that regulates hydrogen peroxide-induced

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Altering the patient’s position to improve ventilationperfusion mismatch, such as the use of special beds that can be tilted horizontally or vertically (“posturing”) to improve ventilation-perfusion matching by increasing hydrostatic pressure in the dependent lung1 Better control of circulatory dynamics, early and more aggressive management of nosocomial pneumonia, therapy with corticosteroids in late-phase ARDS, and anti-inflammatory modalities More timely, aggressive hemodynamic assessment and therapy; increased understanding of underlying pathophysiology; use of echocardiography, computed tomography, and electrical impedance tomography

Despite the apparent decline in mortality associated with isolated ARDS, mortality for multiorgan system failure has not declined. No matter what severity scoring system is used, mortality for ARDS with the failure of one, two, three, or four additional organs is 54%, 72%, 84%, and 99%, respectively. Reducing mortality from multiorgan system failure involves early intervention and aggressive treatment of the underlying causes, with meticulous attention to ventilatory management.

MANAGEMENT Understanding the pathogenesis of ARDS is critical to minimizing the numerous potential adverse consequences. If possible, underlying causes that may have precipitated ARDS must be identified and treated, and associated pathophysiology must be ameliorated or reversed (see Table 86-1). Maintaining adequate (not necessarily optimal) oxygenation and delivery can be challenging. Aggressive interventional strategies should be used to inhibit the activation of inflammatory responses. Especially in patients with sepsis, early treatment may prevent or minimize associated ARDS. An important caveat is that ARDS is a heterogeneous disease in terms of both cause and pathophysiology. Not all alveolar lung units are equally affected, and this can change during acute and resolving ARDS. Early identification of the extent and distribution of the disease process (collapsed lung areas) by computed tomography can guide clinicians in use of PEEP and posturing to improve regional distribution of gas flow and ventilatory pressures. With hypoxia due to ARDS, supplemental oxygenation is required, usually with an artificial airway. With mild acute lung injury, high-flow continuous positive airway pressure (CPAP) mask ventilation may be sufficient. With more severe injury, tracheal intubation and ventilator support may be required to deliver adequate oxygen and reduce the work of breathing. Assisted modes include proportional assist ventilation and synchronized intermittent mandatory ventilation with pressure support. Proportional assist ventilation proportionally amplifies instantaneous patient ventilatory efforts. With very severe injury, PEEP with increased mean airway pressure and lower tidal volumes (matched to the patient’s 1 The editor (JLA) benefited from such posturing therapy when he was treated in 2003 for ARDS secondary to pneumonia and empyema (due to Streptococcus pneumoniae). His condition was compounded by septic shock and multiorgan system failure.

ideal body weight) is used to recruit alveoli and improve ventilation-perfusion matching. Mean airway pressure depends on the degree of lung injury and hemodynamic tolerance, with caution required to avoid barotrauma or volume trauma. “Best” PEEP is difficult to define. Generally, pressure between 5 and 15 cm H2O is sufficient, with mean airway pressures initially maintained at less than 35 cm H2O. PEEP greater than 15 cm H2O may open collapsed alveoli but could expose normal alveoli to injury. PEEP greater than 20 cm H2O may be required on occasion, but this should be critically evaluated on a case-by-case basis. Recruitment of collapsed airways is crucial, especially during mechanical or assisted ventilation, so that derecruitment does not occur. The latter has been observed in dynamic studies in both animal models and humans. Thus, there is still uncertainty about the best level of PEEP for a given patient—one that will avoid untoward pulmonary volume trauma or barotrauma. Prone and, in some centers, postural positioning is used to manage patients with severe acute lung injury. This method is more prevalent in Europe and Canada than in the United States and may be more efficacious early in ARDS. In my opinion, once the clinician has identified the extent of injury to all pulmonary segments, increased PEEP and prone positioning may benefit some patients. However, with a predominant parenchymal component of ARDS (e.g., pulmonary contusion), increasing PEEP may actually worsen oxygenation, even in the prone position or with posturing. Surfactant instillation is used to replenish endogenous surfactant lost due to injury to type I alveolar epithelium. Although surfactant is useful in infants, only anecdotal reports show any benefit in adults. A multicenter study in progress, with direct administration of surfactant into 15 distal lung segments, has shown no encouraging results to date. Although inhaled nitric oxide initially showed some promise in severely ill patients, it has not withstood the test of time or well-designed prospective clinical trials. However, in an animal model of the effects of L-NAME (a nitric oxide synthetase inhibitor) and inhaled nitric oxide on ventilatorinduced lung injury (perfused rabbit lung), L-NAME attenuated the resultant microvascular leak, while nitric oxide appeared to further the induced lung injury. Of note in this study, measuring nitric oxide metabolites in bronchoalveolar lavage fluid may provide a method of measuring lung injury induced by mechanical stress. Prolonged exposure to high inspired oxygen concentrations can produce lung injury similar to ARDS. Thus, FiO2 should be adjusted to the lowest level possible to ensure adequate oxygenation (arterial blood oxygen saturation >90%). Today, lower tidal volumes (6 mL/kg of ideal body weight) are used in patients with ARDS. The idea is to avoid barotrauma while providing satisfactory oxygenation and alveolar ventilation. However, because alveolar ventilation may be decreased by up to 50% with these lower tidal volumes, arterial carbon dioxide tension (PaCO2) invariably rises (“permissive hypercapnia”) to greater than 80 mm Hg. Such high PaCO2 levels are not always benign and may have detrimental hemodynamic effects. Although increasing ventilator rates may reduce such high PaCO2 levels, ventilator rates greater than 30 are often ineffective. Judicious sedation

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PREVENTION At present, there are no clinically proven interventions to prevent ARDS in patients at risk. However, prompt recognition and treatment or removal of mitigating factors (e.g., heart failure, source of sepsis), along with the institution of supportive therapy, may favorably modify the course of ARDS and reduce associated morbidity and mortality. New measures and criteria for ventilatory management, as promulgated by the ARDS Network (www.ardsnet.org) have changed the standards of practice. The goal of maintaining optimal recruitment of alveoli without triggering airway collapse is critical. Thus, it may be necessary for clinicians to

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obtain dynamic computed tomography scans early in ARDS to characterize lung involvement and then use such scans to determine the appropriate management strategy (e.g., higher PEEP levels, prone or postural positioning). There is no proven method (evidence-based practice standard) of preventing all lung injury during ARDS treatment. However, the use of newer protective management strategies discussed in this chapter may help minimize such injury.

Further Reading Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342:1301-1308, 2000. Bouadma L, Schortgen F, Ricard J-D, et al: Ventilation strategy affects cytokine release after mesenteric ischemia-reperfusion in rats. Crit Care Med 32:1563-1569, 2004. Brower RG, Lanken PN, MacIntyre N, et al: Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 351:327-336, 2004. Gainnier M, Michelet P, Thirion X, et al: Prone position and positive end-expiratory pressure in acute respiratory distress syndrome. Crit Care Med 31:2719-2726, 2003. Galic O, Dara SI, Mendez JL, et al: Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med 32:1817-1824, 2004. Goss CH, Brower RG, Hudson LD, et al: ARDS Network: Incidence of acute lung injury in the United States. Crit Care Med 31:1607-1611, 2003. Gunther A, Mosavi P, Heinemann S, et al: Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia: Comparison with the acute respiratory distress syndrome. Am J Respir Crit Care 161:454-462, 2000. Herridge MS, Cheung AM, Tansey CM, et al: One-year outcomes in survivors of the acute respiratory distress syndromes. N Engl J Med 348:683-693, 2003. Hickling KG: Low tidal volume ventilation: A PEEP at the mechanism of derecruitment. Crit Care Med 31:318-320, 2003. Hotchkiss RS: The pathophysiology and treatment of sepsis. N Engl J Med 348:138-150, 2005. Ince C: Microcirculation in distress: A new resuscitation end point? Crit Care Med 32:1963-1964, 2004. Lew TWK, Kwek TK, Tai D, et al: Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome. JAMA 290:374-380, 2003. Lim C-M, Jung H, Koh Y, et al: Effect of alveolar recruitment maneuver in early acute respiratory distress syndrome according to antiderecruitment strategy, etiological category of diffuse lung injury, and body position of the patient. Crit Care Med 31:411-418, 2003. Machino T, Hashimoto S, Maruoka S, et al: Apoptosis signal-regulating kinase 1-mediated signaling pathway regulates hydrogen peroxideinduced apoptosis in human pulmonary vascular endothelial cells. Crit Care Med 31:2776-2781, 2003. Oczenski W, Hormann C, Keller C, et al: Recruitment maneuvers after a positive end-expiratory pressure trial do not induce sustained effects in early adult respiratory distress syndrome. Anesthesiology 101: 620-625, 2004. van Genderingen HR, van Vught AJ, Jansen JRC: Regional lung volume during high-frequency oscillatory ventilation by electrical impedance tomography. Crit Care Med 32:787-794, 2004. van Kaam AH, Haitsma JJ, Dik WA, et al: Response to exogenous surfactant is different during open lung and conventional ventilation. Crit Care Med 32:774-780, 2004. Victorino JA, Borges JB, Okamoto VN, et al: Imbalances in regional lung ventilation: A validation study on electrical impedance tomography. Am J Respir Crit Care Med 169:791-800, 2004. Young MP, Manning HL, Wilson DL, et al: Ventilation of patients with acute lung injury and acute respiratory distress syndrome: Has new evidence changed clinical practice? Crit Care Med 32:1260-1265, 2004.

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and neuromuscular relaxation (rarely) may help reduce agitation, carbon dioxide production, and high spontaneous respiratory rates with permissive hypercapnia. Also, coordinating spontaneous respiratory efforts with any mechanical ventilation is key to avoiding lack of synchrony, diaphragmatic wasting, or the triggering of mechanical ventilator responses to spontaneous respirations. The strategy for selecting the best inspiration/expiration (I/E) ratio is based on a consideration of internal or external PEEP. Internal PEEP may be increased with higher tidal volumes, shorter expiratory time, or higher ventilatory constants (e.g., inverse I/E ratio). External PEEP is applied from the ventilator. It must be remembered that respiration is dynamic, and distended alveoli can collapse during expiration if the pressure applied is too low. Fast alveolar compartments expire easily and may collapse prematurely; external PEEP may be helpful in this situation. Conversely, increased internal PEEP may be required to match slower alveolar compartments and to make ventilation and perfusion more homogeneous. This can be accomplished by shortening expiratory time (inverse I/E ratio ventilation). In general, patients with ARDS have more fast compartments, so PEEP is ideal to prevent alveolar collapse. Yet with inverse I/E ratio ventilation, both external and internal PEEP should be monitored to limit internal PEEP. In summary, management of postoperative ARDS should be problem oriented and aggressive. Causes and contributing factors should be identified and corrected or treated. Aggressive monitoring (pulmonary artery catheter, TEE) is indicated to assess volume status, pulmonary and peripheral hemodynamics, oxygen supply and demand, and right and left heart function. For optimal ventilatory management, a strategy should be implemented to ensure adequate arterial oxygen saturation (>90%) with the lowest possible FiO2. Protective lung strategies, including a tidal volume of 6 mL/kg of predicted body weight, a plateau pressure of 30 to 35 cm H2O, optimal PEEP to avoid derecruitment and overdistention of a significant proportion of compliant alveoli, permissive hypercapnia (in patients without increased intracranial pressure), sedation, and neuromuscular blockers, are required. However, treatment must always be individualized in an effort to optimize outcome. The approach to these patients may be quite diverse, considering the pathologic differences between pulmonary ARDS and extrapulmonary ARDS.

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Avery Tung Case Synopsis A 78-year-old man with chronic ischemic cardiomyopathy and renal insufficiency underwent redo coronary artery bypass grafting and mitral valve repair. Cardiopulmonary bypass time was 200 minutes. Upon weaning from bypass, persistent hypoxemia (PaO2/FiO2 ratio <100) and a low systemic vascular resistance (500 dyne•sec•cm–5) were noted. Intravenous norepinephrine was begun, an intra-aortic balloon pump was placed, and the patient was transferred to the intensive care unit. Over the next 48 hours, the patient continued to require intravenous norepinephrine for reduced systemic vascular resistance. His creatinine levels increased, and there were radiographic changes consistent with acute respiratory deficiency syndrome, with continued hypoxemia despite 15 cm H2O positive end-expiratory airway pressure. He was intermittently agitated and had nonfocal neurologic changes. On the morning of the third postoperative day, he developed atrial fibrillation.

PROBLEM ANALYSIS Definition Complications specific to cardiopulmonary bypass (CPB) range from minor to severe and include mechanical issues, introduction of air and other debris, damage to blood elements, metabolic and electrolyte derangements, and alterations in vital organ perfusion. Mechanical complications of CPB involve abnormalities of blood flow between the CPB machine and the patient and include obstruction, embolization, and damage to the native vasculature. In addition, CPB triggers a systemic inflammatory response that can have significant effects on end-organ function during the immediate postbypass period. Organs commonly affected by the inflammatory response to CPB include the lungs, heart, gastrointestinal tract, brain, and kidneys. Although surgical trauma, blood loss, and hypothermia can all induce an inflammatory response, the physiologic response to CPB is unusual in its complexity. Three distinct mechanisms likely participate in the post-CPB inflammatory state: 1. Direct activation of the cellular and humoral immune system by artificial surfaces of the CPB circuit. This process involves complement and cytokines, leading to activation of both leukocytes and the vascular endothelium. 2. Aortic cross-clamping leads to ischemia-reperfusion injury and the resultant activation of the inflammatory mediator cascade. 3. Damage to mucosal barriers due to hypoperfusion induces endotoxin translocation and immune system activation. This leads to a systemic inflammatory response that alters 352

microvascular perfusion, systemic pressure, endothelial integrity, and end-organ perfusion postoperatively. Figure 87-1 depicts pathways of inflammatory activation during CPB.

Recognition A number of mechanical complications of CPB have been described. Obstruction to either arterial flow or venous drainage, embolization of air or debris, aortic dissection, dislodgment of aortic debris, and malposition of inflow and outflow cannulas can all cause catastrophic injury. Table 87-1 lists mechanical complications of bypass and their detection. Clinical signs and symptoms of the inflammatory response mediated by CPB are more subtle and involve primarily end-organ dysfunction and systemic hypotension. Renal function may decline slowly after CPB and progress to acute renal failure of sufficient severity to require temporary dialysis. Increased capillary endothelial leak may lead to pulmonary edema, with altered lung compliance and worsened gas exchange. Microvascular occlusion from leukocyte aggregates may produce an altered mental status, commonly without focal neurologic findings. Depressed myocardial contractility and arrhythmias can result, leading to increased fluid or vasopressor requirements and worsened perfusion. Finally, systemic activation of complement and cytokines can induce vasodilatation and consequent hypotension. Because of the protean manifestations of the CPBmediated inflammatory response, related signs and symptoms are similar to those resulting from any inflammatory insult and may not be universally present. For example, white blood cell counts may not be elevated, and fever may or may not be present. Urine volumes are typically low,

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Figure 87–1 ■ Pathways of inflammatory activation during cardiopulmonary bypass.

↑ Bradykinin SURGICAL TRAUMA ↑ Kallikrein Factor XII Neutrophil activation Foreign body contact

Complement

Endotoxin translocation

Cytokines

Inflammatory response

Ischemia/reperfusion Monocyte activation Cardiopulmonary bypass

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Detection of Mechanical Complications of Cardiopulmonary Bypass

Complication

Detection

Aortic dissection

Visual inspection of cannula or aorta Abnormal inflow pressure Alterations in peripheral arterial waveform Chest radiography Aortography Transesophageal or epivascular echocardiography Direct palpation Inspection of head and jugular veins Sudden or unexpected changes in CVP while on CPB Transesophageal echocardiography Transcranial Doppler Bubble detectors in CPB circuit Arterial line filters Arterial pressure and flow monitoring during CPB Hypothermia Mixed venous oxygen saturation monitoring Electroencephalography

Dislodgment of aortic debris

Obstruction to venous drainage Embolization

Cerebral hypoperfusion

CPB, cardiopulmonary bypass; CVP, central venous pressure.

Risk Assessment Almost any exposure to CPB induces some degree of systemic inflammation. Nonetheless, several pre-, intra-, and post-CPB factors are known to predispose patients to a clinically relevant, increased inflammatory response. Preoperative Factors. Although the amount and degree of cytokine release does not vary with age, both ischemic heart disease and perioperative left ventricular dysfunction appear to increase the intensity of the cytokine response to CPB. This increased response has been correlated with impaired postoperative hemodynamics and an increase in perioperative complications. Diabetes, particularly when poorly controlled, also appears to increase the inflammatory response. Renal failure, perhaps by impairing the kidneys’ ability to clear pro- and anti-inflammatory mediators, intensifies the inflammatory response as well. In general, a greater perioperative severity of illness predicts a greater inflammatory response. Intraoperative Factors. Both splanchnic hypoperfusion and increased gastrointestinal mucosal permeability occur during CPB. Consequent ischemia-reperfusion injury leads to free radical production, sequestration of pulmonary neutrophils, and possible bacterial translocation and endotoxin formation. Cytokine levels appear to be higher in heart or heart-lung transplant patients, possibly owing to their more severe illness. However, the cytokine levels in patients undergoing valve surgery are similar to the levels in those having coronary artery bypass grafting. Anesthetic Agents. Although most anesthetic agents have some immunomodulatory activity, the clinical impact of their use in patients undergoing CPB is unknown. Both propofol and thiopental (Pentothal) inhibit neutrophil activation, and propofol may enhance anti-inflammatory cytokine production. Morphine down-regulates immune cell function and suppresses the antibody response. Sevoflurane and isoflurane reduce inflammatory cytokine activity.

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and urine sediment frequently demonstrates only acute tubular necrosis. Altered pulmonary mechanics and gas exchange are nonspecific, resemble those of acute respiratory distress syndrome, and can be severe. Neurologic dysfunction may not be focal, manifesting instead as agitation, delirium, or delayed emergence from anesthesia. Hypotension may result from decreased cardiac output or vascular resistance. Systemic vasodilatation responds to α-adrenergic agonists such as norepinephrine, phenylephrine, or vasopressin.

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Although thoracic epidural anesthesia decreases the perioperative stress response, it does not significantly alter the cytokine response due to CPB. Cardiopulmonary Bypass Factors. The data are unclear regarding what effect the type of oxygenator, pump, or extracorporeal circuit and the temperature during CPB have on the duration and extent of the inflammatory response. The duration of CPB has been correlated with interleukin (IL)-8 concentrations and measures of neutrophil adhesion and may alter clinical outcomes for several reasons. Although warm CPB increases the inflammatory response when compared with cold CPB, warm cardioplegia appears to reduce consequent inflammation. Membrane oxygenators produce less inflammation than bubble oxygenators do, but the effects are not sustained and do not alter clinical pulmonary function. No clear effect on outcome has been observed based on CPB prime, type of pump, or pulsatility, although pulsatile flow is associated with less endotoxin release and lower cytokine levels. Transfusion Factors. Allogeneic blood transfusion clearly increases the intensity of the CPB inflammatory response. Autotransfusion of mediastinal blood may not be any better, because such blood contains high levels of tumor necrosis factor-α and IL-6. CPB reservoir blood processed through washing devices typically has higher neutrophil counts than blood in the circulation but significantly lower levels of inflammatory mediators (e.g., IL-1, IL-6, tumor necrosis factor-α). However, cell-saver or similar techniques have no significant effects on bleeding or other CPB-related morbidity and mortality.

Implications The effects of CPB-mediated systemic inflammation can be severe. Global immunosuppression can predispose to sepsis, potentially altering outcomes in susceptible individuals. CPB results in neutrophil sequestration into the lung, with damage to pulmonary epithelial and endothelial surfaces. The consequent increase in pulmonary vascular permeability produces interstitial and alveolar edema, reducing oxygenation and lung compliance. Detectable changes in lung function are present in up to 12% of CPB patients, with severe acute lung injury in as many as 3%. Increased duration of CPB increases both the likelihood and the severity of lung injury. Postoperative neurologic dysfunction is also linked to the CPB inflammatory response. Mechanisms include neutrophilmediated vascular endothelial damage and loss of vasomotor control from inappropriate production of nitric oxide. Mild cognitive dysfunction has been documented in up to 69% of patients, seizures in 5% to 10%, and focal cerebral deficits in 1% to 3%. Perioperative renal dysfunction occurs in 7% to 13% of patients and may increase mortality 20- to 30-fold. The need for dialysis is associated with even greater mortality. Although specific mechanisms linking progression of the CPB inflammatory response to renal dysfunction are incompletely understood, ischemia-reperfusion injury has been shown in animal models. Impaired vascular regulation may play a role in altering glomerular perfusion along with elevated cytokine levels.

Coagulation disorders are an especially relevant sign of the CPB inflammatory response. CPB-induced platelet dysfunction, complement and fibrinolytic cascade activation, and elevated cytokine levels have all been implicated in the hemostatic defects following CPB. Evidence that a reduction in cytokine levels during bypass correlates with less postoperative blood loss supports an inflammatory cause for some of the coagulation deficits that occur after CPB.

MANAGEMENT Management of the inflammatory state following CPB centers primarily on prevention and secondarily on supportive care for end-organ dysfunction. Although no specific agent has been identified that directly modulates the inflammatory response, a number of potentially useful strategies have been studied. Avoidance of Cardiopulmonary Bypass and Aortic Crossclamping. Current evidence suggests that although offpump cardiac surgery does not prevent CPB-induced inflammation, it does diminish the intensity of the response. It is unclear whether this actually improves clinical outcomes. Heparin-Coated Bypass Circuits. The goal of using heparin-coated bypass circuits is to reduce contact-mediated complement activation by decreasing factor XII activation. Use of such circuits does reduce neutrophil and complement activation. When combined with leukocyte filtration, there is a synergistic effect. Trials have shown a benefit only in high-risk groups, with no improvement in outcome in lowrisk patients. It may be that the benefits of heparin-coated circuits are maximal only with prolonged bypass and crossclamp times. Selective Digestive Decontamination. By reducing the endotoxin burden contained in the gut, adverse consequences of gut translocation due to poor perfusion during CPB may be reduced. Early trials of preoperative administration of oral nonabsorbable antibiotics showed decreased endotoxin and cytokine levels after CPB and fewer postoperative infections. However, no decrease in mortality has been observed to date. Hemofiltration and Leukocyte Depletion. By removing inflammatory mediators from the circulation, the CPB inflammatory response may be reduced in scope. In high-risk patients, hemofiltration improves post-CPB renal function and reduces the magnitude of pulmonary complications but has no significant effect on overall outcome. Aprotinin and Other Modulators of the Immune Response. Aprotinin is the best known of the class of agents known as serine protease inhibitors. These drugs reduce systemic inflammation by blocking hydrolysis and activation of inflammatory cascade mediators. Aprotinin is known to reduce blood loss during cardiac surgery, but it also has several anti-inflammatory actions, including limiting platelet activation and decreasing complement and leukocyte activation as well as cytokine levels. Clinical studies have not shown a definite improvement in mortality but have demonstrated reduced blood loss, decreased reoperation rates, fewer perioperative strokes, and less lung reperfusion injury.

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Steroids. Although steroids would seem to have utility in blunting the consequences of uncontrolled inflammation, little outcome benefit has been demonstrated with peri-CPB steroid use. In small studies, steroids have been shown to decrease endotoxin and proinflammatory cytokine levels after CPB. Animal studies have shown that steroids reduce the indicators of pulmonary inflammation and may reduce inflammatory effects on pulmonary, cardiac, renal, and hematologic function. However, no outcome studies clearly show a benefit from perioperative steroid use.

Finally, it should be remembered that systemic infection can mimic the clinical presentation of CPB-related systemic inflammation. The postoperative presence of vasodilatation, pulmonary capillary leak, renal dysfunction, and cardiac dysfunction should thus prompt not only supportive care but also a careful search for infection as a potential treatable cause. Catheter sepsis, mediastinitis, endocarditis, and preexisting pulmonary or urinary tract infections all represent possible sources of systemic infection in postoperative cardiac surgery patients. These causes must be excluded in the presence of systemic inflammation.

PREVENTION

Further Reading Anselmi A, Abbate A, Girola F, et al: Myocardial ischemia, stunning, inflammation, and apoptosis during cardiac surgery: A review of evidence. Eur J Cardiothorac Surg 25:304-311, 2004. Asimakopoulos G, Gourlay T: A review of anti-inflammatory strategies in cardiac surgery. Perfusion 18:7-12, 2003. Chaney MA: Corticosteroids and cardiopulmonary bypass: A review of clinical investigations. Chest 121:921-931, 2002. Laffey JG, Boylan JF, Cheng DCH: The systemic inflammatory response to cardiac surgery: Implications for the anesthesiologist. Anesthesiology 97:215-252, 2002. Mojcik CF, Levy JH: Aprotinin and the systemic inflammatory response after cardiopulmonary bypass. Ann Thorac Surg 71:745-754, 2001. Paparella D, Yau TM, Young E: Cardiopulmonary bypass induced inflammation: Pathophysiology and treatment. An update. Eur J Cardiothorac Surg 21:232-244, 2002. Rady MY, Ryan T, Starr NJ: Early onset of acute pulmonary dysfunction after cardiovascular surgery: Risk factors and clinical outcome. Crit Care Med 25:1831-1839, 1997.

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All the previously described measures are mainly preventive. Once the inflammatory reaction is initiated, treatment is primarily supportive. Maintenance of hemodynamic stability can reduce the extent of subsequent ischemia-reperfusion injury and is obviously mandatory. Mechanical ventilation should be adjusted to avoid overdistention of alveoli and consequent lung injury. Postoperative renal failure may require dialysis; in hemodynamically unstable patients, continuous venovenous hemodialysis may be better tolerated. Hyperglycemia worsens outcomes in cardiac surgery patients, and postoperative blood glucose levels should be kept below 150 mg/dL. Although no truly effective prophylaxis exists for postoperative atrial fibrillation, maintenance of normal electrolytes, perioperative β-blockade, and possibly temporary left or biatrial pacing may reduce its incidence and should be considered in high-risk patients.

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Fast-Track Cardiac Surgery David C. H. Cheng Case Synopsis An 80-year-old man presents with crescendo angina and is scheduled for urgent coronary bypass surgery. Significant medical history includes prior tobacco use, non-insulindependent diabetes mellitus, and prior transient ischemic attacks with occasional slurred speech. Heart catheterization reveals significant coronary artery disease with subtotal occlusion of the left anterior descending coronary artery, complete occlusion of the right coronary artery, and 90% stenosis of the circumflex and acute obtuse marginal branch. Left ventricular ejection fraction is 45%, and the electrocardiogram shows right bundle branch block and an old inferior myocardial infarction. Off-pump coronary artery bypass grafting (CABG) is attempted but is electively converted to on-pump CABG during revascularization, owing to an intramural left anterior descending coronary artery. The aortic cross-clamp is positioned after epiaortic scanning, and all four coronary vessels are revascularized under cardiopulmonary bypass (CPB). A low-dose narcotic and inhalation anesthesia are used for the operation. The patient is separated from CPB with low-dose epinephrine for heart rate control and is transferred to the intensive care unit (ICU) with a sedative dose of propofol. His recovery is uneventful. He is extubated after about 6 hours in the ICU and discharged from the hospital 5.5 days after surgery.

PROBLEM ANALYSIS

between the step-down unit and the ICU, and good communication among cardiac patient management team members.

Definition and Recognition The costs related to the morbidity and mortality associated with cardiac surgery are increasing by about $1.2 billion per year owing to more severe disease, older patients, more extensive medical therapy, and often prior angioplasty or revascularization. Moreover, the number of CABG surgeries doubles every 5 years in the elderly population. With the escalating number of patients requiring cardiac surgery, more efficient use of limited facilities and resources is vital for cost containment in health care delivery. Fast-track cardiac anesthesia (FTCA) is a perioperative anesthetic management regimen designed to facilitate the early tracheal extubation of patients, within 8 hours after cardiac surgery. Although it is feasible to extubate some post-CPB patients in the operating room, the risks (e.g., cardiorespiratory instability, bleeding) outweigh the potential cost-saving benefits, and it is not recommended at most centers. However, it has been demonstrated that early extubation anesthesia is safe and cost-effective and can improve resource use in some cardiac patients. It is important to realize, however, that early tracheal extubation does not necessarily mean early discharge from the ICU or hospital. To achieve maximal cost benefit, a team approach to a FTCA and surgery program must be implemented. This process includes preoperative patient education, same-day admission surgery, an anesthetic protocol conducive to early extubation, expeditious and meticulous surgery, flexibility in ICU nursing shifts, early postoperative extubation, avoidance of complications, horizontal integration 356

Risk Assessment Key considerations for the patient described in the case synopsis are the following: (1) elderly patient with high comorbidity risks (prior myocardial infarction, diabetes, transient ischemic attacks) and critical coronary artery disease; (2) planned off-pump CABG surgery, with unanticipated need for conversion to CPB; and (3) perioperative anesthetic agents and techniques, monitoring, and preventive measures for perioperative anesthetic complications.

Implications MEDICAL Early extubation anesthetic management provides more stable perioperative hemodynamics and adequately suppresses the perioperative stress response without increasing the requirement for vasoactive medications. There is no significant laboratory evidence of greater myocardial injury during the first 48 hours with early versus conventional late extubation (Fig. 88-1). Respiratory mechanics after extubation are comparable between early- and late-extubation patients. The first hour after extubation is most crucial for respiratory care (Table 88-1). Tidal volume and central respiratory drive progressively improve over the first hour after extubation. There is no increased risk for respiratory acidosis, hypoxemia, or atelectasis with early extubation.

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CK:MB enzyme levels (IU/L)

24

Trial

Early Conv

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Favors FTCA

Favors TCA

22 Slogoff 1989

20 18

Bell 1994

16

Cheng 1996

14

Myles 1997

12

Silbert 1998

10

Berry 1998

8 0

6

12

18 24 30 Postoperative hours

36

42

48

Figure 88–1 ■ Comparison of postoperative creatine kinase MB (CK-MB) enzyme levels between early and conventional (Conv) extubation groups over 48 hours. (From Cheng DCH, Karski J, Peniston C, et al: Morbidity outcome in early versus conventional tracheal extubation after coronary artery bypass grafting: A prospective randomized controlled trial. J Thorac Cardiovasc Surg 112:755-764, 1996.)

Table 88–1

■

Apnea* in Early- and Late-Extubated Patients after Coronary Artery Bypass Grafting

Incidence of apnea episodes Duration of apnea (sec) Index (apnea episodes/hr) 1 hr 2 hr 3 hr 4 hr

Early

Late

27.5% (14/51) 17.7 ± 23.0

33.3% (17/51) 15.7 ± 28.6

13 4 2 2

15 8 9 8

*Apnea is defined as expiratory pause of more than 10 seconds or tidal volume of less than 100 mL as measured with inductive plethysmography. From Cheng DCH, Karski J, Peniston C, et al: Morbidity outcome in early versus conventional tracheal extubation after coronary artery bypass grafting: A prospective randomized controlled trial. J Thorac Cardiovasc Surg 112:755-764, 1996.

1.00

10.00

Relative risk

Figure 88–2 ■ Relative risk of mortality with a low-dose opioid regimen (fast-track cardiac anesthesia [FTCA]) and the more traditional high-dose opioid regimen (traditional cardiac anesthesia [TCA]). (From Myles PS, Daly DJ, Djaiani G, et al: A systematic review of the safety and effectiveness of fast track cardiac anesthesia. Anesthesiology 99:982-987, 2003.)

37 randomized trials revealed that off-pump bypass does not significantly reduce mortality, stroke, myocardial infarction, or renal dysfunction compared with conventional CABG with CPB. Further, off-pump CABG may improve selected 30-day clinical outcomes (e.g., reduced postoperative atrial fibrillation, respiratory infections, and need for inotropic support or blood transfusions) without measurable increased risk to the patient. At the same time, off-pump CABG reduces resource utilization, including ventilation time and ICU and total hospital length of stay, leading to potential reductions in hospitalization costs. However, there is an increased risk for significant mortality and morbidity in patients emergently converted from off-pump to conventional CABG with CPB. Economic The strongest predictors of cost for cardiac surgical patients are patient age, operating room time, ICU and hospital length of stay, and postoperative complications. Differences in CABG costs are primarily a reflection of accounting methods (e.g., charges, actual patient costs, reimbursed costs). Additional important factors are the following: ●

●

● ●

Are costs reimbursed by a health maintenance organization or managed care provider? Is CABG performed in a teaching hospital or a community cardiac center? Are physician fees or cardiac catheterization costs included? What is the impact of patient-specific factors (e.g., number of coronary vessels grafted, extent and severity of postoperative complications)?

Early extubation protocols significantly lower CABG costs compared with more traditional management methods. They also reduce the intensity of nursing care by reducing ICU and hospital length of stay and by allowing more timely patient mobilization and hospital discharge. Early extubation

CARDIOTHORACIC & VASCULAR SURGERY

Also, early extubation improves the intrapulmonary shunt fraction by 30% to 40% after CABG. Cognitive function has also been shown to return to baseline earlier in patients given early extubation versus conventional anesthetic management. This allows earlier mobilization and oral intake of food in the early postoperative period, resulting in shorter ICU and hospital length of stay. Importantly, early extubation does not increase ICU readmission or mortality rates. A systematic review and meta-analysis of 10 randomized trials in adult cardiac surgical patients undergoing CABG or valve surgery with CPB showed a nonsignificant reduction in mortality in patients undergoing FTCA versus traditional care based on high-dose opioids, as well as no significant difference between groups with respect to major morbidity (Fig. 88-2). Currently, approximately 25% of all CABG surgery in the United States is off-pump CABG. A meta-analysis of

0.10

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Preoperative Care

Total Costs for Early- and Late-Extubation Anesthesia, Including Complications Costs (Canadian $)

Preoperative Operating room Cardiovascular ICU Postoperative ward CABG: mean CABG: median

Early (n = 50)

Late (n = 50)

P

1347 ± 7619 ± 6463 ± 4169 ± 19,596 17,269

1353 ± 7755 ± 12,046 4963 ± 26,116 19,372

.76 .24 .026 .25 .019 .019

104 499 4943 1426 ± 5766

92 653 ± 16,573 3068 ± 18,175

CABG, coronary artery bypass grafting; ICU, intensive care unit. From Cheng DCH, Karski J, Peniston C, et al: Early tracheal extubation after coronary artery bypass graft surgery reduces costs and improves resource use: A prospective randomized controlled trial. Anesthesiology 85:1300-1310, 1996.

also improves ICU use and allows for increased caseloads with significantly fewer surgery cancellations (0.3% versus 2.0%). Finally, it results in up to a 28% lower rate of ICU readmission. Importantly, to reduce perioperative costs, in addition to improving efficiency, perioperative morbidity rates must be minimized. This is because postoperative complications are far more costly than uncomplicated recoveries. Postoperative myocardial infarction or stroke can increase the cost of CABG three- to fivefold, infection two- to fourfold, and repeat surgery for postoperative bleeding or atrial arrhythmia control by 30% to 40%. Early extubation anesthesia can be performed without increasing CABG complication rates while reducing ICU costs by 53% and overall costs by 25% (Table 88-2). In a 1-year follow-up study of FTCA patients after surgery, there was also evidence of reduced resource utilization after their index hospital discharge. Fifteen patients (25%) from both groups were readmitted to acute care hospitals during the follow-up period. The mean length of stay for acute care readmission was 0.3 day in the FTCA group and 1.6 days in the conventional group at 3 months (95% confidence interval [CI], 0.1 to 5.7; P = .01); it was 0.8 and 2.9 days, respectively, at 12 months (95% CI, 0.2 to 7.5; P = .01). The cost reduction associated with FTCA was 68% at 3 months and 50% at 1 year.

MANAGEMENT An effective FTCA program requires appropriate patient selection, a balanced anesthetic technique (i.e., low-dose opioids and inhalational agents), early tracheal extubation, a short stay in a postoperative unit, and coordinated perioperative care. It is also necessary to avoid postoperative complications such as excessive bleeding, myocardial ischemia, low cardiac output states, stroke, arrhythmias, and renal failure. Finally, it is important for anesthesiologists to participate in the development and implementation of an FTCA and surgery program, based on their knowledge of perioperative medicine and skills with perioperative management.

Preoperative patient education is important to reduce anxiety and to establish realistic patient expectations. A preadmission clinic and same-day surgery program can reduce hospital length of stay by 1 to 2 days. Further, it reduces surgery cancellation or delays due to abnormal test results or patients’ suboptimal clinical condition.

Intraoperative Care The anesthetic regimen consists of balanced anesthesia with a low-dose narcotic, propofol, and inhalational agents: ●

●

●

●

● ●

●

Sedation: intravenous midazolam (1 to 3 mg) for line instrumentation Prophylactic antifibrinolytic treatment: intravenous tranexamic acid (50 to 100 mg/kg over 15 minutes) or aprotinin (6 million units total for induction, CPB, and post-CPB) Induction: propofol (0.5 mg/kg) or thiopental (1 mg/kg), low-dose narcotic (up to 10 μg/kg fentanyl, or 1 to 2 μg/kg sufentanil, or 1 μg/kg per minute remifentanil), rocuronium (0.10 mg/kg), and midazolam (1 to 3 mg) Before CPB: inhalational agent (isoflurane, sevoflurane, or desflurane) During CPB: inhalational agents After CPB: postoperative analgesia (indomethacin 50 to 100 mg as needed, if not contraindicated) is essential, and sedation (propofol) is titrated to allow tracheal extubation within 1 to 6 hours Fluids and arrhythmia: tight fluid balance and aggressive arrhythmia control

Trials of remifentanil in cardiac surgery suggest that it provides excellent hemodynamic stability, minimal elevation of catecholamines, and reliable awakening, with most patients being eligible for early extubation. A remifentanil infusion and a low-dose fentanyl-based anesthetic regimen appear to be equivalent in the following respects: time to tracheal extubation, need for less intense monitoring, ICU and hospital length of stay, and resource utilization after CABG surgery. However, remifentanil’s short duration of action necessitates the use of one or more supplementary methods for postoperative analgesia. These must be started before cessation of the remifentanil infusion. Inhalational anesthetic agents have been recommended to provide cardioprotective effects via preconditioning and the reduction of reperfusion injury. The cardioprotective effects of sevoflurane appear to be most efficacious when the agent is administrated throughout the operation. Shorter-acting neuromuscular blocking drugs should be used in FTCA; at a minimum, reversal of pancuronium neuromuscular blockade should be done before commencing weaning from mechanical ventilation. Hemofiltration, but not steroids, results in earlier tracheal extubation following CPB. Intrathecal morphine doses as low as 250 μg are effective for reducing pain scores and postoperative parenteral opiate requirements, but their effect on time to tracheal extubation is not clear. Also, numerous well-conducted clinical trials have demonstrated a reduced time to tracheal extubation with thoracic epidural anesthesia in patients undergoing

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cardiac surgery. However, when compared with general anesthesia designed to facilitate early tracheal extubation, the differences are arguably of little clinical significance, because the majority of patients receiving thoracic epidural anesthesia still require ICU admission for a brief period of ventilation. Also, the majority of patients having general anesthesia can be extubated within 8 hours, so either technique appears to be consistent with FTCA. Transesophageal echocardiography (TEE) during CABG surgery remains a class II indication and is valuable or informative in 15% to 50% of cases and essential in 5% to 20%. Epiaortic echocardiography is the current gold standard for diagnosing and evaluating patients for ascending aortic atherosclerosis during heart surgery. Results of urgent TEE in hemodynamically unstable patients or those with thromboembolic phenomena in the post-cardiac surgery ICU are unpredictable in more than half of cases. Clinical management is often modified based on TEE findings, and TEE is essential for the management of hemodynamically unstable patients after cardiac surgery.

Postoperative Care

Table 88–3

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Independent Predictors of Delayed Extubation by Multiple Logistic Regression Analysis

Independent Predictors

No. of Patients (%)

Odds Ratio

P

Age (versus <60 yr) 60-69 yr 70-79 yr ≥80 yr Intraoperative inotropes Intraoperative IABP Postoperative atrial arrhythmias

338 (38.1) 193 (21.8) 18 (2.0) 61 (6.9) 57 (6.4) 109 (12.3)

1.67 2.22 1.86 1.86 3.58 1.85

.0004 .0004 .0004 .004 .0001 .003

IABP, intra-aortic balloon pump. From Wong DT, Cheng DCH, Kustra R, et al: Risk factors of delayed extubation, prolonged length of stay in the intensive care unit, and mortality in patients undergoing CABG with fast track cardiac anesthesia: A new cardiac risk score. Anesthesiology 91:936-944, 1999.

■

Fast-Track Cardiac Surgery

359

Tracheal Extubation Guidelines

Central nervous system: Responsive and cooperative Cardiovascular system: CI >2.0; absence of uncontrolled arrhythmia Respiratory system: VC >10 mL/kg, NIF >–20 mm Hg; pH >7.30, PaO2 >80 on FiO2 < 0.5 Bleeding: Chest tube drainage <100 mL/hr Renal: Urine output >0.5 mL/kg/hr Temperature: >36.5°C CI, cardiac index; FiO2, fraction of inspired oxygen; NIF, negative inspiratory force; PaO2, arterial oxygen tension; VC, vital capacity.

extubation protocols. Early extubation may allow for chest tube removal, mobilization, and food intake on postoperative day 1, facilitating early ICU discharge and hospital discharge by days 4 to 5. Finally, health care providers should be cognizant of the need for continuous improvement in quality of care and for cost savings, which can be facilitated by following appropriate weaning and extubation guidelines, arrhythmia management regimens, post-valvular anticoagulation protocols, and ICU and hospital discharge guidelines (Table 88-5).

PREVENTION Bleeding and Chest Re-exploration. The incidence of postoperative bleeding necessitating chest re-exploration ranges from 1% to 5%. The common use of the potent antiplatelet medications (glycoprotein IIb/IIIa receptor antagonists) abciximab, eptifibatide, and tirofiban necessitates the delay of elective cardiac surgery for 1 to 2 days, 2 to 4 hours, or 3 to 4 hours, respectively, after discontinuing these medications. Aprotinin is more effective in preventing postoperative bleeding than either tranexamic acid or ε-aminocaproic acid, and it may provide additional antiinflammatory protection. Because of its high cost, aprotinin is usually reserved for cases with a high likelihood of allogeneic blood transfusion (e.g., reoperations, combined CABG-valve procedures, aortic surgery). Atrial Arrhythmia. Atrial fibrillation is common after cardiac surgery, occurring in up to 35% of patients. Drugs with β-blocking properties are effective at reducing the frequency of postoperative atrial fibrillation. The added benefit versus

Table 88–5

■

Intensive Care Unit Discharge Guidelines

Central nervous system: Alert and cooperative Cardiovascular system: No uncontrolled arrhythmia; stable hemodynamics Respiratory system: PaO2 > 80, PaCO2 < 60, SaO2 > 90% at ≤60% facemask Bleeding: Chest tube drainage <50 mL/hr × 2 hr Renal: Urine output >0.5 mL/kg/hr PaCO2, arterial carbon dioxide tension; PaO2, arterial oxygen tension; SaO2, arterial oxygen saturation.

CARDIOTHORACIC & VASCULAR SURGERY

Although high-risk patients are more likely to incur postoperative complications, both intraoperative and postoperative complications ultimately determine whether early extubation and reduced ICU length of stay are possible (Table 88-3). All patients should be assessed for the feasibility of tracheal extubation once certain criteria are met (Table 88-4). Nonsteroidal anti-inflammatory drugs have been used widely in cardiac surgery patients who lack contraindications such as peptic ulcer, renal impairment, or coagulopathies. Diclofenac appears to be more effective than indomethacin and ketoprofen. Enteric-coated aspirin is routinely given postoperatively and is associated with a reduced risk of death and major complications after CABG surgery. Nursing support is needed to achieve 1-day ICU stays and transfer to the floor or a step-down unit. There must be appropriate changes in analgesia and sedation practices and adherence to accelerated weaning and tracheal

Table 88–4

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the safety of combining class III antiarrhythmic activity (e.g., amiodarone) with β-blocking activity is not clearly defined. Therefore, the use of amiodarone to prevent or manage postoperative atrial fibrillation should be considered on a case-by-case basis (assessing risk versus benefit). The role of magnesium for the prevention of atrial fibrillation is not clearly defined, but it is usually well tolerated. Biatrial pacing is likely to reduce the incidence of postoperative atrial fibrillation, but the ideal pacing strategy (i.e., left, right, or biatrial pacing) remains to be defined. Stroke. Stroke occurs in 2% to 4% of patients after cardiac surgery and carries a high 1-year mortality of 15% to 30%. Steps to reduce the perioperative stroke rate have been suggested and include routine epiaortic scanning for cannulation and cross-clamping, higher CPB perfusion pressure, avoidance of unprocessed cardiotomy blood, and preservation of cerebral oximetry. Renal Failure. Approximately 8% to 15% of cardiac surgery patients sustain moderate renal injury (>1.0 mg/dL peak creatinine rise), with 1% to 5% requiring dialysis. Patients with preexisting renal dysfunction are at greater risk for needing dialysis. However, patients with preexisting renal dysfunction are not at greater risk for additional renal injury relative to baseline. Steps to minimize postoperative acute renal injury include higher CPB flow rates and avoidance of excessive hemodilution during CPB (e.g., hematocrit <20%).

Further Reading Chaney MA: Intrathecal and epidural anesthesia and analgesia for cardiac surgery. Anesth Analg 84:1211-1221, 1997. Cheng DCH: Fast track cardiac surgery pathways: Early extubation, process of care, and cost containment. Anesthesiology 88:1429-1433, 1998. Cheng DC, Bainbridge D, Martin JE, et al: Does off-pump coronary artery bypass reduce mortality, morbidity and resource utilization when compared to conventional coronary artery bypass? A meta-analysis of randomized trials. Anesthesiology 102:188-203, 2005. Cheng DCH, Byrick RJ, Knobel E: Structural models for intermediate care areas. Crit Care Med 27:2266-2271, 1999. Cheng DCH, Karski J, Peniston C, et al: Early tracheal extubation after coronary artery bypass graft surgery reduces costs and improves resource use: A prospective randomized controlled trial. Anesthesiology 85:1300-1310, 1996.

Cheng DCH, Karski J, Peniston C, et al: Morbidity outcome in early versus conventional tracheal extubation after coronary artery bypass grafting: A prospective randomized controlled trial. J Thorac Cardiovasc Surg 112:755-764, 1996. Cheng DCH, Newman M, Duke P, et al: Efficacy and resource utilization of remifentanil and fentanyl in fast track CABG surgery: A prospective randomized double blind controlled multicenter trial. Anesth Analg 92:1094-1102, 2001. Cheng DCH, Wall C, Djaiani G, et al: A randomized assessment of resource utilization in fast-track cardiac surgery one-year after hospital discharge. Anesthesiology 98:651-657, 2003. Cohen DJ, Breall JA, Ho KKL, et al: Economics of elective coronary revascularization: Comparison of costs and charges for conventional angioplasty, directional arthrectomy, stenting and bypass surgery. J Am Coll Cardiol 22:1052-1059, 1993. De Hert SG, Van der Linden PJ, Cromheecke S, et al: Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration. Anesthesiology 101:299-310, 2004. Dowd N, Cheng DCH, Karski J, et al: Intraoperative awareness in fast track cardiac anesthesia. Anesthesiology 89:1068-1073, 1998. Dowd NP, Karski JM, Cheng DCH, et al: Cognitive recovery and resource utilization following fast track cardiac anesthesia for CABG surgery in the elderly: Propofol versus benzodiazepines. Br J Anaesth 86:68-76, 2001. Edgerton JR, Dewey TM, Magee MJ, et al: Conversion in off-pump coronary artery bypass grafting: An analysis of predictors and outcomes. Ann Thorac Surg 76:1138-1143, 2003. Engelman RM, Rousou JA, Flack JE, et al: Fast-track recovery of the coronary bypass patient. Ann Thorac Surg 58:1742-1746, 1994. Hynninen MS, Cheng DC, Hossain I, et al: Non-steroidal anti-inflammatory drugs in treatment of postoperative pain after cardiac surgery. Can J Anaesth 47:1182-1187, 2000. Kogan A, Cohen J, Raanani E, et al: Readmission to the intensive care unit after “fast-track” cardiac surgery: Risk factors and outcomes. Ann Thorac Surg 76:503-507, 2003. Mangano D: Aspirin and mortality from coronary bypass surgery. N Engl J Med 347:1309-1317, 2002. Myles PS, Daly DJ, Djaiani G, et al: A systematic review of the safety and effectiveness of fast track cardiac anesthesia. Anesthesiology 99:982-987, 2003. Wake PJ, Ali M, Carroll J, et al: Clinical and echocardiographic diagnoses disagree in patients with unexplained hemodynamic instability after cardiac surgery. Can J Anaesth 48:778-783, 2001. Westaby S, Pillai R, Parry A, et al: Does modern cardiac surgery require conventional intensive care? Eur J Cardiothorac Surg 7:313-318, 1993. Wong DT, Cheng DCH, Kustra R, et al: Risk factors of delayed extubation, prolonged length of stay in the intensive care unit, and mortality in patients undergoing CABG with fast track cardiac anesthesia: A new cardiac risk score. Anesthesiology 91:936-944, 1999.

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89

Komal Patel and Mark A. Chaney Case Synopsis An obese 53-year-old woman with right-sided heart failure and ovarian cancer has an exploratory laparotomy under general anesthesia for tumor debulking. On postoperative day 1, she experiences sudden-onset shortness of breath.

PROBLEM ANALYSIS Definition and Recognition

● ●

●

●

●

●

●

Coagulation factors circulate in inactive form. Normal blood flow dilutes the concentration of activated factors and removes them from the site of injury. These are subsequently removed from the circulation by the liver and reticuloendothelial system. Some coagulation factors (e.g., factor Xa) require a phospholipid surface (tissue factor, platelet phospholipid) for proper interaction. Antithrombin (AT; formerly known as antithrombin III) complexes with and inactivates thrombin as well as other circulating coagulation factors (with the exception of factor VII). AT molecules have two critical domains: one binds to thrombin and other activated clotting factors, and the other binds heparin. In the presence of heparin, the rate of AT binding to thrombin and other activated clotting factors is markedly accelerated. Thrombin binds to thrombomodulin (a protein located on the vascular endothelial surface), which activates protein C, thereby inactivating factors Va and VIIIa. Protein S is a cofactor (along with protein C) in the inactivation of factors Va and VIIIa. Tissue factor pathway inhibitor is synthesized by vascular endothelium and inhibits factor X in two ways: it directly inhibits factor Xa, and it complexes with factor Xa to inhibit tissue factor VIIIa, thereby inhibiting the extrinsic pathway.

Hypercoagulable states represent a spectrum of processes that increase the activation of coagulation, decrease endogenous anticoagulation, or decrease the activity of thrombolytic systems. These disorders may be qualitative or quantitative, and their clinical manifestations depend on the severity of the disorder. Hypercoagulable disorders are classified as inherited disorders (conditions for which specific defects of the endogenous anticoagulation system have been identified; Table 89-1) or acquired disorders (disease or states associated with increased risk of thrombotic complications compared with that in general population; Table 89-2). 361

CARDIOTHORACIC & VASCULAR SURGERY

More than 150 years ago, Virchow suggested a triad that leads to intravascular coagulation: injury to blood vessels, venous stasis, and hypercoagulability. Injury to blood vessels, as might occur with direct trauma, major burns, surgical manipulation, or central venous access, causes endothelial damage, leading to the formation of local clot (thrombus) and subsequent propagation (thromboembolism). Venous stasis, as might occur in anesthetized surgical or immobilized patients, results in sluggish venous flow and a propensity for thrombus formation. An understanding of hypercoagulability requires a basic knowledge of the coagulation process. Thrombus formation is triggered by endothelial injury, exposing subendothelial collagen to circulating platelets. These adhere and form a platelet plug. As this is forming, the clotting cascade is activated via one of two pathways. In the intrinsic pathway, subendothelial collagen is activated through activation of factor XII (which requires factors VIII, IX, and XI). In the extrinsic pathway, tissue thromboplastin (tissue factor) is released by injured tissue to activate factor VII. The final (common) pathway begins with activated factor X (Xa). Once factor X is activated, it binds with its cofactor, factor V, and platelet phospholipid, and this complex activates prothrombin (factor II) to form thrombin (factor IIa). Thrombin, bound to platelet phospholipid, cleaves fibrinogen to fibrin monomers. These aggregate to form a fibrin polymer that is loosely held together by hydrogen bonds (soluble fibrin, or fibrin S). Subsequently, factor XIII (fibrin stabilizing factor), which is activated by thrombin and calcium ions, mediates the formation of covalent peptide bonds between the fibrin monomers to yield a stable fibrin clot (insoluble fibrin, or fibrin I). Normally, the clotting process is balanced by an endogenous anticoagulant and thrombolytic system that limits clot formation and eventually dissolves the clot. Thrombolysis is initiated by tissue-type plasminogen activator (t-PA) from injured cells near the fibrin clot. As t-PA cleaves circulating plasminogen to plasmin, this dissolves fibrin within the clot matrix.

Several physiologic mechanisms regulate the coagulation process, thus limiting clot formation to the injured area and preventing excessive clotting (i.e., disseminated intravascular coagulation [DIC]):

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Table 89–1

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Inherited Disorders Causing Hypercoagulable States

Affected Component

Expression

Factor V gene mutation

Resistance to activated protein C by factor V Increased prothrombin production Deficiency and dysfunction Deficiency and dysfunction Deficiency Dysfunctional protein Deficiency Deficiency Deficiency or dysfunctional protein Deficiency Elevation

Prothrombin gene mutation Antithrombin Protein C Protein S Fibrinogenemia Heparin cofactor II Procoagulant factor Plasminogen Plasminogen activator Plasminogen activator inhibitor-1

INHERITED HYPERCOAGULABLE DISORDERS Factor V Leiden Mutation and Resistance to Activated Protein C. Activated factor V serves as a cofactor in the conversion of prothrombin to thrombin. Factor Va is inactivated by activated protein C. A single point mutation in the factor V gene (R506Q [factor V Leiden]) makes the molecule resistant to degradation by activated protein C and thus leads to a hypercoagulable state by increasing the generation of thrombin. About 3% of the general population is heterozygous for this mutation. It accounts for 21% to 25% of patients with recurrent deep venous thrombosis (DVT). Prothrombin Gene Mutation. A specific point mutation in the prothrombin gene (G20210A) results in a 30% increase in the plasma prothrombin levels. Heterozygotes account for about 6% to 18% of patients with recurrent DVT.

Table 89–2

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Acquired Disorders Predisposing to Thrombosis

Venous Stasis Immobilization Pregnancy Congestive heart failure Varicosities Obesity

Coagulation Activation Trauma Surgery Malignancies Factor IX concentrates Lupus inhibitor Myocardial infarction Myeloproliferative disorders Nephrotic syndrome Oral contraceptives

Abnormal Vascular Surface Atherosclerosis, hyperlipidemia

Diabetes Homocysteinemia Cigarette smoking Estrogen therapy Prosthetic cardiovascular device Indwelling vascular catheters

Vascular Occlusive Disorders Hyperviscosity, polycythemia Sickle cell disease Plasma cell dyscrasias

Increased Platelet Reactivity Thrombocytosis Surgery

Antithrombin Deficiency. AT is an α2-globulin synthesized in the liver that inactivates thrombin; factors XIIa, XIa, Xa, and IXa; and kallikrein. AT deficiency was the first identified cause of hereditary hypercoagulable disorders. It is inherited in an autosomal dominant fashion and accounts for approximately 0.5% to 1% of patients with recurrent DVT. Protein C and Protein S Deficiency. Proteins C and S are vitamin K–dependent plasma proteins that inactivate factors Va and VIIIa. Their deficiency is transmitted in an autosomal dominant fashion and accounts for 5% to 10% of patients with recurrent DVT. ACQUIRED HYPERCOAGULABLE DISORDERS Acquired Protein C Deficiency. Acquired protein C deficiency has been observed in patients with DIC, acute leukemia, hepatic disease, and nephrotic syndrome; renal transplant patients; and patients taking warfarin or oral contraceptives. Malignancy. The incidence of clinical thromboembolic disease in patients with cancer has been estimated to be as high as 11%. Thrombotic episodes may precede the diagnosis of malignancy by months to years. It may present as migratory superficial thrombophlebitis (Trousseau’s syndrome), DVT, DIC, nonbacterial thrombotic endocarditis, or, rarely, arterial thrombosis. Tumors may secrete procoagulants (cysteine protease, tissue factor–like procoagulant). Tumors can also lead to venous thrombosis by external compression, vascular invasion (renal tumor), or hepatic involvement and dysfunction. Pregnancy. Pregnancy and the postpartum period are associated with the presence of all three components of Virchow’s triad: venous stasis within the lower extremity veins (the gravid uterus impedes venous return), endothelial injury to the pelvic veins produced during delivery, and hypercoagulability. Pregnancy is also associated with increases in factors I, II, VII, VIII, IX, and X, along with decreases in protein S and AT activity. In addition, the activity of fibrinolytic inhibitors PAI-1 and PAI-2 is increased during pregnancy. Surgery. DVT and pulmonary emboli may occur postoperatively. Thrombosis in surgical patients appears to be related to surgical tissue trauma and the liberation of tissue factor, leading to thrombin formation. In addition, inflammation (leukocyte reactivity) and surgery-induced hemostatic changes may contribute to thromboembolism (Table 89-3). Hemostatic changes appear to correlate with the type of surgery and magnitude of surgical intervention and are maximal during the first 48 hours after surgery. Immobilization. It is postulated that venous stasis contributes to thrombosis by causing local hypoxia (with resulting endothelial injury) and inadequate clearance of activated procoagulant proteins. Myeloproliferative Disease. Patients with myeloproliferative disorders (e.g., polycythemia rubra vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, agnogenic myeloid metaplasia, megakaryocytic myelosis, chronic myelocytic leukemia) have an increased incidence of

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Table 89–3

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Surgery-Induced Hemostatic Changes

Increased Platelet Reactivity

↑ Von Willebrand’s factor ↑ Thrombin formation

↑ Aggregation ↑ Dense granule release

Decreased Endogenous Anticoagulants

Increased Leukocyte Reactivity

↓ Antithrombin III ↓ Heparin cofactor II ↓ Tissue factor pathway inhibitor ↓ Protein C, protein S

↑ Free radical release ↑ Surface adhesion molecules

Increased Coagulation Cascade Activation ↑ Fibrinogen ↑ Factor VIII

■

Decreased Fibrinolysis ↑ Plasminogen activator inhibitor-1

Hypercoagulable States: Thrombosis and Embolism

mutations affecting the cystathion β-synthase (CBS) gene or the methylenetetrahydrofolate reductase (MTHFR) gene. Other Factors. Other factors that may be associated with hypercoagulable states are nephrotic syndrome, oral contraceptive use, hormone replacement therapy, prolonged travel, heavy smoking, hypertension, paroxysmal nocturnal hemoglobinuria, heparin-induced thrombocytopenia, thrombocytosis, and inflammatory bowel disease. THROMBOEMBOLISM Arterial thromboembolism may lead to cerebral or other vital end-organ infarction. For all intents and purposes, venous thromboembolism is pulmonary embolism, which has the following pathophysiologic effects: ●

thrombotic events. Both arterial and venous thrombosis may occur at unusual anatomic sites, including the mesenteric, renal, splenic, portal, and hepatic (Budd-Chiari syndrome) circulations.

●

● ●

● ●

Increased pulmonary vascular resistance secondary to vascular obstruction, neurohumoral mediators, cytokines, and reflex vasoconstriction Impaired gas exchange secondary to increased alveolar dead space, ventilation-perfusion mismatch, and rightto-left shunt Compensatory alveolar hyperventilation Right heart dysfunction and dilatation secondary to increased pulmonary artery pressure, wall tension, oxygen consumption, and ischemia Bronchoconstriction and increased airway resistance Reduced lung compliance secondary to edema, hemorrhage, and surfactant loss

Risk Assessment

Lupus Anticoagulant. Lupus anticoagulants are antiphospholipid antibodies (usually immunoglobulin [Ig] G and, rarely, IgM) directed against plasma proteins (e.g., β2glycoprotein I, prothrombin, annexin V) bound to anionic phospholipids. Lupus anticoagulants occur in about 5% to 10% of patients with systemic lupus erythematosus. They block the in vitro assembly of the prothrombinase complex, resulting in a prolongation of protein assays such as activated partial thromboplastin time, dilute Russell viper venom time, kaolin plasma clotting time, and, rarely, prothrombin time. Although these changes suggest impaired coagulation, patients with lupus anticoagulants have a paradoxical increase in the frequency of arterial and venous thrombotic events. The mechanism for thrombosis is incompletely understood but may involve IgG binding to phospholipids that are essential for the normal activating and degrading effects of protein C and protein S, thus shifting the balance in favor of thrombus formation.

INHERITED HYPERCOAGULABLE STATES

Hyperhomocysteinemia. High levels of homocysteine are associated with both venous and arterial thrombosis. The mechanism by which hyperhomocysteinemia predisposes to thrombosis is unclear; however, potential mechanisms include endothelial activation, proliferation of smooth muscle cells, changes in endothelial nitric oxide production, or changes in endothelial sterol metabolism. The disorder can be congenital or acquired. Acquired forms are found in patients with dietary deficiencies of folate, vitamin B12, or vitamin B6. Congenital hyperhomocysteinemia is most commonly due to

Malignancy. Intravascular thrombus formation can occur with any malignancy but is more common with neoplasms of the mucin-secreting organs (gastrointestinal and pulmonary). Migratory superficial thrombophlebitis occurs in up to 10% of patients with pancreatic carcinoma. Patients with malignancy also have other predisposing factors for venous thrombosis (e.g., surgery, immobilization).

The prevalence of factor V Leiden mutation and prothrombin gene mutation in patients with DVT is about 21% to 25% and 6% to 18%, respectively. However, patients with these mutations have a relatively low risk for thrombosis. By age 65 years, only about 6% of carriers of these mutations have experienced venous thrombosis, with most thrombotic events occurring during high-risk periods such as surgery. The frequency of factor V Leiden varies by ethnicity; it is common in people of European descent but rare in those of African or Asian descent. AT deficiency accounts for only 0.5% to 1% of patients with DVT, but more than 50% of affected patients experience venous thrombotic events by age 60 years. Protein C and protein S deficiency accounts for 0.5% to 4% and 1% to 7% of patients with DVT, respectively. ACQUIRED HYPERCOAGULABLE STATES

Pregnancy. Pregnancy is associated with an approximate sixfold increased risk of venous thromboembolism compared

CARDIOTHORACIC & VASCULAR SURGERY

Hyperviscosity Syndrome. Blood viscosity is increased when there is an elevated red cell mass (polycythemia), increased immature adherent leukocytes (aplastic anemia), deformed red cell membrane (sickle cell anemia), and increased globulin concentrations (plasma cell disorders). Sluggish flow associated with these conditions can result in vascular occlusion in any vascular bed. It is believed that immature white cells cause leukostasis; this in turn releases proteases, which promote thrombus formation.

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with nonpregnant patients (see also Chapter 196). Risk is greatest in the third trimester and first month post partum. The incidence of DVT and pulmonary embolism has been estimated to be as high as 0.05% to 0.1%. Pulmonary embolism is estimated to account for 12% of fatalities during pregnancy. Risk factors for thrombosis in pregnancy include increasing age, cesarean delivery, prolonged immobilization, obesity, prior thromboembolism, and coexistent thrombophilia. Surgery. Orthopedic procedures on the hip and lower extremities are among the most thrombogenic surgical procedures. In the absence of prophylaxis, the risk of DVT after total knee replacement ranges from 45% to 70%, and fatal pulmonary embolism has been reported to occur in 1% to 3% of patients undergoing hip surgery. Coronary artery bypass grafting surgery is associated with up to a 20% risk of DVT and a 4% risk of pulmonary embolism. Although the risk of thromboembolism is greatest during the first 2 postoperative days, embolic events may occur weeks to months after knee or hip surgery. Immobilization. Conditions leading to prolonged immobility (e.g., heart failure, stroke, spinal cord injury, old age, obesity, major trauma, surgery) increase the risk for hypercoagulability. DVT incidence rates of 58% in patients after major trauma and 33% in immobilized patients requiring medical intensive care have been reported. Myeloproliferative Disease. There is a correlation between elevated hematocrit, blood viscosity, and occlusive vascular events. Indwelling Vascular Catheters. Thrombotic complications are common with central venous catheters and are often associated with catheter sepsis. Thrombosis can be due to fibrin deposition or vascular occlusion.

Implications Because the heparin effect (anticoagulation) depends on adequate AT levels, patients with AT deficiency may not respond appropriately to heparin. The use of warfarin may produce a deficiency in protein C and protein S before anticoagulation, which is responsible for warfarin-induced skin necrosis. For patients with hypercoagulable states, heparin therapy may be indicated for conditions that significantly increase the risk of venous thrombosis and pulmonary embolism (e.g., surgery, major trauma, immobilization).

MANAGEMENT Except for AT deficiency (see Prevention), there is no specific therapy for hypercoagulable states other than anticoagulation with heparin (standard unfractionated or low molecular weight) or warfarin to prevent pulmonary embolism and thrombolysis (streptokinase, urokinase, recombinant t-PA) to dissolve clots. Nonspecific measures include hemodilution and avoidance of factors that might increase blood viscosity or facilitate coagulation (e.g., packed red blood cells, plasma, calcium).

Treatment of pulmonary embolism may be primary or secondary. Primary treatment to remove clot includes thrombolysis, catheter embolectomy, clot fragmentation, or surgical embolectomy. Secondary treatment for the prevention of recurrences includes systemic anticoagulation (heparin, warfarin) and inferior vena cava filters (e.g., bird’s nest or Greenfield filters).

PREVENTION Preventive measures for venous thrombosis and pulmonary embolism in high-risk patients include subcutaneous lowmolecular-weight or unfractionated heparin, graduated compression stockings, and pneumatic compression devices. Fondaparinux (a synthetic heparin pentasaccharide) has been approved by the Food and Drug Administration for the prophylaxis of DVT in patients undergoing surgery for hip fracture or hip or knee replacement. Recombinant hirudin preparations have been used as prophylactic agents for DVT in European countries. In the United States, they are currently approved only for the treatment of heparin-induced thrombocytopenia. The following preventive measures should be considered for patients with acquired or inherited hypercoagulable states. Antithrombin Deficiency. AT concentrations routinely decrease after surgery but can be increased with the administration of plasma. Recombinant human AT is also available, and its use should be considered perioperatively in patients with AT deficiency, keeping in mind that heparin can decrease AT concentrations. Protein C and Protein S Deficiency. Concentrations of protein C and protein S can be increased by the administration of plasma. Specific protein C concentrate is also available. Myeloproliferative Disease. Because there is a correlation between occlusive vascular events and elevated hematocrit, blood viscosity, and leukocytosis, these three parameters should be returned to a more normal range with the appropriate use of phlebotomy, chemotherapy, or crystalloid solutions.

Further Reading Bucur SZ, Levy JH, Despotis GJ, et al: Uses of antithrombin III concentrate in congenital and acquired deficiency states. Transfusion 38:481-498, 1998. Loscalzo J, Schafer A: Thrombosis and Hemorrhage, 3rd ed. Philadelphia, JB Lippincott–Williams & Wilkins, 2003. Martinelli I, Mannucci PM, De Stefano VD, et al: Different risk of thrombosis in four coagulation defects associated with inherited thrombophilia: A study of 150 families. Blood 92:2353-2358, 1998. Mateo J, Oliver A, Borrell M, et al: Laboratory evaluation and clinical characteristics of 2132 consecutive unselected patients with venous thromboembolism: Results of the Spanish Multicentric Study on Thromboembophilia (EMET-Study). Thromb Haemost 77:444-451, 1997. Santoro SA: Antiphospholipid antibodies and thrombotic predisposition: Underlying pathologic mechanisms. Blood 83:2389-2391, 1994. Sixth ACCP guidelines for antithrombotic therapy for prevention and treatment of thrombosis. American College of Chest Physicians. Chest 119(1 Suppl):1S-370S, 2001. Van Guldener C, Stehouwer CD: Hyperhomocysteinemia, vascular pathology and endothelial dysfunction. Semin Thromb Hemost 26:281-289, 2000.

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One-Lung Ventilation Peter D. Slinger

90

Case Synopsis A 70-year-old woman with recurrent carcinoma of the right lung is scheduled for a right thoracotomy and possible pneumonectomy (Fig. 90-1). After induction of general anesthesia, a 37 French left-sided double-lumen endotracheal tube is placed, and satisfactory positioning is confirmed through auscultation (Figs. 90-2 and 90-3). After the patient is turned to the left lateral decubitus position, the tracheal (right) lumen of the double-lumen tube is clamped, and the bronchial cuff is inflated with 3 cm3 of air. On thoracotomy, the right lung remains inflated, and the patient’s pulse oximetric saturation falls below 85%.

PROBLEM ANALYSIS Definition

Recognition Management of arterial desaturation takes precedence over the diagnosis of tube malposition. Once adequate oxygenation has been ensured, fiberoptic bronchoscopy is performed to confirm double-lumen tube position or assist with repositioning of the bronchial blocker. If a bronchoscope is not immediately available, palpation of the lung hilum and carina by the surgeon may be useful to determine the position of the double-lumen tube. Surgical exploration also helps rule out pneumomediastinum, the most common presenting sign of tracheal or bronchial laceration by the double-lumen tube. There are many other methods that can aid in the intraoperative diagnosis of double-lumen tube malposition, including the following: ●

Figure 90–1 ■ Preoperative chest radiograph of a 70-year-old woman with recurrent carcinoma of the right lung who is scheduled for right thoracotomy and possible completion pneumonectomy. Tracheal deviation is a warning that double-lumen tube placement may be difficult.

●

Chest auscultation. This is difficult to perform after the patient has been prepped and draped for surgery, and it may fail to diagnose lobar obstruction from distal migration of a double-lumen tube. Changes in lung mechanics. These may be revealed by airway pressure changes or changes in flow-volume or pressure-volume loops. Although any of these is a fairly sensitive indicator of changes in lung mechanics, they are 365

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This case synopsis demonstrates two of the major complications of one-lung ventilation: inadequate lung isolation and hypoxemia (Table 90-1). Persistent inflation of the operative lung results from one of three potential causes: (1) doublelumen tube or bronchial blocker malposition or migration due to surgical manipulation or patient positioning;

(2) delayed lung deflation in a patient with obstructive airway disease, bullae or both; or (3) iatrogenic tracheal or bronchial rupture, or both, from the tube. Although there are many potential causes of intraoperative hypoxemia during one-lung ventilation, it usually results from pulmonary shunting through the nonventilated lung. Hypoxemia due to shunting usually becomes clinically evident 10 to 20 minutes after the start of one-lung ventilation. Arterial desaturation very early in the course of one-lung ventilation is often due to inadequate gas exchange in the dependent lung due to malposition of the double-lumen tube. The concurrence of inadequate lung isolation and early desaturation in the patient described in the case synopsis suggests intraoperative migration of the double-lumen tube as the most likely cause.

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1 2

3

Figure 90–2 ■ Three-step method of auscultation to confirm double-lumen endobronchial tube positioning. Step 1: Inflate the tracheal cuff. Auscultate to confirm bilateral ventilation. Step 2: Clamp the tracheal lumen proximally (clamp the short side short) and inflate the bronchial cuff. Open the tracheal port and ventilate. Auscultate to confirm correct unilateral ventilation. Step 3: Release the tracheal lumen clamp, and close the tracheal port. Auscultate to confirm resumption of bilateral ventilation.

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367

2a

3

3

Figure 90–3 ■ Common initial malpositions of double-lumen endobronchial tubes can be detected sequentially during the three-step method of auscultation. Step 1: Overly distal placement in either main bronchus is revealed by unequal breath sounds. Step 2a: Overly proximal placement results in inability to achieve unilateral ventilation during ventilation by the bronchial lumen. Step 2b: Incorrect side of bronchial intubation is revealed by unilateral breath sounds in the incorrect hemithorax. Step 3: Slightly too proximal placement results in appropriate isolation but unequal auscultation with resumption of bilateral ventilation.

●

all relatively nonspecific and can be due to surgical manipulation, pulmonary air leaks, airway blockage due to secretions or tube malposition, inadequate muscle relaxation, and many other causes. Changes in end-tidal carbon dioxide (CO2) tension. The onset of one-lung ventilation is usually associated with

a small (≤5 mm Hg) and transient (≤5 minutes) drop in end-tidal CO2. Sudden, severe, or prolonged declines in end-tidal CO2 suggest inadequate gas exchange in the dependent lung. Because similar changes in end-tidal CO2 can be caused by alterations in cardiac output, this is also a fairly nonspecific indicator.

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2b

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Complications of One-Lung Ventilation and Double-Lumen Endobronchial Tubes

Hypoxemia Malpositioning (primary or delayed) Soiling of healthy lung regions Inadequate ventilation Interference with surgery Airway trauma Laryngeal Tracheal Bronchial Difficulty managing secretions Surgical damage to distal bronchial lumen

Risk Assessment Difficult Lung Isolation. Although techniques to predict difficult endotracheal intubation are well described, the methods of assessment for difficult endobronchial intubation are not widely appreciated. Problems with double-lumen tube or bronchial blocker placement can occasionally be anticipated on the basis of the preoperative history, the physical examination, or a bronchoscopy report that suggests abnormal tracheobronchial anatomy. The majority of potentially difficult endobronchial intubations can be anticipated by examining the preoperative chest radiograph and computed tomography (CT) scan. Hypoxemia during One-Lung Ventilation. Factors associated with increased risk of oxygen desaturation during one-lung ventilation include (1) a larger proportion of preoperative ventilation or blood perfusion to the operative lung, (2) an increased alveolar-arterial oxygen gradient during two-lung ventilation, (3) right-sided thoracotomy, and (4) predictive preoperative spirometry.

Implications Although lung isolation is usually performed to facilitate surgery, in certain circumstances (e.g., bronchopleural fistula, pulmonary hemorrhage, lung abscess), the inability to adequately isolate the lungs can be life-threatening. Iatrogenic tracheal or bronchial rupture due to double-lumen tubes or bronchial blockers is estimated to occur in 0.5 to 2 in 1000 cases.

MANAGEMENT Inadequate Lung Isolation Immediate treatment for inadequate lung isolation is deflation of the bronchial cuff (or blocker, if one is used) and manual ventilation of both lungs to assess compliance. Ventilation of the dependent lung can be confirmed by observing mediastinal movement with lung inflation in the open chest. Ventilation of the nondependent lung can be observed directly. If ventilation of both lungs is not quickly confirmed, the double-lumen tube should be withdrawn

until the distal end of the bronchial lumen is above the carina (<25 cm by the tube markings from the inferior alveolar ridge for most adults) and ventilation is resumed. Once ventilation of both lungs is ensured by the return of satisfactory pulse oximetric oxygen saturations and end-tidal CO2 concentrations, definitive repositioning of the doublelumen tube can be undertaken. The fiberoptic bronchoscope should be passed via the bronchial lumen, and the carina should be identified. During repositioning, if the tube persistently tends to enter the right main-stem bronchus, tube rotation or right flexion or rotation of the patient’s head often facilitates left mainstem bronchial intubation. If this fails, the bronchoscope should be advanced into the left main-stem bronchus and used as a guide to advance the bronchial lumen. This is easier to perform with fiberoptic bronchoscopes, which are specifically designed for anesthesia (e.g., Olympus LF-1 or LF-2) and are more rigid than pediatric bronchoscopes of similar diameter (<4 mm). If bronchoscopy does not help achieve tube repositioning, an attempt can be made to advance a partially withdrawn tube into the left main-stem bronchus while the surgeon compresses the right main-stem bronchus. If this fails, an attempt can be made to ventilate the left lung via the tracheal (incorrect) lumen of the left double-lumen tube with the bronchial lumen malpositioned in the right main-stem bronchus. If it is not possible to position the left-sided doublelumen tube satisfactorily, there are two major options (Fig. 90-4): 1. Continue the surgery with the double-lumen tube positioned above the carina and two-lung ventilation. 2. Replace the airway catheter or choose another technique for lung isolation (e.g., right-sided double-lumen tube, single-lumen endotracheal tube plus a bronchial blocker or single-lumen left endobronchial tube). The left double-lumen tube can be changed to a singlelumen tube or a right-sided tube without repositioning the patient with the use of a specifically designed, commercially available tube exchanger or with the fiberoptic bronchoscope. The problem of obstruction of the right upper lobe, which is seen commonly with right double-lumen tubes, is not a concern during left lung ventilation. If a single-lumen tube is used, a bronchial blocker (e.g., Arndt Blocker, Cook Critical Care, Bloomington, Ind.) can be passed intraluminally and positioned in the right main-stem bronchus under direct fiberoptic bronchoscopic vision. Alternatively, some bronchial blockers can be passed through the vocal cords extraluminally to a single-lumen tube. Another method for bronchial blockade is the use of a Univent tube (Fugi Corp., Tokyo), which is a single-lumen tube with an enclosed bronchial blocker. However, all forms of bronchial blockers are more likely than double-lumen tubes to migrate intraoperatively, causing loss of lung isolation, particularly when placed in the shorter right main-stem bronchus. A final option is to advance a small (<7 mm internal diameter) single-lumen tube as an endobronchial tube under fiberoptic guidance. However, this may be difficult in a patient with distorted carinal anatomy.

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Figure 90–4 ■ Management options for failure to achieve lung isolation with a left-sided double-lumen tube.

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Hypoxemia Hypoxemia should resolve with reinstitution of two-lung ventilation. During one-lung ventilation with an appropriately placed double-lumen tube or blocker and a fraction of inspired oxygen (FiO2) of 1.0, hypoxemia occurs in less than 5% of cases. Airway suctioning should be performed to ensure that thick bronchial secretions are not obstructing ventilation. When hypoxemia occurs during one-lung ventilation despite correct double-lumen tube positioning, continuous positive airway pressure (CPAP) with 2 to 5 cm H2O to the reinflated, nonventilated lung is the only therapy required in most cases. Positive endexpiratory pressure (PEEP) to the ventilated lung is not useful in patients with obstructive lung disease who develop auto-PEEP during one-lung ventilation. However, low levels of PEEP (<5 cm H2O) are useful in children or patients with normal lungs.

PREVENTION Inadequate lung isolation can be prevented by following the “ABCs”: ●

●

Anatomy: A thorough knowledge of the lobar bronchial anatomy is necessary to achieve successful lung isolation (Fig. 90-5). Understanding the lengths and diameters of the bronchi and their variations with age and sex enables the anesthesiologist to plan the appropriate technique for lung isolation. Bronchoscope: The anesthesiologist should always use a fiberoptic bronchoscope to assess double-lumen tube or bronchial blocker position and to gain familiarity with bronchial anatomy. This familiarity will be useful when there is distorted anatomy or blood or pus in the airway. Because double-lumen tubes or bronchial blockers commonly

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RIGHT LUNG

LEFT LUNG 19 Apical posterior

Apical 22

Posterior

UPPER LOBE

Anterior

50 16

10

13

Anterior

UPPER LOBE

Superior Superior

9

Inferior

LINGULA

Superior

Lateral MIDDLE LOBE Medial

Anterior basal Lateral basal

Anterior basal Medial basal Posterior basal Posterior basal

Lateral basal

LOWER LOBE

LOWER LOBE Figure 90–5 ■ Diagram of the tracheobronchial tree. Mean lengths and diameters are given in millimeters. Note that the right middle lobe bronchus exits directly anteriorly, whereas the superior (also called apical) segments of both lower lobes exit posteriorly. If the superior segment of the right lower lobe is called the apical, the segments from top to bottom on the right spell the mnemonic APALM.

●

migrate during patient positioning, the most important time to perform bronchoscopy is after final positioning of the patient for surgery and just before the start of onelung ventilation. Chest radiography and CT scanning: Examining the preoperative chest radiographs and CT scans can provide information about anatomic problems and airway size (see Fig. 90-1). This information is useful when selecting lung isolation methods and tube sizes.

Prevention of hypoxemia is most reliably performed with the use of an FiO2 of 100% and prophylactic application of CPAP to the nonventilated lung in selected high-risk patients (e.g., those with large alveolar-arterial oxygen gradients during two-lung ventilation, right-sided thoracotomies, and good preoperative spirometry). CPAP must be applied to a reinflated lung for optimal effect. To reduce the risk of tracheobronchial trauma during endobronchial tube or blocker insertion, use the appropriate size tube; avoid nitrous oxide, which can cause bronchial cuff overinflation; always manipulate the tube or blocker gently; and position the double-lumen tube under direct bronchoscopic guidance when problems are anticipated

or encountered. The suggested double-lumen tube sizes based on gender and height are as follows: females less than 160 cm tall, 35 French; females greater than 160 cm tall, 37 French; males less than 170 cm tall, 39 French; and males greater than 170 cm tall, 41 French. Smaller double-lumen tubes (26 to 28 French) are available for children and small adults. The bronchial cuff volume required to seal the airway is usually less than 3 mL. The bronchial cuff should be slowly inflated to the minimal volume required to achieve isolation. It is important to be aware that airway trauma is always a risk whenever a double-lumen tube or blocker is used.

Further Reading Arndt GA, Kranner PW, Rusy DA, Love R: Single-lung ventilation in a critically ill patient using a fiberoptically directed wire-guided endobronchial blocker. Anesthesiology 90:184-186, 1999. Bardoczky G, Szegedi L, d’Hollander A: Two-lung and one-lung ventilation in COPD patients: The effects of position and FiO2. Anesth Analg 90:35-41, 2000. Bauer C, Winter C, Hentz JG, et al: Bronchial blocker compared to doublelumen tube for one-lung ventilation during thoracoscopy. Acta Anaesth Scand 45:250-254, 2001.

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Fujiwara M, Abe K, Mashimo T: The effect of positive end-expiratory pressure and continuous positive airway pressure on the oxygenation and shunt fraction during one-lung ventilation with propofol anesthesia. J Clin Anesth 13:473-477, 2001. Licker M, de Perrot M, Spiliopoulos A: Risk factors for acute lung injury after thoracic surgery for lung cancer. Anesth Analg 97:1558-1565, 2003.

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Russell WJ, James MF: The effects of increasing cardiac output with adrenalin or isopenaline on arterial haemoglobin oxygen saturation and shunt during one-lung ventilation. Anaesth Intensive Care 28:636-641, 2000. Slinger P, Kruger M, McRae K, Winton T: The relation of the static compliance curve and positive end-expiratory pressure to oxygenation during one-lung ventilation. Anesthesiology 95:1096-1102, 2002.

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Mediastinal Masses Jerome M. Klafta Case Synopsis A 23-year-old previously healthy man presents with a 3-month history of cough (worse when he is lying flat). He says he has “head fullness.” His chest radiograph demonstrates mediastinal lymphadenopathy with no other abnormalities. He is scheduled for parasternal mediastinotomy. After induction with propofol and succinylcholine, the patient is easily intubated, but manual ventilation is extremely difficult.

●

PROBLEM ANALYSIS

● ●

Definition Patients with anterior mediastinal masses are prone to develop certain potentially life-threatening complications because of the influence of these masses on neighboring structures (superior vena cava, tracheal bifurcation or main-stem bronchi, main pulmonary artery, aortic arch, and heart). Principal anesthetic considerations for patients with anterior mediastinal masses involve the following three potential complications: ● ● ●

Tracheobronchial tree compression or obstruction Superior vena cava syndrome Compression of the heart and pulmonary vessels

Also, patients may present for anesthesia or monitored anesthesia care for a variety of reasons, including: ● ●

Excision of intrathoracic tumor (primary or metastatic) Lymph node biopsy (for tissue diagnosis)

Suprasternal notch

●

Central line placement (for chemotherapy) Biopsy of intrathoracic mass (open or thoracoscopic) Any other procedure, either related to the disease (e.g., open reduction and internal fixation of pathologic fracture) or not (cesarean section) Imaging studies (children)

Although these masses are referred to as “anterior,” they are often at the confluence of the anterior, superior, and middle mediastinum (Fig. 91-1).

Recognition TRACHEOBRONCHIAL TREE COMPRESSION

Angle of Louis

Posterior mediastinum

Xiphoid Middle mediastinum

372

OBSTRUCTION

Tracheobronchial tree compression or obstruction is the most common of the three potential complications arising from anterior mediastinal masses. There can be both static and dynamic components to such compression or obstruction. The dynamic components may not be unmasked until

Superior mediastinum

Anterior mediastinum

OR

Figure 91–1 ■ The mediastinum is divided into superior and inferior portions. The inferior mediastinum is divided into anterior, middle, and posterior portions. (From Benumof JL: Anesthesia for Thoracic Surgery, 2nd ed. Philadelphia, WB Saunders, 1995, p 39.)

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Figure 91–2 ■ Fiberoptic bronchoscopic appearance of the lower trachea in an anesthetized patient in the supine position (A) with a large anterior mediastinal mass that almost totally obstructs the trachea in the anteroposterior plane. With the patient in the sitting position (B), the lumen appears normal. (From Prakash UBS, Abel MD, Hubmayr RD: Mediastinal mass and tracheal obstruction during general anesthesia. Mayo Clin Proc 63:1004-1011, 1988.)

A

● ● ●

●

History of orthopnea, positional dyspnea Chest radiograph showing large mass, airway compression Chest computed tomography (CT) scan showing compression of airway or other structures (Fig. 91-3) Flow-volume loops with truncation of expiratory and possibly inspiratory limbs (Fig. 91-4)

Table 91–1

■

SUPERIOR VENA CAVA SYNDROME Superior vena cava syndrome occurs as a result of tumor compression or direct invasion of the superior vena cava and has the following features: ● ● ● ●

●

Facial or upper extremity edema Dilated facial or upper extremity veins with collateralization Respiratory symptoms (nasal congestion, cough, orthopnea) Central nervous system effects (mental status changes, headache) Collateralization evident on chest CT with contrast enhancement

Possible Contributory Causes of Tracheobronchial Tree Compression or Cardiovascular Obstruction after the Induction of General Anesthesia and Tracheal Intubation in Patients with Mediastinal Masses

Cause

Result

Loss of lung volume

The mass remains constant in size, but pressure on the lung increases with applied positive airway pressure The mass remains constant in size, but an increased transmural pressure gradient* created by the mass interferes with cardiac filling, thereby increasing central blood volume The mass remains constant in size, but pressure on more compliant superior, middle, or posterior mediastinal cardiovascular structures (superior or inferior vena cava, left or right atria, or even right ventricle) impairs venous filling and cardiac preload, effectively reducing cardiac output The mass increases the transmural pressure gradient and increases intrapleural pressure and (potentially) vital organ perfusion The mass compresses the wall of the tracheobronchial tree, resulting in tracheobronchial distortion (e.g., bending, unusual curves), and can produce mechanical obstruction at the endotracheal tube tip Airway collapse, atelectasis, increased intrapulmonary shunt, and arterial O2 desaturation can occur Tumor size can increase intraoperatively as a result of surgical manipulation, leading to edema or bleeding into the tumor mass (hematoma) Turbulence created by extrinsic airway compression by the tumor mass may be aggravated by overly vigorous positive-pressure ventilation Especially when the tumor mass involves the RLN, surgical dissection to remove the tumor may damage the nerve, leading to partial or complete vocal cord paralysis

Increase in central blood volume Reduction in cardiac output

Loss of negative pleural pressure Tracheobronchial obstruction at the endotracheal tube tip Associated tracheobronchial tree malacia Intraoperative increase in tumor size Creation of turbulent airway flow Injury to the recurrent laryngeal nerve (RLN)

*Transmural pressure gradient is the difference between a cardiac chamber pressure and the juxtacardiac or pericardial pressure. Modified from Benumof JL: Anesthesia for Thoracic Surgery, 2nd ed. Philadelphia, WB Saunders, 1995, p 569.

CARDIOTHORACIC & VASCULAR SURGERY

after supine positioning (Fig. 91-2), induction of general anesthesia, or administration of paralytic agents (Table 91-1). Difficulty in mask ventilation or difficulty ventilating despite successful endotracheal intubation is a classic scenario. Preoperative features include the following:

B

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Normal Intrathoracic mass

TLC

RV

Figure 91–4 ■ Flow-volume loop for a patient with a normal airway and for a patient with an intrathoracic mass. TLC, total lung capacity; RV, residual volume. (From Pullerits J, Holzman R: Anaesthesia for patients with mediastinal masses. Can J Anaesth 36:681-688, 1989.)

Figure 91–3 ■ Chest computed tomography scan showing extrinsic compression at the level of the trachea (top) and main-stem bronchi (bottom).

COMPRESSION

OF

HEART

AND

PULMONARY ARTERY

Compression of the heart or pulmonary artery is a rare but life-threatening complication. A history of syncope or with Valsalva’s maneuver is suggestive and merits at least a focused preoperative two-dimensional echocardiographic examination (look for extrinsic compression of cardiac chambers or of the pulmonary artery).

Risk Assessment Generally, the larger the mass, the greater physiologic embarrassment it is likely to cause. However, the ability to prospectively identify which patients with mediastinal masses are at high risk for perioperative cardiorespiratory complications with general anesthesia is limited. The incidence of these complications may be significantly higher in pediatric patients. This can be explained by the fact that infants and

small children are more susceptible than adults to extrinsic airway obstruction because their airways are more compressible and because small decreases in airway diameter result in proportionally greater effects on airway crosssectional area and resistance. In children, tracheal cross-sectional area (as measured by CT) less than 50% to 66% of predicted has been suggested as a cutoff below which general anesthesia should be avoided if possible. The only symptom that has been shown to strongly correlate with the degree of tracheal narrowing is orthopnea; however, its value in predicting intraoperative airway collapse is questionable. In another report, pulmonary function testing performed in both sitting and supine positions revealed peak expiratory flow rates below 50% of predicted in 5 of 31 children in whom the tracheal cross-sectional area was more than 50% of predicted. Therefore, peak expiratory flow rate may be more sensitive than cross-sectional area alone in detecting airflow compromise due to the compressive effects of a mediastinal mass. In adults, the presence of a pericardial effusion or mixed pattern of obstructive and restrictive pulmonary disease is associated with a high rate of postoperative respiratory complications. However, in all these studies (both children and adults), patients in the highest risk groups were anesthetized with a local anesthetic and sedation, thus limiting any conclusions regarding the safety of a general anesthetic technique.

Implications ●

●

Tracheobronchial tree compression ● Inability to ventilate or oxygenate, with hypercarbia or hypoxia ● Possible cardiorespiratory arrest Superior vena cava syndrome ● Excessive bleeding if the surgical site involves the head, neck, or upper extremities ● Unreliable drug or fluid delivery via upper extremity intravenous (IV) lines

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Relative contraindication for jugular or subclavian central IV access ● Potential for airway edema Compression of heart and pulmonary vessels ● Hypotension; cardiovascular collapse ●

●

●

Tracheobronchial Tree Compression

●

● ●

●

●

●

●

Superior Vena Cava Syndrome ●

● ●

●

Recognize the effect of associated airway edema on intubation. Elevate the head of the bed to reduce venous pressure. Use lower extremity IV access as a more reliable route to the central circulation. Consider the use of diuretics and steroids.

Compression of Heart and Pulmonary Artery ●

●

●

● ●

Perform intraoperative echocardiography to assess the degree of impairment. Position the patient to minimize compression (lateral or even prone). Maintain venous return, pulmonary artery pressure, and cardiac output as needed with fluids, pressors, and inotropic agents. Spontaneous ventilation may help. Have cardiopulmonary bypass available on a standby basis (have the groins prepped and draped).

PREVENTION In patients with significant vascular, cardiac, or airway compromise, preoperative radiation therapy to shrink the tumor or local anesthesia for the procedure (if feasible) should be strongly considered. A potential disadvantage of preoperative radiation therapy is that it may obscure the histologic diagnosis and jeopardize treatment. CT-guided transsternal core biopsy is an alternative diagnostic technique at some centers. A multidisciplinary approach (oncology, radiation oncology, surgery, and anesthesiology) is required to make an intelligent decision regarding the risk-benefit ratio for proceeding with therapy.

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●

●

Have a low threshold for placing a preinduction arterial line in patients undergoing general anesthesia who have any symptoms or other evidence (e.g., CT scans) of airway compression. This will provide beat-to-beat blood pressure monitoring in the event of respiratory or hemodynamic compromise. A rigid bronchoscope should be available with the attending surgeon in the operating room for induction if there is particular concern about airway collapse. In the absence of contraindications (e.g., aspiration risk, difficult mask airway), slow induction of general anesthesia is preferred (IV or inhalation). Maintain spontaneous ventilation until effective positive-pressure ventilation is confirmed. If needed, perform tracheal intubation with succinylcholine (unless contraindicated); its short duration of action is advantageous in the event that muscle relaxation has a deleterious effect on the ability to ventilate the patient. Also, use the smallest dose of succinylcholine possible (≤1.0 mg/kg ideal or lean body weight). If feasible, perform fiberoptic intubation in an awake, spontaneously breathing patient. The fiberoptic bronchoscope can also be used to assess positional or dynamic airway collapse. Aim for a very smooth emergence and extubation sequence, because excessive coughing and straining can exacerbate both airway obstruction and the symptoms of superior vena cava syndrome. If central venous access or monitoring is required (indications are related to coexisting disease), access should be obtained via the femoral route.

Further Reading Bechard P, Letourneau L, Lacasse Y, et al: Perioperative cardiorespiratory complications in adults with mediastinal mass. Anesthesiology 100:826-834, 2004. Hnatiuk OW, Corcoran PC, Sierra A: Spirometry in surgery for anterior mediastinal masses. Chest 120:1152-1156, 2001. Hoerbelt R, Keunecke L, Grimm H, et al: The value of a noninvasive diagnostic approach to mediastinal masses. Ann Thorac Surg 75: 1086-1090, 2003. Johnson D, Hurst T, Cujec B, et al: Cardiopulmonary effects of an anterior mediastinal mass in dogs anesthetized with halothane. Anesthesiology 74:725-736, 1991. Neuman GG, Weingarten AE, Abramowitz RM, et al: The anesthetic management of the patient with an anterior mediastinal mass. Anesthesiology 60:144-147, 1984. Pullerits J, Holzman R: Anaesthesia for patients with mediastinal masses. Can J Anaesth 36:681-688, 1989. Shamberger RC, Holzman RS, Griscome NT, et al: CT quantitation of tracheal cross-sectional area as a guide to the surgical and anesthetic management of children with anterior mediastinal masses. J Pediatr Surg 26:138-142, 1991. Shamberger RC, Holzman RS, Griscome NT, et al: Prospective evaluation by computed tomography and pulmonary function tests of children with mediastinal masses. Surgery 118:468-471, 1995. Tempe DK, Arya R, Dubey S, et al: Mediastinal mass resection: Femorofemoral cardiopulmonary bypass before induction of anesthesia in the management of airway obstruction. J Cardiothorac Vasc Anesth 15:233-236, 2001.

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●

Change the patient’s position to a lateral or semi-Fowler’s position. Resume spontaneous ventilation. Attempt to advance the endotracheal tube past the obstruction (however, this could cause severe hemorrhage). ● Consider using fiberoptic bronchoscopic guidance or an endotracheal tube changer. ● Consider a smaller endotracheal tube. Attempt to bypass the obstruction and ventilate with a rigid bronchoscope. Oxygenate via femorofemoral cardiopulmonary bypass.

Mediastinal Masses

The anesthetic plan and required setup vary, depending on the proposed operation (and surgical approach), the severity of the patient’s symptoms, and other coexisting conditions and diseases. However, the following guidelines can be used:

MANAGEMENT

The best approach is prevention. However, if tracheobronchial tree compression does occur, the following maneuvers should be attempted:

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Gordon Lee Collins and Eric Jacobsohn Case Synopsis A 74-year-old man is scheduled for a right-sided pneumonectomy for lung cancer. He has a past medical history of hypertension and coronary artery disease, with a coronary artery stent placed in his left anterior descending artery. He has mild chronic obstructive pulmonary disease, with no reversible airway obstruction. He does moderate (>4 METS) daily physical activity without any difficulty. A nuclear medicine stress test performed 1 year previously was negative for myocardial ischemia. Medications include aspirin, simvastatin, and atenolol. Aspirin therapy was discontinued 7 days before surgery. His anesthetic and surgical course is uncomplicated and includes a combined general anesthetic-thoracic epidural technique. There is minimal blood loss, and he receives limited intra- and postoperative fluid. The chest tube is removed on postoperative day 1. Aspirin therapy is restarted on postoperative day 2. On postoperative day 3, the patient has increasing dyspnea, and a chest radiograph shows that the left lung has diffuse bilateral pulmonary infiltrates, in keeping with pulmonary edema. Because of progressive respiratory distress, he is intubated, and mechanical ventilation is commenced. The patient’s oxygen saturation remains between 90% and 94% on 100% oxygen, 10 cm H2O positive end-expiratory pressure, and optimal ventilator settings. A pulmonary artery catheter is judiciously inserted, and appropriate placement is confirmed by chest radiograph. The cardiac output and wedge pressure are low, there is moderate pulmonary artery hypertension and a transpulmonary gradient, and the right atrial pressure is elevated. A transesophageal echocardiogram shows mild right ventricular and right atrial dilatation, with no demonstrable intracardiac shunt. A diagnostic bronchoalveolar lavage is performed and is negative for inflammatory cells or organisms (subsequent cultures are negative). A diagnosis of postpneumonectomy pulmonary edema, complicated by right ventricular dysfunction, is made. Supportive therapy includes diuresis, lung-protective ventilatory support, low-dose dobutamine, and inhaled prostacyclin (for increased pulmonary artery pressure and refractory hypoxemia). On postoperative day 5, hemodynamically unstable atrial fibrillation develops, and the patient is cardioverted. An amiodarone infusion is commenced. The patient’s troponin level increases to 1.1 ng/mL. He is fully heparinized, and β-blockade is intensified. After 14 days of supportive therapy, including an early tracheostomy, he is successfully weaned from mechanical ventilation. After discharge from the intensive care unit, an angiogram shows stable coronary artery disease.

PROBLEM ANALYSIS Definition and Recognition Pneumonectomy is most frequently performed for bronchogenic carcinoma involving the hilum. Occasionally it is performed for inflammatory lung disease, traumatic lung injury, congenital lung disease, and irreversible atelectatic conditions. It is a major operation that results in changes in anatomy and cardiopulmonary physiology. Potentially serious and sometimes life-threatening postpneumonectomy pulmonary, cardiovascular, or other complications are relatively frequent. These are summarized in Table 92-1.

Risk Assessment Many postoperative complications can be minimized by appropriate patient selection. This involves an assessment of 376

pulmonary function, as well as the evaluation of and optimal therapy for any coexisting diseases or conditions, including obesity, cigarette smoking, reversible lung disease, coronary artery disease, and physical nonconditioning. Although baseline pulmonary function testing may have limited predictive value, the results of lung spirometry, lung diffusing capacity, maximal oxygen uptake, and arterial blood gas analysis are the cornerstones of most clinical decisions (Fig. 92-1). There may be less adverse physiologic impact from lung resection in some situations (e.g., resection of an obstructed, nonperfused lobe; concomitant resection of emphysematous bullae).

Implications Right-sided pneumonectomy is associated with greater mortality compared with left-sided pneumonectomy (10% to 12% versus 1% to 3.5%). The indication for pneumonectomy

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Table 92–1

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Complications after Pneumonectomy

Pulmonary Hypoxemia Postoperative respiratory failure Chronic pulmonary debility or deficiency Postpneumonectomy pulmonary edema Postpneumonectomy syndrome Bronchopleural fistula Pulmonary embolism Empyema Esophagopleural fistula Hemothorax Chylothorax Contralateral pneumothorax Pneumomediastinum Mediastinal infection (mediastinitis) Vocal cord paralysis

Postoperative Respiratory Failure. Proper patient selection and the identification and treatment of reversible disorders involving the heart and lungs have greatly reduced postoperative respiratory failure. The following factors may also reduce the incidence of perioperative respiratory complications associated with pneumonectomy: ●

●

●

●

Miscellaneous

Chronic Pulmonary Insufficiency. This condition is largely preventable by appropriate patient selection and preoperative assessment of lung function. Postpneumonectomy Pulmonary Edema. This syndrome develops in up to 5% of patients undergoing pneumonectomy. Mortality exceeds 50%. Postpneumonectomy pulmonary edema results in hypoxemic respiratory failure, with chest radiograph findings of diffuse infiltrates resembling those of acute respiratory distress syndrome. It usually occurs on about the third postoperative day. Its pathogenesis is multifactorial, including the following: ● ● ● ●

●

MANAGEMENT AND PREVENTION Complications occurring after pneumonectomy may be pulmonary, cardiac, or unrelated to either of these systems.

Figure 92–1 ■ Algorithm for the preoperative pulmonary assessment of pneumonectomy patients. DLCO, diffusing capacity of the lung for carbon monoxide; FEV1, forced expiratory volume over 1 second; PFT, pulmonary function test; PPO, predicted postoperative; VO2 max, maximum oxygen uptake.

Surgery performed by a certified thoracic surgeon in a medical center that does a large volume of pulmonary surgeries Appropriate perioperative use of pulmonary rehabilitation, bronchodilators, steroids, and antibiotics Smoking cessation before surgery Effective postoperative physical therapy and incentive spirometry Good postoperative pain control (e.g., thoracic epidural analgesia)

Excessive fluid administration or use of fresh frozen plasma Hyperinflation injury during one-lung ventilation Coexisting pulmonary hypertension Impaired lymphatic drainage due to surgical dissection of hilar lymph nodes Occult pulmonary aspiration

There are no specific methods for managing or preventing postpneumonectomy pulmonary edema. Likely beneficial measures include avoidance of hypervolemia and excessive diuresis, lung-protective ventilatory support, and

Routine PFTs ⇒ FEV1 >60% and DLCO >60% ⇒ Proceed to surgery ⇓ FEV1 <60% and DLCO <60% ⇒ Proceed to lung scan ⇓ PPO FEV1 >40% and PPO DLCO >40% ⇒ Proceed to surgery ⇓ PPO FEV1 <40% and PPO DLCO <40% ⇓ Exercise testing with VO2 max >15 mL/kg/min ⇒ Proceed to surgery ⇓ VO2 max <15 mL/kg/min ⇒ Consider other options before surgery

CARDIOTHORACIC & VASCULAR SURGERY

may affect outcome; for example, pneumonectomy for lung cancer has a mortality of 3% to 4%, whereas that performed for benign disease may be as high as 26%. Emergent pneumonectomy in cases of trauma or massive hemoptysis is associated with mortality rates greater than 30%. Also, pneumonectomy performed by thoracic surgeons has a lower mortality than that performed by general surgeons. Associated lung disease, history of coronary artery disease, history of congestive heart failure, hypertension, atrial fibrillation, cerebrovascular accident, cigarette smoking, and a 10% or greater weight loss over the 6-month period before surgery all contribute to higher mortality.

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Intraoperative Hypoxemia. The differential diagnosis and approach to the prevention and management of hypoxemia during one-lung ventilation are discussed in Chapter 90.

●

Postpneumonectomy paralysis Postpneumonectomy scoliosis Difficulty interpreting pulmonary artery catheter data

Complications after Pneumonectomy

Pulmonary Complications

Cardiovascular Arrhythmias Myocardial infarction Intracardiac shunt Cardiac tamponade or herniation Pneumopericardium

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inhaled pulmonary artery vasodilators if pneumonectomy is associated with refractory hypoxemia or elevated pulmonary artery pressures. Patients with this condition may also benefit from early tracheostomy. Postpneumonectomy Syndrome. This syndrome is the result of extrinsic compression of the distal trachea and mainstem bronchus, caused by a mediastinal shift toward the side of pneumonectomy and hyperinflation of the remaining lung. It occurs about 6 months after surgery, is more common in patients having pneumonectomy during childhood, and is usually a complication of right pneumonectomy. Treatment involves repositioning the mediastinum and filling the empty thorax with a nonabsorbable material. Bronchopleural Fistula. The incidence of bronchopleural fistula ranges from 1.5% to 4.5%; it is associated with 30% to 80% mortality and is more common after right pneumonectomy. It often presents 1 to 2 weeks after pneumonectomy as fever, productive cough, hemoptysis, and subcutaneous emphysema. Other associations include large bronchial stump size, incomplete tumor resection, concurrent radiation or chemotherapy, and poor wound healing (e.g., debilitated patients, steroid therapy). Treatment includes antibiotics, longer-term drainage of the pleural space, and repair of any air leaks with muscle flap procedures when appropriate. Pulmonary Embolism. Most pulmonary emboli arise from the deep veins of the legs. Rarely, they can arise from the pulmonary artery stump or the tumor itself. This complication can be devastating for patients with an already reduced pulmonary vascular reserve. Proper prophylaxis for perioperative deep venous thrombosis is critical. Management includes anticoagulation, but emergent embolectomy may be required immediately postoperatively. In patients further removed from surgery, intravenous thrombolytics should be considered. In those presenting with significant deep venous thrombosis and no pulmonary embolism, retrievable inferior vena cava filter placement may be indicated. Other Pulmonary Complications. Other complications include empyema, chylothorax and acute hemithorax, esophagopleural fistula, contralateral pneumothorax, and vocal cord paralysis. Management may require surgery (incision and drainage, fistula closure, mediastinal repositioning and filling of the empty thorax with nonabsorbable material). For partial or complete vocal cord paralysis, consultation with an otolaryngologist is recommended.

Cardiac Complications Arrhythmia. Atrial tachyarrhythmias (see Chapter 79), especially atrial flutter or fibrillation, are common after thoracic surgical procedures and occur in about 20% of cases. Eighty percent occur within the first 72 hours after surgery. Risk factors for such arrhythmias include age older than 60 years, right pneumonectomy, intrapericardial pneumonectomy, preexisting coronary artery disease, and chronic hypertension. Primary prophylaxis for atrial tachyarrhythmias after pneumonectomy is a β-blocker—either a primary β-blocker or sotalol, which is a β-blocker but also has class III antiarrhythmic activity (see Chapters 11, 12, and 79).

Amiodarone1 may also be effective, but its role in the prophylaxis of postpneumonectomy or thoracotomy atrial tachyarrhythmias has not been established. In addition, pulmonary toxicity with chronic amiodarone administration is known to occur. It is possible that intravenous amiodarone for the prophylaxis or treatment of postpneumonectomy or thoracotomy atrial tachyarrhythmias might aggravate acute lung injury. Hemodynamically unstable atrial flutter or fibrillation requires immediate direct-current cardioversion, with further management and prevention according to established (advanced cardiovascular life support) guidelines (see Chapter 79). Myocardial Infarction. Perioperative myocardial infarction (MI) occurs in 1% to 5% of patients after thoracic surgery. Prophylactic perioperative β-blockers should reduce the incidence of acute MI and other cardiac events after thoracic surgery. Preoperative risk stratification for patients having pneumonectomy should follow existing American Heart Association–American College of Cardiology guidelines, which classify pneumonectomy as an intermediaterisk surgical procedure (see Chapter 38). The patient described in the case synopsis had only one intermediate-risk predictor (remote history of non-Q-wave MI), but he had been revascularized and was physically active. He also had a negative stress test a year before the planned pneumonectomy, making further preoperative testing unnecessary. All patients receiving chronic β-blocker therapy should continue these drugs. Patients with known coronary artery disease or peripheral vascular disease, and those with two or more risk factors for coronary disease (age older than 65 years, treated or untreated hypertension, diabetes mellitus, hypercholesterolemia, current or recent mI [≤ 6 months]), should receive perioperative β-blockers. Routine withdrawal of aspirin therapy before major surgery in patients with coronary artery disease or peripheral vascular disease is probably contraindicated. However, the decision whether to cease such therapy must be individualized. Patients with coronary artery disease on chronic aspirin therapy may develop an aspirin withdrawal syndrome leading to acute MI. Factors such as the severity of cardiovascular and cerebrovascular disease and the presence and age of any stents must also be considered. The risk of withdrawing aspirin must be weighed against the risk of possible increased bleeding. There is accumulating evidence that statin therapy may be protective in the perioperative period in patients with cardiovascular disease. This is likely related to the drugs’ pleiotropic effects. Patients taking statins should not have their therapy interrupted in the perioperative period. Intracardiac Shunting. A patent foramen ovale may be present in 30% of the population. This can cause significant right-to-left shunting and severe hypoxemia if right heart pressure becomes elevated. This could occur due to poor patient selection, increased preoperative pulmonary artery pressures, pulmonary embolism, pneumonia, pneumothorax, postpneumonectomy pulmonary edema, or pulmonary aspiration. 1 Amiodarone is listed as a class III drug, but it has all four VaughanWilliams antiarrhythmic class actions.

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Treatment for the underlying cause of increased right atrial pressure is critical. This includes optimizing right ventricular function and reducing pulmonary artery pressures, if elevated. Measures include inhaled pulmonary artery vasodilators, such as prostacyclin or nitric oxide. Percutaneous closure of the shunt may have to be done in some patients. Cardiac Herniation. Herniation of the heart through a defect in the pericardium can occur at any time after the surgical procedure. In addition to herniation through a pericardial defect, the heart or mediastinal contents may herniate into the pleural space if a chest tube is inadvertently placed on suction. Hence, many surgeons believe that routine chest tubes, even for short periods, are contraindicated after pneumonectomy. Cardiac herniation presents as sudden-onset hypotension and shock, cyanosis, chest pain, and symptoms of the superior vena cava syndrome. Emergent reopening of the thoracotomy is required to immediately reposition the heart. Suturing the edges of the pericardium to the myocardium or placing a prosthetic patch over the pericardial defect during surgery can prevent this complication. If it is caused by inadvertent chest tube suctioning, this must be stopped immediately. Repositioning the patient with the pneumonectomy side up may also be helpful.

Only a few of the more common and difficult to manage complications unrelated to the heart and lungs are discussed here. Postpneumonectomy Spinal Cord Ischemia and Paralysis. This is a rare complication caused by intraoperative injury of the intercostal arteries to the thoracolumbar region of the spinal cord, leading to an anterior spinal artery syndrome. Treatment options are limited and largely unproved. They include maintaining a high spinal cord perfusion pressure and use of cerebrospinal fluid drainage. Postpneumonectomy Scoliosis. Scoliosis is estimated to affect 90% of patients undergoing pneumonectomy. This complication is due to shrinkage of the thoracic cage after surgery. Associated symptoms are usually mild and mostly inconsequential. Difficulty Interpreting Pulmonary Artery Catheter Data. A pulmonary artery catheter or central venous access is not routinely required for pneumonectomy. However, if a pulmonary artery catheter is used during thoracic surgery, it is important to note that data derived from the catheter may vary, depending on which lung or segment it floats to (e.g., dependent or nondependent zone), whether one-lung ventilation is used, and when the readings are made. Depending on the clinical circumstances, a pulmonary artery catheter has the potential to provide misleading data. If placed in the postoperative period, caution must be exercised when floating and inflating the balloon in the newly sutured or stapled pulmonary artery. Further, one should consider floating the pulmonary artery catheter under fluoroscopy or echocardiographic guidance.

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Other Complications. Other complications after pneumonectomy involve primarily the gastrointestinal system and include motility disorders and gastric volvulus. Optimal management may be medical or surgical; if necessary, appropriate consultation should be sought as soon as these complications become apparent.

Further Reading Attar S, Hankins JR, Turney SZ, et al: Paraplegia after thoracotomy: Report of five cases and review of the literature. Ann Thorac Surg 59: 1410-1415, 1995. Bachamn DS: Discontinuing chronic aspirin therapy: Another risk factor for stroke? Ann Neurol 51:137-138, 2002. Cerfolio RJ, Bryant AS, Thurber JS, et al: Intraoperative Solu-Medrol helps prevent postpneumonectomy pulmonary edema. Ann Thorac Surg 76:1029-1033, 2003. Datta D, Lahiri B: Preoperative evaluation of patients undergoing lung resection surgery. Chest 123:2096-2103. 2003. De Wet CJ, Affleck DJ, Jacobsohn E, et al: Inhaled prostacyclin is safe, effective, and affordable in patients with pulmonary hypertension, right heart dysfunction, and refractory hypoxemia after cardiothoracic surgery. J Thorac Cardiovasc Surg 127:1058-1067, 2004. De Wet CJ, McConnell K, Jacobsohn E: Progress in postoperative ICU management. Thorac Surg Clin 15:159-180, 2005. Eagle KA, Berger PB, Calkins H, et al: ACC/AHA update for perioperative cardiovascular evaluation for noncardiac surgery. Circulation 105:1257-1267, 2002. Guggino G, Doddoli C, Barlesi F, et al: Completion pneumonectomy in cancer patients: Experience with 55 cases. Eur J Cardiothorac Surg 25:449-455, 2004. Handschin AE, Lardinois D, Schneiter D, et al: Acute amiodarone-induced pulmonary toxicity following lung resection. Respiration 70:310-312, 2003. Hoff WS, Hoey BA, Wainwright GA, et al: Early experience with retrievable inferior vena cava filters in high-risk trauma patients. J Am Coll Surg 199:869-874, 2004. Kertai MD, Boersma E, Westerhout CM, et al: A combination of statins and beta-blockers is independently associated with a reduction in the incidence of perioperative mortality and nonfatal myocardial infarction in patients undergoing abdominal aortic aneurysm surgery. Eur J Vasc Endovasc Surg 28:343-352, 2004. Khan SN, Stansby G: Cerebrospinal fluid drainage for thoracic and thoracoabdominal aortic aneurysm surgery. The Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD003635. DOI: 10.1002/ 14651858. CD003635.pub2. Miller DL, Deschamps C, Jenkins GD, et al: Completion pneumonectomy: Factors affecting operative mortality and cardiopulmonary morbidity. Ann Thorac Surg 74:876-883, 2002. Poldermans D, Boersma E, Bax JJ, et al: The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 341:1789-1794, 1999. Rahimtoola A, Bergin JD: Acute pulmonary embolism: An update on diagnosis and management. Curr Probl Cardiol 30:61-114, 2005. Senior K: Aspirin withdrawal increases risk of heart problems. Lancet 362:1558, 2003. Sugarbaker DJ, Jaklitsch MT, Bueno R, et al: Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies. J Thorac Cardiovasc Surg 128:138-146, 2004. Van Mieghem W, Coolen L, Malysse I, et al: Amiodarone and the development of ARDS after lung surgery. Chest 105:1642-1645, 1994. Vaporciyan AA, Correa AM, Rice DC, et al: Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: Analysis of 2588 patients. J Thorac Cardiovasc Surg 127:779-786, 2004.

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Complications Unrelated to the Cardiopulmonary System

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Carotid Endarterectomy Vivek Moitra and John Ellis

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Case Synopsis A 72-year-old woman with a significant past medical history of hypertension and coronary artery disease undergoes carotid endarterectomy under general anesthesia. Electroencephalogram (EEG) monitoring is used. Her intraoperative course includes placement of a carotid artery shunt. On the following day, the patient experiences right upper extremity weakness.

PROBLEM ANALYSIS Definition Stroke is the third leading cause of death in the United States. Little can be done after a cerebrovascular accident (stroke) to reverse any permanent vascular brain injury. Stroke may result from aneurysm rupture with intracerebral bleeding, occlusion of intracerebral arteries, or carotid artery occlusion or thromboembolism. For the last, the focus is on prevention. Carotid endarterectomy and stenting are the most commonly performed procedures to minimize the risk of further stroke in patients with carotid atherosclerosis, a systemic and progressive disease. Both symptomatic and asymptomatic patients with carotid lesions (i.e., atheromatous plaques) may benefit from carotid endarterectomy. Frequently, such plaques involve the proximal internal carotid artery and the carotid bifurcation. This may result in luminal narrowing and compromised blood supply to the brain, especially with contralateral atheromatous disease or disease involving the circle of Willis. In addition to luminal narrowing, atheromatous plaques may rupture, leading to thrombus formation and thromboembolism. Transient ischemic attacks and reversible ischemic neurologic deficits are believed to be the result of embolism or hypoperfusion. In many patients, however, carotid disease may manifest only as an asymptomatic carotid bruit. The anesthetic management of candidates for carotid endarterectomy or stenting requires a clear understanding of cerebral circulation and physiology, appropriate monitoring techniques, and the potential for cardiovascular compromise.

thromboembolism, shunt kinking, or air embolism may occur. Methods used to assess the need for a shunt include neurologic assessment of awake patients (if carotid endarterectomy is performed under local or regional anesthesia, such as deep and superficial cervical plexus block), transcranial Doppler, EEG, somatosensory evoked potentials (SEPs), measurement of distal cerebral artery stump pressures (i.e., pressure created by backflow from the contralateral carotid artery across the circle of Willis), or direct measurement of cerebral blood flow with xenon (Table 93-1). The purpose of these measures is to avoid routine shunting, which can cause air embolism or thromboembolism. Different techniques or combinations of these methods may be preferred by different centers. However, the sensitivity of any technique for detecting perioperative ischemia or strokes is limited, because most strokes occur after surgery and are likely caused by thromboembolic phenomena. The gold standard for cerebral monitoring is neurologic assessment of an awake patient. Awake patients having carotid endarterectomy have fewer EEG changes, and many practitioners advocate the use of regional anesthesia to allow the detection of cerebral ischemia, which manifests as acute changes in mental status or motor response to verbal commands. A successful regional anesthetic requires that the patient be comfortable and cooperative throughout the surgery. If combined with general anesthesia, regional blocks may reduce general anesthetic requirements, hasten awakening, and reduce the need for opiate analgesia after surgery.

Table 93–1

Recognition During carotid endarterectomy, the carotid artery is surgically occluded. Early recognition of cerebral ischemia is essential to guide subsequent surgical and anesthetic management. Many surgeons elect to place a shunt to maintain ipsilateral carotid flow, and the use of intraoperative monitors of cerebral perfusion and ischemia can aid the surgeon in making that decision. Placement of a surgical shunt may be routine, or the need for one may be determined by various methods (discussed later). Surgical shunting is not without risk; vessel wall disruption, dislodgment of atheromatous plaque with 380

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Monitors of Cerebral Ischemia during Carotid Endarterectomy

Regional Anesthesia Repeated neurologic examination of the awake patient

General Anesthesia Electroencephalogram Somatosensory evoked potentials Internal carotid artery stump pressure Xenon 133 washout Transcranial Doppler ultrasonography Jugular venous oxygen saturation Transconjunctival oxygen saturation

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Risk Assessment Important risk factors for carotid disease include advanced age, hypertension, tobacco abuse, and a history of diabetes mellitus. Patients with left main coronary artery disease or other peripheral vascular disease are also more likely to have carotid disease. Conversely, patients with carotid disease often have concomitant coronary artery disease. Because these patients are at high risk for stroke but are more likely to die from myocardial infarction, the preoperative risk assessment, workup, and timing of surgery can be challenging and controversial. Cardiac risk assessment may include exercise or dobutamine stress testing to determine the need for preoperative coronary revascularization (e.g., coronary artery bypass grafting or percutaneous coronary transluminal angioplasty, with or without stenting). The appropriate amount of preoperative risk assessment and subsequent preventive intervention is debatable for several reasons. Both the surgeon and the anesthesiologist must consider the risk of neurologic insult if carotid surgery is delayed in favor of a coronary intervention that may prevent the cardiac morbidity associated with

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carotid endarterectomy. Also, both the anesthesiologist and the surgeon must assess the possibility of stroke in patients with carotid stenosis who undergo coronary artery bypass grafting. There are no clear guidelines for anesthesiologists who are managing patients with both carotid and coronary artery disease, and the decision to pursue an invasive intervention is often based on the patient’s clinical history, stability of symptoms, and institutional preference.

Implications A number of trials have demonstrated the benefit of carotid endarterectomy for the prevention of stroke in both symptomatic and asymptomatic patients. This procedure is not without risk, however. In the postoperative period, patients may develop a second neurologic insult, respiratory insufficiency, hemodynamic instability, carotid body damage, hyperperfusion syndrome, or wound hematoma (Table 93-2). Because most perioperative strokes are a result of postoperative thrombus, many vascular surgeons are asking their patients to continue taking antiplatelet agents (e.g., clopidogrel) up until the time of surgery. The use of aggressive antiplatelet therapy in patients with postoperative hypertension may predispose to wound hematoma, which may compromise the airway through laryngeal edema or extrinsic compression. A number of randomized trials have compared carotid endarterectomy to carotid angioplasty and stenting. The challenge during angioplasty is to limit stroke from distal embolization of plaque. Transcranial Doppler has demonstrated that embolic events are far more common with carotid angioplasty than with endarterectomy. Even so, such events are not necessarily associated with increased rates of cognitive dysfunction. “Umbrella” devices that capture embolic particles may improve the results of angioplasty. The ischemic time for angioplasty and stenting is much shorter than for carotid endarterectomy, which may have benefits. Large randomized trials are currently under way, but it will be several years before definitive results are available. Several studies have sought to elucidate predictors of outcome after carotid endarterectomy. Risk factors such as age older than 70 years, history of angina, coronary artery disease, congestive heart failure, severity of preoperative neurologic symptoms, occlusion of the contralateral internal

Table 93–2

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Common Postoperative Problems

Hemodynamic instability Hypertension Hypotension Myocardial infarction Wound hematoma Glossopharyngeal edema with loss of airway Cranial nerve damage Respiratory insufficiency through loss of carotid body function Neurologic dysfunction Acute graft thrombosis (may require re-exploration) Minor focal deficits Hyperperfusion syndrome

CARDIOTHORACIC & VASCULAR SURGERY

Use of superficial or deep cervical plexus block may also minimize the hemodynamic changes associated with general anesthesia. Even so, the vast majority of patients undergo carotid surgery under general anesthesia, and several monitors are available to evaluate the adequacy of collateral circulation and cerebral perfusion. Carotid stump pressure can be measured manually or invasively. The presence of a palpable pulse or a mean stump pressure greater than 60 mm Hg suggests sufficient backflow to prevent ischemia. However, ischemia may occur despite adequate carotid stump pressures if there is middle cerebral artery stenosis on the operative side and distal to the circle of Willis. The EEG represents cortical electrical activity, which decreases with cerebral ischemia. Disadvantages of EEG monitoring include the inability to monitor deep brain structures, the presence of false-negative findings due to preexisting or fluctuating neurologic deficits, and the influence of general anesthesia on EEG patterns. Unlike EEG monitoring, SEPs can monitor deeper brain structures. SEPs are a result of electrical impulses that originate peripherally and travel through first- and second-order neurons to synapse in the brainstem. Subsequently, these impulses are transmitted to the somatosensory cortex. As with EEG monitoring, false-negatives may result if anesthetics produce SEP changes that mimic cerebral hypoxia. Transcranial Doppler measures the velocity of blood flow in the middle cerebral artery. It can be used to detect acute thrombotic occlusion or embolization during or after carotid surgery, or to identify patients at risk for developing a postoperative hyperperfusion syndrome. However, the need for temporal ultrasound probe placement limits surgical and anesthetic access to the head. Cerebral blood flow can also be measured by the intravenous or intracarotid administration of radioactive xenon or krypton. This method requires considerable expertise for the interpretation of data, and it is highly specialized and expensive.

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carotid artery, and so-called siphon stenosis1 have been both supported and refuted, leading many to question their prognostic significance. Perioperative risk may also be affected by the surgeon’s experience.

MANAGEMENT AND PREVENTION The two main goals of intraoperative management are protecting the brain and protecting the heart, but these two goals are often in conflict. For example, increasing blood pressure to augment cerebral blood flow can increase afterload or myocardial contractility, thereby increasing the oxygen demand of the heart. Also, although hypothermia may provide effective cerebral protection, it poses a severe challenge to cardiac homeostasis if the patient is awake and shivering. Thus, the anesthetic plan involves trade-offs if both organs are to be protected.

Cerebral Protection Several strategies have been proposed to protect the brain during carotid endarterectomy. A stable high-normal blood pressure is maintained throughout surgery on the assumption that because blood vessels in ischemic or hypoperfused areas of the brain have lost their normal autoregulation, flow is directly proportional to pressure. Manipulation of arterial carbon dioxide tension (PaCO2) also affects cerebral blood flow. Although permissive hypercapnia dilates cerebral vessels in nonischemic areas of the brain, it may be detrimental if blood flow is diverted from already maximally dilated cerebral arteries perfusing ischemic areas. Conversely, hypocapnia may constrict vessels in adequately perfused, nonischemic areas of the brain to reroute blood to ischemic areas, thereby causing inverse steal. Because neither of these responses is predictable, most experts recommend normocarbia. Hyperglycemia may worsen ischemic brain injury. Elevated blood sugar is associated with elevated glucose levels in the brain and cerebral lactic acidosis from anaerobic glycolysis. Many candidates for carotid endarterectomy are diabetic, and the administration of dextrose-containing intravenous solutions may adversely affect cerebral injury. Although the exact mechanism of hyperglycemia’s adverse effect on ischemic brain injury is unknown, maintaining normoglycemia may be protective. However, isovolemic hemodilution with dextran or hetastarch may be beneficial in cases of cerebral ischemia. Blood viscosity may be reduced, with attendant microcirculatory disturbances thereby ameliorated. Some volatile anesthetic agents (e.g., isoflurane) may offer cerebral protection by reducing cerebral metabolism and decreasing the brain’s requirement for oxygen. Under these circumstances, the brain’s tolerance for temporary ischemia may be enhanced. Barbiturates also offer a degree of brain protection during periods of regional ischemia by

1 Flow to the brain at risk for ischemia or stroke is siphoned from the ipsilateral diseased internal carotid artery by the more normal contralateral internal carotid artery to increase ischemia or stroke risk.

decreasing cerebral metabolic oxygen requirements to about 50% of baseline. Maximal reductions in oxygen requirements correspond to an electrically silent or isoelectric EEG. Hypothermia can depress neuronal activity and reduce reperfusion injury sufficiently to put cellular oxygen requirements below the minimal levels normally required for viability. In theory, hypothermia represents the most effective method of cerebral protection. Even a mild decrease in temperature by about 2°C to 3°C during cerebral arterial hypoxemia has the potential to reduce ischemic damage to the brain.

Cardiac Protection Adequate preoperative preparation and intraoperative monitoring to protect the myocardium can prevent perioperative myocardial infarction. Maintaining the patient’s hemodynamic stability begins before surgery. Patient reassurance during the preoperative evaluation may prevent anxietyinduced myocardial ischemia. If sedatives are necessary, a short-acting premedication facilitates early preoperative neurologic assessment. Blood pressure and heart rate values obtained from the preoperative visit or previous hospital admissions determine the acceptable hemodynamic range for the patient. Chronic antianginal, antihypertensive, and aspirin therapy is generally continued on the day of surgery. β-Blockade has been shown to be cardioprotective in vascular patients with a positive stress test. The American Heart Association and American College of Cardiology 2002 guidelines recommend β-blockers in vascular patients with evidence of stress test–induced ischemia or symptomatic angina, arrhythmias, or hypertension (class I), as well as for patients with untreated hypertension, coronary artery disease, or risk factors for coronary artery disease (class IIa). However, β-blockade may make efforts to increase blood pressure during carotid clamping more difficult, and it may be associated with exaggerated bradycardia if the carotid sinus is stimulated during surgery. Monitoring during carotid endarterectomy includes the usual measures for general or regional anesthesia: temperature probe, blood pressure cuff, pulse oximeter, and end-tidal carbon dioxide. Often, an intra-arterial catheter is placed for beat-to-beat blood pressure monitoring for earlier detection and treatment of changes in blood pressure. Leads II and V4 or V5 of the electrocardiogram should be monitored for ST-T segment changes due to the high incidence of myocardial ischemia after carotid reperfusion. In high-risk patients, monitoring with transesophageal echocardiography may be added.

Further Reading Crawley F, Stygall J, Lunn S, et al: Comparison of microembolism detected by transcranial Doppler and neuropsychological sequelae of carotid surgery and percutaneous transluminal angioplasty. Stroke 31: 1329-1334, 2000. Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 273:1421-1428, 1995. Jordan WD Jr, Voellinger DC, Doblar DD, et al: Microemboli detected by transcranial Doppler monitoring in patients during carotid angioplasty versus carotid endarterectomy. Cardiovasc Surg 7:33-38, 1999.

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Munro FJ, Makin AP, Reid J: Airway problems after carotid endarterectomy. Br J Anaesth 76:156-159, 1996. Naylor AR, Rothwell PM, Bell PR: Overview of the principal results and secondary analyses from the European and North American randomised trials of endarterectomy for symptomatic carotid stenosis. Eur J Vasc Endovasc Surg 26:115-129, 2003. Riles TS, Imparato AM, Jacobowitz GR, et al: The cause of perioperative stroke after carotid endarterectomy. J Vasc Surg 19:206-214, 1994.

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Tangkanakul C, Counsell CE, Warlow CP: Local versus general anaesthesia in carotid endarterectomy: A systematic review of the evidence. Eur J Vasc Endovasc Surg 13:491-499, 1997. Wilke HJ II, Ellis JE, McKinsey JF: Carotid endarterectomy: Perioperative and anesthetic considerations. J Cardiothorac Vasc Anesth 10:928-949, 1996. Zvara DA: Pro: Regional anesthesia is the best technique for carotid endarterectomy. J Cardiothorac Vasc Anesth 12:111-114, 1998.

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Thoracic Aortic Aneurysm Annette Schure and John Ellis Case Synopsis A 67-year-old man underwent repair of a thoracoabdominal aortic aneurysm. The aortic occlusion time was 37 minutes, and left atriofemoral bypass was used during crossclamping for distal perfusion. Blood pressure and heart rate were maintained within 20% of the patient’s preoperative values. Urine output exceeded 0.5 mL/kg per hour in the postrepair period. On emergence from anesthesia, the patient was paraplegic.

PROBLEM ANALYSIS Definition Diseases of the thoracic aorta fall into four categories: 1. Aortic aneurysm: an atheromatous dilatation of the entire vessel wall 2. Aortic dissection (often incorrectly referred to as “dissecting aneurysm”): an expanding hematoma within the aortic wall, caused by either an intimal tear or degeneration of the media 3. Aortic rupture: secondary to trauma involving major shear forces 4. Coarctation: congenital stenosis of the aorta. Exact information about type, location, and extent of the lesion is extremely important, both for surgical approach and for anesthetic management.

Aortic dissections are commonly described according to the Stanford classification (types A and B) or the DeBakey classification (types I, II, IIIA, and IIIB) (Fig. 94-1); for aortic aneurysms, the Crawford classification (types I to IV) is used (Fig. 94-2). Both aneurysms and dissections involving the ascending aorta and the aortic arch are usually approached via a median sternotomy and require cardiopulmonary bypass, often with deep hypothermic circulatory arrest or retrograde or anterograde cerebral perfusion. The perioperative complications and anesthetic management of these aneurysms and dissections are beyond the scope of this chapter. The following discussion focuses on the management of patients with descending thoracic aneurysms.

Recognition Patients with lesions of the descending thoracic aorta may be completely asymptomatic, and the aneurysm may be

Stanford Classification

DeBakey Classification Type I

Type II

Type A

Type III

A

Type B

B

Figure 94–1 ■ DeBakey (types I, II, IIIA, and IIIB) and Stanford (types A and B) classifications of aortic dissection. (From Kouchoukos NT, Dougenis D: Surgery of the thoracic aorta. N Engl J Med 336:1876-1888, 1997.)

384

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II

III

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IV

Figure 94–2 Crawford classification of aortic aneurysms. (From Norris EJ, Frank SF: Anesthesia for vascular surgery. In Miller RD [ed]: Anesthesia, 5th ed. Philadelphia, Churchill Livingstone, 2000, p 1870.) ■

discovered incidentally on a chest radiograph or computed tomography (CT) scan. Alternatively, these aneurysms can present with a wide range of symptoms, depending on type, location, and extent of the lesion (Table 94-1). Imaging studies include a chest radiograph (revealing the classic widened mediastinum and aortic knob), spiral CT, and magnetic resonance imaging to assess the exact location and size of the aneurysm or dissection. Transesophageal echocardiography is useful for the diagnosis of dissections, especially in unstable patients. Angiography is still considered

Table 94–1

■

the gold standard; however, it is invasive, is associated with a high rate of complications (e.g., hemorrhage, nephropathy), and should be reserved for selected cases. Electrocardiogram and laboratory tests provide useful but nonspecific information.

Risk Assessment Patients with aortic disease have a high incidence of comorbidities: coronary artery disease (66%), hypertension (42%), chronic obstructive pulmonary disease (23%), peripheral

Presenting Clinical Signs and Symptoms of Thoracic Aortic Aneurysm and Dissection Aneurysm

Dissection

General presentation Location of pain Cardiovascular

Chronic or acute with leak or rupture Chronic back pain Normal or elevated blood pressure

Respiratory

Dyspnea if associated with left main-stem bronchial obstruction; hoarseness with laryngeal nerve compression; hemoptysis due to erosion Usually normal Possible renal insufficiency with aortic occlusive disease Commonly no associated neurologic symptoms or signs

Dramatic onset and fulminant course Acute-onset back or midscapular pain Elevated blood pressure due to pain; hypotension (possibly shock) if ruptured Dyspnea if associated with left main-stem bronchial obstruction; hemorrhagic pleural effusion

Gastrointestinal (GI) Renal Neurologic

Acute abdomen or GI bleeding Renal insufficiency with involvement of renal arteries Paraplegia if blood supply to spinal cord is impaired

Modified from Skeehan TM, Cooper R Jr: Anesthetic management for thoracic aneurysms and dissections. In Hensley FA, Martin DE, Gravlee GP (eds): A Practical Approach to Cardiac Anesthesia, 3rd ed. Philadelphia, Lippincott Williams & Wilkins, 2003, pp 624-625.

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I

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vascular disease (22%), cerebrovascular disease (14%), diabetes mellitus (8%), and chronic renal disease (3%). The preoperative evaluation should assess the extent, severity, and therapy for any of these comorbidities. Further assessment should focus on the following: ● ●

●

● ●

●

Risk of aspiration (i.e., recent oral intake) Airway evaluation and evidence of tracheal or left mainstem compression on chest radiograph or CT Cardiac evaluation (left ventricular function, regional wall motion abnormalities) Vascular access Preexisting renal insufficiency (diabetic nephropathy, contrast dye load) Preexisting neurologic impairment (possibly associated with dissection or diabetes)

A wide variety of severe perioperative complications can be associated with the surgical repair: ● ●

●

● ● ● ●

Difficult airway management Acute heart failure, myocardial infarction or disadvantageous tachy- or bradyarrhythmias Pulmonary hemorrhage and postoperative respiratory failure Hemorrhage and coagulopathy Hepatic and intestinal ischemia Renal failure Paraplegia

Implications SURGICAL APPROACH

especially in the case of difficult airways, are Univent tubes and Arndt endobronchial blockers. Additionally, extensive postoperative airway edema and facial swelling can complicate extubation or the change of a double-lumen tube to a single-lumen tube, even with a tube exchanger. Sometimes, it is safer to refrain from any such attempt, pull the doublelumen tube tip back into the trachea, and reassess the patient in 24 to 36 hours. HEMODYNAMIC CHANGES AND UNCLAMPING

WITH

CLAMPING

Cross-clamping of the thoracic aorta is often associated with severe hemodynamic and neuroendocrine responses. In contrast to infrarenal clamping, exclusion of the splanchnic circulation significantly reduces the available venous capacitance vasculature, so the sudden increase in impedance to aortic outflow, as well as the proximal shift of blood volume, results in drastic increases in afterload and preload, with the potential for cardiac decompensation or cerebral hemorrhage. Injudicious use of vasodilators (nitroprusside, nitroglycerine, milrinone, inhalational agents) can interfere with hypoxic pulmonary vasoconstriction, which is essential for adequate gas exchange; it can also decrease distal blood flow via the collateral circulation. The goal is careful titration of vasodilators to balance “permissive hypertension” for the maintenance of distal perfusion against the risk of cardiac decompensation. Finally, unclamping of the thoracic aorta can result in severe hypotension. Causes include reactive hyperemia, acidosis, hypercarbia, release of humoral factors such as cytokines and thromboxane, cardiac depression, and blood loss from the anastomosis.

The thoracic aorta is usually approached via a left-sided thoracotomy, with the patient in the right lateral decubitus position. Single-lung ventilation and, depending on the surgeon’s preference and experience, either a simple crossclamping technique (“clamp and sew”) or various forms of distal circulatory support are used. These include heparinbonded shunts (Gott shunts, 7 or 9 mm) that connect the proximal aorta with the femoral artery and provide adequate proximal decompression and maintenance of distal perfusion. Unfortunately, they can be difficult to place and tend to kink. Extracorporeal circulation via an atriofemoral or axillofemoral bypass (partial bypass without oxygenator) and full femorofemoral bypass are alternatives, but they require some degree of heparinization, with the associated risk of increased bleeding.

HEMORRHAGE

AIRWAY MANAGEMENT

The incidence of perioperative acute renal failure ranges from 3% to 14%. Aortic cross-clamping decreases renal blood flow from 80% to 90%, resulting in an ischemic insult. The risk is higher in older patients with coronary artery disease, diabetes, or preexisting renal dysfunction. Acute renal failure is a major predictor of increased morbidity and mortality. Intraoperative urine output is not predictive of postoperative renal function. Acute renal failure may occur despite apparently adequate perfusion (using distal circulatory support) or infrarenal clamping. Various methods of renal protection have been tried, including mannitol, furosemide,

Single-lung ventilation is critical for optimal surgical exposure and prevention of tissue trauma. Preoperative evaluation of the chest radiograph, CT scan, or magnetic resonance image is important, because large thoracic aneurysms can distort or compress the left main-stem bronchus, impairing proper positioning of a left-sided double-lumen tube. If in doubt, the double-lumen tube should be advanced only after fiberoptic examination of the left main bronchus. Right-sided double-lumen tubes, in contrast, easily dislodge and tend to obstruct the right upper lobe. Appropriate alternatives,

Patients undergoing thoracic aneurysm or dissection repair are at increased risk for intra- and postoperative bleeding. Along with renal and cardiac dysfunction, intraoperative blood loss correlates directly with perioperative mortality. In addition to bleeding from the aorta, intrapulmonary hemorrhage may occur due to adhesions and lung manipulations. Heparin use and hypothermia and coagulopathy associated with massive transfusions and liver ischemia are other contributing factors. Liver and bowel ischemia can lead to severe hypocalcemia and endotoxin-induced disseminated intravascular coagulation. RENAL PROTECTION

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fenoldopam, dopexamine, and cold perfusion, all without good scientific evidence. It seems that maintenance of intravascular volume and myocardial function are the most important determinants. SPINAL CORD PROTECTION Paraplegia occurs in about 1% to 11% of surgeries involving the thoracic aorta and is probably the most devastating complication. It usually presents as an anterior spinal artery syndrome with loss of motor function (anterior horn) and partially intact sensation (posterior columns), either immediately on emergence or within the first 24 hours. Interruption of spinal cord blood flow or prolonged hypoperfusion (>30 minutes) results in spinal cord ischemia. The blood supply for the spinal cord is provided by a single anterior spinal artery (75%) and two posterior spinal arteries (25%). In the upper cervical area, the anterior spinal artery is formed by branches of the vertebral arteries, with multiple collaterals from deep cervical and costovertebral arteries. In the middle portion, only a few intercostal arteries provide additional blood supply; the lower part of the spinal cord is

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almost entirely supplied by one intercostal artery branch (artery of Adamkiewicz). This artery is quite variable in origin, arising somewhere between T5 and T8 in 15%, T9 and T12 in 75%, and L1 and L2 in 10% of patients (Fig. 94-3). In addition to an unpredictable blood supply for vulnerable areas, increased cerebrospinal fluid (CSF) pressure can contribute to spinal cord ischemia. Spinal cord perfusion pressure is the mean arterial pressure minus CSF pressure. During aortic cross-clamping, hypertension and increased preload lead to increased intracranial pressure, followed by redistribution of CSF toward the spine and increased CSF pressure. Spinal cord edema after prolonged clamping or with reperfusion can further decrease spinal cord perfusion and contribute to neurologic dysfunction. Somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) are used to monitor spinal cord ischemia. However, SEPs monitor only posterior column function, not the more vulnerable anterior part of the spinal cord, which likely explains the number of case reports of patients with paraplegia despite normal SEPs during clamping. MEPs appear to be more promising in this respect. Also, there can be a substantial delay between the onset of ischemia

Basilar artery Anterior spinal artery

Vertebral artery

1 2 3 4 5

Subclavian artery Cervical segmental arteries

Radicular arteries C3-C4 Radiculomedullary arteries C5-C6

6 7

Radiculomedullary arteries C7-C8 1 2 3 4 5

Radiculomedullary arteries T3-T4 Posterior spinal arteries

6

10 11 12

7 8 9 Great anterior radiculomedullary artery of Adamkiewicz T11-T12

1 2 3 4 5

Lumbosacral radicular arteries

CARDIOTHORACIC & VASCULAR SURGERY

Figure 94-3 Blood supply of the spinal cord. (From Marijic J, El-Magharbel I, Weiss L, Mahajan A: Anesthesia for patients with thoracic aortic disease. In Leung J [ed]: Cardiac and Vascular Anesthesia: The Requisites in Anesthesiology. Philadelphia, Mosby, 2004, p 180.)

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and the appearance of SEP changes. Finally, SEP and MEP monitoring in the operating room is technically cumbersome and influenced by many factors, including anesthetic agents, hypercarbia, temperature, and electrical interference.

MANAGEMENT Monitoring and Intravascular Access Blood pressure should be monitored proximal and distal to the aortic cross-clamp, usually via a right radial artery line (because blood flow to the left subclavian artery might be compromised by the cross-clamp) and a right femoral line. A pulmonary artery catheter and transesophageal echocardiography are useful monitors to assess ventricular function and volume status during clamping and unclamping. In preparation for massive blood loss, one or two 9 French introducers, possibly a dialysis-type catheter in a femoral vein, and one or two large-bore peripheral intravenous lines are advised. Blood warmer and rapid infusion devices should be set up and ready, and an adequate number of blood products should be typed and crossmatched. Also, one or two lumbar CSF drains can be placed and monitored for CSF pressure.

Clamping and Unclamping Anesthetic management depends on the surgical technique and the use of distal circulatory support or electrophysiologic monitoring. An important goal is the prevention of hemodynamic instability (hypertension or hypotension) and myocardial ischemia. Usually, “balanced anesthesia” is used: a combination of potent opioids, benzodiazepines, and lowdose inhalational agents, with or without muscle relaxants. Inotropes or vasodilators are used as required. Some centers advocate the use of combined general-epidural or general-spinal anesthesia, despite the risk of hematoma and medicolegal concerns. In preparation for simple aortic cross-clamping (without bypass), the patient should be allowed to become slightly hypovolemic (pulmonary capillary wedge pressure

Table 94–2

■

5 to 15 mm Hg). Mannitol is often given as a free radical scavenger for renal and spinal cord protection. During clamping, as discussed earlier, vasodilators and inhalational agents should be carefully titrated to balance distal perfusion via permissive hypertension with cardiac function. Before aortic cross-clamp removal, vasodilators and anesthetics are reduced, preload is optimized, and blood products, bicarbonate, and calcium are prepared. A temporary lowdose norepinephrine drip, epinephrine, and occasionally sequential release of the clamp by the surgeon are other useful measures of providing hemodynamic support after aortic cross-clamp release. Adverse hemodynamic changes are usually much less of a concern when extracorporeal circulation systems are used. Flow rates and volume status can be adjusted according to pre- and postclamp pressures, trying to achieve distal aortic pressures greater than 50 to 60 mm Hg.

PREVENTION Many techniques and methods have been described to reduce the risk of spinal cord ischemia (Table 94-2). Unfortunately, the scientific evidence supporting these modalities is inadequate or controversial. Some recent studies support the use of CSF drainage, but only as a component of a multimodal approach to spinal cord protection. Others suggest preoperative identification and selective or serial reimplantation of critical intercostal arteries under SEP or MEP guidance. At present, a combined strategy involving short crossclamp time, some form of distal circulatory support, CSF drainage, adjunctive pharmacotherapy, hypothermia, and avoidance of hyperglycemia is recommended. Finally, the current trend toward endovascular repair has provided a new perspective. So far, the results are promising, but paraplegia can still occur. Further experience and larger case series are necessary before a final recommendation can be made. For the time being, this minimally invasive technique presents anesthesiologists with new challenges.

Methods of Spinal Cord Protection during Descending Thoracic Aortic Surgery

Limitation of cross-clamp duration (<30 min) Distal circulatory support: shunt, atriofemoral or femorofemoral bypass Reattachment of critical intercostal arteries Cerebrospinal fluid drainage Moderate systemic hypothermia (32°C-34°C), epidural cooling, or circulatory arrest Maintenance of proximal blood pressure to improve collateral blood flow Neuroprotective pharmacotherapy Systemic: corticosteroids, barbiturates, naloxone, calcium channel blockers, free radical scavengers, NMDA receptor antagonists, mannitol, magnesium, vasodilators (adenosine, papaverine, prostacyclin), perfluorocarbons, colchicine Intrathecal: papaverine, magnesium, tetracaine, perfluorocarbons Avoidance of postoperative hypotension Sequential aortic clamping Neurologic monitoring for spinal cord ischemia Somatosensory evoked potentials Motor evoked potentials Avoidance of hyperglycemia From Ellis JE, Roizen MF, Mantha S, et al: Anesthesia for vascular surgery. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 4th ed. Philadelphia, JB Lippincott–Williams & Wilkins, 2001, p 952.

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Further Reading Coselli JS, LeMaire SA, K¨oksey C, et al: Cerebrospinal fluid drainage reduces paraplegia after thoracoabdominal aortic aneurysm repair: Results of a randomized clinical trial. J Vasc Surg 35:631-639, 2002. Ellis JE, Roizen MF, Mantha S, et al: Anesthesia for vascular surgery. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 4th ed. Philadelphia, JB Lippincott–Williams & Wilkins, 2001, pp 929-967. Gelman S: The pathophysiology of aortic cross-clamping. Anesthesiology 82:1026-1060, 1995. Greenberg R, Resch T, Nyman U, et al: Endovascular repair of descending thoracic aortic aneurysms: An early experience with intermediateterm follow up. J Vasc Surg 31:147, 2000. Khan RA, Moskowitz DM, Marin M, Hollier L: Anesthetic considerations for endovascular aortic repair. Mt Sinai J Med 69:57-67, 2002. Khan SN, Stansby G: Cerebrospinal fluid drainage for thoracic and thoracoabdominal aortic aneurysm surgery. Cochrane Library, vol 2, 2004. Ling E, Arellano R: Systematic overview of the evidence supporting the use of cerebrospinal fluid drainage in thoracoabdominal aneurysm surgery for prevention of paraplegia. Anesthesiology 93:1115-1122, 2000. Lippman M, Lingham K, Rubin S, et al: Anesthesia for endovascular repair of abdominal and thoracic aortic aneurysms: A review article. J Cardiovasc Surg 44:443-451, 2003.

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Marijic J, El-Magharbel I, Weiss L, Mahajan A: Anesthesia for patients with thoracic aortic disease. In Leung J (ed): Cardiac and Vascular Anesthesia: The Requisites in Anesthesiology. Philadelphia, Mosby, 2004, pp 169-185. O’Connor CJ, Rothenberg DM: Anesthetic considerations for descending thoracic aortic surgery: Part I. J Cardiothorac Vasc Anesth 9:581-588, 1995. O’Connor CJ, Rothenberg DM: Anesthetic considerations for descending thoracic aortic surgery: Part II. J Cardiothorac Vasc Anesth 9:734-747, 1995. Oliver WC Jr, Nuttall G, Murray MJ: Thoracic aortic disease. In Kaplan JA (ed): Cardiac Anesthesia, 4th ed. Philadelphia, WB Saunders, 1999, pp 821-859. Skeehan TM, Cooper R Jr: Anesthetic management for thoracic aneurysms and dissections. In Hensley FA, Martin DE, Gravlee GP (eds): A Practical Approach to Cardiac Anesthesia, 3rd ed. Philadelphia, JB Lippincott–Williams & Wilkins, 2003, pp 617-647. Svensson LG, Patel V, Robinson MF, et al: Influence of preservation or perfusion of intraoperatively identified spinal cord blood supply on spinal motor evoked potentials and paraplegia after aortic surgery. J Vasc Surg 13:355-365, 1991.

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Abdominal Aortic Aneurysm Repair Christopher J. O’Connor Case Synopsis A 74-year-old man with chronic stable angina, hypertension, and a previous myocardial infarction undergoes repair of an infrarenal abdominal aortic aneurysm (AAA) with the use of combined epidural and general anesthesia. Preoperative dipyridamole thallium testing revealed a large, fixed myocardial defect with no evidence of reversible disease. Transient hypotension during aneurysm exposure responds promptly to phenylephrine. After placement of the aortic cross-clamp, there is 1-mm ST segment depression and an increase in the pulmonary capillary wedge pressure. Both resolve with intravenous nitroglycerin therapy. However, moderate hypotension occurs after release of the aortic cross-clamp. Aggressive fluid and cell-saver blood replacement and the administration of phenylephrine restore blood pressure to normal. The patient is successfully extubated at the completion of the procedure and transported to the intensive care unit with an epidural infusion of bupivacaine-fentanyl for perioperative analgesia.

Definition Hypotension is relatively common during infrarenal AAA repair, although it is usually transient and well tolerated. The cause is multifactorial, and treatment depends on the specific cause. Myocardial ischemia, although less frequent, is often encountered in patients with known or previously undiagnosed coronary artery disease (CAD) and may be accompanied by increased pulmonary capillary wedge pressure, reduced cardiac output (Fig. 95-1), and transesophageal echocardiogram (TEE) evidence of regional wall motion abnormalities. In addition to hypotension and myocardial ischemia, other important intraoperative complications include hypertension and left ventricular (LV) dysfunction after aortic occlusion; hypothermia; hypoxemia due to abdominal retraction and underlying obstructive pulmonary disease; severe hemorrhage; and coagulopathy as a result of dilutional changes, hypocalcemia, and acidosis. Mild hypertension is typically encountered after placement of the aortic cross-clamp, although the magnitude of the blood pressure rise is substantially less than that with occlusion at the level of the thoracic aorta. Hypertension during aortic clamping may be absent, however, if blood and third-space fluid losses have not been adequately replaced. Table 95-1 compares the hemodynamic changes with supraceliac and suprarenal versus infrarenal aortic occlusion.

Recognition Recognition of these hemodynamic events is facilitated by the use of direct arterial and central venous pressure monitoring. A pulmonary artery catheter and TEE are monitors for the assessment of preload and LV function and are also used to detect myocardial ischemia. Pulmonary artery 390

catheter and TEE are likely indicated in patients with severe CAD or LV dysfunction. Hypovolemia is diagnosed on the basis of a significant decline in pulmonary capillary wedge pressure, pulmonary artery end-diastolic pressure, or central venous pressure and diminished LV end-diastolic area on TEE. Myocardial ischemia typically manifests as ST segment changes and new regional wall motion abnormalities on TEE. Alterations in pulmonary artery pressure, which also may be observed, are less sensitive indicators of myocardial ischemia. The cause of intraoperative hypotension depends, in part, on the stage of the procedure in relation to the application of

Coronary artery disease

No heart disease

12 Change in pressure after aortic clamping (mm Hg)

PROBLEM ANALYSIS

8 4

* *

*

* *

*

* *

* 0 −4 −8 −12

CVP, P < .01 PA, P < .01 PCW, P < .05

Figure 95–1 ■ Comparison of changes in central venous pressure (CVP), pulmonary artery (PA) pressure, and pulmonary capillary wedge (PCW) pressure in patients with and without coronary artery disease (CAD). Values with asterisks refer to patients developing myocardial ischemia during infrarenal aortic occlusion. Significance values refer to the comparison between patients with and without heart disease. (From Attia RR, Murphy JD, Snider M, et al: Myocardial ischemia due to infrarenal aortic cross-clamping during aortic surgery in patients with severe coronary artery disease. Circulation 53:961-965, 1976.)

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Table 95–1

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Percentage Change in Cardiovascular Variables on Initiation of Aortic Occlusion during Supraceliac versus Infrarenal Aortic Aneurysm Surgery Level of Aortic Occlusion

Variable

Supraceliac

SuprarenalInfraceliac

Infrarenal

+54

+5*

+2*

+38

+10*

0*

+28 +69 −38 +92

+2* +10* −10* +33

+9* +11* −8* 0

Mean arterial blood pressure Pulmonary capillary wedge pressure End-diastolic area End-systolic area Ejection fraction Patients with wall motion abnormalities New myocardial infarction

+8

0

0

*Statistically different (P <.05) from group undergoing supraceliac aortic occlusion. From Roizen MF, Beaupre PN, Alpert RA, et al: Monitoring with two-dimensional transesophageal echocardiography: Comparison of myocardial function in patients undergoing supraceliac, suprarenal-infraceliac, or infrarenal aortic occlusion. J Vasc Surg 1:300-305, 1984.

Figure 95–2 unclamping.

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preparation, may substantially reduce preload, cardiac output, and blood pressure. Also, if myocardial ischemia develops, LV dysfunction may further diminish cardiac output, thereby augmenting the effects of hypovolemia and vasodilatation. It is critical to recognize that hypotension during this stage of the procedure suggests profound hypovolemia, because aortic occlusion usually results in mild hypertension. A thorough assessment of cardiac filling pressures, surgical blood loss, and current fluid replacement is indicated in this situation. Hypotension after release of the aortic cross-clamp is a common and expected event. It is attributed to a decrease in vascular resistance and central hypovolemia. Ischemic vasodilatation develops in the lower extremities during the period of occlusion. With reperfusion of these vascular beds, ischemic metabolites and humoral factors released into the systemic circulation cause a fall in systemic vascular resistance. In addition, pooling of blood in these dilated venous and arterial vessels contributes to reduced venous return. The degree of hypotension encountered depends on the level and duration of occlusion, speed of clamp removal, intravascular volume status before aortic clamp release, and persistent effects of anesthetics and pharmacologic vasodilators. Severe hypotension can be largely avoided with appropriate fluid loading and replacement of blood losses before unclamping the aorta, as well as gradual release of the occlusion. The pathophysiology of hypotension resulting from cross-clamp release is depicted in Figure 95-2.

Risk Assessment Patients with underlying CAD are at the highest risk for myocardial ischemia and ventricular dysfunction during abdominal aortic surgery. Up to two thirds of patients with AAAs have angiographic evidence of significant CAD, and 30% of these will sustain a perioperative cardiac complication, such as myocardial infarction with or without associated heart failure. Although there is ongoing controversy regarding the appropriate preoperative cardiac evaluation of vascular surgical patients, a careful clinical and functional assessment is essential, along with noninvasive tests of

Cause of hypotension after aortic

AORTIC CROSS-CLAMPING Distal ischemia

Local mediator release

Distal venous/arterial dilation

AORTIC UNCLAMPING Mediator washout Systemic vasodilation

Blood pooling in dilated vessels ↓ Venous return

HYPOTENSION

CARDIOTHORACIC & VASCULAR SURGERY

the aortic cross-clamp. Hypotension before placement of the cross-clamp may be secondary to prostacyclin release from bowel eventration and mesenteric traction, causing profound vasodilatation, tachycardia, and facial flushing–the so-called mesenteric traction syndrome. Although this is a transient event, it usually requires treatment with a vasopressor such as phenylephrine. Further, the concomitant use of regional anesthesia may contribute to arterial hypotension by means of reduced vascular resistance and venous return (preload). Hypotension during the period of aortic occlusion is typically due to hypovolemia from ongoing blood loss, evaporative fluid loss from exposure of the abdominal cavity and its contents, and third-space loss. These operative fluid losses, when superimposed on the potential effects of preoperative diuretics, contrast dye administration, and bowel

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coronary vascular reserve, when appropriate. Individuals with LV dysfunction may be more susceptible to intraoperative hemodynamic instability. In addition, blood pressure changes are less pronounced in patients with aorto-occlusive disease compared with those undergoing simple aneurysm repair. Chronic occlusive disease results in the formation of extensive periaortic collateral vessels that continue to perfuse the lower extremities during the period of aortic occlusion; thus, changes in vascular resistance with both aortic clamping and release are considerably attenuated. In addition to these preoperative factors, the degree of preexisting volume depletion and the rate of intraoperative blood loss determine the response to aortic cross-clamping and release. Although blood loss typically ranges from 800 to 1500 mL, hemorrhage may be severe enough to require fresh frozen plasma or platelet transfusions if a dilutional coagulopathy develops.

Implications Hypotension and myocardial ischemia are poorly tolerated in patients with CAD. Mortality rates for elective AAA repair are 2% to 7%. The majority of deaths are due to myocardial infarction and other fatal cardiac events (e.g., acute heart failure, ventricular tachyarrhythmias). Mortality rates may be as much as fivefold higher in patients with clinically evident CAD. In addition, owing to coexisting renal disease, sustained and prolonged intraoperative hypotension and renal artery embolization may contribute to postoperative renal failure. The incidence rates of postoperative complications and a comparison of the causes of early mortality after elective and ruptured AAA repair are given in Tables 95-2 and 95-3, respectively. Endovascular stent-graft repair has become an important alternative to the open treatment of AAA, and it is associated with less morbidity. Even though endovascular repair is typically recommended for high-risk patients, it is still associated with lower complication rates. These devices are typically placed in the operating room by a team of vascular

Table 95–3

■

Incidence of Immediate Postoperative Complications after Elective Abdominal Aortic Aneurysm Repair

Complication Cardiac Myocardial infarction Pulmonary Pneumonia Renal insufficiency Renal failure requiring dialysis Hemorrhage Lower extremity ischemia Ischemic colitis Stroke Ureteral injury

Incidence (%) 15 2-8 8-12 5 5-12 1-6 2-5 1-4 1 1 <1

From Cronenwett JL, Sampson LN: Aneurysms of the abdominal aorta and iliac arteries. In Dean RH, Yao JS, Brewster D (eds): Diagnosis and Treatment in Vascular Surgery. Norwalk, Conn., Appleton & Lange, 1995, pp 230-233.

Causes of Early Mortality after Elective and Ruptured Abdominal Aortic Aneurysm Repair Mortality Rate (%)

Cause Cardiac Pulmonary Renal Colon infarction Hemorrhage Multisystem organ failure Other

Elective

Ruptured

58 6 4 1 0 1 24

20 3 9 9 18 35 6

From Cronenwett JL, Sampson LN: Aneurysms of the abdominal aorta and iliac arteries. In Dean RH, Yao JS, Brewster D (eds): Diagnosis and Treatment in Vascular Surgery. Norwalk, Conn., Appleton & Lange, 1995, pp 230-233.

surgeons and interventional radiologists. Anesthesia is easily provided with either spinal or combined spinal-epidural anesthesia, although some institutions prefer general anesthesia. Comparisons of open versus endovascular repair have demonstrated reduced 30-day mortality rates, bleeding, duration of time in the intensive care unit, and incidence of cardiac and pulmonary complications in patients treated with endovascular devices (Table 95-4). The long-term durability and rupture-free periods following placement of these devices are not yet well established, and largescale, prospective, randomized comparisons of these two approaches are still under way.

MANAGEMENT When hypotension develops, aggressive evaluation of the intravascular volume and degree of blood loss is the first diagnostic maneuver, because hypovolemia is the most

Table 95–4 Table 95–2

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■

Perioperative Complications: Open versus Endovascular Repair of Abdominal Aortic Aneurysms

Complication

Open Repair

Endovascular Repair

30-day mortality (%) Cardiac complications (%) Pulmonary complications (%) Neurologic complications (%) Renal complications (%) ICU stay (days) Transfusion (% transfused) Blood loss (mL) Graft-related complications

1-4 4-22 13-16 3 4-8 2 51 1200 3.8

0-3* 3-11* 3-4* 1* 4.3-5† 0.5-1* 26* 450* 13.8*

*P <.05; endovascular versus open repair. † Not significant; endovascular versus open repair. ICU, intensive care unit. From Miraude A, Bosch JL, Halpern EF, et al: Elective endovascular versus open surgical repair of abdominal aortic aneurysms: Systematic review of short-term results. Radiology 224:739-747, 2002; Elkouri S, Gloviezki P, McKusick MA, et al: Perioperative complications and early outcome after endovascular and open surgical repair of abdominal aortic aneurysms. J Vasc Surg 39:497-505, 2004.

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likely cause. Evidence of myocardial ischemia should be assessed with ST segment analysis, TEE, or both. It is treated by providing adequate coronary perfusion pressure, possibly intravenous nitroglycerin, and β-blockers when there is associated tachycardia. Maintenance of β-blockade throughout the perioperative period is essential for patients at risk for postoperative cardiac morbidity due to CAD. Management of hypotension depends on its relation to aortic occlusion: ●

●

●

PREVENTION Prevention of intraoperative hypotension requires an understanding and anticipation of the specific surgical events that precipitate vasodilatation and blood loss. A fastidious approach to monitoring cardiac filling pressures, along with frequent assessment of ongoing blood and fluid losses, is essential to maintaining a stable blood pressure. Discontinuation of anesthetics and vasodilators, along with appropriate volume loading before the release of aortic occlusion, attenuates accompanying vasodilatation. The incidence of myocardial ischemia may be reduced by recognizing and controlling the determinants of myocardial oxygen supply and demand in high-risk patients. Prophylactic intravenous nitroglycerin is not consistently effective for preventing myocardial ischemia or myocardial infarction in high-risk patients. Although it may be reasonable therapy in patients receiving preoperative nitrates, careful monitoring of preload is essential to avoid possibly deleterious reduced coronary

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perfusion pressure. Finally, substantial data suggest that prophylactic perioperative oral β-blockers and α2-agonists can reduce the incidence of postoperative cardiac events in patients undergoing major noncardiac surgery.

Further Reading ACC/AHA guidelines for perioperative cardiovascular evaluation for noncardiac surgery. Circulation 93:1280-1317, 1996. Attia RR, Murphy JD, Snider M: Myocardial ischemia due to infrarenal aortic cross-clamping during aortic surgery in patients with severe coronary artery disease. Circulation 53:961-965, 1976. Cronenwett JL, Sampson LN: Aneurysms of the abdominal aorta and iliac arteries. In Dean RH, Yao JS, Brewster D (eds): Diagnosis and Treatment in Vascular Surgery. Norwalk, Conn., Appleton & Lange, 1995, pp 230-233. Elkouri S, Gloviezki P, McKusick MA, et al: Perioperative complications and early outcome after endovascular and open surgical repair of abdominal aortic aneurysms. J Vasc Surg 39:497-505, 2004. Ellis JE, Roizen M, Mantha S, et al: Anesthesia for vascular surgery. In Barash PG, et al (eds): Clinical Anesthesia. Philadelphia, Lippincott-Raven, 1997, pp 871-910. Gelman S: The pathophysiology of aortic cross-clamping and unclamping. Anesthesiology 82:1026-1060, 1995. Gewertz BL, Kremser PC, Zarins CK, et al: Transesophageal echocardiographic monitoring of myocardial ischemia during vascular surgery. J Vasc Surg 5:607-613, 1987. Johnston WE, Balestrieri FJ, Plonk G, et al: The influence of periaortic collateral vessels on the intraoperative hemodynamic effects of acute aortic occlusion in patients with aorto-occlusive disease or abdominal aortic aneurysm. Anesthesiology 66:386-389, 1987. Mangano DT, Layug E, Wallace A, et al: Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med 335:1713-1720, 1996. Miraude A, Bosch JL, Halpern EF, et al: Elective endovascular versus open surgical repair of abdominal aortic aneurysms: Systematic review of short-term results. Radiology 224:739-747, 2002. Pevec WC: Morbidity associated with vascular surgery. In Callow A, Ernst C (eds): Vascular Surgery. Stamford, Conn., Appleton & Lange, 1995, pp 1373-1395. Poldermans D, Boersma E, Bax JJ, et al: The effect of bisoprolol on perioperative morbidity and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 341:1789-1794, 1999. Roizen MF, Beaupre PN, Alpert RA, et al: Monitoring two-dimensional transesophageal echocardiography: Comparison of myocardial function in patients undergoing supraceliac, suprarenal-infraceliac, or infrarenal aortic occlusion. J Vasc Surg 1:300-305, 1984. Wallace A, Galindez D, Salahieh A, et al: Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery. Anesthesiology 101:284-293, 2004. Wallace A, Layug E, Tateo I, et al: Prophylactic atenolol reduces postoperative myocardial ischemia. McSPI Research Group. Anesthesiology 88:7-17, 1998.

CARDIOTHORACIC & VASCULAR SURGERY

Hypotension before aortic occlusion: Consider the effects of epidural anesthesia, mesenteric traction, or preoperative hypovolemia. Hypotension during occlusion: Consider severe hypovolemia. Aggressive volume resuscitation with blood and crystalloid solutions is indicated before release of the aortic cross-clamp, to increase central venous pressure or pulmonary capillary wedge pressure by 10% to 20% above baseline levels. Hypotension after release of the aortic cross-clamp: Administration of all anesthetic agents and vasodilators should be temporarily discontinued. Vasopressors such as dopamine or phenylephrine should be available to counteract the accompanying vasodilatation and preload reduction. Blood must be available in case hemorrhage is severe, and cell-saver systems for intraoperative blood salvage are strongly recommended.

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Peripheral Vascular Surgery Ronak Desai Case Synopsis A 74-year-old woman with insulin-dependent diabetes, hypertension, and a long-standing history of smoking requires a redo right lower limb revascularization on a semiurgent basis. There is a possibility of using upper extremity vessels as graft material. A general orotracheal anesthetic is planned. An hour after uneventful surgery, while the patient is in the recovery unit, the surgeon recognizes impending graft thrombosis after the loss of Doppler signals. The graft must be re-explored in the operating room. The surgeon also mentions the possible intraoperative use of urokinase, a thrombolytic agent.

PROBLEM ANALYSIS Definition Lower limb atherosclerotic peripheral vascular disease (PVD) is common in the elderly but is asymptomatic in more than 90% of cases. When it is symptomatic, intermittent claudication is by far the most common complaint. Indications for elective peripheral vascular surgery (PVS) include claudication, ischemic pain at rest, ulceration, and gangrene. Goals of revascularization are to improve the natural course of PVD and ultimately to avoid amputation. However, bypass grafts may fail acutely or long term, with 25% to 60% of grafts occluded after 5 years. Critical leg ischemia occurs in less than 10% of patients and is defined as pain at rest or the presence of gangrene or ulcers. Because such patients are at risk for imminent limb loss, surgery is semiurgent or urgent. During revascularization, aortoiliac (inflow) or distal (outflow) obstructions are bypassed with axillofemoral or femoropopliteal distal bypass grafts, respectively.

Recognition The prevalence of cardiac risk factors is usually greater in patients undergoing PVS than in those having nonvascular surgery. Therefore, careful attention to metabolic and cardiac status is critical. Also, successful surgery and long-term survival of the graft depend on blood flow through the graft, blood coagulability, and the future development of atherosclerotic changes in the graft. Anesthesia care can have an important impact on immediate and longer-term outcomes.

Risk Assessment Primary concerns are the impact of the planned anesthetic technique on the surgical revascularization procedure, the patient’s tolerance of the anesthetic and surgery (which often takes many hours), and preoperative cardiopulmonary risk factors. Another important concern is the effect of anesthetic technique—regional anesthesia (RA) versus general 394

anesthesia (GA)—on the success of revascularization and perioperative outcomes. The following factors should be considered: ●

●

●

●

Sympathectomy. This procedure dilates the venous capacitance bed to reduce cardiac preload, thus increasing fluid requirements to maintain cardiac output. It also reduces systemic vascular resistance. If this decreases cardiac afterload and work, it may improve global and regional left ventricular function for the duration of the sympathetic block. Analgesia. Successful RA provides analgesia and reduces or eliminates the need for systemic narcotics. This benefit is extended with continuous RA techniques. Surgical stress. RA attenuates the surgical stress response, including renin-angiotensin-aldosterone system activation and the associated increased release of vasopressin and catecholamines. Postoperative hypercoagulability. Sympathetic block may reduce stress-related hypercoagulability.

Although it is difficult to compare studies of anesthetic techniques, medications, and surgical factors related to PVD, recent prospective randomized trials have found no difference in mortality between spinal or epidural RA and GA (Table 96-1). The lack of reported differences in outcome may be attributed to improved cardiovascular management in these trials compared with earlier ones. RA continued as postoperative analgesia may improve graft patency, as indicated by a reduced need for regrafting, thrombectomy, or amputation. Two studies in Table 96-1 (Tuman and Christopherson) showed marked differences in graft failure rates between GA alone and RA with or without GA; the other studies found no such difference. Conflicting outcomes may be ascribed to differences in methodology, type of graft material, extent of distal vessel disease, and adjunct anesthetic drugs. Thus, RA for PVD surgery may benefit patients at highest risk for early graft failure or those who require reoperation for whatever reason. For limb salvage surgery, hypercoagulable states and prosthetic conduits are independent risk factors for graft failure. RA may have beneficial effects on some procoagulant parameters (e.g., platelet function, fibrinogen and plasminogen

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Table 96–1

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395

Summary of Studies Comparing Regional Anesthesia and General Anesthesia for Peripheral Vascular Surgery Perioperative Mortality (%)

Study

GA

RA

GA

RA

GA

RA

GA

RA

Remarks

Cook et al 1986

51

50

5.9

2.0

7.8

4.0

—

—

Tuman et al 1991

40

40

0

0

27

10

—

—

Christopherson et al 1993

51

49

3.9

4.1

7.8

8.2

21*

4*

Bode et al 1996

138

285

2.9

3.1

19

23

—

—

Pierce et al 1997

96

86/82

—

—

—

—

2.1

2.3/2.4

145

5.0

3.4

—

—

9.4

14

Spinal anesthesia; higher incidence of hypotension (RA) and HTN (GA); blood loss less with spinal anesthesia; risk of postoperative MI similar GA with postoperative epidural analgesia vs GA with postoperative PCA Controls (N = 40) were randomly selected GA patients (non-CV surgery), but no PVD EA for surgery followed by epidural analgesia, or GA for surgery and IV PCA 11 (GA) vs 2 (RA) patients had regrafting or embolectomy EA (N = 149); spinal anesthesia (N = 136); GA (N = 138) Overall, the patient population included 86% with DM, 69% with HTN, 36% with prior MI, and 41% with a history of smoking Of 423 patients randomized to GA, spinal anesthesia, or EA, 76 did not meet protocol standards, 32 had inadequate anesthesia, 51 were lost to follow-up There were no differences among groups for 30-day graft patency, reoperation rates, 30-day graft occlusion, death, amputation, or length of hospital stay EA vs GA; retrospective analysis of femoralpopliteal-tibial bypass graft patients with similar demographic profiles Conclusion was that EA vs GA choice should be based on preanesthesia findings

Schunn et al 1998 158

Cardiovascular Complications (%)

PVS Graft Thrombosis (%)

*P ≤.05. CV, cardiovascular; DM, diabetes mellitus; EA, epidural anesthesia; GA, general anesthesia; HTN, hypertension; IV, intravenous; MI, myocardial infarction; PCA, patientcontrolled analgesia; PVD, peripheral vascular disease; PVS, peripheral vascular surgery; RA, regional anesthesia.

CARDIOTHORACIC & VASCULAR SURGERY

Number of Patients

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activator inhibitor levels). Furthermore, serologically proven hypercoagulability is known to be associated with inferior long-term graft patency and lower rates of limb salvage and survival after infrainguinal bypass grafts. However, whether RA protects against graft thrombosis remains controversial. As for preoperative cardiopulmonary risk assessment, 20% to 60% of patients with PVD have manifest or silent coronary artery disease. The preoperative history and physical examination should focus on identifying cardiac functional status and associated risk factors (see Chapter 38). In a post hoc review of 10 studies on outcomes after femoropopliteal bypass graft surgery, combined perioperative mortality was 0.8% for patients at low risk versus 4.7% for those at high risk. The cause of death was similar for both groups (multiorgan failure, stroke, or cardiac complications). Cardiac risk factors for those having PVS are similar to those for patients having other major noncardiac surgery (see Chapter 38). They include the following: ● ● ●

● ● ● ●

History of ischemic heart disease History of congestive heart failure Uncontrolled stage 2 hypertension, especially if associated with evidence of end-organ damage1 Associated cerebrovascular disease Preoperative treatment with insulin Preoperative serum creatinine greater than 2 mg/dL High-risk surgery

Implications Although multiple anesthetic techniques have been evaluated to date, the ideal technique for lower limb revascularization surgery, especially femoral-popliteal-tibial (distal) bypass grafting, remains unclear. Nonetheless, a number of medical and surgical factors may help determine the best technique for a particular patient. The duration of surgery is one important consideration. Surgeons may expend considerable time harvesting the patient’s own veins because acute and chronic patency is significantly enhanced with these grafts compared with frozen veins or prosthetic materials. Repeat revascularization procedures are typically longer and more complex. Certainly RA may still be possible, because continuous epidural infusions and spinal catheters are available and routinely employed. However, patients may have difficulty tolerating intravenous sedation for long periods. Another consideration is whether arm veins will be harvested, particularly for reoperations. Reconstructions of this type may preclude the use of RA alone, but combined RA and GA may be appropriate. Patients with severe pulmonary disease may also benefit from RA, but lengthy surgeries that require them to lie flat for prolonged periods may be difficult to tolerate. Further, sudden

1 Stage 2 hypertension is systemic blood pressure of 160/100 mm Hg or higher (sequential measurements on separate days). If stage 2 hypertension is associated with evidence of end-organ damage (e.g., aortic dissection, renal failure, cerebral symptoms, heart failure, retinopathy), this constitutes a true hypertensive emergency; if not, it is a hypertensive crisis. The former requires more urgent therapy (intravenous drugs) than the latter (oral drugs). See Chapter 77.

patient movement due to spasmodic coughing secondary to bronchitis, chronic pulmonary disease, smoking, or reactive airway disease may make creating delicate vascular anastomoses nearly impossible. Similarly, patients with cardiovascular disease may experience orthopnea, especially those with low cardiac ejection fractions (≤0.35) or a past history of congestive heart failure, and they may be unable to remain supine for long periods. Use of modified semi-Fowler positioning2 and back supports may help reduce discomfort or reduce or eliminate orthopnea. If it is determined that RA is optimal for a patient, the use of perioperative anticoagulation must be given consideration. Guidelines of the American Society of Regional Anesthesia address the implications of anticoagulation and offer advice for the prevention and management of bleeding complications with RA (see Chapter 67).

MANAGEMENT In general, all prescribed cardiac medications should be given preoperatively to optimize the cardiovascular dynamics (see Chapter 38). If RA is used, perioperative anticoagulation status must be determined, and appropriate precautions exercised (see Chapter 67).

Monitoring Indicated monitoring includes at least a two-lead electrocardiogram with precise placement of V4 or V5 leads, surface pulse oximetry, end-tidal carbon dioxide and inhalational anesthetic monitoring, and noninvasive blood pressure monitoring. Invasive monitoring is indicated for some patients, especially those with symptomatic or severe cardiovascular disease (e.g., stage III or IV heart failure, chronic atrial fibrillation, symptomatic arrhythmias, stage 2 hypertension). Such monitoring includes an arterial line, central venous pressure, and possibly a pulmonary artery catheter. These are placed before or after anesthesia induction. With severe hypertension,3 poor left ventricular function (ejection fraction ≤0.35), or symptomatic coronary artery disease, preinduction invasive monitoring allows tighter control of hemodynamic changes during induction and tracheal intubation and during periods of increased cardiovascular stress. The anesthetic technique (RA versus GA) should not affect the decision to institute central venous pressure or pulmonary artery catheter monitoring. Central lines may be required for patients with poor peripheral access or when arm veins will be used. Transesophageal echocardiography is useful for monitoring cardiac function and volume status when GA is used, especially for hemodynamically unstable patients or if a cardiac (atrial fibrillation) or aortic (unstable plaque) source for thromboembolism is present.

2 Namely, 15- to 30-degree versus 30- to 45-degree head-up tilt, without compromising surgical groin access. 3 Stage 1 (blood pressure >140/90 but <160/100 mm Hg) or stage 2 hypertension (see footnote 1).

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Hemodynamic Changes

Fluid Management Most patients having PVS require careful attention to fluid status, because there is a fine line between fluid overload with pulmonary edema and hypovolemia with impaired flow to the graft and vital organs. Maintenance crystalloid is used to replace preoperative insensible deficits (e.g., caused by lack or oral intake or by bowel preparation). Inpatients are often dehydrated or may have received dye loads during preoperative angiograms and require volume repletion. Thirdspace fluid loss is moderate for typical lower extremity PVS. The starting point is often 5 mL/kg per hour. Blood replacement is accomplished with colloids or red blood cells as needed. However, vascular surgeons are especially cognizant of the fact that reduced blood viscosity increases blood flow through the bypass graft.4 Thus, some degree of anemia may be beneficial for high-risk grafts; however, it is also associated with reduced vital organ and tissue oxygen delivery. A reasonable trade-off for intraoperative hemoglobin concentration is maintaining a hematocrit of 28 in high-risk patients.

Temperature Temperature homeostasis is important owing to the detrimental cardiovascular effects associated with hypothermia. 4

From Poiseuille’s formula.

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Hypothermia increases the risk for myocardial ischemia, promotes instability in heart rate and blood pressure, and may cause postoperative confusion. Thus, forced air warming blankets, a warm operating room, warmed intravenous fluids, a humidifier on the ventilator circuit, or low fresh gas flows are appropriate for maintaining normothermia.

PREVENTION Any patient having lower extremity PVS is presumed to have generalized atherosclerotic disease and coronary artery disease. Therefore, preoperative considerations are similar to those for patients with known cardiac disease having major noncardiac surgery (see Chapter 38). Aggressive preventive strategies such as risk factor modification and drug therapy (e.g., β-blockers, lipid-lowering agents, antiplatelet drugs) are needed. Antiplatelet drugs and RA may reduce the rate of postoperative graft thrombosis. β-Blockers reduce the risk for myocardial ischemia and myocardial infarction, which are responsible for most of the morbidity associated with PVS. The superiority of RA or GA for preventing adverse cardiovascular outcomes, graft thrombosis, or mortality has not been established. As discussed earlier, a number of proposed mechanisms may explain the trend toward improved outcomes with RA, but these have not been firmly established. Thus, the choice of anesthetic management should be made on a case-by-case basis after discussions with both the surgeon and the patient. Medical and surgical factors, as well as patient preferences, can help determine the best strategy for each patient.

Further Reading Bode RH, Lewis KP, Zarich SW, et al: Cardiac outcome after peripheral vascular surgery: Comparison of general and regional anesthesia. Anesthesiology 84:3-13, 1996. Breslow MJ, Parker SD, Frank SM, et al: Determinants of catecholamine and cortisol responses to lower extremity revascularization. The PIRAT study group. Anesthesiology 79:1202-1209, 1993. Caldicott L, Lumb A, McCoy D: Lower limb revascularization. In Caldicott L, Lumb A, McCoy D (eds): Vascular Anaesthesia: A Practical Handbook. Oxford, Butterworth-Heinemann, 1999, pp 198-224. Christopherson R, Beattie C, Frank SM, et al: Perioperative morbidity in patients randomized to epidural or general anesthesia for lower extremity vascular surgery. Anesthesiology 79:422-434, 1993. Collins CC, Peterson NJ, Suarez-Almazor M, et al: The prevalence of peripheral arterial disease in a racially diverse population. Arch Intern Med 163:1469-1474, 2003. Cook PT, Davies MJ, Cronin KD, et al: A prospective randomized trial comparing spinal anaesthesia using hyperbaric cinchocaine with general anaesthesia for lower limb vascular surgery. Anaesth Intensive Care 14:373-380, 1986. Criqui MH, Denenberg JO: The generalized nature of atherosclerosis: How peripheral arterial disease may predict adverse events from coronary artery disease. Vasc Med 3:241-245, 1998. Curi MA, Skelly CL, Baldwin ZK, et al: Long-term outcome of infrainguinal bypass grafting in patients with serologically proven hypercoagulability. J Vasc Surg 37:301-306, 2003. Dormandy J, Heeck L, Vig S: The fate of patients with critical leg ischemia. Semin Vasc Surg 12:142-147, 1999. Frank SM, Beattie C, Christopherson R, et al: Unintentional hypothermia is associated with postoperative myocardial ischemia. Anesthesiology 78:468-476, 1993. Hertzer NR, Beven EG, Young JR, et al: Coronary artery disease in peripheral vascular patients: A classification of 1000 coronary angiograms and results of surgical management. Ann Surg 199:223-233, 1984.

CARDIOTHORACIC & VASCULAR SURGERY

Careful assessment of hemodynamic parameters and myocardial ischemia during a stress test is invaluable. The purpose of serially recording the patient’s blood pressure during stress (e.g., admission to hospital, invasive procedures) is to gain knowledge of its range and lability. Notation of the range of blood pressure at night provides an idea of how well low blood pressure values will be tolerated. Also, during RA, vasopressor support (e.g., phenylephrine) for hypotension may be better (safer) than increased fluid infusion. Sustained tachycardia is one of the least tolerated hemodynamic alterations. It is important to determine and correct the cause, such as surgical stimulation or excessive or rapid blood loss; the latter often occurs during thrombectomy. Changing anesthetic depth or administering β-blockers is first-line therapy. Patients at high risk for cardiovascular complications (see Chapter 38) benefit from perioperative β-blockade, especially when GA is used. However, it is unclear whether this advice applies to similar patients having the same surgical procedures performed under RA. In large part, this will depend on whether RA produces cardiac sympathetic blockade (which, in itself, blocks against heart rate increases). Emergence from GA is a common time for perioperative myocardial ischemia to occur. It may be associated with hypertension and tachycardia due to subconscious or conscious pain awareness. Labetalol or esmolol can attenuate elevated heart rate responses. These drugs as well as nitroglycerin, hydralazine, or nicardipine can be used to reduce blood pressure or treat ischemia if it persists after a favorable heart rate has been restored.

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Hickey NC, Wilkes MP, Howes D, et al: The effect of epidural anaesthesia on peripheral resistance and graft flow following femoro-distal reconstruction. Eur J Endovasc Surg 9:93-96, 1995. Horlocker TT, Wedel DJ, Benzon H, et al: Regional anesthesia in the anticoagulated patient: Defining the risks (the Second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Reg Anesth Pain Med 28:172-197, 2003. Hunink MGM, Wong JB, Donaldson MC, et al: Revascularization for femoropopliteal disease: A decision and cost-effectiveness analysis. JAMA 274:165-171, 1995. Johnson WC, Lee KK: A comparative evaluation of polytetrafluoroethylene, umbilical vein, and saphenous vein bypass grafts for femoral-popliteal above-knee revascularization: A prospective randomized Department of Veterans Affairs cooperative study. J Vasc Surg 32:268-277, 2000. Lee TH, Marcantonio ER, Mangione CM, et al: Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 100:1043-1049, 1999. Mangano DT, Layug EL, Wallace A, et al: Effect of atenolol on mortality and cardiovascular morbidity after non-cardiac surgery. N Engl J Med 335:1713-1720, 1996. Modig J, Borg T, Bagge L, et al: Role of extradural and of general anesthesia in fibrinolysis and coagulation after total hip replacement. Br J Anaesth 55:625-629, 1983. Nelson AH, Fleisher LA, Rosenbaum SH: Relationship between postoperative anemia and cardiac morbidity in high-risk vascular patients in the intensive care unit. Crit Care Med 21:860-866, 1993. Pierce ET, Pomposelli FB, Stanley GD, et al: Anesthesia type does not influence early graft patency or limb salvage rates of lower extremity bypass. J Vasc Surg 25:226-233, 1997. Poldermans D, Boersma E, Bax JJ, et al: The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 341:1789-1794, 1999.

Raby KE, Brull SJ, Timimi F, et al: The effect of heart rate control on myocardial ischemia among high-risk patients after vascular surgery. Anesth Analg 88:477-482, 1999. Roizen MF: Anesthesia for vascular surgery. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia. Philadelphia, JB Lippincott, 1989, pp 1041-1043. Rosenfeld BA, Beattie C, Christopherson R, et al: The effects of different anesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis. Anesthesiology 79:435-443, 1993. Schunn CD, Hertzer NR, O’Hara PJ, et al: Epidural versus general anesthesia: Does anesthetic management influence early infrainguinal graft thrombosis? Ann Vasc Surg 12:65-69, 1998. Sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 157:2413-2446, 1997; erratum, Arch Intern Med 158:573, 1998. Stone JG, Foex P, Sear JW, et al: Myocardial ischemia in untreated hypertensive patients: Effect of a single small oral dose of a beta-adrenergic blocking agent. Anesthesiology 68:495-500, 1988. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 269:3015-3023, 1993. Tuman KJ, McCarthy RJ, March RJ, et al: Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesth Analg 73:696-704, 1991. Vandermeulen EP, Van Aken H, Vermylen J: Anticoagulants and spinalepidural anesthesia. Can J Anaesth 43:R129-R141, 1996. Wildsmith JA, McClure JH: Anticoagulant drugs and central nerve blockade [editorial]. Anaesthesia 46:613-614, 1991. Wulf H: Epidural anaesthesia and spinal haematoma. Can J Anaesth 43:1260-1271, 1996.

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John L. Atlee Case Synopsis

PROBLEM ANALYSIS Definition Pacemakers (PMs) and internal cardioverter-defibrillators (ICDs) have evolved rapidly since the first asynchronous single-chamber PM and ICD implantations in 1958 and 1980, respectively. Today, more than 500,000 persons in the United States have PMs, and more than 115,000 new devices are implanted each year. Also, more than 50,000 ICDs are implanted worldwide each year. Contemporary single- and dual-chamber PMs and ICDs are sophisticated devices. Both types of cardiac rhythm management devices (CRMDs) incorporate some or all of the following features or capabilities: ●

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AV universal pacing: single- or dual-chamber sequential sensing and pacing. Adaptive-rate pacing: activity or metabolic sensors1 increase pacing rates in response to exercise-related increases in metabolic demand. Multisite pacing: two or more pacing electrodes are used to synchronize left ventricular (LV) or right ventricular (RV) contractions (or both) in patients with ventricular conduction delay. Cardiac resynchronization therapy (CRT): biventricular or LV pacing to synchronize RV and LV contractions (Fig. 97-1). With LV pacing alone, LV contraction must be timed with

1 Piezoelectric crystals or accelerometers that detect changes in motion, acceleration, vibration, or pressure with exercise. However, minute ventilation or stimulus or Q-T interval sensors may provide a rate response that is more proportional to increased metabolic demand with exercise.

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respect to atrial and RV contractions (i.e., RV conduction cannot be delayed). Programmable lead configuration: this can be unipolar or bipolar. Tachycardia sensing and discrimination: detects and diagnoses tachyarrhythmias as atrial or ventricular in origin and decides on the sequence of therapy (pacing or shocks). Antitachycardia pacing (ATP): ATP terminates reentry atrial or ventricular arrhythmias. Biphasic shock waveforms: such shocks are delivered when ATP fails to terminate a tachyarrhythmia or the disturbance is not amenable to termination by a programmed pacing sequence (e.g., atrial or ventricular fibrillation). Such shocks are more efficient (require less energy) than their monophasic counterparts used in earlier ICDs.

Recognition Pacing may be temporary or permanent. If temporary, an external pulse generator (PG) transmits pulses either indirectly to the heart via leads on the body’s surface or within the esophagus or directly to the heart via endocardial or epicardial electrodes within or on the heart’s surface. For permanent pacing, an implantable PG (or “can”) transmits pulses directly to the heart via endocardial or epicardial leads to electrodes within the heart or on its surface, respectively. Pacing leads can have a unipolar or bipolar configuration. With the former, the PG serves as an anode (+) and the cardiac electrode as a cathode (−). With the latter, both electrodes are within the heart (endocardial), on its surface (epicardial), immediately behind the heart (transesophageal), or on the body’s surface (transcutaneous). With implanted CRMDs, the PG is often located in the left or right pectoral region. However, it may be subcostal, 399

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A 32-year-old man with congenital complete heart block has been pacemaker dependent since early childhood. He has an adaptive-rate atrioventricular (AV) universal pacemaker (DDDR) and presents for elective orthognathic surgery. His preoperative electrocardiogram (ECG) reveals sinus rhythm with AV synchronous (atrial-triggered) pacing artifacts. The electrocautery grounding pad is placed on the patient’s left thigh before surgery. Intermittently, with electrocautery, the anesthesiologist notices no pulse pressure in the radial artery pressure tracings. Several hours into the procedure, the patient suffers cardiac arrest. Despite aggressive attempts at resuscitation, including external pacing, the resuscitation is unsuccessful and the patient dies.

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DCM baseline

A

DCM—abnormal LV contraction pattern; early septal movement

DCM-CRT

B

CRT—better LV contraction pattern with decreased systolic dimension

especially in infants or small children. Knowledge of the PG’s location and leads is important for predicting the CRMD’s susceptibility to malfunction in the hospital or other environments where electromagnetic interference (EMI), or “noise,” is present (see “Implications”). Aside from pacing in cases of acute myocardial infarction, there are no consensus indications for temporary pacing (see later). Temporary pacing is often used for rate support with transient, hemodynamically disadvantageous bradycardia or escape rhythms or for slow atrial fibrillation, bradyasystole, or high-degree AV heart block in acute myocardial infarction. It is widely used in cardiac surgery; in fact, epicardial pacing wires are routinely placed as a precautionary measure in many centers. In other settings, atrial or ventricular transvenous pacing leads (or both) are widely used (especially in cardiac intensive care units and in high-risk patients before cardiac surgery). Noninvasive pacing includes transcutaneous pacing (causes global myocardial depolarization) and transesophageal pacing (primarily for atrial pacing, but feasibility for ventricular pacing has been shown). Indications for temporary pacing are summarized in Table 97-1.

Table 97–1

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Figure 97–1 ■ Cardiac resynchronization therapy (CRT) in a patient with dilated cardiomyopathy (DCM) and left ventricular (LV) conduction delay. A, Before CRT, the echocardiogram (EC) shows early septal movement, with the lower interventricular septum moving toward the LV cavity. Note that the lateral wall of the left ventricle has not yet begun to contract (due to conduction delay), and on the electrocardiogram (ECG), the QRS complex beneath the EC is widened. B, After CRT (biventricular pacing to synchronize contraction of both ventricles), the LV septum and lateral wall contract nearly simultaneously, and the ECG QRS complexes beneath the EC are now narrowed.

Indications for permanent PMs and ICDs are summarized in Tables 97-2 and 97-3. These indications are based on the 1998 American College of Cardiology (ACC)–American Heart Association (AHA) guidelines and the most recent (2002) update by a task force comprising ACC and AHA members and a committee appointed by the North American Society of Pacing and Electrophysiology (NASPE; now the Heart Rhythm Society). Only class I and III indications are listed. Class I indications are conditions for which there is evidence or general agreement that a procedure or treatment is useful and effective. Class III indications are those for which there is evidence or general agreement that the procedure or treatment is not useful or effective and in some cases may be harmful. Class II indications are conditions for which there is conflicting evidence or a divergence of opinion about the usefulness or efficacy of a procedure or treatment. Class II indications are subdivided into IIa if the weight of evidence favors usefulness or efficacy and IIb if usefulness or efficacy is less well established by evidence or opinion (hereafter, class IIa and IIb indications are collectively considered as “possible” indications).

Indications for Temporary Pacing in Children or Adults

Common Indications

Less Common Indications

Sinus bradycardia or escape rhythms due to reversible causes, with symptoms or signs of disadvantageous hemodynamics As a bridge to insertion of an implanted CRMD for any class I or IIa indication (see text and Tables 97-2 and 97-3) With acute MI: asystole; new bifascicular block with first degree AVHB; alternating BBB; bradycardia with symptoms of hemodynamic compromise not responsive to drugs*; type II second degree† or advanced second degree AVHB‡ Bradycardia-dependent tachyarrhythmias (e.g., torsades de pointes with long QT syndromes)

During acute MI: new or age-indeterminate right BBB with LAFB, LPFB, or first degree AVHB, or with left BBB; recurring sinus pauses refractory to atropine; overdrive pacing for incessant VT; new or age-indeterminate bifascicular block or isolated right BBB During heart surgery: during overdrive disadvantageous lower pacemaker escape rhythms; to pace or terminate reentry SVT or VT; to prevent pause- or bradycardia-dependent tachyarrhythmias; during PAC insertion with left BBB

*Especially in cardiac surgery or if atrioventricular conduction is intact and transesophageal atrial pacing is available, pacing is preferable to drugs because they may have unpredictable and deleterious effects on cardiac rate and rhythm. † No progressive P-R prolongation before nonconducted atrial beats, as with type I second degree AVHB. ‡ Two or more nonconducted atrial beats before conducted atrial beats. AVHB, atrioventricular heart block; BBB, bundle branch block; CRMD, cardiac rhythm management device; LAFB, left anterior fascicular block; LPFB, left posterior fascicular block; MI, myocardial infarction; PAC, pulmonary artery catheter; SVT, supraventricular tachycardia; VT, ventricular tachycardia.

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Class I and III indications for Permanent Pacing in Adults

Class I (Useful and Effective)

Class III (Not Useful or Effective)

Acquired Atrioventricular Heart Block

Acquired Atrioventricular Heart Block

Third degree and advanced second degree AVHB at any anatomic level, with any of the following: AVHB and bradycardia with symptoms Arrhythmias or conditions that require drugs leading to bradycardia with symptoms Proven asystole ≥3.0 sec or escape rate <40 bpm (awake patient without symptoms) After catheter ablation or modification of AV junction Postoperative AVHB not expected to resolve after cardiac surgery Neuromuscular diseases with AVHB (with or without symptoms owing to unpredictable disease progression) Second degree AVHB, regardless of type or site, with bradycardia and symptoms

Asymptomatic first degree AVHB Type I* second degree AVHB above the His bundle without symptoms AVHB expected to resolve or unlikely to recur (e.g., drug toxicity, Lyme disease, sleep apnea without symptoms)

Atrioventricular Heart Block after Acute Myocardial Infarction

Atrioventricular Heart Block after Acute Myocardial Infarction

Persistent second degree AVHB in His-Purkinje system with bilateral BBB or third degree AVHB within or below the His-Purkinje after acute MI Transient advanced (second or third degree) infranodal AVHB with BBB; if site is uncertain, EPS may be necessary Persistent second or third degree AVHB with symptoms

Transient AVHB in absence of intraventricular conduction defects Transient AVHB with isolated LAFB without AVHB Acquired LAFB in absence of AVHB Persistent first degree AVHB with old or age-indeterminate BBB

Sinus Node Dysfunction

SND with documented bradycardia and symptoms, including frequent sinus pauses (possibly the result of essential long-term drug therapy for which there are no acceptable alternatives) Symptomatic chronotropic incompetence

SND in asymptomatic patients, including those with substantial sinus bradycardia (heart rate <40 bpm) caused by long-term drug treatment SND in patients with symptoms suggesting bradycardia that is clearly documented as not being associated with slow heart rate SND with bradycardia and symptoms due to nonessential drug therapy

Hypersensitive Carotid Sinus and Neurally Mediated Syndromes

Hypersensitive Carotid Sinus and Neurally Mediated Syndromes

Recurrent syncope with CSS; minimal carotid sinus pressure induces ventricular asystole >3 sec in absence of drug that depresses sinus node or AV conduction

Hyperactive cardioinhibitory response to CSS with no symptoms or vague ones (e.g., dizziness, lightheadedness) Recurrent syncope, lightheadedness, or dizziness in absence of hyperactive cardioinhibitory response Situational vasovagal syncope in which avoidance behavior is effective

AV, atrioventricular; AVHB, AV heart block; BBB, bundle branch block; bpm, beats per minute; CSS, carotid sinus stimulation; EPS, electrophysiologic study (cardiac); LAFB, left anterior fascicular block; MI, myocardial infarction; SND, sinus node dysfunction.

Table 97–3

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Class I and III Indications for an Internal Cardioverter-Defibrillator for Primary* or Secondary Prevention†

Class I (Always Indicated)

Class III (Never Indicated)

Cardiac arrest due to VT or VF not due to transient or reversible cause Spontaneous sustained VT (lasting >30 sec) in patients with SHD Syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at EPS when AD therapy is ineffective, not tolerated, or not preferred NSVT in patients with CAD, prior MI, LV dysfunction, and inducible VF or sustained VT at EPS not suppressed by class I AD Spontaneous sustained VT in patients without SHD amenable to other treatments

Syncope of undetermined cause in patients without inducible tachyarrhythmias or SHD Incessant VT or VF VT or VF due to arrhythmias amenable to surgical or catheter ablation (e.g., atrial tachyarrhythmias in WPW, RV outflow tract VT, idiopathic LV VT, fascicular VT) VT or VF due to transient or reversible cause (e.g., acute MI, electrolyte imbalance, drugs, trauma) when correction is feasible and will likely reduce risk for further VT or VF Significant psychiatric illness that may be aggravated by ICD implantation or may preclude systematic follow-up Terminal illness and life expectancy <6 mo CAD patients with LV dysfunction and QRS >130 msec, and without spontaneous or inducible sustained or NSVT having CABG NYHA class IV drug-refractory congestive heart failure in patients not candidates for cardiac transplantation

*ICDs are used for primary prevention in patients with class I or II indications but without a history of cardiac arrest due to VT or VF or without inducible sustained VT or VF at EPS. † ICDs are used for secondary prevention in patients with a history of sudden cardiac death or who have documented or inducible (at EPS) sustained VT or VF. AD, antiarrhythmic drug; CABG, coronary artery bypass grafting; CAD, coronary artery disease; EPS, electrophysiologic study (cardiac); ICD, internal cardioverterdefibrillator; LV, left ventricular; MI, myocardial infarction; NSVT, nonsustained VT; NYHA, New York Heart Association; RV, right ventricular; SHD, structural heart disease; VF, ventricular fibrillation; VT, ventricular tachycardia; WPW, Wolff-Parkinson-White syndrome.

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Permanent pacing is indicated for any patient with symptomatic bradycardia or slow escape rhythms due to sinus node dysfunction or AV heart block. Also, pacing is indicated for syncope due to neurally mediated syndromes (e.g., hypersensitive carotid sinus syndrome) with a more prominent cardioinhibitory component in response to carotid sinus stimulation (i.e., bradycardia or escape rhythm) than a vasodepressor response (i.e., vasodilatation with hypotension). Further, the syncope must not be due to a reversible condition or a medication for which there is no suitable alternative therapy. In the 1998 and 2002 guidelines, the indications for pacing in infants, children, or adolescents with congenital heart disease are similar to those in adults, except that they are based on the correlation of symptoms with bradycardia rather than on arbitrary rate criteria per se. Also, pacing is indicated for bradycardia only after the exclusion of other causes (e.g., seizures, breath holding, apnea, neurally mediated mechanisms). Revisions in the 2002 guidelines include the following: (1) substituting “ventricular dysfunction” for “congestive heart failure” in pacing for advanced second or third degree AV heart block, (2) specifying greater than 7 days for advanced second or third degree AV heart block after cardiac surgery, and (3) adding the qualifier “with complex ventricular ectopy” to class I indications for congenital third degree AV heart block. New qualifiers for class IIa indications in children with congenital heart disease are the following: (1) congenital third degree AV heart block “associated with symptoms,” (2) increasing the resting heart rate from 35 to 40 beats per minute in children with complex congenital heart disease, and (3) adding the phrases “and impaired hemodynamics due to sinus bradycardia” or “loss of AV synchrony” to the indication for pacing in children with complex congenital heart disease. For updates to Class IIb indications for pacing in patients with congenital heart disease, see the 2002 ACC-AHA-NASPE guidelines. The indications for pacing in other conditions (e.g., chronic bifascicular and trifascicular block, hypertrophic or obstructive cardiomyopathy, idiopathic dilated cardiomyopathy, cardiac transplantation, detection and pacing to terminate tachycardias) are beyond the scope of this chapter (see the 1998 and 2002 ACC-AHA-NASPE guidelines). Class II indications are constantly evolving. For example, what constitutes a class II indication in AV heart block revolves around whether second or third degree block at any anatomic site is expected to persist, and certainly not any arbitrary rate if the block is associated with cardiomegaly or LV dysfunction. Even asymptomatic first degree AV heart block is a class IIa indication if associated symptoms are similar to those of the pacemaker syndrome.2 However, the patient must have LV dysfunction and symptoms of heart failure, especially when first degree AV heart block is associated with neuromuscular disease. This is due to the unpredictable progression of associated AV conduction system disease.

2 This syndrome was originally reported with ventricular-inhibited pacing but can occur with any pacing mode if there is associated AV dissociation. The most common symptoms are shortness of breath, dizziness, fatigue, pulsations in the back or abdomen, apprehension, and cough.

For sinus node dysfunction, the important element is whether there is a clear association between bradycardia (<40 beats per minute) and symptoms. A clear association constitutes a class I indication, and the 2002 guidelines specify that even in the absence of a clear, documented association between significant symptoms and the actual presence of bradycardia, this constitutes a class IIa indication. The 1998 guidelines specified chronic heart rates less than 30 beats per minute with minimal symptoms as class IIb. For hypersensitive carotid sinus syncope, there must be recurrent syncope, no clear provocative events, and a hypersensitive cardioinhibitory response. For neurocardiogenic syncope, the patient must be significantly symptomatic. Also, syncope must be associated with bradycardia documented spontaneously or during tilt-table testing (class IIa). Finally, biventricular pacing (simultaneous LV and RV pacing) in medically refractory and symptomatic New York Heart Association class III or IV heart failure or dilated ischemic cardiomyopathy, with a QRS duration of ≥130 msec, LV end-diastolic diameter of ≥55 mm, or ejection fraction of 0.35, is listed as a class IIa indication for CRT in the 2002 ACC-AHA-NASPE Guidelines. However, given recent additional evidence (e.g., COMPANION trial, CARE-HF study) and similar findings from other large trials of biventricular pacing in comparable patients, it is possible that it might soon become a class I indication. Finally, ICDs are prescribed for the primary or secondary prevention of destabilizing atrial or ventricular tachyarrhythmias (see Table 97-3). For primary prevention, ICDs have been used in patients with asymptomatic coronary artery disease and nonsustained ventricular tachyarrhythmias. Other settings include after coronary artery bypass surgery or percutaneous coronary intervention in patients with ejection fractions less than 35%. Also, they have been used in patients with abnormal signal-averaged ECGs or those awaiting heart transplantation. For secondary prevention, the patient must have survived an incident of sudden death, usually due to coronary artery disease, but possibly due to other causes, such as the following: ● ● ● ●

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Congenital or acquired long QT syndromes Brugada syndrome Idiopathic ventricular fibrillation Ventricular tachycardia with infiltrative, dilated, or hypertrophic cardiomyopathy Bundle branch reentry ventricular tachycardia Idiopathic monomorphic ventricular tachycardia (subdivided into RV outflow tract obstruction or arrhythmogenic RV dysplasia) Idiopathic LV tachycardia

Tachycardia discrimination algorithms used with ICDs have evolved and can now distinguish between atrial fibrillation with ventricular aberration and polymorphic ventricular tachycardia or fibrillation. Thus, ICDs are prescribed that provide lower-energy atrial shocks for atrial fibrillation (i.e., indicated for “atrioversion”).

Risk Assessment Both PMs and ICDs are subject to primary or secondary malfunction. The former is due to device failure. The latter

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may be caused by electromagnetic or mechanical interference. Because all ICDs incorporate at least single- or dual-chamber and adaptive-rate pacing, they are also subject to any PM malfunction. Malfunctions unique to devices for CRT have not yet been adequately defined.3 PACEMAKER MALFUNCTION

thereby significantly reducing the need for painful shocks. Actual ICD malfunctions include the following: ●

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Primary PM malfunction is rare (<2% of all device-related problems in one large center over a 6-year period). Some devices have programmed functions (e.g., rate hysteresis), whereby the pacing cycle duration lengthens after sensed versus paced events. Although this simulates true CRMD malfunction, it is actually a pseudomalfunction. True PM malfunction includes the following: ●

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INTERNAL CARDIOVERTER-DEFIBRILLATOR MALFUNCTION Specific ICD malfunctions include inappropriate delivery of ATP therapy, failure to deliver or ineffective pacing or shock therapies, and interactions with drugs or other devices that affect the efficacy of such therapies. Because any unsuccessful ATP is sequenced to shock delivery, such ATP “malfunction” is not really a true ICD malfunction. In fact, in studies cited by Atlee and Bernstein, ATP effectively converted 89% to 96% of episodes of ventricular tachycardia,

3 A MEDLINE OVID database search (April 6, 2005) failed to identify any case reports or other literature pertaining to primary or secondary malfunction unique to CRT devices. 4 The PM must be programmed to an atrial tracking mode (VAT, VDD, DDD; see ASA practice advisory for code designations), and the patient must have intact retrograde (ventriculoatrial) conduction; PM reentrant tachycardia is often initiated by a premature ventricular beat.

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Inappropriate delivery of shocks: electrical artifact due to lead malfunction or caused by surgical electrocautery artifact may be misinterpreted as tachycardia, leading to shocks. Failure to deliver or ineffective pacing or shock therapies: magnet application may disable sensing and therefore the ability to deliver therapy for tachyarrhythmias. Lead-related problems may also cause such failure. Acute myocardial infarction, drugs, and other imbalances may also affect sensing or increase shock thresholds, influencing the efficacy of ICD therapies. Imbalances may also affect the rate or morphology of ventricular tachycardia, leading to misdiagnosis or unnecessary pacing or shock therapies. Interactions with drugs or other implanted devices: antiarrhythmic drugs are prescribed with ICDs to suppress the need for frequent shocks and for other reasons (e.g., to suppress atrial fibrillation). Possible adverse effects of such interactions are (1) proarrhythmia (see Chapters 12 and 81); (2) slowing of the heart rate below the detection threshold (e.g., with the use of amiodarone); (3) increased defibrillation thresholds; (4) altered P or T waves or QRS intervals, leading to overcounting and spurious shocks; or (5) morphologic alterations, leading to failure to detect or discriminate ventricular tachycardia or fibrillation. Device-device interactions: in the past, it was not uncommon for patients to have both a PM and an ICD, with the potential for adverse interactions between the two. This is rare today.

Implications PMs and ICDs are subject to EMI from nonphysiologic sources. Most devices implanted today are effectively shielded or protected from EMI. The use of bipolar lead configurations (electrodes on PM or ICD leads) reduces the sensing “antenna” and has greatly reduced EMI-related CRMD malfunction (Fig. 97-2). With unipolar leads, the PG is the anode, and electrodes on the lead are the cathode, greatly increasing the antenna and the susceptibility to EMI (Fig. 97-3). Importantly, EMI signal frequencies between 5 and 100 Hz are not filtered by CRMDs because they overlap the frequency range of intracardiac signals. Therefore, EMI entering the CRMD in this frequency range has the potential to cause abnormal behavior, including the following: ● ●

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Inhibition or triggering of pacing stimulation. Asynchronous pacing (asynchronous interference mode) when continuous EMI is sensed throughout the lower rate interval (e.g., surgical electrocautery). The device appears to have reverted to asynchronous pacing (VOO), but in fact, it senses EMI as noise after the ventricular refractory period and restarts the ventricular refractory period. This continues until the programmed lower rate interval times out with the delivery of stimulation—in effect, VOO pacing. EMI may cause a change to another mode that persists after the noise stops (backup or reset mode). The rate may be similar to the battery end-of-life indicator. Random or “phantom” reprogramming, reported in the early 1980s,

CARDIOTHORACIC & VASCULAR SURGERY

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Failure to pace: no pacing artifacts in one or both chambers (atrium and ventricle). Failure to capture: visible (12-lead ECG) pacing artifacts are present for one or both chambers, but there are no or only intermittent atrial or ventricular depolarizations. Pacing at an abnormal rate: this can occur in a singleor dual-chamber device and may be normal (elective battery replacement indicator or response to an adaptiverate sensor) or abnormal behavior (e.g., pacemaker runaway due to more than two system component failures, with the upper rate limited by contemporary devices to 200 beats per minute). Dual-chamber PMs may show such behavior as PM reentrant tachycardia4 or 1:1 tracking of supraventricular tachycardia by the ventricular chamber. Undersensing (failure to sense): the intracardiac electrogram must have a sufficient amplitude and frequency to be sensed properly, and there are many potential causes of failure (e.g., progression of cardiac disease, effect of drugs; component malfunction). Oversensing: any electrical signal of sufficient amplitude occurring during the PM alert period (i.e., sensing in one or both chambers) can reset the device’s timing. For example, if the atrial chamber senses ventricular depolarization, this may inhibit atrial stimulus delivery.

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Figure 97–2 ■ Illustration of a cardiac rhythm management device with a bipolar lead configuration. With bipolar leads, both the anode (+) and the cathode (−) are on the lead and near the site of stimulation (apex of the right ventricle [RV]). Such proximity reduces interelectrode distance and the “antenna” (as shown by the TV antenna). PG, pulse generator.

is considered virtually impossible with today’s CRMDs, because unique radiofrequency sequences (code) are required to reprogram a CRMD. Damage to the CRMD’s PG or circuitry, causing output failure, PM runaway (see earlier), or other malfunction that necessitates PG replacement. Triggering of unnecessary (spurious) ICD shocks and ATP therapies.

Although unipolar surgical electrocautery (bovie)5 is the most widely recognized source of EMI in hospitals, other sources also exist: external defibrillator-cardioverter shocks, magnetic resonance imaging (MRI), radiation therapy (but not diagnostic radiographs or computed tomography scans), electroconvulsive therapy, extracorporeal shock wave lithotripsy, radiofrequency catheter ablation, and transcutaneous nerve stimulation units. (For a more complete discussion of the risks associated with specific EMI, see part II of the review by Atlee and Bernstein and the American Society of Anesthesiologists [ASA] practice advisory under “Further Reading.”) Less risky alternatives to surgical electrocautery include bipolar cautery and the harmonic scalpel, neither of which appears to pose a risk of EMI-related malfunction of implanted CRMDs. With bipolar cautery, the current pathway is between the two tips (electrodes) of the cautery tool, which are usually less than 1 cm apart during the application of bipolar cautery. Unless the CRMD leads are actually between these electrodes (in the current pathway) or in the immediate vicinity (within 1 cm of the PG or leads) when bipolar cautery is used, there is virtually no risk of CRMD malfunction, because the “antenna” (i.e., the ability to sense EMI) is very small.

MANAGEMENT Patients with CRMDs have significant heart disease and often significant coexisting medical conditions as well. They may be taking medications with implications for perioperative CRMD management. Preoperative and preprocedural evaluation is indicated before any planned intervention, regardless of where it will be performed (e.g., operating room, radiology suite, critical care unit, ambulatory facility), that might put a CRMD patient at risk for adverse events related to EMI or other device malfunction. It is important to determine what risk the planned intervention poses to the patient or the CRMD. This may require consultation with the hospital’s CRMD follow-up service or a cardiologist. Most patients with implanted CRMDs carry cards that identify the device and manufacturer, the date of implantation, serial numbers of the CRMD and lead systems, and a 24-hour toll-free hotline; thus, relevant information can be obtained, even in emergencies, from the manufacturer. Based on the advice given, it may be Figure 97–3 ■ With unipolar leads, the cardiac rhythm management device’s pulse generator serves as the anode (+), and the most distal electrode on the pacing lead serves as the cathode (−). Compared with the bipolar configuration (see Fig. 97-2), this greatly increases the “antenna” and susceptibility to electromagnetic interference.

5 With unipolar cautery, the cautery tool (cathode) is variably removed from the grounding plate (anode), which creates a small or large current pathway between the two, depending on the distance between them.

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PREVENTION Precautions for some specific EMI are listed here. However, these cannot guarantee that there will be no CRMD-related malfunction due to EMI during surgical or other interventions. ●

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Evaluate the patient before the procedure to determine whether a CRMD is present, the type of device, and whether the patient is PM dependent and the device is functioning. For a patient undergoing a procedural or surgical intervention: ● ● ●

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Determine whether EMI is likely to occur. Program the PM adaptive-rate therapy off. Program the PM to an asynchronous mode, especially if the patient is PM dependent. Program all antitachycardia therapies off. Use bipolar electrocautery or a harmonic scalpel if possible. Ensure the availability of external temporary pacing and a cardioverter-defibrillator. Consider possible untoward effects of any drugs or interventions on CRMD function.

Use appropriate monitoring: ● Continuous ECG and arterial oxygen saturation monitoring by pulse oximetry.

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End-tidal carbon dioxide monitoring when general anesthesia is used.

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For procedures that require surgical electrocautery: ● Use bipolar cautery or harmonic scalpel if possible. ● Position the electrocautery grounding (receiving) plate so that the current pathway does not pass through or near the PG or leads. ● Avoid proximity or contact of the cautery tool with the PG or leads. ● Use short, intermittent, irregular bursts of cautery and the lowest possible energy.

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For radiofrequency ablation (e.g., for arrhythmogenic foci or reentry pathways): ● Avoid direct contact between the radiofrequency catheter and CRMD or leads. ● Keep the current path (electrode to return plate) as far away from the PG or leads as possible.

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For MRI and radiation therapy: ● MRI is generally contraindicated for CRMD patients, but exceptions have been reported (consult the device manufacturer before proceeding with MRI). ● CRMD malfunction or damage to PG circuitry or components is related to the cumulative dose of radiation; thus, device function should be checked after each session. Alternatively, the device may have to be explanted and reimplanted away from the ionizing beam of radiation; shielding can also be used.

Further Reading American Society of Anesthesiologists Task Force on Perioperative Management of Patients with Cardiac Rhythm Management Devices: Practice advisory for the perioperative management of patients with cardiac rhythm management devices: Pacemakers and implantable cardioverter-defibrillators. Anesthesiology 103:186-198, 2005 (additional material available at http://www.anesthesiology.org). Atlee JL, Bernstein AD: Cardiac rhythm management devices (part I). Anesthesiology 95:1265-1280, 2001. Atlee JL, Bernstein AD: Cardiac rhythm management devices (part II). Anesthesiology 95:1492-1506, 2001. Baller MR, Kirsner KM: Anesthetic implications of implanted pacemakers: A case study. AANA J 63:209-216, 1995. Bristow M, Saxon LA, Boehmer J, et al: Comparison of medical therapy, pacing, and defibrillation in heart failure (COMPANION) investigators: Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350:2140-2150, 2004. Cleland JGF, Daubert J-C, Erdmann E, et al: The effect of cardiac resynchronization therapy on morbidity and mortality in heart failure. N Engl J Med 352:1539-1549, 2005. Epstein MR, Mayer JE Jr, Duncan BW: Use of an ultrasonic scalpel as an alternative to electrocautery in patients with pacemakers. Ann Thorac Surg 65:1802-1804, 1998. Furman S, Robinson G: The use of an intracardiac pacemaker in the correction of total heart block. Surg Forum 9:245-248, 1958. Gregoratos G, Abrams J, Epstein AAE, et al: ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices. Summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). Circulation 106:2145-2161, 2002. Gregoratos G, Cheitlin M, Conill A, et al: ACC/AHA guidelines for implantation of cardiac pacemakers and antiarrhythmia devices: A report of the ACC/AHA Task Force on Practice Guidelines (Committee on Pacemaker Implantation). Circulation 97:1325-1335, 1998.

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necessary to have the device reprogrammed to an asynchronous mode (i.e., if the patient is PM dependent) or to have ATP or shock therapies programmed off. This can be done by a manufacturer’s representative, a cardiologist, or the hospital CRMD service. For any elective intervention, all the necessary information for optimal CRMD perioperative or peri-interventional management must be obtained. If the risk to the patient is high (e.g., MRI scans, therapeutic radiation, unipolar cautery in the vicinity of the PG, leads in the current pathway) or even moderate, the PM is programmed to sense (e.g., AAI, VVI, VAT, VDD, DDI, DDD; see ASA practice advisory for code designations), and the patient is mostly PM dependent, then it may be necessary to interrogate and reprogram the CRMD to an asynchronous mode (AOO, VOO, DOO). Generally, it is ill advised to place a magnet over the PG of a CRMD without knowing what the magnet response is. Again, this information can be obtained from the manufacturer or CRMD service. In some devices, the magnet response may be programmed off; in others, it may not confer immunity to sensing and potential malfunction during the planned intervention or after the patient has been discharged. However, for emergent intervention or surgery, when one cannot take the previously mentioned precautions (or have someone else obtain the needed information), it is reasonable to place a magnet over the PG if unusual pacing behavior is observed or spurious shocks or ATP therapies are initiated in response to sensed EMI. Finally, the CRMD should be interrogated after the procedure for any alteration in programmed settings. For patients with CRMDs who are receiving sequential radiation therapy for the treatment of cancer, the CRMD should be checked after each session.

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Kleinman B, Hamilton J, Heriman R, et al: Apparent failure of a precordial magnet and pacemaker programmer to convert a DDD pacemaker to VOO mode during use of the electrosurgical unit. Anesthesiology 86:247-250, 1997. Mirowski M, Reid PR, Mower MM, et al: Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. N Engl J Med 303:322-324, 1980. Nichol G, Kaul P, Huszti E, et al: Cost-effectiveness of cardiac resynchronization therapy in patients with symptomatic heart failure. Ann Intern Med 141:343-351, 2004.

Ozeren M, Dogan OV, Duzgun C, et al: Use of an ultrasonic scalpel in the open-heart reoperation of a patient with a pacemaker. Eur Cardiothorac Surg 21:761-762, 2002. Smith CL, Frawley G, Hamar A: Diathermy and the telectronics “META” pacemaker. Anaesth Intensive Care 21:452-454, 1993.

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Mechanical Assist Devices Sheela S. Pai and Avery Tung

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Case Synopsis A 78-year-old man with New York Heart Association class III heart failure, hypertension, type 2 diabetes mellitus, and chronic renal insufficiency had coronary artery bypass grafting with mitral valve repair. A prebypass transesophageal echocardiogram (TEE) revealed an ejection fraction of 20%, septal akinesis, severe mitral regurgitation with annular dilatation, and a patent foramen ovale. Owing to the low prebypass ejection fraction, an intra-aortic balloon pump (IABP) was placed before initiation of cardiopulmonary bypass (CPB). Total CPB time was 210 minutes. Despite the use of IABP support and dobutamine and epinephrine infusions, repeated attempts to separate the patient from CPB failed. Therefore, a left ventricular assist device (LVAD) was placed. On postoperative day 2, the patient developed acute right-sided weakness and facial palsy. A computed tomography scan revealed a large translucent defect in the territory supplied by the left middle cerebral artery.

PROBLEM ANALYSIS

Mechanical circulatory assist devices are artificial devices that perform some or all of the functions of the heart. They vary significantly in design and indication but are typically used to provide either partial or full support for a heart that is unable to function adequately. Those used for temporary support include the IABP, extracorporeal membrane oxygenation (ECMO), LVAD, and right ventricular assist device (RVAD). Those used for full support include biventricular assist device (BiVAD) and total artificial heart (TAH). Indications for mechanical assist devices are evolving but fall into three broad categories: 1. Temporary support for a heart that is expected to recover 2. Bridge therapy to cardiac transplantation 3. Destination therapy for a patient whose heart is unlikely to regain adequate function Also, as shown in Table 98-1, devices are classified according to (1) the indication for the device (emergent versus urgent), (2) the expected duration of therapy (short versus long term), or (3) the degree of support provided (augmentation of intrinsic cardiac function versus full cardiac support). The modern era of mechanical cardiac assist devices began in 1957, with the first successful use of CPB. Although it was first intended to provide intraoperative circulatory support, CPB’s success led physicians to consider mechanical circulatory support for other indications as well. In 1966 DeBakey first used a pneumatic ventricular assist device (VAD) for a patient with left ventricular failure. In 1967 the IABP was first used to treat patients with acute heart failure, but it subsequently became a mainstay of therapy for severe, decompensated heart failure and unstable angina. In 1994 pneumatically driven VADs for partial (LVAD or RVAD) or complete (BiVAD) support of the heart were approved by the Food and Drug Administration. Today, single-chamber assist devices (e.g., IABP, LVAD, RVAD) are used to treat

Table 98–1

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Classification of Mechanical Assist Devices

By Indication Urgent (unstable angina or uncontrolled congestive heart failure with worsening symptoms) IABP VAD Emergent (hypotension incompatible with life or inability to separate from cardiopulmonary bypass) IABP VAD ECMO

By Duration of Therapy Short term IABP Abiomed VAD ECMO Long term Thoratec VAD Implantable VAD

By Degree of Support Provided Augmentation (IABP) LVAD or RVAD alone Total support (BiVAD, ECMO) BiVAD, biventricular assist device; ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; LVAD, left ventricular assist device; RVAD, right ventricular assist device; VAD, ventricular assist device.

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Definition

failure due to a wide variety of causes; dual-chamber assist devices (BiVAD, TAH) allow patients without any native heart function to survive. Unlike an IABP or VAD, ECMO is similar to CPB because it provides both oxygenation and circulatory support, bypassing the heart and lungs altogether. Although experience with ECMO in adults is limited, venoarterial ECMO is a therapeutic option if intractable cardiovascular instability and inadequate pulmonary gas exchange are encountered after cardiac surgery. ECMO drains blood from either the arterial or venous circulation and delivers it to the arterial circulation.

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Institution of ECMO can be quick (i.e., CPB tubing can be used), but an experienced CPB perfusionist must be present to monitor and adjust anticoagulation and to troubleshoot. Although ECMO has been used successfully in children, good outcomes in adults are mostly anecdotal. Because the management of patients on ECMO is by CPB perfusionists under the supervision of cardiovascular surgeons and is confined to intensive care settings, ECMO is not discussed further here.

Recognition INTRA-AORTIC BALLOON PUMP The IABP is the most commonly used assist device in cardiac surgery. IABPs are inserted percutaneously or via surgical cutdown from the femoral artery. A Seldinger introducer is used for placement of the large-diameter IABP introducer sheath. The IABP catheter is passed via the introducer and positioned with its tip at the junction of the descending aorta and the aortic arch, just distal to the subclavian artery. This position minimizes the risk of subclavian or renal artery injury or occlusion. If the IABP is placed intraoperatively, TEE can determine proper balloon tip location before pump initiation. Patients with femoral atherosclerotic vascular disease may require IABP insertion into a subclavian artery or directly into the aorta with transthoracic access. Patient suitability for IABP depends on the presence of appropriate access, the stability of the proximal descending aorta, the absence of aortic dissection, and the absence of aortic insufficiency. Perioperative indications for IABP include the following: ●

●

Preoperative placement for patients undergoing emergent coronary artery bypass grafting or with low ejection fractions Intraoperative placement for left ventricular failure despite maximal inotropic support or unabated regional myocardial ischemia not amenable to surgical revascularization

The definitions used for low ejection fraction, left ventricular failure, maximal inotropic support, and ongoing regional myocardial ischemia can vary widely among institutions performing coronary artery bypass graft surgery. Contraindications to placement of an IABP are aortic insufficiency, sepsis, and severe vascular disease. Because the IABP inflates in the descending thoracic aorta during diastole to promote retrograde flow into the ascending aorta, this has the potential to increase aortic regurgitation and further distend the left ventricle at the expense of coronary perfusion. As with any prosthetic intravascular device, infectious bacteremia is difficult to treat if surfaces of the prosthesis become seeded with bacteria. In addition to technical difficulties with placing an IABP in patients with severe vascular disease, such patients are prone to aortic rupture and thromboembolic complications (see “Risk Assessment” and “Implications”). Although use of an IABP was once considered primarily after one or more failed attempts at separation from CPB in the operating room, today the number of IABPs placed in the cardiac catheterization laboratory approaches or exceeds the number placed in the operating room in some centers.

VENTRICULAR ASSIST DEVICE VADs are designed to completely replace the function of the native heart. They can be left-sided (LVAD), right-sided (RVAD), or biventricular (BiVAD). VADs bypass the left or right ventricle by withdrawing blood from the circulation as it enters the failing ventricle and pumping it back into the circulation immediately downstream from the failing ventricle. Flow from the patient into the VAD is from systemic (RVAD inflow) or pulmonary (LVAD inflow) venous drainage. Venous cannulas are placed in the ventricle (series cannulation) or the atria (parallel cannulation). Outflow is via pulmonary (RVAD) or systemic (LVAD) arterial cannulas. Arterial cannulas are usually placed in the aorta (LVAD), pulmonary artery (RVAD), or both (BiVAD or TAH). The two primary types of VADs are displacement and rotary pumps. The former are used mostly in adults, and the latter are used in both children and adults. Displacement pumps can be intracorporeal or extracorporeal, designating the pumping chamber’s location within or outside the body, respectively. Displacement pumps provide pulsatile flow, and rotary pumps do not. Rotary pumps are smaller in size and weight, operate more quietly, and have relatively low power consumption. However, they are more prone than displacement pumps to thrombus formation and bearing failure, which limits their longevity to several weeks. Indications for VADs are as follows: ●

●

●

●

Post-CPB: Patients with post-CPB ventricular failure that persists despite maximal pharmacologic support (often in combination with IABP support) require placement of a pneumatic VAD if they are to survive the immediate postoperative period. Post–myocardial infarction: Formerly, mortality rates associated with early VAD placement for severe left ventricular failure after acute myocardial infarction were dismal (>75%). However, more recent rates are closer to 15%. This is encouraging, given the high mortality rate reported for this patient population without such therapy. Bridge to cardiac transplantation: Technologic advances have allowed VADs to become mostly intracorporeal, with increasingly smaller extracorporeal components. Also, as the incidence of adverse side effects has declined, the acceptable duration of VAD circulatory support has increased to longer than 3 months. Destination therapy: Improved VAD portability and reduced associated morbidity have enabled more patients to survive many months with intracorporeal VADs. As a result, and because of the limited availability of human hearts, VADs are now being given serious consideration as “destination therapy” (i.e., TAH as an alternative to cardiac transplantation).

Accepted hemodynamic criteria for long-term VAD placement include the following: ● ● ●

Cardiac index less than 2 L/minute per square meter Pulmonary capillary wedge pressure greater than 20 mm Hg Systolic blood pressure less than 80 mm Hg

Other considerations can also affect the decision to implant a VAD. For example, for LVADs, the status of right ventricular function is an important concern. Associated right

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ventricular disease (e.g., high preoperative central venous pressure, TEE evidence of right ventricular free wall hypokinesis) may be aggravated by the sudden increase in cardiac output and right ventricular preload following LVAD placement.

Risk Assessment INTRA-AORTIC BALLOON PUMP The incidence of IABP complications has decreased significantly since its first use, but significant associated morbidity still exists. The most frequent complications are vascular in nature, with a reported morbidity of 6% to 33%: ● ● ● ● ●

Limb ischemia Compartment syndrome Mesenteric infarction Aortic perforation Aortic dissection

VENTRICULAR ASSIST DEVICE Patients who require a VAD are severely ill, and the necessary surgery is extensive. Thus, the decision to place a VAD should involve a careful, individualized evaluation of benefit, risk, and likelihood of an acceptable outcome. In addition, careful attention should be paid to patient status at the time of device placement. Although VADs are typically reserved for acute, lifesaving indications, placement during a more stable period may be better tolerated. Ideal candidates for VAD placement are patients with preserved end-organ function. Further, post-VAD survival appears to be better in patients who are hemodynamically stable and have lower APACHE scores than in those in shock or with higher APACHE scores. Although altered mental status and pulmonary or hepatic dysfunction do not predict outcome after VAD placement, preplacement confirmation of adequate renal function plays a critical role. For example, preplacement dependence on dialysis has been associated with 50% or more mortality after VAD placement. Additional predictors of adverse outcomes after VAD placement include age older than 65 years and the presence of multiple medical comorbidities. Technical aspects of placement should also play a significant role in the decision to implant a VAD. Increased bleeding and poor myocardial function often accompany repeat sternotomy and CPB. Further, there may be injury to myocardial structures that adhere to the sternum or to previously placed bypass grafts. Finally, VAD cannulas have the potential to limit intrathoracic volume, prevent complete ventricular filling, and possibly decrease coronary blood flow by compressing bypass grafts.

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Implications INTRA-AORTIC BALLOON PUMP IABP inflation exerts mechanical stress forces on the aortic wall. Therefore, known aortic dissection or a proximal aortic graft is a contraindication to IABP placement. Also, in patients with aortic insufficiency, the IABP will exacerbate regurgitant blood flow into the left ventricle during diastole, leading to ventricular dilatation and compromised coronary perfusion. There are few restrictions to IABP use. However, it is important to remember that the IABP provides support to the left ventricle only and is unlikely to improve primary right ventricular systolic dysfunction. Further, the IABP’s ability to augment cardiac output and unload the left ventricle is limited because it does not directly alter left ventricular function. With severe left ventricular failure, an IABP will not provide enough flow to sustain the circulation, and a VAD will have to be considered. The risk of air embolism to the brain from the IABP pressure monitoring line is greater than that from a radial or femoral arterial line. This is because the IABP monitoring port is at the tip of the balloon catheter, which resides close to the origin of the carotid arteries. Samples for blood gas determinations should be drawn from the IABP monitoring line only if there is no other suitable site. Also, one must be sure that no air bubbles or other debris is flushed through the IABP line. Inappropriate timing of IABP inflation and deflation can worsen myocardial oxygen supply and increase myocardial oxygen balance. Early inflation (before closure of the aortic valve) can be detected by an arterial waveform demonstrating IABP inflation before the dicrotic notch and results in dramatically increased afterload, end-diastolic wall stress, and myocardial oxygen consumption. Delayed IABP inflation (after aortic valve closure) is detected by balloon inflation after the dicrotic notch and results in suboptimal coronary perfusion. Similarly, early deflation during diastole results in suboptimal coronary perfusion and afterload reduction, as well as increased myocardial oxygen consumption. Also, late deflation may lead to ineffective afterload reduction and excessive impedance of left ventricular ejection. IABPs are foreign bodies and may promote clot formation. Although anticoagulation is not routine with IABP placement, a low degree of anticoagulation may be required to prevent thromboembolic phenomena. As with any large-bore femoral arterial access catheter, the IABP introducer sheath poses a significant infectious risk. It must be placed under strictly sterile conditions and removed as soon as possible. VENTRICULAR ASSIST DEVICE The venous cannula may be placed in either the ventricle (series cannulation) or the atria (parallel cannulation). Often, series cannulation allows more effective ventricular emptying, but it requires that the cannula be placed through ventricular myocardium. Although the associated myocardial trauma is less important to a transplant candidate, even a small amount of direct myocardial injury in a post-CPB patient with cardiogenic shock may significantly impede myocardial recovery.

CARDIOTHORACIC & VASCULAR SURGERY

Risk factors for these complications include a history of peripheral vascular disease, female gender, tobacco smoking, diabetes mellitus, and postoperative IABP placement. Other complications of IABP include infection (primarily at the groin site of the IABP introducer sheath), coagulopathies, and balloon rupture with gas embolism. The last may be related to aortic arteriosclerotic severity and associated aortic calcifications, which become increasingly severe in elderly patients.

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MANAGEMENT AND PREVENTION Intra-aortic Balloon Pump In the United States, IABP balloon catheters are available in four lengths: 25, 34, 40, and 50 inches. The patient’s height determines the appropriate length; 34 inches (for patients 64 inches tall or less) and 40 inches (for taller patients) are the most commonly used sizes. Placement of an IABP may be technically difficult in patients with extensive atherosclerosis, and these patients are more prone to arterial thrombosis during use of an IABP. Therefore, for patients with severe aortoiliac or femoral artery disease, another option is to place the balloon directly into the descending thoracic aorta. Proper balloon tip placement is 2 inches below the origin of the left subclavian artery. This is necessary to prevent occlusion of the artery during balloon inflation. Correct placement can be confirmed radiographically or by TEE. The balloon is timed to inflate immediately after aortic valve closure (dicrotic notch, which signals aortic valve closure and the start of diastole). Inflation too early will impede left ventricular ejection. If inflation is too late, its effectiveness for increasing coronary perfusion pressure and reducing afterload will be less than optimal. Also, balloon deflation must be timed so that arterial pressure has reached its minimal level at the onset of the next ventricular systole. If it deflates too soon, the aorta will not be maximally evacuated before the next ventricular systole, and coronary perfusion will be suboptimal. If the balloon deflates too late, it will impede left ventricular ejection systole. Appropriate timing of balloon inflation and deflation is depicted in Figure 98-1. Two methods are used to synchronize the IABP inflations with the cardiac rhythm: (1) the largest detectable

Ventricular Assist Device Patients with valvular dysfunction or artificial heart valves are challenges to VAD placement. The cannulas should be

A = cardiac cycle

R

B = unassisted aortic end-diastolic pressure (EDP)

T

P

Q

ventricular electrocardiographic (ECG) signal (e.g., QRS complex) or (2) the arterial pressure waveform. If intrinsic arterial pulse pressure is greater than 40 mm Hg, the arterial waveform is preferred in the operating room because electrocautery artifact can inhibit some ECG-triggered IABP consoles. However, this has become less of a problem with the incorporation of electronic artifact suppression circuitry that makes IABPs less susceptible to electrocautery inference. Further, contemporary IABP consoles can differentiate pacing artifacts, thereby allowing proper balloon inflation timing, even if atrial or ventricular pacing is used. Balloon inflation is often initiated at a ratio of 1:2 (one IABP beat for every two cardiac beats). Thus, natural and augmented ventricular beats can be compared to determine IABP timing and efficacy. Depending on the patient’s condition, the ratio may be increased to 1:1 to produce maximal augmentation, or it may be decreased to 1:3, 1:4, or less during weaning. Typically, the volume of balloon inflation is set at 50% to 60% of the patient’s ideal stroke volume. Overinflation risks balloon rupture and arterial gas embolization. During extended use of IABP, anticoagulation is generally indicated. However, in the early postoperative period, anticoagulation may not be instituted until the chest tube drainage is acceptable (<100 to 150 mL/hour). Some surgeons prefer low-molecular-weight dextran to heparin because its antithrombogenic effects are fairly mild, even though no specific reversal agent exists.

S

C = unassisted systole

D

C

F B E A

Inflation occurs at the onset of diastole (aortic valve closure— i.e., dicrotic notch), giving rise to the sharp V wave on the arterial waveform. This leads to increased coronary perfusion.

D = diastolic augmentation E = reduced aortic EDP F = reduced systolic pressure

Deflation occurs at the end of diastole prior to systole, resulting in reduced aortic end-diastolic and systolic pressures. This leads to decreased afterload, myocardial oxygen consumption (MVO2), and increased cardiac output.

Figure 98–1 ■ Appropriate timing of IABP balloon inflation and deflation. (Adapted from Rao V, Slater JP, Edwards NM, et al: Surgical management of valvular heart disease in patients requiring left ventricular assist device support. Ann Thorac Surg 71:1448-1453, 2001.)

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medications (steroids), mechanical ventilation, and intravascular catheters. It is imperative to correct as many of these factors as possible before device implantation. Further, all vascular access lines and drains should be removed as soon as possible, drive-line sites should be inspected routinely, and aseptic conditions should be aggressively maintained during dressing changes. Treatment depends on the type of infection. Pocket infections may require surgical drainage. VADrelated endocarditis is extremely challenging. Often, the VAD must be explanted and replaced, with all the attendant complications of reoperation. Many patients requiring VAD implantation for left ventricular failure have coexistent pulmonary disease and pulmonary hypertension. For such patients, placement of an LVAD may result in inadequate VAD flow rates due to right ventricular failure and reduced blood flow to the left ventricle, where the inflow cannula is located. In these patients, careful attention to factors influencing pulmonary vascular resistance (e.g., hypoxemia, hypercarbia, acidosis, bronchospasm, vasopressors) is important to reduce the likelihood of right ventricular failure. In extreme cases, an RVAD may be necessary to ensure adequate blood return to the LVAD.

Further Reading Baskett RJF, Ghali WA, Maitland A, et al: The intraaortic balloon pump in cardiac surgery. Ann Thorac Surg 74:1276-1287, 2002. Datascope Cardiac Assist CS100. Datascope Corporation, Cardiac Assist Division, Fairfield, NJ. Available at http://www.datascope.com/ca/ caeducmaterials.html. Frazier OH, Delgado RM: Mechanical circulatory support for advanced heart failure: Where does it stand in 2003? Circulation 108:3064-3068, 2003. Harter RL, Michler RE: Circulatory assist devices. In Hensley FA Jr, Martin DE, Gravlee GP (eds): Practical Approach to Cardiac Anesthesia, 3rd ed. Philadelphia, JB Lippincott–Williams & Wilkins, 2003, pp 557-573. Holman WL, Rayburn BK, McGiffin DC, et al: Infection in ventricular assist devices: Prevention and treatment. Ann Thorac Surg 75:S48-S57, 2003. Ko W, Jin C, Chen RJ, et al: Extracorporeal membrane oxygenation support for adult postcardiotomy shock. Ann Thorac Surg 73:538-545, 2002. Loebe M, Koerner MM, Lafuente JA, et al: Patient selection for assist devices: Bridge to transplant. Curr Opin Cardiol 18:141-146, 2003. Melhorn U, Kroner A, deVivie ER: 30 Years of clinical intra-aortic balloon pumping: Facts and figures. Thorac Cardiovasc Surg 47(Suppl 2): 298-303, 1999. Rao V, Slater JP, Edwards NM, et al: Surgical management of valvular heart disease in patients requiring left ventricular assist device support. Ann Thorac Surg 71:1448-1453, 2001. Rose EA, Gelijns AC, Moskowitz AJ, et al: Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) study group: Long-term mechanical left ventricular assistance for end-stage heart failure. N Engl J Med 345:1435-1443, 2001. Smedira NG, Blackstone EH: Postcardiotomy mechanical support: Risk factors and outcomes. Ann Thorac Surg 71:S60-S66, 2001. Smith C, Bellomo R, Raman JS, et al: An extracorporeal membrane oxygenation-based approach to cardiogenic shock in an older population. Ann Thorac Surg 71:1421-1427, 2001. Thoratec TLC-II VAD Portable Driver and System Operator’s Manual, rev ed. Pleasanton, Calif, Thoratec Corporation, 2004. Available at www.thoratec.com. Tisol WB, Mueller DK, Hoy FB, et al: Ventricular assist device use with mechanical heart valves: An outcome series and literature review. Ann Thorac Surg 72:2051-2055, 2001.

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aligned such that there is maximal flow across the mechanical valve. There is also some evidence that maximizing flow across the valves (valve washing) by adjusting VAD flow rates (depending on myocardial recovery) may decrease the incidence of thrombus formation. If aortic valve insufficiency is present, regurgitant flow may prevent a VAD from effectively decompressing the left ventricle to reduce myocardial oxygen consumption. Inadequate decompression is particularly problematic when aortic insufficiency is severe and with apical versus left atrial LVAD placement. Because VAD placement can (and is expected to) reduce left atrial and left ventricular pressures, atrial and ventricular septal defects should be identified and repaired before VAD placement to prevent potentially dangerous right-to-left shunting. The presence of native or prosthetic valvular heart disease can complicate VAD placement. Severe mitral stenosis limits VAD filling during serial cannulation and may result in restricted VAD flow. In contrast, VAD placement in patients with mitral regurgitation results in complete unloading of the left ventricle and improved valve function. Aortic stenosis alone is not a contraindication to placement of an LVAD. However, aortic insufficiency will allow regurgitant blood flow from the VAD outflow cannula across the incompetent aortic valve to distend the left ventricle and compromise end-organ perfusion. Even mild to moderate aortic insufficiency may become more severe with institution of LVAD support. Because inflow and outflow VAD cannulas must be placed in the thoracic cavity, they may compromise cardiac filling in the early postoperative period. Therefore, most VADs are approved for use in patients with a body surface area greater than 1.5 m2 or weighing more than 42 kg. Often, left ventricular preload improves over 12 to 24 hours as intrathoracic contents shift to accommodate the VAD cannulas. Anticoagulation is usually required with most VAD devices except the HeartMate LVAS (for left ventricular assist system; Thoratec Laboratories, Pleasanton, Calif.). The goal for anticoagulation is the same as for patients with prosthetic valves. The usual practice is to start heparin after postoperative bleeding from the chest tubes is less than 50 mL/hour and then to switch to warfarin after adequate anticoagulation has been obtained. With the HeartMate LVAS, only aspirin (80 mg/day) is required after the initial postoperative bleeding has subsided. Infectious complications of VAD placement are classified into two types: device related and non–device related. Non-device-related infections include pneumonia, urinary tract infection and sepsis. Device-related infections tend to involve the blood-contacting surface of the VAD, the outer surface of an implanted VAD, or the VAD inflow or outflow cannulas. Because the VAD cannot be removed, all infections with the potential for VAD colonization are potentially life threatening. Usually, Staphylococcus, Pseudomonas, Enterococcus, or Candida species are the offending agents, but other infectious causes have been described. Patient risk factors for infectious complications include preoperative infection, malnutrition, immunosuppressive

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99

Hyperglycemia and Diabetic Ketoacidosis Martin L. De Ruyter and Barry A. Harrison Case Synopsis A 75-year-old woman with type 2 diabetes mellitus, controlled by glyburide 5 mg twice a day, presents for scheduled coronary artery bypass grafting. She has diabetic nephropathy with a serum creatinine of 1.8 mg/dL. The patient did not take her oral antidiabetic medication before surgery, and her fasting plasma glucose was 130 mg/dL. After cardiopulmonary bypass, the intraoperative plasma glucose was 236 mg/dL. There was a brisk diuresis. The serum potassium was 5.8 mEq/L with a base deficit of –4.0 mEq/dL. The patient received furosemide and mannitol while on cardiopulmonary bypass and repeated doses of cardioplegia. Cardiopulmonary bypass took 130 minutes.

PROBLEM ANALYSIS Definition

Recognition Preoperatively, clinical symptoms and signs of hyperglycemia may be absent or vary widely. One third of patients with DM are unaware that they have the condition. Symptoms and signs include the following: ● ●

Polyphagia Polydipsia Table 99–1

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Normal Values for Plasma Glucose

Fasting plasma glucose: <100 mg/dL Peak plasma glucose*: <200 mg/dL 2-hr postprandial glucose: <140 mg/dL *After glucose tolerance testing.

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Hyperglycemia in adults is defined as a random plasma glucose level greater than 200 mg/dL, but this definition does not reflect today’s target for glucose control. Perioperative plasma glucose levels are determined by many factors, including preoperative glucose and nutritional status, metabolic activity, catecholamines, cortisol, glucagon, and insulin levels. At times of illness or acute severe stress, hyperglycemia may be present; this is referred to as hyperglycemic stress syndrome. In some patients this may reflect the unmasking of an abnormality of glucose tolerance, which should be treated to reduce the risk of increased morbidity and mortality. The patient should subsequently be reevaluated and reclassified after recovering from surgery or acute illness. A similar approach is used in the management of gestational diabetes. Diabetes mellitus (DM) is a chronic, multisystem disease heralded by signs and symptoms of persistent hyperglycemia and confirmed by a random plasma glucose level greater than 200 mg/dL, a fasting plasma glucose level greater than 126 mg/dL, or a plasma glucose level of 200 mg/dL or greater based on 2-hour postprandial testing or 2 hours following an oral glucose tolerance test. In the absence of acute metabolic decompensation or severe hyperglycemia, these criteria should be reconfirmed at least 24 hours apart. Type 1 DM is due to a failure to produce endogenous insulin. Type 2 DM is a metabolic syndrome characterized by relative degrees of reduced insulin secretion, increased insulin receptor resistance, and increased glucose availability. Impaired glucose tolerance is defined as a 2-hour postprandial or glucose tolerance test plasma glucose level between 140 and 200 mg/dL. Normal values for plasma glucose are given in Table 99-1.

Diabetic ketoacidosis is usually associated with type 1 DM. It generally occurs in the setting of absent insulin, poor glucose utilization, and often some pathologic stressor (e.g., illness, infection, trauma). The body attempts to preserve energy stores via gluconeogenesis, which is the mobilization of fats and amino acids into glucose-producing pathways, resulting in hyperglycemia and ketosis (Fig. 99-1). Nonketotic hyperosmolar syndrome occurs in type 2 diabetics with insufficient production of insulin or altered receptor sensitivity to insulin. Endogenous insulin is present in sufficient quantities to prevent these patients from developing ketoacidosis; however, they present with an anion gap metabolic acidosis secondary to lactic acidosis. This acid-base derangement occurs as a result of cellular hypoxia, likely due to hypovolemia, inadequate organ perfusion, or a shock state. Nonketotic hyperosmolar syndrome is characterized by severe hyperosmolarity (>320 mOsm/L), hyperglycemia (>600 mg/dL), and marked dehydration.

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Figure 99–1 ketoacidosis.

Insulin deficiency / Glucagon excess

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Pathogenesis of diabetic

Activation of lipolysis

Hepatic ketogenesis

Increased glycogenolysis/ gluconeogenesis

Ketoacidosis

● ● ●

Impaired glucose utilization

Hyperglycemia

Polyuria Confusion Coma Intraoperative signs are as follows:

● ● ● ●

Unexplained diuresis Tachycardia and hypotension Anion gap metabolic acidosis Hyponatremia and hyperkalemia

Frequently hyperglycemia is first recognized by an increased plasma blood glucose level.

Risk Assessment Causes of perioperative hyperglycemia are listed in Table 99-2. Emergency surgery increases the risk of type 1 diabetics developing diabetic ketoacidosis and type 2 diabetics developing nonketotic hyperosmolar syndrome. In emergency situations (e.g., trauma), patients may miss their usual insulin dose, interrupt their usual caloric intake, or encounter excessive pathologic stresses, which alter the normal counterregulatory hormone balance. The patient’s inability to increase insulin production results in hyperglycemia. DM is associated with significant complications, including retinopathy, neuropathy, gastropathy, and nephropathy. DM also accelerates atherosclerosis, leading to increased coronary artery disease, cerebrovascular disease, and peripheral vascular disease.

Implications The effects of hyperglycemia are related to the severity and duration of increased plasma glucose levels. Cellular. Hyperglycemia leads to nonenzymatic glycosylation of immunoglobulins, granulocyte dysfunction, and reduction

of both CD4 and CD8 lymphocyte populations. It also exaggerates ischemia-reperfusion cellular injury, induces cardiac cell death, and reduces coronary collateral blood flow. Hyperglycemia induces platelet hyperreactivity, which increases thrombosis, and it increases levels of interleukin-6, interleukin-8, and tumor necrosis factor-α, reflecting

Table 99–2

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Causes of Perioperative Hyperglycemia

Diabetes mellitus (types 1 and 2) Dextrose-containing intravenous fluids Maintenance solutions or parenteral nutrition Medications Catecholamine-induced stress response Burns Trauma Surgery Sepsis Stroke Pain Cardiopulmonary bypass Excess counterregulatory hormones Cushing’s disease or syndrome Pheochromocytoma Acromegaly Glucagonoma Drugs Thiazide diuretics Glucocorticosteroids Phenytoin Pentamidine β-Adrenergic receptor blockers Oral contraceptives Pancreatic disease Pancreatitis or pancreatic trauma Hemochromatosis Pregnancy

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a proinflammatory action. Hyperglycemia and insulin resistance lead to endothelial cell dysfunction, inactivation of nitric oxide, decreased synthesis of prostacyclin, and increased synthesis of endothelin-1, which all lead to decreased local blood flow.

Cardiovascular. A meta-analysis of patients admitted for acute myocardial infarction, with or without a prior diagnosis of DM, found that hyperglycemia (>110 mg/dL) was associated with increased hospital mortality and congestive heart failure. Inpatients. Newly noted hyperglycemia in medical and surgical inpatients resulted in an 18-fold increase in hospital mortality and longer hospital stays. Major Surgery. Thirty percent to 40% of cardiac surgical patients have DM. Hyperglycemia is associated with increased mortality and deep-seated infections in cardiac surgical patients.

Intraoperative Hyperglycemia In December 2003 the American Association of Clinical Endocrinologists published a position statement on inpatient diabetes and metabolic control. For intensive care unit patients (including cardiac, vascular, thoracic, and major surgical patients), the consensus as to the tolerable upper limit for glucose is 110 mg/dL. For non–critically ill patients, the consensus is 110 mg/dL for preprandial plasma glucose levels and 180 mg/dL for maximal glucose levels. During the perioperative period, intravenous (IV) infusion of insulin is advocated. In hospitalized patients, high IV doses of insulin may be necessary to achieve acceptable plasma glucose levels. Studies have demonstrated that the use of standardized protocols, developed by multidisciplinary teams, can successfully control hyperglycemia, decrease hypoglycemia, decrease length of stay, and improve outcome in diabetic patients. A continuous IV insulin infusion algorithm is presented in Table 99-3. Subcutaneous regular insulin is not advocated in the critically ill and those undergoing major surgery but may find applications in less severe cases. Table 99-4 illustrates a regimen of regular insulin dosing via the subcutaneous route.

Algorithm for Continuous Intravenous Infusion of Insulin*

Blood Glucose (mg/dL) >400 351-400 301-350 250-300 200-249 150-199 120-149 100-119 70-99 <70

Insulin Infusion Rate (U/hr) 8 6 4 3 2.5 2 1.5 1 0 0

*Algorithm is designed for the average 70-kg patient. Adjustments should be based on hourly glucose determinations.

Diabetic Ketoacidosis Diabetic ketoacidosis is a medical emergency. Initial assessment includes the following: ●

●

● ● ● ●

●

●

MANAGEMENT

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Identification of the precipitating event—infection, ischemia, missed insulin administration Volume status ● Tachycardia, hypotension ● Increased urea and creatinine Mental status—cerebral edema Hyperglycemia—increased plasma glucose and urine glucose Ketosis—increased serum ketones and β-hydoxybutyrate Increased anion gap acidosis ● Increased respiratory rate (Kussmaul’s respiration) ● Serum bicarbonate <15 mEq/dL; pH <7.3 Potassium—initially increased secondary to metabolic acidosis, but decreased total potassium stores Sodium—laboratory measurement secondary to hyperglycemia

Fluid resuscitation, IV insulin administration, and correction of electrolytes are crucial. Fluid Resuscitation. The fluid deficit is often between 4 and 8 L of sodium and free water. Initial resuscitation includes infusion of normal saline (0.9% NaCl). Within the first 2 hours, patients should receive enough fluid to stabilize their hemodynamic parameters (usually 2 to 3 L of nonglucose-containing crystalloid solution). After initial rehydration with isotonic saline, subsequent administration of

Table 99–4

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Subcutaneous Supplementation of Regular Insulin

Blood Glucose (mg/dL) 200-250 251-300 301-350 >350

Regular Insulin Dose (U)* 2 4 6 8

*Subcutaneous insulin dosing is approximately every 4 to 6 hr.

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Critical Illness. In 1826 critically ill patients, there was a direct and proportional correlation between increasing blood glucose levels and mortality.

Hyperglycemia and Diabetic Ketoacidosis

Table 99–3

Renal. Blood glucose levels in excess of 250 mg/dL overwhelm renal tubular absorption capabilities, which leads to hypovolemia secondary to an osmotic diuresis. A profound diuresis may result in prerenal azotemia, altered organ perfusion, cellular hypoxia, and lactic acidosis. Cerebral. Patients with DM or newly recognized hyperglycemia are at increased risk for severe strokes and increased mortality. A meta-analysis of studies of stroke patients found increased mortality in patients with blood glucose levels of 110 to 126 mg/dL. Serum osmolarity greater than 330 mOsm/L is associated with central neurologic dysfunction and coma.

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0.45% normal saline should be started, because free water loss typically exceeds the natriuresis. Once blood glucose levels have declined to less than 250 mg/dL, 5% dextrose is added to the IV fluids to maintain acceptable glucose levels and reduce the risk of cerebral edema. Infusions with hypotonic fluid may cause cerebral edema secondary to reverse osmotic shifts. Hypertonic solutions have no role because they may worsen the acidosis, dehydration, and hyperosmolar state. Insulin Therapy. Regular insulin is administered as a bolus (0.1 to 0.2 unit/kg), followed by a continuous IV insulin infusion (0.1 unit/kg per hour) and hourly determinations of blood glucose levels. Additional glucose supplementation may be necessary, but care must be taken to avoid hypoglycemia. Blood glucose levels of 200 to 250 mg/dL are a reasonable initial goal. As the patient improves, titration to 150 to 200 mg/dL should be the goal. A continuous IV infusion algorithm is presented in Table 99-3. Metabolic Acidosis. The administration of bicarbonate is controversial. A paradoxical rebound central nervous system acidosis can be observed with excessive bicarbonate therapy. IV bicarbonate replacement should be reserved for patients with an arterial pH less than 7.0 after initial rehydration, and it should be discontinued once the pH rises above this value. Electrolytes. Serum potassium may be elevated despite a depletion in total body stores. Hyperglycemic osmotic diuresis causes systemic potassium wasting (up to 10 mEq/kg), whereas an extracellular shift in potassium secondary to metabolic acidosis results in an elevated serum concentration. Provided the patient’s urine output is adequate, acute renal failure is not evident, and a normal serum potassium level is documented, potassium should be repleted promptly. In general, replacement with potassium chloride at a rate of 20 to 30 mEq/hour should be sufficient. Electrocardiographic monitoring is recommended during repletion of potassium. Measured hyponatremia is a laboratory phenomenon secondary to the dilutional effect of hyperglycemia. In general, for each 100 mg/dL increase in glucose above normal levels, serum sodium levels decrease by 1.6 to 2.0 mEq/L. No specific therapy is required other than correction of the hyperosmolar state. Phosphate levels may be depleted because this anion is excreted with osmotic diuresis. Routine replacement is controversial because rapid replacement can cause hypocalcemia. Phosphate replacement should be guided by periodic surveillance of magnesium, calcium, and phosphate levels.

PREVENTION Diabetes affects 18.2 million Americans and is the seventh leading cause of death in the United States. Preoperatively, random plasma glucose testing is advised for patients older

than 60 years and those with symptoms or with DM. Diabetic patients need a complete medical evaluation to detect diabetic complications and comorbidities. Oral agents need to be stopped before surgery. Long-acting sulfonylureas or chlorpropamide are stopped for at least 72 hours, whereas shorter-acting sulfonylureas and metformin are stopped the night before surgery. For type 1 DM patients and patients with uncontrolled type 2 DM, it is essential to administer insulin. The aim of any regimen is to maintain good control without hypoglycemia. It also must be practical and easy to use as the patient is transferred from the ward to the operating room, to the recovery room, and back to the ward. It is important to monitor plasma glucose at frequent intervals. One regimen that fulfills all these criteria is the continuous IV administration of regular insulin. With an increasing number of type 1 DM patients on continuous subcutaneous insulin maintenance, the use of a continuous IV infusion perioperatively is advised. For stable type 2 DM patients having minor or moderately stressful surgery, oral therapy can resume postoperatively. Unless insulin is part of a type 2 diabetic patient’s usual regimen, it can be reserved for glucose levels exceeding 180 mg/dL.

Further Reading American College of Endocrinology position statement on inpatient diabetes and metabolic control. Endocr Pract 10:77-82, 2004. Clement S, Braithwaite SS, Mangee MF, et al: Management of diabetes and hyperglycemia in hospitals. Diabetes Care 27:553-591, 2004. Coursin DB, Connery LE, Ketzler JT: Perioperative diabetic and hyperglycemic management issues. Crit Care Med 32:S116-S125, 2004. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20:1183-1197, 1997. Furnary AP, Gao G, Grunkemeier GL, et al: Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 125:1007-1021, 2003. Malmberg K, Norhammar A, Wedel H, Ryde´n L: Glycometabolic state at admission: Important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: Long-term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study. Circulation 99:2626-2632, 1999. Pittas AG, Siegel RD, Lau J: Insulin therapy for critically ill hospitalized patients: A meta-analysis of randomized controlled trials. Arch Intern Med 164:2005-2011, 2004. Savage MW, Mah PM, Weetman AP, Newell-Price J: Endocrine emergencies Postgrad Med J 80:506-515, 2004. Van den Berghe G, Wouters P, Weekers F, et al: Intensive insulin therapy in critically ill patients. N Engl J Med 345:1359-1367, 2001. Wass T, Lanier W: Glucose modulation of ischemic brain injury: Review and clinical recommendations. Mayo Clin Proc 71:801-812, 1996.

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Hypothermia Christopher C. Young and Robert N. Sladen Case Synopsis A 74-year-old woman with insulin-dependent diabetes mellitus is found several hours after a fall. She is admitted for emergency surgery with epidural and general anesthesia for repair of a fractured hip. She receives 4 units of packed red blood cells. In the postanesthesia care unit, she is confused and disoriented after tracheal extubation. Her heart rate is 110 beats per minute; blood pressure, 160/90 mm Hg; temperature, 33.8°C (oral); arterial oxygen tension (PaO2), 63 mm Hg; and arterial carbon dioxide tension (PaCO2), 54 mm Hg (on nasal oxygen at a rate of 6 L/minute).

PROBLEM ANALYSIS Definition Normal body temperature is 37°C (98.6°F). Hypothermia is classified as mild to moderate (33°C to 36°C), severe (23°C to 33°C), or profound (< 23°C). Accidental (Table 100-1) or iatrogenic (Table 100-2) causes may contribute to hypothermia. The patient in the case synopsis is at increased risk for hypothermia owing to the following factors: ● ● ●

Age-impaired thermoregulatory responses Anesthesia-impaired thermoregulatory responses Ambient factors (e.g., cold environment, air conditioning)

Table 100–1

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Accidental Causes of Hypothermia

Environmental Wind chill Cold water immersion

Impaired Thermoregulation Extremes of age (neonates, elderly) Prolonged immobilization Drugs Alcohol Central nervous system depressants Drug overdose

●

Radiation (heat exchange from one surface to another), such as from the skin or mucosa to the colder environment of the operating room

1 Before air conditioning was introduced, inadvertent hyperthermia was not uncommon.

Medical Conditions Hypothyroidism Large body surface area burns Infection or sepsis Malnutrition Hypoglycemia Hypothalamic stroke or tumor Unconsciousness

Table 100–2

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Iatrogenic Causes of Hypothermia

Prolonged anesthesia and surgery Prolonged cardiopulmonary resuscitation Blood or blood product transfusions* Large-volume fluid resuscitation* *Without adequate warming.

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Age-related impairment involves decreased perception of cold, decreased ability to prevent heat loss (blunted vasoconstrictor response), and diminished ability to increase heat production (reduced muscle mass). Microvascular atheroma and diabetic autonomic neuropathy also impair thermoregulatory vasoconstriction in response to cold. General and regional anesthesia disrupts physiologic thermoregulatory responses (Fig. 100-1). For example, the hypothermic vasoconstriction threshold (about 37°C) is

suppressed 2°C to 4°C in a dose-dependent manner by volatile or opioid anesthesia, with significantly greater suppression occurring in the elderly. Regional anesthesia induces a sympathetic blockade that prevents vasoconstriction in the affected dermatomes, and heat generation from muscle activity is reduced in proportion to the extent of segmental motor blockade. Spinal thermoregulatory centers may be depressed by central neuraxial anesthesia or analgesia. Shivering is abolished by anesthetic agents and neuromuscular blocking agents. Conversely, physiologic thermoregulatory responses to warmth (i.e., vasodilatation and sweating) are also suppressed by anesthetic agents, such that their thresholds are elevated about 1°C above normal. The interthreshold range is the range of core temperatures within which no physiologic responses are evoked. Normally, this is very narrow (about 0.5°C). However, from Figure 100-1, it is apparent that anesthesia widens the interthreshold range to as much as 4°C. This implies, for example, that the central temperature could vary from 34°C to 38°C without any physiologic responses to conserve or eliminate heat. Within this range, the patient is poikilothermic (i.e., the central temperature varies directly with ambient temperature). This and the widespread use of air conditioning in operating rooms put anesthetized patients at high risk for inadvertent hypothermia.1 Also, heat balance is the sum of heat production and loss, with heat production (via exercise or metabolism) negligible during anesthesia. In fact, heat loss dominates due to the following physical factors, in decreasing order of importance:

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Risk Assessment and Implications

Figure 100–1 ■ Schematic illustration of thermoregulatory thresholds in nonanesthetized (normal) and anesthetized humans. The intersection of each regulatory response (e.g., shivering, sweating) with the temperature scale (core body temperature) is the threshold. The interthreshold range is shown as the distance between the first cold response (vasoconstriction) and the first warm response (sweating); temperatures within this range do not elicit autonomic thermoregulatory compensation. Because each thermoregulatory response has its own threshold and gain, there is an orderly progression of responses, and response intensities, in proportion to need. During general anesthesia (bottom), the thresholds for vasoconstriction and nonshivering thermogenesis are shifted down to about 34.5°C (depending on anesthetic type and dose). Similarly, thresholds for active precapillary vasodilatation and sweating are increased about 1°C. Interthreshold range thus increases from 0.2°C to about 4°C. (From Sessler DI: Temperature monitoring. In Miller RD [ed]: Anesthesia, 4th ed. New York, Churchill Livingstone, 1994, pp 1363-1382.)

●

●

●

Evaporation (heat lost by the movement of molecules from liquid to gas phase), such as from cold skin preparation and irrigation solutions, and evaporative loss from exposed body serosal surfaces Convection (heat lost by eddy currents), such as from drafts and the infusion of cold blood and fluids Conduction (heat exchanged by direct molecular contact), such as from the skin to the cold operating table

Recognition During general and regional anesthesia, intraoperative hypothermia has three distinct stages: 1. Internal redistribution: abrupt decline of about 0.5°C to 1.0°C in central temperature caused by redistribution of heat from the warm central core to the cold periphery due to anesthetic-induced peripheral vasodilatation. The colder the skin at anesthetic induction, the greater the central temperature decline. 2. Environmental heat loss: passive heat loss by radiation, evaporation, convection, and conduction continues to the extent that physiologic responses are depressed, usually to about a central temperature of 34°C to 35°C. Advanced age and diabetes can contribute to depression of the vasoconstrictor threshold to less than 34°C, as in the patient described in the case synopsis. 3. Plateau phase: once thermoregulatory vasoconstriction is evoked, heat loss becomes constrained, and the central temperature reaches a plateau. However, further declines can be caused by massive blood loss and transfusion, for example.

Hypothermia may benefit the patient by providing organ protection against ischemia. Oxygen utilization is halved for each 10°C decrease in normal body temperature. Mild hypothermia (33°C to 36°C) provides important central nervous system protection. There is increasing evidence that it may play a protective role after stroke and cardiac arrest due to ventricular fibrillation. Even mild hypothermia induces platelet dysfunction and may increase intraoperative bleeding. Platelet thromboxane generation, required for platelet aggregation and local hemostatic vasoconstriction, is impaired by cold. Quantitative laboratory assessment is misleading because blood samples are warmed to 37°C. Massive transfusion of cold blood can induce severe hypothermic coagulopathy with irreversible bleeding. There is now evidence that even mild intraoperative hypothermia may increase the risk for postoperative wound infection, possibly due to vasoconstriction with low tissue oxygen tension. This impairs chemotaxis and facilitates bacterial growth. Severe hypothermia (<33°C) has adverse effects on almost every organ system (Table 100-3; Fig. 100-2). Emergence from anesthesia may be delayed by a number of cold-induced factors, including impairment of central nervous system function (e.g., obtundation, confusion, somnolence), slowed hepatic or renal clearance of anesthetic drugs and neuromuscular blocking agents, and impaired ventilatory response to hypoxemia and hypercarbia. Cold-induced vasoconstriction and increased systemic vascular resistance may exacerbate postoperative hypertension (blood pressure of 160/90 mm Hg in the patient in the case synopsis is characteristic). Together with high norepinephrine concentrations, both may produce myocardial ischemia in susceptible patients. The consequences of rewarming from hypothermia may outweigh the implications of hypothermia itself. Postoperative shivering greatly increases oxygen demand and carbon dioxide production, leading to increased minute ventilation, work of breathing, and oxygen consumption. If minute ventilation is fixed (mechanical ventilation) or suppressed (by anesthetic agents or opioids), hypercarbia and acute respiratory acidosis may result. When oxygen consumption is increased but cardiac output cannot compensate, oxygen extraction increases, setting the stage for hypoxemia and its sequelae. Shivering can also cause patient discomfort and other adverse sequelae, such as wound disruption and increased bleeding or intracranial and intraocular pressures. Subsequently, rewarming vasodilatation may unmask hypovolemia, resulting in even more dangerous hypotension and tachycardia.

MANAGEMENT AND PREVENTION The management and prevention of hypothermia are inseparable and include the following. ● ● ●

Preoperative skin warming Adjusted ambient temperature in the operating room Intraoperative temperature monitoring

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Table 100–3

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Hypothermia

421

Adverse Effects of Hypothermia on Organ System Function

Cardiovascular Early: tachycardia, hypertension, increased cardiac output, vasoconstriction (catecholamine release) Late: bradycardia, decreased cardiac output, hypotension ECG: Generalized slow conduction, sinus bradycardia, T-wave inversion, Q-T prolongation, ventricular ectopy (32°C, Osborne waves; 30°C, ventricular fibrillation; see Fig. 100–2)

Respiratory Early: increased respiratory rate Late: reduced respiratory rate and tidal volume, diminished hypoxic pulmonary vasoconstriction and responsiveness to hypoxemia and hypercarbia, diminished mucociliary activity

Renal Early: initial “cold” diuresis (increased central blood volume with peripheral vasoconstriction); diuresis continues due to impaired renal tubular sodium reabsorption Late: oliguria and azotemia

Hematologic Early: hemoconcentration, increased viscosity (sludging, poor tissue perfusion, ischemia), decreased oxygen availability (left shift of oxyhemoglobin dissociation curve) Late: disseminated intravascular coagulation, thrombocytopenia

Metabolic Early: hyponatremia, hyperkalemia, hyperglycemia (inhibition of insulin release and block of its cellular uptake) Late: metabolic acidosis

Neurologic Cerebral blood flow decreases 6% to 7% per 1°C decrease in temperature: 34°C: amnesia 30°C: obtundation 26°C: loss of pupillary and deep tendon reflexes 18°C: loss of brain activity (isoelectric electroencephalogram)

Gastrointestinal Early: decreased intestinal motility (full stomach), diminished hepatic clearance Late: ulceration of stomach, ileum, and colon; hemorrhagic pancreatitis ECG, electrocardiogram.

● ● ● ● ●

Heated and humidified anesthesia circuits Forced-air warming blankets and other devices Warmed intravenous fluids and blood products Postoperative mechanical ventilation Prevention and treatment of postoperative shivering Anticipation and treatment of rewarming vasodilatation

A simple way to prevent redistribution hypothermia is to warm the patient’s skin before anesthetic induction. In many cases, warming with a forced-air blanket can be initiated in the preoperative holding area or preinduction room. Before anesthetic induction, the ambient temperature in the

operating room should be increased to 23°C to 26°C to maintain normothermia. Once the patient is fully draped and protected, the temperature can be decreased so that it does not impair the performance of the surgeon or assistants. Ambient room temperature should be increased again at the end of the operation. Temperature monitoring is mandatory for all procedures lasting 30 minutes or longer. However, “normal” temperature (like blood pressure) depends on where it is measured. Monitors for core body temperature include the tympanic membrane (susceptible to injury), nasopharynx (influenced by anesthetic gas temperature), esophagus

Figure 100–2 ■ Two electrocardiographic leads obtained during cooling with cardiopulmonary bypass. Sinus bradycardia (about 30 beats per minute) and prominent J (Osborne) waves (arrows) distinguish the first three complexes. Ventricular ectopy increases in frequency and progresses to fibrillation as the patient rapidly becomes hypothermic. Bladder and nasopharyngeal temperatures were 35.8°C and 31.4°C, respectively. (From Mark JB: Atlas of Cardiovascular Monitoring. New York, Churchill Livingstone, 1997, p 331.)

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(dependent on depth of insertion),2 and pulmonary artery (if a thermistor-equipped pulmonary artery catheter is used). The rectum and bladder may reflect central core body temperature if the patient is warm and vasodilated, or peripheral body temperature if the patient is cold and vasoconstricted. Skin temperature may be useful to evaluate gradients but may have little or no relationship to core temperature changes. Routine use of heated and humidified anesthesia circuits is not warranted in adult patients except to reduce further heat loss in an already hypothermic patient or for extended, major surgical procedures. Such circuits do little to increase core temperature. After the induction of anesthesia, reduction of the total fresh gas flow to less than 2 L/minute will help reduce heat and moisture loss from the airway, as will an “artificial nose” (i.e., a heat- and moistureexchanging filter or hygroscopic condenser humidifier). A forced-air warming blanket should be placed to prevent intraoperative hypothermia and even induce rewarming. Full-body or half-body blankets are available, and this convection-based device is by far the most effective system for perioperative warming. One caveat is that it should not be placed over the lower body3 during aortic cross-clamping, because this will exacerbate the tissue oxygen demandsupply imbalance. Passive insulation (blankets, drapes) and circulating water mattresses are not nearly as effective, and there is a risk of thermal injury with the latter if water temperature exceeds 40°C. Although an overhead radiant heater is frequently used for infants and small children, the patient’s skin must be left exposed for heat transfer to occur. Heat transfer is blocked by interposed surgical or nursing personnel. Also, overhead heaters restrict access to the patient. Whenever large volumes of crystalloid, colloid, or blood products are infused, a fluid warming device should be used. Four units of refrigerated blood at 4°C or 1 L of roomtemperature crystalloid can decrease mean body temperature by about 1°C. During massive blood transfusion, the use of a rapid infusion device (which can deliver up to 1000 mL/minute at 37°C) is essential to prevent potentially life-threatening hypothermia and irreversible hypothermic coagulopathy. When patients are hypothermic to less than 35°C following anesthesia and surgery, it is prudent to consider deferring tracheal extubation and providing mechanical ventilation until the core temperature has normalized. Capnometry is useful to detect early increases in carbon dioxide production and facilitate appropriate adjustments in minute ventilation. The most effective means of preventing postoperative shivering is to warm the skin (e.g., with a forced-air warming blanket). Impulses from skin thermoreceptors govern the

2 If the thermistor is behind the trachea, core temperature will be <0.2°C below its true value. 3 Or, if a lower body warming blanket is in place, it must not be used at this time.

hypothalamic response to cold; the warmer the skin, the lower the central temperature threshold for the onset of shivering. There is considerable evidence that premedication with α2-adrenergic receptor agonists (clonidine, dexmedetomidine) suppress postoperative shivering. Active shivering can be treated with intravenous meperidine (12.5 to 25 mg), which likely has a specific hypothalamic effect. However, it is effective only about 50% to 60% of the time. Intravenous dexmedetomidine is also an effective treatment for postoperative shivering and has an additive effect when used with meperidine. Rewarming vasodilatation begins variably after the patient’s arrival in the postanesthesia care unit and depends on hypothermia severity. Increased muscle tone (i.e., subclinical shivering) initially generates heat during persistent peripheral vasoconstriction. As a result, core temperature climbs and may even “overshoot” to 38°C to 40°C, especially after hypothermic cardiopulmonary bypass. When peripheral vasodilatation finally occurs, heat generation is balanced by heat loss, so that the central temperature reaches a plateau before returning to normal. If patients are hypovolemic, rewarming vasodilatation can produce acute hypotension, reflex tachycardia, and myocardial ischemia. Thus, in the early postoperative period, patients who are hypothermic, vasoconstricted, and hypertensive may benefit from vigorous fluid replacement, along with judicious use of vasodilator therapy (e.g., nitroprusside, nitroglycerin). Once rewarming vasodilatation occurs, fluid replacement is essential, together with a vasopressor if needed.

Further Reading Doufas AG, Lin CM, Suleman MI, et al: Dexmedetomidine and meperidine additively reduce the shivering threshold in humans. Stroke 34: 1218-1223, 2003. Frank SM, Higgins MS, Breslow MJ, et al: The catecholamine, cortisol, and hemodynamic responses to mild perioperative hypothermia: A randomized clinical trial. Anesthesiology 82:83-93, 1995. Giesbrecht GG, Ducharme MB, McGuire JP: Comparison of forced-air patient warming systems for perioperative use. Anesthesiology 80:806-810, 1994. Kurz A, Sessler DI, Lenhardt R: Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. N Engl J Med 334:1209-1215, 1996. Nesher N, Zisman E, Wolf T, et al: Strict thermoregulation attenuates myocardial injury during coronary artery bypass graft surgery as reflected by reduced levels of cardiac-specific troponin I. Anesth Analg 96:328-335, 2003. Sessler DI: Temperature monitoring. In: Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 1571-1598. Young CC, Sladen RN: Temperature monitoring. Int Anesth Clin 34: 149-174, 1996.

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Hyperthermia Melissa M. Vu Case Synopsis A 24-year-old, 62-kg, gravida I para 0 woman presents at 39 + 5 weeks for elective induction of labor under combined spinal-epidural analgesia. After approximately 5 hours of labor, the patient’s oral temperature is noted to be 38°C (100.4°F). The fetal heart rate is 120 to 130 beats per minute, with normal variability.

PROBLEM ANALYSIS Definition

Recognition Optimal detection of temperature disturbances during anesthesia is achieved by monitoring core body temperature. Core temperature can be assessed from a variety of locations, including the pulmonary artery (the gold standard, but even this may be misleading in some surgeries), nasopharynx, tympanic membrane (a reflection of brain temperature), and distal esophagus.1 Sites outside the core compartment include the bladder, rectum, axilla, and skin, with the last being the least reliable. These sites can be used when clinical circumstances preclude the use of core temperature monitoring, such as surgery under regional anesthesia. Peripheral temperature (skin, extremity) may show a large discrepancy with core temperature as a result of the

1 The thermistor element should be 2 to 3 cm beyond the tracheal bifurcation or point of best breath sounds. Exposure to cooler inspired gases will reduce core temperature by about 0.3°C, depending on inspired gas flow, respiratory rate, and tidal volume.

Risk Assessment Hyperthermia itself has a variety of physiologic implications. Of greatest significance is that hyperthermia or fever may be a sign of a more serious underlying pathologic process (Table 101-1). As previously mentioned, hyperthermia occurs far less often than hypothermia during general anesthesia. The incidence of hyperthermia depends largely on its cause. Malignant hyperthermia is reported to occur in 1 in 5000 to 65,000 cases of general anesthesia in which triggering agents such as inhalational agents or succinycholine are used. Approximately 50% of patients in whom malignant hyperthermia is triggered (see also Chapter 162) have undergone prior uneventful general anesthesia. Ninety percent of all transfusion reactions are associated with increased temperature. Temperature elevation occurs in about 1% to 2% of all transfusions. The incidence of other causes of hyperthermia (e.g., infection, thyrotoxicosis, neuroleptic malignant syndrome, other hypermetabolic conditions) is variable. Passive hyperthermia is common in pediatric patients brought to a heated operating room and placed on the operating table under warming lights. Nonetheless, hyperthermia should alert the anesthesiologist to search for a cause rather than to simply treat the elevated temperature elevation itself.

Implications Hyperthermia has physiologic effects on multiple organ systems. First, elevated temperature results in increased metabolic rates, with consequent increased oxygen consumption. To meet this increase in oxygen demand, cardiac output and heart rate are increased. Acidosis may develop if cellular metabolic demand exceeds oxygen delivery. Myocardial ischemia will occur if the oxygen supply is insufficient. Also, compensatory thermoregulation (perspiration, vasodilatation) may lead to decreased intravascular volume and preload, with possible worsening of oxygen delivery. Perspiration may also cause electrolyte abnormalities due to loss of electrolytes or free water. Hypothermia is known to provide some measure of cerebral protection during periods of ischemia, whereas 423

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Normal core body temperature is 36.7°C to 37.0°C ± 0.2°C to 0.4°C and is maintained via a complex system of neuroregulatory sensors and responses. A person’s age and level of activity, the time of day, medications, the hormonal milieu, and other factors determine the hypothalamic “setpoint” to which core body temperature is compared. Consequently, whether the core temperature is below or above this setpoint determines whether the body will generate, conserve, or lose heat. Hyperthermia exists if body temperature during homeostatic conditions rises above the normal range. This may be due either to heat production exceeding heat loss or to heat storage. The opposite is true for hypothermia. During general and regional anesthesia, thermoregulation is impaired via pharmacologic and central mechanisms. Mild hypothermia commonly occurs in a characteristic pattern during anesthesia and surgery due to this impairment, as well as exposure to the cooler operating room environment. Thus, a less common but more functional definition of hyperthermia is a rise in core temperature more than 2°C per hour or more than 0.5°C over 15 minutes. Such a rise typically warrants further investigation.

physiologic thermal gradient between the two sites. A reasonable alternative is axillary temperature, which may be closer to core temperature values. Transitional zone temperatures (rectal, bladder) fall between core and peripheral temperatures.

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Causes of Hyperthermia during General Anesthesia

Iatrogenic Increased room temperature Warming devices Airway humidifiers or warmers Excessive rewarming after cardiopulmonary bypass

or even death. Transfusion reactions may be fatal. Pheochromocytoma and thyrotoxicosis are associated with severe hemodynamic disturbances as well as endocrine complications. Neuroleptic malignant syndrome may behave very similarly to malignant hyperthermia. Although elevated temperature is typically not the only sign of these conditions, it may serve as an early indicator of underlying pathology and assist in the diagnosis.

Infectious Preoperative fever associated with upper respiratory tract infection or condition related to surgical indication Sepsis Bacteremia or sepsis associated with surgical manipulation (e.g., oral surgery)

Pulmonary Aspiration pneumonia Atelectasis Deep venous thrombosis or pulmonary embolus

Metabolic Pheochromocytoma Thyrotoxicosis or thyroid storm Adrenal insufficiency

Central Nervous System Status epilepticus Hypothalamic pathology Parkinson’s disease

Drug Induced Malignant hyperthermia Neuroleptic malignant syndrome Anticholinergic effect Cocaine, tricyclic antidepressants Antibiotic-induced drug fever Monoamine oxidase inhibitors interacting with opioids, especially meperidine

Miscellaneous Monitoring error Connective tissue diseases Hematoma Transfusion reactions Infusion of blood components with infectious contamination

hyperthermia has been shown to worsen neurologic injury following ischemic events or status epilepticus. Numerous central nervous system effects may occur, including the following: ●

●

● ●

●

Cerebral blood flow increases 5% to 7% for each degree change in temperature. Release of excitatory neurotransmitters, such as glutamate, is increased with temperatures greater than 39°C during ischemia. Hyperthermia can result in seizure activity in children. Permanent central nervous system damage can occur with temperatures above 42°C. Increased temperature affects somatosensory evoked potentials by reducing latency.

Hyperthermia causes a rightward shift of the oxygenhemoglobin dissociation curve. This rightward shift means that hemoglobin has a lower affinity for oxygen and is less saturated at a given arterial oxygen tension. Further, the cause of hyperthermia may have a variety of untoward effects. Malignant hyperthermia may lead to acidosis, renal dysfunction, hematologic disturbances,

MANAGEMENT Management for hyperthermia is directed primarily at the underlying cause (i.e., fever from infection versus other conditions). One should review the patient’s history and examine the patient for clues to possible causes of hyperthermia. The perioperative course, including drugs administered, the nature of the surgical procedure, and any other perioperative complications, should also be examined. Patients with sepsis require antibiotics and possibly hemodynamic support as well. Patients with malignant hyperthermia should be treated with dantrolene and supportive therapy. Those in whom fever develops during a transfusion need to be evaluated to rule out a possibly severe transfusion reaction. Active patient cooling should be considered when the temperature exceeds 39°C. Treatment of hyperthermia itself may be as simple as lowering the room temperature, removing drapes or coverings, turning off warming devices, and blowing cool air over the patient. In more severe cases, one may consider the following: ● ● ●

●

Apply ice to the groin, axilla, or neck. Use cooled intravenous solutions. Undertake ice-water lavage into the surgical wound, bladder, stomach, or rectum (ice-water peritoneal lavage has also been used in extreme cases). In desperate situations, use cardiopulmonary bypass to provide rapid cooling.

PREVENTION Prevention of intraoperative hyperthermia begins with a preoperative history and physical examination. Does the patient have a history of malignant hyperthermia? Does the patient have known sepsis, pheochromocytoma, thyroid dysfunction, or other possible preoperative causes of hyperthermia? What was the patient’s temperature preoperatively? Iatrogenic hyperthermia or hypothermia is prevented by monitoring the patient’s core body temperature after the establishment of a baseline temperature and using a blanket cooling or warming device as necessary. If hyperthermia occurs, one should review recent intraoperative events: ● ● ● ●

Has a transfusion just begun? Were malignant hyperthermia–triggering agents used? Where is the site of surgery? What drugs have been given recently?

Although some mild hyperthermia or fever may be beneficial with infection, the potential physiologic effects on the heart and brain can be detrimental, especially in the elderly. If so, the condition must be treated aggressively.

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Further Reading Baughman V: Brain protection during neurosurgery. Anesthesiol Clin North Am 20:315-327, 2002. Cereda M, Maccioli GA: Intraoperative temperature monitoring. Int Anesthesiol Clin 42:41-54, 2004. Chiharu N, Lenhardt R: Fever during anaesthesia. Best Pract Res Clin Anesthesiol 17:499-517, 2003. Oku G, Rosenberg H: Thermoregulation in the postoperative patient. In Brown M, Brown EM (eds): Comprehensive Postanesthesia Care. Baltimore, Williams & Wilkins, 1997, pp 283-301.

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Rosenberg H, Frank S: Causes and consequences of hypothermia and hyperthermia. In Benumof JL, Saidman U (eds): Anesthesia and Perioperative Complications. St. Louis, Mosby–Year Book, 1999, pp 338-356. Sessler DI: Temperature monitoring. In Miller RD (ed): Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2004, pp 1571-1597.

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Angioedema and Urticaria Saeed Habibi and Catherine Drexler

102

Case Synopsis A 24-year-old woman with a vague history of swelling of the lips and tongue and wheezing associated with exercise, anxiety, and cold temperature receives general anesthesia for shoulder arthroscopy. After induction of general anesthesia and tracheal intubation, severe bronchospasm develops, followed by generalized angioedema and cardiovascular collapse.

PROBLEM ANALYSIS Definition Angioedema and urticaria are clinical signs that may result from a vast array of causes, including immune-mediated and non-immune-mediated mechanisms. They often occur together and represent a clinical spectrum ranging from a minor irritating reaction to life-threatening laryngeal edema or anaphylaxis. Urticaria is characterized by erythematous, pruritic wheals of cutaneous edema. These blanch with pressure but remain surrounded by a “flare” of erythema. Although angioedema is a similar process, it occurs in the deeper subcutaneous tissues and produces more diffuse swelling. Sites of involvement may include the face, tongue, larynx, and gastrointestinal tract, as well as the extremities. Involvement of the upper respiratory tract has potential to cause life-threatening airway obstruction. Most episodes of urticaria and angioedema are acute but may recur during a period of 6 weeks or less. Periodic episodes lasting longer than 6 weeks are viewed as chronic, and most are idiopathic in origin. Hereditary angioneurotic edema (HAE), or complement 1 esterase inhibitor (C1-INH) deficiency, is a rare form of angioedema. HAE is an autosomal dominant inherited disease characterized by absolute (type 1) or relative (type 2) deficiency of C1-INH activity. The deficiency of C1-INH allows C1 esterase to cleave C1 and subsequently to activate the complement cascade, resulting in vasodilatation and angioedema. The diagnosis of HAE is crucial, because the treatment for an acute episode of C1-INH deficiency differs dramatically from that for other types of angioedema. Further, HAE has a significant mortality rate due to associated laryngeal edema. Acquired C1-INH deficiency is associated with systemic diseases such as autoimmune disorders, B-cell lymphomas (type I), and carcinomas. It can also be secondary to immunoglobulin (Ig) G anti–C1-INH autoantibodies (type II). Acute urticaria or angioedema results from activation and degranulation or degradation of mast cells and basophils due to IgE-mediated or non-IgE-mediated mechanisms (e.g., complement-mediated or direct mast cell– releasing agents). These cells release or generate several mediators that cause vasodilatation and increased vascular permeability. These include histamine, histamine-releasing 426

factors, prostaglandin D2, leukotrienes C4 and D4, plateletactivating factor, anaphylatoxins (C3a, C4a, C5a), bradykinin, kallikrein, cytokines such as interleukin (IL)-4 and IL-5, and interferon γ. The clinical features of mast cell degradation are similar, regardless of the classification and underlying cause (Table 102-1).

Recognition Perioperative urticaria or angioedema warrants immediate recognition and careful evaluation for laryngeal edema, which may be life threatening, particularly in pediatric patients with small airways. Intraoperative diagnosis of urticaria or angioedema may be difficult for several reasons. Surgical drapes, warming blankets, and surgical preparation solutions may obscure and limit patient exposure, thereby delaying recognition of

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Classification of Angioedema

Idiopathic Immune-mediated angioedema Immunoglobulin E mediated Physical urticaria Contact reactions

Complement Mediated C1 esterase inhibitor (C1-INH) deficiency Hereditary angioneurotic edema Acquired C1-INH deficiency Serum sickness Urticarial vasculitis Systemic lupus erythematosus Transfusion reactions

Non–Immune Mediated Direct mast cell or histamine release Angiotensin-converting enzyme inhibitor related

Other Rare Syndromes Systemic mastocytosis C3b inactivator deficiency Infection Helminthic Fungal Viral Systemic diseases Hyperthyroidism Collagen vascular diseases Malignancies

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any cutaneous manifestations. Further, bronchospasm secondary to histamine release may be incorrectly attributed to airway manipulation or asthma. Also, hypotension consequent to vasodilatation from more generalized reactions may wrongly be assumed to be secondary to myocardial depression, anesthetic effects, or blood loss. Finally, multiple drugs capable of immunologic or nonimmunologic mast cell activation and degranulation may be administered over a brief period; these include antibiotics, induction and neuromuscular blocking agents, and opioids. Therefore, even when a reaction is recognized, it is often difficult to identify the cause or to determine whether a true “allergic” reaction has occurred. Once urticaria or angioedema is recognized, it is crucial to document the temporal relation between the administration of drugs and the onset of the reaction. The reaction may be significantly delayed from the presumed time of contact with the causal agent.

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the magnitude of reaction is related to both the dose and the rate of administration).

Implications Acute intraoperative urticaria or angioedema can progress to laryngeal edema or anaphylaxis with respiratory failure or hemodynamic collapse. In an immune-mediated reaction, repeated exposure may increase the risk of a reaction. In a patient with a past history of intraoperative urticaria or angioedema reactions, the options for anesthetic drugs are limited, depending on the mechanism and cause of such reactions. Preoperative prophylaxis with anabolic steroids (danazol, stanozolol) or glucocorticoids may be useful in certain patients with a history of perioperative angioedema.

MANAGEMENT AND PREVENTION Risk Assessment

It is essential to avoid known causative agents and those with the potential for cross-reactivity. Although prophylactic use of antihistamines or corticosteroids is common, and although leukotriene antagonists have been used with some success, their efficacy in preventing and modulating perioperative allergic or nonimmunologic reactions is unknown. With suspected acute urticaria or angioedema, the causative agent should be removed when possible. Because laryngeal edema may develop rapidly, the adequacy of ventilation must be assessed immediately. If indicated, the airway should be secured by tracheal intubation. Difficult intubation should be anticipated, and the airway must be evaluated for residual edema before extubation. Urticaria or angioedema may be associated with significant intravascular volume depletion. Consequently, fluid resuscitation is mandatory. Epinephrine is used if cardiovascular collapse, anaphylaxis, or severe respiratory compromise occurs. Other β-agonists (e.g., terbutaline, albuterol) may replace epinephrine for the treatment of isolated bronchospasm. Antihistamines may be used alone or in conjunction with epinephrine when clinical features do not warrant the sole use of epinephrine. Although H2-blockers alone have minimal effects, they may be effective when used in combination with H1-blockers. Corticosteroids are used for the management of acute, recurrent, or persistent angioedema or urticaria. However, long-term use of these drugs is associated with frequent complications. In HAE, the goal is to increase C1-INH activity to at least 50% of its normal level. This can be achieved by transfusion of fresh frozen plasma, which contains C1-INH, antifibrinolytics, attenuated androgens, and C1-INH concentrate. ε-Aminocaproic acid and tranexamic acid have been used for perioperative prophylaxis. Anabolic steroids (danazol, stanozolol) can induce hepatic synthesis of C1INH and provide effective preoperative prophylaxis for HAE. For short-term prophylaxis, these agents are administered for several days before and after the scheduled surgery (e.g., danazol 10 mg/kg per day, to a maximum of 600 mg/day; stanozolol 6 mg/day). C1-INH concentrate has been used as preoperative prophylaxis in a dose of 500 or 1000 units;

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Approximately 15% to 20% of the population will experience an episode of angioedema or urticaria during their lifetime, and it is more prevalent in middle-aged women. However, it is extremely difficult to identify patients at risk for angioedema or urticaria because of the multitude of potential initiators. Patients with a history of past reactions, HAE, collagen vascular diseases, B-cell lymphoma or other malignancies, occult infections, or thyroid disorders may be at increased risk. The mainstays of the evaluation of acute or chronic urticaria and angioedema are a thorough history, physical examination, and identification of all medication administered. The appropriate initial laboratory evaluation of chronic urticaria is controversial. In general, it may include a complete blood cell count with (manual) differential cell count, erythrocyte sedimentation rate, and thyroid gland studies (thyroid-stimulating hormone, antithyroglobulin, and antithyroid peroxisomal antibody titers). In atypical cases, or if urticarial vasculitis is suspected, complement studies, hepatocellular enzyme tests, and skin biopsies are advised. Further testing depends on the individual circumstances. It may include blood chemistries, serologic studies, skin testing for IgE-mediated reactions, and radioallergosorbent testing (RAST) for specific IgE antibodies. In the evaluation of patients with suspected intraoperative urticaria or angioedema reactions, meticulous documentation of the time course of events in relation to drug administration is of paramount importance. Unfortunately, even when a specific drug is suspected, proving a causal relationship is often difficult. Specific IgE antibodies may be demonstrated in immunologically mediated reactions (e.g., to thiopental, latex, succinylcholine, blood products, protamine, plasma expanders, antibiotics). A positive skin test or RAST indicates sensitization and a potential risk of generalized reaction with re-exposure to the agent. Although rechallenge with the drug may confirm the diagnosis, it is potentially dangerous and not usually recommended. Although a past history of anaphylaxis to a specific drug contraindicates its future use, a nonimmunologic reaction is more difficult to interpret and may not be a contraindication to such use (e.g., for drugs causing histamine release,

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however, C1-INH is expensive and is currently not available in the United States. It has been used mainly in Europe. Antihistamines, corticosteroids, and epinephrine are usually ineffective in treating acute episodes of HAE, but they are often administered when the specific mechanism of the reaction is unclear.

Further Reading Abraham D, Grammer L: Idiopathic anaphylaxis. Immunol Allergy Clin North Am 21:783-794, 2001. Agostoni A, Aygoren-Pursun E, Binkley KE, et al: Hereditary and acquired angioedema: Problems and progress. Proceeding of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol 114(Suppl):S51-S131, 2004.

Dibbern DA Jr, Dreskin SC: Urticaria and angioedema: An overview. Immunol Allergy Clin North Am 24:141-162, 2004. Hepner DL, Castells MC: Anaphylaxis during the peioperative period. Anesth Analg 97:1381-1395, 2003. Ledford DK: Allergy, anaphylaxis, and general anesthesia. Immunol Allergy Clin North Am 21:795-812, 2001. Lieberman P: Anaphylactic reactions during surgical and medical procedures. J Allergy Clin Immunol 110(Suppl):S64-S69, 2002. Mertes PM, Laxenaire MC, Alla F: Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000. Anesthesiology 99:536-545, 2003. Muller BA: Urticaria and angioedema: A practical approach. Am Fam Physician 69:1123-1128, 2004.

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103

Disorders of Water Homeostasis: Hyponatremia and Hypernatremia Brenda G. Fahy, J. Thomas Murphy, and John L. Atlee

HYPONATREMIA Case Synopsis A 55-year-old man with small cell lung carcinoma presents for preanesthetic evaluation for right upper lobectomy. His past medical history includes emphysema, hypertension, and insulin-dependent diabetes mellitus. On physical examination, his blood pressure is 140/80 mm Hg, and his pulse is 86 beats per minute, with good skin turgor. His laboratory values are as follows: serum sodium, 126 mEq/L; serum osmolality, 390 mOsm/kg; serum uric acid, 3.7 mg/dL; urine sodium, 30 mEq/L; and normal glucose, blood urea nitrogen (BUN), and thyroid and adrenal function tests. The patient denies nausea, lethargy, or weakness.

Definition Serum sodium concentration and osmolality are closely regulated by water homeostasis. This is mediated by thirst, arginine vasopressin, and the kidneys. A disruption in water homeostasis is manifested by an abnormal serum sodium concentration—either hyponatremia or hypernatremia. The former is defined as a serum sodium concentration less than 135 mEq/L, with severe hyponatremia occurring at values less than 120 mEq/L. The patient described in the case synopsis had hypo-osmotic hyponatremia and was euvolemic with normal thyroid and adrenal function. Causes of true hyponatremia are listed in Table 103-1; causes of pseudohyponatremia are listed in Table 103-2. The case presented is due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) related to small cell lung carcinoma (Table 103-3).

Recognition Symptoms of hyponatremia are related to the serum sodium concentration and how rapidly it decreases. The blood-brain barrier is virtually impermeable to sodium. Thus, rapid decreases in serum sodium cause water entry into the cells of the brain and other tissues. This can lead to cerebral edema, with progression to intracranial hypertension. Both the magnitude and the rapidity of water entry into brain cells explain the central nervous system (CNS)

symptoms associated with hyponatremia. These also correlate with symptom severity (Fig. 103-1). Early symptoms of hyponatremia-related CNS water entry are lethargy, weakness, and somnolence. Unabated, there may be progression to seizures, coma, and death. Therefore, hyponatremia must always be considered in the differential diagnosis of any mental status deterioration. The diagnosis of hyponatremia is based on laboratory testing, specifically, serum sodium concentration (Fig. 103-2). The next step is to measure plasma osmolality. This may help establish the diagnosis of pseudohyponatremia (see Table 103-2). Pseudohyponatremia occurs when the extracellular fluid compartment contains an impermeable solute (e.g., lipids) or there has been translocation or extravasation of large volumes of non-salt-containing fluids (e.g., transurethral resection of prostate or bladder tumor, hysteroscopy). This causes a shift of water from the intracellular to extracellular fluid compartment, causing dilutional hyponatremia. With more laboratories using ion-selective electrodes to measure serum sodium concentrations, dilutional hyponatremia has become less of a problem. Normal values for plasma osmolality range from 274 to 290 mOsm/kg. Calculated plasma osmolality (Posm) is determined by the following formula: Posm = (2.0 × [Na+]) + Glucose (mg/dL)/18 + BUN (mg/dL)/2.8 Patients with disorders such as hyperproteinemia or hyperlipidemia, which cause increased osmolality and pseudohyponatremia, have an abnormal osmolality gap (measured Posm – calculated Posm >10 mOsm/L). These disorders highlight 429

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Causes of True Hypo-osmotic Hyponatremia

Table 103–3

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Causes of Syndrome of Inappropriate Secretion of Antidiuretic Hormone

Hypovolemia

Hypervolemia Renal causes (urinary sodium >20 mEq/L) Renal failure Other causes (urinary sodium <20 mEq/L) Congestive heart failure Hepatic cirrhosis Nephrotic syndrome Pregnancy

Euvolemia (Urinary Sodium >20 mEq/L) Glucocorticoid deficiency Hypothyroidism Syndrome of inappropriate antidiuretic hormone (SIADH) Reset osmostat—psychosis, malnutrition

the importance of measuring plasma osmolality in hyponatremic patents. Other important laboratory tests are urine osmolality and sodium and a complete chemistry panel, including uric acid concentrations. Other electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia) are often associated with hyponatremia. Once pseudohyponatremia has been excluded, the next diagnostic step is to determine the volume status, because true hypo-osmotic hyponatremia may be hypovolemic, hypervolemic, or euvolemic (see Table 103-1). This is assessed by clinical signs and symptoms in conjunction with hemodynamic and laboratory data. The serum uric acid level may be helpful in determining the patient’s volume status. A low serum uric acid level (<4 mg/dL) likely indicates euvolemia, whereas an elevated uric acid level may be present with hypovolemia or hypervolemia.

Malignancy Lung (especially small cell carcinoma) Central nervous system Pancreas

Pulmonary Pneumonia Tuberculosis Fungal Abscess

Neurologic Infection Trauma Cerebrovascular accident

Drugs (Most Common) Amitriptyline Chlorpropamide Cyclophosphamide Desmopressin Morphine Nicotine Nonsteroidal anti-inflammatory drugs Oxytocin Selective serotonin reuptake inhibitors Vincristine

500

normal Brain water, g/100g dry weight

Renal losses (urinary sodium >20 mEq/L) Diuretic therapy Mineralocorticoid deficiency Cerebral salt wasting syndrome (e.g., subarachnoid hemorrhage) Renal disease Renal tubular acidosis (bicarbonaturia with renal tubular acidosis and metabolic alkalosis) Renal tubular defect (salt wasting nephropathy) Extrarenal losses (urinary sodium <20 mEq/L) Gastrointestinal diseases—vomiting, diarrhea, and gastric suctioning Skin—burns, sweating, cystic fibrosis Pancreatitis Trauma

died

asymptomatic

lethargic

450

400

350

300

Table 103–2

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Causes of Pseudohyponatremia

Normal Plasma Osmolarity Hyperlipidemia Hyperproteinemia Transurethral resection of prostate or bladder tumor; hysteroscopy

Increased Plasma Osmolarity Hyperglycemia Mannitol administration From Rose BD: Hypoosmolal states: Hyponatremia. In Jeffers JD, Navrozov M (eds): Clinical Physiology of Acid-Base and Electrolyte Disorders. New York, McGraw-Hill, 1994, pp 651-694.

Plasma Na 139 mEq/L

Plasma Na Plasma Na Plasma Na 139-119 mEq/L 140-122 mEq/L 139-99 mEq/L in 2h in 3.5 days in 16 days

Figure 103–1 ■ Brain water content in control and hyponatremic rabbits. When plasma sodium was acutely lowered to 119 mEq/L over 2 hours, brain water content increased to 17% above normal. This was associated with severe symptoms and death. In contrast, slowly lowering plasma sodium to the same level over 3.5 days resulted in a smaller increase in brain water (7%) and no symptoms. Finally, gradually reducing plasma sodium to extremely low levels (99 mEq/L) produced a small increase in brain water and only mild neurologic symptoms. (From Arieff AI, Llach F, Massry SG: Neurological manifestations and morbidity of hyponatremia: Correlation with brain water and electrolytes. Medicine 55:121-129, 1976.)

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Hyponatremia

Figure 103–2 ■ Major steps in the initial evaluation of hyponatremia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Exclude pseudohyponatremia History and physical examination Exclude thiazide diuretics

History of fluid loss Postural hypotension Prerenal azotemia

Hyponatremia resolves when thiazides stopped

Equivocal volume status by history and physical examinaion

Edematous conditions

Exclude advanced renal failure Congestive Cirrhosis heart with failure ascites

Urinary sodium

Matches sodium intake

<20 mEq/L

Hypovolemic hyponatremia

Nephrotic syndrome

Isovolemic hyponatremia

Hypervolemic hyponatremia

Pursue differential diagnosis of SIADH

Pharmacologic agents

Hyponatremia is a common clinical electrolyte disorder. Fifteen percent to 22% of hospitalized patients have serum sodium values less than 135 mEq/L, and 1% to 4% have values less than 130 mEq/L. Hyponatremia can occur preoperatively, intraoperatively, or postoperatively. It can be diagnosed during the preoperative assessment as being caused by SIADH (as was the case in the patient presented earlier) or as a known side effect of medical management (e.g., thiazide diuretics, carbamazepine). Hyponatremia often presents perioperatively as hypovolemic hyponatremia. Intraoperative hypervolemic hyponatremia occurs with transurethral resection of prostate (TURP), transurethral resection of bladder tumor (TURBT), or hysteroscopy with intravascular translocation of irrigating solutions (e.g., glycine, sorbitol). The manifestations of such absorption are due to combined hyponatremia and hypoosmolality. Severe hyponatremia can cause problems in the absence of hypo-osmolality, however. Most other causes of hyponatremia also result in hypo-osmolality, and the manifestations attributed to low serum sodium concentrations cannot be separated from those occurring as a consequence of concomitant hypo-osmolality. During procedures utilizing irrigating solutions, hyponatremia can develop quickly, presenting with CNS manifestations. Prompt recognition and therapy are key. One cause of postoperative hyponatremia is the increased effect of antidiuretic hormone (ADH). This occurs if the sodium in perioperative intravenous fluids is excreted while

Endocrine disorders

Neurologic disorders

Tumorassociated

some of the infused water is retained. If extreme, postoperative hyponatremia may cause death. Hyponatremia is often accompanied by other electrolyte abnormalities (see also Chapters 14 to 16). For example, hypokalemia may be associated with hypovolemic hyponatremia due to gastrointestinal losses (vomiting, diarrhea), use of loop diuretics, or renal tubular acidosis. Metabolic alkalosis may accompany vomiting or diuretic use, and metabolic acidosis may accompany diarrhea or mineralocorticoid deficiency. With euvolemic hyponatremia, there may be associated hypokalemia due to SIADH and polydipsia (psychogenic water drinking). In contrast, hyperkalemia accompanies glucocorticoid deficiency. Azotemia is common with hypervolemic hyponatremia. Serum sodium serves as a marker for disease severity with hypervolemic hyponatremia.

Implications The risk for hyponatremia is related to the absolute level of serum sodium. However, more critical is how rapidly the serum sodium falls due to accompanying fluid shifts. Upon exclusion of pseudohyponatremia, it is necessary to determine the type of hyponatremia, because therapy differs. Whether correction of hyponatremia is required and how fast it should be accomplished depend on the severity of symptoms. With acute CNS symptoms, the risk of cerebral edema outweighs the risk of rapid correction; thus, correction is undertaken quickly, while realizing that too rapid correction may cause excess morbidity or even mortality.

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Risk Assessment

Pulmonary conditions

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MANAGEMENT Major steps in the initial evaluation of hyponatremia are outlined in Figure 103-2. Treatment involves two basic principles: identifying and treating the underlying cause, and increasing serum sodium safely when indicated. With serious CNS symptoms or serum sodium less than 110 mEq/L, rapid sodium replacement with hypertonic saline (3%) may be required to prevent death. Under these circumstances, the goal of hypertonic saline replacement should be to increase serum sodium 1 to 2 mEq/L per hour over a maximum of 3 hours. Careful monitoring is required throughout this process. Sodium replacement should not exceed 12 mEq/L over 24 hours, or 25 mEq/L over 48 hours. Despite the risks associated with acute, severe hyponatremia, too rapid correction may cause demyelinating lesions in the pons, which can develop over several days. This disorder, termed central pontine myelinolysis or the osmotic demyelination syndrome, can lead to quadriparesis, coma, and death. Diagnostic confirmation is by computed tomography or magnetic resonance imaging; however, changes may not be detectable for up to 4 weeks. Risk factors for central pontine myelinolysis include (1) sodium correction rate greater than 12 mEq/L in 24 hours or 25 mEq/L in 48 hours, (2) overcorrection of serum sodium greater than 140 mEq/L within 2 days, (3) hypoxic or anoxic episodes before therapy, (4) hypercatabolic states (e.g., burns) or malnutrition (e.g., chronic alcoholism), and (5) chronic rather than acute hyponatremia. Unfortunately, determining the duration of hyponatremia may be difficult. Chronic hyponatremia is less likely to be accompanied by CNS manifestations because it develops more slowly. If rapid correction of serum sodium is not required, a hypovolemic hyponatremic patient may receive isotonic saline with any required electrolyte supplementation to correct the fluid deficit and hyponatremia. If diuretics are the cause, these should be stopped, and appropriate fluids and electrolytes administered. Mineralocorticoids should be replaced if indicated. Euvolemic hyponatremia therapy requires free water restriction. Steroid or thyroid hormone replacement may be required. If SIADH is determined to be the cause, treatment includes strict fluid restriction, especially free water. Isotonic saline should not be used to treat SIADH hyponatremia

because it can result in urinary sodium excretion, exacerbate water retention, and worsen hyponatremia. Reversible causes of SIADH should be sought and treated (see Table 103-3). If SIADH is caused by medications that inhibit ADH (e.g., demeclocycline, phenytoin, loop diuretics, lithium), these may need to be discontinued. Hypervolemic hyponatremia is due to excessive secretion of ADH. This occurs when a disease process (e.g., cirrhosis, nephritic syndrome, congestive heart failure) results in increased total body fluids (i.e., hypervolemia), but there is an associated decrease in effective circulating intravascular volume and glomerular filtration rate. This triggers ADH secretion. Therapy focuses on the underlying disease process and fluid restriction, especially free water. The patient in the case synopsis had SIADH from small cell carcinoma of the lung, with euvolemic hypo-osmotic hyponatremia. His hyponatremia was likely chronic, based on absent CNS symptoms. Free water should be restricted, with serial serum sodium monitoring. Aggressive intraoperative hydration with isotonic saline could potentially worsen this patient’s hyponatremia.

PREVENTION Identifying high-risk patients and having a high index of suspicion for hyponatremia can help prevent hyponatremic complications. Because of the high frequency of hyponatremia in hospitalized patients, serum sodium should be monitored. Hyponatremia can occur throughout the perioperative period, and vigilance for its development during procedures that use irrigating solutions (TURP, TURBT, hysteroscopy) is required. Once hyponatremia is diagnosed, and pseudohyponatremia has been excluded, it is important to evaluate the patient’s volume status to seek treatable causes of hypo-osmotic hyponatremia. Careful monitoring of serum sodium can help prevent the development of hyponatremia during high-risk procedures, as well as in high-risk patients. If slower correction of serum sodium is indicated for hypo-osmotic hyponatremia, the volume status determines treatment. With euvolemia, free water is restricted; with hypervolemia, free water and salt are restricted; with hypovolemia, isotonic saline is administered.

HYPERNATREMIA Case Synopses Case 1 A 62-year-old woman with postoperative ileus had a nasogastric suctioning tube placed. Within 3 days, she had reduced skin turgor and mild orthostatic hypotension. Her serum sodium was 155 mEq/L, serum potassium was 3.8 mEq/L, and body weight was 62 kg. Case 2 A 7-year-old boy with severe colitis had a diverting colostomy placed. Subsequently, he received intravenous and nasogastric nutrition for several years. Over that period,

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he presented two times with confusion, hypernatremia, and weight gain. However, on both occasions, there was no fever, diarrhea, or vomiting. Plasma and urine samples collected on the second visit revealed plasma and urine sodium concentrations of 155 and 172 mEq/L, respectively.

PROBLEM ANALYSIS Definition

Recognition The signs and symptoms of hypernatremia mostly reflect CNS dysfunction. They are more prominent when the increase in serum sodium concentration is large or occurs rapidly (i.e., over a few hours). Most outpatients with hypernatremia are either very young or very old. Common presenting symptoms in the young include hyperpnea, agitation, irritability, insomnia, and a typical high-pitched cry. These can progress to muscle weakness, confusion, listlessness, lethargy, and coma. Neurologic examination often reveals increased tone, nuchal rigidity, and brisk reflexes. Myoclonus, asterixis, and chorea can be present. Tonic-clonic and absence seizures have been described. Hyperglycemia is an especially common consequence of hypernatremia in children. Severe hypernatremia also can result in rhabdomyolysis. Finally, although hypocalcemia was once believed to be associated with hypernatremia, this has not been a common finding in more recent reports. Unlike infants, elderly patients generally have few symptoms until the serum sodium concentration exceeds 160 mEq/L. Intense thirst may be present early, but it dissipates as the disorder progresses, and it is absent in those with hypodipsia. Convulsions in either age group are typically absent, except with inadvertent sodium loading or overly aggressive rehydration. The level of consciousness correlates with the severity of hypernatremia. Muscle weakness,

Risk Assessment Hypernatremia represents a deficit of water relative to whole body sodium stores. This can result from a net water loss or a gain in hypertonic sodium Table 103-4. Net water loss accounts for the majority of cases. Because sustained hypernatremia can occur only when the thirst sensation is impaired or access to water is limited, persons at highest risk are those with impaired mental status, those on mechanical ventilators, infants, and the elderly. Hypernatremia in infants usually results from gastroenteritis (vomiting and diarrhea); in the elderly it is usually associated with thirst impairment, febrile illness, or infirmity. Also, frail nursing home residents and hospitalized patients are prone to hypernatremia because they depend on others for their water requirements.

Implications Hypernatremia results in the efflux of fluid from the intracellular space to the extracellular space to maintain osmotic equilibrium. This leads to transient cerebral dehydration and brain shrinkage. Brain cell volume can decrease by as much as 10% to 15% acutely, but it adapts quickly. Within 1 hour, the brain significantly increases its intracellular content of sodium and potassium, amino acids, and unmeasured organic substances or idiogenic osmoles (i.e., rapid adaptation). Normalization of brain volume is completed by 1 week (slow adaptation), as the brain regains approximately 98% of its water content. When severe hypernatremia develops acutely, the brain may not be able to increase its intracellular solute sufficiently to preserve its volume. If so, resulting cellular shrinkage can lead to structural changes. Cerebral dehydration from hypernatremia can result in physical separation of the brain from the meninges, leading to rupture of delicate bridging veins and subarachnoid or intracerebral hemorrhage, with permanent neurologic damage or death. Venous sinus thrombosis progressing to cerebral infarction can also develop. Acute hypernatremia has also been shown to cause cerebral demyelinating lesions in both animal models and humans. Patients with hepatic encephalopathy appear to be at higher risk for developing such lesions.

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Hypernatremia is defined as a serum sodium concentration greater than 145 mEq/L. In both children and adults, hypernatremia is seen primarily in persons with restricted access to water for a variety of reasons (e.g., patients in hospitals, convalescence facilities, or homes for the elderly; those who are debilitated or mentally impaired). Hypernatremia can also be iatrogenic, resulting from inappropriate fluid therapy or excessive administration of sodium bicarbonate during cardiopulmonary resuscitation. The body has two defense mechanisms to protect against hypernatremia: the ability to produce concentrated urine, and a powerful thirst mechanism. Release of ADH occurs when plasma osmolality exceeds 275 to 280 mOsm/kg, and the urine becomes maximally concentrated when plasma osmolality exceeds 290 to 295 mOsm/kg. Thirst provides the ultimate protection against hypernatremia, however. If the thirst mechanism is intact and there is unrestricted access to free water, it is rare for an individual to develop sustained hypernatremia from either excess sodium ingestion or a renal concentrating effect.

confusion, and coma may be manifestations of coexisting disorders rather than of hypernatremia itself. Finally, unlike outpatient hypernatremia, that acquired in hospital settings affects patients of all ages. In addition, the clinical symptoms are even more elusive, because these patients often have preexisting neurologic dysfunction. As in children, rapid sodium loading can result in convulsions and coma. In patients of all ages, orthostatic hypotension and tachycardia reflect marked hypovolemia.

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Table 103–4

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Causes of Water Deficit Relative to Whole Body Sodium Stores

Net Free Water Deficit Pure Water Unreplaced insensible loss Hypodipsia Neurogenic diabetes insipidus Post-traumatic Due to brain tumor, cyst, histiocytosis, tuberculosis, sarcoidosis Idiopathic Due to aneurysm, meningitis, Guillain-Barre´ syndrome Due to ethanol ingestion (transient) Congenital or acquired nephrogenic diabetes insipidus Renal disease (e.g., medullary cystic disease) Hypercalemia or hypokalemia Drugs (lithium, demeclocycline, foscarnet, methoxyflurane, amphotericin B, vasopressin V2-receptor antagonists)

Hypertonic Fluids Renal causes Loop diuretics Osmotic diuresis (glucose, mannitol, urea) Postobstructive diuresis Polyuric phase of acute tubular necrosis Intrinsic renal disease Gastrointestinal causes Vomiting Nasogastric drainage Enterocutaneous fistula Diarrhea Osmotic cathartics (e.g., lactulose) Cutaneous causes Burns Excessive sweating

Hypertonic Sodium Gain Hypertonic sodium bicarbonate Hypertonic feeding preparations Ingestion of sodium chloride Ingestion of sea water Sodium chloride–rich emetics Hypertonic saline enemas Intrauterine injection of hypertonic saline Hypertonic sodium chloride infusion Hypertonic dialysis Primary hyperaldosteronism Cushing’s syndrome

The amount of fluid required depends on the fluid composition. For example, to correct a 3-L free water deficit, approximately 4 L of 0.2% saline or 6 L of 0.45% saline would be needed, because these solutions contain approximately 75% and 50% free water, respectively. The calculated deficit does not account for insensible or ongoing urinary or gastrointestinal losses. Maintenance fluids, which include replacement of urine volume with hypotonic fluids, are given in addition to the deficit. If there are signs of severe hypovolemia or circulatory collapse, fluid resuscitation with normal saline, lactated Ringer’s solution, or colloid should be instituted before correcting the free water deficit. The type of therapy depends largely on the cause of hypernatremia and should be tailored to the pathophysiologic events involved in each patient (Table 103-5). Oral hydration should be started as soon as it can be safely tolerated. Plasma electrolytes should be measured every 2 to 3 hours until the patient is neurologically stable. In patients with hypernatremia that has developed over hours (e.g., accidental sodium overloading), rapid correction improves the prognosis without increasing the risk of cerebral edema. This is because accumulated electrolytes are rapidly extruded from brain cells. In such patients, reducing the serum sodium concentration by 1 mEq/L per hour is appropriate. A slower pace of correction is advised for patients with hypernatremia of longer or unknown duration, because full dissipation of brain solutes occurs over a period of days. In such patients, reducing the serum sodium concentration at a maximal rate of 0.5 mEq/L per hour prevents cerebral edema and convulsions. Consequently, some authorities (e.g., Adrogué and Madias) advise a target reduction in serum sodium concentration of 10 mEq/L per day for all patients with hypernatremia, except those in whom the disorder has developed over a period of hours. The goal of treatment is to reduce serum sodium concentration to 145 mEq/L. The preferred route for administering fluids is orally or via a feeding tube. If neither is feasible, fluids are given intravenously. The more hypotonic the fluid is (see Table 103-5), the lower the infusion rate should be. This reduces the risk for cerebral edema formation. Finally, except in cases of

From Adrogue´ HJ, Madias NE: Hypernatremia. N Engl J Med 342:1493-1499, 2000.

MANAGEMENT AND PREVENTION

Table 103–5

Treatment for hypernatremia must correct the underlying cause, normalize the serum sodium concentration, and restore the normal circulatory volume. The therapeutic cornerstone is the provision of adequate free water to correct the serum sodium concentration. The free water deficit cannot be easily assessed by physical examination in patients with hypernatremic dehydration, because most of the free water losses are intracellular. Accordingly, the signs of volume depletion are less apparent owing to better preservation of extracellular volume. A simple method for estimating the minimum amount of fluid necessary to correct the serum sodium concentration is the following equation:

Cause

Treatment

Sodium and water loss* Gastroenteritis Primary water loss* Ineffective breast feeding Hypodipsia Nephrogenic diabetes insipidus*

0.45% NaCl in 5% dextrose and water 0.2% NaCl in 5% dextrose and water

Free water deficit (mL) = 4 mL × Lean body weight (kg) × [Desired Δserum Na+ (mEq/L)]

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Management of Hypernatremia

Central diabetes insipidus* Sodium overload*

0.1% NaCl in 2.5% dextrose and water† Desmopressin acetate 5% dextrose and water‡

*See also Table 103-4. † Acute management. ‡ Diuretics may be needed. Adapted from Moritz ML, Ayus JC: Disorders of water metabolism in children. Pediatr Rev 23:371-380, 2002; and Adrogué HJ, Madias NE: Hypernatremia. N Engl J Med 342:1493-1499, 2000.

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frank circulatory compromise, 0.9% normal saline or lactated Ringer’s solution is unsuitable therapy for hypernatremia.

Further Reading Adrogué HJ, Madias NE: Hypernatremia. N Engl J Med 342:1493-1499, 2000. Adrogué HJ, Madias NE: Hyponatremia. N Engl J Med 342:1581-1589, 2000. Arieff AI, Llach F, Massry SG: Neurological manifestations and morbidity of hyponatremia: Correlation with brain water and electrolytes. Medicine 55:121-129, 1976. Berl T: Treating hyponatremia: Damned if we do and damned if we don’t. Kidney Int 37:1006-1018, 1990. Brunner JE, Redmond JM, Haggar AM, et al: Central pontine myelinolysis and pontine lesions after rapid correction of hyponatremia: A prospective magnetic resonance imaging study. Ann Neurol 27:61-66, 1990. Coulthard MG, Haycock GB: Distinguishing between salt poisoning and hypernatraemic dehydration in children. BMJ 326:157-160, 2003. Estes CM, Maye JP: Severe intraoperative hyponatremia in a patient scheduled for elective hysteroscopy: A case report. AANA J 71:203-205, 2003. Issa MM, Young MR, Bullock AR, et al: Dilutional hyponatremia of TURP syndrome: A historical event in the 21st century. Urology 64:298-301, 2004.

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Janicic N: Evaluation and management of hypo-osmolality in hospitalized patients. Endocrinol Metab Clin North Am 32:459-481, 2003. Moritz ML, Ayus JC: Disorders of water metabolism in children. Pediatr Rev 23:371-380, 2002. Nguyen MK, Kurtz I: New insights into the pathophysiology of the dysnatremias: A quantitative analysis. Am J Physiol Renal Physiol 287: F172-F180, 2004. Norenberg MD, Papendick RE: Chronicity of hyponatremia as a factor in experimental myelinolysis. Ann Neurol 15:544-547, 1984. Ofran Y, Lavi D, Opher T, et al: Fatal voluntary salt intake resulting in the highest ever documented sodium plasma level in adults (255 mmol L-1): A disorder linked to female gender and psychiatric disorders. J Intern Med 256:525-528, 2004. Oster JR, Singer I: Hyponatremia, hypoosmolalilty and hypotonicity: Tables and fables. Arch Intern Med 159:333-336, 1999. Rose BD: Hypoosmolal states: Hyponatremia. In Jeffers JD, Navrozov M (eds): Clinical Physiology of Acid-Base and Electrolyte Disorders. New York, McGraw-Hill, 1994, pp 651-694. Steele A, Gowrishankar M, Abrahamson S, et al: Postoperative hyponatremia despite near-isotonic saline infusion: A phenomenon of desalination. Ann Intern Med 126:20-25, 1997. Weisberg LS: Pseudohyponatremia: A reappraisal. Am J Med 86:315-318, 1989.

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Mark Nunnally and Patrick Neligan Case Synopsis A 56-year-old man is chronically critically ill. Serum chemistries and blood gas analysis are performed. The data are as follows: sodium (Na+) 130 mEq/L, potassium (K+) 4 mEq/L, chloride (Cl–) 100 mEq/L, total carbon dioxide (CO2) 24 mEq/L, urea 10 mg/dL, creatinine 1.0 mg/dL, albumin 1.0 g/dL, lactate 6.0 mEq/dL, pH 7.42, CO2 tension (PCO2) 40 mm Hg, bicarbonate (HCO3) 24 mEq/L, and base excess (BE)+1 mEq/L.

PROBLEM ANALYSIS Definition Acid-base analysis is a method of identifying abnormalities of ventilation or electrolyte balance that relies on the chemical properties of water. Water is a highly ionizing solvent and exists in high concentration (55 M), but there is little dissociation into its components: hydrogen and hydroxyl ions. The potential for such dissociation is determined by electrical charge and temperature. Electrical neutrality is always constant. Clinical quantification of water dissociation relies on measurement of the hydrogen ion concentration in arterial blood, which averages 0.00004 mEq/L. For convenience, this is expressed in negative logarithmic form as pH. The physiologic pH of serum is meticulously maintained by the body and is 7.4 at 37°C. If serum pH is less than 7.35, a state of acidemia exists. If it is greater than 7.45, a state of alkalemia exists. The extracellular fluid is a cellular and ionic mix of chemicals and organic proteins whose charges influence the dissociation of water. An acid substance may increase the hydrogen ion concentration of extracellular fluid (lower the pH), whereas a base substance may decrease the hydrogen ion concentration of extracellular fluid (raise the pH). Acids either dissociate in solution to yield an anion or associate with a hydroxyl ion to form water. Bases either dissociate to form a cation plus a hydroxyl ion or associate with a hydrogen ion to form water. Thus, anions are acids, and cations bases. This process is governed by three principles: 1. Electrical neutrality: The number of positive charges must equal the number of negative charges. 2. Mass conservation: The quantity of a substance remains constant unless added, generated, or destroyed. 3. Dissociation equilibria: The dissociation equilibria for all partially dissociated substances must be satisfied. In all cases, the water dissociation equilibrium readjusts to the ionic milieu. Although a variety of complicated approaches have been used to explain acid-base chemistry, the approach proposed by Stewart is most applicable to perioperative medicine. 436

Using a complex mathematical model, Stewart determined that only three independent variables govern water dissociation and thus acid-base balance (Table 104-1): 1. Arterial partial pressure of carbon dioxide (PaCO2): CO2 hydrates to form carbonic acid, which is transported in blood bound to hemoglobin and as bicarbonate. 2. Strong ion difference (SID): Strong ions are fully dissociated in solution. One example is lactate, whose pKa is 3.4. The SID is the electrical difference between the positively charged strong cations (sodium, potassium, magnesium, calcium) and the negatively charged strong anions (chloride, lactate, ketones, sulfate, formate). The SID is always positive and is determined mainly by the relative concentrations of sodium and chloride. Removal of strong cations or anions, or a change in their volume of distribution (e.g., the extracellular fluid volume of free water), alters the SID. Normally, the SID is 44 mEq/L. If it increases, the net effect is alkalinizing; if it decreases, the net effect is acidifying. 3. Total concentration of partially dissociated weak anions (ATOT): The major weak acids are albumin and phosphate. Both quantity and dissociation equilibria determine the effect of ATOT on water dissociation. There are two reasons why acid-base disorders are important. First, tissue dysfunction occurs at extremes of acidosis and alkalosis. Second, and perhaps more important, acidosis and alkalosis may be indicators of serious underlying pathology, such as tissue hypoperfusion, dehydration, and renal failure. As such, acid-base abnormalities are critical manifestations of underlying pathologies.

Recognition Four primary disturbances of acid-base balance exist: respiratory acidosis, respiratory alkalosis, metabolic acidosis, and metabolic alkalosis. Mixed respiratory acidosis and metabolic acidosis is common in severely injured or infected patients, while mixed respiratory acidosis and metabolic alkalosis is seen in chronic respiratory failure. Respiratory acid-base disorders arise from the partial pressure of CO2 in the blood and are related to ventilation. Respiratory acidosis results from hypoventilation due to loss

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Classification of Primary Acid-Base Abnormalities Acidosis

Alkalosis

At-a-Glance Pearls

Respiratory Metabolic Abnormal SID

Increased PCO2

Decreased PCO2

↓pH 0.08 for each 10 mm Hg in PCO2

Due to water

Water excess, dilutional ↓ SID, ↓ [Na+]

Water deficit, contraction ↑ SID,↑ [Na+]

Dilutional acidosis is usually present when NaCl <136 mEq/L, contraction alkalosis when >148 mEq/L

Chloride excess – ↓ SID, ↑ [Cl ]

Chloride deficit – ↑ SID, ↓ [Cl ]

Hyperchloremic acidosis is usually present if – corrected serum Cl >112 mEq/L, hypochloremic alkalosis if <100 mEq/L – – [Cl CORRECTED] = [Cl MEASURED] × ([Na+ NORMAL] / [Na+ MEASURED]) – Most, but not all, [A ] behave as strong anions; – in renal failure, [A ] consist of formate and sulfate (hyperphosphatemia is also a common acidosis) Hypoalbuminemic alkalosis is usually present when the serum albumin is >35 g/dL Hyperphosphatemic acidosis is usually present when the serum phosphate is >2.0 mmol/L

Due to electrolytes Chloride

Unmeasured anions [A–], e.g., lactate, keto acids

↓ SID, ↑ [A–]

Abnormal ATOT Albumin [Alb]

↑ [Alb] (rare)

↓ [Alb]

Phosphate [Pi]

↑ [Pi]

↓ [Pi]

ATOT, total concentration of partially dissociated weak anions; SID, strong ion difference. From Fencl V, Jabor A, Kazda A, et al: Diagnosis of metabolic acid-base disturbances in critically ill patients. Am J Respir Crit Care Med 162:2246-2251, 2000.

1. Lactic acidosis: This is caused by increased glycolysis and lactate production. It may be due to hypoxemia, hypoperfusion, congenital errors of metabolism, or exposure to biguanide or toxins. 2. Ketoacidosis: Ketones include acetate, acetoacetate, and β-hydroxybutyrate. All act as strong anions. Ketoacidosis results from starvation or insulin deficiency. Diabetic ketoacidosis is characterized by ketosis and hyperglycemia. 3. Acute renal failure: Renal acidosis is caused by the accumulation of ions excreted exclusively by the kidney— sulfate, formate, and the weak acid phosphate. A variety of other processes can also cause metabolic acidosis. Low serum sodium (<135 mEq/L) should alert the clinician to the possibility of a dilutional acidosis.

Alcohol toxicity is suspected with an osmolar gap. A difference between measured and calculated serum osmolality greater than 12 mOsm indicates the presence of unmeasured osmoles. Following infusion of large volumes of 0.9% saline, 5% albumin, or 6% hetastarch, hyperchloremic acidosis is common. All of these contain 154 mEq of both Na+ and Cl– (SID = 0) and thus reduce serum SID. Metabolic alkalosis can be caused by chloride loss, an increase in sodium relative to chloride, or loss of weak acid. Renal chloride loss is a compensatory response to chronic respiratory acidosis. Chloride may also be lost via the gastrointestinal tract with vomiting or nasogastric suctioning. The sodium concentration increases due to a loss of free water (contraction alkalosis) or after administration of sodium with a weak anion (e.g., bicarbonate, citrate, acetate). Finally, albumin is the most contributory weak acid, and hypoalbuminemia is a common cause of metabolic alkalosis in critically ill or malnourished patients.

Risk Assessment Historically, the gradual introduction of serum assays directly influenced the evaluation of acid-base abnormalities. Early assays for pH resulted in quantification of serum or blood by titration to a pH of 7.4. The base deficit-excess (BDE) is the amount (in mEq/L) of strong cation or anion required to return pH to 7.4, with PaCO2 adjusted to 40 mm Hg. Current algorithms for computing BDE are derived from the Van Slyke equation. Modern analyzers sample PCO2, electrolytes, and lactate and make more comprehensive analysis possible. However, BDE is still a useful tool for quantitative comparison. Figure 104-1 demonstrates a stepwise approach to acid-base disorders that includes BDE.

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

of respiratory drive, neuromuscular or chest wall disorders, rapid or shallow breathing, ventilation-perfusion mismatching, or an increase in the fraction of dead space ventilation. Respiratory alkalosis arises from increased alveolar minute ventilation (e.g., with pain, anxiety, sepsis, or hepatic insufficiency). Acute respiratory alkalosis usually accompanies acute metabolic acidosis. Metabolic acidosis is caused by a decrease in SID or an increase in ATOT. A change in SID can be caused by anion gain (as occurs with lactic, renal, keto-, and hyperchloremic acidosis) or cation loss (severe diarrhea, renal tubular acidosis). Acidosis can also be caused by strong ion dilution in a larger extracellular volume (dilutional acidosis), excessive hypotonic fluid intake, certain poisons (methanol, ethylene glycol, isopropyl alcohol), hyperglycemia, mannitol administration, or reduced ability to excrete free water. In acute metabolic acidosis, three possible diagnoses should be investigated immediately:

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<7.35 = Acidosis

7.35–7.5 = Normal or compensated

>7.5 = Alkalosis

Pure respiratory acidosis? Rule of thumb: pH ↓ 0.08 for every 10 mm Hg ↑ in PCO2

Compensated chronic respiratory acidosis or respiratory compensation for metabolic alkalosis

Metabolic alkalosis with inadequate compensation

Metabolic acidosis without compensation (suspect respiratory failure)

Normal physiologic value, may be balanced metabolic acidosis and alkalosis

Metabolic alkalosis with inadequate compensation

Metabolic acidosis with inadequate compensation (suspect respiratory failure)

Compensated metabolic acidosis

Pure respiratory alkalosis? Rule of thumb: pH ↑ 0.08 for every 10 mm Hg ↓ in PCO2

BD < −5 = metabolic acidosis

BDE +5 to −5 = normal range

BE >5 = alkalosis

Acidosis, PCO2 < 35 mm Hg, ± BD < −5 = metabolic acidosis

Normal range pH, PCO2 > 45, BE > +5 = prolonged respiratory acidosis

Alkalosis, PCO2 >45, BE > +5 = metabolic alkalosis

OR

OR

OR

Acidosis, PCO2 > 45 mm Hg, BDE normal range = respiratory acidosis, possibly acute

Normal-range pH PCO2 < 35 mm Hg, BD < −5 = metabolic acidosis + compensation

Alkalosis, PCO2 < 35 mm Hg, BDE normal range = respiratory alkalosis

Figure 104–1 ■ Stepwise approach to blood gas analysis. Analysis of measured variables and base deficitexcess (BDE). If the acid-base picture does not conform to any of these, a mixed picture is present, and the Stewart-Fencl-Gilfix method should be used to tease out coexisting acidifying and alkalinizing processes. BD, base deficit; BE, base excess.

Step 2. Evaluate respiratory component (volatile acid = CO2)

PCO2 > 45 mm Hg = respiratory acidosis PCO2 = 35–45 mm Hg = normal range PCO2 < 35 mm Hg = respiratory alkalosis

Step 3. Analyze the metabolic component (e.g., buffer base utilization) Step 4. Synthesize

Implications The anion gap theory was developed by Emmett and Narins in 1977 as a method to evaluate simple metabolic acidosis. The system is based on the contribution of weak acids (i.e., phosphate and albumin) and unmeasured anions to electrical neutrality. The sum of the difference in charge of common extracellular ions reveals an unaccounted for “gap” of 10 to 12 mEq/L—the anion gap: Na+ + K+ – (Cl– + HCO3–). If a patient develops a metabolic acidosis and the gap widens to, for example, 16 mEq/L, the acidosis is caused by unmeasured anions, such as lactate or ketones. If the gap does not widen, then the anions are measured and the acidosis is hyperchloremic. Figure 104-2 depicts an approach to the diagnosis of metabolic acidosis using the anion gap. Although this is a useful tool, it is weakened by the assumption of what is or is not a “normal” gap and should be corrected in critically ill patients for hypoalbuminemia using the following formula: Anion gap = Calculated anion gap + 2.5 × (4.5 g/dL – Observed albumin [g/dL]).

The most comprehensive approach to acid-base physiology is Stewart’s quantitative approach. This technique permits quantitative comparison of the relative contributions of the different components of acid-base balance. It is the most complete assessment of the variables influencing acid-base chemistry, but it is too cumbersome for rapid application. A simpler, more workable approach is to use a modification of this approach, the BDE gap. This allows recalculation of BDE using strong ions, free water, and albumin. The resulting BDE gap should mirror the SID and reveal the true anion gap: BDE = Standard base deficit-excess Modern blood gas analyzers calculate the BDE by the following equation: –

BDE = 0.9287 × [HCO3 – 24.4 + 14.83 × (pH – 7.4)] BEfw = Changes in free water = 0.3 × (Na – 140) BECl = Changes in chloride = 102 – ([Cl] × 140 [Na])

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Figure 104–2 ■ Evaluation of metabolic acidosis using the anion gap. BUN, blood urea nitrogen.

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Is the acidosis caused by measured (chloride) or unmeasured anions? Review the blood chemistry. Calculate the anion gap: Na+ + K+– (Cl− + HCO3−)

If the gap is normal, there is too much chloride due to excessive administration, excess loss of sodium (diarrhea, ileostomy), or renal tubular acidosis.

If the gap is wide (>12), there are other unmeasured anions present, causing the acidosis.

Is the gap acid lactate? Check a serum lactate: if >2, probably lactic acidosis.

Yes

For previously healthy patients, [lactate] = [base deficit].

No Is there renal failure? Evaluate the creatinine and urine output.

Yes

If the patient is in renal failure, renal acids are invariably present.

No Is there ketoacidosis? Send blood and urine for ketone levels.

Yes

If all of these tests are negative, less common causes must be sought. Send toxicology labs (particularly salicylates) and serum osmolality, and calculate osmolality using the following formula: 2(Na+ + K+) + Glucose/18 + BUN/2.8. Measured osmolality/calculated osmolality?

BEalb = Changes in albumin = 3.4 × (4.5 – Albumin [g/dL]) CBE = Calculated BDE = BEfw + BECl + BEalb BEG = Base excess caused by unmeasured anions = BDE – CBE This useful approach separates multiple simultaneous acid-base disturbances, such as those that occur in critically ill patients. A further simplification of this approach has been proposed and validated by Story and colleagues: Sodium-chloride effect (mEq/L) = [Na+] – [Cl—] – 38 Albumin effect (mEq/L) = 0.25 × (42 – [Albumin (g/L)]) Thus, the sodium-chloride effect on the BDE plus the albumin effect minus the calculated BDE equals the BDE gap.

MANAGEMENT Therapy is directed at the cause of the acid-base abnormality. Respiratory alkalosis is corrected by reducing iatrogenic

Yes

Consider alcohol ingestion.

hyperventilation or removing the causes of an increased respiratory drive (e.g., hypoxemia, pain, anxiety). Respiratory acidosis may require reversal of hypnotics or opioids or an increase in minute ventilation, but in isolation it is probably a minor abnormality. Hypercapnia is often well tolerated (e.g., patients with acute respiratory distress syndrome and multiorgan system dysfunction). Lactic acidosis due to circulatory failure is treated with resuscitation and hemodynamic optimization. Electrolyte abnormalities are corrected by replacement of specific deficiencies, correction of free water disturbances, and hemodialysis, if necessary. Toxic ingestions may require specific therapies (e.g., ethanol infusion in methanol poisoning, methemoglobin induction in cyanide toxicity), purging, adsorption, or hemodialysis. Ketoacidosis compels a search for a cause (starvation, diabetes, excessive alcohol consumption) and appropriate therapy. Figure 104-2 outlines an approach to the management of metabolic acidosis. Metabolic alkalosis (Fig. 104-3) is generally well tolerated but may be treated with chloride replacement if it is the result of hypochloremia. This is accomplished by the administration of 0.9% saline solution.

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

No

If the patient is hyperglycemic and ketotic, this is diabetic ketoacidosis. If the patient is ketotic and normoglycemic, this is either alcoholic or starvation ketosis.

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Is this due to hypernatremia/free water deficit?

Yes

No

Is this due to excessive chloride loss?

Yes

Hypernatremia. Correct free water deficit

The component of the base excess contributed by hypernatremia can be calculated as 0.3 × (Na − 140)

Chloride replacement. Evaluate urine chloride if renal loss (mineralocorticoid effect, Bartter’s syndrome) suspected

The component of the base excess due to hyperchloremia is calculated as 102 – ([Cl] ×140/[Na])

No

Yes

Is this due to excessive sodium solution administration (sodium acetate, bicarbonate, citrate, massive transfusion)? No Yes Is this due to hypoalbuminemia?

Figure 104–3 ■ Evaluation of metabolic alkalosis.

Check the serum albumin; the component of the base excess due to hypoalbuminemia is calculated as 3.4 × (4.5 −[albumin]). Albumin is in g/dL.

Chloride replacement

Nutrition

No Is this due to hypophosphatemia?

Check the serum phosphate.

Hypoalbuminemia is a marker of severe illness and resolves with treatment of the underlying cause.

PREVENTION Significant perioperative acid-base derangements are better avoided rather than managed after the fact. Adequate prevention requires vigilance for common sources of acid-base abnormalities. Serum lactate is used to follow the quality of resuscitation for patients in shock, particularly hemorrhagic shock. The magnitude of the base deficit and speed of resolution have prognostic implications. Type 1 diabetics should be treated with insulin perioperatively, and patients with acute or chronic renal failure may have to undergo dialysis. Care should be taken to avoid hyperventilation, especially in the setting of chronic respiratory acidosis. Hyperventilation reduces the central respiratory drive, making it more difficult to subsequently wean the patient from the ventilator. Appropriate fluid selection avoids SID disturbances due to

Table 104–2

■

Phosphate replacement

dilution or excess chloride administration. Hypotonic and dextrose-containing fluids are best avoided. Fluid choice makes little difference in patients having small-volume resuscitation. If larger-volume resuscitation is expected, then solutions that more closely match the electrolyte content of extracellular fluid (lactated Ringer’s, Normosol, Plasma-Lyte) are advised. Many commercially available colloids also contain high concentrations of chloride. Human albumin solution, some hetastarches, and gelatins are formulated in sodium chloride; large volumes of these can cause hyperchloremic acidosis. In the setting of chloride loss from nasogastric suctioning, normal saline can be administered until the base excess returns to zero. Normal saline is also therapeutic with excess sodium citrate administration (e.g., large-volume blood or fresh frozen plasma transfusions). Proactive management strategies minimize the risk of patients developing multiple complex acid-base disturbances in the postoperative setting. Using the approach advocated by Fencl and colleagues and Gilfix and associates, correcting the BDE for acidifying and alkalinizing processes for the patient presented in the

Correction of Base Deficit-Excess

Acidifying Process

Magnitude

BDC

Alkalinizing Process

Magnitude

BEC

Hyponatremia Hyperchloremia Lactate Total

130 mEq/L 100 mEq/L 6 mEq/L

–3 –3 –6 –12

Hypoalbuminemia

1.0 g/dL

+11.9

BDC, base deficit corrected; BEC, base excess corrected. BDC − BEC = 0.9

Total

+11.9

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case synopsis is complex (Table 104-2). In this example, the patient has three significant acidifying processes. The presence of lactic acidosis is ominous. However, by using traditional approaches to acid-base analysis (bicarbonate or BDE), the presence of this abnormality would not be apparent.

Further Reading Alfaro V, Torras R, Ibanez J, et al: A physical-chemical analysis of the acidbase response to chronic obstructive pulmonary disease. Can J Physiol Pharmacol 11:1229-1235, 1996. Balasubramanyan N, Havens PL, Hoffman GM: Unmeasured anions identified by the Fencl-Stewart method predict mortality better than base excess, anion gap, and lactate in patients in the pediatric intensive care unit. Crit Care Med 27:1577-1581, 1999. Emmett M, Narins RG: Clinical use of the anion gap. Medicine 56:38-54, 1977. Fencl V, Jabor A, Kazda A, et al: Diagnosis of metabolic acid-base disturbances in critically ill patients. Am J Respir Crit Care Med 162: 2246-2251, 2000. Figge J, Jabor A, Kazda A, et al: Anion gap and hypoalbuminemia. Crit Care Med 26:1807-1810, 1998. Figge J, Rossing TH, Fencl V: The role of serum proteins in acid-base equilibria. J Lab Clin Med 117: 453-467, 1991.

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Gilfix BM, Bique M, Magder S: A physical chemical approach to the analysis of acid-base balance in the clinical setting. J Crit Care 8:187-197, 1993. Hickling KG: Permissive hypercapnia. Respir Care Clin N Am 8:155-169, 2002. Morgan TJ, Clark C, Endre ZH: Accuracy of base excess—an in vitro evaluation of the Van Slyke equation. Crit Care Med 28:2932-2936, 2003. Morgan TJ, Venkatesh B, Hall J: Crystalloid strong ion difference determines metabolic acid-base change during in vitro hemodilution. Crit Care Med 30:157-160, 2002. Rutherford EJ, Morris JA Jr, Reed GW, et al: Base deficit stratifies mortality and determines therapy. J Trauma 33:417-423, 1992. Salem MM, Mujais SK: Gaps in the anion gap. Arch Intern Med 152: 1625-1629, 1992. Schlichtig R, Grogono AW, Severinghaus JW: Human PaCO2 and standard base excess compensation for acid-base imbalance. Crit Care Med 26:1173-1179, 1998. Siggaard-Andersen O: The Van Slyke equation. Scand J Clin Lab Invest 37:S15-S20, 1977. Stewart PA: Modern quantitative acid-base chemistry. Can J Physiol Pharmacol 61:1444-1461, 1983. Story DA, Morimatsu H, Bellomo R: Strong ions, weak acids and base excess: A simplified Fencl-Stewart approach to clinical acid-base disorders. Br J Anaesth 92:54-60, 2004.

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COEXISTING DISEASE AND ALTERED STATES

Adrenal Insufficiency Jonathan T. Ketzler and Douglas B. Coursin

105

Case Synopsis A 68-year-old, 5-foot 10-inch tall, 100-kg man develops refractory hypotension toward the end of a laparotomy to remove the left colon because of recurrent diverticulitis and suspected peridiverticular abscess. The patient remains intubated at the end of the procedure and is taken to the intensive care unit (ICU), where a pulmonary artery catheter is placed. The pulmonary artery occlusion pressure is 6 mm Hg, the systemic vascular resistance is 475 dynes/cm5, cardiac output is 10 L/minute and cardiac index is 6 L/minute/m2. The patient is being mechanically ventilated; he has a heart rate of 128 beats per minute in sinus rhythm and blood pressure of 88/42 mm Hg on norepinephrine at 0.1 μg/kg per minute and dobutamine at 5 μg/kg per minute. The patient’s medical history is remarkable for hypertension and type 2 diabetes chronically treated with lisinopril and metformin (Glucophage), respectively. Both were withheld on the day of surgery. Shortly after his admission to the ICU, a diagnostic test is performed and a new medication is added to the therapeutic regimen. After several hours, the patient is hemodynamically stable, and vasopressors have been discontinued.

PROBLEM ANALYSIS Definition Adrenal insufficiency (AI) is a relatively rare but potentially life-threatening condition that can be quiescent until unmasked by medical stressors such as sepsis, traumatic insults, or surgical procedures. Sir Thomas Addison described primary AI in 1855. Approximately a century later Harvey Cushing developed the concept of secondary AI. Causes for primary and secondary AI are listed in Table 105-1. The hypothalamic-pituitary-adrenocortical (HPA) axis (Fig. 105-1) regulates the amount of cortisol released by the adrenals. The cycle begins with the release of corticotropinreleasing factor from the hypothalamus, which stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary. ACTH then stimulates the release of cortisol from the adrenal cortex at a rate of about 20 mg/day. Cortisol (or a synthetic analogue) acts on the hypothalamus to inhibit the release of corticotropin-releasing factor and on the anterior pituitary to inhibit the release of ACTH. The associated diurnal variation in cortisol release peaks in the morning and midafternoon and then tapers off to a nadir in the evening. Although normal adults secrete about 5 to 10 mg/m2 of cortisol (or hydrocortisone) each day, during periods of acute stress the adrenal cortex can secrete as much as 100 mg/m2 per 24 hours. Primary adrenal failure is rare and may be caused by trauma, hemorrhage, infection, or infiltrative disease. Secondary adrenal failure may be brought about by adrenal atrophy due to acute or chronic glucocorticoid therapy. Patients with adrenal atrophy may show no symptoms of AI. 442

However, when subjected to the stress of even modest surgery or acute illness, these patients may develop life-threatening symptoms of AI. Along with the classification of AI as a primary or secondary process, there is now recognition of absolute or relative AI. Classic Addison’s disease due to autoimmune destruction of the adrenals is an example of primary, absolute AI. In contrast, the normal stress-induced increase in cortisol production may be blunted during life-threatening illnesses (e.g., sepsis) in some patients owing to relative AI. Alternatively, there may be down-regulation of cortisol binding and adrenergic receptors despite the normal stress-induced increase in steroid genesis, another explanation for relative AI. It is still uncertain whether etomidate blunts normal adrenal steroid genesis (see Table 105-1) to cause relative AI in critically ill patients. Finally, as illustrated in the case synopsis, relative AI may underlie life-threatening hemodynamic instability. However, if it is recognized as such and treated with stress doses of glucocorticoids, this process may be reversed.

Recognition The presentation of acute AI varies from a gradual onset over many days in a patient who is not stressed to a sudden fall in blood pressure associated with major stress such as an operation, trauma, or infection. Hypotension associated with AI can be severe and refractory to treatment. Chronic AI can be insidious and nonspecific in onset and remain undiagnosed for months. The prevalence of signs and symptoms associated with AI are detailed in Table 105-2. The most specific sign of primary AI is hyperpigmentation of the skin and mucosal surfaces caused by the high levels of corticotropin resulting from decreased cortisol feedback.

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Table 105–1

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Adrenal Insufficiency

Causes of Adrenal Insufficiency

443

HYPOTHALAMUS

Primary Adrenal Insufficiency

Secondary Adrenal Insufficiency Exogenous steroid administration Pituitary or hypothalamic diseases Infiltrative tumor (adenoma) Sarcoid Hemorrhage Autoimmune Isolated ACTH deficiency Surgical Pituitary surgery Removal of a functioning adrenal adenoma *Still unproven and therefore speculative. ACTH, adrenocorticotropic hormone.

Because primary AI (Addison’s disease) develops from failure of the adrenal gland itself, there is evidence of both glucocorticoid and mineralocorticoid deficiencies. Because secondary AI is an interruption of the pituitary-hypophysial axis that stimulates the adrenal glands to secrete cortisol, but spares the gland itself, it presents as pure glucocorticoid deficiency. In this case, the patient may also have hyponatremia;

inhibition Corticotropin-releasing factor (CRF)

ANTERIOR PITUITARY inhibition Adrenocorticotropin (ACTH)

ADRENAL CORTEX

Cortisol Figure 105–1

■

Hypothalamic-pituitary-adrenocortical axis.

this is not related to sodium excretion but rather to water intoxication secondary to an elevated level of antidiuretic hormone (ADH), as well as a primary defect in free water excretion related to glucocorticoid deficiency. Hypotension can be a common finding in both chronic and acute AI. Hypotension associated with acute AI has been reported as high-output circulatory failure with hallmarks of elevated cardiac output and index, normal pulmonary artery occlusion pressure, and decreased systemic vascular resistance. The pathogenesis of such hypotension is unknown but may include a combination of three possible mechanisms: (1) impairment of the direct effect of glucocorticoids on vascular smooth muscle, (2) loss of the “permissive” glucocorticoid effect on catecholamine synthesis and action, and (3) a decrease in the effects of glucocorticoids on vasoactive peptides. Dehydration can also be a factor in the hypotension associated with acute and chronic AI.

Table 105–2

■

Prevalence of Signs and Symptoms of Chronic Adrenal Insufficiency

Signs and Symptoms Weakness and fatigue Weight loss Hyperpigmentation Hypertension Hyponatremia Hyperkalemia Gastrointestinal symptoms Postural dizziness Adrenal calcification Hypercalcemia Muscle and joint pain Vitiligo

Prevalence (%) 74-100 56-100 92-96 59-88 88-96 52-64 56 12 9-33 6-41 6 4

Data from De Rosa G, Corsello SM, Cecchin L, et al: Clinical study of Addison’s disease. Exp Clin Endocrinol 90:232-242, 1987.

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Autoimmune Polyglandular autoimmune syndrome types I and II Infectious Tuberculosis Histoplasmosis Blastomycosis Coccidiomycosis Cryptococcosis Human immunodeficiency virus Cytomegalovirus Mycobacterium avium-intracellulare Cryptococcus Toxoplasmosis Kaposi’s sarcoma Fibrosis Infarction Adrenal hemorrhage Waterhouse-Friderichsen syndrome Lupus anticoagulant Antiphospholipid antibodies Immune thrombocytopenic purpura Heparin-induced Thrombocytopenia Anticoagulants Metastatic disease Lung Gastric Breast Malignant melanoma Lymphoma Drugs Decreased steroid synthesis Metyrapone Aminoglutethimide Mitotane Etomidate* Ketoconazole Increased steroid catabolism Rifampin Dilantin Phenobarbital Familial Familial glucocorticoid deficiency Adrenoleukodystrophy Adrenomyeloneuropathy

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Risk Assessment Using clinical indicators, there is no way to predict consistently which patients are at risk for developing AI during the stress of a surgical procedure or severe illness. Patients with certain comorbid diseases such as asthma, inflammatory bowel disease, collagen vascular disease, and rheumatoid arthritis may have received corticosteroids within 1 year, and the HPA axis can be suppressed by a relatively modest dose of exogenous steroids administered for as short a period as 7 to 10 days. Except for low-dose (prednisone ≤5 to 7.5 mg/day) and alternate-day regimens, chronic administration of corticosteroids suppresses the HPA axis, and recovery of its function can take up to 12 months. Normalization of pituitary function comes first; adrenocortical function returns more gradually. The reported incidence of perioperative AI is between 0.01% and 0.7%. A report by Rivers and colleagues suggested that older patients may have a greater risk of relative AI. The incidence during septic shock also appears to be significant, and steroid replacement therapy has been reported to significantly improve outcome in a selected subpopulation of such patients. Even though there are ample case reports of hypotension and even death secondary to AI, there are also many reports of glucocorticoid-treated patients undergoing major surgery without any perioperative glucocorticoid coverage. Most of these patients had uneventful perioperative courses, probably because they had normal perioperative biochemical indices of HPA function. This suggests that a historical assessment of glucocorticoid administration alone is unreliable. Endocrine evaluation is necessary in patients with suspected adrenal failure. A random screening cortisol level less than 25 μg/dL is abnormal when measured during the stress of an acute illness. A higher level does not preclude a subsequent abnormal cosyntropin stimulation test. A low cortisol level (<25 μg/dL) during a stressful illness or following stressful surgery mandates further evaluation. Major trauma and surgical stress usually result in a two- to threefold increase in plasma cortisol levels, with levels returning to normal 4 to 5 days after the stress. Levels may remain increased if there are complications. The cosyntropin stimulation test is still the best test for evaluating adrenal function in critically ill patients. After injection of 250 μg of cosyntropin, cortisol levels are compared with baseline levels at 30 and 60 minutes. The exact interpretation of test results remains controversial, but the best outcomes in septic patients occur in those with baseline values greater than 36 μg/dL and with at least a 9 μg/dL difference between baseline and peak values. Finally, if life-threatening AI is strongly suspected, treatment need not be delayed for diagnostic testing. Dexamethasone provides glucocorticoid coverage without interfering with cosyntropin studies.

During such times of stress, the patient is unable to secrete adequate amounts of cortisol to maintain hemodynamic stability.

MANAGEMENT Because AI can progress rapidly, early recognition and intervention are essential to improve outcome. Adrenal crisis is a medical emergency, and treatment cannot be delayed for extensive diagnostic studies. Therapy is directed toward rapidly increasing the circulating levels of cortisol. Without such treatment, even symptomatic treatment for volume depletion and electrolyte imbalance is inadequate. If AI is suspected, baseline plasma cortisol levels can be obtained just before treatment. Serum electrolytes, complete blood count, glucose, blood urea nitrogen, and creatinine are analyzed to assess for sodium depletion, potassium retention, and hypoglycemia. During adrenal crisis, patients can lose up to 20% of their circulating intravascular blood volume. This can result in hypovolemic shock and tissue hypoperfussion, both of which can lead to lactic acidemia. Therefore, rapid infusion of intravenous fluid is started to correct dehydration and hypovolemia. Normal saline is the initial fluid of choice. Subsequent treatment of electrolyte abnormalities, volume deficits, and hypoglycemia can be guided by laboratory measurements and the patient’s response to treatment. If a patient is known to have AI, replacement therapy should be individualized, depending on the degree of surgical or medical stress. For patients at high risk who undergo major procedures or have life-threatening injuries or illnesses, hydrocortisone 100 mg can be given, with additional intravenous doses of 50 to 100 mg every 6 to 8 hours (see also Chapter 34). Such doses can usually be rapidly tapered as the patient’s clinical condition improves. If the patient has no known history of AI, dexamethasone 4 to 10 mg can be given as an intravenous bolus. Dexamethasone does not interfere with the measurement of serum cortisol levels, so diagnostic tests can still be performed. However, because dexamethasone has no aldosterone activity, fludrocortisone, a mineralocorticoid, may also be needed. Patients usually respond quickly to initial therapies, and improvement is usually seen within several hours. Adrenal dysfunction has been shown to be present in as many as 70% of patients with septic shock, and the outcome can be significantly improved with replacement therapy in 20% of such patients. Finally, because 40% to 65% of critically ill patients have high plasma renin activity, previous recommendations did not include the administration of a mineralocorticoid. Based on more recent data, some experts now advise the addition of fludrocortisone 50 μg/day or greater by mouth in patients with sepsis-induced relative AI.

Implications

PREVENTION

An acute adrenal crisis can occur spontaneously or in response to significant emotional or physiologic stress. Stressors may include extreme psychological stress, trauma, withdrawal from alcohol or opioids, infection, general anesthesia, or surgery.

There are many ways to approach the administration of steroids in stressed patients with likely adrenal suppression. Some studies suggest tailoring the dose of hydrocortisone to the magnitude of the stress. Others advocate testing the HPA

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axis in patients at risk for AI. This is done using the cosyntropin stimulation test, which is easy and safe. However, there is controversy over how to interpret the test and even over what dose of cosyntropin to use. Some advocate the use of a more physiologic dose (e.g., 1 μg) instead of the currently recommended 250 μg for stimulation. Because the risk of steroids is so small in most stressed patients, most authorities suggest the use of stress doses in any patient at risk for AI. Because cortisol production under extreme stress is as much as 300 mg/day, hydrocortisone can be administered in 100-mg intravenous doses every 8 hours for 2 days or as a continuous infusion of 300 mg/day for 2 days (see also Chapter 34). In the absence of continued stress, these doses can be tapered to 50 mg every 8 hours for 1 to 2 days and then stopped, or continued at 25 mg every 8 hours for 1 to 2 days and then stopped. How steroids are tapered must be determined on a case-by-case basis, depending on the amount and duration of stress in patients with likely adrenal suppression. Finally, some have reported better outcomes with weight-related dosing for the treatment of chronic AI.

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Coursin DB, Wood KE: Corticosteroid supplementation in adrenal insufficiency. JAMA 287:236-240, 2002. Eichacker PQ, Parent C, Kalil A, et al: Risk and the efficacy of anti-inflammatory agents: Retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med 9:1197-1205, 2002. Goldberg PA, Inzucchi SE: Critical issues in endocrinology. Clin Chest Med 24:583-606, 2003. Holmes CL, Walley KK: The evaluation and management of shock. Clin Chest Med 24:775-789, 2003. Mah PM, Jenkins RC, Rostami-Hodjegan A: Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency. Clin Endocrinol 61:367-375, 2004. Marik PE, Zaloga GP: Adrenal insufficiency in the critically ill: A new look at an old problem. Chest 122:1784-1796, 2002. Minneci PC, Deans KJ, Banks SM, et al: Meta-analysis: The effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med 1:47-56, 2004. O’Brien JM Jr, Abraham E: New approaches to the treatment of sepsis. Clin Chest Med 24:521-548, 2003. Oelkers W: Adrenal insufficiency. N Engl J Med 335:1206-1211, 1996. Rivers EP, Gaspari M, Saad GA, et al: Adrenal insufficiency in high-risk surgical ICU patients. Chest 119:889-896, 2001. Salem M, Tainsh RE, Bromberg J, et al: Perioperative glucocorticoid coverage: A reassessment 42 years after emergence of a problem. Ann Surg 219:416-425, 1994.

Further Reading Connery LE, Coursin DB: Assessment and therapy of selected endocrine disorders. Anesthesiol Clin North Am 22:93-123, 2004. Cook DM: Safe use of glucocorticoids: How to monitor patients taking these potent agents. Postgrad Med 93:145-154, 1992.

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HIV Infection and AIDS Michael S. Avidan and Nicola Jones

106

Case Synopsis A 34-year-old woman with known human immunodeficiency virus (HIV) infection and a recent diagnosis of acquired immunodeficiency syndrome (AIDS) with Pneumocystis jirovecii (previously carinii) pneumonia presents for elective cesarean section at 38 weeks’ gestation. She has been taking antiretroviral therapy throughout her pregnancy. She is very short of breath and has a dry cough, and her peripheral arterial oxygen saturation is 84% on room air. She weighs 62 kg, and her height is 164 cm. Her tympanic temperature is 37.2°C. She is alert and oriented, with no localizing neurologic signs. Her blood pressure is 90/50 mm Hg; her heart rate is 115 beats per minute, with no respiratory variation; and her respiratory rate is 26 breaths per minute. Recent laboratory tests show a CD4 T-cell count of 186 cells/mL and an HIV viral load of 240,000 copies/mL.

PROBLEM ANALYSIS Definition AIDS was first described in 1981 in the United States. HIV and the AIDS pandemic pose a major threat to global health. It is estimated that more than 40 million people worldwide are infected with HIV, which is thought to have caused more than 20 million deaths to date. The infection continues to spread apace, with the most rapid increases observed in southern and central Africa and in South Asia. The predominant mode of HIV transmission is heterosexual sex, and women represent a high proportion of new infections, including in developed countries. Increasing numbers of patients presenting for surgery are HIV-seropositive or have AIDS. Anesthesiologists should be familiar with this disease and be aware of the impact of HIV on anesthesia. An understanding of the pathogenesis of HIV and an awareness of the possible drug interactions occurring with HIV therapy may help guide the choice of anesthetic technique. The possibility of nosocomial transmission of HIV highlights the need for anesthesiologists to enforce rigorous infection control policies to protect themselves, other health care workers, and their patients. Antiretroviral therapy decreases the rate of disease progression, but there is no cure available, nor is a vaccine likely in the foreseeable future.

Recognition HIV belongs to the family Retroviridae and the genus Lentivirus. Members of this genus are cytopathic (cell damaging), have long latent periods, and run a chronic course. When cases of AIDS first appeared, its pathogenesis was frustratingly elusive because the disease does not appear immediately on infection with HIV. There is a variable period during which the patient remains healthy but is viremic. Acute seroconversion illness occurs with a high viral load soon after infection. After several months, there is a gradual decrease in the viremia as the immune response occurs. The viral load is often at a steady state as the rate of viral 446

production equals the rate of destruction. Up to 98% of T-helper lymphocytes (CD4 T cells) are located in lymph nodes, which are the major site of viral replication and T-cell destruction. There is a gradual involution of the lymph nodes, with a concomitant decrease in CD4 T cells and an increase in viral load as the inexorable onset of AIDS occurs (Fig. 106-1). Before 1995, prospects for the treatment of HIV were gloomy. Subsequently, the situation changed dramatically as a result of four factors: 1. Improved understanding of the pathogenesis of HIV infection 2. Availability of surrogate markers of immune function and plasma viral burden 3. Development of new and more powerful drugs, such as the protease inhibitors and non-nucleoside reverse transcriptase inhibitors 4. Completion of several large clinical end-point trials that conclusively demonstrated that antiretroviral combinations significantly delayed the progression of HIV disease to AIDS and improved survival

Risk Assessment HIV is a virus found mainly in CD4 T cells, macrophages, and monocytes, and it requires a large infecting dose for transmission. HIV has been isolated from blood, cerebrospinal fluid, tears, saliva, semen, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, amniotic fluid, vaginal secretions, and breast milk. Modes of transmission are through oral, rectal, and vaginal sexual intercourse, blood product transfusion, shared intravenous needles, occupational acquisition, and vertical transmission from mother to child. The screening of blood products for HIV antibodies has reduced the risk of transfusion-associated infection (<1 per 750,000 donor units); the exact risk is difficult to quantify, however, and it may increase as the HIV infection rate increases in the general population. Antibody screening fails to detect the virus in the so-called window period before antibody formation, which lasts about 3 months. Nuclear amplification is an alternative technique that may allow for early virus detection.

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HIV Infection and AIDS

Infection

447

Death Seroconversion Symptomless

Symptomatic

AIDS

10,000,000 1,000,000

1000

CD4 T cell count (cells/mL)

100,000 10,000

500

1000

Plasma viral load (copies/mL)

100 10 copies/mL

CD4 T cells/mL

Viral Load 4-8 weeks

~10 years (off HAART) to decades (on HAART)

2-3 Years

Figure 106–1 ■ Progression to acquired immunodeficiency syndrome (AIDS) of those infected with human immunodeficiency virus (HIV). Note that highly active antiretroviral therapy (HAART) greatly delays development of clinical AIDS.

Implications UNIVERSAL PRECAUTIONS Universal precautions for the prevention of transmission of blood-borne viruses were recommended in 1987 by the Centers for Disease Control. These precautions advise that every patient be regarded as potentially infected with a blood-borne virus.

Following accidental exposure to a high-risk body fluid, such as a (hollow) needle-stick injury, postexposure prophylaxis is recommended for health care workers. This should commence as soon as possible after the injury, ideally within 1 to 2 hours, but it can be considered up to 1 to 2 weeks after the injury. Very-high-risk exposures may be treated beyond this time with a view to modifying rather than preventing infection. A recommended postexposure prophylaxis regimen of 4 weeks’ duration is the following: ● ● ●

Zidovudine 300 mg every 12 hours Lamivudine 150 mg every 12 hours Indinavir 800 mg every 8 hours

However, the high rate of toxicity and noncompliance may necessitate other regimens.

MANAGEMENT Antiretroviral Drug Therapy Three major classes of antiretroviral agents are currently in use (Table 106-1): 1. Nucleoside analogue reverse transcriptase inhibitors (NRTIs) bind to the evolving viral DNA and prevent the completion of reverse transcription. 2. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) interfere with the transcriptional activity of reverse

Table 106-1 lists examples of these major classes of antiretroviral agents currently in use, as well as routes of administration and common side effects. A typical antiretroviral regimen consists of three agents: a PI or NNRTI combined with two NRTIs. Such combined therapy has been termed highly active antiretroviral therapy (HAART). In some circumstances, combinations of four or more drugs are used. The aim of therapy in treatment-naïve patients is to achieve an undetectable viral load by 24 weeks of therapy and to improve and extend the length and quality of life. However, there is a downside to HAART. The AIDS pandemic, one of the most devastating to ever affect humankind, has now entered its third decade, and there is still no cure in sight. The initial enthusiasm that greeted HAART has been tempered by the recent discovery of multidrug-resistant viral strains. Also, there is the issue of important adverse side effects. SIDE EFFECTS

OF

HAART REGIMENS

Numerous side effects and drug interactions complicate HAART regimens and decrease compliance. Patients may experience drug hypersensitivity reactions, causing fever, hypotension, and acute interstitial pneumonitis with respiratory failure. Concurrent use of zidovudine and corticosteroids may result in severe myopathy and respiratory muscle dysfunction. In addition, reports have documented several cases of respiratory failure related to HAART initiation and immune reconstitution resulting in a paradoxical worsening of Pneumocystis pneumonia; distinguishing this event from a superimposed respiratory infection is often clinically challenging. Of particular importance to anesthesiologists is that patients receiving HAART are subject to

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

POSTEXPOSURE PROPHYLAXIS

transcriptase by binding to it directly, downstream of the active catalytic site. 3. Protease inhibitors (PIs) inhibit the HIV protease, which cleaves the polyprotein precursors that ultimately make up the core proteins of the mature virions. PIs bind specifically to the active cleavage site.

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Major Classes of Antiretroviral Agents Currently in Use

Drug Name

Dosing

Common Side Effects

Nucleoside Analogue Reverse Transcriptase Inhibitors Zidovudine (AZT/ZDV) Didanosine (DDI) Zalcitabine (DDC) Stavudine (D4T) Lamivudine (3TC) Abacavir

Oral/IV Oral Oral Oral Oral Oral

Bone marrow suppression (neutropenia), GI upset, headache Peripheral neuropathy, pancreatitis, diarrhea Peripheral neuropathy, pancreatitis, oral ulcers Peripheral neuropathy Anemia, GI upset GI upset, potentially fatal acute hypersensitivity

Non-nucleoside Analogue Reverse Transcriptase Inhibitors Nevirapine Delavirdine Efavirenz

Oral Oral Oral

Rash, hepatitis, increased liver enzymes Rash, increased liver enzymes Dizziness, rash, dysphoria, increased liver enzymes

Ritonavir

Oral Oral + ≥1.5 L H2O/24 hr Oral

Nelfinavir

Oral

Diarrhea, raised transaminases, hyperlipidemia, cytochrome P-450 inhibition Nephrolithiasis, hyperbilirubinemia, hyperlipidemia, lipodystrophy, cytochrome P-450 inhibition GI upset, circumoral paresthesia, hyperlipidemia, lipodystrophy, cytochrome P-450 inhibition Diarrhea, hyperlipidemia, lipodystrophy, cytochrome P-450 inhibition

Protease Inhibitors Saquinavir Indinavir

GI, gastrointestinal.

long-term metabolic complications, including lipid abnormalities and glucose intolerance, which may result in the development of diabetes, coronary artery disease, and cerebrovascular disease. A syndrome resembling acute gram-negative sepsis has been reported in patients taking NRTIs. Lactic acidosis and hepatic steatosis are usually found. Patients develop high fever and can rapidly become confused and comatose. Nucleoside analogue drugs may cause inhibition of DNA polymerase gamma, the sole DNA polymerase required for the replication of mitochondrial DNA. This in turn causes mitochondrial dysfunction and impaired aerobic cellular respiration. Inhibition of oxidative phosphorylation and derangement of respiratory chain enzymes have been implicated. Riboflavin has been suggested as a potential treatment. Unfortunately, most patients die despite intensive care unit (ICU) support. HAART DRUG INTERACTIONS PIs, particularly ritonavir, are inhibitors of cytochrome P450 (see Table 106-1). In contrast, drugs such as nevirapine are inducers of hepatic microsomal enzymes. These variable effects on liver enzymes complicate the dosing of drugs, including anesthetic and analgesic agents, many of which undergo hepatic metabolism.

Respiratory Complications Pneumocystis jirovecii pneumonia (PJP) does not usually occur until the CD4 T-cell count is less than 200 cells/mL. Breathlessness, night sweats, and weight loss are frequent complaints. The chest examination of may be unremarkable, and the chest radiograph is normal in many instances. Complications include respiratory failure, pneumothorax. and chronic pulmonary disease. The chest radiograph typically shows bilateral “groundglass” shadowing. Pneumothoraces may be evident, and there

may be multiple pneumatoceles. High-resolution computed tomography scanning reveals a ground-glass appearance even when the radiograph is normal. Lung function tests show reduced lung volumes with decreased compliance and diminished diffusing capacity for carbon monoxide. Oxygen saturation measurements during exercise may be more helpful than lung function tests. If PJP is suspected, fiberoptic bronchoscopy and bronchoalveolar lavage should be performed. The advantage of an early diagnosis compensates for the high frequency of negative examinations. Combined high-dose sulfamethoxazole (100 mg/kg per day) with trimethoprim (20 mg/kg per day) remains the treatment of choice. Systemic steroid therapy, such as prednisolone 1 mg/kg per day, is advised for patients with low oxygen saturation values. Respiratory support and supplementary oxygen are invariably required. Use of continuous positive airway pressure can, in some instances, obviate the need for positive-pressure mechanical ventilation. The prognosis for patients who require mechanical ventilation despite adjunct corticosteroid therapy is poor. Further, the use of positive end-expiratory pressure may cause pneumothorax. Cavitary lung disease can be due to a pyogenic bacterial lung abscess, pulmonary tuberculosis (TB), fungal infection, and Nocardia species. Kaposi’s sarcoma (KS) and lymphoma can also affect the lung. Adenopathy can lead to tracheobronchial obstruction or compression of the great vessels. Endobronchial KS may cause massive hemoptysis. HIV also directly affects the lungs, causing a destructive pulmonary syndrome similar to emphysema. Disseminated TB is a potential cause of severe respiratory failure, and respiratory secretions should be examined routinely for acid-fast bacilli in AIDS patients with pulmonary infiltrates. Bacterial pneumonia (Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa) can also cause severe acute respiratory failure. Empirical antibacterial treatment to cover

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these microorganisms should be given when a bacterial agent is suspected. Outbreaks of multidrug-resistant TB have occurred in patients with HIV infection and in health care workers. Airborne transmission by inhalation of infective aerosols justifies appropriate isolation measures to protect medical staff and other patients from TB transmission.

Central Nervous System Complications Neurologic disease ranging from AIDS dementia to infectious or neoplastic involvement may complicate AIDS. Three entities constitute mostly focal cerebral processes: cerebral toxoplasmosis, primary central nervous system (CNS) lymphoma, and progressive multifocal leukoencephalopathy. Focal lesions may increase intracerebral pressure, thereby precluding neuraxial anesthesia. Spinal cord involvement, peripheral neuropathy, and myopathy may occur with cytomegalovirus or HIV infection itself. Giving succinylcholine may be hazardous in this setting. Cryptococcus neoformans, HIV, and TB can cause meningitis. HIV infection is associated with autonomic neuropathy, and this can manifest as hemodynamic instability during anesthesia or in the ICU.

Cardiovascular Disease

HIV Infection and AIDS

449

Obstetric Patients HIV and AIDS are increasing in women of childbearing age. In one study, zidovudine monotherapy was shown to dramatically reduce the incidence of vertical transmission of HIV from 25.5% to 8.3%. However, zidovudine monotherapy has limited long-term benefits because HIV resistance develops rapidly. Therefore, in pregnancy, combination therapy is now believed to be preferable. There are limited data on the use of PIs in pregnancy. A recent meta-analysis strongly suggested that cesarean section independently reduces the incidence of vertical transmission. Combined antiretroviral therapy and elective cesarean section reduce the rate of vertical transmission to 2%. However, cesarean section is a major surgical intervention with wellknown complications (see Section 9). There is a higher incidence of morbidity following cesarean compared with vaginal delivery, even in healthy women, including more prolonged and intense pain, longer duration of bed rest, increased blood loss, and more frequent venous thrombosis and wound infection. Many practitioners today do not recommend elective cesarean section to HIV-infected women who are compliant with antiretroviral therapy and have undetectable HIV viral loads. Unfortunately, HIV-positive women with low CD4 lymphocyte counts, whose infants would theoretically benefit most from cesarean delivery, are also those who are most likely to experience significant postoperative complications. In a study of HIV-seropositive parturients receiving regional anesthesia, there were no infectious or neurologic complications related to the anesthetic or obstetric courses. In the immediate postpartum period, immune function measurements remained essentially unchanged, as did the severity of the disease. There have been concerns that epidural and lumbar puncture in HIV-seropositive patients may allow entry of the virus into the CNS. However, the natural history of HIV includes CNS involvement early in the clinical course, and expression of CNS infection varies widely. Finally, epidural blood patches for the treatment of post–dural puncture headache have been reported as safe and effective in HIV-seropositive patients. Nevertheless, given the very small theoretical risk of introducing virus to the CNS, other analgesic strategies should be tried first.

Surgery and Anesthesia HIV infection does not increase the risk for postprocedural complications, including death, up to 30 days after the procedure. Thus, surgical intervention should not be limited because of HIV status and concern for subsequent complications. However, during anesthesia, tachycardia is more frequently seen in HIV-seropositive patients. Also, high fever, anemia, and tachycardia are more frequent postoperatively. Several studies indicate that general anesthesia and opiates may impair immune function. Although this is likely of little clinical importance in healthy individuals, the implications for HIV-infected patients are not known. Immunosuppression due to general anesthesia occurs within 15 minutes of induction and may persist for as long as 3 to 11 days. Postoperative immunosuppression may last longer in inherently immunosuppressed patients and may predispose to the development of postoperative infections or facilitate tumor growth or metastasis.

Intensive Care Unit Complications APACHE II scoring significantly underestimates mortality risk for HIV-seropositive patients admitted to a medical ICU with a total lymphocyte count less than 200 cells/mL. This is particularly true for those admitted with pneumonia or sepsis. There is a diverse range of indications for critical care in patients with HIV infection. Historically, respiratory failure due to PCP has been the most common reason for admission to an ICU, accounting for 34% of cases. Mechanical ventilation for PCP and other pulmonary disorders is associated with a mortality rate greater than 50%. In contrast, ICU admission and mechanical ventilation for nonpulmonary disorders are associated with a mortality rate less than 25%. In patients with septic shock, HIV infection is an independent predictor of poor outcome. In the era of HAART, fewer patients with HIV infection are admitted to ICUs with AIDS-defining illnesses such as PJP. In fact, many

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Cardiac involvement in the course of HIV is common but is often clinically silent. Up to 50% of patients with HIV have abnormal echocardiographic findings at some point in their disease. Approximately 25% have pericardial effusions. Myocarditis is more common in advanced HIV and may be caused by toxoplasmosis, disseminated cryptococci, coxsackievirus B, cytomegalovirus, lymphoma, Aspergillus species, and HIV itself. Ventricular dilatation and cardiac dysfunction may result. With PIs, glucose intolerance and disorders of lipid metabolism are common. Aggressive generalized vascular disease, including cardiac and cerebral, may occur as a complication of antiretroviral therapy. If patients exhibit unexplained hypotension, adrenal insufficiency should be considered, because this may occur with advanced HIV infection.

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patients are now admitted with unrelated critical illnesses and are coincidentally found to be infected with HIV. Nonetheless, initiation of HAART in patients with PCP is known to improve outcome. However, this benefit must be weighed against problems associated with immune reconstitution, which may occur in septic patients when HAART is initiated.

PREVENTION There is little specific information concerning the overall risk of anesthesia and surgery in HIV-seropositive patients. The American Society of Anesthesiologists’ physical status assessment and the inherent surgical risk probably provide a measure of global risk. This information, when combined with the Centers for Disease Control and Prevention stage of HIV infection, the degree of immunosuppression, and the presence and severity of opportunistic infection or neoplasm, may offer the best predictor of global preoperative risk for HIV-seropositive patients. With regard to choice of anesthetic technique to minimize complications, regional anesthesia is the technique of choice, except in certain cases of neuropathies. Finally, anesthesiologists and intensivists have contact with a broad range of patients, many of whom may be HIVseropositive. Therefore, rigorous adherence to infection control practices is imperative. Further, all clinicians should

keep abreast of current knowledge about HIV therapy to ensure that their patients are receiving optimal treatment.

Further Reading Afessa B, Green B: Bacterial pneumonia in hospitalized patients with HIV infection: The Pulmonary Complications, ICU Support, and Prognostic Factors of Hospitalized Patients with HIV (PIP) Study. Chest 117:1017-1022, 2000. Avidan MS, Groves P, Blott M, et al: Low complication rate associated with cesarean section under spinal anesthesia for HIV-1-infected women on antiretroviral therapy. Anesthesiology 97:320-324, 2002. Avidan MS, Jones N, Pozniak AL: The implications of HIV for the anaesthetist and the intensivist. Anaesthesia. 55:344-354, 2000. Casalino E, Mendoza-Sassi G, Wolff M, et al: Predictors of short- and longterm survival in HIV-infected patients admitted to the ICU. Chest 113:421-429, 1998. Casalino E, Wolff M, Ravaud P, et al: Impact of HAART advent on admission patterns and survival in HIV-infected patients admitted to an intensive care unit. AIDS 18:1429-1433, 2004. Evron S, Glezerman M, Harow E, et al: Human immunodeficiency virus: Anesthetic and obstetric considerations. Anesth Analg 98:503-511, 2004. Hughes SC, Dailey PA, Landers D, et al: Parturients infected with human immunodeficiency virus and regional anesthesia: Clinical and immunologic response. Anesthesiology 82:32-37, 1995. Morris A, Wachter RM, Luce J, et al: Improved survival with highly active antiretroviral therapy in HIV-infected patients with severe Pneumocystis carinii pneumonia. AIDS 17:73-80, 2003. Vincent B, Timsit JF, Auburtin M, et al: Characteristics and outcomes of HIV-infected patients in the ICU: impact of the highly active antiretroviral treatment era. Intensive Care Med 2004;30:859-866.

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Hypothyroidism: Myxedema Coma Pamela R. Roberts and Richard C. Prielipp Case Synopsis A 59-year-old man with history of a previous myocardial infarction with preserved left ventricular function underwent three-vessel coronary artery bypass grafting. He remained intubated and was taken to the intensive care unit (ICU) for postoperative care. On arrival in the ICU, he was receiving continuous infusions of propofol, phenylephrine, and fenoldopam. After several hours, he was awake and following commands and showed evidence of good perfusion and cardiac function, but he had a mild respiratory acidosis (PaCO2 49 mm Hg). Subsequently he was extubated and had persistent respiratory acidosis over the next few hours. His vital signs were remarkable overnight for a temperature that remained below 36°C (measured via a pulmonary artery catheter), heart rate paced at 90 beats per minute, blood pressure 95/62 to 105/68 mm Hg, respiratory rate 10 to 18 breaths per minute, and cardiac index greater than 2.4 L/minute/m2. About 8 hours after extubation, his oxygenation, ventilation, cardiac index, and mental status deteriorated, and he was reintubated. A chest radiograph showed mild pulmonary edema. Thyroid function studies revealed very elevated thyrotropin and very low thyroxine levels; the cortisol level was appropriate for a stress response. Therapy with thyroid hormone was initiated, after which the patient improved; he was extubated the following day. Later discussions with the patient revealed a previous diagnosis of hypothyroidism and noncompliance with medical therapy.

Definition Hypothyroidism is thyroid gland hypoactivity with decreased synthesis and secretion of thyroxine (T4). Normal regulation and activity of thyroid hormone can be summarized as follows: ●

●

●

●

●

●

●

● ●

Thyrotropin-releasing hormone (TRH) is released from the hypothalamus. TRH stimulates the synthesis and release of thyrotropin (also called thyroid-stimulating hormone [TSH]) from the pituitary gland. Circulating TSH stimulates the thyroid gland to produce and secrete thyroid hormone (about 80% as T4 and about 20% as triiodothyronine [T3]). The remainder of T3 (the physiologically active form of thyroid hormone) is produced in extrathyroidal tissues (mainly the liver and kidneys) by monodeiodination of circulating T4. T3 and T4 circulate bound to serum proteins, but free T3 and T4 are metabolically active. T3 feeds back on the pituitary gland to inhibit the production of TSH. Some of the circulating T4 is metabolized to the inactive product “reverse T3.” Both T3 and reverse T3 are rapidly cleared from the serum. Thyroid hormone activity begins with the binding of T3 to receptors on cell nuclei, which is needed for normal cellular function.

Recognition HISTORY Patients may present with previously undiagnosed hypothyroidism or may have been noncompliant with thyroid hormone replacement therapy. They may manifest decreased mental acuity, hoarseness, somnolence, cold intolerance, dry skin, brittle hair, and weight gain. Myxedema is usually precipitated by a stressful event such as an acute infection, trauma, myocardial infarction, or surgery or following anesthesia. PHYSICAL EXAMINATION The following findings may be evident on physical examination: ● ● ●

● ● ● ● ●

Hypothermia (core temperature typically <35°C) Dry skin, with a thickened and doughy appearance Facial and generalized puffiness (periorbital edema, large tongue) Depressed mental status (lethargy, coma) Hypoventilation (slow respiratory rate, shallow breaths) Sinus bradycardia Hypotension Low-output cardiac failure and cardiomyopathy (possibly pericardial effusion with muffled heart sounds) 451

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

PROBLEM ANALYSIS

Myxedema or myxedema coma is a life-threatening complication of hypothyroidism characterized by a decreased level of consciousness or even coma.

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Disorders of muscle function (paralytic ileus, urinary retention, atonic bowel)

Thyroid hormone is essential for the normal metabolism of all cells, and deficiency presents with widespread symptoms. For example, thyroid hormone is required for the synthesis of many proteins (e.g., β-receptors), and deficiency contributes to a lack of responsiveness to vasoactive drugs. In myxedema, decreased circulating levels of thyroid hormones contribute to decreased mental responsiveness, bradycardia, and reduced stroke volume. This leads to low cardiac output and decreased cerebral perfusion. Hypothermia results from a decreased metabolic rate and an inability to shiver. Decreased plasma volume and intense peripheral vasoconstriction are common. Alveolar hypoventilation is secondary to (1) respiratory center depression (exacerbated by use of analgesics, sedatives, and anesthesia); (2) defective respiratory muscle function; and (3) occasionally, airway obstruction due to tongue enlargement. The actual mechanism whereby hypothyroidism deteriorates into severe illness and coma is poorly understood, but it most often occurs after a stressful event, as illustrated in the case synopsis. Regardless of the cause, the resulting syndrome consists of a severe hypometabolic state. The reported mortality rate for untreated myxedema coma is over 80%. However, with treatment, the mortality rate is decreased to less than 10%. Hypothyroidism occurs secondary to autoimmune thyroid disease (Hashimoto’s thyroiditis), previous chronic treatment with lithium or amiodarone, iodine excess or deficiency (extremely rare in the United States, but an important cause of goitrous hypothyroidism in many countries), radioactive thyroid ablation, surgical resection, and pituitary or hypothalamic disease. The last two can be secondary or tertiary causes of hypothyroidism. Occasionally a patient may have thyroid hormone resistance or congenital thyroid agenesis. The incidence of hypothyroidism is three times higher in females than in males, and elderly women seem to be most susceptible to myxedema coma.

Risk Assessment and Implications The diagnosis of myxedema is based on clinical suspicion, and confirmation relies on thyroid studies with the following results (Table 107-1): ● ● ●

Decreased T4 Decreased T3 Elevated TSH (but not in secondary or tertiary hypothyroidism)

Other routine studies include complete blood count, electrolytes, urinalysis, arterial blood gases, chest radiograph, electrocardiogram, and blood and urine cultures. Serum cortisol levels should be drawn initially to evaluate for concomitant adrenal insufficiency. Additional studies should evaluate for infection as indicated by the history and physical examination. Associated laboratory abnormalities that may be present include hyponatremia, hypoglycemia, hypercholesterolemia, and normochromic normocytic anemia. The chest radiograph may reveal signs of pleural or pericardial effusion or infection. The electrocardiogram may reveal many associated or potential abnormalities, including sinus bradycardia, small-voltage

Table 107–1

■

Thyroid Function Studies in Thyroid Disorders Disorder

Test

Hyperthyroid

Hypothyroid

TSH

Low

High

Total T4 Total T3 Reverse T3 Free T4 T3 resin uptake*

High High High High High

Low Low Low to normal Low Low

Euthyroid Sick Syndrome Low to slightly high Low to normal Low High Normal Normal to high

*Approximates serum hormone binding by thyroxine-binding globulin (normal range is 33-48%). T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone.

QRS complexes, prolonged Q-T intervals, isoelectric T-wave changes, or supraventricular tachycardia. Arterial blood gases may reveal hypoxemia, hypercarbia, and respiratory acidosis. Sepsis should be considered in the differential diagnosis. Other causes for depressed mental status, such as stroke, electrolyte disturbances (e.g., hyponatremia), hypoglycemia, or renal failure with uremia, should also be considered. Hypopituitarism causing both hypothyroidism and adrenal insufficiency should be ruled out. Finally, the differential diagnosis should include hypothermia and drug overdose with β-receptor or calcium channel antagonists, encephalitis, and hypothalamic strokes.

MANAGEMENT AND PREVENTION Do not wait for laboratory values to begin treatment if there is sufficient clinical suspicion of myxedema. Appropriate treatment includes the following: ●

Thyroid hormone replacement ● Intravenous (IV) administration is necessary owing to unreliable gastrointestinal absorption. ● The best therapeutic regimen remains controversial, and clinical trials are unlikely because the disease is so rare. We prefer a combination of T3 and T4: T3 20 μg IV bolus followed by 10 μg every 8 hours and T4 200 μg IV followed by 100 μg IV every 24 hours for 1 to 2 days, followed by T4 alone. ● If IV T is not immediately available, IV T (in the pre3 4 ceding dosage) can be given with oral T3 (25 μg every 12 hours) until the patient can be treated with oral T4 alone. ● Previously, T alone was frequently used (200 to 500 μg 4 IV bolus followed by 50 to 100 μg IV every 24 hours). ● Peripheral conversion of T to T requires the presence 4 3 of some T3 for enzyme activity. ● An advantage of IV T includes a more rapid onset of 3 action than T4; also, peripheral conversion of T4 is not required for activity. ● T is more arrhythmogenic than T , so careful monitor3 4 ing is essential.

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●

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453

of myxedema coma because of potential cardiac complications. In addition, definitive treatment may require diagnosis and treatment of the underlying cause (e.g., infection, stroke, myocardial infarction, narcotics, gastrointestinal bleeding). Mortality in myxedema coma may approach 80%, and improved survival depends on early, aggressive therapy. One retrospective study suggested that delaying surgery did not improve the outcome in patients with severe hypothyroidism. However, optimizing a patient’s chance for the best outcome may be achieved by preoperative therapy when the need for surgery is not urgent.

Further Reading Cone AM: Anaesthesia in a patient with untreated myxoedema coma. Anaesth Intensive Care 22:295-298, 1994. Hellman DE: The thyroid gland. Contemp Anesth Pract 3:109-145, 1980. James ML: Endocrine disease and anaesthesia: A review of anaesthetic management in pituitary, adrenal, and thyroid diseases. Anaesthesia 25:232-252, 1970. Marcaine JM: Anesthesia and hypothyroidism: A review of thyroxine physiology, pharmacology, and anesthetic implications. Anesth Analg 61:371-383, 1982. Myers L, Hays J: Myxedema coma. In Zaloga GP (ed): Critical Care Clinics—Endocrine Crises. Philadelphia, WB Saunders, 1991, pp 43-56. O’Connor CJ, March R, Tuman K: Severe myxedema after cardiopulmonary bypass. Anesth Analg 96:62-64, 2003. Rodriguez I, Fluiters E, Perez-Mendez LF, et al: Factors associated with mortality of patients with myxoedema coma: Prospective study in 11 cases treated in a single institution. J Endocrinol 180:347-350, 2004. Smallridge RC: Metabolic and anatomic thyroid emergencies: A review. Crit Care Med 20:276-291, 1992. Weinberg AD, Brennan MD, Gorman CA, et al: Outcome of anesthesia and surgery in hypothyroid patients. Arch Intern Med 143:893-897, 1983.

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Monitor T3 and T4 levels after 5 days, and adjust doses accordingly if the patient remains unconscious. General supportive measures ● Give IV fluids to restore intravascular volume. ● Use passive warming (active warming can cause peripheral vasodilatation and worsen shock). ● Mechanical ventilation may be required. ● Seizures can be treated with standard anticonvulsant drugs. ● Use sedatives judiciously. ● Hydrocortisone (100 mg IV every 8 hours) should be given until initial evaluation of hypothalamic-pituitaryadrenal axis function is performed; this therapy may be lifesaving in patients with secondary or tertiary hypothyroidism. Cardiovascular supportive measures ● After restoring intravascular volume, inotropic or vasopressor therapy may be required for cardiovascular support. ● Hypotension is poorly responsive to vasopressors until thyroid hormone replacement is initiated. ● Monitor for the presence of arrhythmias (the dosage of thyroid hormone replacement may have to be decreased). ● Hypothyroidism is associated with a high incidence of coronary artery disease, and patients should be monitored for evidence of myocardial ischemia, which is exacerbated by increased myocardial oxygen consumption during T3 and T4 treatment. Special considerations ● Euthyroid patients tolerate short-term administration of thyroid hormone well. ● Delay of treatment in a myxedematous patient can make the difference between survival and death. ● This treatment regimen should not be routinely instituted in hypothyroid patients without clinical evidence ●

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108

Hyperthyroidism: Thyroid Storm Richard C. Prielipp and Pamela R. Roberts Case Synopsis A 32-year-old woman undergoes general anesthesia with 1% isoflurane in a mixture of 60-40 nitrous oxide and oxygen for open fixation of a humeral fracture. Preoperative history is significant for anxiety and intolerance to heat. Physical examination is noteworthy for periorbital swelling; warm, moist skin with sweaty palms; and a midline lower neck mass consistent with an enlarged thyroid. Thirty minutes after induction, sinus tachycardia (128 beats per minute), arterial hypertension (190/100 mm Hg), and hyperpyrexia (core temperature 38.1°C despite a cool operating room environment) are noted. Increasing the depth of anesthesia with 2% isoflurane results in occasional ventricular premature beats. Muscle rigidity is absent.

PHYSICAL EXAMINATION FINDINGS

PROBLEM ANALYSIS Definition Normal regulation and activity of thyroid hormone are summarized in Chapter 107. The following definitions apply to the discussion of hyperthyroidism: ●

●

●

●

True hyperthyroidism is thyroid gland hyperactivity with increased synthesis and secretion of thyroid hormone. Thyrotoxicosis refers to the clinical and biochemical manifestations of excess thyroid hormone. It affects 2% of women and 0.2% of men in the general population. Thyrotoxic crisis or thyroid storm is a life-threatening complication of hyperthyroidism characterized by a severe, sudden exacerbation of thyrotoxicosis. Patients with uncontrolled hyperthyroidism presenting for surgical or trauma care are at considerable risk of developing thyrotoxicosis. Therefore, anesthesiologists should ensure that patients are euthyroid before proceeding with elective surgery. Thyrotoxicosis factitia refers to thyrotoxicosis without true hyperthyroidism (e.g., ingestion of thyroid hormone, ectopic thyroid hormone production) and is associated with decreased synthesis of thyroid hormone.

Findings on physical examination that support the diagnosis of hyperthyroidism include the following symptoms (in decreasing order of frequency): ●

● ● ●

● ●

Signs of hyperthyroidism include the following (in decreasing order of frequency): ●

●

● ● ● ● ●

●

Recognition, Risk Assessment, and Implications

Altered mental status (nervousness, agitation, anxiety, confusion, possible psychosis or even coma) Sweating, heat intolerance Weight loss, fatigue, muscle weakness Increased appetite, diarrhea, other gastrointestinal symptoms Prominent, dry eyes Leg swelling

●

Sinus tachycardia (virtually 100% incidence) and tachyarrhythmias Goiter—neck mass with potential airway compromise (Fig. 108-1) Warm, moist skin Muscle tremor Systolic hypertension; widened pulse pressure Enlarged thyroid with thyroid bruit Ophthalmic signs, including exophthalmos, lid lag, lid retraction, periorbital swelling, and conjunctival injection Pretibial edema Atrial fibrillation, classically in the elderly (about 10% incidence)

HISTORY Patients with undiagnosed hyperthyroidism often have a history of anxiety (occasionally progressing to psychosis or even coma), significant recent weight loss, heat intolerance, gastrointestinal disturbances (diarrhea, nausea, vomiting, abdominal pain), unexplained fever, muscle weakness, and tremor. Thyroid storm is usually precipitated by a stressful event such as surgery, childbirth, infection, myocardial infarction, diabetic ketoacidosis, or trauma. 454

PATHOPHYSIOLOGY The actual mechanism whereby thyrotoxicosis decompensates into thyroid crisis is poorly understood, but it most often develops after a stressful precipitating event. Whatever the cause, the resulting syndrome resembles prolonged, severe β-adrenergic agonist overdose. Catecholamine concentrations appear to be normal, despite the apparent hypermetabolic state.

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Table 108–2

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455

Results of Thyroid Function Studies in Patients with Thyroid Disorders Disorder

Test

Hyperthyroid

Hypothyroid

TSH Total T4 Total T3 Reverse T3 Free T4 T3 resin uptake*

Low High High High High High

High Low Low Low to normal Low Low

*Approximates serum hormone binding by thyroxine-binding globulin (normal range is 33-48%). T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone.

Figure 108–1 ■ Computed tomography scan (with intravenous contrast) of lower neck–upper thorax region reveals an enlarged thyroid gland (goiter) compressing the trachea and esophagus. Anesthetists must recognize the potential for significant airway compromise during induction of anesthesia in patients with large goiters in the neck and anticipate possible extension of the goiter to the retrosternal space. Up to 6% of tracheal intubations in patients anesthetized for thyroid surgery are difficult.

CAUSE

DIAGNOSIS The diagnosis of thyroid storm is clinical. Corroboration and confirmation rely on thyroid studies with the following findings (Table 108-2): ● ● ●

Elevated thyroxine (T4) Elevated triiodothyronine (T3) Decreased thyroid-stimulating hormone (TSH)

Table 108–1

■

Disorders Associated with Thyrotoxicosis

Graves’ disease (may account for 85% of cases) Toxic multinodular goiter Toxic adenoma Subacute thyroiditis Neonatal thyrotoxicosis (consequent to maternal Graves’ disease) TSH-secreting pituitary tumor Labor and childbirth Hydatidiform mole Metastatic (hyperfunctioning) thyroid carcinoma Thyrotoxicosis factitia TSH, thyroid-stimulating hormone.

DIFFERENTIAL DIAGNOSIS Malignant hyperthermia must be investigated simultaneously and treatment initiated if triggering anesthetic agents are used. This is especially true in children or when severe hypercarbia, acidosis, hyperkalemia, and increased creatine phosphokinase are present. Other hypermetabolic states such as sepsis, pheochromocytoma, or thyrotoxicosis without crisis should be considered. Last, the differential diagnosis should include severe drug intoxication with either cocaine or amphetamines.

MANAGEMENT Do not wait for laboratory results to begin treatment if there is sufficient clinical suspicion. Appropriate treatment includes general supportive measures; inhibition of thyroid hormone synthesis, thyroid hormone release, peripheral β-adrenergic activity, and peripheral conversion of T4 to T3; and regulation of intracellular calcium.

General Supportive Measures ● ●

● ●

Intravenous (IV) fluids to restore intravascular volume Acetaminophen for hyperthermia (avoid aspirin, because it displaces T4 from thyroid-binding globulin, thereby increasing free T4) Cooling blankets Magnesium salts to reduce the severity and incidence of cardiac arrhythmias

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Undiagnosed hyperthyroidism (usually Graves’ disease or toxic multinodular goiter) in a patient with major stress is the most common cause of thyroid storm. Another cause may be inadequate treatment in a known hyperthyroid patient. Disorders associated with thyrotoxicosis are listed in Table 108-1. The many causes of thyrotoxicosis can be distinguished by a 24-hour radioactive iodine uptake study performed when the patient’s condition is stable.

However, T4 and T3 concentrations may correlate poorly with the severity of clinical signs. Other routine studies include complete blood cell count, electrolyte levels, urinalysis, chest radiograph, and electrocardiogram. Additional studies looking for infectious processes should be performed. Associated laboratory abnormalities (present 5% to 20% of the time) include hypercalcemia, hypokalemia, hyperglycemia, hypocholesterolemia, microcytic anemia, lymphocytosis, granulocytopenia, hyperbilirubinemia, and increased alkaline phosphatase level.

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Inhibition of Thyroid Hormone Synthesis ●

●

Propylthiouracil (PTU)—up to 1000 mg initially as a loading dose, then 200 to 300 mg orally or via nasogastric tube every 4 to 6 hours. It may take 6 to 8 weeks to achieve a full euthyroid state; PTU also inhibits peripheral conversion of T4 to T3. Methimazole—20 to 30 mg orally or via nasogastric tube every 4 to 6 hours. Achieves a euthyroid state more quickly than PTU and has a lower incidence of agranulocytosis, hepatitis, and vasculitis.

●

Dexamethasone 2 mg intravenously or orally every 6 hours, or hydrocortisone 50 mg intravenously every 6 hours

Intracellular Calcium Regulation Dantrolene in doses of 1 mg/kg (equivalent to that used for malignant hyperthermia) has been reported in anecdotal cases; however, its utility and efficacy in the setting of thyroid storm are not well defined.

PREVENTION Iodide Therapy Iodide inhibits thyroid hormone synthesis (Wolff-Chaikoff effect). Delay iodide therapy at least 4 hours after beginning PTU therapy. ● ●

●

Sodium iodide—1 g intravenously every 8 hours Potassium iodide (SSKI, a saturated solution of potassium iodide), such as Lugol solution—10 drops orally every 6 hours. Lugol solution was once widely administered for 7 to 10 days before elective thyroidectomy in an effort to reduce vascularity of the gland. Iopanoic acid—0.5 to 1.0 g/day (also blocks peripheral conversion of T4 to T3)

Inhibition of Peripheral β-Adrenergic Activity ●

β-blockers, which also block peripheral conversion of T4 to T3 ● Propranolol—0.5 to 1.0 mg/minute intravenously, up to a total dose of 2 to 10 mg; repeat every 3 to 4 hours. After initial control with IV drug, treat with 20 to 40 mg orally every 6 hours; occasionally, a patient may require up to 2 g/day orally owing to the variability of hepatic metabolism in thyrotoxic individuals. ● Esmolol—IV bolus with 0.5 to 0.75 mg/kg, followed by IV infusion with 50 μg/kg per minute. If effect is inadequate after 5 minutes, repeat IV bolus and increase IV infusion to 100 μg/kg per minute; it may even be necessary to increase the infusion to 300 μg/kg per minute. ● Titrate β-blockade to achieve a heart rate of 80 to 90 beats per minute. ● If the patient has a history of reactive airway disease, use caution and a short-acting cardioselective agent such as esmolol, atenolol, or metoprolol. ● If β-blockers are contraindicated, other sympatholytic drugs (e.g., reserpine, a depleter of catecholamines, or guanethidine, an inhibitor of catecholamine release) may be useful as second-line agents.

Inhibition of Peripheral Conversion of T4 to T3 ● ●

PTU (see dosages given earlier) β-blockade (see dosages given earlier)

Prevention of complications in patients with hyperthyroidism (especially thyroid storm) relies on recognition of the stigmata of undiagnosed hyperthyroidism during the preoperative evaluation. In addition, anesthesiologists must anticipate potential airway difficulties during tracheal intubation, which occurs in 6% of patients anesthetized for thyroid surgery (see Fig. 108-1). Mortality with thyroid storm may be as high as 20%. Improved survival relies on early, aggressive therapy. In addition, definitive therapy requires treatment of any associated disorders, such as infection or diabetic ketoacidosis.

Further Reading Ambus T, Evans S, Smith NT: Thyrotoxicosis factitia in the anesthetized patient. Anesthesiology 81:254-256, 1994. Bennett MH, Wainwright AP: Acute thyroid crisis on induction of anaesthesia. Anaesthesia 44:28-30, 1989. Benua RS, Becker DV: Thyroid storm. In Bardin CW (ed): Current Therapy in Endocrinology and Metabolism, 4th ed. Philadelphia, BC Decker, 1991, pp 68-70. Burch HB, Wartofsky L: Life-threatening thyrotoxicosis. Endocrinol Metab Clin North Am 22:263-277, 1993. Connery LE, Coursin DB: Assessment and therapy of selected endocrine disorders. Anesthesiol Clin North Am 22:93-123, 2004. Farling PA: Thyroid disease. Br J Anaesth 85:15-28, 2000. Gavin LA: Thyroid crises. Med Clin North Am 75:179-193, 1991. Knighton JD, Crosse MM: Anaesthetic management of childhood thyrotoxicosis and the use of esmolol. Anaesthesia 52:62-76, 1997. Lacoste L, Gineste D, Karayan J, et al: Airway complications in thyroid surgery. Ann Otol Rhinol Laryngol 102:441-446, 1993. Nishiyama K, Kitahara A, Natsume H, et al: Malignant hyperthermia in a patient with Graves’ disease during subtotal thyroidectomy. Endocr J 48:227-232, 2001. Pandey CK, Raza M, Dhiraaj S, et al: Rapid preparation of severe uncontrolled thyrotoxicosis due to Graves’ disease with iopanoic acid. Can J Anaesth 51:38-40, 2004. Peters KR, Nance P, Wingard DW: Malignant hyperthyroidism or malignant hyperthermia? Anesth Analg 60:613-615, 1991. Pugh S, Lalwani K, Awal A: Thyroid storm as a cause of loss of consciousness following anaesthesia for emergency caesarean section. Anaesthesia 49:35-37, 1994.

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Sarcoidosis Barry A. Harrison and Martin L. De Ruyter Case Synopsis A 50-year-old African American woman with stage III pulmonary sarcoidosis is scheduled to undergo a thoracotomy for resection of a right upper lobe aspergilloma. Chronically, she has a hoarse voice, dyspnea at rest, and swollen ankles. She is receiving corticosteroids and ambulatory oxygen therapy at a rate of 2 L/minute. She complains of palpitations and fainting spells.

PROBLEM ANALYSIS Definition Sarcoidosis is a systemic granulomatous disease of unknown cause. A complex interaction of genetic, environmental, and infectious agents triggers a type 1 T-lymphocyte response that is characterized by chronic inflammation, monocyte recruitment, and granuloma formation. Characteristic pathohistologic findings include noncaseating granulomas that are both discrete and compact. These granulomas are composed of mononuclear phagocytes, including epithelioid cells, multinucleated central giant cells, and lymphocytes. The multinucleated central giant cells are surrounded by fibroblasts and mast cells (Fig. 109-1).

CLINICAL FEATURES Sarcoidosis occurs mainly in individuals between the ages of 20 and 40 years, with a prevalence in the United States of approximately 20 in 100,000. It is slightly more common in females than in males and has a black-white ratio of 15:1. Sarcoidosis may present acutely, subacutely, or insidiously. Between 30% and 60% of cases are asymptomatic, detected incidentally by an abnormal chest radiograph. Constitutional symptoms may occur and consist of fever, fatigue, anorexia,

PULMONARY PRESENTATION Upper Airway. Although laryngeal sarcoid involvement may be an isolated finding, it is usually associated with systemic manifestations. It occurs in <5% of patients with sarcoidosis. Symptoms and signs of laryngeal sarcoidosis include dysphagia, hoarseness, throat pain, dyspnea, and stridor. Granulomas or nodules involving the supraglottic larynx or the entire larynx are often found (Fig. 109-2). Airway obstruction can occur, and a tracheostomy may be necessary in some cases. Recurrent laryngeal nerve involvement can result in unilateral vocal cord paralysis. Lower Airway. Enlarged intrathoracic lymph nodes can compress large airways, potentially causing tracheal and bronchial stenosis, airflow obstruction, and pulmonary atelectasis. Pulmonary Parenchyma. The lung and intrathoracic lymph nodes are involved in >90% of cases. Approximately 50% of patients develop permanent pulmonary abnormalities, with 5% to 15% developing pulmonary fibrosis. Chronic hypoxemic respiratory failure and cor pulmonale may result from pulmonary sarcoidosis.

Figure 109–1 ■ Sarcoid granulomas in lung tissue. (Photomicrograph courtesy of Dr. Thomas A. Gaffey, Department of Pathology, Mayo Clinic and Foundation, Rochester, Minn.)

Chest Radiographic and Laboratory Findings. Ninety percent of patients with sarcoidosis have an abnormal chest radiograph at some time. Three classic chest radiographic patterns have been described, with higher stages correlating with an increased frequency of dyspnea (Table 109-1). An increase in the serum concentration of angiotensin-converting enzyme (ACE), which is secreted by sarcoid granulomas, can assist in making the diagnosis. Unfortunately, other chronic inflammatory conditions are also associated with increased 457

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Recognition

cough, dyspnea, and vague retrosternal discomfort. Syndromes such as erythema nodosum, anterior uveitis, arthritis, parotid enlargement, and facial nerve palsy occur in acute sarcoidosis. In patients with an insidious presentation, respiratory symptoms usually predominate. Diagnosis requires relevant clinical features and a tissue biopsy showing characteristic noncaseating granulomas. The degree and variability of disease activity together with the organ involved determine the clinical presentation. These factors contribute to the delay in diagnosis observed in sarcoid patients. Death from sarcoidosis usually results from progressive pulmonary, cardiac, or neurologic involvement.

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disease elsewhere. Cardiac involvement may manifest as cardiac arrhythmias (ventricular more often than supraventricular), conduction disorders, cardiomyopathy, pericarditis, wall motion abnormalities, or cardiac arrest. Electrocardiography, echocardiography, and, in select patients, cardiac catheterization with myocardial biopsy may be helpful in evaluating patients with cardiac findings. Myocardial sarcoidosis may be difficult to diagnose in the absence of systemic manifestations. Myocardial biopsy may be falsely negative owing to sampling bias. Cor pulmonale may result from pulmonary parenchymal disease. Sudden death is associated with cardiac sarcoidosis; however, with progress in the development of antiarrhythmic drugs, cardiac pacemakers, and implantable defibrillators, congestive heart failure associated with myocardial sarcoidosis is now a more frequent cause of death. MULTISYSTEM PRESENTATION Sarcoidosis is a systemic disease; multiple organ systems can be involved and have implications for the anesthesiologist (Table 109-2). Figure 109–2 ■ Granulomas involving the supraglottic region. (From Neel HB, McDonald TJ: Laryngeal sarcoidosis. Ann Otol Rhinol Laryngol 91:361, 1982.)

Risk Assessment Risk assessment is dependent on the extent and severity of sarcoidosis and the organ system affected.

serum ACE. Recent findings demonstrate that serum ACE is not consistently correlated with disease activity or treatment response. Computed Tomography. High-resolution computed tomography (CT) is helpful if the chest radiograph is equivocal; a diagnosis can be made in up to 75% of cases. Highresolution CT can be used to diagnose small, well-defined nodes and peribronchial interstitial thickening, whereas conventional CT is better for the evaluation of diffuse parenchymal sarcoidosis (Fig. 109-3). Transbronchial Biopsy. Transbronchial biopsy is diagnostic in 90% of cases. The yield is excellent even if interstitial infiltrates are not detectable on chest radiography. Bronchoalveolar Lavage. Lavage may be helpful, especially if the lymphocyte population is analyzed. A CD4/CD8 ratio greater than 3.5 is 94% specific for sarcoidosis. CARDIAC PRESENTATION Clinically overt cardiac involvement occurs in about 5% of patients with sarcoidosis, usually without evidence of

Table 109–1

■

PULMONARY ASSESSMENT As elastic resistance of the lungs is increased, patients with sarcoidosis adapt to reduce the work of breathing by taking rapid, shallow breaths. Most commonly there are reductions in lung volume and the diffusing capacity for carbon monoxide (Fig. 109-4). Expiratory flow rates may also be decreased, suggesting airflow obstruction. Arterial hypoxemia with exercise occurs frequently; arterial hypoxemia at rest indicates severe disease. Although sarcoid lung pathology is caused by granuloma and fibrosis, pulmonary function testing may reflect disease extent but not necessarily disease activity. However, such testing may provide objective data when following a patient’s response to therapy. CARDIAC ASSESSMENT Electrocardiography and 24-hour electrocardiographic monitoring, echocardiography, and cardiac catheterization with myocardial biopsy may be helpful in the evaluation of cardiac sarcoidosis. Thallium 201 myocardial imaging may demonstrate segmental defects consistent with sarcoid granulomas or fibrous scars. Magnetic resonance imaging has

Three Classic Chest Radiograph Patterns in Sarcoidosis

Chest Radiograph Pattern

Radiographic Findings

Stage I Stage II Stage III

Hilar and mediastinal abnormality without pulmonary parenchymal abnormality Hilar and mediastinal abnormality associated with pulmonary parenchymal abnormality Diffuse pulmonary disease without node enlargement

ACE, angiotensin-converting enzyme.

Incidence of ACE Elevation (%) 67 88 95

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Figure 109–3 ■ Left, Bilateral hilar lymphadenopathy (stage I). Middle, Bilateral hilar lymphadenopathy and interstitial infiltrates (stage II). Right, Highresolution chest computed tomography scan showing extensive nodular interstitial process. (Radiographs courtesy of Department of Radiology, Mayo Clinic and Foundation, Rochester, Minn.)

also been used to identify areas of myocardium affected by sarcoidosis and to guide myocardial biopsy.

Self-Limited Disease

Implications

■

Over a 3-year period following diagnosis, approximately 30% to 50% of cases remit spontaneously. Of the remaining approximately 50% of cases that do not show remission, over the next 5 to 10 years, 30% of those patients show disease progression, while the remaining 20% remain stable. Thus, not all patients with sarcoidosis require specific therapy, especially those with a stage I radiographic pattern.

Corticosteroids, Cytotoxics, and Immunosuppressive Therapy Treatment for sarcoidosis is indicated for progressive symptomatic disease. Clear-cut examples include cardiac and neurologic sarcoidosis and hypocalcemia secondary to sarcoidosis. Pulmonary sarcoidosis with respiratory symptoms

Multisystem Involvement in Sarcoidosis

Organ System (Incidence of Involvement) Nervous (5%)

Manifestations

Hepatic (12%) Hematopoietic (26%)

Peripheral neuropathies, central nervous system symptoms: meningitis, encephalitis, epilepsy, cranial nerve disturbances Arthritis of peripheral joints: ankles, knees, wrists, hands; ankylosis of temporomandibular joints Hypercalciuria with or without hypercalcemia, nephrocalcinosis, nephrolithiasis Hepatomegaly, abnormal liver function tests Anemia, thrombocytopenia, neutropenia, eosinophilia, splenomegaly

Eye (12%) Skin (15%)

Uveitis, conjunctival nodules, keratoconjunctivitis sicca Erythema nodosum, plaques, subcutaneous nodules

Endocrine (4%)

Posterior pituitary: diabetes insipidus, hypercalcemia

Musculoskeletal (1%) Renal (1%)

Anesthetic Implications Use caution with muscle relaxants Examine the airway Altered drug excretion Altered drug metabolism Check complete blood count Standard eye precautions Lesions may be tender and painful Monitor serum Ca2+, Na+, and urine output

From Baughman RP, Teirstein AS, Judson MA, et al: Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 164:1885–1889, 2001.

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Patients with sarcoidosis undergo procedures for biopsy and diagnosis that may require anesthesia. These include fiberoptic bronchoscopy with transbronchial biopsy, scalene node biopsy, and mediastinoscopy for hilar lymph node biopsy and lung biopsy, either by video-assisted thoracoscopy or thoracotomy. Many patients with sarcoidosis require anesthesia owing to a complication of therapy (e.g., perforated duodenal ulcer secondary to corticosteroid therapy). Sarcoid patients routinely require anesthesia for comorbid conditions. In the case synopsis, the patient had developed an aspergilloma fungus ball in a lung cavity due to cystic destruction of lung tissue by sarcoidosis. Progressive pulmonary sarcoidosis with chronic hypoxemic respiratory failure and right heart failure or progressive cardiac sarcoidosis can cause problems with anesthesia and increase risk.

Table 109–2

MANAGEMENT

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Maximal expiratory flow (L/sec)

12 Spirometry FVC FEV1 FEV1/FVC FEF 25-75 Lung volumes TLC (Pleth) VC RV RV/TLC Diffusing capacity DLCO(SB) Alveolar volume

10 8 6 4

Found

Predicted(%)

1.19 1.14 95.8 2.6

37 42

2.02 1.19 0.83 41.1

47 37 77 164

4 1.80

18 42

94

2 0

0

1

2

3 4 5 Expired volume (L)

6

7

8

Figure 109–4 ■ Expiratory flow volume loop. Solid line is the patient with sarcoid; dashed line is the normal predicted loop. The insert contains the values of spirometry, lung volumes, and diffusing capacity of a patient with pulmonary sarcoidosis. DLCO(SB), diffusing capacity of carbon monoxide, single breath; FEF25-75, forced expiratory flow rate between 25% and 75% of a forced vital capacity; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; RV, residual volume; TLC, total lung capacity; VC, vital capacity. (Data from Pulmonary Function Laboratory, Mayo Clinic and Foundation, Rochester, Minn.)

Chronic Hypoxemic Respiratory Failure and Cor Pulmonale Long-standing progressive pulmonary sarcoidosis may give rise to chronic hypoxemic respiratory failure and cor pulmonale. The latter is pulmonary arterial hypertension resulting from diseases affecting lung structure or function. Pulmonary arterial hypertension results in right ventricular enlargement (hypertrophy or dilatation) and may progress over time to right heart failure. The treatment of both conditions is first and foremost the titration of continuous oxygen to increase arterial oxygen saturation to above 90%. If right-sided heart failure is present, diuresis, initially with bed rest and then, if necessary, with diuretics (often furosemide), should be initiated. Excessive fluid loss is dangerous, however, because it may decrease right ventricular preload. Digitalis use is controversial because the potential for digitalis toxicity is high, even with low serum concentrations, when hypoxemia, alkalosis-induced hypokalemia, and cor pulmonale are present. The use of pulmonary vasodilators is undergoing investigation.

PREVENTION associated with progressive loss of lung function also requires treatment. A systemic evidence-based review of corticosteroids in sarcoidosis found that they improved radiographic assessment (stage II and III radiographic patterns) and pulmonary function. However, no data exist demonstrating that corticosteroids have a significant effect on long-term disease progression. A 3-month trial of corticosteroids is required before reevaluating the patient. Although inhaled corticosteroids have been tried, insufficient clinical trials have been conducted to determine their efficacy. Cytotoxics and antimalarials are used in sarcoidosis to control disease progression, especially if cortocosteroids have failed or in an effort to decrease the corticosteroid dosage. Methotrexate, azathioprine, and chloroquine have all been used. However, such use has usually been reported anecdotally or in small case series. There have been only four studies evaluating these drugs in a prospective, controlled manner. Results were inconclusive, and all the drugs were associated with severe side effects. Activated T lymphocytes secreting interleukin-2 may play a role in sarcoidosis, which has led to trials of cyclosporine for the treatment of sarcoidosis. Unfortunately, these trials have also failed to show any benefit. Thalidomide and antagonists to tumor necrosis factor-α are currently undergoing therapeutic trials.

Lung Transplantation Single or bilateral lung transplantation has been tried in patients with end-stage lung disease who are refractory to aggressive medical therapy. Recurrence of sarcoid granulomas within the lung allografts occurs in a majority of patients but rarely causes clinical symptoms. The survival rate for single- or double-lung transplantation is 70% at 2 years.

Preoperative Because sarcoidosis is a multisystem disease, all systems must be evaluated for possible sarcoid involvement during the preoperative assessment. Symptoms and signs of upper airway involvement with sarcoidosis must be specifically addressed before tracheal intubation. Chronic corticosteroid use and the associated potential for adrenal insufficiency must be evaluated, and preoperative corticosteroids should be administered if necessary.

Operative If chronic hypoxemic respiratory failure and right-sided heart failure are present, hypoxia, hypercapnia, and acidosis must all be avoided because they act to increase pulmonary artery pressure, further exacerbating right heart failure. Central venous pressure monitoring to guide intravascular fluid administration and the use of a pulmonary artery catheter to determine pulmonary artery pressure and cardiac output may also be necessary. Regional anesthesia may be advantageous if the surgical site is below the level of the umbilicus. In patients with ventilatory compromise, the usual accessory function of the intercostal muscles may make a larger contribution to overall ventilation. If so, high central neuraxial blockade may interfere with intercostal muscle function and exacerbate the tenuous oxygen supplydemand balance. Large-volume intravenous fluid administration to treat hypotension associated with sympathetic blockade may exacerbate right-sided heart failure. Therefore, blood pressure is maintained with intravenous vasopressors (e.g., phenylephrine) to ensure adequate venous return to the right heart. During general anesthesia, mechanical ventilation may be necessary. If so, titration of positive endexpiratory pressure and oxygen to maintain an oxygen saturation of at least 90% is necessary. Limit the plateau airway

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pressure to less than 35 cm H2O by adjusting the tidal volume and inspiratory flow rates. Careful titration of all these parameters may help prevent further lung injury.

Postoperative With sarcoidosis-induced chronic hypoxemic respiratory failure and right-sided heart failure, careful consideration must be given to postoperative analgesia. Systemic opioid administration may depress ventilation and precipitate hypoxia. Thus, a central neuraxial technique may be preferable, with the use of local anesthetic agents, opioids, or both. Also, use of local anesthetics via continuous peripheral nerve blockade optimizes analgesia and limits respiratory side effects. Titration of inspired oxygen is advised to maintain oxygen saturation greater than 92%.

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Further Reading Baughman RP, Lower EE, Du Bois R: Sarcoidosis. Lancet 361:1111-1118, 2003. Clark D, Mitchell AW, Dick R, et al: The radiology of sarcoidosis [review]. Sarcoidosis 11:90-99, 1994. Karl TK: Sarcoidosis. JAMA 289:3300-3303, 2003. Paramothayan S, Jones PW: Corticosteroid therapy in pulmonary sarcoidosis: A systematic review. JAMA 287:1301-1307, 2002. Paramothayan S, Lasserson T, Walters EH: Immunosuppressive and cytotoxic therapy for pulmonary sarcoidosis. Cochrane Database of Syst Rev 2:2004. Weitzenblum E: Chronic cor pulmonale. Heart 89:225-230, 2003. Wills MH, Harris MM: An unusual airway complication with sarcoidosis. Anesthesiology 66:554-555, 1987.

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Klaus D. Torp Case Synopsis A 43-year-old gas station attendant is scheduled for emergency exploratory laparotomy after sustaining an abdominal stab wound during an attempted robbery. He is dialysis dependent and awaiting renal transplantation. His last hemodialysis was 52 hours earlier. He is awake and alert. His blood pressure is 102/90 mm Hg; heart rate, 114 beats per minute; and respiratory rate, 24 breaths per minute. His hemoglobin level is 8.2 g/dL after receiving 3 units of packed red blood cells; the serum potassium level before the transfusion was 6.0 mEq/L. While cricoid pressure is applied, anesthesia is induced with etomidate, fentanyl, and rocuronium. Soon after the operation begins, the surgeon complains of difficulty achieving hemostasis. T waves on the electrocardiogram are tall and peaked.

PROBLEM ANALYSIS Definition Approximately 500,000 patients are affected by end-stage renal disease (ESRD) in the United States, with an estimated incidence of about 333 per 1 million persons (quadrupled from 1980) and a prevalence of 1435 per 1 million (quintupled from 1980). Prevalence rates are 1.4 times higher for males than for females and 4 times higher for African Americans than for whites. Those aged 45 to 64 years account for the largest number of patients. About 45% of all ESRD patients have a primary diagnosis of diabetes, another 30% are hypertensive, and less than 20% have glomerulonephritis; the remainder have rarer diseases, such as the following: ● ● ● ● ● ● ● ●

Polycystic kidney disease Immunoglobulin (Ig) A and IgM nephropathies Systemic lupus erythematosus Wegener’s granulomatosis Multiple myeloma Amyloidosis Acquired immunodeficiency syndrome (AIDS) nephropathy Miscellaneous causes or conditions

Patients with these rarer causes tend to be younger and are less likely to present with the typical comorbidities of dialysis patients. In 2002 about 100,000 patients began treatment for ESRD with hemodialysis, peritoneal dialysis, or renal transplantation. Dialysis is usually required when the glomerular filtration rate falls below 20 mL/minute. Dialysis may also be indicated for hospitalized patients with volume overload refractory to diuretics, severe metabolic acidosis, hyperkalemia, seizures or other neurologic symptoms, or pericarditis. It is usually started when the blood urea nitrogen is 462

greater than 100 mg/mL or the creatinine level approaches 10 mg/dL. Regardless of cause, ESRD affects virtually all organ systems (Table 110-1) and has implications for anesthesiologists, intensivists, and surgeons. These abnormalities result from the failure to excrete urea and other waste products of metabolism or the loss of metabolic and endocrine functions normally performed by the kidney.

Recognition Perioperative complications of ESRD are listed in Table 110-2. The most frequent life-threatening perioperative complication is hyperkalemia. It is frequently associated with acidosis and with trauma due to the release of potassium from damaged tissue and hematomas. Hyperkalemia can cause progressive cardiac conduction defects, ending in ventricular fibrillation or, less commonly, asystole (Table 110-3). Electrocardiographic changes are critically dependent on the rate of rise in serum potassium levels (i.e., acute versus chronic hyperkalemia). An increased propensity for bleeding often occurs in the presence of uremia because of an acquired defect in primary hemostasis. Tests of coagulation are typically normal, although a slight reduction in platelet counts may be seen. The pathogenesis is multifactorial, and the major defects involve decreased platelet–vessel wall adhesion and plateletplatelet interactions manifesting as impaired aggregation in response to epinephrine, adenosine diphosphate, collagen, and fibrinogen. Platelets from uremic patients release less adenosine triphosphate and serotonin and also display reduced cyclooxygenase activity. The activation-dependent receptor function of the glycoprotein IIb/IIIa complex is defective in uremia, as shown by decreased binding of both von Willebrand’s factor (vWF) and fibrinogen to stimulated platelets. Cutaneous bleeding time remains the most readily

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Table 110–1

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Perioperative Management of Dialysis-Dependent Patients

Clinical Abnormalities in End-Stage Renal Disease

Nervous System Sleep disorders Motor weakness Polyneuritis Asterixis Seizures Coma

Hematologic System Anemia Increased fragility of red blood cells Platelet dysfunction with bleeding Thrombosis

Metabolic and Endocrine Systems Glucose intolerance Hyperparathyroidism Hypogonadism

Immunologic System Increased susceptibility to infection

Integumentary System Pruritus

Cardiovascular System Hypertension Hypotension Cardiomyopathy Diastolic dysfunction Left ventricular hypertrophy Congestive cardiac failure Pericarditis

Gastrointestinal System

Acid-Base and Electrolytes Anion gap metabolic acidosis Hyperkalemia Hyponatremia Hypermagnesemia or hypomagnesemia Hyperphosphatemia

■

Electrocardiographic Changes with Progressive Hyperkalemia

K+ (mEq/L)

Electrocardiographic Abnormality

5.0 6.0 7.0

Usually none or tenting of T waves Tall and peaked T waves Prolonged P-R interval with depressed ST segments Sinoatrial arrest with “sine wave” QRS complex Ventricular fibrillation

8.0 9.0

frequently noted. In fact, some patients receive antiplatelet agents to prevent thrombosis of arteriovenous grafts, as well as for cardiovascular disease, which in turn may contribute to the bleeding tendency. Cardiovascular dysfunction is common in patients with ESRD. This is not surprising, given the high prevalence of hypertension, left ventricular hypertrophy, and coronary artery disease in patients on chronic dialysis. Further, diminished responsiveness of cardiac α- and β-adrenergic receptors due to dysautonomia results in poor compensatory responses to acute hemodynamic changes. Hypoxemia and dysequilibrium syndrome are two complications of which anesthesiologists should be aware. They can occur either during or soon after dialysis. Hypoxemia is more common when acetate rather than bicarbonate is used in the dialysate, and it is due to both alveolar hypercapnia and complement-induced pulmonary inflammation. Any associated hypoxemia is usually transient. Dysequilibrium is caused by rapid removal of urea and other osmotically active agents while the blood-brain barrier prevents their rapid removal from brain cells. These become relatively hypertonic. Fluid diffuses into brain cells along an osmotic gradient. Therefore, cerebral edema may result.

Musculoskeletal System

Risk Assessment

Renal osteoporosis or osteomalcia

Patients who are dialysis dependent and undergo major surgical procedures have a higher perioperative mortality rate than patients with normal renal function. It is particularly high for patients undergoing open-heart surgery (approximately 12%, versus 2.9% in nondialysis patients). The risk of major surgery is related to abnormalities directly attributable to ESRD, as well as to the underlying disease process (e.g., hypertension). In dialysis patients, diastolic dysfunction is as common a cause of congestive heart failure as dilated cardiomyopathy is. Therefore, in patients with ESRD, a relatively small excess of ingested sodium chloride and water can lead to a large increase in left ventricular enddiastolic pressure, resulting in pulmonary edema. The probability of having angina or a myocardial infarction requiring hospitalization is 10% per year, and cardiac disease accounts for 45% of deaths in patients on dialysis. Anemia and hypertension are independent predictors of mortality. The 5-year survival rate after the initiation of dialysis is around 33%, and the life expectancy is only about one fourth that of the general population. Anesthetic drugs such as succinylcholine (which causes an increase in serum potassium levels after intubating doses)

available test of platelet function, although its accuracy is often questioned. A markedly prolonged bleeding time with a relatively normal platelet count should trigger efforts to correct this abnormality. Despite the bleeding tendency in patients with ESRD, hypercoagulability markers (e.g., elevated vWF activity and thromboelastographic amplitudes) are

Table 110–2

■

Perioperative Complications of End-Stage Renal Disease

Hyperkalemia Bleeding Cardiovascular dysfunction Hypertension or hypotension Congestive heart failure Ischemia Sepsis Graft thrombosis

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Gastrointestinal bleeding Pancreatitis

Table 110–3

463

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can contribute to the risk of death. The need for multiple blood transfusions also increases serum potassium levels, as does acidosis resulting from long periods of hypoperfusion or the failure to adequately compensate for increasing metabolic acidosis with an increase in minute ventilation. Drug overdoses can occur owing to reduced renal clearance of the drug itself or its active metabolites, which is more of a concern with repeat dosing. However, increased unbound fractions of a drug caused by decreased plasma proteins may lead to relative overdose with initial intravenous dosing of some drugs (e.g., thiopental, methohexital, diazepam). All anesthetic techniques have the potential to reduce renal perfusion and adversely affect any residual renal function, with important implications for the patient’s health.

Implications The potential for serious life-threatening problems relating to electrolyte, coagulation, and acid-base problems is always present. This is compounded by any underlying or coexistent diseases, especially serious cardiovascular abnormalities.

MANAGEMENT General principles for the management of all ESRD patients undergoing surgery, regardless of the cause of ESRD, are listed in Table 110-4.

Hyperkalemia The management of acute hyperkalemia can be divided into three steps (Table 110-5). First, treatment is directed toward antagonizing the adverse effects of increased potassium by administering intravenous calcium. Second, potassium is shifted intracellularly by stimulating Na+,K+-ATPase or using its electrochemical gradient. Third, potassium is removed from the body with dialysis or exchange resins.

Bleeding in Uremic Patients Treatment with erythropoietin or infusion of washed red blood cells has been shown to significantly reduce bleeding times in uremic patients with a hematocrit above 30%. Erythrocytes enhance platelet function by releasing adenosine

Table 110–5

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Table 110–4

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General Management Principles for Patients with End-Stage Renal Disease Undergoing Surgery

Dialysis within 24 hr of surgical procedure Serum potassium in normal range Serum bicarbonate ≥20 mEq/L desirable Euvolemic or minimally hypovolemic before surgical procedure Hematocrit around 30% Use potassium-free fluid; wash red blood cells to minimize transfused potassium load Use caution with succinylcholine Choose drugs that do not depend on renal elimination; adjust (decrease) dosages of drugs that depend on renal metabolism or that are highly protein bound Use strict aseptic techniques when placing intravascular devices Identify and adequately protect functioning shunts during surgical procedures Pay attention to padding of pressure points

diphosphate, inactivating prostacyclin, and increasing platelet–vessel wall contact (i.e., directing platelets toward the vessel wall instead of the usual axial flow). Infusion of desmopressin (DDAVP), which has less pressor effect than vasopressin, stimulates the release of vWF from endothelial cells. This may explain its therapeutic effect in uremia. DDAVP is given intravenously at a dose of 0.3 μg/kg in 50 mL of normal saline over 15 to 30 minutes. It shortens bleeding times in 50% to 75% of uremic patients. This correction occurs in 30 to 60 minutes and lasts for about 4 hours, correlating with increased plasma concentrations of vWF, as well as an increase in the proportion of high-molecularweight multimers of vWF. Tachyphylaxis typically occurs after the second DDAVP dose, possibly owing to depletion of endothelial multimer stores. Cryoprecipitate, which is rich in factor VIII and vWF, can also be used at an initial dose of 10 to 20 units. Its onset of action is similar to that of desmopressin, but the beneficial effects persist for 24 to 36 hours. Conjugated estrogen (Premarin 0.6 mg/kg per day intravenously for 5 days) is effective before elective major operations, and its beneficial effects persist for 3 to 4 weeks. Hemodialysis significantly ameliorates platelet dysfunction and should be used, if required, within 24 hours of the planned operation.

Treatment Modalities for Acute Hyperkalemia

Mechanism

Intervention

Antagonism of K+ effects Shift K+ intracellularly (effective within 30 min)

Calcium chloride or calcium gluconate 1-2 g (slow IV push) Moderate hyperventilation Insulin 20 units/dextrose 50 g IV infusion over 20-30 min Sodium bicarbonate 50-100 mEq IV Albuterol 10 mg (nebulized) Epinephrine 0.01 μg/kg/min IV Sodium polystyrene sulfonate (Kayexalate: 30 g sodium polystyrene sulfonate in 100 mL 20% sorbitol) administered via nasogastric tube (100 mL = 30 g) or rectally (100-200 mL = 30-60 g) Caution: This exchanges potassium for sodium and may lead to pulmonary edema Emergency hemodialysis (even intraoperatively, if required) Caution: Increases risk for hypotension and bleeding

Remove K+ from the body

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PREVENTION Complications of ESRD in the perioperative period are best prevented by consulting a nephrologist to perform dialysis the day before surgery and to arrange for dialysis in the immediate postoperative period or intraoperatively if necessary. There is accumulating evidence that more aggressive treatment of predialysis hypertension is a potent intervention for reducing subsequent perioperative cardiovascular mortality. Also, early treatment of anemia is recommended because it may delay or prevent left ventricular hypertrophy and reduce bleeding problems. Prevention and treatment of acidosis (serum bicarbonate >20 mEq/L) to establish an acid buffer can help reduce the risk of hyperkalemia. After major surgery, any of these methods has the potential to reduce the high morbidity and mortality rates formerly associated with ESRD and improve patient outcomes.

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Janson PA, Jubelirer SJ, Weinstein MJ, et al: Treatment of bleeding tendency in uremia with cryoprecipitate. N Engl J Med 303:1318-1322, 1980. Kasiske BL: Dialysis in special clinical situations: Anesthesia. In Jacobs C, et al (eds): Replacement of Renal Function by Dialysis. Dordrecht, The Netherlands, Kluwer Academic Publishers, 1996, pp 954-957. Kentro TB, Lottenberg R, Kitchens CS: Clinical efficacy of desmopressin acetate for hematocrit control in patients with primary platelet disorder undergoing surgery. Am J Hematol 24:215-219, 1987. Morbidity and mortality of renal dialysis: An NIH consensus conference statement. Ann Intern Med 121:62-70, 1994. Remuzzi G, et al: Effect of renal failure on hemostasis. In Brenner & Rector’s The Kidney, 7th ed. Philadelphia, WB Saunders, 2004, pp 2173-2178. Sladen R: Anesthetic considerations for the patient with renal failure. Anesthesiol Clin North Am 18:863-882, 2000. United States Renal Data System 2004 Annual Data Report. Bethesda, Md, National Institute of Diabetes and Digestive and Kidney Diseases, 2004. Available at www.usrds.org.

Further Reading Boccardo P: Platelet dysfunction in renal failure. Semin Thromb Hemost 30:579-589, 2004. Foley RN, Parfrey PS, Harnett JD, et al: Clinical and echocardiographic cardiovascular disease in patients starting end stage renal disease therapy: Prevalence, association and progress. Kidney Int 47:186-192, 1995.

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Perioperative Care for Patients with Hepatic Insufficiency (Cirrhosis) Laurence C. Torsher Case Synopsis A 67-year-old man is scheduled for a right total hip arthroplasty. He has consumed more than 80 g/day of alcohol for the past 15 years. The physical examination is remarkable for numerous spider angiomas, hepatosplenomegaly, and moderate ascites. Laboratory results (with range of normal values) are as follows: hemoglobin, 11.2 g/dL (13.6 to 17.2 g/dL); platelet count, 87 × 109/L (150 to 300 × 109/L); total bilirubin, 2.4 mg/dL (0.3 to 1.0 mg/dL); aspartate aminotransferase, 117 units/L (0 to 35 units/L); alanine aminotransferase, 52 units/L (0 to 35 units/L); and prothrombin time, prolonged by 5 to 15 seconds, with an international normalized ratio (INR) of 1.5.

PROBLEM ANALYSIS Definition As the prevalence of liver disease, as well as the survival of those affected, increases, patients with hepatic insufficiency presenting for elective surgery will become more common. Cirrhosis is a disease characterized by irreversible fibrous scarring of the liver in response to hepatocyte injury and death, with regenerative parenchymal nodule formation that disrupts the normal hepatic architecture. Cirrhosis results in loss of functioning hepatocyte mass, and associated scarring and hepatocellular regeneration disorganize the usual hepatic vasculature, leading to portal hypertension. Cirrhosis impairs the liver’s normal function, which includes filtration of portal blood; metabolism of protein, carbohydrates, fat, hormones, and exogenous chemicals, including drugs; synthesis and excretion of bile; and synthesis of coagulation factors. The most common cause of cirrhosis in the United States is excessive and prolonged consumption of alcohol, but it can result from other chronic diseases as well (Table 111-1). Complications of cirrhosis are listed in Table 111-2.

Recognition As many as 10% of men and 5% of women are alcoholic at some time in their lives; however, only 10% to 15% of alcoholics develop cirrhosis. Up to 50% of all hospitalized patients have abused alcohol at one time or another. Ten percent of patients with liver disease undergo operative procedures during the final 2 years of their lives. Cirrhosis has numerous signs and symptoms that may involve many organ systems. Cardiovascular. Cirrhosis is usually associated with a hyperdynamic circulatory state and an increased cardiac output. 466

The increase in cardiac output may be secondary to arteriovenous malformations, especially in the lungs; hypoviscosity secondary to anemia; and increased intravascular volume. Chronic alcohol ingestion can also lead to an alcoholinduced cardiomyopathy that manifests with arrhythmias, low cardiac output, and congestive heart failure.

Table 111–1

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Causes of Cirrhosis

Alcohol Biliary cirrhosis Primary Secondary Sclerosing cholangitis Biliary atresia Bile duct stricture or tumor Infection Viral (hepatitis A, B, C; cytomegalovirus; Epstein-Barr; herpes) Bacterial (brucellosis) Parasitic (capillariasis, echinococcosis, schistosomiasis, toxoplasmosis) Autoimmune chronic active hepatitis Drugs and toxins Methotrexate Methyldopa Amiodarone Isoniazid Steroids Oral contraceptives Arsenic Inherited and metabolic disorders Hemochromatosis Wilson’s disease α1-Antitrypsin deficiency Galactosemia Cystic fibrosis Cryptogenic Graft-versus-host disease Nonalcoholic steatohepatitis

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Perioperative Care for Patients with Hepatic Insufficiency (Cirrhosis)

Complications of Cirrhosis

Portal hypertension Varix formation and variceal bleeding Splenomegaly with hypersplenism and platelet sequestration Ascites formation Spontaneous bacterial peritonitis Decreased gastric emptying Decreased appetite Hydrothorax Hepatorenal syndrome Hepatic encephalopathy Portopulmonary hypertension Coagulopathy Thrombocytopenia Decreased coagulation factor production Low-grade disseminated intravascular coagulation Anemia Hepatocellular carcinoma Malnutrition Osteoporosis Altered immune defenses

Hematologic. Patients with liver disease have multiple hemostatic defects due to reduced synthesis of clotting and fibrinolytic factors. Vitamin K–dependent factors (II, VII, IX, and X) are decreased, as are plasminogen and fibrinogen levels. Owing to splenomegaly caused by portal hypertension, thrombocytopenia and leukopenia are common. Abnormal platelet function has also been observed in patients with cirrhosis. Anemia is due to acute and chronic gastrointestinal blood loss, nutritional deficiency, and bone marrow depression. Gastrointestinal. Portal hypertension may lead to collateral circulation, causing large varices of the stomach, esophagus, anus (hemorrhoids), and umbilicus. These are susceptible to bleeding. Portal venous blood flow is reduced. Ascites and splanchnic congestion can lead to decreased bowel motility and gastric emptying. Renal. Fluid and electrolyte disorders can present as ascites, edema, hyponatremia, hypokalemia, or the hepatorenal syndrome. There is also the potential for hypoalbuminemia and hypoglycemia. Patients with cirrhosis have decreased glomerular filtration rate, avid sodium and water retention, and impaired free water clearance. Secondary hyperaldosteronism and diuretic-induced hypovolemia may lead to

increased water retention, hyponatremia, and other electrolyte abnormalities. Multiple factors may lead to abnormalities in functional circulating fluid volume. Thus, prerenal renal failure is common. Measurement of creatinine levels may underestimate the degree of renal impairment. Central Nervous System. The symptoms of hepatic encephalopathy can range from apathy and restlessness to coma. It is believed to be secondary to inadequate removal of toxins or nitrogenous compounds. Asterixis is a common finding in hepatic encephalopathy. Also, patients who are still actively consuming alcohol are at risk for alcohol withdrawal during hospitalization.

Risk Assessment The history should focus on (1) risk factors for liver disease (e.g., alcohol, drug, or chemical exposure), (2) family history, and (3) symptoms suggestive of liver disease (e.g., jaundice, easy bleeding, expanding abdominal girth). The physical examination focuses on identifying findings compatible with liver disease (e.g., hepatosplenomegaly, right upper quadrant tenderness, ascites, encephalopathy, asterixis, palmar erythema, gynecomastia in men). If the history and physical examination suggest liver disease, blood should be tested for prothrombin time, aspartate aminotransferase and alanine aminotransferase concentrations, total and direct bilirubin, alkaline phosphatase, albumin, complete blood count, creatinine, electrolytes, glucose, and hepatitis viral serology. Other laboratory tests based on comorbid conditions should be carried out as indicated. Table 111-3 lists other perioperative risk factors.

Implications The modified Child-Pugh score (Table 111-4) identifies patients as class A, B, or C, based on prothrombin time, albumin and bilirubin concentrations, and the presence of ascites or encephalopathy. Although originally developed for the risk stratification of patients undergoing esophageal surgery, the Child-Pugh score has also been validated for patients undergoing other abdominal surgeries. Mortality rates for abdominal surgery in one study were 10%, 30%, and 80% for Child-Pugh class A, B, and C patients, respectively. Although patients with mild chronic liver disease tolerate surgery well, for those with higher Child-Pugh scores, an honest discussion of nonsurgical options is warranted.

Table 111–3

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Factors Associated with Poor Perioperative Outcomes in Patients with Cirrhosis

Elevated creatinine American Society of Anesthesiologists risk classification ≥3 History of gastrointestinal bleeding Perioperative infection Need for intraoperative blood transfusion Intraoperative hypotension Hepatic encephalopathy Emergency operation

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Pulmonary. Hepatopulmonary syndrome, which results in an increased alveolar-arterial gradient due to the reduced transit time of blood through the lungs (caused by the hyperdynamic circulatory state and the presence of rightto-left intrapulmonary and intrahepatic shunts), occurs to some degree in 47% of patients. Resultant hypoxia may be worsened by ventilation-perfusion mismatching from altered respiratory mechanics, impairment of diaphragmatic function by ascites, presence of hydrothorax, or generalized weakness from malnutrition. Hyperventilation with primary respiratory alkalosis is common. Two percent of patients may exhibit portopulmonary hypertension—the presence of pulmonary hypertension in conjunction with portal hypertension.

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Modified Child-Pugh Score Points*

Presentation Albumin (g/dL) Prothrombin time Prolonged (sec) INR Bilirubin (mg/dL)† Ascites Encephalopathy

1

2

3

>3.5

2.8-3.5

<2.8

<4.0 <1.7 <2 Absent None

4-6 1.7-2.3 2.0-3.0 Slight-moderate Grade I-II

6.0 >2.3 >3.0 Tense Grade III-IV

*Class A, 5-6 points; class B, 7-9 points; class C, 10-15 points. † For cholestatic diseases (e.g., primary biliary cirrhosis), the bilirubin level is disproportionate to the impairment of hepatic function. For these conditions, assign 1 point for bilirubin level <4 mg/dL, 2 points for bilirubin 4-10 mg/dL, and 3 points for bilirubin >10 mg/dL. INR, international normalized ratio.

Usual causes of perioperative mortality include hemorrhage, sepsis, and acute hepatic function decompensation with or without associated hepatorenal syndrome. Abnormalities in protein concentration, drug clearance, and volume of distribution may have unexpected effects on the onset and duration of medications. Reduced platelet numbers and function and coagulation factor deficiencies associated with low-grade disseminated intravascular coagulation can lead to significant hemorrhage. Moreover, reduced intravascular volume, surgical traction, poor patient positioning, hypocapnia, and impairment of autoregulatory mechanisms may lead to decreased hepatic blood flow, with possible further liver damage. Finally, untreated alcohol withdrawal in the perioperative period with delirium tremens has a mortality rate of 20%. However, with appropriate treatment, mortality rates from withdrawal can be reduced to 1%.

MANAGEMENT AND PREVENTION Preoperatively, if diaphragmatic movement is impaired by tense ascites, respiratory function may be improved by paracentesis. Coagulopathy should be corrected with platelet transfusion (for severe thrombocytopenia), administration of vitamin K, and transfusion of fresh frozen plasma (for prolonged prothrombin time). Cryoprecipitate and desmopressin (DDAVP) may also be helpful. If hemoglobin is less than 10 g/dL, transfusion of red blood cells should be considered to maintain oxygen carrying capability, particularly to the liver. Careful assessment of volume status (with normalization, if necessary) is important, especially for patients receiving diuretics to control ascites or who have undergone recent paracentesis. Evaluation of the patient’s preoperative mental status and function is helpful if there are concerns about worsening encephalopathy perioperatively. Preoperative nutrition consultation may be helpful. Premedication with sedative drugs is usually unnecessary and may have unpredictable effects. In addition to routine intraoperative monitors, an arterial cannula is useful for beat-to-beat monitoring of blood pressure and frequent blood sampling. Use of a peripheral

nerve stimulator to monitor the response to neuromuscular blocking agents is necessary. A pulmonary artery catheter may help with fluid management for patients with significant ascites or for procedures in which large fluid shifts are anticipated. Transesophageal echocardiography may also be helpful for assessing volume status and cardiac function. However, one must be cautious when placing the probe in patients at risk for or with known esophageal varices. Rapid volume administration may be necessary. If so, one should consider at least two large-bore cannulas for venous access. Medication doses may need to be individually tailored owing to altered drug metabolism and volume of distribution in cirrhotic patients. The influence of cirrhosis on a specific drug’s pharmacokinetics depends on its first-pass hepatic extraction. Most sedatives and opioids have prolonged effects and may exacerbate encephalopathy. Neuromuscular blocking agents that depend on hepatic elimination may have prolonged effects. Because atracurium and cisatracurium are eliminated by Hoffman degradation, they offer the advantage of increased predictability of duration of action. The effects of succinylcholine may be prolonged owing to reduced pseudocholinesterase concentrations, but this is rarely clinically significant. Titration to effect, rather than using precalculated doses, is the safest approach for various anesthetic drugs. One must be cautious of medications with potential hepato- and nephrotoxicity (e.g., halothane, nonsteroidal anti-inflammatory drugs, aminoglycoside antibiotics). Patients with cirrhosis may undergo a regional anesthetic technique if no coagulopathy exists and blood pressure is well maintained. With a general anesthetic, rapidsequence induction is necessary. Decreased arterial blood pressure or cardiac output, positive-pressure ventilation, and elevated central venous pressure impair hepatic blood flow, as does surgical trauma to the liver or splanchnic bed. Isoflurane and desflurane appear to increase hepatic blood flow, and sevoflurane maintains it, provided that blood pressure and cardiac output are maintained. Fluid management to correct hypovolemia due to bleeding or reaccumulation of ascites is required to maintain cardiac output and hepatic blood flow. Colloid-containing solutions have theoretical benefits as replacement fluids, especially for patients with hypoalbuminemia. However, this has not been conclusively shown in clinical trials. Postoperatively, observation in a closely monitored setting facilitates the management of fluids, electrolytes, coagulation, respiratory function, and alcohol withdrawal. Finally, if the patient is cirrhotic because of viral hepatitis, the risk of transmission to caregivers is an important concern. All health care workers should be vaccinated against hepatitis B. Universal precautions are recommended for all patients, not just those with a diagnosis of viral hepatitis. In the event of high-risk exposure of a health care worker to contaminated body fluids or tissues from a patient with viral hepatitis, the hospital employee health service should be notified immediately.

Further Reading Gatecel C, Losser M, Payen D: The postoperative effects of halothane versus isoflurane on hepatic artery and portal vein blood flow in humans. Anesth Analg 96:740-745, 2003.

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Ginès R, Càrdenas A, Arroyo V, et al: Management of cirrhosis and ascites. N Engl J Med 350:1646-1654, 2004. Mansour A, Watson W, Shayani V, et al: Abdominal operations in patients with cirrhosis: Still a major surgical challenge. Surgery 122:730-735, 1997. O’Riordan J, O’Beirne HA, et al: Effects of desflurane and isoflurane on splanchnic microcirculation during major surgery. Br J Anaesth 78:95-96, 1997.

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Patel T: Surgery in the patient with liver disease. Mayo Clin Proc 74: 593-599, 1999. Schuckit MA: Alcohol and alcoholism. In Braunwald E, Fauci AS, Kaper DL, et al (eds): Harrison’s Principles of Internal Medicine. New York, McGraw-Hill, 2001, p 2561. Ziser A, Plevak DJ, Wiesner RH, et al: Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery. Anesthesiology 90:42-53, 1999.

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Porphyrias Bradly J. Narr Case Synopsis A 56-year-old woman with a 23-year history of intermittent abdominal pain was admitted to the hospital. For 24 hours before admission, she had nausea, vomiting, and palpitations, and on admission, she was “out of her head.” She retched during the evaluation, so rapid-sequence induction was performed with thiopental (350 mg) and succinylcholine (100 mg); maintenance was with nitrous oxide and fentanyl (700 μg). Following abdominal computed tomography (the scan was normal), she was lethargic and had increased pulse (125 beats per minute) and blood pressure (196/110 mm Hg). Because the bladder appeared distended, catheterization was performed, which produced 400 mL of dark red urine.

PROBLEM ANALYSIS Definition The porphyrias are rare, inherited disorders of one of the steps in the biosynthesis of heme (Fig. 112-1). Each porphyria has a characteristic set of symptoms and a specific pattern of heme precursor (porphyrin) overproduction that distinguish it from the others. Carriers of abnormal genes encoding porphyrias often do not have clinical symptoms. Porphyrins that accumulate as a result of individual enzyme defects may be deposited into a variety of tissues, based on the lipid solubility and size of the porphyrin

Succinyl CoA

Glycine

δ-Aminolevulinic acid (ALA)

Porphobilinogen (PBG)

Hydroxmethylbiline

Acute intermittent porphyria

Uroporphyrinogen

Coproporphyrinogen

Hereditary coproporphyria

molecule. The porphyrins that occur in the first half of the heme synthetic pathway (see Fig. 112-1) are water soluble and are excreted in urine. Those that accumulate in the nervous system cause neuroporphyrias, and those that accumulate in skin cause cutaneous porphyrias. Those that accumulate in both cause neurocutaneous porphyrias. The disorders of most interest to anesthesiologists fall into the class called acute porphyrias (Table 112-1). Enzymeinducing drugs are the most important triggering factor during anesthesia.

Recognition The neuroporphyrias and neurocutaneous porphyrias are characterized by acute attacks that can be precipitated by infection, fasting, alcohol intoxication, or administration of some drugs (Tables 112-2 and 112-3). These events stimulate heme synthesis, but because of the enzyme defects, heme is not produced. Therefore, negative feedback to the rate-limiting step (glycine + succinyl coenzyme A → δ-aminolevulinic acid catalyzed by the enzyme δ-aminolevulinic acid synthetase) does not occur. The resulting buildup of porphyrins is believed to cause acute symptoms and signs. The disease is hereditary and is transmitted most often by an autosomal dominant path. Everyone inherits two copies of each of the heme synthetic enzyme genes. Mutation of one allelle, which results in a 50% reduction in enzyme activity, may be completely asymptomatic until the stresses on the heme synthetic system noted earlier provoke an acute problem. More than 90 mutations that cause acute intermittent porphyria have been identified. There is no evidence that any specific genotype determines the severity of an acute attack.

Protoporphyrinogen Variegate porphyria Protoporphyrin ⫹Fe2⫹ Heme Figure 112–1 ■ Simplified diagram of the metabolic pathways for heme synthesis. As shown, the porphyrias are inherited disorders of one of the steps in the biosynthesis of heme.

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Table 112–1

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Disorders of Heme Biosynthesis of Most Importance to Anesthesiologists

Acute intermittent porphyria Variegate porphyria Hereditary coproporphyria δ-Aminolevulinic acid dehydratase deficiency

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Table 112–2

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Conditions That May Precipitate Acute Porphyrias

Fasting Hormones Alcohol (excessive use) Drugs (barbiturates and sulfonamides)

Risk Assessment

471

the use of drugs with no or low risk (see Table 112-3)—has made the risk of inducing acute porphyria during administration of anesthesia a remote possibility.

Data comparing drugs of different classes are incomplete in that there are no prospective, randomized studies. Lists have been published categorizing drugs as safe, probably safe, and unsafe (see Table 112-3), based on personal experience, case reports, and the screening of different drugs in animal (chemically primed rats) or tissue (chick embryo) models. Recent reviews have recommended a more permissive attitude toward precipitating factors, especially during the quiescent phase of the disease, which accounts for a great majority of patients with porphyria. Triggering events vary among patients. Those who are very sensitive may require strict avoidance of all potentially porphyrinogenic events.

MANAGEMENT Appropriate therapy is difficult without an accurate diagnosis, which is hindered by other variables. These include lack of specific symptoms, latent disease that may recur in only 10% of susceptible individuals, and the high response rate of acute porphyria to supportive therapy. Supportive therapy includes dextrose-containing intravenous fluids because fasting, dehydration, or alcohol intoxication1 may induce acute porphyria. Additional measures include analgesics and anxiety relief (anxiolytics)2 and treatment of any associated hypertension and tachycardia. The use of intravenous heme preparations (hematin and its analogues) to provide exogenous negative feedback to the rate-limiting steps in heme synthesis may be lifesaving when employed early in severe attacks. 1 Alcohol (ethanol) inhibits the release of antidiuretic hormone, resulting in enhanced diuresis. 2 Droperidol and phenothiazines, but possibly not all benzodiazepines, appear to be safe (see Lambrecht, Gildemeister, Pepe, et al under “Further Reading”).

Drugs Relevant to Anesthesia that May Produce Acute Porphyrias

Use/Safety*

Induction

Maintenance

Other

Do not use (unsafe)

Barbiturates

Enflurane

Use carefully (probably safe)

Ketamine Etomidate

Use (safe)

Propofol

Isoflurane Sevoflurane Desflurane Nitrous oxide Halothane

Pentazocine, hydralazine, calcium channel blockers†, chlordiazepoxide, ketorolac, sulfonamides Atracurium, mivacurium, vecuronium, rocuronium, mepivacaine, benzodiazepines, cimetidine, ranitidine, ondansetron, sodium nitroprusside, metoclopramide, clonidine, ACE inhibitors, β-blockers‡ Analgesics or antagonists: narcotics, aspirin, acetaminophen, naloxone Muscle relaxants or reversal agents: pancuronium, succinylcholine, glycopyrrolate, neostigmine Local anesthetics: procaine, bupivacaine, tetracaine, prilocaine Supportive: droperidol, phenothiazines, atropine, corticosteroids, α-agonists

*The evidence against the use of drugs in the “do not use” category is robust. There is much less evidence, conflicting evidence, or only educated guesses based on chemical structure–activity relationships (CSAR) in the “use carefully” category. For drugs in the “use” category, there is no hard or CSAR evidence against their use. † Based on animal studies, dihydropyridine calcium channel blockers are more likely than diltiazem or verapamil to cause acute porphyria. ‡ Based on a single report (Moore et al; see “Further Reading”), β-blockers appear to be safe for treating tachycardia associated with acute porphyria. ACE, angiotensin-converting enzyme.

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

In the past, anesthesia posed a real risk for patients with unrecognized porphyria. In South Africa, which had the highest world incidence of variegate porphyria, a study was conducted at Groote Schur Hospital in Cape Town between 1950 and 1971. It showed that 31 of 145 hospital admissions for acute attacks of porphyria were likely precipitated by thiopental induction of anesthesia. Since that time, this incidence has been markedly reduced by better clinical and historical assessment, improved biochemical testing, and an awareness of the potential for drug interactions in patients with porphyria. Historically, acute porphyria was always considered in the differential diagnosis of patients presenting with an acute abdomen. However, the proliferation of modern imaging techniques has made exploratory surgery a thing of the past in most medical centers. This evolution in patient care, in concert with modern, balanced anesthetic techniques—including

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Porphyrias

Implications

The clinical presentation includes recurrent unexplained abdominal pain, sensory or motor neuropathy, autonomic dysfunction (e.g., hypertension, tachycardia), nausea, vomiting, and a history of red or dark urine. Acute porphyria attacks are always associated with elevated levels of δ-aminolevulinic acid, porphobilinogen, or both. Diagnosis is based on biochemical investigation. Only a doubling of the upper normal limits for δ-aminolevulinic acid and porphobilinogen justifies further workup. Also, symptoms should not be attributed to porphyria without a marked increase (several times normal) in urinary porphyrin excretion.

Table 112–3

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PREVENTION Many drugs considered unsafe for patients who have been diagnosed with porphyria have been implicated on theoretical grounds. Such drugs either induce heme synthesis or stimulate the cytochrome P-450 system. There is sufficient evidence to recommend complete avoidance of barbiturates, sulfonamides, and excessive alcohol use. Enzyme-inducing drugs remain the most important triggering factor related to porphyria and anesthesia. Use of drugs based on the recommendations in Table 112-3 should provide a good outcome for patients with documented porphyria. Blood loss with a resultant increase in heme demand does not stimulate the heme synthetic pathway enough to result in acute porphyria.

Further Reading Elder GH, Hift RJ, Meissner PN: The acute porphyrias. Lancet 349: 1613-1617, 1997. Harper P, Hybinette T, Thunell S: Large phlebotomy in variegate porphyria. J Intern Med 242:255-259, 1997. Harrison GG, Meissner PN, Hift RJ: Anaesthesia for the porphyric patient. Anaesthesia 48:417-421, 1993.

James MFM, Hift RJ: Porphyrias. Br J Anaesth 85:143-153, 2000. Kauppinen R, Mustajoki P: Prognosis of acute porphyria: Occurrence of acute attacks, precipitating factors, and associated disease. Medicine 71:1-13, 1992. Lambrecht RW, Gildemeister OS, Pepe JA, et al. Effects of antidepressants and benzodiazepine-type anxiolytic agents on hepatic porphyrin accumulation in primary cultures of chick embryo liver cells. J Pharmacol Exp Ther 291:1150-1155, 1999. Lambrecht RW, Gildemeister OS, Williams A, et al: Effects of selected antihypertensives and analgesics on hepatic porphyrin accumulation: Implications for clinical porphyria. Biochem Pharmacol 58:887-896, 1999. Marks GS, Goldman DR, McCluskey SA, et al: The effects of dihydropyridine calcium antagonists on heme biosynthesis in chick embryo liver cell culture. Can J Physiol Pharmacol 64:438-443, 1986 Meissner PN, Meissner DM, Sturrock ED, et al: Porphyria: The University of Cape Town experience. S Afr Med J 72:755-761, 1987. Moore MR, McColl KE, Goldberg A: The porphyrias. Diabete Metab 5: 323-336, 1979. Mustajoki P, Nordmann Y: Early administration of heme arginate for acute porphyric attacks. Arch Intern Med 153:2004-2008, 1993. Pierach CA: Did Ulysses have porphyria? J Lab Clin Med 144:7-10, 2004. Tefferi A, Colgan JP, Solberg LA Jr: Acute porphyrias: Diagnosis and management. Mayo Clin Proc 69:991-995, 1994. Tefferi A, Solberg LA Jr, Ellefson RD: Porphyrias: Clinical evaluation and interpretation of laboratory tests. Mayo Clin Proc 69:289-290, 1994.

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Acute Pancreatitis David M. Rothenberg Case Synopsis A 56-year-old woman is admitted to the intensive care unit (ICU) following 5 days of increasing abdominal pain, nausea, and vomiting. The patient describes repeated episodes of right upper quadrant pain after certain meals for the past 2 years, but she has not sought medical attention. On physical examination she is noted to have tachypnea, tachycardia, and hypotension. Her sclerae are mildly icteric. Breath sounds are diminished in the lower left lung field, and abdominal palpation reveals diffuse rebound tenderness. Arterial blood gas analysis reveals a mixed respiratory and metabolic alkalosis with an arterial oxygen tension (PaO2)of 70 mm Hg (fraction of inspired oxygen [FiO2], 0.5). The white blood cell count is 8000/mm3. The serum amylase level is normal, although lipase, bilirubin, and alanine aminotransferase levels are elevated. Computed tomography (CT) of the abdomen shows an enlarged pancreas with two peripancreatic fluid collections.

PROBLEM ANALYSIS Definition

Recognition Signs and symptoms of acute pancreatitis include the following: ●

● ●

Diffuse, constant abdominal pain, typically radiating to the back and flank areas, in association with nausea and vomiting Tachycardia and tachypnea (common findings) Hypotension relative to the degree of hypovolemia, hemorrhage, or systemic vasodilatation

Table 113–1

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Causes of Acute Pancreatitis

Biliary tract disease (e.g., choledocholithiasis, ampullary tumor, pancreas divisum) Ethanol abuse Hypertriglyceridemia Hypercalcemia Trauma Postsurgical (e.g., cardiopulmonary bypass, endoscopic retrograde cholangiopancreatography) Vascular insufficiency (e.g., hypoperfusion, shock, vasculitis) Drugs (e.g., azathioprine, furosemide, pentamidine) Infection (e.g., mumps, ascariasis, Mycobacterium tuberculosis, AIDS) Other toxins (e.g., methanol, scorpion bites) Idiopathic AIDS, acquired immunodeficiency syndrome.

473

PHYSIOLOGIC IMBALANCE & COEXISTING AND COEXISTINGDISEASE DISEASE

Acute pancreatitis commonly presents as a mild, self-limited disorder, but severe systemic manifestations may develop in 20% to 25% of patients, resulting in sepsis, shock, and multiorgan dysfunction syndrome. The majority of cases of acute pancreatitis are associated with gallstones and alcohol abuse, but the link between cause and pathogenesis remains poorly understood. It appears that dysfunction of the acinar cell, the most active protein-synthesizing cell in the body, is responsible for initiating a host response that may lead to local edema, hemorrhage, or necrosis, with subsequent release of inflammatory mediators into the peritoneal space and circulation. The acinar cell normally secretes and packages digestive and lysosomal enzymes into vacuoles; these enzymes eventually mature into zymogen granules and lysosomes, respectively. Fusion occurs at the luminal surface, allowing the release of enzyme precursors in a process known as exocytosis. Experimental studies have noted that luminal enzyme secretion is decreased in acute pancreatitis, whereas synthesis remains normal. It is speculated that the clinical process is the result of reflux of bile into or septal compression of the pancreatic ductal tree. Intra-acinar activation of the proteolytic enzyme trypsin, from its precursor trypsinogen, is instrumental in precipitating acute pancreatitis. Intracellular activation of trypsin leads to the conversion of other proteolytic enzymes, such as elastase and phospholipase A2, to their active forms, causing autodigestive damage of the pancreas. In mild cases of acute pancreatitis it is presumed that trypsin combines with intracellular α1-antitrypsin to inactive trypsin. The complex is transferred to α2-macroglobulin for eventual consumption by circulating monocytes and macrophages. In severe forms of acute pancreatitis this process is overwhelmed, resulting in a more systemic inflammatory response. The release of elastase into the peripancreatic space may cause degradation

of blood vessels and produce local hemorrhage; the release of phospholipase A2 may degrade surfactant and be the factor by which acute lung injury occurs. Mediators such as kallikreins, complement, thrombin, and chymotrypsin are also released and modulate the degree of local or systemic injury, most likely through a complex interplay of cytokines and reactive oxygen metabolites. The more common causes of acute pancreatitis are listed in Table 113-1.

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Tenderness, guarding, and diminished bowel sounds on abdominal examination Periumbilical and flank ecchymosis (Cullen’s and Grey Turner’s signs, respectively; these occur less commonly and represent pancreatic hemorrhage and dissection of blood into the retroperitoneal space) Jaundice (seen in 15% of cases, usually in association with biliary tract obstruction from gallstones)

Elevation of the serum amylase level is a characteristic, albeit somewhat nonsensitive, marker of acute pancreatitis. Amylase is released early in the course of the disease and tends to peak within 5 days of the onset of symptoms, yet it may be undetectable in 20% to 30% of cases. Hyperamylasemia is also nonspecific, as it may exist in other disease states (e.g., perforated peptic ulcer, small bowel obstruction, mesenteric infarction, pelvic inflammatory disease, diabetic ketoacidosis, all of which are characterized by acute abdominal pain). Fractionated serum amylase levels, urine amylase levels, and amylase-creatinine clearance ratios do not appear to contribute to diagnostic accuracy in acute pancreatitis. The serum lipase level is a more accurate test for acute pancreatitis (90% sensitive and specific), and it tends to remain elevated long after the onset of symptoms. Elevation in alanine aminotransferase, alkaline phosphatase, and bilirubin levels points toward a diagnosis of gallstone-induced pancreatitis. Additional serum markers that may be useful in predicting the severity of acute pancreatitis include C-reactive protein (a nonspecific acute-phase reactant), polymorphonuclear elastase, and trypsinogen-activating peptide. Elevated trypsinogen-activating peptide levels in either urine or peritoneal fluid have been shown to be highly indicative of pancreatic necrosis. Imaging techniques are invaluable in diagnosing acute pancreatitis. Chest radiographs may show basilar atelectasis or pleural effusions (these effusions are exudative in nature and characterized by high levels of amylase and lipase). Plain abdominal films may be useful if only to rule out a perforation or to reveal a “sentinel loop,” signifying a localized ileus due to acute pancreatitis. Ultrasonography, though important in detecting gallstones or complications of acute pancreatitis (e.g., pseudocysts, abscesses), has a limited role in the detection of acute pancreatitis, because findings may be obscured by obesity or the presence of overlying bowel gas. Contrast-enhanced CT of the abdomen is the most accurate method of diagnosing acute pancreatitis and its local complications. Pancreatic abnormalities are discovered in more than 90% of patients with acute pancreatitis, the severity of which can be graded by CT to correlate with pancreatic abscess or necrosis. Table 113-2 presents a useful grading system for acute pancreatitis. Patients with grades A through D have a less than 2% incidence of abscess formation, whereas those classified as grade E have a 57% incidence of abscess formation. In addition to contrast-enhanced CT, dynamic CT pancreatography offers the possibility of detecting pancreatic perfusion abnormalities that correlate with the location and extent of pancreatic and retroperitoneal fat necrosis. Finally, magnetic resonance imaging may be beneficial in distinguishing between uncomplicated pseudocysts and those associated with necrosis. Identifying these patients early in the course of the disease is critical for the prevention

Table 113–2

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Grading System for Pancreatitis

Grade A: Normal pancreas Grade B: Pancreatic enlargement, focal or diffuse Grade C: Pancreatic enlargement with mild peripancreatic inflammation Grade D: Enlarged pancreas associated with fluid in anterior pararenal space Grade E: Enlarged pancreas with fluid collections in at least two areas

of subsequent infection and in the timing of surgical debridement.

Risk Assessment A number of prognostic grading systems have been used to gauge the severity of acute pancreatitis and determine optimal treatment. Despite their inability to predict late morbidity or mortality, Ranson’s criteria (Table 113-3) are the most frequently used method of predicting early complications of acute pancreatitis. Mortality rates are 1% for patients with fewer than three signs, 15% for those with three to four signs, 40% for those with five to six signs, and up to 100% for patients with seven or more signs. The addition of CT data may improve the accuracy of this scoring system. The acute physiologic assessment and chronic health evaluation (APACHE) II scoring system (Table 113-4) is a specific and sensitive method of assessing the severity of acute pancreatitis. Unlike Ranson’s criteria, it is applicable throughout the course of the illness. One study in young patients with gallstone pancreatitis identified heart rate greater than 110 beats per minute, white blood cell count greater than 14.5/mm3, blood urea nitrogen greater than 12 mmol/L, serum glucose greater than 150 mg/dL, and APACHE II score greater than 5 as predictive of the development of serious complications, such as necrotizing pancreatitis. Finally, obesity is thought to be a major risk factor for increased mortality from acute pancreatitis (36% in obese patients versus 6.9% in nonobese patients). The higher mortality is thought to be due to increased peripancreatic fat and greater necrosis.

Table 113–3

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Causes of Acute Pancreatitis

At Admission Age >55 yr White blood cell count >16,000/mm3 Blood glucose level >200 mg/dL Serum lactate dehydrogenase level >350 IU/L Serum glutamic-oxaloacetic transaminase level >250 units/dL

During Initial 48 Hours Hematocrit decline >10% Blood urea nitrogen level rise >5 mg/dL Serum calcium level <8 mg/dL Arterial PO2 <60 mm Hg Base deficit >4 mEq/L Estimated fluid sequestration >6 L From Ranson JHC: Etiological and prognostic factors in human acute pancreatitis: A review. Am J Gastroenterol 77:633-638, 1982.

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Table 113–4

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■

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Acute Pancreatitis

APACHE II Severity of Disease Classification System High Abnormal Range

Physiologic Variable

+4

+3

+2

Low Abnormal Range +1

0

+1

+2

+3

+4

APS, APACHE score. From Knaus WA, Draper EA, Wagner DP, et al: APACHE II: A severity of disease classification system. Crit Care Med 13:818-829, 1985.

Implications Although the majority of patients with acute pancreatitis have an uncomplicated course, 20% to 25% develop sequelae that may be life threatening, requiring either ICU support or surgical intervention. Local complications include sterile or infected tissue necrosis, pseudocysts, abscesses, colonic fistulas, gastrointestinal hemorrhage, and splenic rupture. Systemic complications include shock, acute renal failure, acute lung injury, coagulopathy, hyperglycemia, hypocalcemia, retinopathy, and psychosis.

MANAGEMENT The treatment of uncomplicated acute pancreatitis is primarily supportive, with the judicious use of intravenous fluids and parenteral analgesia. Nasogastric suctioning is beneficial only in patients with documented ileus. Recent randomized, controlled trials have confirmed the benefits of early enteral feedings in patients with severe acute pancreatitis, noting

less end-organ failure, a diminished systemic inflammatory response, and shorter length of hospital stay compared with parenteral feedings. The use of prophylactic antibiotics for severe acute pancreatitis remains controversial. A 1998 metaanalysis of eight prospective, randomized, controlled trials found that reduced mortality was limited to patients who were administered broad-spectrum antibiotics that could penetrate pancreatic tissue. However, a more recent study cited an increase in the incidence of fungal infections and higher perioperative mortality. Also, controlled trials investigating the use of H2-antagonists, protease inhibitors, and peritoneal lavage were unable to document improved outcomes. Early use of endoscopic retrograde cholangiopancreatography (ERCP) and papillotomy for biliary pancreatitis is also controversial. One prospective multicenter study in the late 1990s failed to show a benefit from ERCP. In more severe forms of acute pancreatitis, ICU support with mechanical ventilation for respiratory failure, dialysis for acute renal failure, and infusions of vasoactive drugs may be required. Urgent surgery is indicated only in cases of deteriorating condition or evidence of pancreatic sepsis. The diagnosis of

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Temperature, rectal (°C) ≥41 39-40.9 38.5-38.9 36-38.4 34-35.9 32-33.9 30-31.9 ≤29.9 Mean arterial pressure (mm Hg) ≥180 130-179 110-129 70-109 50-69 ≤49 Heart rate (ventricular response) ≥180 140-179 110-139 70-109 55-69 40-54 ≤39 Respiratory rate (nonventilated or ≥50 35-49 25-34 12-24 10-11 6-9 ≤5 ventilated) Oxygenation: PAO2 – PaO2, or PaO2 (mm Hg) a. FiO2 ≥0.5: 500 350-499 200-349 <200 record PAO2 – PaO2 b. FiO2 <0.5: PO2 >70 PO2 61-70 PO2 55-60 PO2 <55 record only PaO2 Arterial pH ≥7.7 7.6-7.69 7.5-7.59 7.33-7.49 7.25-7.32 7.15-7.24 <7.15 Serum sodium (mmol/L) ≥180 160-179 155-159 150-154 130-149 120-129 111-119 <110 Serum potassium (mmol/L) ≥7 6-6.9 5.5-5.9 3.5-5.4 3-3.4 2.5-2.9 <2.5 Serum creatinine (mg/100 mL) ≥3.5 2-3.4 1.5-1.9 0.6-1.4 <0.6 (double point score for acute renal failure) Hematocrit (%) ≥60 50-59.9 46-49.9 30-45.9 20-29.9 <20 White blood cell count ≥40 20-39.9 15-19.9 3-14.9 1-2.9 <1 (total/mm3, in 1000s) Glasgow coma score (GCS): Score = 15 minus actual GCS A Total APS: Sum of the 12 individual variable points Serum HCO3 (venous, mmol/L) ≥52 41-51.9 32-40.9 22-31.9 18-21.9 15-17.9 <15 (not preferred; use if no arterial blood gases) B Age points: C Chronic health points: APACHE II Score Assign points as follows: If the patiet has a history of severe organ system insufficiency Sum of A + B + C Age (yr) Points or is immunocompromised, assign points as follows: A APS points _____________ ≥44 0 a. For nonoperative or emergency postoperative patients— B Age points _____________ 45-54 2 5 points 55-64 3 or C Chronic health points _________ 65-74 5 b. For elective postoperative patients—2 points ≥75 6 Total APACHE II ___________

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infected necrotizing pancreatitis is often made by CT-guided fine-needle aspiration and signals the need for urgent surgical debridement. The role of surgical intervention for sterile necrotizing pancreatitis remains controversial. Intraoperative management relies on the maintenance of intravascular volume, monitoring of serum electrolytes and glucose levels, and recognition of sepsis and acute lung injury. In this regard, pulmonary artery catheterization may be useful in directing vasopressor or other supportive therapies.

PREVENTION Episodes of acute pancreatitis are prevented by avoiding exposure to precipitating factors such as alcohol and by early surgical therapy for choledocholithiasis. Use of biochemical and radiographic markers to facilitate the early recognition of necrotizing pancreatitis may further reduce the morbidity and mortality from acute pancreatitis.

Further Reading Arnell TD, de Virgilio C, Chang L, et al: Admission factors can predict the need for ICU monitoring in gallstone pancreatitis. Am Surg 62: 815-819, 1996.

Balthazar EJ: Acute pancreatitis: Assessment of severity with clinical and CT evaluation. Radiology 223:603-613, 2002. Folsch UR, Nitsche R, Ludtke R, et al: Early ERCP and papillotomy compared with conservative treatment for acute biliary pancreatitis: The German Study Group on Acute Biliary Pancreatitis. N Engl J Med 336:237-242, 1997. Funnell IC, Bornman PC, Weakley SP, et al: Obesity: An important prognostic factor in acute pancreatitis. Br J Surg 80:484-486, 1993. Golub R, Siddiqi F, Pohl D: Role of antibiotics in acute pancreatitis. J Gastrointest Surg 2:496-503, 1998 Gudgeon AM, Heath DI, Hurley P, et al: Trypsinogen activation peptides assay in the early prediction of severity of acute pancreatitis. Lancet 335:4-8, 1990. Gumaste V, Dave P, Sereny G: Serum lipase: A better test to diagnose acute alcoholic pancreatitis. Am J Med 92:239-242, 1992. Isenmann R, Runzi M, Kron M, et al: Prophylactic antibiotic treatment in patients with predicted severe acute pancreatitis: A placebocontrolled, double-blind trial. Gastroenterology 126:997-1004, 2004. Ranson JHC: Etiological and prognostic factors in human acute pancreatitis: A review. Am J Gastroenterol 77:633-638, 1982. Swaroop VS, Chari ST, Clain JE: Severe acute pancreatitis. JAMA 291: 2865-2868, 2004. Wilson C, Heath DI, Imrie CW: Prediction of outcome in acute pancreatitis: A comparative study of APACHE II, clinical assessment and multiple factor scoring systems. Br J Surg 77:1260-1264, 1990. Yousaf M, McCallion K, Diamond T: Management of severe acute pancreatitis. Br J Surg 90:402-420, 2003.

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Autonomic Hyperreflexia C. Lee Parmley and Steven J. Allen

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Case Synopsis A 25-year-old woman develops headache and severe hypertension following a urologic procedure performed with topical anesthesia. She has C6 quadriplegia resulting from a motor vehicle accident 5 years ago. Examination reveals blood pressure 240/130 mm Hg, pulse 45 beats per minute, facial flushing, and cool lower extremities.

PROBLEM ANALYSIS Definition

Table 114–1

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Autonomic Hyperreflexia Triggers

Bladder or large or small bowel distention Cutaneous stimulation Uterine contractions Lower or upper extremity surgery Sexual pathology Urogenital pathology Cystoscopy and other genitourinary instrumentation Extracorporeal lithotripsy

Autonomic hyperreflexia should be suspected when headache or hypertension develops in any patient with paraparesis of greater than 2 weeks’ duration. Autonomic hyperreflexia’s onset is variable among patients, and some may exhibit signs as early as the fourth postinjury day. Clinical findings are related to the level of intact innervation. Evidence of sympathetic stimulation below the level of the lesion may include skin pallor, pilomotor erection, spastic muscle contraction, and increased muscle tone. Above the lesion, one may find flushing of the face and neck, diaphoresis, mydriasis, and lid retraction. Awake patients frequently complain of headache, dyspnea, blurred vision, chest pain, nausea, and a sense of ill ease.

Risk Assessment The severity of autonomic hyperreflexia is dependent on the amount of cord below the lesion that is involved with sympathetic outflow. Thus, lesions below T10 generally are not associated with autonomic hyperreflexia, because there are few sympathetic spinal synapses to disinhibit. Conversely, lesions above T5 tend to be associated with the worst autonomic hyperreflexia–related problems, because the majority of spinal sympathetic efferents arise below this level. The site and nature of the planned procedure may also play a role. The majority of patients come to the operating room for urologic procedures, all of which are likely to produce autonomic hyperreflexia. One group of at-risk patients that has been the subject of increased interest in recent years is spinal cord–injured parturients. Because uterine contractions may result in strong sympathetic outflow, these patients pose a unique challenge during labor. The literature suggests that the incidence of autonomic hyperreflexia is as high as 75% in this population. In addition, it may be difficult to distinguish autonomic hyperreflexia from preeclampsia. Accordingly, some clinicians advise epidural anesthesia for all spinal cord–injured women in labor to prevent autonomic hyperreflexia.

Implications If untreated, autonomic hyperreflexia can lead to serious complications and even death. Cardiovascular complications include left ventricular failure, myocardial ischemia, and possibly arrhythmias, all related to increased demands related to severe hypertension or central nervous system complications. 477

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Autonomic hyperreflexia is a disturbance arising in patients with chronic spinal cord injury. It is also termed autonomic dysreflexia, hypertensive autonomic crisis, and mass reflex. Autonomic hyperreflexia is characterized by massive sympathetic activity set off by reflex stimulation from a variety of triggers (Table 114-1). It has been reported in 85% of patients within 2 to 3 weeks of spinal cord injury. Because it requires viable spinal cord below the level of injury or transaction, the disturbance does not occur in patients with paraplegia due to spinal cord infarction. Autonomic hyperreflexia occurs when the hypothalamus and brainstem can no longer modulate segmental spinal sympathetic nerves and thereby inhibit their output. In the acute phase following spinal cord injury, there is low sympathetic activity. However, sympathetic activity returning to viable cord below the lesion is isolated from upper inhibitory control. This can result in an uncontrolled sympathetic response to a stimulus. The sympathetic activity causes vasoconstriction in the vasculature below the spinal cord lesion, leading to systemic hypertension. The hypertension stimulates the baroreceptors in the aortic arch and carotid sinus, inducing bradycardia and vasodilatation above the spinal cord defect. The vasodilatation is thought to be the cause of headaches and flushing. The severity of autonomic hyperreflexia is dependent on the amount of cord below the lesion that is involved with sympathetic outflow. Thus, higher cord lesions have a more profound response than do lower lesions.

Recognition

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Central nervous system complications are typically those associated with hypertensive encephalopathy, such as confusion, seizures, and stroke. Autonomic hyperreflexia may also increase surgical blood loss.

MANAGEMENT The onset of hypertension requires immediate intervention, because systemic blood pressure can quickly escalate to dangerous levels. The first maneuver should be to remove the offending stimulus (e.g., relieving a distended bladder). If hypertension develops during a general anesthetic, the concentration of volatile agent should be increased. If an epidural catheter is being used, raising the level of the block may help. Pharmacologic intervention can consist of any agent that interrupts the sympathetic reflex and has the characteristics of rapid onset, short duration, and low toxicity. The most frequently recommended drugs are sodium nitroprusside and nifedipine. Sodium nitroprusside has the advantages of reliability, rapid onset, and titratability. However, continuous use may require monitoring for cyanide toxicity. Also, nitroprusside may be harder to titrate to the desired effect (requiring more dosing changes), and it may be associated with untoward hypotension.1 Nifedipine has an acceptable degree of effectiveness in treating autonomic hyperreflexia. Its advantages are oral (sublingual) administration, relatively short duration, and minimal toxicity in this patient population. Disadvantages are unreliable or delayed absorption, possibly leading to excessive dosing and hypotension. Nicardipine’s actions are similar to those of nifedipine; it has a short half-life of elimination (minutes) after intravenous bolus administration and no specific organ toxicity during prolonged infusion.2 For these reasons, nicardipine might be preferred over nifedipine or sodium nitroprusside for hypertensive emergencies in patients with autonomic hyperreflexia, but there is little precedent for such use. There are also anecdotal reports of excellent results with magnesium sulfate.

PREVENTION The main goal in patients at risk for autonomic hyperreflexia is to prevent hypertension. The purpose of anesthetic management is not to prevent pain in an insensate area but rather to prevent enhanced sympathetic activity due to visceral organ stimulation. Although topical and general anesthesia may be used, regional anesthesia is associated with the lowest incidence of perioperative hypertension.

1 Nicardipine is a primary arterial dilator, whereas sodium nitroprusside has both venodilator (reduces preload) and arterial dilator properties that are about equal. 2 Nicardipine differs from nifedpine in two important respects, however. First, it has no vehicle (polysorbate). Polysorbate has direct myocardial depressant and vasodilatory properties on both venous capacitance and arterial beds. Second, nicardipine is approved for intravenous dosing.

This is because regional techniques most directly block conduction of the afferent nerves in the spinal cord. For urologic procedures, most of the stimulation is via the sacral nerves, suggesting that a subarachnoid block is an appropriate technique. Lumbar epidural anesthesia is less reliable, because the sacral nerve roots may not be completely blocked. Regional anesthesia also has the advantage of providing muscle relaxation and preventing sudden leg flexion during visceral organ manipulation. Some clinicians are reluctant to perform a regional technique in the presence of a neurologic deficit. One reason is that the level of the block is difficult to determine owing to the lack of sensation. As an alternative, some clinicians employ nifedipine or nicardipine for hypertension prophylaxis. General anesthesia can be problematic in patients with autonomic hyperreflexia. Inadequate anesthesia (especially for tracheal intubation, electroconvulsive therapy, aortic cross-clamping, and the like) may trigger dangerous hypertension, whereas anesthetic overdose may result in profound hypotension. Typically, anesthesia must be deep to prevent autonomic hyperreflexia. For that reason, a technique based solely on nitrous oxide and opioids may not be satisfactory. Isoflurane and sevoflurane have been used successfully, likely owing to their salutary vasodilatory effects (i.e., reducing both preload and afterload). Emergence must be carefully managed, because patients with high spinal cord injury have some degree of respiratory compromise. The adequacy of ventilation must be ensured before and after extubation.

Further Reading Amzallag M: Autonomic hyperreflexia. Int Anesthesiol Clin 31:87-102, 1993. Baker ER, Cardenas DD, Benedetti TJ: Risks associated with pregnancy in spinal cord-injured women. Obstet Gynecol 80:425-428, 1992. Bernstein A, Richlin D, Sotolongo JR Jr: Nifedipine pretreatment for prevention of autonomic hyperreflexia during anesthesia-free extracorporeal shock wave lithotripsy. J Urol 147:676-677, 1992. Jones NA, Jones SD: Management of life-threatening autonomic hyperreflexia using magnesium sulphate in a patient with a high spinal cord injury in the intensive care unit. Br J Anaesth 88:434-438, 2002. Kobayashi A, Mizobe T, Tojo H, et al: Autonomic hyperreflexia during labour. Can J Anaesth 42:1134-1136, 1995. Krassioukov AV, Furlan JC, Fehlings MG: Autonomic dysreflexia in acute spinal cord injury: An underrecognized clinical entity. J Neurotrauma 20:707-716, 2003. Lambert DH, Deane RS, Mazuzan JE Jr: Anesthesia and the control of blood pressure in patients with spinal cord injury. Anesth Analg 61:344-348, 1982. Maehama T, Izena H, Kanazawa K: Management of autonomic hyperreflexia with magnesium sulfate during labor in a woman with spinal cord injury. Am J Obstet Gynecol. 813:492-493, 2000. Pereiara L: Obstetric management of the patient with spinal cord injury. Obstet Gynecol Surg 58:678-687, 2003.

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Perioperative Management of Patients with Muscular Dystrophy

115

Katarzyna Luba

Case Synopsis

PROBLEM ANALYSIS Definition Muscular dystrophies are a clinically and genetically diverse group of hereditary disorders of the structure of striated muscle, characterized by progressive muscle weakness and wasting. The diagnosis of a muscular dystrophy is based on elevated serum CK, myopathic electromyogram features, and muscle biopsy. The morphologic changes common to all forms of muscular dystrophy present a random pattern of normal or hypertrophic muscle fibers, necrotic and necrotizing fibers, and interstitial accumulation of fatty and fibrous tissue. The latter changes result in the characteristic pseudohypertrophy of the calf muscles seen in Duchenne’s muscular dystrophy. The previous classification of muscular dystrophies was based on patterns of inheritance and clinical features. A more recently proposed classification takes into account the type, localization, and function of defective proteins involved in the pathogenesis of different muscular dystrophies.

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

An 8-month-old boy undergoes myringotomy tube removal. His previous general anesthesia for tube placement was uneventful. Anesthesia is induced with intravenous thiopental and atropine and is maintained with nitrous oxide, halothane, and oxygen via a facemask. After removal of the myringotomy tube, the surgeon performs a digital examination and decides to perform an adenoidectomy. Airway obstruction at this time necessitates emergency intubation. After succinylcholine 2 mg/kg intravenously, an increase in masseter muscle tone is noted. The electrocardiogram (ECG) monitor shows a wide complex tachycardia progressing to bradycardia. End-tidal carbon dioxide (CO2) of 40 to 50 mm Hg gradually decreases to 25 mm Hg. Arterial saturation decreases from 100% to 80%, then cannot be detected. Halothane is discontinued. Calcium chloride, epinephrine, and sodium bicarbonate are given intravenously. The ECG becomes increasingly dysmorphic, and pulses cannot be palpated. Chest compressions start. Venous blood analysis shows that pH is 7.13, CO2 tension (PCO2) is 73 mm Hg, and potassium level is more than 10 mmol/L. Calcium, epinephrine, and bicarbonate are repeated. After 13 minutes of cardiopulmonary resuscitation, the ECG shows the return of a narrow complex tachycardia, and systolic blood pressure increases to 100 mm Hg. Twenty minutes after succinylcholine administration, a venous blood sample shows pH 7.30, PCO2 49 mm Hg, and potassium 7.1 mmol/L. A urinary catheter reveals red urine. The patient is transported to a pediatric intensive care unit. The creatine kinase (CK) level is 285,760 units/L. The patient is treated with vigorous intravenous hydration. He is discharged home in good condition. DNA studies before discharge show a deletion of the dystrophin gene, consistent with a diagnosis of Duchenne’s muscular dystrophy.

PLASMA MEMBRANE–ASSOCIATED PROTEINS Defective plasma membrane–associated proteins or the lack of such proteins causes the most common muscular dystrophies, including Duchenne’s muscular dystrophy (DMD), Becker’s muscular dystrophy (BMD), the sarcoglycanopathies, and other forms of limb-girdle muscular dystrophy (LGMD). Dystrophinopathies. The most common muscular dystrophies are X-linked recessive disorders caused by mutations of the dystrophin gene. Dystrophin is a sarcolemmal protein that plays a role in maintaining the integrity of the sarcolemma. The severe DMD form results from deficiency of dystrophin. The milder allelic form (BMD) is associated with a reduced amount of the truncated protein. The incidence of DMD is 1 in 3500 live male births. Affected males have delayed motor development, and when they start walking, they present with gait abnormalities. By age 5 years, muscle weakness is evident. Calf enlargement is due to replacement of necrotic muscle by fat and fibrous tissue. Lumbar hyperlordosis and toe-walking result from progressive loss of muscle strength and tendon contractures. By age 479

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12 years, most patients are confined to a wheelchair. Scoliosis, chest deformity, and diaphragmatic weakness lead to restrictive pulmonary disease by age16 to 18 years. Respiratory failure, the most common cause of death, occurs in the third decade of life. Almost all patients have cardiomyopathy, but this rarely causes death. Intellectual impairment is common. Compared with DMD, BMD has a later onset and a milder clinical course. Symptoms of proximal muscle weakness commonly start between ages 5 and 15 years, although the onset may be delayed until the third or fourth decade of life. Patients generally ambulate beyond age 15 years. Calf hypertrophy occurs early and is prominent. Patients have a short life expectancy, but many live to their 30s or 40s. Mental retardation is milder than in DMD. In patients with mild or subclinical BMD, cardiomyopathy may be the presenting feature of the disease. Most BMD patients die of complications of cardiomyopathy. Sarcoglycanopathies. These disorders are caused by mutations of genes encoding four transmembrane glycoproteins of the sarcoglycan complex. Mutations of any of the four sarcoglycan genes (alpha, beta, gamma, and delta) result in LGMD 2D, 2E, 2C, and 2F. Both males and females are affected. Proximal leg muscle weakness generally appears in the second or third decade but may be delayed. Upper limb involvement with scapular winging develops. Diaphragmatic weakness with respiratory insufficiency, cardiomyopathy, congestive heart failure (CHF), and arrhythmias may develop. Intellectual function is normal. Caveolin Deficiency. This is a rare form of autosomal dominant muscular dystrophy. LGMD 1C is caused by deficient caveolin, a ubiquitous plasma membrane protein. EXTRACELLULAR MATRIX PROTEINS Deficiencies in extracellular matrix proteins result in congenital muscular dystrophies (CMDs), a group of autosomal recessive disorders that become symptomatic at birth or in infancy. They are diagnosed by hypotonia and a dystrophic muscle biopsy. The most severe form is merosin-deficient CMD. The maximal functional ability of a child with CMD is sitting unsupported. Further, cardiomyopathy may be present. PROTEINS WITH ENZYMATIC ACTIVITY Mutations in Genes Encoding Glycosyltransferases. These mutations are a recently identified mechanism for CMDs. The gene encoding the fukutin-related protein (FKRP—a glycosyltransferase) is mutated in a severe form of muscular dystrophy, CMD type 1C, as well as a mild form, LGMD 2I. Central nervous system involvement is present in the severe form, with cerebellar cysts, seizures, and developmental delay. Mild cardiomyopathy may also be present. Protein Kinases. Heterozygosity for a trinucleotide repeat ([CTG]n) expansion mutation in the 3′ untranslated region of a protein kinase gene on chromosome 19 is the cause of myotonic dystrophy, the most common adult form of muscular dystrophy. This has a prevalence of 1 in 8000. Myotonic dystrophy is an autosomal dominant disorder characterized by myotonia, slowly progressive muscle weakness and wasting,

frontal baldness, cataracts, and insulin resistance secondary to aberrant insulin receptor expression. Type 2 diabetes may develop. OTHER MUSCLE PROTEINS Sarcomeric Proteins. Mutations in the titin gene, encoding a giant sarcomeric protein, underlie an autosomal dominant form of congenital dilated cardiomyopathy. Recently, mutations of the same gene have been found in patients with isolated tibial muscular dystrophy. Nuclear Proteins. Defects in two nuclear proteins are responsible for two distinct forms of Emery-Dreifuss muscular dystrophy (EDMD). X-linked EDMD is due to mutations in the gene encoding the nuclear protein emerin. Autosomal dominant EDMD results from mutations in the lamin A/C gene, encoding a protein of the nuclear lamina. Mutations in this gene also lead to a form of dominant proximal LGMD 1B and dilated cardiomyopathy. Skeletal muscle involvement in EDMD is usually mild and slowly progressive. Cardiac involvement is the predominant feature of the disease. CARDIOMYOPATHY

IN

MUSCULAR DYSTROPHIES

Cardiac involvement is a universal feature of muscular dystrophies. The severity of cardiac involvement may determine the long-term prognosis for persons with any type of muscular dystrophy. In DMD and BMD, lacking or faulty dystrophin has been demonstrated in both cardiac and skeletal muscle. Heart failure is often the proximate cause of death, alone or in association with respiratory failure. Myocardial damage is initially subclinical but can be recognized through minor ECG and echocardiographic changes. Myocardial involvement progresses to a clinically evident stage of hypertrophy; arrhythmias, characterized by conduction defects (atrioventricular block, bundle branch block) or severe supraventricular or ventricular arrhythmias; and, finally, dilated cardiomyopathy due to widespread myocardial fibrosis. Heart failure is the most common cause of death in patients with BMD. Female carriers of DMD and BMD have a 10% incidence of cardiomyopathy that is age-progressive. Sarcoglycanopathies (LGMD 2C, 2D, 2E, 2F) may have associated dilated cardiomyopathy. This results from disrupted sarcoglycan complexes in both skeletal and cardiac muscle. LGMD due to mutations in the FKRP gene (LGMD 2I) may be associated with myocardial fibrosis, leading to dilated cardiomyopathy and repolarization abnormalities. In myotonic dystrophies, cardiac conduction defects are a major cause of sudden death. The incidence of complete atrioventricular block among these patients is higher than in the general population. A prolonged His-ventricular conduction interval puts these patients at risk of paroxysmal atrioventricular block and justifies early pacemaker implantation. In congenital (neonatal) myotonic dystrophy, abnormal myocardial relaxation results in left ventricular diastolic dysfunction. Severe cardiac involvement is common in EDMD. Both X-linked and autosomal dominant forms involve the risk of

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bradyarrhythmias (often requiring pacemaker implantation) and atrial fibrillation or flutter. Atrial fibrillation often precedes atrial standstill and may be the cause of embolic stroke at a young age. Prophylactic anticoagulation is recommended in EDMD patients with atrial arrhythmias or standstill. Finally, left ventricular failure is rare but may be severe enough to require a heart transplant.

Recognition

Risk Assessment All patients with muscular dystrophy are at risk for cardiomyopathy or conduction disorders. Signs and symptoms of myocardial dysfunction at the time of preoperative evaluation may be overt or masked by confinement to a wheelchair. Therefore, all patients with muscular dystrophy should have their cardiac function evaluated preoperatively. ECG abnormalities (sinus tachycardia or bradycardia, short P-R interval, signs of left ventricular hypertrophy, conduction defects) are very common. However, the best correlation between severe

cardiac involvement and mortality is the degree of left ventricular echocardiographic dysfunction. Guidelines for the assessment of cardiac involvement in patients with DMD and BMD advise that those with DMD have an echocardiogram and ECG at the time of diagnosis, every 2 years up to the age of 10, and annually thereafter. BMD patients should have an echocardiogram and ECG at the time of diagnosis and then every 5 years. The same recommendations apply to patients with other forms of muscular dystrophy. Additional echocardiograms or ECGs should be obtained before surgery or if clinically indicated. Patients with EDMD should have an ECG and echocardiogram at the time of diagnosis and annually thereafter. They should also be monitored annually for arrhythmias with a Holter monitor. An implanted pacemaker is justified for symptomatic patients or for asymptomatic patients whose ECG shows sinus node or atrioventricular node dysfunction. In autosomal dominant EDMD, sudden death is a possibility, even in patients with pacemakers. Therefore, a pacemaker with the full range of internal cardioverter-defibrillator capabilities should be considered whenever antibradycardia pacing is indicated. When atrial fibrillation or atrial standstill is diagnosed, antithromboembolic prophylaxis with warfarin is indicated. Intracardiac conduction should be evaluated in all adult myotonic dystrophy patients. Patients are selected to undergo cardiac electrophysiologic investigation based on the results of signal-averaged ECGs. In patients with DMD, a steady decrease in vital capacity (VC) follows progressive muscle weakness and the development of scoliosis. Once VC falls below 20% of predicted values, ventilatory failure is inevitable, and 73% of patients die of respiratory failure. Obstructive sleep apnea is common, leading to chronic hypoxemia and right ventricle failure. Preoperative pulmonary function tests and sleep studies are indicated to assess the severity of restrictive pulmonary disease and obstructive sleep apnea.

Implications Patients with muscular dystrophies are at increased risk of perioperative CHF, arrhythmias, and respiratory failure. If the VC is less than 30% of predicted, the patient will likely require prolonged postoperative ventilatory support. Obstructive sleep apnea and weak pharyngeal muscles increase the risk for early postoperative airway obstruction and hypoxia. Outpatient general anesthesia is not advised owing to the risk of delayed respiratory depression. Also, delayed gastric emptying increases the risk of aspiration. Succinylcholine can trigger MH or cause hyperkalemic cardiac arrest; therefore, its use is not advised. Nondepolarizing muscle relaxants (NDMRs) may have prolonged effects. Also, neostigmine reversal is unpredictable. Volatile anesthetics may trigger MH in DMD patients. In patients with myotonic dystrophy, hypothermia, shivering, succinylcholine, neostigmine, and direct muscle stimulation may precipitate a myotonic crisis, characterized by prolonged contracture of the skeletal muscles. For these reasons, regional or local anesthesia, when suitable, is preferred for all patients with muscular dystrophy.

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Patients with muscular dystrophy usually present for muscle biopsy, tendon contracture release, correction of kyphoscoliosis, or pacemaker implantation. Pediatric patients with undiagnosed muscular dystrophy may present for procedures unrelated to the disease. All patients with muscular dystrophy should be suspected of having respiratory and cardiac dysfunction. Pulmonary function tests should be performed in all patients with muscle weakness because of the high incidence of restrictive lung disease secondary to diaphragmatic weakness and scoliosis. In asymptomatic patients with the diagnosis of muscular dystrophy, the specific type of dystrophy and the risk of cardiac involvement determine the need for further cardiac workup. Intraoperative CHF may present as tachycardia and hypotension unresponsive to intravenous fluids. Physical signs of CHF include jugular vein distention, pulmonary rales, and dyspnea in a spontaneously breathing patient. Severe CHF results in acute pulmonary edema, with hypoxia and pink, frothy respiratory secretions. Diagnosis may be confirmed by hemodynamic parameters measured with a pulmonary artery catheter. Typically, pulmonary artery occlusion pressure is elevated (>18 mm Hg), cardiac index is low (<2.2 L/minute/m2 body surface area), and systemic vascular resistance is high (>1200 dynes•sec•cm–5). In children with undiagnosed DMD, succinylcholine has been reported to induce hyperkalemic cardiac arrest. On the basis of these reports, the Food and Drug Administration recommended against the use of succinylcholine for nonemergent intubation in children. Malignant hyperthermia (MH), a rare inherited disorder of sarcolemmal calcium flux, may be triggered by volatile anesthetics and succinylcholine in genetically susceptible individuals. Patients with DMD may be susceptible to MH. Signs of MH include muscle rigidity; an unanticipated, rapid rise in temperature and end-tidal CO2; hypertension; metabolic acidosis; tachyarrhythmias; myoglobinuria; and elevated serum CK.

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Finally, patients with DMD previously treated with glucocorticoid steroids require supplemental perioperative steroids.

MANAGEMENT The need to minimize the use of myocardial depressant and MH-triggering agents favors the use of regional anesthesia or total intravenous general anesthesia. Agents used for the latter include propofol, ketamine, dexmedetomidine, and opioids. Short-acting opioids (remifentanil, sufentanil) may be preferable to reduce the risk of postoperative respiratory depression. Premedication with benzodiazepines and opioids may cause respiratory depression, airway obstruction, and delayed emergence from anesthesia and should be avoided. Airway management should take into account the increased risk of aspiration. Premedication with an H2-blocker and metoclopramide is advised. Modified rapid-sequence endotracheal intubation with the use of an NDMR is the method of choice. The choice of agent is limited by contraindications to succinylcholine and increased sensitivity to NDMRs. Shortacting NDMRs (mivacurium, cisatracurium) should be used, and their dose should be titrated to the train-of-four response. Even with the use of short-acting NDMRs, prolonged recovery has been reported in children with DMD. Reversal of NDMRs with neostigmine has been reported without adverse events. However, as mentioned earlier, reversal with neostigmine may be unpredictable. The management of intraoperative CHF depends on hemodynamic stability. Diuresis and positive end-expiratory pressure may be sufficient. If hypotension develops, an inotrope (dobutamine or dopamine) should be used, and an arterial line placed. An arterial line is advised for all major surgery in patients with muscular dystrophy. Further management is guided by transesophageal echocardiography or pulmonary artery catheter measurements. If preload is adequate, inotropy and afterload reduction may help increase cardiac output and tissue perfusion. In patients with myotonic dystrophy, anesthetic goals should include avoidance of the triggers of myotonic contractures. Severe contractures may result in jaw and chest rigidity, impeding efforts to intubate and ventilate. Contractures do not respond to NDMRs; they may respond to intravenous quinidine, infiltration of the muscle with local anesthetic, and rewarming the patient. MH management requires immediate discontinuation of inhalational anesthetics, administration of dantrolene, 100% oxygen, active cooling, and treatment of associated arrhythmias, hyperkalemia, and acidosis. To prevent acute renal failure secondary to rhabdomyolysis, patients should be treated with intravenous hydration, alkalinization of urine with intravenous sodium bicarbonate, and mannitol. Patients with impaired respiratory function require admission to the intensive care unit for prolonged ventilatory support after extensive surgical procedures under general anesthesia.

PREVENTION Prevention of perioperative complications in patients with muscular dystrophy requires thorough evaluation of the surgical risk. Surgery for the correction of scoliosis in patients with DMD should be performed before pulmonary function declines and precludes a safe anesthetic and postoperative course. Knowledge of the severity of myocardial involvement is necessary to prevent perioprative exacerbation of CHF or life-threatening arrhythmias. The preoperative evaluation should include a recent ECG, echocardiogram, and electrophysiologic testing if indicated by the results of signal-averaged ECGs. In the presence of severe cardiomyopathy and respiratory dysfunction, invasive hemodynamic monitoring and postoperative critical care management should be anticipated for major surgical procedures. Outpatient surgery in this patient population is discouraged, because overnight monitoring for delayed respiratory complications after general anesthesia of any duration is warranted. Aspiration risk should be minimized by premedication with H2-blockers and metoclopramide and by the use of an appropriate intubation technique. Succinylcholine should never be used. Also, inhalational anesthetics should be avoided because of their MH-triggering potential. The use of regional or local anesthesia, whenever feasible, may help avoid respiratory, cardiac, and metabolic complications of general anesthesia in patients with muscular dystrophy.

Further Reading Abraham RB, Cahana A, Krivosic-Horber RM, Perel A: Malignant hyperthermia susceptibility: Anesthetic implications and risk stratification. QJM 90:13-18, 1997. Baraka A, Jalbout MI: Anesthesia and myopathy. Curr Opin Anaesthesiol 15:371-376, 2002. Barresi R, Di Blasi C, Negri T: Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by β-sarcoglycan mutations. J Med Genet 37:102-107, 2000. Boriani G, Gallina M, Merlini L, et al: Clinical relevance of atrial fibrillation/flutter, stroke, pacemaker implant, and heart failure in EmeryDreifuss muscular dystrophy: A long-term longitudinal study. Stroke 34:901-908, 2003. Buckley AE, Dean J: Cardiac involvement in Emery Dreifuss muscular dystrophy: A case series. Heart 82:105-108, 1999. Corrado G, Lissoni A, Beretta S, et al: Prognostic value of electrocardiograms, ventricular late potentials, ventricular arrhythmias, and left ventricular systolic dysfunction in patients with Duchenne muscular dystrophy. Am J Cardiol 89:838-841, 2002. Do T: Orthopedic management of the muscular dystrophies. Curr Opin Pediatr 14:50-53, 2002. Dubowitz V: What is muscular dystrophy? Forty years of progressive ignorance. J R Coll Physicians Lond 34:464-468, 2000. Frankowski GA, Johnson J, Tobias J: Rapacuronium administration to two children with Duchenne’s muscular dystrophy. Anesth Analg 91: 27-28, 2000. Le Corre F, Plaud B: Neuromuscular disorders. Curr Opin Anaesthesiol 11:333-337, 1998. Mathieu J, Allard P, Gobeil G, et al: Anesthetic and surgical complications in 219 cases of myotonic dystrophy. Neurology 49:1646-1650, 1997. Melacini P, Fanin M, Danielli GA, et al: Myocardial disease: Myocardial involvement is very frequent among patients affected with subclinical Becker’s muscular dystrophy. Circulation 94:3168-3175, 1996.

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Muntoni F: Cardiomyopathy in muscular dystrophies. Curr Opin Neurol 16:577-583, 2003. Parker SF, Bailey A, Drake AF: Infant hyperkalemic arrest after succinylcholine. Anesth Analg 80:206-207, 1995. Politano L, Nigro V, Nigro G, et al: Development of cardiomyopathy in female carriers of Duchenne and Becker muscular dystrophies. JAMA 275:1335-1338, 1996. Ririe DG, Shapiro F, Sethna NF: The response of patients with Duchenne’s muscular dystrophy to neuromuscular blockade with vecuronium. Anesthesiology 88:351-354, 1998.

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Rosenberg H, Gronert GA: Intractable cardiac arrest in children given succinylcholine [letter]. Anesthesiology 77:1054, 1992. Schramm CM: Current concepts of respiratory complications of neuromuscular disease in children. Curr Opin Pediatr 12:203-207, 2000. Stevens R: Neuromuscular disorders and anesthesia. Curr Opin Anaesthesiol 14:693-698, 2001. Uslu M, Mellinghoff H, Diefenbach C: Mivacurium for muscle relaxation in a child with Duchenne’s muscular dystrophy. Anesth Analg 89: 340-341, 1999.

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Case Synopsis A 22-year-old woman, 154 cm tall and weighing 44.2 kg, presents with a 4-month history of myasthenia gravis and mild generalized weakness (Osserman’s class II). The diagnosis is confirmed by the patient’s rapid improvement after the administration of intravenous edrophonium chloride and by the presence of antibodies to acetylcholine receptors (12.3 nmol/L; reference value <0.25 nmol/L). The patient is scheduled for transcervical-sternal thymectomy. Preoperatively, she took pyridostigmine 60 mg orally three times a day and had plasmapheresis. Results of her preoperative pulmonary function tests were as follows: forced vital capacity (FVC), 2.79 L/second (79% of predicted); maximum expiratory flow at 50% of FVC, 3.2 L/second (68% of predicted); and forced midexpiratory flow between 25% and 75% of FVC, 3.03 L/second (77% of predicted). Anesthesia was induced with fentanyl and propofol and maintained with a thoracic epidural block supplemented with propofol and 70% nitrous oxide in oxygen. Tracheal intubation was performed under topical laryngotracheal anesthesia (4 mL 4% lidocaine). No neuromuscular blockers were used. She required mechanical ventilation for 12 hours postoperatively.

PROBLEM ANALYSIS Definition Neuromuscular transmission is dependent on a coordinated mechanism involving (1) synthesis, storage, and release of acetylcholine from the presynaptic motor nerve endings at the neuromuscular junction; (2) binding of acetylcholine to nicotinic receptors on the postsynaptic region of the muscle membrane, with consequent generation of the action potential; and (3) rapid hydrolysis of acetylcholine by acetylcholinesterase enzyme present in the synaptic cleft. Autoimmune or genetic defects at the presynaptic region, synaptic basal lamina, or postsynaptic structure of the neuromuscular junction can compromise the safety margin of neuromuscular transmission. This can result in a diverse array of myasthenic disorders (Fig. 116-1). Fluctuating muscle weakness and fatigability are the main characteristics of myasthenic disorders (mys, meaning “muscle”; aesthenia, meaning “weakness”). Myasthenic disorders affect the motor system only. Sensory and autonomic functions are not impaired. The exception is Lambert-Eaton syndrome, a myasthenic syndrome in which a significant minority of patients have autonomic dysfunction. Myasthenic disorders can be classified into three main categories: myasthenia gravis, congenital myasthenic syndromes, and LambertEaton myasthenic syndrome (Tables 116-1 and 116-2).

Recognition, Risk Assessment, and Implications MYASTHENIA GRAVIS Myasthenia gravis (MG) is the most common myasthenic disorder. MG is an antibody-mediated autoimmune disease with a prevalence of 0.25 to 2 per 100,000. Antibodies against 484

the α-subunit of nicotinic acetylcholine receptors are present in approximately 80% to 85% of patients with MG. In the remaining 15% to 20% of patients (called seronegative patients), nicotinic acetylcholine receptor antibodies are not detectable. The majority of these seronegative patients have antibodies against the muscle-specific receptor tyrosine kinase; these antibodies are not present in seropositive patients. Muscle-specific kinase mediates the agrin-induced clustering of nicotinic acetylcholine receptors during synapse formation and is also expressed at the mature neuromuscular junction. Triggers for the immune response in MG are not known. Thymic lymphoid follicular hyperplasia with germinal centers that produce antibodies to nicotinic acetylcholine receptors is present in approximately 70% of MG patients. A small percentage of MG patients develops autoantibodies as part of a paraneoplastic syndrome (12% of MG patients have thymoma). It is believed that antibodies to nicotinic acetylcholine receptors are produced in other locations, because thymectomy does not cure MG and does not protect against the occurrence of MG. There is also some evidence that antibodies generated in response to microbial antigens may constitute a trigger for MG in some patients. The antirheumatic drug D-penicillamine can induce a reversible form of MG. MG can occur at any age. Extraocular and bulbar muscles are initially affected in a large majority of patients, resulting in ptosis, diplopia, dysphagia, and respiratory failure. As the disease progresses, neck and limb-girdle muscle weakness becomes apparent. In the rat model of MG, there is also evidence that diaphragmatic function is impaired. The clinical features of seropositive and seronegative patients are very similar. Osserman and Genkins proposed the following clinical classification of MG: class I (ocular signs and symptoms only), class II (mild generalized weakness), class III (moderate generalized weakness with or without bulbar involvement), and

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Presynaptic

Defective resynthesis or vesicular packing of ACh → CMS (genetic)

SV Nerve terminal

SV LEMS (autoimmune)

Postsynaptic Synaptic

Myasthenic disorders

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Figure 116–1 ■ Myasthenic disorders. AChE, acetylcholinesterase; CMS, congenital myasthenic syndrome; LEMS, Lambert-Eaton myasthenic syndrome; MG, myasthenia gravis; MuSK, musclespecific kinase; nAChR, nicotinic acetylcholine receptor; SV, synaptic vesicle; VGCC (P/Q), voltage-gated calcium channel (P/Q type).

VGCC (P/Q)

AChE deficiency CMS (genetic)

Synaptic cleft

Seropositive MG (autoimmune) Slow- and fast-channel CMS (genetic)

■

nAChR MuSK

Seronegative MG (autoimmune) Rapsyn-deficiency CMS (genetic)

Rapsyn

CONGENITAL MYASTHENIC SYNDROMES Congenital myasthenic syndromes (CMSs) are a rare group of heterogeneous disorders that are caused not by autoantibodies but by inherited mutations in the synaptic vesicles, acetylcholinesterase, or nicotinic acetylcholine receptors. This results in either an increase (gain of function) or decrease (loss of function) in the magnitude of response to acetylcholine. The most frequent type of postsynaptic CMS is the slow-channel syndrome. The inheritance of CMS is either autosomal dominant or recessive. In contrast to neonatal MG, caused by passive transfer of antibodies to the fetus from a myasthenic mother, the mothers of infants with CMS do not have myasthenia. The onset of CMS usually occurs before 2 years of age. In contrast to autoimmune MG, immunosuppression and plasmapheresis are not effective in the management of CMS because antibodies play no role in its pathogenesis. In patients with MG and CMS, electromyography is characterized by decremental responses on repetitive stimulation and block with single-fiber recordings. However, patients

with a slow-channel CMS can also show characteristic repetitive discharges in response to a single supramaximal stimulus, the so-called double response. LAMBERT-EATON MYASTHENIC SYNDROME Lambert-Eaton myasthenic syndrome (LEMS) is an acquired disorder resulting from autoantibodies targeting the presynaptic P/Q voltage-gated calcium channels and possibly another presynaptic component (synaptotagmin), leading to a reduction in acetylcholine release. Synaptotagmin is an exocytotic calcium sensor and plays an important role in synaptic vesicle fusion and the fast release of acetylcholine. Anti-P/Q-type voltage-gated calcium channel antibodies are detected in 85% of patients with LEMS (seropositive). A fraction of seronegative LEMS patients have antisynaptotagmin antibodies in their sera. In approximately 60% of LEMS patients, the syndrome is a paraneoplastic disorder, most often associated with small cell carcinoma of the lung. In patients without malignancy, LEMS is an autoimmune disorder. LEMS is characterized by proximal muscle weakness in the lower and upper extremities, fatigability, and autonomic dysfunction. Involvement of bulbar or respiratory muscles is uncommon in LEMS patients. In patients with LEMS, electromyography typically shows low-amplitude compound muscle action potentials, associated with fade at slow rates of stimulation (2 Hz). Facilitation of response is seen after brief exercise or at high rates of repetitive stimulation (30 to 50 Hz).

MANAGEMENT AND PREVENTION Thymectomy is an elective procedure and should be performed after optimization of the patient’s condition. Preoperative assessment and preparation of MG patients should include

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

class IV (severe generalized weakness with or without bulbar involvement). Improvement in strength after intravenous injection of edrophonium (Tensilon) helps confirm the diagnosis of MG. After a test dose of 1 to 2 mg, a total dose of 10 mg is administered intravenously. A positive response is expected within 5 minutes. There is no specific immunotherapy for MG. Nonspecific immunosuppression with steroids and immunosuppressants (e.g., azathioprine) and plasmapheresis are often combined with thymectomy. Anticholinesterases are used to treat symptoms. Thymectomy is the standard treatment for young patients and for those with thymoma. Plasmapheresis and intravenous immunoglobulin are effective in myasthenic crisis and for the preoperative optimization of the patient’s condition.

Muscle

486 Genetic

Postsynaptic Myasthenia Autoimmune gravis: Seropositive or seronegative

AChE deficiency

Antibodies to MuSK

Antibodies to nAChRs

Mutations in the gene encoding the collagenic tail subunit of the enzyme anchoring AChE in the synaptic cleft decrease the expression or the catalytic efficacy of the enzyme

Choline acetyltransferase mutations cause insufficient ACh resynthesis

Choline Genetic acetyltransferase deficiency

Synaptic

Antibodies target voltage-gated calcium (Ca2+) channels at motor nerve terminal and possibly another presynaptic component (synaptotagmin), leading to reduction in ACh release

LambertAutoimmune Eaton myasthenic syndrome

Cause

Presynaptic

Type

Myasthenic Disorders Clinical Features

Management

Normal ACh contents and NMJ architecture

≈ 60% of patients With malignancy, successful treatment can lead to have paraneoplastic marked improvement in symptoms response, often 3,4-Diaminopyridine blocks prejunctional in association with potassium (K) channels to (1) prevent K efflux, small cell lung (2) increase action potential duration, (3) prolong carcinoma activation of voltage-gated Ca2+ channels, and Weakness and (4) increase intracellular Ca2+ stores and ACh release fatigability Pyridostigmine potentiates response to 3, 4-diaminopyridine Often, plasmapheresis or IV immunoglobulin provides transient improvement Number of Characteristic AChE inhibitors nAChRs apneic attacks and end-plate along with structure myasthenic are normal symptoms Absent or Autosomal recessive Due to deficiency of AChE enzyme, patients do not reduced AChE disease with benefit from anticholinesterase therapy activity (by variable phenotypic histochemical expression staining) Moderately severe, Secondary loss generalized of nAChR and weakness and postsynaptic scoliosis with region restrictive lung degeneration disease are common End-plate regions Age at onset of Preoperative optimization by plasmapheresis and have simplified myasthenic continued pyridostigmine therapy architecture symptoms is earlier Patients are extremely sensitive to NDMRs with smaller in MuSK antibody- Response to SCh and mivacurium depends on folds and positive patients butyrylcholinesterase activity, which is expected marked Neck muscles are to decrease after plasmapheresis or pyridostigmine reduction commonly involved in nAChR— in MuSK antibody≈30% of that positive patients, in normal and limb muscles NMJ in MuSK antibodynegative patients

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Kinetic defects and/or gain-of-function mutations in nAChR cause lengthy nAChR opening and excessive Ca2+ influx with postsynaptic degeneration

Mutations in nAChR markedly reduce binding affinities, resulting in rapid ACh dissociation from binding sites, reducing the rate of channel opening, and increasing its closure rate

Slow-channel Genetic congenital myasthenic syndromes

Fast-channel Genetic congenital myasthenic syndromes

Patients exhibit myasthenic symptoms from birth or infancy Facial malformations are common in rapsyn deficiency

Usual dominant inheritance Selective weakness in cervical, scapular, and finger extensor muscles; variable weakness in other muscles NMJ structure Dominant or recessive normal; density inheritance of nAChRs Moderate symptoms normal or from birth to decreased infancy Partial response to AChE inhibitors

Changes in end-plate regions are similar to those seen with autoimmune MG Postsynaptic degeneration with loss of nAChRs; AChE is normal

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Combination treatment with 3,4-diaminopyridine and AchE

Open channel blockers (quinidine, fluoxetine) normalize slow-channel mutant opening durations No response to AChE medications Avoid SCh because it can worsen excitotoxicity

Response to anticholinesterase is incomplete Combined therapy with 3,4-diaminopyridine (which increases ACh release) is beneficial

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ACh, acetylcholine; AChE, acetylcholinesterase; MG, myasthenia gravis; MuSK, muscle-specific kinase; nAChR, nicotinic acetylcholine receptor; NDMR, nondepolarizing muscle relaxant; NMJ, neuromuscular junction; SCh, succinylcholine.

Mutations in nAChR or in rapsyn decrease expression of nAChRs

Reduced Genetic expression of nAChR or rapsyn deficiency

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488 Facilitation Transient Minimal therapeutic value

Absent After rest From myasthenic mother to fetus, causing neonatal MG Injecting healthy animals with MG IgG causes signs of MG Fade Transient Effective in managing symptoms No effect

Dysautonomias

Improvement in muscle strength Antibody transfer

Electromyography (response to 30-50 Hz stimulation) Effect of plasmapheresis Anticholinesterases

Response to 3,4-diaminopyridine

Significant improvement in symptoms

Present in ≈30% of patients (dry mouth, impotence) After exercise IgG from LEMS patients can block Ca2+ channels, inhibiting muscle contraction

Presynaptic

Effective in fast-channel congenital myasthenic syndromes

No effect Minimal therapeutic value

Fade

After rest Antibodies are not present

Presynaptic, synaptic, or postsynaptic component of NMJ Absent

Genetic mutations of presynaptic, synaptic, or postsynaptic proteins Dominant or recessive inheritance (no antibodies against nAChRs, MuSK, or P/Q type Ca2+ channels)

Congenital Myasthenic Syndromes

ACh, acetylcholine; IgG, immunoglobulin G; LEMS, Lambert-Eaton myasthenic syndrome; MG, myasthenia gravis; MuSK, muscle-specific kinase; nAChR, nicotinic acetylcholine receptor; NMJ, neuromuscular junction.

Target location

60% of LEMS patients have paraneoplastic autoimmune response Small cell lung carcinomas express voltagesensitive Ca2+ channels; antitumor antibodies to these channels cross-react with prejunctional voltage-gated Ca2+ channels at the NMJ to impair ACh release

Thymic lymphoid follicular hyperplasia present in 70% of MG patients Thymoma present in 12% of MG patients (paraneoplastic autoimmune response) Associated autoimmune conditions include thyrotoxicosis, systemic lupus erythematosus, rheumatoid arthritis, and pernicious anemia Postsynaptic

Autoantibodies targeting presynaptic voltagegated (P/Q) calcium (Ca2+) channels or synaptotagmin

Lambert-Eaton Myasthenic Syndrome

Associated conditions

Myasthenia Gravis

Differential Diagnosis of Myasthenic Disorders

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Table 116–2

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anesthetics on neuromuscular transmission. Therefore, it may be safer to use a small dose of an intermediate nondepolarizing neuromuscular blocker to facilitate tracheal intubation than to use deep inhalation anesthesia. Total intravenous anesthesia with a propofol-opioid infusion is a suitable alternative to a volatile anesthetic technique. A thoracic epidural anesthetic in combination with balanced general anesthesia provides excellent analgesia both intraoperatively and following transsternal thymectomy. Regional anesthesia has also been used successfully to provide labor analgesia in parturients with MG. However, local anesthetics are known to potentiate neuromuscular blocking drugs, and the metabolism of ester local anesthetics may be impaired if butyrylcholinesterase activity is reduced due to pyridostigmine therapy. Patients with LEMS are sensitive to depolarizing and nondepolarizing neuromuscular blockers. In patients with LEMS, neostigmine is an ineffective antagonist for residual neuromuscular block. Oral 3,4-diaminopyridine should be continued after surgery. All myasthenic patients should be closely monitored for neuromuscular weakness postoperatively in the surgical intensive care unit. The differential diagnosis of postoperative weakness in myasthenic patients should include the residual effects of neuromuscular blockers or anesthetic drugs, drugs that interfere with neuromuscular transmission (e.g., aminoglycoside antibiotics, antiarrhythmics, psychotropics), and myasthenic or cholinergic crisis.

Further Reading Abel M, Eisenkraft JB: Anesthetic implications of myasthenia gravis. Mt Sinai J Med 69:31-37, 2002. Baraka A: Onset of neuromuscular block in myasthenic patients. Br J Anaesth 69:227-228, 1992. Drachman DB: Myasthenia gravis. N Engl J Med 330:1797-1810, 1994. Engel AG, Ohno K, Sine SM: Congenital myasthenic syndromes: Progress over the past decade. Muscle Nerve 27:4-25, 2003. Leveque C, Hoshino T, David P, et al: The synaptic vesicle protein synaptotagmin associates with calcium channels and is a putative LambertEaton myasthenic syndrome antigen. Proc Natl Acad Sci U S A 89:3625-3629, 1992. Lindstrom JM: Acetylcholine receptors and myasthenia. Muscle Nerve 23:453-477, 2000. Naguib M, el Dawlatly AA, Ashour M, Bamgboye EA: Multivariate determinants of the need for postoperative ventilation in myasthenia gravis. Can J Anaesth 43:1006-1013, 1996. Naguib M, Flood P, McArdle JJ, Brenner HR: Advances in neurobiology of the neuromuscular junction: Implications for the anesthesiologist. Anesthesiology 96:202-231, 2002. Takamori M, Maruta T, Komai K: Lambert-Eaton myasthenic syndrome as an autoimmune calcium-channelopathy. Neurosci Res 36:183-191, 2000. Vincent A: Unravelling the pathogenesis of myasthenia gravis. Nat Rev Immunol 2:797-804, 2002. Vincent A, Palace J, Hilton-Jones D: Myasthenia gravis. Lancet 357: 2122-2128, 2001. Whitney KD, McNamara JO: Autoimmunity and neurological disease: Antibody modulation of synaptic transmission. Annu Rev Neurosci 22:175-195, 1999.

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(1) review of the patient’s neurologic history and a neurologic examination; (2) preoperative drug therapy (e.g., pyridostigmine and immunosuppressant drugs); (3) evaluation of bulbar symptoms or signs, such as dysphagia, dysarthria, or oropharyngeal weakness (because patients with bulbar involvement are at increased risk for postoperative respiratory complications); (4) search for the presence of other autoimmune diseases, such as diabetes mellitus, thyroid disease, systemic lupus erythematosus, or rheumatoid arthritis; (5) evaluation of pulmonary function tests, which should include flow-volume loops to help predict the need for postoperative mechanical ventilation; and (6) optimization of the patient’s condition by preoperative plasmapheresis or highdose intravenous immunoglobulin. Pyridostigmine therapy should be continued preoperatively. Myasthenic patients are generally resistant to succinylcholine owing to the decreased number of nicotinic acetylcholine receptors. However, butyrylcholinesterase (plasma cholinesterase) activity may be decreased in myasthenic patients by preoperative plasmapheresis or the administration of pyridostigmine, and this may result in the potentiation of succinylcholine. In the final analysis, the interplay between these factors (resistance to succinylcholine versus reduction in butyrylcholinesterase activity) should be considered when administering succinylcholine (or mivacurium) to patients with MG. Succinylcholine should be avoided in patients with slow-channel CMS because it can worsen excitotoxicity. Patients with MG are extremely sensitive to nondepolarizing neuromuscular blockers due to the significant loss of postsynaptic nicotinic acetylcholine receptors. Nevertheless, nondepolarizing neuromuscular blockers are not contraindicated in these patients. With careful titration and with adequate monitoring of neuromuscular function, nondepolarizing agents have been safely used in myasthenic patients undergoing thymectomy. Long-acting neuromuscular blocking drugs should be avoided in these patients. Intermediate-acting drugs are better alternatives. Approximately one fifth the ED95 of an intermediate-acting neuromuscular blocker should be given as a test dose. This helps estimate the patient’s drug requirement as guided by a quantitative neuromuscular monitoring device. Myasthenic patients typically exhibit marked variations in their sensitivities to nondepolarizing neuromuscular blockers. In myasthenic patients, reversal of residual block after surgery may be ineffective because acetylcholinesterase inhibition already exists as a result of chronic pyridostigmine therapy. Therefore, it is advisable to allow spontaneous recovery from relaxation postoperatively, while continuing supportive mechanical ventilation. Different anesthetic techniques have been used in myasthenic patients. Although surgical relaxation can be provided using only a potent inhaled anesthetic without neuromuscular blockers, this technique may be associated with a prolonged recovery from anesthesia due to the effects of inhalational

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Case Synopsis A 74-year-old man is seen in the preoperative holding area for repair of a fractured hip. For the past 10 years, he has been treated for Parkinson’s disease with carbidopalevodopa (Sinemet); pramipexole (Mirapex) was added 4 years ago. On examination, facial masking and bradykinesia are apparent. He also has a tremor, muscle rigidity, and pain. He has been taking his medications as directed, but because of off-period symptoms, he has recently begun using apomorphine (Apokyn) and domperidone for related nausea.

PROBLEM ANALYSIS Definition and Recognition James Parkinson described the disease that bears his name in 1817. He highlighted the characteristic stooped posture, as well as the triad of tremor, muscle rigidity, and bradykinesia. The most common initial symptom, exhibited by 70% of people with Parkinson’s disease (PD), is a resting tremor of the hand. Although the precise cause of PD is unknown, the symptoms are the result of increased depletion of dopamineproducing cells in the substantia nigra. The subsequent imbalance between acetylcholine and dopamine leads to the aforementioned motor symptoms and often causes dysautonomia as well. Posited factors related to the decrement in nigral cells include age, genetics, exposure to environmental toxins, and a combination thereof.

Risk Assessment As life expectancy has increased, so too has the likelihood that anesthesiologists will encounter patients with PD in their practices. The primary risk factor for PD is advanced age. Improvements in the pharmacotherapy of PD, particularly the development of levodopa, have also increased the life expectancy of the estimated 1 million people in the United States with PD (as well as 3% of the population of Europe older than 65 years), leading to an increased prevalence of this movement disorder. Because current treatments provide relief from most symptoms but not the associated postural instability of PD, the possibility of patients’ falling and requiring surgical repair of hip or long bone fractures has also increased. Patients also commonly require anesthesia for the surgical treatment of PD itself, such as deep brain thalamic or globus pallidus stimulation, and for urologic, ophthalmic, gastrointestinal, orthopedic, or vascular surgery.

Implications Correction of the imbalance in the neurotransmitters in the basal ganglia includes increasing dopamine levels, decreasing acetylcholine levels, or both (Table 117-1). Levodopa has been the principal therapy for PD since its introduction in 490

the 1960s; however, the use of dopamine receptor agonists has increasingly become first-line therapy in patients with early PD or as add-on therapy in later disease. Levodopa is converted to dopamine after crossing the blood-brain barrier and is administered with a decarboxylase inhibitor (carbidopa) to reduce the peripheral breakdown of levodopa, thereby increasing its availability in the brain and reducing peripheral side effects such as hypotension, nausea, and vomiting. The catechol-O-methyltransferase (COMT) inhibitors tolcapone and entacapone may be given with levodopa-carbidopa to further prevent the peripheral conversion of levodopa to dopamine. The short half-life of levodopa (30 to 60 minutes) may be implicated in the development of dyskinesias associated with its use. A rapidly dissolving tablet form of levodopa (Parcopa) has recently been approved by the Food and Drug Administration for the treatment of PD and has an onset of action of 10 minutes. However, other forms of levodopa must be discontinued 12 hours or more before introduction of the short-acting form. Dopamine receptor agonists, which enhance dopamine levels by mimicking the effects of dopamine in the brain, typically have a half-life of 3 to 69 hours: bromocriptine, 3 to 8 hours; pergolide, 27 hours; pramipexole, 7 to 17 hours; ropinirole, 6 hours; and cabergoline, 63 to 69 hours. All of these dopaminergic drugs are available only in parenteral form. However, a continuous duodenal infusion of a gel form of levodopa-carbidopa (Duodopa) and a transdermal patch containing a newly developed dopamine receptor agonist (rotigotine) are currently under investigation. Apomorphine, which is injected or infused subcutaneously, has recently been approved as rescue therapy for the “off ” periods of late-stage PD—a wearing-off or end-ofdose phenomenon during which motor and nonmotor symptoms are most severe. The onset of action is generally 5 to 15 minutes, with effects lasting from 45 to 90 minutes. Because apomorphine is highly emetogenic, patients are typically started on domperidone by mouth at a dose of 20 mg three times a day 3 days before starting apomorphine therapy. Domperidone is a dopamine receptor blocking agent that does not cross the blood-brain barrier and is therefore one of the few antiemetic agents that can be used in patients with PD; however, it is not approved for sale in the United States. Patients usually import this medication from Canada.

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Drugs Used in the Treatment of Parkinson’s Disease

Category Dopaminergic agents Dopamine enhancers Dopamine receptor agonists

MAO-B inhibitor Anticholinergic agents

Antiviral agent COMT inhibitors

Drug

Administration

Levodopa-carbidopa (Sinemet) Levodopa-carbidopa (Parcopa) Levodopa-carbidopa-entacapone (Stalevo) Apomorphine (Apokyn) Bromocriptine (Parlodel) Cabergoline (Dostinex) Pergolide (Permax) Pramipexole (Mirapex) Ropinirole (Requip) Selegiline (Eldepryl) Trihexyphenidyl (Artane, Trihexane, Trihexy) Procyclidine (Kernadrin) Benztropine (Cogentin) Ethopropazine (Parsidol) Amantadine (Symmetrel) Entacapone (Comtan) Tolcapone (Tasmar)

Oral Oral* Oral Subcutaneous† or intravenous injection Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral

*Rapidly dissolving oral agent that is metabolized in the gut, not sublingually. † Subcutaneous injection or infusion. COMT, catechol-O-methyltransferase; MAO-B, monoamine oxidase B.

MANAGEMENT AND PREVENTION The perioperative care of patients with PD is complicated by (1) potential anesthetic interactions with pharmacotherapy for PD, (2) the effects of anesthetic drugs on the dopamine

Table 117–2

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system and the patient’s symptoms, and (3) the fact that many patients with PD have decreased pulmonary function and gastrointestinal motility and autonomic nervous system derangements. The use of levodopa predisposes individuals to develop cardiac arrhythmias, as well as hypotension related to dopamine’s effects on renal blood flow. Therefore, ketamine and epinephrine-containing local anesthetics and inhalational agents that sensitize the heart to the effects of catecholamines (i.e., produce ventricular arrhythmias) should be avoided, and vasopressors such as phenylephrine may be required for hemodynamic support. A variety of other drugs used in the perioperative period may have deleterious effects on the symptoms of PD (Table 117-2). These include the typical antipsychotic drugs and most antiemetic agents—in particular, droperidol, prochlorperazine, metoclopramide, and thiethylperazine. Analgesic agents that may have an adverse effect on patients with PD include meperidine (particularly in patients receiving monoamine oxidase B

Drugs Contraindicated in Patients with Parkinson’s Disease

Category

Drug

Comments

Butyrophenones Inhalational agents

Haloperidol, droperidol Halothane, enflurane

Antiemetic Phenothiazines Analgesics

Metoclopramide Chlorpromazine, fluphenazine, prochlorperazine Fentanyl, sufentanil, morphine Meperidine

Block dopamine receptors Increase myocardial sensitivity to catecholamines (ventricular arrhythmias) Blocks dopamine receptors Block dopamine receptors May increase muscle rigidity Causes severe reaction in patients taking monoamine oxidase B inhibitors May cause acute dysautonomia May increase dyskinesias; may obliterate tremor during stereotactic procedures

Intravenous induction agent

Alfentanil Propofol

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Other drugs used to treat PD include the monoamine oxidase B inhibitor selegiline (rasagiline is currently undergoing clinical trials); the anticholinergic agents trihexyphenidyl and benztropine, which are effective primarily in treating tremor and rigidity but have potentially severe side effects in the elderly; and amantadine. Surgical treatment includes pallidotomy, thalamotomy, and deep brain stimulation of the subthalamic nucleus, globus pallidus internus, or thalamus. Ablative procedures have increasingly been abandoned in favor of deep brain stimulation.

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inhibitors), fentanyl, sufentanil, and alfentanil. Antihypertensive drugs to avoid include clonidine, propranolol, rauwolfia serpentina, and reserpine. Maintaining the required levels of dopaminergic agents is of the utmost importance in optimizing the perioperative care of patients with PD. Patients should continue their medications as long as possible before coming to the operating room. If a regional or local anesthetic is used, patients may be able to receive their medications during surgery, either by mouth or via a nasogastric tube. The use of apomorphine may be continued, but not initiated, throughout the perioperative period and delivered as a subcutaneous bolus or an intermittent infusion, if necessary. Patients who do not take their medications are at risk of developing increased muscle rigidity and laryngospasm, which could interfere with airway management, including ventilation and tracheal intubation or extubation. Other abnormalities in the control and function of the upper airway, which may lead to an obstructive airway pattern in as many as one third of patients with PD, also have an impact on the perioperative management of ventilation. Because of associated dysautonomia, many patients with PD are at risk for problems with temperature regulation throughout the perioperative period. Patients who experience increased symptoms in the preoperative holding area are treated with an anticholinergic (e.g., atropine, glycopyrrolate) or antihistamine (e.g., diphenhydramine). The latter can be especially helpful for managing exacerbations of tremor and for sedation, and the former for decreasing secretions. Regional and local techniques should be used to the extent possible in patients with PD to avoid the cognitive and emetogenic effects of general anesthesia. These techniques also allow for continued communication with the patient and the oral administration of dopaminergic agents, as needed. When general anesthesia is required, there is no agent of choice for induction, but halothane and, to a lesser extent, enflurane are best avoided because of their arrhythmogenic properties (i.e., sensitization of the heart to the effects of catecholamines). In particular, caution is warranted in patients on long-term levodopa therapy who are at risk of developing hemodynamic flux due to autonomic instability, catecholamine depletion, sensitization to catecholamines, and relative hypovolemia. Significant hypotension is treated with directacting α-adrenergic receptor agonists (e.g., phenylephrine). In general, there are no concerns about the use of neuromuscular blocking agents. A review of the literature indicates that although hyperkalemia and profound bradykinesia

occurred in one patient who received intravenous succinylcholine, there is little additional evidence of such a link. Support for the use of propofol is equivocal, as this drug may increase the severity of dyskinesias. However, it is also known to have antiparkinsonian effects. Propofol may be contraindicated in patients undergoing stereotactic procedures because this drug has been shown to abolish tremor. During emergence from anesthesia and before extubation, ventilation, airway reflexes, and the ability to follow commands should be assessed. Particular care should be exercised in optimizing respiratory function, owing to increased secretions and the propensity to develop aspiration pneumonia and compromised ventilatory function. If the patient develops confusion, as is common in patients with PD, the use of a benzodiazepine in the postoperative period rather than a typical antipsychotic agent may be preferred. However, care should be taken not to depress the respiratory drive. Morbidity and mortality rates during the perioperative period are increased in patients with PD compared with patients of similar age without PD. However, careful assessment and reduction of risk, optimization of cardiac and respiratory systems, and maintenance of dopaminergic therapy to the extent possible go a long way toward leveling the playing field.

Further Reading Anderson BJ, Marks PV, Futter ME: Propofol-contrasting effects in movement disorders. Br J Neurosurg 8:387-388, 1994. Bowron A: Practical considerations in the use of apomorphine injectable. Neurology 62(Suppl 4):S32-S36, 2004. Brindle GF: Anesthesia in the patient with parkinsonism. Primary Care 4:513-528, 1977. Eventou I, Moreno M, Geller E, et al: Hip fractures in patients with Parkinson’s syndrome. J Trauma 33:98-101, 1983. Furuya R, Hirai A, Andoh T, et al: Successful perioperative management of a patient with Parkinson’s disease by enteral levodopa administration under propofol anesthesia. Anesthesiology 89:261-263, 1998. Lozano AM, Mahant N: Deep brain stimulation surgery for Parkinson’s disease: Mechanisms and consequences. Parkinsonism Relat Disord 10(Suppl 1):S49-S57, 2004. Mason LJ, Cojocaru TT, Cole DJ: Surgical intervention and anesthetic management of the patient with Parkinson’s disease. Int Anesthesiol Clin 34:133-150, 1996. Nicholson G, Pereira AC, Hall GM: Parkinson’s disease and anaesthesia. Br J Anaesth 89:904-916, 2002. Schramm BM, Orser BA: Dystonic reaction to propofol attenuated by benztropine (Cogentin). Anesth Analg 94:1237-1240, 2002 Shults CW: Treatments of Parkinson disease. Arch Neurol 60:1680-1684, 2003.

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Alzheimer’s Disease Michael J. Murray and Catherine Friederich Murray Case Synopsis A 72-year-old woman with anemia is found to have adenocarcinoma of the colon, for which she is scheduled to have a laparotomy and resection of the lesion. The patient is anxious. A woman at the bedside in the preoperative holding area tells you that the patient, her mother, has Alzheimer’s disease and that she, the daughter, has a durable power of attorney for her mother’s health care.

PROBLEM ANALYSIS Definition

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Mini–Mental Status Examination

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Alzheimer’s disease (AD) is the most common neurodegenerative disease, accounting for approximately two thirds of all cases of dementia and affecting up to 20% of individuals older than 80 years. AD is progressive, leading to irreversible loss of neurons in the cerebral cortex and hippocampus. The pathologic hallmarks of the disease are neurofibrillary tangles, which contain the hyperphosphorylated form of the microtubular protein tau and extracellular plaques, which contain the peptide β-amyloid. β-Amyloid is cleaved from a larger protein, β-amyloid precursor protein, by the α, β, and γ secretases. The γ secretases cleave to Aβ42, a 42–amino acid sequence amyloid protein, which forms insoluble fibrils that accumulate in senile plaques isolated at autopsy from patients with AD. In some patients with familial disease, a genetic defect accounts for the increased activity of γ secretases. In the majority of patients, however, there is no identified defect that explains the presence of the neurofibrillary tangles and senile plaques.

during the perioperative period are goals in patients with AD. Much has been written about informed consent for surgical procedures and anesthesia. Patients with AD, by definition, have cognitive impairment, but in many states, depending on the degree of impairment, they may drive, vote, and give informed consent. The anesthesiologist must be able to assure himself or herself that the patient understands the procedure, the options, and the risks. If not, then

Recognition There is a broad spectrum of disease, but progressive impairment in memory, judgment, decision making, awareness of surroundings, and ability to care for oneself are the hallmarks of AD. Some patients who are seen preoperatively for unrelated problems may appear lucid and able to give informed consent. An accompanying family member, a person with a durable power of attorney for health care, or a review of the medical record may bring to the anesthesiologist’s attention the fact that the patient has AD. Other patients with more advanced disease or uncommon presentations may be belligerent or may have aphasia or spastic paraparesis. There is no clinical test to diagnose AD, although neurocognitive testing confirms the presence of dementia (Table 118-1). Anesthesiologists may use simpler tests to assess whether a patient is oriented and able to understand and provide informed consent.

Risk Assessment Obtaining informed consent, minimizing the chance of postoperative confusion, and optimizing management

From http://www.emedicine.com/neuro/topic13.htm.

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consent should be obtained from the next of kin. Obviously, if the patient has a representative with a durable power of attorney for health care, the process is easier. In either case, as with adolescents, it is best to have the patient sign the consent form to “assent” to the procedure and have a legal representative give “legal consent.” Agitation in patients with AD is not uncommon. Therefore, patients with AD may receive a benzodiazepine to reduce preoperative agitation. However, because postoperative cognitive impairment is often associated with anesthesia, benzodiazepines should not be part of the routine anesthetic plan for these patients. If they are used at all, benzodiazepines should be administered only after a risk-benefit analysis has been performed.

Implications There are no specific recommendations for managing anesthesia in patients with AD. Consent, as mentioned, is often an issue. However, regardless of who provides consent, the anesthesiologist must be patient when educating and calming a patient with AD. Many such patients have advanced directives. Discussion of the implications of the directive must occur preoperatively with the patient, the patient’s legal surrogate, or both. Regional anesthesia may seem preferable because there is less risk of worsening the patient’s cognitive impairment compared with general anesthesia. However, because many patients with AD are disoriented, agitated, and uncooperative, regional anesthesia can present quite a challenge. There is no single best type of anesthesia or anesthetic agent for patients with AD. They often have reduced reserves in vital organ function—pulmonary, cardiac, neurologic—and these factors must be taken into account.

MANAGEMENT There is no known cure for AD. As the disease progresses, patients are often institutionalized in nursing homes or their equivalent. Behavioral therapies include patient-centered approaches to try to minimize the effects of memory loss (e.g., established daily routines); caregiver training enables aides and therapists to recognize and deal with the common behavioral manifestations of AD. Psychotropic medications such as risperidone, olanzapine, and quetiapine are recommended at low doses to treat common manifestations of the disease such as anxiety, agitation, and depression. Decreased levels of acetylcholine in the cerebral cortex of AD patients are thought to account for many of the symptoms and signs of the disease. Therefore, drugs targeted at inhibiting the degradation of acetylcholine by cholinesterases in the cerebral cortex have been developed and are used to treat AD (e.g., tacrine, donepezil, rivastigmine, galantamine). Cholinesterase inhibition has been associated with improvement in cognitive function. Patients taking cholinesterase inhibitors should take their medication with a small sip of water the morning of surgery, because acute, severe cognitive and behavioral decline has been reported in patients who abruptly discontinue their medication.

In addition, an N-methyl-D-aspartate antagonist (memantine) has been approved in the United States to treat AD patients and is of some benefit in other patients with dementia. Patients with AD should have a responsible family member present with them whenever possible—someone they recognize and who can reassure and calm them during the perioperative period. This individual should also have the capacity to give informed consent for the anesthetic. Although these patients may be anxious, sedating drugs are avoided because they contribute to the postoperative confusion and delirium that often occur. Regional anesthesia, if indicated, should be attempted only if the patient is cooperative. Inhalational agents are used if general anesthesia is indicated, mainly owing to their rapid elimination. Glycopyrrolate does not cross the blood-brain barrier and is therefore preferred if an anticholinergic agent is required.

PREVENTION There are no known agents to prevent AD. Even drugs such as donepezil are effective in less than half of AD patients, and in those who do show a benefit, it lasts for only a few years at best. Although cognitive impairment is associated with general anesthesia, there is no evidence that general anesthesia increases the severity of AD. Caregivers may think so, because borderline cognitive impairment may worsen after an anesthetic. However, such worsening is transient, and patients should return to baseline within days to weeks following anesthesia. As discussed earlier, there is no ideal anesthetic type, technique, or agent. In developing an anesthetic plan, the anesthesiologist must consider the degree of cognitive impairment, the amount of agitation, the degree of cooperation, comorbid conditions, and possible drug interactions. With careful planning and management, the patient’s caregiver should notice only mild, if any, worsening of neurologic function postoperatively.

Further Reading Bohnen N, Warner MA, Kokmen E, et al: Early and midlife exposure to anesthesia and age of onset of Alzheimer’s disease. Int J Neurosci 77:181-185, 1994. Clark CM, Ewbank D, Lee VM-Y, et al: Molecular pathology of Alzheimer’s disease: Neuronal cytoskeletal abnormalities. In Growdon JH, Rosser MN (eds): The Dementias, vol 19 of Blue Books of Practical Neurology. Boston, Butterworth-Heinemann, 1998, pp 285-304. Dickson DW: Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: Cause or effect? J Clin Invest 114:23-27, 2004. Esler WP, Wolfe MS: A portrait of Alzheimer secretases—new features and familiar faces. Science 293:1449-1454, 2001. Fernandez CR, Fields A, Richards T, et al: Anesthetic considerations in patients with Alzheimer’s disease. J Clin Anesth 15:52-58, 2003. Gasparini M, Vanacore N, Schiaffini C, et al: A case-control study on Alzheimer’s disease and exposure to anesthesia. Neurol Sci 23:11-14, 2002. Hutton M, Perez-Tur J, Hardy J: Genetics of Alzheimer’s disease. Essays Biochem 33:117-131, 1998. Iwatsubo T, Odaka A, Suzuki N, et al: Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: Evidence that an initially deposited species is A beta 42(43). Neuron 13:45-53, 1994.

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Langa KM, Foster NL, Larson EB: Mixed dementia: Emerging concepts and therapeutic implications. JAMA 292:2901-2908, 2004. Larson EB, Kukull WA, Buchner D, et al: Adverse drug reactions associated with global cognitive impairment in elderly persons. Ann Intern Med 107:169-173, 1987.

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Nussbaum RL, Ellis CE: Alzheimer’s disease and Parkinson’s disease. N Engl J Med 348:1356-1364, 2003. Selkoe DJ: Alzheimer disease: Mechanistic understanding predicts novel therapies. Ann Intern Med 140:627-638, 2004.

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Jacob Gutsche and Clifford S. Deutschman Case Synopsis A 22-year-old man presents with fever and abdominal pain. A computed tomography scan indicates that he has appendicitis. Laparoscopic exploration reveals a perforated appendix with pus and stool in the abdomen. The patient undergoes laparotomy and appendectomy. The open abdomen is irrigated extensively with antibiotic-containing saline. During the procedure the patient develops hypotension and oliguria, requiring the administration of significant volumes of intravenous fluid. The anesthesiologist inserts an arterial line and pulmonary artery catheter to monitor the resuscitation. Peritoneal fluid and blood cultures are obtained, and broad-spectrum antibiotics are started.

PROBLEM ANALYSIS Definition and Recognition The systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) were first described in the 1970s. Early reports of MODS heralded our ability to support patients through such major medical or surgical catastrophes as ruptured aortic aneurysms, severe trauma, pancreatitis, multiple transfusions, and major systemic infections. Unfortunately, surviving patients subsequently developed dysfunction in organs that were unaffected by the initial injury. Multiple terms were applied to these syndromes, which led to confusion and limited the ability to stratify risk and compare therapeutic options. In 1991 the American College of Chest Physicians and Society of Critical Care Medicine convened a consensus conference to formalize definitions, allowing the comparison of patient populations from different institutions or geographic regions. These deliberations generated the new term SIRS, which was necessary because there were patients who developed signs and symptoms of systemic inflammation but without identifiable infection. The presence of any two of four criteria is sufficient to establish the diagnosis of SIRS (Table 119-1). In addition, the consensus conference provided formal definitions for sepsis (Table 119-2), and the syndrome of organ failure following SIRS or sepsis was renamed MODS. Although these definitions greatly improved our ability to compare patient populations and conduct more meaningful clinical trials, several problems remained. Key was the 496

excessive sensitivity and lack of specificity inherent in the definition of SIRS. Namely, many events or interventions provoke a stress response in patients sufficient to meet the criteria for SIRS. For example, virtually every postoperative patient meets the SIRS criteria, but it is clear that most should not be included in studies of the pathogenesis of MODS. Primarily for this reason, North American and European critical care societies convened an International Sepsis Definitions Conference in 2001 to revisit and modify the definitions established in 1991. Conference participants chose to de-emphasize the use of the term SIRS and to lengthen the list of signs and symptoms characterizing sepsis (Table 119-3). In addition, more specific criteria for organ dysfunction were adopted (Table 119-4).

Risk Assessment and Implications Humans respond to physiologic stress such as trauma, stroke, pneumonia, ischemia, pancreatitis, bowel perforation,

Table 119–1

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Criteria for Systemic Inflammatory Response Syndrome

Fever (core temperature >38.3°C) or hypothermia (core temperature <36°C) White blood cell count >12,000 or < 4000 Heart rate >90 beats/min or >2 standard deviations above normal for age Tachypnea

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Consensus Definitions of Sepsis and Septic Shock

Severe sepsis: sepsis with the presence of dysfunction in at least one organ Septic shock: sepsis with persistent hypotension Mean arterial pressure <60 mm Hg Systolic blood pressure (SBP) <90 mm Hg Decrease in SBP >40 mm Hg from patient’s normal baseline, despite adequate volume resuscitation

large-volume blood loss, and infection in a specific manner. This characteristic physiologic response is referred to as the stress response, and it may have evolved as a way to promote recovery from localized trauma or infection. The initial phase of the response is commonly called shock. In most cases, shock is rapidly reversible. The second phase includes hypermetabolism and can be thought of as occurring to facilitate the repair of damaged tissue. This second phase also includes leukocytosis, which features (1) mobilization of leukocytes to the area of damage, (2) enhanced hepatic gluconeogenesis to provide fuel for these leukocytes, (3) increased oxygen extraction at the tissue level, and (4) breakdown of endogenous proteins, primarily by catabolism of skeletal muscle. This process provides the necessary substrates for gluconeogenesis, increased hepatic protein synthesis, and repair of damaged tissue. Further, the process is driven by catecholamines, cortisol, glucagon, and cytokines

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Criteria for Suspected or Documented Sepsis

General Variables Fever (core temperature >38.3°C) Hypothermia (core temperature <36°C) Heart rate >90 beats/min or >2 SD above normal for age Tachypnea Altered mental status Significant edema or positive fluid balance (>20 mL/kg over 24 hr) Hyperglycemia (plasma glucose >120 mg/dL) in patients without diabetes

Inflammatory Variables Leukocytosis (WBC count >12,000) Leukopenia (WBC count < 4000) Normal WBCs with >10% immature forms C-reactive protein >2 SD above normal value Plasma procalcitonin >2 SD above normal value

Hemodynamic Variables Arterial hypotension (SBP <90 mm Hg, MAP <70 mm Hg, or SBP decrease ≥40 mm Hg or to <2 SD below normal for age) SvO2 >70% (this level can be normal in children, so this is not a criterion for pediatric patients) Cardiac index >3.5 (this level can be normal in children, so this is not a criterion for pediatric patients)

Tissue Perfusion Variables Hyperlactatemia (>1 mmol/L) Decreased capillary refill or mottling MAP, mean arterial pressure; SBP, systolic blood pressure; SD, standard deviations; SvO2, venous oxygen saturation; WBC, white blood cell. Adapted from Levy MM, Fink MP, Marshall JC, et al: 2001 SCCM/ESICM/ ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 29:530-538, 2003.

released by leukocytes. The resultant hyperglycemia is associated with an increased release of insulin. Finally, substrate delivery is facilitated by vasodilatation, fluid retention, increased cardiac output, and capillary leak, all of which appear to be essential, because damaged tissue is avascular. The hypermetabolic phase of the stress response can evolve via two possible pathways; one is normal, and the other is pathologic. In the normal pathway, completion of angiogenesis by postinjury day 4 leads to the resolution of inflammation, hypermetabolism, and the hyperendocrine state. This is the more common scenario and is normal. Although it meets all the criteria for SIRS, it is clearly not what the 1991 consensus conference participants had in mind when they coined the term “systemic inflammatory response syndrome.” In some patients, however, inflammation becomes pathologic. The mechanism of such transformation is unknown. These patients have SIRS or, with infection, sepsis. Either of these is characterized by important changes in metabolism and regulation: ●

●

●

In contrast to simple stress, the ability to extract and use oxygen is diminished, despite increased cellular demand. The increased demand for energy by white blood cells, coupled with an inability to use molecular oxygen, leads to aerobic glycolysis. That is, oxygen delivery is adequate, but the inability to use oxygen increases lactate production. This causes persistent hyperglycemia, impaired glucose utilization, and a state of relative glucose intolerance. Endocrine abnormalities become prominent. The production and release of some hormones, notably vasopressin, are reduced, resulting in relative deficiency. Also, tissues become resistant to the effects of other hormones. This is exemplified by the development of insulin resistance or the diminished ability of catecholamines to modulate vascular tone.

Cellular dysfunction leads to biochemical abnormalities without overt organ failure. For example, hepatic dysfunction impairs gluconeogenesis, which prevents the conversion of lactate to pyruvate. Also, oxidation of long-chain triglycerides and the expression of key β-oxidative enzymes are decreased. As a result, amino acids become an increasingly important fuel source, despite the fact that hepatic dysfunction compromises ureagenesis. Importantly, contractile dysfunction is often observed in patients with MODS. In each case, compensatory mechanisms (increased substrate delivery to the liver, vasodilatation, and increased diastolic volume in the heart) may mask organ dysfunction.

MANAGEMENT AND PREVENTION There is no “magic bullet” to cure SIRS, sepsis, or MODS. It is not known what causes a controlled inflammatory response to become pathologic. In the absence of a specific target for therapy, management is based on source control, supportive care, and prevention of further complications.

Source Control The patient history, physical examination, and laboratory or diagnostic studies are used to identify infectious causes of continuing inflammation.

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Criteria for Organ Dysfunction Severity of Dysfunction

Body System

Mild

Severe

Pulmonary

Hypoxia or hypercarbia requiring assisted ventilation for ≥ 3-5 days Bilirubin ≥ 2-3 mg/dL; prothrombin time or other liver function tests ≥2 times normal Oliguria (<500 mL/day) or increasing creatinine (≥ 2-3 mg/dL) Intolerance of gastric feeding >5 days

ARDS requiring PEEP ≥10 cm H2O and FiO2 ≥0.5

Hepatic Renal Gastrointestinal Hematologic Central nervous system Peripheral nervous system Cardiovascular

Partial thromboplastin time ≥125% of normal, platelets < 50,000-80,000 Confusion Mild sensory neuropathy Decreased ejection fraction, persistent capillary leak

Jaundice with bilirubin ≥8-10 mg/dL Need for dialysis Stress ulceration with need for transfusion; acalculous cholecystitis Disseminated intravascular coagulation Coma Combined motor and sensory deficit Hypodynamic state not responsive to pressors

ARDS, acute respiratory distress syndrome; FiO2, fraction of inspired oxygen; PEEP, positive end-expiratory pressure.

Supportive Care Supportive care includes the following. Fluid Resuscitation. The goal of fluid resuscitation is to maintain intravascular volume despite ongoing capillary leak. This can be accomplished with colloid-based fluids such as albumin or hetastarch, crystalloid (use of a balanced salt solution is preferred to saline, to avoid the development of hyperchloremic metabolic acidosis), or blood or blood products if appropriate. The Canadian Transfusion Trial suggests that a hemoglobin of 7 mg/dL is sufficient for most critically ill patients. Goals for appropriate fluid resuscitation vary with the patient’s underlying disease and premorbid cardiac, pulmonary, and renal status. A study by Rivers and colleagues indicated that early goal-directed therapy designed to achieve a central venous pressure of 8 to 12 mm Hg, mean arterial pressure greater than 65 mm Hg, urine output greater than 0.5 mL/kg per hour, and mixed venous oxygen saturation greater than 70% improved outcomes. Vasopressors and Inotropes. In cases of severe sepsis or septic shock, fluid resuscitation may not be sufficient to restore organ perfusion. Clinically, it is difficult to distinguish between vasodilatation and myocardial depression. Consequently, vasoactive drugs are an important treatment adjuvant. Most recent studies favor the use of norepinephrine. If cardiac output is severely depressed, primary inotropes, such as dobutamine, may be useful. Dopamine administration is of historical interest only. This agent is arrhythmogenic and can cause maldistribution of splanchnic flow; putative renal sparing effects have been disproved in myriad studies, although stimulation of D1 receptors on the distal renal tubule does cause a diuretic effect. Mechanical Ventilation. Respiratory control is best viewed as having two components: hypoxia or, as in severe sepsis, acute respiratory distress syndrome (ARDS). Either may require an increase in the fraction of inspired oxygen (FiO2), although it is customary to try to keep FiO2 less than 0.5 to

0.6 to prevent “oxygen toxicity.” However, there are no human data to indicate that higher levels of FiO2 at one atmosphere of pressure are truly damaging. One recent trial indicated that keeping plateau pressures below 30 cm H2O or tidal volumes less than 6 mL/kg in patients with ARDS limits secondary lung injury and improves outcomes. Positive endexpiratory pressure (PEEP) is useful both to improve pulmonary compliance and to maintain recruitment of alveoli. We strongly advocate the “open lung” strategy of Amato. This somewhat controversial approach involves titrating PEEP to a level above the “lower inflection point” in the pressurevolume curve, increasing functional residual capacity and recruiting collapsed alveoli. Additional ventilatory adjuvants include the use of sighs and other recruitment maneuvers (e.g., tiltable and rotating posturing beds to improve ventilation/ perfusion mismatch). Keeping the head of the patient’s bed elevated above 30 degrees limits aspiration and decreases the incidence of nosocomial pneumonia. Broad-Spectrum Antibiotics. Early use of broad-spectrum antibiotics improves the outcome in septic patients. If cultures reveal a causative organism, antibiotic therapy is directed at that organism. This reduces the risk of resistant organisms or superinfections. Endocrine Support. Recent studies indicate that sepsis can rapidly progress to a state of relative endocrine insufficiency. For example, data by Landry and coworkers convincingly show a loss of vasopressin stores from the posterior pituitary, which is problematic. Vasopressin is most active in controlling tone in the splanchnic circulation, and the major component of sepsis-associated vasodilatation arises in this bed. Infusion of replacement vasopressin (0.01 to 0.04 unit/minute) restores normotension and may help wean the patient from other vasoactive substances. However, the use of corticosteroids in sepsis remains controversial. The debate centers on the inability to determine what constitutes a “normal” hypothalamic-pituitary-adrenal response in severe sepsis. Nonetheless, recent studies indicate that low doses of

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exogenous corticoids (hydrocortisone 50 mg/day) may improve refractory hypotension and facilitate weaning of exogenous catecholamines. Early Dialysis. Recent studies support the use of dialysis early in sepsis. Continuous dialysis is favored because it is associated with less hemodynamic instability. High flows seem to offer better solute clearance. When conventional hemodialysis is used, daily dialysis appears to be more effective than the more standard every-other-day approach.

Prevention of Further Complications Activated Protein C. In 2001, one multicenter, randomized trial examined the effects of activated protein C (APC) infusion started within 24 hours of the diagnosis of sepsis associated with major organ dysfunction. This was continued for 96 hours and led to a 6% reduction in 28-day mortality. However, protocol concerns and the risk of serious bleeding led the Food and Drug Administration to limit the indications for APC. Thus, APC has been approved for use in patients with severe sepsis and APACHE II scores greater than 25. However, newer data suggest that the improvement seen at 28 days is not sustained. In addition, APC is quite expensive. Thus, this drug is rarely used.

A New Syndrome The incidence of SIRS, sepsis, and MODS is difficult to quantify. This reflects both the diverse group of entities giving rise to these conditions and confusion about what does and does not constitute SIRS. However, recent studies indicate

that while mortality from sepsis has declined, the incidence of sepsis is steadily increasing. Indeed, the natural history of these conditions is rapidly evolving. Initial descriptions of what we now call SIRS, sepsis, and MODS arose when our ability to treat these conditions was dismal (with almost certain early mortality). We now have the ability to support most forms of major organ dysfunction, and this has led to the emergence of a new syndrome. There is no consensus name or definition for this new entity, which is characterized by a stable but highly abnormal state involving endocrine and inflammatory exhaustion. The failure of multiple components of the neuroendocrine system in the chronically, critically ill has been well described, and the concept of immune incompetence has recently been reviewed by Hotchkiss and Karl. More often than not, modern medical technology can maintain survival in this state. Reversal of the disorder, however, is difficult. What is increasingly clear is that mortality from SIRS, sepsis, or MODS most often occurs when exogenous life support is discontinued.

Further Reading Angus DC, Wax S: Epidemiology of sepsis: An Update. Crit Care Med 29:S109-S116, 2001. Bernard GR, Vincent JL, Laterre PF, et al: Recombinant Human Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group: Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699-709, 2001. Bone RC, Balk RA, Cerra FB, et al: Definition for sepsis and organ failure and guidelines for use of innovative therapies in sepsis: American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644-1655, 1992. Deitch EA: Multiple organ failure: Pathophysiology and potential future therapy. Ann Surg 216:117-134, 1992. Dellinger RP, Carlet JM, Masur H, et al: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 32:858-873, 2004. Deutschman CS: The systemic inflammatory response syndrome and the multiple organ dysfunction syndrome. In Fishman AP (ed): Pulmonary Diseases and Disorders. New York, McGraw-Hill, 1997. Hotchkiss RS, Karl IE: The pathophysiology and treatment of sepsis. N Engl J Med 348:138-150, 2003. Landry DW, Levin HR, Gallant EM, et al: Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 95:1122-1125, 1997. Rivers E, Nguyen B, Havstad S, et al: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368-1377, 2001. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 342:1301-1308, 2000.

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Tight Glucose Control. Another single-center study examined tight glucose control (>80 but <110 mg/dL) with insulin in critically ill patients. Results showed clear improvement in many outcome variables. However, results should be applied cautiously to septic patients. The study population was homogeneous, and more than 65% had undergone cardiopulmonary bypass. Further, all patients received significant exogenous glucose. Subsequent studies by the same group and others revealed that primary outcomes were determined by the glucose concentration, not the use of insulin. In severe stress states (e.g., SIRS, sepsis, MODS), glucose is not used as a fuel and probably is best avoided. Thus, logic would dictate that limiting glucose may be as effective as giving insulin. If so, we advise limiting glucose administration and controlling serum glucose at less than 150 mg/dL.

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Perioperative Care of Immunocompromised Patients Shubjeet Kaur and Stephen O. Heard Case Synopsis A 45-year-old man with renal failure secondary to chronic diabetes mellitus underwent cadaveric renal transplantation 1 month before admission. He now presents with a perforated duodenal ulcer and is scheduled to undergo emergency exploratory laparotomy. His temperature is 39.6°C, blood pressure is 88/60 mm Hg, and pulse is 110 beats per minute. His medications include NPH insulin, cyclosporine, ranitidine, diltiazem, and prednisone. Pertinent laboratory values are a white blood cell count of 2300 cells/mm3, hematocrit 28%, creatinine 2.1 mg/dL, blood glucose 550 mg/dL, and amylase 459 units.

and various malignancies may receive immunosuppressive chemotherapy. Because a significant proportion of these patients may present for elective or emergency surgical procedures, perioperative care presents a challenge.

PROBLEM ANALYSIS Definition An immunocompromised patient is at increased risk for infection due to defective defense mechanisms (Table 120-1). These can be specific (immune) or nonspecific (nonimmune). Immunosuppression exists if immune defenses are present but are deficient rather than defective. Recent data suggest that 0.25% to 1.5% of the total population in the United States may be immunocompromised. An unknown proportion of patients may be immunocompromised due to underlying disease or to surgical or medical interventions (Table 120-2). Patients with human immunodeficiency virus (HIV) infection, massive burns, diabetes mellitus, cirrhosis, or cancer may also be immunosuppressed. Immunosuppressive drugs used to prevent the rejection of transplanted organs also place patients at risk for infection. Similarly, patients with autoimmune diseases

Table 120–1

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Host Defense Mechanisms

Type of Immunity

Components

Innate

Epithelial barriers (nonimmune) Complement Macrophages Cytokine and chemokine release Acute phase response Expression of adhesion molecules Chemoattractants and neutrophils Interferons Natural killer cells “Primitive lymphocytes” T cells B cells Memory

Early induced responses

Adaptive and protective immunity

500

Recognition In many patients, the presence of immunosuppression is obvious from the history and physical examination. However, subtle and less obvious alterations in immune function may be present in a significant number of surgical patients. The findings on physical examination are often nonspecific; however, there may be signs suggestive of immunosuppression, such as the cushingoid appearance in a patient with chronic corticosteriod use or thrush in a patient with HIV infection. Any device that traverses anatomic barriers or impairs defense mechanisms, such as intravenous catheters or endotracheal tubes, increases the risk of nosocomial infection (see Chapter 51).

Table 120–2

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Causes of Immunosuppression

Diseases or Conditions Human immunodeficiency virus (HIV) Cancer Massive burns Trauma Advanced age Asplenia Autoimmune diseases

Medical or Surgical Therapy Antirejection agents Chemotherapy for malignancies and autoimmune diseases Anesthetic agents Blood transfusions Chronic steroid therapy

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Readily available laboratory values that may suggest immunosuppression include a complete blood count with a differential smear and serum immunoglobulin levels. More sophisticated tests, such as HIV testing, quantification of blood mononuclear cell populations, complement assays, and T-cell function (e.g., delayed hypersensitivity skin testing) and B-cell function (e.g., presence of antibodies to common antigens), are required to diagnose and determine the magnitude of the immunocompromised state.

Risk Assessment

Implications Common infections may have an atypical presentation in immunocompromised or immunosuppressed patients. Clinical symptoms or signs of significant underlying infection may be absent, subtle, or misleading in these patients, and a high index of suspicion for the presence of infection is necessary. A careful physical examination may provide clues to the presence of infection, but often ancillary laboratory testing, imaging, serology, and microbiology (including cultures for fungal, mycobacterial, and viral pathogens) are necessary to diagnose an opportunistic infection. Important drug interactions can occur in the perioperative period. For example, there is the potential for adverse interactions between antirejection drugs and antibiotics prescribed for suspected infection. Cyclosporine, a commonly used antirejection medication, is cleared by the cytochrome P-450 enzyme system. Cyclosporine toxicity may result from

501

a concomitantly prescribed antibiotic such as amphotericin B, erythromycin, or ketoconazole. Similarly, the risk of nephrotoxicity may increase in a patient who is simultaneously receiving vancomycin and an aminoglycoside. Tacrolimus is the primary agent used for immunosuppression in patients who have undergone solid organ transplantation. Neurotoxic side effects of this agent such as headache, tremor, and paresthesia are the most frequent and predominant. Commonly used drugs in the perioperative period, such as calcium channel blockers, gastrointestinal prokinetic agents, azole antifungal agents, macrolide antibiotics, and protease inhibitors, increase serum tacrolimus concentrations, whereas phenytoin decreases tacrolimus serum concentrations. OKT-3 is a mouse monoclonal antibody that binds to the CD3 antigen on T lymphocytes and is used for steroidresistant graft rejection. Toxicity includes central nervous system effects and a cytokine release syndrome that ranges from a mild flulike response to severe shock and acute respiratory distress syndrome. This latter response can be minimized by the administration of high-dose steroids. Basiliximab and daclizumab are monoclonal antibodies directed against the interleukin-2 receptor on the surface of activated T lymphocytes; they inhibit the activation and proliferation of T lymphocytes. The risk of infection with the use of these agents appears to be no higher than with other immunosuppressive regimens. Some antirejection drugs interact with anesthetic drugs. Animal data suggest that cyclosporine may potentiate the effect of barbiturates, opioids, and neuromuscular blocking agents. Clinical studies demonstrate that azathioprine, another antirejection agent, has weak antagonistic effects on neuromuscular blockade. Additionally, there is an increased risk for the development of acute respiratory failure in patients who have been treated with bleomycin and are subsequently exposed to fractional inspired concentrations of oxygen greater than 0.30. Many patients who receive corticosteroids as part of their therapy present to the operating room. The effect of steroids on adrenal function and reserve is complex and unpredictable. In general, large doses of steroids with a long halflife (e.g., dexamethasone) administered frequently are much more likely to cause adrenal suppression than are less potent steroids administered less frequently. If there is doubt about adrenal reserve, low-dose (1 μg) or high-dose (250 μg) cosyntropin testing can be performed preoperatively, or stressdose corticosteroids (up to 300 mg/day of hydrocortisone) can be administered perioperatively and rapidly tapered. Patients with chronic hepatitis C are treated with interferon alfa-2a, PEG-interferon alfa-2a, or PEG-interferon alfa-2b. These agents can cause a dose-dependent neutropenia and thrombocytopenia. In addition, ribavirin, an antiviral agent used in conjunction with an interferon, often causes a hemolytic anemia. Likewise, patients with multiple sclerosis are often treated with interferon beta-1b. Adverse reactions similar to those seen with the other interferons can be expected. Tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) are important cytokines involved in the systemic inflammation and cartilage destruction associated with rheumatoid arthritis. Anti-TNF-α and anti-IL-1 inhibitors are used in patients with rheumatoid arthritis who are

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

The lung is the single most commonly infected organ, and pneumonia may account for up to 40% of all deaths in immunocompromised patients. Patients who have undergone organ transplantation and are taking antirejection medications have a biphasic infection risk pattern. In the initial 6 weeks following transplantation, these patients are generally susceptible to the same infections observed in the postoperative period after any major surgical procedure. From 6 weeks to 6 months, they are highly susceptible to opportunistic infection such as Pneumocystis jirovecii pneumonia, surgical infections, and other unusual infections. As the dose of the immunosuppressive drug is tapered, the infection risk diminishes progressively if the allograft function is good and there is no chronic viral infection. Patients with autoimmune disorders, such as rheumatoid arthritis or scleroderma, may have problems with mouth opening and joint mobility. Careful assessment of the airway is important to determine whether tracheal intubation will be difficult. In patients with HIV infection, there is a significant risk of infection from uncommon pathogens. Systemic fungal infections are especially common, including pneumonia from Pneumocystis jirovecii. In addition to their primary therapeutic effects, immunosuppressive drugs and antimicrobial agents used to treat nosocomial and opportunistic infections have side effects that can adversely affect other organ systems. In addition, immunocompromised patients often have multisystem disease, poor general health, and diminished reserves of vital organ function (e.g., decreased pulmonary and myocardial reserves).

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refractory to conventional therapy (Table 120-3). The risk of serious infections (particularly tuberculosis) increases with the use of these drugs, and autoantibodies to the drugs can develop. Immunocompromised or immunosuppressed patients frequently have coexisting multiple organ dysfunction. These alterations in organ function may affect the choice of anesthetic agents and techniques. Some published data suggest that anesthetics and operations may alter some immune responses secondary to the release of cortisol and catecholamines. The effect of anesthetic agents themselves on perioperative immune function is unclear. Animal and in vitro studies suggest that natural killer cell cytotoxicity, B-cell and T-lymphocyte activity, and macrophage and polymorphonuclear neutrophil function are altered by volatile anesthetics or opioids. However, the clinical significance of these changes is unclear; one study of volunteers exposed to general anesthesia, lumbar epidural anesthesia, or opioids showed minimal change in immune function.

of glucose (80 to 110 mg/dL) with an insulin infusion in the intensive care unit has a dramatic impact on outcome: reduced mortality and morbidity (infection, neuropathy, acute renal failure requiring dialysis, and need for blood transfusion). Similar results have been reported with intraoperative control of glucose. More controversial is the intraoperative use of high concentrations of inspired oxygen; randomized studies have reported disparate results. Induced hypercarbia improves subcutaneous tissue oxygenation and might reduce the risk of perioperative wound infection, but large, randomized trials are needed to confirm the efficacy of this treatment modality. Blood transfusions have immunosuppressive properties and can increase the risk of perioperative infection. Thus, careful consideration should be given to the transfusion “trigger.” In a stable patient with minimal blood loss and without a high risk of myocardial ischemia, waiting to transfuse until the hemoglobin is between 7 and 8 g/dL is safe and reasonable. Use of preoperative autologous blood donation, intraoperative hemodilution, and red blood cell scavenging may reduce the need for perioperative allogeneic blood transfusion. The anesthetic plan should be based on the preoperative assessment. Regional anesthetic techniques are not necessarily contraindicated in immunocompromised or immunosuppressed patients, but the absence of a central nervous system infection and adequate coagulation status must be documented. In patients with diminished hepatic or renal reserve, sedation, analgesia, and neuromuscular blockade may be prolonged. These patients may need monitoring in an intensive care unit, especially if there is evidence of preoperative pulmonary compromise or hemodynamic instability. For patients who have been treated previously with corticosteroids, consideration should be given to testing the adrenal reserve or treatment with stress-dose steroids.

MANAGEMENT

PREVENTION

The patient’s medical status should be fully evaluated and optimized before the surgical procedure, with careful attention paid to subtle signs of incipient infection. Invasive monitoring, which itself poses a risk of infection, should be predicated on the proposed surgical procedure and the patient’s medical condition. Because these patients are at higher risk for developing perioperative infections, scrupulous precautions must be taken. Simple hand washing or the use of alcohol foam soaps is an often overlooked and underutilized method of reducing the transmission of nosocomial infections. Strict aseptic technique, including maximum barrier precautions, should be used when placing invasive hemodynamic monitoring catheters. If indicated, prophylactic antibiotics should be administered at least 30 minutes before skin incision; however, antibiotic administration 2 hours or more before or after incision is ineffective in preventing surgical wound infection. Recent data suggest that the anesthesiologist can have a significant beneficial impact on reducing perioperative infection and improving patient outcome. Well-designed prospective trials have shown that prevention of intraoperative hypothermia during colorectal surgery reduces the risk of perioperative wound infection. In addition, tight control

Deterioration in an already fragile patient can be prevented by compulsive and vigilant perioperative care. Adherence to hand washing and aseptic techniques is mandatory. Prevention of intraoperative hypothermia and rigid control of blood glucose can reduce perioperative wound infection. A high index of suspicion when seeking and treating infection and the goal of optimizing underlying organ function can improve the outcome in these patients.

Table 120–3

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Biologic Agents Used in the Therapy of Rheumatoid Arthritis

Class

Drug

Side Effects

Inhibitors of tumor necrosis factor-α

Infliximab

Infection; worsening of congestive heart failure Infection Infection Infection; neutropenia

Inhibitor of interleukin-1

Adalimuab Etanercept Anakinra

Adapted from O’Dell JR: Therapeutic strategies for rheumatoid arthritis. N Engl J Med 350:2591-2602, 2004.

Further Reading Cirella VN, Pantuck CB, Lee YJ, et al: Effects of cyclosporine on anesthetic action. Anesth Analg 66:703-706, 1987. de Maat MM, Ekhart GC, Huitema AD, et al: Drug interactions between antiretroviral drugs and comedicated agents. Clin Pharmacokinet 42:223-282, 2003. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther 39:21-28, 1997. Evron S, Glezerman M, Harow E, et al: Human immunodeficiency virus: Anesthetic and obstetric considerations. Anesth Analg 98:503-511, 2004. Gramstad L, Gjerlow JR, Hysing ES, et al: Interaction of cyclosporine and its solvent cremophor with atracurium and vecuronium. Br J Anaesth 58:1149-1155, 1986. Kozyra EF, Wax RS, Burry LD: Can 1 μg of cosyntropin be used to evaluate adrenal insufficiency in critically ill patients? Ann Pharmacother 39:691-698, 2005.

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Kumar A, Hota B: Infections in the immunocompromised. In Murray MJ, Coursin DB, Pearl RG, Prough DS (eds): Critical Care Medicine: Perioperative Management, 2nd ed. Philadelphia, Lippincott-Raven, 2002, pp 649-671. Kurz A, Sessler DI, Lenhardt R: Perioperative normothermia to reduce the incidence of surgical wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. N Engl J Med 334:1209-1215, 1996.

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Rubin RH: Fungal and bacterial infections in the immunocompromised host. Eur J Clin Microbiol Infect Dis 12(Suppl 1):S42-S48, 1993. Vallejo R, Hord ED, Barna SA, et al: Perioperative immunosuppression in cancer patients. J Environ Pathol Toxicol Oncol 22:139-146, 2003. van den Berghe G, Wouters P, Weekers F, et al: Intensive insulin therapy in the critically ill patient. N Engl J Med 345:1359-1367, 2001.

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Thermally Injured Patients Avery Tung and Michael F. O’Connor

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Case Synopsis A 59-year-old man falls asleep in bed while smoking. He sustains deep partial- and fullthickness burns to approximately 50% of his body surface, including his face and extremities. He arrives in the emergency room intubated. The anesthesiologist is called to assist with his early management.

PROBLEM ANALYSIS Definition Burn injuries are classified in terms of their cause, depth, and extent. Each factor plays an important role in the evaluation and management of burn injury patients. Reports by emergency medical personnel and the initial history and physical examination are the primary means of identifying the causes and mechanisms of burn injuries. Burns may be thermal, chemical, or electrical. Thermal injury requires the application of sufficient heat for a sufficient period so that cutaneous tissue heats to a temperature at which injury can occur. Chemical burns generally do not cause injury from the effects of heat; rather, injury is caused by corrosion, desiccation, or a chemical reaction. Although some chemicals have specific antidotes (e.g., calcium gel for hydrofluoric acid burns), the recommended initial treatment for most chemical burns is early and copious irrigation to dilute the offending agent. Electrical burns produce injury via three mechanisms: (1) nerves or blood vessels act as conduits for heat to cause injury in affected tissue; (2) electrical current may arc across two points on the body surface, thereby generating high temperatures and producing focal areas of external tissue injury; and (3) electrical energy may ignite clothing or other combustible materials, thereby producing secondary thermal injury due to the heat generated by the burning materials. Finally, chemical and thermal injury may coexist, as in burns caused by gasoline or other flammable materials.

Recognition Regardless of the mechanism of burn injury, burns of any type are categorized as first, second, or third degree, based on the depth of tissue injury. First-degree burns (e.g., mild sunburns) involve the epidermis only and heal readily without specific interventions. Such burns may be painful and appear as reddened areas of intact skin that blanch with pressure. Second-degree burns, often referred to as partialthickness burns, partially involve the dermis and require specific wound therapy. They may or may not require skin grafting, depending on the amount of nonaffected dermal tissue. Second-degree burns are moist, blanch with pressure, retain sensation, and often are extremely painful. Third-degree (full-thickness) burns destroy all dermal elements and penetrate into the subcutaneous tissue. The third-degree burn 504

surface appears white and has a waxy feel; often it is speckled with red dots (i.e., heat-congealed hemoglobin) and devoid of any sensation. Left untreated, third-degree burns heal via central migration of the wound edges. Because this process may cause crippling contractures, third-degree burns should be grafted to preserve function. Often, the depth of thirddegree thermal injuries is difficult to ascertain. Moreover, inappropriate therapy may convert a partial (second-degree) skin injury to a full-thickness (third-degree) injury.

Risk Assessment and Implications The amount of heat delivered to tissue depends on the temperature, duration of exposure, and susceptibility of the tissue to thermal injury. Thus, similar intensity and duration of heat produce different burn depths at different skin locations. For example, relatively high blood flow to the face tends to disperse heat, rendering facial skin relatively resistant to deep thermal injury. Skin on the surface of the back is relatively thick, so it too is relatively resistant to thermal injury. However, where the skin is thin and the blood flow is low (e.g., in the extremities), exposure to a 77°C heat source for as little as 1 to 2 seconds can produce a full-thickness burn injury. Pathophysiologic changes brought about by evolving thermal injury are categorized as early, intermediate, or late. In the early postburn period, localized inflammation increases capillary permeability and edema formation. The consequent loss of effective circulating volume is the most salient feature of the early clinical course. This loss reduces preload, so that cardiac output falls and end-organ perfusion is compromised. Also, hypothermia is common owing to the loss of skin thermoregulatory control and aggressive fluid resuscitation. In addition, inhalation of toxins such as carbon monoxide or cyanide may cause metabolic injury. Inhaled irritants may also cause laryngeal or glottal edema. Intermediate and late postburn changes include a persistent inflammatory state, immunosuppression, severe protein catabolism, and increased susceptibility to infection. Neutrophil and lymphocyte function may be impaired for several weeks after thermal injury. Finally, owing to the prolonged hospitalization required for major burns, serious complications, including ventilator-associated pneumonia, deep venous thrombosis, and multiorgan system dysfunction, may occur (see Chapters 51, 89, and 119). Early complications of thermal injury are related to the injury itself and to the aggressive resuscitation patients

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Table 121–1

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Complications in Burn Patients

Coexisting traumatic injury Inhalation injury Carbon monoxide poisoning Hypovolemia Compartment syndrome

Table 121–2

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Thermally Injured Patients

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extensive tissue necrosis, rhabdomyolysis, and secondary renal injury. During the second 24 hours after hospitalization, fluid losses decrease somewhat but may still be elevated due to weeping, open wounds. The increased capillary leak usually abates during this period, and edema formation is much less significant. Patients remain hypermetabolic and require dose adjustments for most drugs, including antibiotics, sedatives, neuromuscular blockers, and opioids. Protein catabolism continues until wound closure occurs. With significant direct exposure to smoke, acute respiratory distress syndrome (ARDS) may develop. This syndrome usually occurs 48 to 72 hours after admission. Therapy includes limiting tidal volumes, permissive hypercapnia, high inspired oxygen concentrations, and the use of positive end-expiratory pressure (PEEP). Unlike ARDS caused by sepsis, however, mucosal sloughing due to smoke exposure can require extensive suctioning and significantly increases the risk for occlusion of the endotracheal tube. Such sloughing can be particularly important in patients initially intubated in the field with smaller-diameter endotracheal tubes. Burn wound infection is the most common cause of death in patients with major (>60%) burns, and patients remain at high risk until wound closure. Burn wound sepsis can have an extremely rapid onset and an unusually severe course. Infected burn wounds require immediate debridement to maximize the chances for survival.

MANAGEMENT AND PREVENTION Severely burned patients may require rapid application of the basic ABCs (airway, breathing, circulation) during initial

Classification of Smoke Inhalation

Mechanism of Injury

Clinical Symptoms and Effects

Heat injury to glottis and upper larynx

Soot on face or in mouth and nose Redness or blistering of mouth, nose, or hard palate Difficulty phonating or swallowing Resuscitation edema may cause airway to swell dramatically Prophylactic tracheal intubation should be strongly considered if thermal injury to glottis is suspected Tachypnea, tachycardia, headache, dyspnea May progress to frank seizure, hypotension, malignant arrhythmias Cyanide poisoning acts synergistically with carbon monoxide to cause vital organ injury Although carbon monoxide can be readily detected on blood gas analysis, there is no rapid assay for cyanide; empirical therapy with sodium thiosulfate should be started if suspicion is high Toxicity of smoke depends on its temperature and the nature of burning materials and cannot be easily predicted There is no ready test for this component of inhalation thermal injury Unusually high fluid resuscitation volumes strongly suggest pulmonary involvement Symptoms usually manifest within 48 hr after thermal injury, including: Tachypnea Sputum production Fever Leukocytosis Hypoxemia Atelectasis Tracheal intubation to maintain oxygenation is often required; recovery occurs over a period of 2-3 wk

Ingested toxins (cyanide and carbon monoxide)

Irritant damage from contact with chemicals contained in smoke

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

require to survive extensive burn injuries (Table 121-1). Patients burned in an indoor environment or closed space are at risk for inhalation injury. Smoke inhalation can manifest as laryngeal or glottal swelling, metabolic poisoning caused by carbon monoxide or cyanide, or sloughing of lung mucosa due to direct toxin exposure (Table 121-2). Patients at risk for such complications commonly have a supportive history, such as soot on their faces or in the nares or oropharnyx or blistering of the mouth and hard palate. Carbon monoxide poisoning commonly manifests as neurologic symptoms (ranging from agitation and confusion to frank seizures) and cardiovascular symptoms (including malignant arrhythmias and hypotension). Hypovolemia is due to fluid translocation caused by capillary leak and possibly blood loss if there is associated trauma. Electrolyte abnormalities due to thermal injury and resuscitation include hyponatremia, acidosis, and hypocalcemia. The aggressive fluid administration required may cause pulmonary and peripheral edema. Increased intra-abdominal pressure may also result from edema formation and may reduce urine output or compromise ventilation. Finally, compartment syndromes are common in patients with circumferential burns. If unrecognized, these may be associated with

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resuscitation, followed by other indicated management and preventive measures. There are two indications for emergent surgery: 1. Burn wound sepsis. This condition is diagnosed by positive quantitative wound cultures and signs of systemic sepsis. Although wound infection without systemic sepsis can be treated topically, severe wound sepsis with associated systemic changes often requires aggressive operative debridement to maximize survival. 2. Peripheral edema. Increased extremity compartment pressures, circumferential chest burns, or increased intraabdominal pressures (bladder pressure >25 mm Hg) require emergent surgical intervention to reduce compression injury. Because of large protein losses with thermal injury, patients with severe burns are often fed aggressively via an enteral route. Therefore, preoperative NPO orders should strive to minimize periods when patients are not being fed.

Fluid Requirements Fluid requirements for burn-injured patients are difficult to estimate, even for experienced practitioners. Underresuscitation may worsen injury, increase circulatory instability, and lead to end-organ dysfunction. Conversely, overresuscitation worsens edema and may increase the risk of abdominal compartment syndrome. Fluid replacement guidelines for the first 24 hours are provided in Table 121-3. These guidelines represent only starting fluid infusion rates. Because of the risk of edema formation, infusion rates should be titrated to the minimum amount needed to keep urine output at 0.5 mL/kg per hour. The “rule of nines” is used to estimate burn surface area (Table 121-4).

Intraoperative Care The intraoperative care of burn-injured patients undergoing debridement or grafting procedures can be extremely challenging. Wounds are typically debrided down to briskly bleeding tissue, with partial hemostasis achieved using topical phenylephrine. Because of the large wound surface and topical vasopressor use, blood loss may be difficult to assess.

Table 121–3 ■ Burn Life Support Guidelines for Initial Volume Resuscitation (First 24 Hours) Adults: 2-4 mL × body weight (kg) × burn area (%) Children: 3-4 mL × body weight (kg) × burn area (%) First half of volume to be infused over the first 8 hr, with remainder over next 16 hr Example: A 70-kg man with 50% BSA partial- and full-thickness burns: 2-4 mL × (70) × (50) = 7000-14,000 mL of lactated Ringer’s solution in the first 24 hr, with 3500-7000 mL given in the first 8 hr. Note that these are initial estimates only and that fluid therapy should be titrated to no more than 0.5 mL/kg/hr of urine output to minimize edema-related complications. BSA, body surface area. Adapted from Sheridan RL, et al: ABLS Provider’s Manual. Chicago, American Burn Association, 2001.

Table 121–4

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Rule of Nines for Calculating Percentage of Body Surface Area Burned Body Surface Area

Body Part Arm Head and neck Leg Anterior trunk Posterior trunk

Adult 9 9 (and 1) 18 18 18

Child 9 18 14 18 18

Although tourniquets can be used on the extremities to reduce blood loss, they cannot be used for debridement involving the head, face, neck, chest, or back. Further, due to the greater vascularity of the head and face, blood loss can be especially severe during debridement of these areas. Careful attention to intravascular volume status and avoidance of the adverse consequences of overly aggressive fluid administration (acidosis, hypothermia, coagulopathy, pulmonary edema) are the cornerstones of intraoperative care. Preplanning, adequate intravenous (IV) access, and ongoing communication among members of the burn care team are essential to avoid hypovolemia in the perioperative period. Because of the risk of infection, burn patients usually have only the minimum necessary IV access on arrival to the operating room. Establishment of large-bore IV access is mandatory for debridement involving the head or if it is likely to be extensive. Alternating debridement with grafting can spread the requirement for transfusions over a longer time, allowing the anesthesia team greater opportunity to maintain adequate fluid balance. Surgical debridement should stop if the patient develops a coagulopathy, refractory hypotension, hypothermia (temperature <35°C), or acidosis (pH <7.2).

Hypothermia Thermally injured patients may become severely hypothermic during burn debridement and grafting. This complication is a consequence of evaporative loss from wet bandages, a cool operating room environment, and dysfunctional thermoregulatory mechanisms. Severe intraoperative hypothermia can cause arrhythmias and worsen existing coagulopathies. Warming the operating room (>30°C) and the use of heat lamps; IV fluid warmers; heated, humidified inspired gases; and low fresh gas flows are helpful for maintaining normothermia. Bear in mind that for patients swathed in wet bandages, forced air warming can worsen hypothermia by increasing evaporative losses. In patients with large wounds and wet bandages, heat lamps may be more effective. If the patient’s temperature falls to 35.5°C, any remaining grafts should be placed quickly, hemostasis achieved, wounds dressed with occlusive dressings, and the procedure terminated.

Oxygenation and Ventilation Thermal injury can significantly alter ventilation, even in patients without smoke inhalation. As discussed earlier,

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patients with inhalation injury may require early intubation for glottal swelling, extensive suctioning to maintain endotracheal tube patency with mucosal sloughing, and antidotes to counter cyanide and carbon monoxide poisoning. Because few laboratories offer in-house cyanide assays, the diagnosis of cyanide poisoning often must be made empirically. In patients without inhalation injury, the consequences of aggressive fluid resuscitation and increased capillary leak can affect respiration. Circumferential burns involving the chest wall can dramatically reduce chest wall compliance. Increased intra-abdominal pressure due to edema formation can have similar effects. Pulmonary edema is common and requires a high fraction of inspired oxygen and PEEP for adequate oxygenation. Minute ventilation requirements may also be higher in burn patients because of increased carbon dioxide production with an ongoing hypermetabolic state. The increased minute ventilation, high levels of PEEP, and elevated peak inflation pressures required for some patients may be beyond the capability of the ventilators on some anesthesia machines. Therefore, intensive care unit (ICU) ventilators are often needed for patients with inhalation injuries and ARDS. Also, it may be difficult or impossible to adequately ventilate these patients with manual transport devices. If the ability to maintain stable blood gases during transport is questionable, a brief period of manual ventilation at the bedside in the ICU may allow clinicians to identify and treat potential problems there, rather than during transport.

Vascular and Monitoring Access

Positioning Intraoperative positioning should facilitate surgical exposure for both the donor and recipient sites. In general, to avoid harvesting unused skin, the recipient site is debrided first to verify the existence of an adequate wound bed.

Thermally Injured Patients

507

Because shear injury can be a primary cause of failed graft adherence, attention should be paid to previously grafted areas so that shearing injuries do not occur during positioning. Many thermally injured patients develop severe contractures in spite of aggressive physical therapy and must be positioned carefully to avoid related complications.

Securing Access It is often difficult to secure endotracheal tubes and vascular access or monitoring lines in burn patients. Tape rarely adheres to burned areas and may come loose from normal skin in these patients. Essential tubes, catheters, and access lines should be sutured. Endotracheal tubes may be wired to gums and teeth or secured with twill tape around the neck and tube. Nonessential lines are removed as soon as possible to avoid the risk of infection and accidental line removal.

Pharmacology Owing to the hypermetabolic state, the redistribution of many drugs occurs more rapidly in thermally injured patients than in normal individuals. Hepatic and renal elimination may be enhanced. Burn patients often become tolerant to the effects of benzodiazepines and opiates and may require extraordinarily high doses. The duration of neuromuscular blockade with nondepolarizing drugs may be considerably reduced. Succinylcholine is contraindicated because it may cause exaggerated potassium release and life-threatening ventricular arrhythmias. This response occurs within 24 hours of injury and may persist for up to 1 year after the patient recovers from the injury.

Further Reading Benson A, Dickson WA, Boyce DE: Burns. BMJ 332:649-652, 2006. Demling RH: Smoke inhalation injury. New Horiz 1:422-434, 1993. Herndon DN: Total Burn Care. Philadelphia, WB Saunders, 1996. Sheridan RL, et al: ABLS Provider’s Manual. Chicago, American Burn Association, 2001. Sheridan RL, Schulz JT, Ryan CM, et al: A 35-year-old woman with extensive, deep burns from a nightclub fire. N Engl J Med 350:810-821, 2004. Tung A: Management of burns. In Hall J, Schmidt G, Wood L (eds): Principles of Critical Care Companion Handbook. New York, McGraw-Hill/Appleton & Lange, 1998, pp 801-822. Young CJ, Moss J: Smoke inhalation: Diagnosis and treatment. J Clin Anesth 5:377-386, 1989. Yowler CJ: Recent advances in burn care. Curr Opin Anaesth 14:251-255, 2001.

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Vascular and monitoring access may be difficult, because there may be little unburned skin available after grafting. Further, access is frequently minimized to reduce the risk of infection. Access for invasive monitoring and IV cannulas should be decided in conjunction with the surgical team and after a review of the surgical site, the degree of coagulopathy, and the nature of the planned procedure. Debridement and grafting for patients with large burns are often staged.

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Jeffrey S. Kelly Case Synopsis A 25-year-old man involved in a motor vehicle accident presents acutely for repair of bilateral open tibial fractures. Loss of consciousness was reported at the scene, but cranial computed tomography findings are negative. The patient’s Glasgow coma scale score is currently 15. He is normotensive, and a thorough evaluation (including a negative cervical spine series) has ruled out other significant injuries. He admits to ingestion of alcohol and amphetamines just before the accident. Other findings are as follows: blood pressure, 110/50 mm Hg; pulse, 124 beats per minute; breaths, 24 per minute; and temperature, 37.1°C. Significant laboratory findings include hematocrit, 24; pH, 7.27; a base deficit of –10 mEq/L; and blood alcohol content, 279 mg/dL.

PROBLEM ANALYSIS Definition and Recognition Exposure to toxic substances occurs commonly, as evidenced by the 2.4 million calls received by poison control centers in 2002. Such calls typically involved an acute (92%), unintentional (85%), oral (76%) exposure to a single toxin (92%) by a child (58%) at a private residence (92%). Although almost 75% of such cases were managed outside the health care system, there were almost 528,000 physician visits, more than 156,000 hospital admissions, major morbidity in 15,000 patients, and 1153 deaths. Drug classes associated with the largest number of deaths, in descending order of frequency, were analgesics, sedatives, hypnotics, antipsychotics, antidepressants, stimulants, street drugs, cardiovascular drugs, and the alcohols. However, poison control center data appear to significantly underestimate the true incidence of adverse outcomes from poisoning. This is due in part to the heavy weighting toward pediatric exposures, which uniformly have favorable outcomes.

Risk Assessment Most poisoning ingestions tend to follow one of two general patterns. Children usually take small quantities of a single toxin unintentionally; they seldom manifest significant morbidity (6.4%) or mortality (2.5%). In contrast, adolescents and adults ingest larger amounts of multiple toxins intentionally and suffer the vast majority of morbidity and mortality. Large series of mixed adult overdoses suggest that the co-ingestion of ethanol occurs in approximately 50% of cases, and alcohol significantly confounds the initial clinical assessment in a similar percentage of trauma patients. Ethanol-related motor vehicle accidents during 2002 caused more than 17,400 deaths, with an associated cost of $15.7 billion. Fifty-six percent of the affected drivers in these fatal accidents demonstrated a blood alcohol content greater than 0.16% (twice the legal limit in most states). 508

One should therefore assume that adolescent and adult trauma victims have acute ethanol intoxication until proved otherwise. The clinician should also have a high index of suspicion for the ingestion of other recreational drugs in this patient population and should evaluate the patient for evidence of substance abuse during the initial history and physical examination. Important historical data include the specific toxin or toxins, quantity taken, ingestion time, signs and symptoms since ingestion, past medical and psychiatric history (including suicidal intent), current medications, allergies, and trauma (accidental, incidental, or self-inflicted). Because the history can be unreliable or incomplete in acute poisoning, supplemental data from other sources (e.g., public safety personnel, family, medical records, area pharmacies, local poison control centers) may be helpful in diagnosing toxic exposures. A rapid, systematic, and thorough physical examination is mandatory, given the vague history that often surrounds poisoning scenarios. Barrier precautions should be exercised where appropriate to prevent self-intoxication (such as cutaneous exposure to organophosphate insecticides). The assessment should initially focus on the ABCs (airway, breathing, and circulation), with aggressive intervention to stabilize any abnormalities discovered. Further assessment includes the following: ●

●

●

●

Gag reflex. This has implications for airway protection, aspiration prophylaxis, and selective early institution of gastric emptying maneuvers (see “Management”). Core temperature disturbances. These may reflect toxic (salicylates, stimulants) rather than environmental or infectious causes. Central nervous system dysfunction. Detection of central nervous system dysfunction should stimulate the active consideration of early pharmacologic therapy or radiographic imaging for possible intracranial abnormalities, cervical spine injury, or both. Incidental trauma and stigmata of substance abuse. The patient should be examined for puncture wounds, needle tracks, and nasal septal perforation.

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Constellation of signs and symptoms (“toxidromes”). The ingestion of certain toxins may present as characteristic toxidromes that typically involve abnormal vital signs, altered mental status, pupillary changes, and a variety of miscellaneous effects that can be attributed to the pharmacologic properties of the offending agent. Examples are provided in Table 122-1.

Laboratory evaluation is typically not helpful for diagnosing toxic exposure, other than to support the initial clinical diagnosis. Concomitant trauma and poisoning may confound the accurate assessment of each individual entity, as exemplified by the case synopsis. Normal blood pressure and pulse pressure in the presence of anemia, tachycardia, and metabolic acidosis likely reflect hypovolemic shock that is partially masked by amphetamine-associated vasoconstriction.

MANAGEMENT The vast majority of acutely poisoned patients have satisfactory outcomes when given appropriate supportive care, with an emphasis on aggressive, early intervention to stabilize vital organ function. Initial efforts should focus on maintaining a stable, patent airway; establishing adequate ventilation and oxygenation; and stabilizing cardiovascular function, just as one would do for other medical emergencies. All patients with depressed mental status or seizures should receive oxygen, 2 mg of intravenous naloxone, and 25 g of IV dextrose if the finger-stick blood glucose level is low. Ideally, intravenous or intramuscular thiamine 100 mg should precede

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Complications from Toxic Ingestion

509

dextrose administration to prevent or treat Wernicke’s encephalopathy. Tonic-clonic seizures that are refractory to initial therapy are treated with titrated doses of a benzodiazepine, barbiturate, phenytoin, or a combination of these. Given the high incidence of ethanol abuse in both poisoning and trauma patients, empirical alcohol withdrawal therapy should be considered. Definitive poisoning management usually includes early use of specific antidotes (where appropriate); selective early (within 1 hour of ingestion) use of gastric emptying (preferably orogastric lavage; more rarely, ipecacinduced emesis); routine administration of activated charcoal, where effective; and perhaps a single dose of an osmotic cathartic (Tables 122-2 to 122-7). Hemodialysis is rarely used and is usually reserved for patients who, despite maximal supportive care, remain unstable from dialyzable toxins. Whole bowel irrigation with large quantities of isosmotic polyethylene glycol solutions may be considered in stable patients who have ingested specific toxins for which charcoal is ineffective and delayed sequelae are possible (Table 122-8). The signs and symptoms of amphetamine use in the patient described in the case synopsis were obscured by the concomitant effects of central nervous system depressants (i.e., ethanol), hypovolemic shock from long bone fractures, and environmental exposure to low ambient temperatures. Classic physical findings of amphetamine toxicity are consistent with a diffuse hyperadrenergic state and include hypertension, tachycardia, hyperthermia, diaphoresis, mydriasis, and hyperactivity. Psychiatric symptoms include agitation, paranoid ideation, and hallucinations in the presence of a clear sensorium. Specific therapy is directed toward “pharmacologic cooling” with benzodiazepines (e.g., diazepam 10 mg

Common Toxidromes

Syndrome

Common Clinical Signs

Potential Toxic Agents

Anticholinergic

Tachycardia, fever, dry skin, urinary retention, ileus, mydriasis, delirium, seizures

Cholinergic

Bradycardia, diaphoresis, urinary or fecal incontinence, emesis, miosis, central nervous system depression, weakness, fasciculations, wheezing Tachycardia (bradycardia with pure α-agonist), hypertension, mydriasis, diaphoresis, piloerection, fever, delusions, paranoid ideation, restlessness, agitation

Antihistamines, phenothiazines, tricyclic antidepressants, antipsychotics, atropine, scopolamine, jimsonweed, amantadine, antiparkinson drugs, Amanita mushrooms, baclofen Organophosphate and carbamate insecticides, physostigmine, pyridostigmine, edrophonium, certain mushrooms

Sympathomimetic (stimulants)

Narcotic Sedative-hypnotic Serotonin Hallucinogenic Extrapyramidal

Mental status depression, hypoventilation, miosis, ileus, hypotension, bradycardia Confusion, slurred speech, mental status depression, respiratory depression, ataxia, hypothermia Fever, diaphoresis, flushing, diarrhea, hyperreflexia, tremor, myoclonus, trismus Hallucinations, psychosis, paranoid ideation, panic, fever, mydriasis Tremor, rigidity, opisthotonos, torticollis, choreoathetoid movements, trismus, hyperreflexia

Cocaine, amphetamines, over-the-counter decongestants (pseudoephedrine, phenylpropanolamine, phenylephrine)

Opioids Benzodiazepines, barbiturates, ethanol, antipsychotics, anticonvulsants Selective serotonin reuptake inhibitors, trazodone, clomipramine. Cocaine, amphetamines, cannabinoids, phenylcyclohexyl (PCP), lysergic acid diethylamide (LSD) Butyrophenones, phenothiazines, risperidone, olanzapine

Adapted from Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York, McGraw-Hill, 2002; and Mokhlesi B, Leiken JB, Murray P, et al: Adult toxicology in critical care. Part 1. General approach to the intoxicated patient. Chest 123:577-592, 2003.

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Table 122–1

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Selected Poisoning Antidotes

Toxin

Antidote

Opiates Benzodiazepines Anticholinergics Cholinesterase inhibitors

Naloxone Flumazenil Physostigmine Atropine, pralidoxime (for insecticides) Calcium chloride Glucagon Digoxin-specific antibody N-acetylcysteine Fomepizole, ethanol, folate Fomepizole, ethanol, pyridoxine Pyridoxine Amyl nitrate, sodium nitrite, sodium thiosulfite, hydroxycobalamin Methylene blue Deferoxamine

Calcium channel blockers β-Blockers Digoxin Acetaminophen Methanol Ethylene glycol Isoniazid Cyanide Methemoglobin Iron

Adapted from Mokhlesi B, Leiken JB, Murray P, et al: Adult toxicology in critical care. Part 1. General approach to the intoxicated patient. Chest 123:577-592, 2003; and Trujillo MH, Guerrero J, Fragachan C, et al: Pharmacologic antidotes in critical care medicine: A practical guide for drug administration. Crit Care Med 26:377-391, 1998.

intravenously as needed and aggressively titrated until the patient is calm). Goals of treatment are to (1) decrease motor agitation and treat tonic-clonic seizures, (2) provide active physical cooling maneuvers to treat significant hyperthermia, (3) initiate intravenous hydration with isotonic crystalloid to induce diuresis (1 to 2 mL/kg per hour) for hyperthermia-mediated rhabdomyolysis, and (4) control

Table 122–3

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Factors that Cumulatively Increase the Appropriateness of Gastric Emptying

Substantial risk of consequential toxicity (e.g., ingestion of aspirin, chloroquine, colchicines, cyclic antidepressants, calcium channel blockers) Evidence of consequential toxicity (e.g., repeated seizures, apnea, hypotension, cardiac arrhythmias, acid-base or other metabolic disturbances) Antidotal and adjunctive therapy ineffective or nonexistent (e.g., colchicine, paraquat) Recent ingestion (<1-2 hr) Ingestion exceeds adsorptive capacity of initial activated charcoal dosing (e.g., >100 mg/kg of pills such as aspirin, sustained-release verapamil, or sustained-release theophylline) Ingested agent not adsorbed by activated charcoal (e.g., iron, lithium) Ingested agent likely to form durable mass after overdose (e.g., large amounts of aspirin, enteric-coated agents, iron, meprobamate) Ingestion of extended or sustained-release formulations (e.g., calcium channel blockers, theophylline) No antecedent vomiting Gastric tube placement required for activated charcoal administration No contraindications to gastric emptying Adapted from Smilkstein MJ: Techniques used to prevent absorption of toxic compounds. In Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York, McGraw-Hill, 2002, p 46.

Table 122–4

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Poisoning Treatment: Emesis with Syrup of Ipecac

Indications Early treatment for potentially toxic ingestion—particularly for children at home, when there are no contraindications (see below)

Dose Adults: 30 mL (2 tbsp) Children: 6-12 mo: 5-10 mL (2 tsp) 1-12 yr: 15 mL (1 tbsp) Older than 12 yr: 30 mL (2 tbsp) For both adults and children: One additional dose may be given if the patient has not vomited within 30 min

Contraindications Caustic ingestion Sharp materials Easily aspirated substance (e.g., pure petroleum distillate) with little systemic toxicity in amount ingested Comatose patients Seizing patients Patients expected to deteriorate rapidly Patients with compromised gag reflex Patients with hemorrhagic diathesis, esophageal and gastric varices, thrombocytopenia Children younger than 6 mo Significant prior vomiting, or when vomiting will delay timeliness of oral antidote or activated charcoal administration Nontoxic ingestion

Adverse Effects Intractable vomiting Mallory-Weiss tears Gastric rupture Pneumothorax or pneumomediastinum Aspiration Delayed emesis after patient loses consciousness Diarrhea (with chronic use) Electrolyte abnormalities (with chronic use or abuse) Cardiac and neurologic manifestations (with chronic use or abuse) Adapted from Flomenbaum NE, et al: Managing the symptomatic patient with a possible toxic exposure. In Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York, McGraw-Hill, 2002, pp 460-462.

severe hypertension that is unresponsive to benzodiazepine sedation by using α-adrenergic blocking agents, nicardipine, or nitroprusside. The last should be done with caution, because long-term amphetamine abuse contributes to relative intravascular volume depletion in a manner similar to chronic hypertension. As with pheochromocytoma, the use of β-blockers leads to unopposed α-adrenergic stimulation and possible exacerbation of hypertension. Hyponatremia resulting from certain amphetamine congeners should be treated initially with isotonic or 3% saline, depending on its magnitude. Because the patient described in the case synopsis required surgical intervention 4 hours after ingestion, and because he lacked significant amphetamine-related symptoms, definitive antipoisoning therapy consisted of a single dose of activated charcoal early in the perioperative period and close observation in a monitored bed in an adequately staffed area. Scheduled oral and as-needed “rescue” intravenous benzodiazepines were ordered perioperatively in

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Poisoning Treatment: Gastric Lavage

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Table 122–6

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Poisoning Treatment: Activated Charcoal

Indications

Indications

Life-threatening exposures when toxin is expected to be accessible in the stomach and evacuation is expected to contribute to improved outcome

Single dose: Ingestions of drugs or toxins that bind to activated charcoal, when no contraindications exist and an improved outcome is expected Multiple doses: Ingestions of drugs or toxins that bind to activated charcoal when (1) a prolonged absorption phase is expected, (2) potential toxicity is great, and (3) gastrointestinal dialysis is expected to be beneficial; drugs with a small volume of distribution (<1 L/kg), low endogenous clearance, low plasma protein binding, biliary or gastric secretion of drug, or active metabolites that recirculate are most amenable to gastrointestinal dialysis

Tube Type and Size Adults and adolescents: 36-40 French Children: 22-28 French

Procedure If there is potential airway compromise, orotracheal or nasotracheal intubation should precede orogastric lavage; vomiting commonly follows lavage Place the patient in the left lateral decubitus position Before insertion, measure and mark the proper length of tubing to be passed; after the tube is introduced, confirm that the distal end of the tube is in the stomach Withdraw any material present, and consider instillation of activated charcoal Via a funnel (or lavage syringe), instill aliquots of a saline lavage solution, as follows: Adults: 250-mL aliquots Children: 10-15 mL/kg aliquots, not to exceed 250 mL Continue lavage for at least several liters in an adult and 500 mL to 1 L in a child, or until no particulate matter returns and the effluent lavage solution is clear Following lavage, use the same tube to instill activated charcoal and a cathartic, if indicated

Contraindications

Adverse Effects Inadvertent tracheal intubation or airway trauma Aspiration pneumonitis Emesis Gastrointestinal hemorrhage or perforation Adapted from Flomenbaum NE, et al: Managing the symptomatic patient with a possible toxic exposure. In Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York, McGraw-Hill, 2002, pp 460-462.

light of the patient’s significant blood alcohol content on admission.

PREVENTION It would be unethical to conduct prospective, controlled trials to assess complications arising from toxic ingestion. Epidemiologic studies, retrospective data, and case reports provide sufficient insight into the consequences of specific toxic ingestions. Thus, prevention of toxic sequelae requires a thorough and systematic clinical assessment, as well as familiarity with the specific pharmacology, pharmacodynamics, and pharmacokinetics of the ingested agents.

Adults and children: 1 g/kg body weight or 10:1 ratio of activated charcoal to drug, whichever is greater Following massive ingestions: 2 g/kg may be indicated if such a large dose can be easily administered and tolerated

Repeated Doses* Adults and children: 0.25-0.5 g/kg body weight every 1-6 hr, in accordance with the dose and dosage form of drug ingested (larger doses and shorter dosing intervals may occasionally be indicated)

Procedure Add 8 parts water to the selected amount of powdered form; all formulations, including prepacked slurries, should be shaken well for at least 1 min to form a transiently stable suspension before drinking or instillation via orogastric or nasogastric tube Activated charcoal can be administered with a cathartic for the first dose only If the patient vomits the dose of activated charcoal, it should be repeated; smaller, more frequent doses or continuous nasogastric administration may be better tolerated, or an antiemetic may be needed If a nasogastric or orogastric tube is used for multiple-dose administration, allow time for the last dose to pass through the stomach before suctioning the remaining activated charcoal and removing the tube; this may prevent aspiration of activated charcoal

Contraindications Patient at risk for aspiration who has an unprotected airway Caustic ingestion (activated charcoal is ineffective as an adsorbent in these cases and may accumulate in burned areas, interfering with endoscopy) Ileus (a contraindication for multiple dosing)

Adverse Effects Aspiration pneumonitis Emesis Obscuring of gastrointestinal mucosa (for endoscopy) Constipation *Can be given orally or via an orogastric or nasogastric tube. Adapted from Flomenbaum NE, et al: Managing the symptomatic patient with a possible toxic exposure. In Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York, McGraw-Hill, 2002, pp 460-462.

PHYSIOLOGIC IMBALANCE & COEXISTING DISEASE

Caustic ingestion Sharp materials Drug-packet ingestion Significant hemorrhagic diathesis, esophageal and gastric varices, thrombocytopenia (relative contraindication) Prior significant emesis Nontoxic ingestion

Dose* Initial Dose (Single or Multiple)

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Poisoning Treatment: Cathartics

Table 122–8

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Poisoning Treatment: Whole Bowel Irrigation

Indications Drugs or toxins that remain in the gastrointestinal tract and may continue to be absorbed (or desorbed from activated charcoal) if not rapidly eliminated Cathartics should be used only with the first dose of activated charcoal and not repeated Cathartics should not be used routinely and may cause serious fluid and electrolyte disturbances in children

Types and Doses Magnesium citrate (adults and children): 4 mL/kg, to a maximum of 300 mL Magnesium sulfate (adults and children): 250 mg/kg, to a maximum of 30 g/day Sorbitol Adults: 1-2 mL/kg of 70% solution (orally) Children: 4 mL/kg of 25%-30% solution (rectally)

Precautions Cathartics are not warranted for routine management in patients with trivial ingestions Cathartics should not be used more than once for any ingestion— beware of packaging and labeling of activated charcoal and cathartic (sorbitol) combinations that appear similar to activated charcoal alone Sorbitol should not be routinely administered to children; if used at all, strict attention to fluid and electrolyte status is mandatory Phospho-Soda preparations should not be used in children or adults Oil-based cathartics should not be used because of the risk of aspiration and enhanced toxin absorption

Contraindications Abdominal trauma Intestinal obstruction Adynamic ileus Renal failure (a contraindication for magnesium citrate and magnesium sulfate cathartics) Diarrhea

Adverse Effects Volume depletion Emesis Electrolyte imbalance (hypermagnesemia, hypokalemia, hypernatremia) Diarrhea

General Indications Whole bowel irrigation with polyethylene glycol electrolyte lavage solution may be helpful in managing poisonings and overdoses when it is desirable or necessary to (1) rapidly clear the entire gastrointestinal tract without emesis or causing fluid or electrolyte disturbances or (2) prepare the gastrointestinal tract for visualization; it should not be substituted for activated charcoal when the latter is indicated

Specific Indications Intoxication with a sustained-release medication Slowly dissolving substances (e.g., iron tablets, paint chips, bezoars, concretions) Drug packets (e.g., heroin, crack vials, cocaine) swallowed by “body packers” or “body stuffers” Drugs or toxins not adsorbed by activated charcoal (e.g., lithium, iron)

Dose* Adults: 1-2 L/hr for 4-6 hr, or until the rectal effluent is clear Children: 25-40 mL/kg/hr for 4-6 hr, or until the rectal effluent is clear Note: Activated charcoal should be administered before and during whole bowel irrigation if a charcoal-adsorbable drug or toxin is involved; an antiemetic such metoclopramide or a serotonin antagonist may be indicated to achieve compliance

Contraindications Gastrointestinal pathology (e.g., ileus, perforation, obstruction) Caustic ingestion Patients at risk for pulmonary aspiration

Adverse Effects Rectal itching Vomiting (especially with rapid administration) Bloating Decreased efficacy of activated charcoal Desorption of toxin from activated charcoal *Can be given orally or via nasogastric tube. Adapted from Flomenbaum NE, et al: Managing the symptomatic patient with a possible toxic exposure. In Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York, McGraw-Hill, 2002, pp 460-462.

Adapted from Flomenbaum NE, et al: Managing the symptomatic patient with a possible toxic exposure. In Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York, McGraw-Hill, 2002, pp 460-462.

Further Reading Bond GR: The role of activated charcoal and gastric emptying in gastrointestinal decontamination: A state-of-the-art review. Ann Emerg Med 39:273-286, 2002. Chiang WK, Goldfrank LR: Amphetamines. In Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York, McGraw-Hill, 2002, pp 1020-1033. Flomenbaum NE, et al: Managing the symptomatic patient with a possible toxic exposure. In Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York, McGraw-Hill, 2002, pp 460-462. Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York, McGraw-Hill, 2002. Hoppe-Roberts JM, Lloyd LM, Chyka PA: Poisoning mortality in the United States: Comparison of national mortality statistics and poison control center reports. Ann Emerg Med 35:440-448, 2000. Jurkovich GJ, Rivara FD, Gurney JG, et al: Effects of alcohol intoxication on the initial assessment of trauma patients. Ann Emerg Med 21: 704-708, 1992.

Kosten TR, O’Connor PG: Management of drug and alcohol withdrawal. N Engl J Med 348:1786-1795, 2003. Krenzelok EP: New developments in the therapy of intoxications. Toxicol Lett 127:299-305, 2002. Kulig K, Bar-Or D, Cantrill SV, et al: Management of acutely poisoned patients without gastric emptying. Ann Emerg Med 14:562-567, 1985. Mokhlesi B, Leiken JB, Murray P, et al: Adult toxicology in critical care. Part 1. General approach to the intoxicated patient. Chest 123:577-592, 2003. National Highway Traffic Safety Administration (NHTSA): People: Injury prevention: Impaired driving: Program update. Washington, DC, NHTSA. Available at www.nhtsa.dot.gov/people/injury/alcohol/ index.html. Smilkstein MJ: Techniques used to prevent absorption of toxic compounds. In Goldfrank LR, Flomenbaum NE, Lewin NA, et al (eds): Goldfrank’s Toxicologic Emergencies, 7th ed. New York, McGraw-Hill, 2002, p 46. Trujillo MH, Guerrero J, Fragachan C, et al: Pharmacologic antidotes in critical care medicine: A practical guide for drug administration. Crit Care Med 26:377-391, 1998. Watson WA, Litovitz TL, Rodgers GC Jr, et al: 2002 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 21:353-421, 2003.

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Pipeline Source Failure James F. Szocik Case Synopsis It is the first day of operation of the hospital’s new outpatient surgery wing. The anesthesiologist reports to work looking forward to a day of easy cases consisting of healthy American Society of Anesthesiologists class I outpatients. During the first case, however, a tiny chirp is heard, accompanied by an advisory stating that the oxygen (O2) supply is low. Several seconds later, the anesthesiologist notices that the ventilator bellows is not filling, the comforting sound of the cycling ventilator is absent, and a cacophony of alarms is sounding, including apnea pressure and volume alarms and minute volume alarms.

PROBLEM ANALYSIS Definition A pipeline failure can be one of two types: a quantitative problem, with too little or too much pressure; or a qualitative error, indicating that a contaminant is present (Table 123-1). In the extreme case of switched pipelines, the contamination consists of 100% undesired gas. The pipeline is made up of a large number of components (Fig. 123-1), any of which can fail.

Recognition

Risk Assessment All patients receiving gas other than room air are at risk. Most pipeline problems involve the quantitative aspect of pressure (either too high or too low). A case reported in 2004 involving a triply redundant system (i.e., primary, secondary,

Table 123–1

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Pipeline Failure

Quantitative Problems Low pipeline pressure Kinked hose to machine Leak in hose to machine Leak in coupling hose to machine Obstruction in pipeline Valve in hall turned off Leak in pipeline Oxygen supply empty Failure of reserve supply to activate Regulator frozen in closed position High pipeline pressure Regulator frozen in open position Liquid gas in line expanding

Qualitative Problems Contamination in piping Error in indexed safety system, allowing cross-connection Piping crossover Foreign body in pipeline Cleaning solution in pipeline Contamination at source Tank filled with wrong gas Cleaning solution in tank Wrong connection at source

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Quantitative errors in pipeline supply can be detected via a pressure-sensing device. A machine checkout using guidelines recommended by the Food and Drug Administration will detect a lack of pipeline pressure or an excess of pressure. During a procedure, modern anesthesia machines are equipped with a low O2 pressure alarm that sounds to alert the operator that the O2 supply is failing. A nitrous oxide (N2O) pipeline failure does not sound an alarm. Qualitative errors are more difficult to detect. Gross contamination of O2 can be detected by using an O2 sensor, which is calibrated to read 21% in room air, and confirming that the sensor reads greater than 90% with 100% pipeline O2. A properly calibrated O2 sensor will advise if a different gas has been switched into the O2 pipeline. However, no currently available monitor or analyzer can detect the entire spectrum of potential contaminants in a pipeline system (e.g., carbon monoxide, trilene, solvents), especially at low concentrations. One’s olfactory sense may detect some contamination, but this exposes the tester to potentially dangerous contaminants.

and reserve tanks) highlighted the resiliency of such a system. Despite a shutdown of the primary and secondary tanks due to a massive spill of liquid oxygen from a failed connection, the reserve tank was able to supply the demands of multiple operating rooms and intensive care unit beds. In a survey of more than 200 anesthesia departments at academic institutions, 37 of 76 reported mishaps involved low pressure in the O2 pipeline. These can be detected during the standard anesthesia machine checkout. More serious is a crossover in the pipeline supply, which can result in hypoxia. Crossover errors involving the O2 source are detected when verifying that the O2 analyzer reads greater than 90%, using pipeline gas as part of the standard anesthesia machine checkout. Contaminated gases are more insidious. They can occur as part of the manufacturing or refining of gases, from

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Heat exchanger

Primary supply

Machine connection

Anesthesia machine

Figure 123–1 ■ Schematic diagram of a piped-gas delivery system. The primary supply may be liquid, large cylinders, or on-site compression. For the anesthesiologist, detection of pipeline problems occurs at the anesthesia machine (either pressure gauge or oxygen sensor), which is the final common pathway for the large number of components constituting the piped-gas supply.

Oxygen sensor Reserve supply Relief valve Manual valve Pressure regulator Pressure gauge Wall connection

the improper use of cleaning solutions in the pipeline, or from improper welding techniques. Detailed analysis of the gas at the patient end is the only way to detect this kind of failure. Many failures and instances of contamination are associated with construction and modification of the pipeline system. Greater vigilance is needed whenever construction is ongoing in the vicinity of the pipeline.

Implications Pipeline pressure that is too low can result in inadequate delivery of gases to the patient. In the case of N2O, inadequate anesthetic depth and patient awareness may occur. Lack of O2 is far more serious and can result in hypoxia and organ damage. Pipeline pressure that is too high can damage the anesthesia machine, resulting in broken flowmeters, inaccurate readings, or internal rupture of components. If this occurs, the anesthesia machine must be replaced immediately intraoperatively. Qualitative problems with gas delivery can asphyxiate the patient if a non-life-sustaining gas is substituted for O2 or poison the patient if the contaminant is toxic. As reported by Moss and Evans, tricholorethylene contamination was implicated in four deaths in Texas. Hospital workers initially detected the problem when they noticed an odor in the delivered O2. In summary, quantitative errors are easily detected. No patient should be harmed by lack of O2 or N2O. In contrast, except for pipeline crossover, qualitative errors are more insidious. Aside from detailed gas analysis, there is no failproof method to detect contamination of piped gases.

MANAGEMENT One strategy can accommodate all permutations of pipeline failure, including contaminations (Fig. 123-2). In all cases of pipeline failure, O2 and ventilation must be provided to the patient. If the anesthesia machine is functional, O2 and ventilation are most easily provided by changing to the anesthesia machine O2 tank supply and disconnecting from the wall O2 supply. Because the anesthesia machine preferentially draws from the wall (pipeline) O2 source, the pipeline should be disconnected from the anesthesia machine to prevent additional contamination from entering the system. Because most ventilators are driven by pressure from the O2 supply, changing to manual ventilation will conserve O2 in an emergency. However, if the anesthesia machine has been damaged by high pressure, or if both the pipeline supply and the tank supply have failed or are suspected of being contaminated, a self-inflating Ambu bag with room air will keep most patients alive until reserve equipment becomes available. Anesthetic needs can be met by total intravenous anesthesia. Vital time should not be wasted trying to troubleshoot and fix a potentially damaged anesthesia machine. Finally, notice of a failure needs to be communicated quickly to other patient care areas, so that more global failures or contaminations can be dealt with properly. At this point, the hospital’s biomedical engineering department should be asked to determine the nature and origin of the failed component. Analogous to the low-pressure strategy, the source of the failed component (most likely a regulator) can be identified by determining whether the entire system or only a portion of the system is affected.

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Pipeline failure suspected 1. Low pressure 2. High pressure 3. Suspected contaminant

Is anesthesia machine functional? No Go to Ambu bag with either 100% O2 or room air

Arrange for replacement anesthesia machine

Is patient stable? Yes

Continue case (discuss with surgeon)

Is patient stable? No

ACLS protocols

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Open O2 reserve tank Disconnect from pipeline supply Change to manual ventilation

Yes

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Yes Change to IV anesthetic technique Continue case (discuss with surgeon)

Figure 123–2 ■ Simple algorithm for dealing with pipeline failure. ACLS, advanced cardiovascular life support; biomed, hospital biomedical engineering department.

If a contaminant is suspected, the tank supply should be activated, the machine disconnected from the pipeline source, and the biomedical engineers notified to take a sample of the gas for analysis. Construction or maintenance records are helpful to determine when any work was done on the pipeline.

Further Reading Anderson WR, Brock-Utne JG: Oxygen pipeline supply failure: A coping strategy. J Clin Monit 7:39-41, 1991. Dorsch JA, Dorsch SE: Understanding Anesthetic Equipment, 2nd ed. Baltimore, Williams & Wilkins, 1984, pp 1-37. Ehrenwerth J, Eisenkraft JB: Anesthesia Equipment: Principles and Applications. St. Louis, Mosby–Year Book, 1993, pp 3-26. Feeley TW, Hedley-Whyte J: Bulk oxygen and nitrous oxide delivery systems: Design and dangers. Anesthesiology 44:301-305, 1976. Gilmour IJ, McComb RC, Palahniuk RJ: Contamination of a hospital oxygen supply. Anesth Analg 71:302-304, 1990. Moss E, Evans F: Hospital deaths reportedly due to contaminated O2. Anesth Patient Safety Foundation Newslett 11:13-24, 1996. Schumacher SD, Brockwell RC, Andrews JJ, et al: Bulk liquid oxygen supply failure. Anesthesiology 100:186-189, 2004.

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Notify biomed to determine cause of failure Notify other patient care areas

Prevention of pipeline catastrophes has both mechanical and human elements. Pipeline gas supplies are mechanical constructions, and all mechanical constructions have a failure rate. Given enough time, a valve, regulator, or other pipeline component will fail. Automatic systems to activate reserve and secondary supplies, pressure relief valves, and other mechanical safety devices help prevent patient injury. Proper inspection and maintenance carried out by trained personnel will help prevent mechanical failures. Computercontrolled systems, however, can fail catastrophically without warning. If so, the human element becomes most important. Prevention of patient injury involves all the mechanical safeguards mentioned earlier plus a more important human element. Because all mechanical safeguards can fail, it is up to a vigilant anesthetist to detect malfunctions and activate appropriate secondary systems. In the operating room environment, this means that a properly checked-out anesthesia machine must be available for every anesthetic administration.

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Flowmeters Robert G. Loeb Case Synopsis Anesthesia induction has just been completed on a healthy 20-year-old man undergoing inguinal herniorrhaphy. Gas flows are set to 1 L/minute of oxygen (O2) and 2 L/minute of nitrous oxide (N2O). The O2 saturation begins to fall as the O2 analyzer alarms (Fig. 124-1). Actuating the O2 flush valve resolves the problem temporarily.

PROBLEM ANALYSIS Definition Flowmeter malfunction is a rare cause of anesthesia machine failure, because modern anesthesia machines are designed to prevent many flowmeter problems. The last flowmeter incident was reported in 2004. The flowmeter assembly of modern anesthesia machines consists of a single flow control valve and one or two glass flowmeter tubes, connected in series, for each compressed gas. Additionally, new anesthesia machines have a proportioning device that restricts the relative flow rates of O2 and N2O to prevent the administration of hypoxic gas mixtures. Flowmeter tubes comprise a float within a tapered glass tube whose inner diameter is larger at the top than at the bottom. To be accurate, the flowmeter tube must be in a vertical position, and the movement of the float must not be restricted by static electricity or dirt within the tube. Flowmeters are calibrated as a matched tube and float set; replacement of either component can result in significant inaccuracy. Modern anesthesia flowmeters are permanently sealed to prevent mistakes in matching the float and tube during maintenance. Each flowmeter is calibrated for a specific gas, and it is not accurate for measuring the flow of any other gas. To prevent mistakes during anesthesia machine maintenance, modern flowmeters are indexed so that they fit only into the housing for the appropriate gas. To protect flowmeter tubes from breakage, they are housed behind a plastic shield. Patients have died from breathing hypoxic gas mixtures administered from erroneously set flowmeters. Poor flowmeter design was sometimes a contributing factor, because in the past, anesthesia machines were designed with two flowmeter assemblies connected in parallel for each gas (Fig. 124-2). Improved flowmeter design now decreases the chance of user error, and an N2O-to-O2 proportioning system prevents such tragedies from occurring. For example, anesthesia machines manufactured by Dräger are equipped with an O2 proportioning regulator called the Oxygen Ratio Monitor Controller, and those manufactured by GE Healthcare are fitted with a mechanical linkage called the Link-25. Both are generally reliable, but occasional malfunctions of the Link-25 have been reported. Some contemporary anesthesia machines (e.g., Dräger Fabius, Datex-Ohmeda ADU) have electronic flowmeters instead of glass flow tubes. Advantages of electronic flowmeters 518

include improved reliability and reduced maintenance, improved precision and accuracy at low flows, and the ability to automatically record and control gas flows. The electronic sensors operate on the principle of heat transfer, measuring the energy required to maintain the temperature of a heated element in the gas flow pathway. Each sensor is calibrated for a particular gas, because every gas has a different specific heat index. Gas flows are shown on dedicated LED displays or on the main anesthesia machine’s flat-panel display. Displays on the anesthesia machine’s flat panel can be configured as numeric or graphic and can also be configured to show individual flow rates or calculated total flow rate and set O2 concentration. There have been no reported problems with the electronic flowmeters, except for the loss of calibration factors due to RAM battery failure.

Recognition A malfunctioning flowmeter is most easily detected during the anesthesia machine preuse checkout. The Food and Drug Administration (FDA) has developed a checkout procedure (which can be downloaded from http://www.fda.gov/cdrh/ humfac/anesckot.html) that detects most serious anesthesia machine malfunctions. The leak check of the machine’s low-pressure system detects a missing, leaking, cracked, or broken flowmeter. Visual inspection of the flow tubes may reveal a cracked or broken flowmeter. A float that sticks to the tube can be detected by adjusting the flow of all gases through their full range, while checking for smooth operation of the floats. The O2 proportioning device should be tested by attempting to create a hypoxic O2-N2O mixture. It should be noted, however, that it is unlikely that an improperly calibrated flowmeter would be detected by the FDA anesthesia apparatus checkout. During intraoperative use, a malfunctioning flowmeter results in different than expected gas concentrations in the breathing circuit (e.g., higher or lower concentrations of O2 than dialed) or unexpected flow rates from the anesthesia machine to the breathing circuit. The anesthesia practitioner may not notice a problem unless it is dramatic, because there are no direct and independent monitors of anesthesia machine output. There is no monitor of the gas flow emanating from the anesthesia machine, although in extreme cases, the practitioner may notice that the reservoir bag or ventilator bellows is not filling normally. The respiratory gas analyzer at the Y-piece and the O2 analyzer in the breathing circuit are the closest downstream monitors of the gas

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Figure 124–1 ■ The inspired oxygen concentration is dangerously low and is not consistent with the flowmeter settings.

to check the composition of gases flowing from the anesthesia machine.

Risk Assessment Anesthesia machine malfunction is an uncommon cause of critical events. For instance, only 4 of the first 2000 incidents

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Figure 124–2 ■ Flowmeter arrangements. Left, When flowmeters are arranged in parallel, there are two control knobs and two flow tubes for a single gas. A potential hazard is that the user can erroneously turn the wrong knob or read the wrong tube. Middle, The series arrangement is safer, because there is only a single control knob. Right, The safest layout is a single flowmeter for each gas, but a single flowmeter may not be precise enough for low-flow techniques. (From Loeb RG: Preventing anesthesia machine-induced hypoxemia. Welcome Trends Anesthesiol 8:2-10, 1990.)

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concentrations coming from the anesthesia machine. The readings on these monitors, however, rarely match the settings on the anesthesia machine, because of rebreathing. The discrepancy between dialed concentrations and breathing circuit gas concentrations is especially apparent during low gas flows. If a flowmeter problem is suspected, the anesthesia practitioner can sample gas from the fresh gas hose

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reported to the Australian Incident Monitoring Study involved anesthesia machine failures. Two of these incidents, however, resulted from flowmeter problems and were considered potentially life threatening. Regular maintenance of the anesthesia machine is necessary to prevent malfunction due to wear. Ironically, some anesthesia machine failures have been attributed to mistakes made during maintenance. The clinician should therefore be vigilant for equipment problems when using a machine that has recently been serviced. Old anesthesia machines may pose the greatest safety hazard. A survey of anesthesia machines in Iowa found that machines ranged from 1 to 28 years old (average, 8 years). Although older machines did not malfunction more often than newer ones, they often lacked safety features and essential monitoring (e.g., O2-N2O flow ratio alarms, O2 analyzers). Thus, clinicians should be wary of older machines without these features.

Implications Flowmeter malfunction can present as a breathing circuit leak or an inappropriate gas composition within the breathing circuit. Although gas cannot flow retrograde from the breathing circuit to a broken flowmeter, leakage of gas from a broken or missing flowmeter can quickly lead to insufficient gas volume in the breathing circuit. This manifests as an empty breathing bag or ventilator bellows and can lead to a misdiagnosis of the malfunction as a breathing circuit leak or disconnection, because these malfunctions occur more commonly. A large leak from the flowmeter assembly is a serious problem because it prevents effective ventilation of the patient. Flowmeter inaccuracy or a small leak from a cracked O2 flowmeter can cause the anesthesia machine to dispense a hypoxic gas mixture into the breathing circuit. The O2 analyzer in the latter is designed to detect such an occurrence. Other flowmeter problems are not liable to lead to patient injury. Leakage of a gas other than O2 should not result in a hypoxic mixture, because flowmeters are arranged to prevent the preferential loss of O2 in such a situation.

MANAGEMENT An O2 flush should temporarily rectify loss of circuit volume or hypoxia due to a flowmeter problem. The O2 flush bypasses many internal components of the anesthesia machine, including the flowmeter assembly. Also, retrograde leakage of O2 after a flush is prevented on most anesthesia machines by a one-way valve (or a vaporizer that incorporates a oneway valve). When serious flowmeter malfunction is detected intraoperatively, the patient should be ventilated with an alternative system, such as an Ambu bag, while the defective anesthesia

machine is replaced. The defective machine should be removed from service until it has been repaired and thoroughly inspected by a trained technician.

PREVENTION Most flowmeter failures are preexisting. If so, a thorough preuse check of the anesthesia machine should prevent most critical events due to flowmeter malfunction. Many problems, including a missing, leaking, cracked, or broken flowmeter, can be detected with the FDA-recommended anesthesia machine checkout procedure. This procedure is also designed to test the function of the O2-N2O proportioning system. Flowmeter calibration, however, is not verified during this checkout procedure. Although many equipment-related malfunctions are prevented by routine preuse inspection, anesthesia practitioners are not proficient in detecting anesthesia machine faults. For instance, anesthesiologists and certified registered nurse anesthetists detected an average of only 44% of intentionally created anesthesia machine faults at a conference exhibit. Only 15% of participants detected that the O2 flowmeter was miscalibrated to deliver 10% of the indicated flow. Checklists do not necessarily improve performance either. Anesthesiologists detected 26% of anesthesia machine faults when they used their own checkout methods, and 29% of the faults when they used the FDA checkout procedure (1986 version). However, they were not instructed in the use of the FDA checklist, and intensive instruction can improve the performance of apparatus checkout procedures.

Further Reading Buffington CW, Ramanathan S, Turndorf H: Detection of anesthesia machine faults. Anesth Analg 63:79-82, 1984. Chandradeva K: A serious incident with the Blease Frontline Genius anaesthetic machine. Anaesthesia 59:627, 2004. Cooper M, Ali D: Oxygen flowmeter dislocation [letter]. Anaesth Intensive Care 17:109-110, 1989. Eger EI II, Hylton RR, Irwin RH, et al: Anesthetic flow meter sequence— a cause for hypoxia. Anesthesiology 24:396-397, 1963. Hay H: Delivery of an hypoxic gas mixture due to a defective rubber seal of a flowmeter control tube. Eur J Anaesthesiol 17:456-458, 2000. Kumar V, Hintze MS, Jacob AM: A random survey of anesthesia machines and ancillary monitors in 45 hospitals. Anesth Analg 67:644-649, 1988. March MG, Crowley JJ: An evaluation of anesthesiologists’ present checkout methods and the validity of the FDA checklist. Anesthesiology 75: 724-729, 1991. McHale S: A critical incident with the Ohmeda Excel 410 machine [letter]. Anaesthesia 46:150, 1991. Olympio MA, Goldstein MM, Mathes DD: Instructional review improves performance of anesthesia apparatus checkout procedures. Anesth Analg 83:618-622, 1996. Webb RK, Russell WJ, Klepper I, Runciman WB: The Australian Incident Monitoring Study. Equipment failure: An analysis of 2000 incident reports. Anaesth Intensive Care 21:673-677, 1993.

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Proportioning Systems Stewart J. Lustik and Michael P. Eaton Case Synopsis A healthy 45-year-old woman presents for total abdominal hysterectomy to be done under general anesthesia. After dentirogenation with 100% oxygen (O2), anesthesia is induced with thiopental. The patient is paralyzed with succinylcholine and easily intubated. Nitrous oxide (N2O) and isoflurane are added. Desaturation occurs quickly, despite a normal end-tidal carbon dioxide tracing, clear bilateral breath sounds, and normal blood pressure. The O2 analyzer reads 14%. The flowmeters reveal the delivery of 5 L/minute of N2O and 0.8 L/minute of O2.

PROBLEM ANALYSIS Definition

N2O gear

Gear moves this way as N2O decreases (or O2 increases)

Kick-in tab on gear O2 gear

O2 gear

O2 knob and collar

N2O knob

Chain

Stop screw O2 knob on collar and collar O2 valve body

Stop screw Kick-in tab Gear moves this way as N2O increases (or O2 decreases)

Figure 125–1 ■ Ohmeda Link-25 proportioning system. As the nitrous oxide–to–oxygen (N2O-to-O2) ratio increases, the O2 gear moves toward the O2 knob. When the N2O-to-O2 ratio reaches 3:1, the O2 gear interfaces with the O2 knob, and the O2 and N2O knobs become linked. (Courtesy of Ohmeda.)

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A hypoxic mixture was delivered to this patient due to a faulty proportioning system. The proportioning system is one of several safety devices designed to prevent the delivery of hypoxic gas mixtures to the patient. A properly functioning proportioning system does not allow the delivery of a mixture of more than 75% N2O with 25% O2. A Link-25 proportion-limiting control system was used on the previously manufactured Modulus, Modulus II, and Excel series, as well as the current Aestiva anesthesia machines produced by GE Healthcare (previously DatexOhmeda). The delivery of more than a 3:1 ratio of N2O to O2 is prevented by the combination of an interlocking gear mechanism and regulation of the gas inlet pressures. The N2O control valve has a 24-tooth sprocket, which is connected by a chain to the freewheeling 48-tooth sprocket of the O2 control valve (Fig. 125-1). N2O and O2 control valves

may be moved independently to deliver up to 75% N2O; however, when the ratio of N2O to O2 rises to 3:1, the kickin tab on the O2 gear engages with the stop screw on the O2 control knob. Thus, the N2O and O2 control valves become linked. Any further increase in N2O proportionally increases the O2 flow to prevent a more than 3:1 ratio. Similarly, an attempt to decrease the O2 flow would proportionally decrease the N2O flow to maintain a 3:1 ratio When the N2O and O2 control valves are linked, the 2:1 sprocket ratio results in the final 3:1 ratio of gases delivered due to the adjustment of gas inlet pressures. The second-stage N2O regulator reduces the inlet pressure to 38 ± 0.5 pounds per square inch gauge, and the O2 regulator is adjusted to 20.75 ± 3.75 pounds per square inch gauge. The proportioning system of the anesthesia machines manufactured by North American Dräger is called the Oxygen Ratio Controller (ORC) (Fig. 125-2). Supplied O2 and N2O are modulated through respective resistors to exert a backpressure on the upper (O2) and lower (N2O) diaphragms. This backpressure, in conjunction with the

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O2

O2 Diaphragm

Piston N2O Diaphragm

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Figure 125–2 ■ Narkomed Oxygen Ratio Controller. When oxygen (O2) flow is reduced below 25% ± 3%, O2 pressure on the upper rolling diaphragm becomes less than nitrous oxide (N2O) pressure on the lower diaphragm, and the piston moves upward. This allows the spring beneath the ball valve to force the ball valve up, partially occluding the flow of N2O until a new equilibrium is reached. Increasing the O2 flow until it is more than 25% ± 3% pushes the piston and ball valve downward to reduce the obstruction to N2O flow. (Courtesy of North American Dräger.)

differing spring constants of the upper and lower springs, causes movement of a piston attached to the proportioning valve. An increase in N2O flow beyond 72% to 78% moves the piston, which raises the proportioning valve and limits further N2O flow. For example, if the O2 flowmeter is set at 1 L/minute, the ORC will not allow more than 3 L/minute of N2O. If the N2O control knob is turned to increase the flow to more than 3 L/minute, the pressure of N2O on the diaphragm will move the piston to prevent a further increase in N2O flow. Similarly, if the O2 flow is reduced to less than 22% to 28%, the N2O flow will be reduced proportionally to maintain the O2 percentage required. The more recently designed anesthesia machine by GE Healthcare (S/5 ADU) uses an electronic proportioning system. The O2 and N2O flows are electronically measured, and if the N2O flow is too high, a current-driven proportional valve limits N2O flow to allow a minimum of 25% O2. The proportional valve must be checked for calibration every 6 months.

Recognition Diagnosis of a faulty proportioning system requires recognition of the signs of mechanical failure, delivery of a hypoxic mixture, receipt of a hypoxic mixture, or all of these: ●

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Mechanical failure ● Absence of the audible and palpable “clink” of the Link-25 system when the increase in N2O flow results in a mixture of more than 75% N2O. ● Heights of the N O and O 2 2 flowmeter bobbins or bar graphs indicate a ratio of more than 3:1. A stuck flowmeter bobbin may also be the cause. Delivery of a hypoxic mixture ● Low reading of the O analyzer. 2 Receipt of a hypoxic mixture ● Hypoxia enhances adrenergic tone, leading to tachycardia and hypertension. If uncorrected, it will ultimately lead to bradycardia, hypotension, and asystole.

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●

Peripheral hemoglobin oxygen desaturation is indicated by pulse oximetry measurements. The patient appears cyanotic.

Risk Assessment

●

● ●

●

Proportioning systems control only the ratio of O2 and N2O; thus, a hypoxic mixture could be delivered if another gas (e.g., helium) is added to the mixture. It is possible to deliver less than 21% O2 when desflurane is mixed only with air, even with the S/5 ADU, which compensates for desflurane when used with N2O. A gas other than O2 is in the O2 pipeline or cylinder. There is a leak downstream from the proportioning system, including the O2 flowmeter. The ORC (North American Drager) may result in the inadvertent delivery of N2O. If the flow of O2 is reduced while N2O is delivered at a 3:1 ratio, N2O will be reduced proportionally. If it is later desired to increase the O2 concentration, increasing the flow of O2 will cause N2O to rise in a 3:1 ratio until the initial N2O flow is achieved.

Implications The delivery of a hypoxic mixture may result in arterial O2 desaturation, organ ischemia, cardiovascular collapse, and eventually death if not corrected.

Proportioning Systems

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MANAGEMENT If delivery of a hypoxic mixture is due to a malfunctioning proportioning system, the N2O control knob should be shut off. The proportioning system can be bypassed by using the O2 flush valve or a separate O2 tank. The anesthesia machine should be removed from use until a service representative can inspect and replace the proportioning system, if necessary.

PREVENTION The proportioning system should be included in the routine anesthesia machine check before the initiation of anesthesia. The Food and Drug Administration’s anesthesia apparatus checkout guidelines recommend, “Attempt to create hypoxic O2/N2O mixture, and verify correct change in gas flows and/or alarm.” On Ohmeda machines, attempts to increase the N2O flow to more than a 3:1 ratio with O2 should proportionally increase the flow of O2; likewise, attempts to decrease the O2 flow to less than a 1:3 ratio with N2O should proportionally decrease N2O. On the North American Drager and S/5 ADU GE Healthcare anesthesia machines, it should not be possible to increase the N2O-to-O2 flow ratio to more than 3:1, and decreasing O2 below a 1:3 ratio should proportionally decrease the N2O flow. Measurement of the fraction of inspired O2 during anesthesia is required by American Society of Anesthesiologists guidelines. The O2 analyzer must be calibrated before the administration of anesthesia, because this is the most reliable method of detecting the delivery of a hypoxic mixture. A positive-pressure leak test in the North American Drager machine, and a negative-pressure leak test with Ohmeda machines, must be performed preoperatively to detect a leak downstream from the proportioning system that could lead to the delivery of a hypoxic mixture.

Further Reading Abraham ZA, Basagoitia J: A potentially lethal anesthesia machine failure. Anesthesiology 6:589-590, 1987. Anesthesia Apparatus Checkout Recommendations. Rockville, Md, Food and Drug Administration, 1986. Cheng CJ, Garewal D: A failure of the chain-link mechanism on the Ohmeda Excel 210 anesthesia machine. Anesth Analg 92:913-914, 2001. Eisendraft JB: The anesthesia machine. In Ehrenwerth J, Eisenkraft JB: Anesthesia Equipment: Principles and Applications. St. Louis, Mosby– Year Book, 1993, pp 43-45. Gordon PC, James MF, Lapham H, et al: Failure of the proportioning system to prevent hypoxic mixture on a Modulus II Plus anesthesia machine. Anesthesiology 82:598-599, 1995. Modulus II Anesthesia System Operation and Maintenance Manual. Madison, Wis., Ohmeda, the BOC Group, Inc., 1985. Narkomed Service Group: Operating Principles of Narkomed Anesthesia Systems, 2nd ed. Telford, Pa., WE Andrews, 1997. Rice J, Kolek B: Explore the Anesthesia System. Madison, Wis., Ohmeda, 1996, pp 43-44. Richards C: Failure of a nitrous oxide-oxygen proportioning device. Anesthesiology 71:997-998, 1989.

EQUIPMENT & MONITORING

Although delivery of a hypoxic mixture due to a broken proportioning system is rare, there are several potential causes of proportioning system failure. First, defective mechanics in the proportioning system may result in the delivery of a hypoxic mixture. There have been case reports of malfunctions of the Link-25 proportioning system on Ohmeda machines. In one case, a broken chain connecting the sprockets allowed N2O to increase to hypoxic concentrations. The chain on later models was made of stainless steel as opposed to plastic, which increased its tensile strength. In another case, malposition of the O2 control knob on its stud caused failure of the knob to engage, despite delivery of 100% N2O. In addition, loosening the stop screw on the collar of the O2 control knob has led to the delivery of a hypoxic mixture in at least three cases. Although there are no reports to date of failure of the S/5 ADU’s electronic proportioning system, a valve failure could lead to delivery of a hypoxic mixture. Mechanical failure on the North American Drager machine is also rare, although defects in any of the ORC components (e.g., diaphragm, spring, piston, adjusting screw, resistor) could lead to the delivery of a hypoxic mixture. Second, pneumatic components of the Ohmeda machine may fail. If the second-stage O2 or N2O regulators on Ohmeda machines lose calibration, delivery of more than 75% N2O oxide may result. The North American Drager machines do not use second-stage regulators. Third, electronic components of the S/5 ADU proportioning system may fail, although the N2O flow is automatically shut off if the total gas flow to the patient is more than the set flows for N2O plus O2. Fourth, a hypoxic mixture or inadvertent N2O may be delivered to the patient despite a properly functioning proportioning system. This could occur as follows:

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Oxygen Flush Valve Ivar Gunnarsson

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Case Synopsis At the end of a laparotomy on a 45-year-old asthmatic patient, the oxygen (O2) flush valve is pressed to clear the circuit of residual volatile agent. The patient’s lung inflation pressures become elevated, hypotension develops, and the clinical examination suggests a pneumothorax.

PROBLEM ANALYSIS Definition Activating the O2 flush valve (Fig. 126-1) allows delivery of 100% O2 directly to the patient’s breathing system from the pressure-reducing valve at pressures between 20 and 50 pounds per square inch (equivalent to 1000 to 2500 cm H2O) and flows of 35 to 75 L/minute (Fig. 126-2). This is 100-fold greater than the pressure normally required to inflate the lungs. Therefore, it is possible to cause direct lung injury (barotrauma) and increased intrathoracic pressure. The latter can impede venous return and cause hypotension. Possible complications resulting from activating the O2 flush valve and their analysis and causes are listed in Table 126-1. The American Society for Testing and Materials developed standard specifications for the minimum performance and safety of anesthesia machines. The latest standards, published in 1998 (see “Further Reading”), require that anesthesia machines be equipped with a manually operated, single-purpose flush valve for the delivery of a limited but unmetered flow of O2 directly to the common gas outlet (i.e., a direct communication between the O2 high-pressure

40-50 PSIG

To machine outlet

and the low-pressure circuits). As part of the machine checkout, use of the O2 flush valve to test for leaks in the low-pressure circuit is inappropriate and can be misleading. The flush valve should deliver a steady flow of O2 at not less than 35 L/minute and not more than 75 L/minute. Also, it should deliver O2 to the common gas outlet without passing through a vaporizer. In addition, the flush valve should have the following characteristics: ● ● ●

Be permanently marked to show its intended function Be designed to minimize unintended accidental operation Be self-closing

Recognition Changes in anesthesia machine design have made it difficult to activate the O2 flush valve accidentally. The following monitors are intended to alert anesthesia providers to activation of the flush valve or to signal the presence of leaks: ● ● ●

High-pressure or constant-pressure alarms Inspired and expired volatile agent concentrations Inspired O2 and end-tidal carbon dioxide concentrations

The O2 flush valve can provide a high-pressure O2 source suitable for jet ventilation when the anesthesia machine is equipped with a one-way check valve positioned between the anesthetic vaporizer and the O2 flush valve and when a positive-pressure relief valve exists downstream from the anesthetic vaporizer.

Risk Assessment

Ball valve retaining spring

All patients are at potential risk for complications from inappropriate use of the O2 flush valve (Table 126-2). A defective or damaged flush valve can stick in the fully open position, compounding the risk of barotrauma or patient awareness. Specific risk factors for other complications are discussed in Table 126-2.

Ball valve Valve seat

Pin

Implications Flush button

Inappropriate use of the O2 flush valve can have severe consequences for the patient. ●

Figure 126–1 ■ Oxygen flush valve in the open position. (Courtesy of Ohmeda Inc., Madison, Wis.)

524

●

Barotrauma can progress to pneumothorax and cardiovascular collapse. Compensating for leaks can lead to awareness, hypoxia, and hypercapnia.

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Figure 126–2 ■ Position of the oxygen flush valve in a machine circuit. (Courtesy of Ohmeda Inc., Madison, Wisc.)

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Oxygen Flush Valve

525

O2 wall supply N2O wall supply Pipeline inlet with check valve

Oxygen flush valve Machine outlet

Absorber

●

Inability to ventilate can lead to hypoxemia, with consequent brain damage.

Table 126–2 Complication

MANAGEMENT

PREVENTION Disconnecting the patient from the anesthesia breathing circuit before activating the O2 flush valve can eliminate the

Table 126–1

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Potential Complications with Oxygen Flush Valves

Complication

Analysis and Cause

Barotrauma Awareness

High gas flows at high pressures Bypassing the vaporizer leads to dilution of volatile anesthetic agent Using the flush valve to pressurize the breathing system closes any check valve between the vaporizers and the common gas outlet and prevents detection of leaks by the machine’s internal components When high flows or pressures are required (e.g., open bronchus, transtracheal jet ventilation), a nonworking valve or pressurelimiting mechanism at the common gas outlet reduces flow

Masking of machine leak

Inability to ventilate

Risk Factors for Complications with Oxygen Flush Valves Risk Factor

Barotrauma

Small patients with low-volume lungs or patients with low lung compliance Awareness Repeated use of the O2 flush valve to refill the rebreathing bag when gas is being lost from the circuit Masking of Risk is greater if the user is unfamiliar with machine leaks the anesthesia machine, if inappropriate checks are performed before use, and if the machine has recently been serviced Inability to During thoracic surgery with an open ventilate bronchus or with emergent transtracheal jet ventilation, the machine may be incapable of delivering high flows owing to its design

risk of pneumothorax. Familiarity with the anesthesia machine and performance of the standard preoperative checks, as recommended by each manufacturer, can also minimize the risk of undetected leaks. Finally, a pressurelimiting device at the common gas outlet should alert the anesthetist that the machine cannot be used for temporary jet ventilation in an emergency.

Further Reading Berner MS: Profound hypercapnia due to disconnection within an anesthetic machine. Can J Anaesth 34:622-626, 1987. Comm G, Rendell-Baker L: Back pressure check valves: A hazard. Anesthesiology 56:327-328, 1982. Davies AO: Detecting disconnections within anesthetic machines. Can J Anaesth 35:437-438, 1988.

EQUIPMENT & MONITORING

The potential for barotrauma can be limited by early recognition and by the use of appropriate monitoring. Pneumothorax may require the insertion of a chest tube. Other complications are largely preventable.

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Dodgson BG: Inappropriate use of the oxygen flush to check an anesthetic machine. Can J Anaesth 35:436-437, 1988. Dorsch JA, Dorsch SE: Understanding Anesthesia Equipment: Construction, Care and Complications, 4th ed. Baltimore, JB Lippincott–Williams & Wilkins, 1999, pp 96-97, 412, 942-944. Eisenkraft JB: The anesthesia machine. In Ehrenwerth J, Eisenkraft JB: Anesthesia Equipment: Principles and Applications. St. Louis, Mosby– Year Book, 1993, pp 35-37. Gaughan SD, Benumof JL, Ozaki GT: Can an anesthesia machine flush valve provide for effective jet ventilation? Anesth Analg 76:800-808, 1993.

Miller R: Oxygen flush valve. In Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2004, pp 283-284. Newton NI: Safety in the operating theatre: The meaning of excessive pressure. Br J Hosp Med 25:504-509, 1981. Standard Specification for Minimum Performance and Safety Requirements for Components and Systems of Anesthesia Gas Machines (F29.01.09), sec 10. Philadelphia, American Society for Testing and Materials, 1998.

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127

Anesthesia Circuit Ramachandran Satya-Krishna Case Synopsis A 57-year-old woman who is a heavy smoker experiences a difficult endotracheal intubation during induction of anesthesia. Mask ventilation is also difficult, owing to the high inspiratory pressures needed for ventilation and a poor mask fit. This results in a considerable leak between the mask and the face. The first and subsequent attempts at intubation lead to a stiff bag and the lack of a carbon dioxide (CO2) waveform on the capnogram. After each attempt, esophageal intubation is diagnosed, and the tube is quickly removed. After each attempted tracheal intubation, mask ventilation becomes progressively more difficult. Throughout this episode, the patient becomes intermittently hypotensive. About 30 minutes after induction, an observer notices that the expiratory check valve of the anesthesia breathing system remained seated during the entire breathing cycle. Replacement of the valve solves the problem, and ventilation becomes possible. Thus, this “cannot ventilate, cannot intubate” scenario has an unexpected “twist.”

PROBLEM ANALYSIS Definition

Table 127–2

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EQUIPMENT & MONITORING

The anesthetic breathing system (ABS) is defined by the American Society for Testing and Materials as “a gas pathway in direct connection with the patient through which gas flows occur at respiratory pressures, in which directional valves may be present, and into which a mixture of controlled composition may be dispensed.” An important component of the ABS, the CO2 absorber, is discussed in Chapter 129. Almost every medical device carries at least some risk for misuse or failure. ABSs lend themselves to critical incidents and patient injury because of multiple mechanical components and connections (Table 127-1) and variations in manufacture and design. A listing of possible ABS failures is given in Table 127-2. Critical incidents involving ABSs can be classified broadly as equipment misuse and equipment failure. The following definitions were used in the American Society of Anesthesiologists (ASA) closed claims analysis and accurately describe the various ABS-related issues. Equipment misuse refers to incidents originating from human fault or error associated with the preparation, maintenance, or deployment of a medical device. In contrast, equipment failure refers to a

situation in which the device appears to malfunction unexpectedly, despite routine maintenance and previous uneventful use. One example of the latter is a unidirectional valve on the ABS that suddenly fails to open. A disconnect is defined as the loss of attachment or continuity in an ABS that was initially configured in a functional and conventional manner. A misconnect is a nonfunctional and unconventional configuration of the ABS components or attachments. The situation described in the case synopsis represents one of the many potentially lethal or injurious complications

Possible Anesthesia Breathing Circuit Failures

Disconnection See Table 127-1 for possible sites of disconnection

Blockage (Raised Airway Pressure) Mechanical distortion Foreign body within circuit Heated hoses Improperly connected scavenging system Water condensation Slowly progressing block of microbial filters

Leaks (Lowered Airway Pressure) Inspiratory limb Expiratory limb Any other tube or small connection

Valve Malfunction

Table 127–1

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Components of the Circle System

Fresh gas flow inlet Inspiratory limb Expiratory limb Respiratory check valves Carbon dioxide absorber Y-piece Ventilator reservoir bag APL (pop-off) valve Anesthetic gas scavenging system

Obstruction or incompetence Reverse flow or rebreathing

Carbon Dioxide Absorber Failure Exhausted soda lime Carbon monoxide production Dry soda lime Overheating Retained canister wrapping

Contamination Microbes, viruses Particulate matter

APL, airway pressure limiting.

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related to the ABS. In fact, according to the most extensive surveys available, the ABS is the leading cause of critical incidents, with disconnections being the single most frequent cause. Obstruction within the expiratory limb of the ABS, however, can be one of the most rapidly injurious incidents. With a closed expiratory system, gases entering the lungs cannot exit, and airway pressure increases rapidly to a level at which the lungs may rupture.

Recognition Recognition of ABS problems can be extremely difficult, as illustrated in the case synopsis. These incidents are potential time bombs, because they do not seem to be related to anything done by the anesthesiologist, such as turning a dial, injecting a drug, or inserting an endotracheal tube. Unless a high index of suspicion is present, the anesthesiologist may concentrate on more likely causes—in this case, esophageal intubation. Contemporary monitors alone may offer little help with ABS problems. In the ASA closed claims analysis, however, reviewers judged that appropriate monitoring could have prevented injury in 78% of gas delivery claims. More importantly, in 21% of claims, a critical mechanical monitor or alarm (e.g., high- or low-pressure circuit alarm) had been turned off, broken, or omitted. In a very small minority of claims, better monitoring would not have improved the outcome when the initiating event progressed rapidly to injury. Above all, the most important monitor is a vigilant anesthetist who monitors breath sounds and chest wall excursions and continually observes the monitors. A simulation and discussion of the events that transpired in the case synopsis are provided in Figure 127-1.

Risk Assessment All patients having general anesthesia are at risk for ABSrelated complications. High tidal volumes, high respiratory rates, and fresh gas flows increase this risk, especially in small patients. Patients with lung disease, especially those with emphysematous bullae, are especially susceptible to injury produced by increased airway pressure (barotrauma). The state of anesthesia decreases protective cardiovascular reflexes and contributes to cardiovascular compromise during positivepressure ventilation. Rapidly rising airway pressure quickly impedes venous return, which reduces stroke volume and arterial pressure, even in healthy patients. This may be more evident in patients with decreased blood volume or impaired cardiac function. In the seminal report by Cooper and colleagues, the following ABS-related incidents ranked high on the list of critical problems: ABS circuit disconnection during mechanical ventilation (5.2%), ABS circuit leak (1.7%), ABS circuit misconnection (1.7%), and ABS control errors (1.4%). ABS control errors most often involved maladjustment of the airway pressure limiting (APL) valve; this is especially true on older machines, where the APL valve had to be shut off when the ventilator was turned on. In Cooper’s report, critical incidents related to the ABS accounted for 10% of all incidents. The Australian survey of critical incidents revealed similar results: ABS circuit disconnection (6%), partial failure

Figure 127–1 ■ Simulation of the case synopsis. Anesthesia is induced with 5 mg/kg of thiopental and 1.5 mg/kg of succinylcholine. Repeated doses of thiopental and succinylcholine are necessary to optimize conditions in a difficult situation. A, A recording of the ventilatory and airway variables during the simulation. Tidal volume (VT) and the carbon dioxide (CO2) curve are never satisfactory after apnea has been induced, but this was attributed to the “cannot ventilate” situation. Airway pressure (AP) and lung volume (VL) increase rapidly and markedly every time the Y-piece is connected to the sealed endotracheal tube. The leaking mask prevents dangerous increases during mask ventilation. After denitrogenation, as long as an oxygen (O2) supply is connected to the airway, there will be sufficient O2 to keep the SpO2 above 100%. B, A recording of cardiovascular and blood gas variables during the simulation. PaO2 remains at a satisfactory level, despite all the “airway” problems; SpO2 never decreases below 100% (not shown). Mean arterial pressure (MAP) and stroke volume (SV) dive precipitously every time the Y-piece is connected to the sealed endotracheal tube. The last response is related to the enormously and rapidly increased airway pressure seen in A. Note, for example, the marked and simultaneous decrease in central venous pressure (CVP), MAP, and SV in B with increases in airway pressure in A.

to ventilate or a circuit leak (5.2%), and unidirectional valve malfunction (3%). In that report, the total number of incidents related to the ABS was 282 (14.1%). In the ASA closed claims analysis, equipment misuse was three times more common than equipment failure (75% versus 24%). Two thirds of all claims involving equipment misuse resulted directly (in fact, almost exclusively) from the actions of the primary anesthesia care provider. Causes of or contributors to ABS problems include wear and tear, damaged components, improper or infrequent

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maintenance, improper assembly, carelessness, and failure to check the anesthesia workstation before use. Failure to check equipment is a common factor in a large proportion of critical incidents. In the survey by Cooper and colleagues, 20.5% of incidents involved failure to check; in the Australian survey, failure to check was involved in 11.8% of all incidents. In the ASA closed claims analysis, the most frequent sites of disconnections and misconnections were the junction between the ABS circuit and the gas delivery ventilator outlet, the junction between the distal breathing circuit and the endotracheal tube, and a configuration of the inspiratory limb of the ABS circuit that allowed the interposition of a positive end-expiratory pressure valve. Other causes of initiating events were operator errors (e.g., failure to turn on a device, selection of a wrong knob or dial, faulty valve installation).

Implications

Anesthesia Circuit

529

disconnections may be slow enough to permit safe management of the problem before patient injury occurs. This underscores the importance of using ABS circuit monitors that can issue prompt alarms for high- and low-pressure conditions. Thus, human error plays a major role in the initiation and propagation of ABS complications. Patient injury from ABS complications is characterized by high severity of injury and high cost. The ABS circuit represents the single largest source of claims related to gas delivery equipment, and almost all these claims result from misconnections or disconnections.

MANAGEMENT Management, especially if an ABS-related condition is recognized relatively early, is usually simple. Sometimes a malfunctioning anesthesia machine must be replaced intraoperatively, and this is not a trivial or a brief matter. While this exchange is taking place, or often while a diagnosis is being confirmed, a method should be devised to supply oxygen, ventilation, and anesthesia independently. The equipment for these maneuvers should always be available in every operating room, perhaps in the form of a self-inflating resuscitation bag and an accessory oxygen flowmeter on the anesthesia workstation.

PREVENTION The optimal way to prevent ABS-related incidents is the anesthesia workstation checkout. The Food and Drug Administration (FDA) compiled a formal list for this checkout in 1986, with the most recent revision occurring in 1993. A summary pertinent to the ABS is given in Table 127-3. Checkout protocols typically entail four basic activities: verification of backup equipment and supplies (e.g., pressurized gas cylinders), inspection of equipment configurations (e.g., breathing circuit connections), inspection of equipment mechanics (e.g., proper action of unidirectional valves), and preparation of monitors (e.g., calibration, verification of function, and activation of alarms). The ASA closed claims analysis revealed that better selection and use of monitoring equipment could have prevented the vast majority of complications in gas delivery system claims. In the case synopsis, the simple act of disconnecting the Y-piece from the inspiratory and expiratory limbs of the ABS and trying to breathe in and out through both of them individually would have increased the chances of preventing this disaster. Because of the serious implications of high airway pressures, an alarm alone may not provide clinicians with enough time for alarm recognition, diagnosis of the problem, and appropriate remedial action. For this reason, every anesthetic workstation must have a fixed breathing pressure limiting protection module (BPLPM) whose maximum pressure cannot exceed 125 cm H2O (12.5 kPa). Further, modern anesthesia workstations must have an adjustable BPLPM if the fixed BPLPM is greater than 80 cm H2O. If there is no ventilator, or if the anesthesia workstation is in the manual or spontaneous mode, the reservoir bag may be considered

EQUIPMENT & MONITORING

Consequences of ABS circuit complications can be disastrous. During the past 2 decades, a few large-scale surveys of anesthetic outcome have examined gas delivery equipment as the cause of serious injury. These studies attribute 1% to 5% of anesthesia-related deaths and brain injuries to problems with gas delivery equipment. The ASA closed claims project provides similar data, with gas delivery equipment accounting for 2.7% of claims for death (34 of 1277) and 4.5% of claims for brain damage (21 of 466). Cooper and colleagues listed 9 ABS-related incidents in 67 patients with “substantive negative outcomes,” or 13.4% of such outcomes. Circulatory collapse, ruptured lungs, and severe hypoxia were three of the major adverse outcomes. Although gas delivery equipment plays a prominent role in critical incident studies, often contributing to more than 20% of all reported events, claims involving gas delivery equipment account for less than 2% (72 of 3791) of the overall ASA closed claims database. Critical incidents are events that have the potential to cause injury; fortunately, many critical incidents are detected and remedied before an identifiable injury occurs. In previous studies, only 17% to 26% of incidents were associated with a major physiologic change, morbidity, or death. Thus, it can be surmised that inadequate responses to critical incidents cause patient injury in the vast majority of cases. Equipment misuse accounts for the significant majority of ABS-related complications and was three times more common than equipment failure in the ASA closed claims analysis. Previous studies have also stressed the prominent role of human error in equipment-related critical incidents and adverse outcomes. This fact explains the disproportionately high incidence of complications with the ABS, compared with more complex ventilators, vaporizers, and anesthesia machines. Another interesting feature of ABS claims is that misconnections were as prevalent as disconnections. This differs from critical incident studies, in which disconnections are significantly more common, as discussed earlier. This reflects a key difference in the speed of evolution of high- and low-pressure injuries to the airway. Misconnections typically occur in an intact circuit and thereby lead to high airway pressure and the potential for pneumothorax. In contrast, the evolution of hypoxia and hypercapnia caused by

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Table 127–3

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Food and Drug Administration Recommendations for Anesthesia Checkout Pertinent to Anesthesia Breathing Circuit

Initial status of the breathing system Set selector switch in “bag” mode Check that breathing circuit is complete, undamaged, and unobstructed Verify that CO2 absorbent is adequate Install breathing circuit accessory equipment (e.g., humidifier, PEEP valve) to be used during the case Leak check of breathing system Set all gas flows to zero (or minimum) Close APL (pop-off) valve and occlude Y-piece Pressurize breathing system to 30 cm H2O with O2 flush Open APL valve and ensure that pressure decreases Ventilation system and unidirectional valves Place second breathing bag on Y-piece Set appropriate ventilator parameters for next patient Switch to automatic ventilation (ventilator) mode Fill bellows and second breathing bag with O2 flush and then turn ventilator on Set O2 flow to minimum and other gas flows to zero Verify that, during inspiration, bellows delivers appropriate tidal volume, and during exhalation, bellows fills completely Set fresh gas flow to about 5 L/min Verify that ventilator bellows and simulated lungs fill and empty appropriately and without sustained pressure at end-exhalation Check for proper action of unidirectional valves Examine breathing circuit accessories to ensure proper function Turn ventilator off and switch to manual ventilation (bag/APL) mode Ventilate manually and ensure inflation and deflation of artificial lungs and appropriate feel of system resistance and compliance Remove second breathing bag from Y-piece APL, airway pressure limiting; PEEP, positive end-expiratory pressure.

an APL protection module. However, a BPLPM would have offered limited protection in the case synopsis, because expired gases could not reach the bag or the ventilator owing to the obstructed expiratory check valve. In summary, suspicion, observation, and compulsive attention to detail can contribute to the prevention, recognition, and management of ABS-related complications. The anesthesiologist’s motto of “vigilance” is important at all times; however, to prevent ABS complications, unremitting vigilance is required. Acute increases in airway pressure and complete loss of tidal volume due to leaks are true emergencies that may present during anesthesia and may cause fatal or crippling injuries in a matter of seconds.

Further Reading Adams AP: Breathing system disconnections. Br J Anaesth 73:46-54, 1994. Anesthesia Apparatus Checkout Recommendations, 1993. Federal Register, July 11, 1994 (59 FR 35373).

ASTM F1208 (Anesthesia breathing systems). In Medical Devices, Emergency Medical Services. 13.01. West Conshohocken, Pa., American Society for Testing and Materials, 1994. Caplan R, Vistica M, Posner K, et al: Adverse anesthetic outcomes arising from gas delivery equipment: A closed claims analysis. Anesthesiology: 87:741-778, 1997. Cooper JB, Newbower RS, Kitz RJ: An analysis of major errors and equipment failures in anesthesia management: Considerations for prevention and detection. Anesthesiology 60:34-42, 1984. Russell WJ, et al: Problems with ventilation: An analysis of 2000 incident reports. Anaesth Intensive Care 21:617-620, 1993. Webb RK, et al: Equipment failure: An analysis of 2000 incident reports. Anaesth Intensive Care 21:673-677, 1993. Webb RK, et al: Which monitor: An analysis of 2000 incident reports. Anaesth Intensive Care 21:529-542, 1993.

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128

Vaporizers Mark Abel and James B. Eisenkraft Case Synopsis A 34-year-old woman, who is American Society of Anesthesiologists physical status I, undergoes general anesthesia for total abdominal hysterectomy. The anesthesia vaporizer dial is set to deliver 1% isoflurane. Her blood pressure is noted to be 60/40 mm Hg, and the calibrated respiratory gas analyzer shows an inspired isoflurane concentration of 4%.

PROBLEM ANALYSIS Definition Assuming that the agent analyzer reading is correct (see Chapter 141), the breathing circuit contains an agent concentration that greatly exceeds the one set on the concentration dial. This may be due to malfunction of the vaporizer or to the presence of liquid anesthetic agent in the breathing circuit. Vaporizer problems that result in increased anesthetic vapor concentration include tipping, overfilling, use of the oxygen (O2) flush valve upstream of a freestanding vaporizer, and gas flow reversal through a vaporizer. High concentrations of a potent inhaled agent also may result from the presence of volatile anesthetic liquid in the patient breathing circuit.

Recognition

Risk Assessment VAPORIZER MALFUNCTION Contemporary anesthesia vaporizers are concentration calibrated, with the exception of the Ohmeda Tec 6 (desflurane) vaporizer, which is of the variable-bypass design. A variablebypass vaporizer splits the incoming fresh gas into two pathways. Most of the gas flows through a bypass and is not exposed to anesthetic vapor, whereas a lesser flow enters the vaporizing chamber and emerges with the anesthetic agent at its saturated vapor concentration. When the two flows mix at the vaporizer outlet, the greater bypass flow mixes with the vaporizing chamber output to produce the desired (dialed-in) concentration. OVERFILLING

AND

TIPPING

Overfilling or tipping of a vaporizer can cause liquid agent from the vaporizing chamber (or sump chamber) to enter the bypass, which is designed for respiratory gases (e.g., O2, nitrous oxide, air, nitrogen, helium) and vapor only. This can lead to the delivery of a lethal concentration of anesthetic agent to the patient circuit. In the United States, vaporizers may be of the funnel-fill or key-fill design, whereas in Canada, the key-fill design is mandated. Funnel-fill vaporizers should be inspected during filling to ensure that the level of liquid in the sump chamber does not exceed the maximum fill line indicated on the sight glass. Overfilling of key-fill vaporizers has been extensively described. Key-fill systems are designed for use with an airtight joint between the bottle containing the anesthetic liquid and the matching 531

EQUIPMENT & MONITORING

The common factor in all these situations is an anesthetic agent concentration that exceeds the one intended. This manifests as clinical and hemodynamic signs of anesthetic overdose and, in the case synopsis, low blood pressure. Measurement of the agent concentration in the breathing circuit is critical to making a correct diagnosis. Before locating the source of the excess agent, the clinician should immediately disconnect the patient from the breathing circuit and ventilate the patient’s lungs with an alternative system, such as a self-inflating resuscitation bag (e.g., Ambu bag) or another anesthesia circuit connected to an O2 source. Some investigative work is required to distinguish whether the problem is with the vaporizer or the breathing circuit. Because almost all potent volatile anesthetics are delivered with the use of machine-mounted, calibrated, agent-specific vaporizers, the vaporizer concentration dial is set to a certain value (e.g., 1%), and the concentration of agent in the gas flowing from the common gas outlet (CGO) of the anesthesia machine is sampled and analyzed. The CGO is the sampling point in the delivery system that is closest to the vaporizer outlet. With the fresh gas flow set to 5 L/minute of the carrier gas (air for Dräger vaporizers; O2 for Ohmeda and Penlon vaporizers), the vaporizer is calibrated at the factory; the concentration dial is set to 1%, and the concentration of agent in the gas flowing from the CGO is measured with the use of a calibrated agent analyzer. The measured concentration should be within 10% to 15%

of the vapor concentration dial setting (e.g., if the dial is set to 1%, the concentration measured should be between 0.85% and 1.15%) if the vaporizer is in calibration (according to manufacturers’ specifications). If a higher concentration is detected, it is likely that the problem is with the vaporizer and not the breathing circuit. If the measured agent concentration agrees with the dial setting concentration, the likely problem is liquid agent in the anesthesia circuit. In the unlikely event that a freestanding vaporizer is being used (i.e., one placed in series between the CGO of the machine and the breathing circuit), it should be inspected to ensure that the direction of fresh gas flow through the vaporizer is correct (i.e., the fresh gas enters via the vaporizer inflow, not the outflow, connection).

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vaporizer, with the vaporizer dial turned to the off position. Correct use prevents overfilling by two mechanisms. First, intake of air into the bottle of anesthetic agent is interrupted when filling has reached the maximum safe level of liquid in the vaporizing chamber. Second, when the vaporizer is in the off position, the air space at the top of the vaporizing chamber is sealed, thereby preventing overfilling. Because filling of a key-fill vaporizer is slow, this has led to improper practices to expedite the process. Such practices include loosening the seal between the bottle and vaporizer, which allows direct entry of room air into the bottle, and turning the concentration dial to the “on” position. This double-fault condition allows an excessive amount of air to enter the agent bottle and, therefore, an excessive amount of liquid agent to enter the vaporizer. Such vaporizer overfilling has led to anesthetic overdose and neurologic injury. PUMPING EFFECT The pumping effect may result from intermittent backpressure applied to the vaporizer through pressure changes downstream in the breathing system. Such pressure changes may be caused by intermittent positive-pressure ventilation in the patient circuit or normal operation of the O2 flush. Gas flow distribution changes within the vaporizer may occur, leading to increased vapor concentration output. This effect is greatest at low fresh gas flow rates, at low concentration dial settings, when small amounts of liquid agent are present in the vaporizer sump, and with large, rapid changes in pressure. Although the mechanism is not completely understood, it is likely that gas is compressed in the vaporizer (in both the vaporizing chamber and the bypass) during pressurization. When the pressure decreases, anesthetic vapor leaves the vaporizing chamber through both the normal exit and the vaporizing chamber inlet, resulting in vapor in the bypass flow. This effectively increases the vapor output. FREESTANDING VAPORIZERS Although modern delivery systems involve the use of vaporizers that are securely mounted to a manifold on the anesthesia machine, freestanding vaporizers are still used on cardiopulmonary bypass machines, in veterinary facilities, in laboratories, and sometimes during clinical trials of investigational inhaled volatile agents. Freestanding vaporizers are especially hazardous for several reasons. Tipping of a freestanding vaporizer is a long-recognized problem that has resulted in cardiac arrest; it may result in dramatically increased vaporizer concentration outputs compared with the concentration dial setting. Tipping of a variable-bypass vaporizer, by tilting either a freestanding unit or the entire anesthesia machine, may result in liquid agent entering the vaporizer bypass or the gas outlet pathway of the vaporizing chamber, resulting in an overdose of potent inhaled agent. Reversal of the direction of gas flow through a variablebypass, concentration-calibrated, agent-specific vaporizer can profoundly affect its performance, depending on the model. With freestanding vaporizers in clinical practice, this has been reported to result in dangerously high concentrations of volatile anesthetics. Finally, unauthorized tampering with an anesthesia machine could result in reversed gas flow connections to the vaporizer manifold.

Although never clinically reported, a laboratory study has shown that application of the O2 flush valve upstream of a variable-bypass vaporizer results in delivered anesthetic concentrations that exceed the concentration dial setting. Although the increases in delivered anesthetic concentrations were transient and resulted in a maximum agent concentration of 2.1% in excess of that set on the concentration dial, it is theoretically possible for increased anesthetic delivery to occur in a clinical setting in which application of the O2 flush valve is required. LIQUID AGENT

IN THE

PATIENT BREATHING CIRCUIT

Liquid volatile anesthetic agent may enter the breathing circuit either intentionally or unintentionally. Deliberate administration of volatile anesthetic agent directly into the breathing circuit is typically done into the expiratory limb. If this is performed in an uncontrolled fashion, liquid volatile agent in the circuit may produce vapor concentrations that greatly exceed safe levels, because the saturated vapor concentrations of these liquids at 1 atmosphere and 20°C range from 21% for sevoflurane to 87% for desflurane, with other agents having intermediate values. One milliliter of liquid agent produces approximately 200 mL of vapor at 20°C and 1 atmosphere (Table 128-1). Because a typical adult circle breathing circuit (with 5-foot-long inspiratory and expiratory limbs) has a volume of approximately 7 L, 1 mL of a volatile anesthetic liquid in such a circuit will produce a concentration of nearly 3% (approximately 200 mL/7000 mL) on complete mixing. Incomplete mixing can result in far greater concentrations. The delivered concentrations resulting from volatile liquid in the circuit are potentially lethal if excessive volatile liquid enters the circuit or mixing is inadequate. If unexpectedly high concentrations of a potent volatile agent are detected, and analysis of the gas emerging from the machine CGO excludes a problem with the vaporizer, the presence of a volatile agent in the circuit may be confirmed by sampling the gas in the patient breathing system.

Implications Anesthetic agent concentrations that exceed those set on the vaporizer concentration dial may result in complications ranging from mild hemodynamic instability to total cardiovascular collapse. All potent inhaled agents are myocardial

Table 128–1

Anesthetic Desflurane Enflurane Halothane Isoflurane Sevoflurane

■

Volume of Anesthetic Vapor per Milliliter of Liquid Anesthetic at 20°C Vapor/Liquid (mL/mL) 182 195 226 196 182

From Eisenkraft JB: Anesthesia vaporizers. In Ehrenwerth J, Eisenkraft JB (eds): Anesthesia Equipment: Principles and Applications. St. Louis, Mosby–Year Book, 1993, pp 57-88.

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depressants and peripheral vasodilators. Liquid agent in the breathing circuit that reaches the patient directly is especially dangerous.

MANAGEMENT An anesthetic agent analyzer with the appropriate high-concentration alarm limits set, although not currently a standard of care, is critical because this is the most sensitive way to detect excessive concentrations. Standard monitors, including electrocardiogram and blood pressure monitors, are critical for detecting the hemodynamic consequences of such potential overdoses. If the patient is breathing spontaneously, changes in the respiratory pattern may be noted. When vapor concentrations greatly exceed the concentration dial setting, an alternative breathing system should be immediately available (as recommended in 1993 by the Food and Drug Administration); then the source of the excess anesthetic agent should be found, as described earlier. Hemodynamic supportive measures should be used as appropriate.

PREVENTION

Vaporizers

533

from the machine flowmeters; therefore, the use of downstream check valves limits, but does not eliminate, the risk of the pumping effect. A level anesthesia machine avoids the problems associated with machine tipping with machinemounted anesthesia vaporizers. If a vaporizer is inadvertently tipped, it should be purged with high fresh gas flow from the machine flowmeters, with the vaporizer concentration dial turned to the highest setting, until no trace of the agent is detectable. The vaporizer is then refilled, and the output is checked as described earlier. The temperature of the vaporizer should be allowed to stabilize for 2 hours before its next clinical use. Freestanding vaporizers are potentially more hazardous than machine-mounted ones. They generally are used only in laboratory and veterinary facilities, but Ohmeda vaporizers may be mounted on cardiopulmonary bypass machines with a specially designed bracket available from Ohmeda. When such freestanding vaporizers are used, care should be taken to avoid tipping during both transport and use. Fresh gas inflow and outflow connections to the vaporizer should be checked to ensure that they are not reversed, because reversal of these connections may result in increased vapor concentration output. The proper use of a vaporizer limits the potential for malfunctions that may result in overdose of an anesthetic agent. If such a malfunction occurs, analysis of the gas in the breathing circuit should lead to prompt recognition and appropriate action to prevent harm to the patient.

Further Reading Eisenkraft JB: Anesthesia vaporizers. In Ehrenwerth J, Eisenkraft JB (eds): Anesthesia Equipment: Principles and Applications. St. Louis, Mosby– Year Book, 1993, pp 57-88. Greg AS, Jones RS, Snowdon SL: Flow reversal through a Mark III halothane vaporizer. Br J Anaesth 71:303-304, 1993. Hardy JF: Vaporizer overfilling [editorial]. Can J Anaesth 40:1-3, 1993. Kelly DA: Free-standing vaporizers: Another hazard. Anaesthesia 40: 661-663, 1985. Philip JH: Closed circuit anesthesia. In Ehrenwerth J, Eisenkraft JB (eds): Anesthesia Equipment: Principles and Applications. St. Louis, Mosby– Year Book, 1993, pp 617-635. Ralton R, Inglis MD: High halothane concentrations from reversed flow in a vaporizer. Anaesthesia 41:672-673, 1986. Rosenwarne FA, Duncan IN: Reversed connexions of free-standing vaporizers. Anaesthesia 45:338-339, 1990. Sinclair A, Van Bergen J: Vaporizer overfilling. Can J Anaesth 40:77-78, 1993.

EQUIPMENT & MONITORING

Overfilling a vaporizer can be avoided by not exceeding the maximum fill line in the sight glass and, in the case of keyfill vaporizers, by following the manufacturer’s instructions (i.e., filling the vaporizer with the dial set to the “off ” position and ensuring an airtight seal between the key-filling nozzle and the vaporizer). Modern vaporizers have incorporated certain design features that minimize the significance of the pumping effect. Some older vaporizer models, such as the Ohio Calibrated Vaporizer, have a check valve in the vaporizer outlet to prevent transmission of increases in downstream pressure. Some delivery systems contain a check valve downstream of the vaporizer (e.g., Ohmeda Modulus I, Modulus II, and Ohmeda Excel). These valves prevent transmission of downstream pressures back to a vaporizer that lacks modern design features, and they are intended to prevent the pumping effect. It should be noted, however, that when the check valve is closed, the pressure upstream of it, and hence in the vaporizer, increases because of continuous fresh gas flow

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Carbon Dioxide Absorbers Gaury S. Adhikary

129

Case Synopsis A 40-year-old, 70-kg man undergoes an exploratory laparotomy while under general anesthesia with the use of a semiclosed circuit. Thirty minutes into the surgery, he is noted to have an end-tidal carbon dioxide (CO2) level of 55 mm Hg with a constant minute ventilation of 7 L/minute.

PROBLEM ANALYSIS

3.

Definition Hypercarbia under general anesthesia can be caused by CO2 absorber-related problems (e.g., exhausted CO2 absorber; channeling of gases through the granules, causing inefficient removal of CO2 from the circuit) (Fig. 129-1). Hypercarbia also may be due to increased dead space and rebreathing brought about by sticky or leaking inspiratory or expiratory valves. Mild hypercarbia during constant minute ventilation is usually due to increased CO2 production as a result of increased catecholamine levels with light anesthesia or stress. The extremely rapid increase in CO2 production accompanying malignant hyperthermia manifests as severe hypercarbia, along with progressive hypoxemia and acidosis, despite constant minute ventilation.

Recognition Problems with CO2 absorbers can present as follows: ●

●

●

● ● ●

Increased end-tidal CO2 tension (rising plateau in capnography) Phase III of capnography trace fails to touch the baseline (rebreathing pattern) Increased ventilatory drive reflected by overriding of the ventilator Hypertension, arrhythmias, or hypotension Excessive sweating, increased oozing from the wound CO2 absorbent feels “too warm” to the touch

CO2 absorption by soda lime or barium hydroxide lime (Baralyme) in the anesthetic circuit generates heat, so a CO2 absorbent normally feels warm to the touch if it is absorbing CO2 properly. Excessive production of CO2 is reflected by excessive production of heat by the CO2 absorbent, so the CO2 canister will feel hot as opposed to warm. The chemistry of CO2 absorption by soda lime and Baralyme is as follows: A. Soda Lime 1.

CO2 + H2O = H2CO3

2.

H2CO3 + 2NaOH (or KOH) = Na2CO3 (or K2CO3) + 2H2O + Energy

534

Na2CO3 (or K2CO3) + Ca(OH)2 = CaCO3 + 2NaOH (or 2KOH) B. Baralyme

1. Ba(OH)2 + 8H2O + CO2 = BaCO3 + 9H2O + Energy 2.

9H2O + 9CO2 = 9H2CO3 Then by direct reactions and by NaOH or KOH:

3. 9H2CO3 + 9Ca(OH)2 = 9CaCO3 + 18H2O + Energy An exhausted CO2 absorber does not feel warm. Usually, a CO2 absorber changes from colorless to violet when ethyl violet is used as the pH indicator and it starts to absorb CO2 from the circuit. However, an exhausted CO2 absorbent shows no color change. Dyes are not a very sensitive test for CO2 absorption capacity, however, because fluorescent light can deactivate the dyes, and the absorbent may appear white even though exhausted. A soda lime absorbent is best judged by the length of time it has been used in the circuit. The maximum CO2 absorbing capacity of absorbent is 26 L of CO2/100g of absorbent. In practice, however, channeling of gas through the granules may decrease the absorbent efficiency substantially and allow only 10 to 20 L of CO2 to be absorbed. Amsorb (Armstrong Medical Ltd., Coleraine, Northern Ireland) has half the CO2 absorbing capacity of soda lime, and it does not have strong bases (i.e., the activators NaOH and KOH). These strong bases have been implicated in the production of carbon monoxide (CO) by methyl ethers and compound A by sevoflurane (see later). Because Amsorb does not contain strong bases, it does not degrade volatile anesthetics to compound A (from sevoflurane) or produce CO (from desflurane, enflurane, and isoflurane). The chemistry of Amsorb is as follows: 1. 2.

CO2 + H2O = H2CO3 H2CO3 + Ca(OH)2 = CaCO3 + 2H2O + Energy

Sevoflurane reacts with CO2 absorbents to produce degradation products. The major degradation product is fluoromethyl-2-2-difluoro-1-(trifluoromethyl) vinyl ether, or compound A. In addition, CO poisoning, though very rare, has been reported with the use of low-flow anesthesia. Although the mechanism is not clear, it is thought that CO

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Figure 129–1 ■ Causes of mechanical and chemical complications with carbon dioxide absorbers.

trichloroethylene along with a CO2 absorbent in the circuit is strongly contraindicated, as is the use of a CO2 absorbent in a patient who has recently (<24 to 36 hours) received trichloroethylene (e.g., postpartum tubal ligation).

Risk Assessment Hypercarbia secondary to CO2 absorbent malfunction may be due to exhaustion of the soda lime or barium hydroxide lime, with channeling of fresh gas flow through the CO2 absorbent canister. Or it may be due to loss of fresh gas flow through the CO2 absorbent canister housing owing to leaks. Any leak in the circuit, nonfunctioning inspiratory or expiratory valve, or exhausted CO2 absorbent increases the dead space in the circuit, which in turn causes rebreathing and results in hypercarbia. Hypermetabolic states, such as sepsis, cause excessive CO2 production and result in hypercarbia unless total minute ventilation is increased accordingly. In malignant hyperthermia, CO2 production is increased very rapidly due to a hypermetabolic state, with attendant hypercarbia accompanied by tachycardia, hyperthermia, and increasing metabolic acidosis. Because large quantities of CO2 are taken up by the CO2 absorbent, the temperature rise within the CO2 canister is substantial, and the canister may feel too hot.

Implications Hypercarbia causes sympathetic stimulation, which raises plasma catecholamine levels. High blood catecholamine levels increase blood pressure, sweating, and tachycardia and may cause ventricular arrhythmias with some older volatile anesthetics (sensitization). These may cause severe hemodynamic compromise. Factors leading to a rise in the concentration of compound A in the circuit are low-flow anesthesia techniques

EQUIPMENT & MONITORING

produced by the body is absorbed by the CO2 absorbent and later released into the circuit when the temperature is raised. This mechanism is postulated because most of the reported cases of CO poisoning have been the first case on a Monday morning, after the circuit was idle over the weekend. If so, CO2 absorbent with CO-laden granules would release CO into the circuit on Monday morning when the CO2 canister temperature rose. The Anesthesia Patient Safety Foundation has received reports of fire or extreme heat generation occurring in the CO2 canister. Common elements in these reports of fire include use of a Baralyme absorber, desiccation of the absorbent, and use of sevoflurane. Holak and colleagues reported that with simulated anesthetic conditions in their laboratory and use of dehydrated Baralyme and sevoflurane, a dial setting of 8% was required to deliver 1 MAC (2.1%) of sevoflurane to the “patient.” In the absence of sevoflurane uptake by the “patient,” the high breakdown of sevoflurane was presumed to be secondary to reaction with the absorbent. In this experiment the investigators recorded a temperature greater than 110°C at the upper absorbent canister in less than 10 minutes; at 15 minutes, the canister was too hot to touch. CO production increased exponentially above 70°C, and at 45 minutes the temperature was greater than 200°C. Finally, at 53 minutes, the absorber exploded and burst into flames. It was suggested that the initial delayed rate of rise of inspired agent concentration could serve as an early warning before the absorbent’s dramatic rise in temperature. Trichloroethylene (Trilene) is a general anesthetic agent still in use in some parts of the world. Trichloroethylene in the presence of heat and alkali forms breakdown products: the neurotoxin dichloroacetylene and the pulmonary irritant phosgene. Phosgene induces pneumonitis, leading to acute respiratory distress syndrome. Dichloroacetylene can produce cranial nerve lesions and encephalitis. The use of

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(fresh gas flow <2 L/minute), the use of barium hydroxide lime instead of soda lime, a high concentration of sevoflurane, a high absorbent temperature, and the use of fresh absorbents. Because compound A has been shown to cause renal injury in rats, it is prudent to avoid the use of sevoflurane in patients with renal impairment.

MANAGEMENT AND PREVENTION Hypercarbia during general anesthesia related to soda lime or barium hydroxide lime can be prevented by checking the freshness of the absorbent. When in doubt, it is advisable to change the absorbent too early rather than too late. It is important to make sure that the soda lime or barium hydroxide lime is packed properly in the canister to avoid any possibility of channeling, thereby reducing its ability to absorb CO2 in the circuit. Soda lime canisters should be fitted onto the canister housing, and checks for any leak in the circuit should be performed; this prevents rebreathing. Whenever sevoflurane is used, fresh gas flow of at least 2 L/minute must be maintained to reduce risk of compound A production and possible renal dysfunction. If synthetic zeolites (molecular sieves) are used instead of soda lime or barium hydroxide lime to remove CO2 from the circuit, compound A is not produced with sevoflurane. It is possible that molecular sieves for use with sevoflurane will become available in the future. Amsorb does not produce compound A or CO when used with sevoflurane or other volatile anesthetics (e.g., desflurane, enflurane, isoflurane). To address the rare and isolated cases of canister fire while using sevoflurane, Abbott Laboratories issued a letter in 2003 suggesting some preventive measures. These include replacing any CO2 absorber that has not been used for an extended period (it could be desiccated), turning off the vaporizer when not in use, shutting off the anesthesia machine and fresh gas flow when not in use for extended periods, periodically monitoring the temperature in the CO2 canister, and monitoring the rate of rise of inspired sevoflurane in relation to the dial setting of the vaporizer. An unusually delayed rise or unexpected decline of sevoflurane concentration compared with the vaporizer setting may

be associated with excessive heating of the CO2 absorbent canister. If excessive heat is detected, the patient should be disconnected from the anesthesia circuit and the CO2 absorber replaced. The patient should be monitored for CO exposure and the potential for chemical thermal injury. Trichloroethylene must not be used when soda lime or barium hydroxide lime is present in the circuit or when either was used recently (within 24 to 36 hours). Because the phenomenon of CO poisoning during low-flow anesthesia is so rare and because its mechanism is not clearly understood, it is best to keep a high level of suspicion. The anesthesia provider should check blood carboxyhemoglobin levels when in doubt and manage the patient accordingly.

Further Reading Andrews JJ: Inhaled anesthetic delivery systems. In Miller RD (ed): Anesthesia, 5th ed. New York, Churchill Livingstone, 2000, pp 193-195. “Dear Health Care Professional” [letter from Abbott Laboratories, Nov 17, 2003]. Available at http://www.fda.gov/medwatch/SAFETY/2003/ Ultane_deardoc.pdf. Fang ZX, Kendel L, Laster MJ, et al: Factors affecting production of compound A from the interaction of sevoflurane with Baralyme and soda lime. Anesth Analg 82:775-781, 1996. Fee JPH, Murray M, Luney SR: Molecular sieves: An alternative method of carbon dioxide removal which does not generate compound A during simulated low-flow sevoflurane anaesthesia. Anaesthesia 50:841-845, 1995. Gonsowskic CT, Laster M, Eger EL II, et al: Toxicity of compound A in rats: Effect of 3-hour administration. Anesthesiology 80:556-565, 1994. Gravenstein JS, Pulus DA, Hayes TJ: Capnography in Clinical Practice. Boston, Butterworths, 1989, pp 24-26. Higuchi H, Adachi Y, Arimura S, et al: The carbon dioxide absorption capacity of Amsorb is half that of soda lime. Anesth Analg 93:221-225, 2001. Holak EJ, Mei DA, Dunning MB III, et al: Carbon monoxide production from sevoflurane breakdown: Modeling of exposures under clinical conditions. Anesth Analg 96:757-764, 2003. Humphrey JH, McClelland M: Cranial-nerve palsies with herpes following general anesthesia. BMJ 1:315-318, 1944. Moon RE: Cause of CO poisoning, relation to halogenated agents still not clear. J Clin Monit 1:11, 1995. Morio M, Fujii K, Satoh N, et al: Reaction of sevoflurane and its degradation products with soda lime. Anesthesiology 77:1155, 1992. Olympio MA, Morrel RC: Canister fires become hot safety concern. Anesthesia Patient Safety Foundation Newsletter, winter 2003.

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Mechanical Ventilators Brian J. Woodcock Case Synopsis A 100-kg, 68-year-old man is anesthetized and intubated. Bilateral breath sounds are verified. The ventilator is turned on and set to a tidal volume of 600 mL, respiratory rate of 10, and inspiratory-expiratory ratio of 1:2. Two minutes later, the lowering tone of the pulse oximeter alerts the anesthesiologist, who notices an absence of chest wall movement. The ventilator appears to be cycling normally, so the anesthesiologist picks up a stethoscope and reaches to adjust the switch-over valve to manual, but it is already in the manual position.

PROBLEM ANALYSIS Definition Failure to change the ventilator-manual switch to the ventilator position after a period of manual ventilation is the source of many mechanical ventilator complications that can cause serious harm to patients. In the American Society of Anesthesiologists (ASA) closed claim analysis of adverse anesthetic outcomes, there were threefold more claims related to misuse of equipment or operator error compared with equipment failure. Examples of ventilator misuse or operator error include the following:

closed claim analysis, 12 cases were associated with ventilator problems; 7 resulted in death and 5 in brain injury. There is only a small window of opportunity to correct the malfunction of the ventilator before adverse physiologic events take place as a result of it. TURNING

● ● ● ● ● ●

Equipment failure or incorrect assembly can include the following problems: ● ●

● ●

Hole in the bellows Bellows mounted incorrectly, so no seal is formed between the bellows and the casing Electrical or mechanical failure, stalling the mechanism Failure of the alarms for pressure, apnea, or FiO2

Other causes of ventilator failure actually arise elsewhere on the anesthesia machine. These complications, covered in other chapters, include failure of driving gas pressure (Chapter 123); circuit disconnection, sticking valves, and misconnections of the circuit hoses (Chapter 127), and scavenger errors (Chapter 131).

Recognition The failure to recognize and promptly rectify problems with ventilators can have catastrophic consequences. In the ASA

ON

● ●

Loss of the end-tidal carbon dioxide (ETCO2) waveform Activation of the ETCO2 apnea alarm Distention of the reservoir bag and rising airway pressure on the manometer if the pop-off valve is closed

If the ventilator has not been turned on but the ventilatormanual switch has been turned to the ventilator position, the signs are as follows: ● ● ●

Loss of the ETCO2 waveform No airway pressure perceived by the manometer Activation of the apnea pressure and ETCO2 apnea alarms

VENTILATOR RATE

AND

TIDAL VOLUME

Inappropriate settings for tidal volume or respiratory rate may cause either inappropriate tidal volume size and hyperventilation or hypoventilation leading to falling or rising ETCO2. In the case of a child or small adult, hypotension may result from the decrease in venous return due to large tidal volumes and increased intrathoracic pressures. Barotrauma may also occur, with consequent pneumothorax or subcutaneous emphysema. In the case of an adult with ventilator settings for a small child, the most notable feature would be hypoventilation, including a low peak airway pressure, a rising ETCO2, and O2 desaturation if hypoventilation is severe. PRESSURE LIMIT An inappropriately high pressure limit setting may allow excessive tidal volumes and pressures, leading to barotrauma. A low pressure limit setting may lead to inadequate tidal volume and hypercarbia. 537

EQUIPMENT & MONITORING

●

Failure to turn the ventilator on after a period of manual ventilation Inappropriate set rate or tidal volume for patient size Maximum pressure limit set too high for patient size Maximum pressure limit set too low, causing low tidal volume Inappropriate inspiratory-expiratory ratio High fresh gas flow causing increased tidal volume Oxygen (O2) flush during ventilator inspiration Alarms for pressure, volume, or fraction of inspired oxygen (FiO2) inactivated by the operator, causing a delay in noticing other malfunctions

VENTILATOR

Failure to actually turn the ventilator on is common. This usually occurs soon after induction and may be unnoticed for many minutes. If the ventilator-manual switch has not been turned to the ventilator position, the signs are as follows:

● ●

THE

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INSPIRATORY-EXPIRATORY RATIO An inappropriate inspiratory-expiratory ratio may be set when unusual ventilator rates are used—for example, at the end of a case when the rate is set very low to allow arterial CO2 tension to rise. At low rates, an inspiratory-expiratory ratio of 1:2 might result in very prolonged inspiratory times. FRESH GAS FLOW Failure to reset the fresh gas flow to a lower rate after intubation of a patient may lead to hyperventilation. The set tidal volume on the bellows is supplemented by the amount of fresh gas entry into the circuit during the inspiratory period. For example, with a fresh gas flow of 10 L/minute, a respiratory rate of 10, and an inspiratory-expiratory ratio of 1:2, each tidal volume is increased by 333 mL above that set by the bellows. This may cause significant hyperventilation or barotrauma in a small patient if the maximum pressure limit is set too high. Pressing the O2 flush during ventilator inspiration can lead to large volumes of gas entering the patient, leading to the development of pneumothoraces due to barotrauma. VENTILATOR ALARMS Ventilators have two alarms, the ventilator alarm and the threshold pressure alarm limit (TPAL) alarm. The ventilator alarm has two buttons, the “silence alarm” button and the “alarm off ” button. Pressing the “silence alarm” button druing a period of manual ventilation can prevent the ventilator alarm from sounding when a period of apnea ensues. When the intent is to use manual ventilation or to hold ventilation for a limited period, the “silence alarm” button should be pressed to cancel that alarm for a period of 60 or 120 seconds. Pressing the ventilator “alarm off ” button, which indefinitely cancels the ventilator alarm, removes the ability of the ventilator alarm to automatically be re-armed if the operator fails to turn the ventilator back on. The TPAL alarm delineates the airway pressure level at which inspiration is detected. When this is adjustable, it should be set at less than 5 cm H2O below the peak inspiratory pressure. This allows the alarm to be triggered when a leak in the system causes a reduction in peak inspiratory

pressure but not a complete loss of the waveform (Fig. 130-1). The Narkomed 2B anesthesia machine gives a (silent) advisory notice when the pressure is set too low for the current peak pressure. The ventilator alarm should be considered the most important alarm in the operating room. A vigilant anesthesia provider should feel uncomfortable whenever this alarm sounds. Even if the reason for the alarm is known and anticipated (e.g., after switching to spontaneous ventilation following reversal of muscle relaxation at the end of a case), the alarm should not be allowed to continue unattended. Any ventilator alarm condition should be corrected, or the alarm should be reset to the appropriate level for the new status of the patient. Similarly, when leaving the operating room at the end of a case, the ventilator alarms should not be left sounding. VENTILATOR BELLOWS Development of a hole in the bellows can be recognized by the following: ● ● ● ●

Decreasing concentration of the inhaled anesthetic gas Rising FiO2 if the driving gas is O2 Falling FiO2 if the driving gas is air or an O2-air mixture Hyperventilation or hypoventilation

If the bellows is mismounted or a hole develops in it, the O2 used to power the bellows is directly connected to the circuit gases. Because the driving gas is at a higher pressure, it enters the bellows and mixes with the circuit gases. It therefore dilutes the anesthetic gases in the circuit and raises the FiO2, unless air is used as the driving gas, in which case the FiO2 would fall (see also Chapter 123). The main result of a leaking bellows is its inability to hold volume after the O2 flush valve is used to fill it. Although such a malfunction could cause hypoventilation, it is more likely that the driving gas will hyperventilate the patient. This occurs because the bellows moves inadequately to operate the sensing mechanism, and large tidal volumes are delivered. Also, a hanging bellows can entrain room air during expiration if there is a circuit disconnection or leak. A leak caused by a hole is more likely in an old, wornout bellows. A hole in a new bellows might result from inadequate inspection at the factory. Mismounting may occur if the person mounting the bellows is not familiar with the equipment. Because the bellows may be changed when an adult case follows a pediatric case, or vice versa, this is a time to be especially vigilant for problems related to mismounted bellows. VENTILAOR FAILURE

Figure 130–1 ■ The threshold pressure alarm limit (TPAL; dashed lines) delineates the airway pressure level at which inspiration is detected. When the TPAL is adjustable, it should be set at less than 5 cm H2O below the peak inspiratory pressure (setting A). With a correct TPAL setting, a reduced peak airway pressure breath, such as that occurring in the presence of an airway breathing system leak (second breath), will be sensed as being absent, and the apnea alarm will sound if the condition continues. However, if the TPAL is too low (setting B), the reduced breath will be detected, but the ventilator alarm will not sound. Appropriately high TPAL settings allow the alarm to be triggered when a leak in the system causes a reduction in peak inspiratory pressure, even with an airway pressure waveform.

The ventilator control assembly can be the cause of ventilator failure due to electrical or mechanical problems. Total electrical failure is easily recognized, but partial mechanical problems due to internal leaks or faulty valves may be more difficult to discern.

Risk Assessment Some circumstances are associated with greater risk of ventilator problems. Failure to correctly set the ventilator on-off

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switch or the changeover valve may occur in the following circumstances: ● ● ● ●

Soon after induction After a period of manual ventilation When the anesthetist is distracted When multiple providers are present

The period of greatest risk is immediately after induction, after bilateral breath sounds have been confirmed and the anesthetist is distracted by placing other monitors or by the patient’s hemodynamic instability. Resuming ventilation after coronary artery bypass is another period of high risk, because the ventilator has been off for a lengthy period. The “inverse anesthetist ratio” states that the care given to the patient is inversely related to the number of anesthetists present. When multiple anesthesia personnel are present, each may assume that someone else turned on the ventilator. Inappropriate ventilator settings often occur when beginning a pediatric case following an adult case or when beginning an adult case following a pediatric case. Wrong settings for the tidal volume or respiratory rate produce a minute ventilation that is inappropriate for that patient. At high risk is a very small pediatric patient placed on a ventilator set for a full-sized adult. The pediatric patient is put at very high risk for barotrauma, secondary to high inspiratory pressure, and hyperventilation. Conversely, an adult placed on a ventilator set for a child is at risk for severe hypoventilation.

Implications

The initial response to any problem with mechanical ventilation is to immediately switch to manual ventilation (Fig. 130-2). First, this is done using the anesthesia circuit. If the patient is still inadequately ventilated, a self-inflating manual resuscitator bag or mouth–to–tracheal tube ventilation is used. Once manual ventilation is established, the ventilator can be thoroughly inspected for the source of the error. The settings should be verified as correct for that patient; if not, they should be reset. If there is a hole in the bellows, it should be replaced immediately, or the anesthesia machine should be exchanged. It is never appropriate to repair a machine while it is in use in the operating room.

PREVENTION Preventing problems related to mechanical ventilators depends on the following: ●

●

Inspect ventilator (wrong settings, hole in bellows, and easy fix?)

Ventilation adequate

Yes. Machine checks out

No. More serious problem

Yes. New machine checks out

Replace machine

Ventilation inadequate

Self-inflating, manual resuscitator bag* (ventilation adequate)

Yes. New machine checks out

Continue case

Figure 130–2 ■ Suggested algorithm for responding to a problem with mechanical ventilation. *If a manual resuscitator bag is not immediately available, use mouth–to–tracheal tube ventilation. Solid lines, immediate action; dashed lines, remedial action. Under no circumstances should a machine be repaired while in use.

Operator vigilance Monitoring of airway pressures and expiratory volume, and appropriately set alarms Skilled routine maintenance Thorough checkout procedure performed before each case, following Food and Drug Administration guidelines: ● If a switching valve is present, test its function in both bag and ventilator mode. ● Close the pop-off valve (airway pressure leak) if necessary and occlude the system at the patient’s end. ● Test for leaks and pressure relief by appropriate cycling (exact procedure varies with the type of ventilator). ● Attach the reservoir bag at the mask fitting, fill the system, and cycle the ventilator. Ensure that the bag is properly filling and emptying.

Further Reading Brockwell RC, Andrews JJ: Complications of inhaled anesthesia delivery systems. Anesthesiol Clin North Am 20:539-554, 2002. Brockwell RC, Andrews JJ: Inhaled anesthetic delivery systems. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 298-303. Caplan RA, Vistica MF, Posner KL, et al: Adverse anesthetic outcomes arising from gas delivery equipment: A closed claims analysis. Anesthesiology 87:741-748, 1997. Dorsch JA, Dorsch SE: Understanding Anesthesia Equipment. Philadelphia, JB Lippincott–Williams & Wilkins, 1999. Ehrenwerth J, Eisenkraft J: Anesthesia Equipment: Principles and Applications. St. Louis, Mosby–Year Book, 2004.

EQUIPMENT & MONITORING

Manual ventilation (anesthesia circuit)

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MANAGEMENT

●

Mechanical ventilation failure?

Mechanical Ventilators

Prolonged absence of ventilation may lead to hypoxia. The length of time before hypoxia occurs is variable, depending on the FiO2 before apnea and the respiratory status of the patient. Other complications include severe hypotension secondary to reduced venous return and significant barotrauma from hyperinflation.

●

Most of the problems discussed here eventually cause a ventilatory abnormality, such as hypercarbia or hypocarbia.

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Scavenging Systems Isaac Azar

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Case Synopsis A 30-year-old patient is undergoing abdominal surgery under general anesthesia. Suddenly, his chest progressively expands, and the pressure in the anesthesia breathing circuit rises. The anesthesiologist immediately disconnects the patient from the breathing circuit. This releases the pressure in the breathing circuit, and the patient’s chest relaxes. While an assistant examines the anesthesia machine, the anesthesiologist ventilates the patient with an Ambu bag. Examination of the scavenging system of the anesthesia machine reveals a partial obstruction of the suction line and a faulty positive-pressure relief valve. The obstruction is released, and the relief valve is repaired. This resolves the problem, and the administration of anesthesia using the breathing circuit continues uneventfully.

PROBLEM ANALYSIS Definition Over the past 30 years, several scientific reports have suggested that adverse health effects are caused by chronic exposure to trace anesthetic agents in the operating room (OR). Although there is presently no consensus, the National Institute for Occupational Safety and Health recommends that the trace level of nitrous oxide in the OR ambient air be no higher than 25 parts per million. Primarily, this has been achieved by adding a waste anesthetic gas scavenging system to the anesthesia machine. All modern anesthesia machines are equipped with such a scavenging system. The purpose of the system is to safely dispose of the waste anesthetic gases from the breathing circuit into the wall suction. Interposed between the breathing circuit and airway pressure limiting (APL) valve and the wall suction disposal line is a scavenging interface system (Fig. 131-1). The purpose of the APL valve and the scavenging interface system is to protect the patient from negative or excessive positive airway pressures.

Breathing circuit

APL valve

Scavenging interface system

Disposal line

Wall suction

Dedicated vacuum

Ventilation grille

Through-the-wall exhaust

Figure 131–1 ■ Alternative methods of waste anesthetic gas disposal. APL, airway pressure limiting.

540

Typically, the scavenging interface system includes a reservoir that collects the waste anesthetic gases before they are discarded into the suction system. The interface system may be either closed or open. A closed system, such as that usually found on Ohmeda anesthesia machines, consists of a reservoir bag and two pressure relief valves—one positive and one negative (Fig. 131-2). An open reservoir system, such as that usually found on Dräger anesthesia machines, consists of a metallic reservoir in the form of a cylinder with open ports (Figs. 131-3 and 131-4). When a closed interface system is in use, negative pressure in the system opens the negative-pressure relief valve, which allows room air to rush into the reservoir bag. Excessive positive pressure in a closed system opens the positivepressure relief valve, which allows waste anesthetic gases to escape into the room air. In either case, opening of the relief valve restores normal atmospheric pressure in the system. The reservoir bag of a closed system also serves as an indicator of how well the interface system is functioning. If the bag is excessively distended, it indicates abnormally high positive pressure in the system. This usually occurs when the vacuum force is too weak, and the positive-pressure relief valve fails to open. When the bag is collapsed, it indicates negative pressure in the system. This usually occurs when the vacuum force is too strong, and the negative-pressure relief valve fails to open. When an open interface system is in use, the ports in the metal reservoir allow air to move in when the system pressure is negative, and they allow waste anesthetic gases to move out when the system pressure is positive. As long as the ports are free of obstructions, pressure in the system is atmospheric. If the ports are obstructed, excessive vacuum force generates negative pressure in the system. An inadequate vacuum force allows the buildup of excessive positive pressure in the system. In some hospitals, the waste anesthetic gases are discarded into the OR ventilation system. A disposal line directs the waste anesthetic gases from a scavenging interface to the OR ventilation grill. The interface system in such a scavenging system usually consists of a reservoir bag and positivepressure relief valve. If the disposal line is inadvertently

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Figure 131–2 ■ Representation of an Ohmeda anesthesia machine with a closed interface scavenging system. Inset, Exploded view of closed interface scavenging system.

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Scanning interface (detailed in inset)

Waste gas control valve Central vacuum line Waste gas flow indicator

Vacuum

Waste gas reservoir bag

Positivepressure relief valve

Negativepressure relief valve

occluded, the positive-pressure relief valve opens and allows waste anesthetic gases to escape into the room air. If the valve fails to open, the pressure in the system rises. The reservoir bag also serves as an indicator of whether the scavenging system is functioning appropriately. An overdistended bag suggests an obstructed disposal line and a faulty pressure relief valve.

Vent

APL To vacuum

Recognition

Open port

Open reservoir scavenging system

Figure 131–3 enging system.

■

Dräger anesthesia machine with an open interface scav-

Open port

Reservoir

Figure 131–4 ■ Details of the open interface scavenging system of a Dräger anesthesia machine. APL, airway pressure limiting.

EQUIPMENT & MONITORING

Whenever an abnormal pressure occurs in the breathing circuit, a rapid examination of the anesthesia machine should

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include an inspection of the scavenging system. If a closed system is in use, first the reservoir bag should be observed. If it is distended, the vacuum force is too weak and the positive-pressure relief valve is faulty. If it is empty, the vacuum force is too strong and the negative-pressure relief valve is faulty. When an open interface system is used, first examine the ports of the metallic reservoir to rule out accidental obstruction. If the OR air-conditioning is used to dispose of waste anesthetic gases, first check the reservoir bag of the interface system. If it is distended, rule out inadvertent obstruction of the disposal line by portable OR equipment and a faulty pressure relief valve. Rarely, an obstruction may occur between the APL valve and the scavenging interface system. In such a case, positive pressure builds up rapidly in the breathing circuit, despite a properly functioning interface system.

Risk Assessment The incorporation of scavenging systems in anesthesia machines has increased the risk of mechanical failure. Malfunction of the scavenging system may cause negative or excessive positive pressure in the breathing circuit.

Implications Excessive positive pressure in the breathing circuit adversely affects ventilation and may cause severe physiologic disruption and barotrauma of the respiratory system. A particularly dangerous complication of excessive positive pressure is tension pneumothorax. Negative pressure in the breathing circuit may interfere with ventilation, sucking air out of the lungs and causing alveolar collapse and pulmonary edema, with consequent severe hypoxemia.

MANAGEMENT If abnormal pressure is detected in the breathing circuit, the patient should be disconnected immediately from the anesthesia machine and, if necessary, ventilated with an Ambu bag until the problem is resolved. In the meantime, anesthesia can be maintained by the administration of intravenous drugs. If the cause of the abnormal pressure in the breathing system cannot be rapidly detected and corrected, the anesthesia machine should be replaced.

Injuries caused by abnormal pressure in the breathing circuit may be life threatening and should be promptly treated. If negative pressure causes lung collapse or pulmonary edema, this should be treated by manually applying positive-pressure ventilation with 100% oxygen. Because pulmonary edema in such cases is not associated with circulatory overload, the administration of diuretics is not necessarily indicated. If excessive positive pressure in the breathing circuit causes tension pneumothorax, a chest tube should be inserted as soon as possible.

PREVENTION In addition to regular servicing of the anesthesia machine and its scavenging system, it is important to briefly inspect the scavenging interface before the induction of anesthesia. No loose objects, such as empty plastic bags, should be allowed near the interface pressure relief valves or ports. If the OR air-conditioning system is used to discard waste anesthetic gases, it is preferable that the disposal line be kept off the floor. If the line does rest on the floor, portable OR equipment should not be parked on it. When testing the breathing circuit, any difficulty in filling or emptying the breathing bag should be evaluated carefully, and a defective scavenging system ruled out.

Further Reading Abramowitz M, McGill W: Hazard of anesthetic scavenging device [letter]. Anesthesiology 51:276, 1979. Buring JE, Hennekens CH: Health experiences of operating room personnel. Anesthesiology 62:325-330, 1985. Cohen EN, Brown BW, et al: Occupational disease among operating room personnel: A national study. Anesthesiology 41:321-340, 1974. Guirguis SS, Pelmear PL, Roy ML, et al: Health effects associated with exposure to anaesthetic gases in Ontario hospital personnel. Br J Ind Med 47:490-497, 1990. Hamilton R, Byrne J: Another cause of gas scavenging line obstruction. Anesthesiology 51:365, 1979. Mor Z, Stein E, Orkin L: A possible hazard in the use of a scavenging system. Anesthesiology 47:302-303, 1977. NIOSH: Criteria for a recommended standard-occupational exposure to waste anesthetic gases and vapors. DHWE (NIOSH) No. 77-140. Cincinnati, Ohio, National Institute for Occupational Safety and Health, 1977. Patel K, Dalal F: A potential hazard of the Drager scavenging interface system for wall suction. Anesth Analg 58:327-328, 1979. Sharrock N, Leith D: Potential pulmonary barotrauma when venting anesthetic gases to suction. Anesthesiology 46:152-154, 1977. Tavakoli M, Habeeb A: Two hazards of gas scavenging. Anesth Analg 57: 286-287, 1978.

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Humidifiers Kelly T. Shannon and Sivam Ramanathan Case Synopsis After a prolonged delay during transport, a 59-year-old woman is brought to the operating room (OR) for an exploratory laparotomy for ovarian carcinoma. A semiclosed circle system with an in-circuit humidifier is used for general anesthesia During induction of anesthesia, it becomes difficult to manually ventilate the patient, and an occlusion is noted in the humidifier circuit. Shortly thereafter, the low-pressure alarm sounds, and a “hissing” noise is heard emanating from the humidifier circuit.

PROBLEM ANALYSIS Definition

10 4

7

2

9 3

8 6

1

5

Figure 132–1 ■ Hot-water humidifier with an electrically heated wire unit placed inside the inspiratory limb of the patient circuit. 1, Soda lime absorber; 2, expiratory valve; 3, inspiratory valve; 4, breathing circuit; 5, humidifier; 6, water-fill level mark; 7, inspiratory limb with heated wire; 8, patient end; 9, thermistor probe; 10, expiratory limb. Arrows indicate the direction of gas flow within the circuit. Overheating of the inspiratory limb may lead to melting of the delivery hose, thereby causing occlusion or gas leakage.

543

EQUIPMENT & MONITORING

Heated humidification systems are commonly used during the provision of mechanical ventilation. Mechanical ventilation remains the primary modality of respiratory support during the administration of general endotracheal anesthesia. In addition, it is a hallmark of the management of critically ill patients in the intensive care unit. Mechanical ventilation leads to undue heat and moisture loss from the respiratory system, as the endotracheal tube bypasses the upper respiratory tract. This loss increases the viscosity of airway secretions, alters the activity of surfactant, and reduces ciliary motility. These events further compromise other efforts used to preserve physiologic levels of systemic hydration and temperature in anesthetized or critically ill patients. Heated humidifiers serve to maintain and even augment the temperature and humidity levels within the respiratory tract. Their action offsets the cooling and drying effects of the inspired gases. Humidifiers are typically added via an accessory hose attached to the inspiratory limb of the anesthesia machine or mechanical ventilator circuit (Fig. 132-1). This arrangement creates the potential for circuit misconnection, disconnection, occlusion, and leakage. The possibility of these adverse events, along with availability of safer warming devices, such as convective warming blankets and heat and moisture exchangers, has led to a decrease in the

use of heated humidifiers, at least in the OR. In fact, a recent survey of usage patterns in one large academic medical center revealed that heated humidifier circuits were no longer used for routine anesthetic management. Thus, their predominant use is for mechanical ventilation provided outside the OR. The primary mechanisms for heat and moisture generation define the two types of humidifiers available today: hot-water humidifiers and aerosol generators. The hot, moist environment created by these devices enhances the possibility of humidifier-related complications. Hot-water humidifiers are designed so that the inspired gases either bubble through or flow over an electrically heated reservoir of water. The types of adverse consequences possible with such a system are detailed in Table 132-1. Hot-water humidifiers may also incorporate an electrically heated wire in their hosing to prevent the cooling and condensation of water (“rain-out”) from occurring downstream, as gases flow away from the humidifier in the ventilator circuit. If this wire overheats, occlusion, leakage, melting of the hose, or fire may occur, resulting in the possible inhalation of toxic fumes or debris. A less popular type of humidifier is the nebulizer, which generates microaerosols. Ultrasonic and pneumatic nebulizers are two examples. Microaerosol nebulizers generate very small droplets of water and are capable of delivering larger quantities of water vapor to the respiratory tract than are hot-water humidifiers. This increases the likelihood of overhydration, especially in infants and children.

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Table 132–1

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Adverse Consequences of Heated Humidification Systems

Mechanical Circuit obstruction or occlusion Melting Heating coils Rain-out of water Circuit misconnection Circuit disconnection Circuit leakage

Electrical Hazard Macroshock Hose fire Burns (patient and health care workers) Toxin or debris inhalation

Thermal Respiratory mucosa injury Burning Edema Necrosis Scar or stricture formation Hyperthermia Hemorrhagic tracheitis

Humidification Water intoxication Hyponatremia Increased secretions Cilia inactivation Surfactant inactivation Atelectasis

Respiratory Mechanics Increased airway resistance Decreased forced residual capacity Decreased static compliance

Contamination Bacterial Fungal Heavy metals (tap-water usage)

Miscellaneous Capnometer failure Rain-out of water

the presence of excess leakage current in a defective humidifier, and thus may prevent macroshock. Unlike with mechanical problems, the amount of time before the harmful effects of overheating occur (thermal injury, overhumidification, bacterial contamination) ranges from hours to days. Although increases in airway resistance and pulmonary shunting, atelectasis, and arterial hypoxemia may result, changes in respiratory mechanics and blood gas oxygen tension may be immediate or delayed. Serum sodium and serum osmolality measurements help detect acute overhydration or water intoxication.

Risk Assessment The overall incidence of humidifier-associated complications is unknown. Specific factors that may increase the likelihood of humidification system failure have been identified. A humidifier hose composed of polyvinylchloride, which has a low melting point, has been linked to circuit occlusion and perforation when used with a heated wire. Acute bends in the hose, which increase the chance of direct contact between the hose and the wire, also contribute to circuit melting. The chance of a hose melting is enhanced if the humidifier is left on for an extended period with little or no active gas flow through it. In the case synopsis, the transport delay was largely responsible for the problems that occurred. The humidifier circuit melted, leading to obstruction and subsequent gas leak caused by disruption of the wall of the hose. Among the circumstances that heighten the chance of thermal or moisture-related problems is prolonged use (e.g., lengthy operations or protracted mechanical ventilation). Prolonged use also predisposes to rain-out in the delivery hose, which, if severe, may occlude the hose lumen. Bacterial contamination is more likely with the use of nonsterile water, especially if it is changed at infrequent intervals. This is more applicable to aerosol generators than hot-water systems. Similarly, the use of tap water may cause exposure to heavy metals.

Implications Additionally, bacterial and fungal contamination is a risk, because these microorganisms may be suspended within the water microdroplets. Colonization and subsequent infection may ensue.

Recognition The timely discovery of humidifier malfunction and associated mechanical problems relies on clinical vigilance and the presence and proper functioning of several safety monitors and alarms. Routine monitoring of the patient’s temperature detects hyperthermia. Humidifiers are equipped with several safety features, including alarms and automatic shut-off devices for sensing both high and low circuit temperature, as well as the low circuit pressure produced by leakage or disconnection. Anesthesia machines and mechanical ventilators also signal the presence of the high circuit pressure produced by occlusion. A line isolation monitor and ground fault circuit interrupter may uncover a grounding fault or

Thermal injury to the tracheobronchial tree may cause mucosal damage, edema, hemorrhage, and necrosis. In turn, these may lead to pulmonary edema, scar and stricture formation, shunting, increased arterial-alveolar oxygen difference, and arterial hypoxemia. Positive water balance also has adverse effects on the lungs. Overhydration may precipitate pulmonary edema; it also impairs ciliary motility and surfactant activity and increases airway secretions. The accumulation of secretions can obstruct the airway and promote atelectasis. Pulmonary shunting, increased arterial-alveolar gradient, and arterial hypoxemia are worsened. The loss of respiratory mucosa and the inactivation of the mucociliary elevator also predispose the lungs to infection. Water intoxication and the subsequent development of hyponatremia and hypo-osmolality can have cardiac and central nervous system manifestations. Hyponatremia may impair normal cardiac and central nervous system electrophysiology. Cardiac effects include slowed conduction, widened QRS complexes, and elevated ST segments. Arrhythmias are

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more common. Further, myocardial contractility may be depressed. Possible adverse central nervous system effects are cerebral edema, altered sensorium, seizures, and loss of consciousness.

MANAGEMENT Emergent reestablishment of the anesthetic or ventilatory circuit’s integrity is imperative if occlusion or leakage occurs. If hyperthermia is suspected, heating of respiratory gases should be lowered or even terminated. Thermal injury to the respiratory tract necessitates the provision of supplemental oxygen, further mechanical ventilatory support, and positive end-expiratory pressure to maintain normal oxygenation until the injury resolves. Diagnostic or therapeutic bronchoscopy for secretion and debris removal may be required. An appropriate prophylactic antibiotic regimen is also encouraged. Therapy to counteract the positive water balance depends on the severity. If pulmonary edema and cardiac instability are present, invasive monitoring of arterial blood pressure and ventricular filling pressures may help guide treatment. Vasopressor and inotropic support may be warranted. If dilutional hyponatremia is extreme, infusion of loop diuretics (e.g., furosemide) or hypertonic saline (3% to 5%), or both, may be therapeutic.

PREVENTION

Humidifiers

545

should evaluate all humidifiers for microshock and macroshock hazards. A line isolation monitor and ground fault circuit interrupter should be incorporated into the electrical system to prevent macroshock. The lowest heat setting on the humidifier that sustains a normal thermal environment should be used. Abandoning the use of a heated humidifier in favor of incorporating a heat and moisture exchanger (HME, or “artificial nose”) in the circuit has become common practice. HMEs are not associated with electrical hazards or problems related to overhydration. They are designed to passively conserve moisture already present in the respiratory tract; temperature conservation, however, is negligible. HMEs are small, disposable, inexpensive, and user-friendly. Moreover, they may provide bacterial and viral filtration. Commercially available HMEs are quite capable of providing sufficient humidification under most circumstances, especially when low fresh gas flow rates are used. Composite hygroscopic and hydrophobic membrane filters are the most commonly used HMEs. However, there are some trade-offs. The large-pored hygroscopic filters offer more efficient heat and moisture maintenance, whereas the small-pored hydrophobic membrane filters enhance microbe barrier and filtration properties. Both types of filters add dead space and resistance to the circuit. Further, there is the potential for them to become occluded with circuit water or pulmonary secretions.

Further Reading Bench S: Humidification in the long-term ventilated patient: A systematic review. Intensive Crit Care Nurs 19:75-84, 2003. Dick W: Aspects of humidification: Requirements and techniques. Int Anesthesiol Clin 12:217-239, 1991. Dorsch JE, Dorsch SE: Humidification methods. In Dorsch JE, Dorsch SE (eds): Understanding Anesthesia Equipment. Baltimore, Williams & Wilkins, 1999, pp 287-308. Klein EF, Graves SA: “Hot pot” tracheitis. Chest 65:225-226, 1974. Lemmons HJM, Brock-Utne JG: Heat and moisture exchange devices: Are they doing what they are supposed to do? Anesth Analg 98:382-385, 2004. Peterson BD: Heated humidifiers: Structure and function. Respir Care Clin N Am 4:243-259, 1998. Ramanathan S: Humidification and humidifiers. In Ehrenwerth J, Eisenkraft JB (eds): Anesthesia Equipment: Principles and Applications. St. Louis, Mosby–Year Book, 1992, pp 172-197. Rhame FS, Streifel A, McComb RC, et al: Bubbling humidifiers produce microaerosols which can carry bacteria. Infect Control 7:403-406, 1986. Ricard JD, Cook D, Griffith L, et al: Physician’s attitude to use heat and moisture exchangers or heated humidifiers: A Franco-Canadian survey. Intensive Care Med 28:719-725, 2002. Shelly MP, Lloyd GM, Park GR, et al: A review of the mechanisms and methods of humidification of inspired gases. Intensive Care Med 14:1-9, 1988. Wong DH: Melted delivery hose: A complication of a heated humidifier. Can J Anaesth 35:183-186, 1988.

EQUIPMENT & MONITORING

Many of the potential complications related to heated humidifiers can be avoided by vigilant and careful clinical practice. Strict adherence to published standards and specific device manuals on the safe operation of these devices is mandatory. A detailed inspection of the components of the humidifier, the humidifier hose, and its connections is advised. The anesthesia delivery system and the mechanical ventilator circuit should be tested for leaks immediately before use. Prolonged periods of circuit inactivity while the humidifier is on should be avoided. Instead, the humidifier should be turned on just before the patient is connected to the circuit. Acute bends in the humidifier hoses should be averted to minimize contact between the hose tubing and the heated wire. If rain-out occurs, the breathing circuit hoses should be periodically emptied to prevent occlusion. This also minimizes capnometer failure or damage due to accumulated water in the circuit. Only sterile water should be used in the humidifier, and it should be changed at frequent intervals. When manipulating any humidifier components, close attention to aseptic technique must also be maintained. Periodically, the clinical engineering department

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Intravenous Drug Delivery Systems

133

Rajamani Sethuraman Case Synopsis A 35-year-old man weighing 90 kg undergoes maxillofacial fracture fixation. He receives oxygen, air, propofol, and remifentanil infusion (0.5 μg/kg per minute) for 4 hours. The infusions are stopped 10 minutes before the end of surgery. At the conclusion of the operation he wakes up restless and combative and requires 15 mg of morphine to make him comfortable.

Definition The patient described in the case synopsis awoke with significant pain due to the redistribution and elimination of remifentanil. These two factors play an important role in the declining plasma concentration of the drug, which in turn is affected by the duration of infusion. However, the latter is not so important with remifentanil, which is quickly eliminated by plasma esterases. The bolus dose before initiation of an infusion to produce a given drug plasma concentration is calculated by the following formula: Amount = Ct × VD, where Ct is the target concentration and VD is the volume of distribution for a given drug. The trouble with this concept is that several volumes must be taken into account—those in the central and peripheral compartments. As time progresses, a steady-state concentration in the VD is reached. Calculating a dose according to initial VD would be too low, just as the dose would be too high if calculated using the final VD. Hence, this introduces the concept of VD at the drug’s peak effect, which can be calculated due to the fact that plasma and effector site concentrations are similar at the time of peak effect. Maintenance infusion rate (Mir) is calculated as follows: Mir = Ct × Cls, where Ct is the target concentration and Cls is the rate of clearance. The context-sensitive half-time is the time it takes for the plasma concentration to decrease by 50% after stopping a continuous infusion that maintained a constant concentration in plasma. The concept of context-sensitive half-time needs to be understood when using a continuous infusion of anesthetic drugs that exhibit multicompartmental kinetics. In this setting, the net distribution of the drug in and out of the peripheral compartments varies according to the duration of the infusion. The “context” in this instance is the duration of 546

the infusion (Fig. 133-1). In certain situations, decreases in plasma concentration other than 50% may be more clinically relevant. A more general term, context-sensitive decrement time, applies to this situation. Here, a decrease in the effector site concentration occurs, as noted by a falling plasma concentration, which is presumed to model the decrease at the effector site. The context-sensitive decrement time provides a clinically useful framework for understanding the relationship between the duration of the infusion and the time before recovery occurs (Fig. 133-2). Automated drug delivery systems can provide precise predictions of the time required for the plasma (or effector site) concentration to change, based on the actual dosing regimen. These predictions can help clinicians terminate the infusion at the appropriate time. However, the postinfusion kinetics do not correlate with the elimination half-life. This is clearly demonstrated by a remifentanil infusion, because even after 3 hours, the context-sensitive half-time is shorter than its terminal half-life.

100 Time to 50% drop (min)

PROBLEM ANALYSIS

Fentanyl Alfentanil Sufentanil Remifentanil

75

50

25

0 0

100

200

300

400

500

600

Infusion duration (min)

Figure 133–1 ■ Context-sensitive half-times as a function of infusion duration for each of the pharmacokinetic models simulated. Solid and dashed lines are used only to permit overlapping lines to be distinguished. (From Glass PA, Shafer SL, Reves JG: Intravenous drug delivery systems. In Miller RD [ed]: Anesthesia, 5th ed. New York, Churchill Livingstone, 2000.)

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Intravenous Drug Delivery Systems

Fentanyl

Recovery time (min)

547

Alfentanil

% % % % 0% 80 70 60 50 4

120

30%

90

60

0%

8

120

0%

7

90

60%

60

50%

20% 40%

30

30

30% 20% 10%

10%

0

0 Sufentanil 90%

120

Recovery time (min)

Figure 133–2 ■ Recovery (decrement time) curves for fentanyl, alfentanil, sufentanil, and remifentanil showing the time required for decreases of a given percentage (labeled for each curve) from the maintained intraoperative effector site concentration after termination of the infusion. After the loading dose, an initially high infusion rate should be used to account for the redistribution and then titrated to the lowest infusion rate that will maintain adequate anesthesia or sedation. For sedation, the loading dose is given over 5 to 10 minutes and adjusted according to the patient’s response. For anesthesia, midazolam is administered with an opiate. (From Glass PA, Shafer SL, Reves JG: Intravenous drug delivery systems. In Miller RD [ed]: Anesthesia, 5th ed. New York, Churchill Livingstone, 2000.)

■

80%

Remifentanil

70%

60%

25 20

90

90%

15 50%

60

80%

10 70%

40%

30 30% 20% 10%

0 0

120

240

360

480

60% 50% 40% 30% 20% 10%

5 0

600

0

120

240

360

480

600

Time since beginning infusion (min)

Excessive opioid administration is characterized by slow respirations, bradycardia, and pinpoint pupils. This situation responds to the administration of an opioid antagonist. With the advent of shorter-acting opioids (e.g., remifentanil), an opposite response may be noted if the infusion is terminated too early and further analgesia is not instituted in time. Although it is important to understand the pharmacokinetics of the drugs used, one should not overlook practical errors in the setup of the system. The most common problems are as follows: ● ● ● ● ● ● ●

Disconnected intravenous (IV) line Air in the IV line Line occlusion Low battery Syringe or cassette disengagement Tubing disconnection Empty carrier fluid

Another factor that may influence the onset of anesthesia and subsequent dose adjustment is the proximity of the infusion’s connection to the patient. When an infusion is connected in a piggyback fashion, the rate at which the drug reaches the circulation is directly related to the IV flow rate and, inversely, to the volume of IV dead space between the infusion connection and the IV cannula. Therefore, the

connection should be as close to the IV catheter as possible to minimize the effect of carrier IV fluid rate on drug delivery. Because of all these issues, vigilance with regard to the IV drug delivery device is very important. Additionally, most manufacturers have installed audible alarms for an idle pump, battery failure, and empty syringe.

Risk Assessment The context-sensitive half-time and context-sensitive decrement time play an important role in running IV drug infusions safely. For most IV anesthetic agents, a 50% reduction in concentration is required before the patient returns to an awake state, and an 80% to 90% decrease is required before a patient can be safely discharged in an outpatient setting. Drug elimination half-lives are usually consistent. However, this is not true for context-sensitive half-times and contextsensitive decrement times. As in the case synopsis, the contextsensitive decrement time is shorter for remifentanil compared with other opioids, owing to its rapid metabolism as well as its minimal translocation to peripheral compartments. Complications related to the use of IV drug delivery systems are often user related. If a routine checklist is followed, these errors can be minimized (Table 133-1). Use of AC power, use of a dedicated IV cannula, removal of all air from the tubing and syringes, and constant vigilance should prevent interruptions in flow.

EQUIPMENT & MONITORING

Recognition

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Common Problems with Intravenous Drug Delivery Systems and Recommended Preventive Measures

Problem

Reason

Prevention

Pump setup errors

Error in concentration or rate

Underinfusion

Drawing up and pump-setting errors Faulty device

Two-person check Use prefilled syringes or bags Double-check units and rates (e.g., mg/hr or mL/hr) Check service date Check that clamp and delivery mechanism movement is smooth Normally, alarms sound when switched on, performing self-check

Delayed onset because of mechanical slack Air in line Occlusion Overinfusion

Faulty device Siphonage

Postocclusion bolus Bolus drug treatment Communication

Absent or incorrect label Absent or incorrect record Absent or incorrect information during patient transfer or handover of care

Purge and prime the line Check the IV line Check the need to increase the occlusion pressure limit As above Check for cracked syringe; check that syringe barrel and plunger are firmly engaged Position the device at the same level as the patient Use an antisiphon valve Release the line pressure before relieving the obstruction Add an antireflux valve in the second line Place the pump at the level of the patient Disconnect the infusion line whenever the syringe is removed from the pump Use correct labeling, color coding Check that the volume infused matches the dose and duration of infusion Provide complete and accurate information regarding patient’s course before transfer of care

Modified from Keay S, Callander C: The safe use of infusion devices. BJA Contin Educ Anaesth Crit Care Pain 3:81-85, 2004.

Implications Commercial target-controlled infusion systems are now available, at least in Europe. Diprifusor is a total IV anesthesia system that can be set to achieve a desired plasma concentration of propofol. The system can be set according to the patient’s age and ideal weight and the plasma concentration desired by the clinician. It is widely used in Europe but is awaiting approval in the United States. This system can also predict how long it will take for the patient to wake up once the infusion is stopped. There are also newer closed-loop systems that can adjust the rate of infusion according to feedback from auditoryevoked potentials and a bispectral index. In the near future,

these systems will be part of everyday anesthesia practice. Their pumps are driven by pharmacokinetic models using software algorithms, and pharmacokinetic parameters for various drugs can be programmed into the devices. Figure 133-3 illustrates the potential sources of error in pharmacokinetic model drug delivery systems. An understanding of pharmacokinetics is important when giving any drug, but this is especially true with IV drugs. For example, remifentanil has a different elimination profile compared with fentanyl, alfentanil, and sufentanil. Because this difference was not considered for the patient in the case synopsis, the result was poor analgesia upon recovery.

Figure 133–3 ■ Commercially available target-controlled infusion systems have computer functions incorporated into the device itself. Potential sources of error in drug delivery systems based on pharmacokinetic models are shown. (From Glass PA, Shafer SL, Reves JG: Intravenous drug delivery systems. In Miller RD [ed]: Anesthesia, 5th ed. New York, Churchill Livingstone, 2000.)

Pharmacokinetic Infusion modeling algorithm Infusate Software

Incorrect concentration

Host computer

Infusion device

Patient

Power failure Hardware failure Software “bug” Algorithmic error Communication error

Inaccurate delivery Malfunction Communication error

IV line disconnection Pharmacokinetic variability Acute pharmacokinetic changes Sampling error/assay error

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Table 133–2

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Intravenous Drug Delivery Systems

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Manual Infusion Schemes When Combined With 66% Nitrous Oxide and Oxygen Anesthesia

Sedation or Analgesia

Drug

Loading Dose (μg/kg)

Maintenance Dose (μg/kg/min)

Alfentanil Fentanyl Sufentanil Remifentanil Ketamine Propofol Midazolam Methohexital

50-150 5-15 0.25-2 0.5-1 1500-2500 1000-2000 50-150 1000-1500

0.5-3 0.03-0.1 0.01-0.05 0.1-0.4 25-75 50-150 0.25-1.5 50-150

Loading Dose (μg/kg) 10-25 1-3 0.1-0.5 *

500-1000 250-1000 25-100 250-1000

Maintenance Dose (μg/kg/min) 0.25-1 0.01-0.03 0.005-0.01 0.025-0.1 10-20 10-50 0.25-1 10-50

*

No loading dose necessary if used for IV sedation.

MANAGEMENT Drug delivery failure is investigated by asking the following questions: ● ● ● ● ●

Is the pump working? Is the drug physically moving? Is the carrier fluid moving? Are connections secure and not leaking? Is the vascular access patent?

PREVENTION If one bases the loading dose on the initial volume of distribution, an incorrect dose may be given. Equilibration with

Further Reading Eyres R: Update on TIVA. Pediatr Anesth 14:374-379, 2004. Glass PSA, Shafer SL, Reves JG: Intravenous drug delivery systems. In Miller RD (ed): Anesthesia, 5th ed. New York, Churchill Livingstone, 2000. Kapila A, Glass PSA, Jacobs J, et al: Measured context sensitive half-times of remifentanil and alfentanil. Anesthesiology 83:968-975, 1995. Keay S, Callander C: The safe use of infusion devices. BJA Contin Educ Anaesth Crit Care Pain 3:81-85, 2004. Leslie K, Absalom A, Kenny GNC: Closed loop control of sedation for colonoscopy using the bispectral index. Anaesthesia 57:693-697, 2002. Milne SE, Kenny GNC: Future applications for TCI anaesthesia. Anaesthesia 53:56-60, 1998.

EQUIPMENT & MONITORING

If the cause of a failure cannot be identified and corrected quickly, one should switch to an alternative anesthesia technique. If the patient is in pain because the infusion was turned off too early, supplemental analgesia and anesthesia should be instituted as appropriate. Use of tagged and prefilled syringes avoids incompatibility with commercial target-controlled infusion systems. Target-controlled infusion systems need to be reset in between patients; otherwise, the wrong patient information will be used by the infusion pump. Total IV anesthesia infusion pumps are associated with a median absolute performance error, which represents over- or underinfusion. Adequate depth of anesthesia must be maintained while using total IV anesthesia, especially when the patient is paralyzed. Awareness of the potential problems listed in Table 133-1 will help avoid most errors.

other compartments should be taken into account when calculating the dose. Titration of doses and infusion rates should be modified according to clinical requirements. Over time, as the peripheral compartments equilibrate with the plasma concentration, the infusion rate must decrease in order to maintain the desired concentration at the effector site. This is achieved by understanding the pharmacokinetic and dynamic characteristics of individual drugs and patients and by titrating the infusion to specific effects, similar to using an inhalation anesthetic end-tidal concentration analyzer. Unfortunately, unlike with the latter, there is no in-line plasma drug concentration analyzer. Examples of some dosing regimens are given in Table 133-2. Familiarity with IV drug delivery systems will avoid the peaks and troughs of intermittent IV bolus dosing, ultimately improving the patient’s hemodynamic stability and recovery time, reducing IV drug usage, and increasing patient satisfaction.

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Patient Warming Systems Michael P. Eaton and Stewart J. Lustik

134

Case Synopsis A 26-year-old man is brought to the operating room emergently for the treatment of injuries sustained in a motor vehicle accident. The hose of a forced-air warming system had been placed between the patient’s legs, unattached to the blanket, and the unit was turned on to the maximum setting. Postoperatively, the patient is noted to have partialand full-thickness burns to the inner thighs.

PROBLEM ANALYSIS Definition Perioperative hypothermia is known to be associated with significant increases in morbidity. Thus, the prevention of hypothermia is an important goal of anesthetic care, but the use of devices to prevent hypothermia is not without risk. The primary complication resulting from these devices is tissue burns. Other complications include hyperthermia, hypothermia (from incorrectly set or malfunctioning devices), and electrocution. Patient warming devices can be divided into two main categories: (1) items not designed for patient warming that are nonetheless used for that purpose, and (2) devices specifically designed and manufactured for the purpose of preventing and treating hypothermia. In the American Society of Anesthesiologists (ASA) closed claims analysis of injuries caused by patient warming devices, the former category accounted for the majority of claims. Included in this category are the following: ● ● ●

Heated intravenous (IV) solution bags Heated bottles of irrigating or other fluids Reheated “hot packs”

Devices specifically designed and manufactured for the prevention and treatment of hypothermia include the following: ● ●

● ● ● ● ●

Circulating water blankets Blankets or pads containing electrical heating elements (hot pads) Forced-air warming blankets Radiant heaters Regular or reflective blankets Breathing circuit heated humidifiers Intravenous fluid warmers

The last two devices are discussed in Chapters 132 and 135, respectively. Table 134-1 provides further details about the mechanism of injury, risk factors, and preventive measures for some of the listed devices.

Recognition Intraoperative hyperthermia and hypothermia are recognized by continuous monitoring of the patient’s core temperature. 550

The existing ASA standards require temperature monitoring whenever temperature instability is expected. Unfortunately, recognition of burns usually occurs postoperatively, when it is too late to prevent the injury. Typically, patients complain of pain in the burn-injured area. Analgesics given to treat pain related to surgery may mask pain due to a burn injury and delay the diagnosis. Inspection of the patient’s back or other area of contact at the end of the procedure is important whenever a warming device has been used. Early recognition may allow aggressive treatment to prevent infection, which has the potential to be life threatening.

Risk Assessment Risk from the two categories of warming devices seems to accrue to different patient groups. In the closed claims analysis of burns from heated IV solution bags, the average patient was a female, age 38 years, having surgery for which significant hypothermia would not be expected. The primary risk factor for these patients was the use of a device that was not intended for the warming of patients. Frequently the bags were kept in blanket warmers or ovens whose temperature was poorly regulated. Alternatively, they were heated in microwave ovens with no temperature control. A recent survey of hospitals using heated IV bags perioperatively found that several institutions allowed these bags to be heated to more than 50°C. Two hospitals kept bags at temperatures higher than 70°C, which would produce burns within only a few seconds of exposure (Fig. 134-1). Injury from devices designed for patient warming is more likely to be related to patient factors or to device malfunction or misuse. A search of the Food and Drug Administration’s Manufacturer and User-Facility Device Experience (MAUDE) database for reports of injuries from one company’s forcedair warming device found that in 24 of 30 cases in which the cause of injury could be determined with some certainty, the device was used without the blanket “hosing” or otherwise contrary to the manufacturer’s recommendations. A common patient factor is the likelihood of poor local tissue perfusion at the site of contact with the warming device. These injuries are usually most severe in areas overlying bony prominences. Patients undergoing vascular surgery, diabetic patients, and those having procedures involving cardiopulmonary bypass are at increased risk for thermal injury related to warming devices. These patients

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Table 134–1

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551

Patient Warming Systems

Injury from Patient Warming Devices

Device

Mechanism of Injury

Risk Factors

Preventive Measures

Heated IV solution bags Electrical resistance heating pads

Conduction heat transfer Conduction heat transfer Electrocution

Overly heated solutions High settings Device malfunction

Circulating water blankets

Conduction heat transfer

Heat lamps

Radiant heat transfer

Patients with poor tissue perfusion High heat output from machine Machine malfunction Too close to patient Lamp modified

Forced-air warmers

Convective heat transfer

Do not use Use only for awake, alert patients Use lowest effective settings Check before each use Perform routine maintenance Use on top of patient, rather than beneath (to eliminate pressure component of injury) Use lowest effective settings Check before each use Perform routine maintenance Maintain proper distance from patient as per manufacturer’s recommendations Use recommended diffuser or lens Use blanket only from the same manufacturer Use only operating room-approved machine on lowest effective setting Use lower settings on patients with vascular insufficiency Do not use distal to tourniquet or cross-clamp

No blanket or wrong blanket used PACU machine or high settings used Patients with poor (or no) tissue perfusion

PACU, postanesthesia care unit.

have poor regional tissue perfusion related to their disease state, surgery, or cardiopulmonary bypass, which allows local temperature to increase to the point of injury because blood flow is inadequate to redistribute applied heat. Pressure applied to the skin at the site of contact with the warming device also compromises perfusion and increases the likelihood of injury. The MAUDE database showed that of six reports of injury caused by a new circulating water system, all six identified pressure at the contact point as a contributing factor.

EQUIPMENT & MONITORING

Figure 134–1 ■ Time required for contact with an object at various temperatures to produce burn injury. (Data from Moritz AR, Henriques FC Jr: Studies of thermal injury. II. The relative importance of time and surface temperature in the causation of cutaneous burns. Am J Pathol 23:695-720, 1947.)

Patients at the extremes of age also appear to be at higher risk for thermal injury, most likely because they are at increased risk for the development of hypothermia and are therefore more likely to have heating devices applied during surgery. Elderly patients also may suffer from poor tissue perfusion, as discussed earlier. Device malfunction may cause injury if proper routine maintenance has not been performed or if the equipment is not used according to the manufacturer’s directions. Even properly used and maintained machines may produce injury

70

65 TISSUE INJURY 60

°C

55

50

45

Seconds

40 1

Hours

Minutes 10

100

1,000

Time, Seconds (Log Scale)

10,000

100,000

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if tolerances allowed by the device exceed the ability of tissue to safely absorb and transfer the energy. This is especially likely when high temperature gradients exist between the device and the patient. Some commonly used circulating water blankets allow water temperatures as high as 48°C, even when properly calibrated and maintained. Temperatures greater than 45°C may predictably produce thermal injury, depending in part on the time of exposure (see Fig. 134-1). Patient warming systems draw high levels of electrical current, and poorly maintained devices or those contaminated with fluids may overheat and cause a fire, presenting a hazard to the caregivers as well as to the patient.

Implications Patients having major vascular procedures or those involving cardiopulmonary bypass often have such diminished cardiovascular reserve that major burns can be a fatal complication. Less severe burns can also cause major morbidity. Permanently disfiguring scars that result from well-intended but ill-advised warming methods can put practitioners at significant medicolegal risk. Hyperthermia may cause an increase in cardiac and respiratory work and oxygen demand that produces undue stress on patients with limited physiologic reserves. Vasodilatation and sweating may produce relative or absolute hypovolemia and acidosis, and a hypermetabolic state may cause hypoglycemia. Extreme hyperthermia may result in central nervous system damage and death.

Injuries from approved patient warming devices are more difficult to prevent, but attention to a few important details should make injury unlikely: ●

●

●

●

●

●

●

MANAGEMENT Upon recognition that a burn injury has occurred, prompt referral to a physician skilled in the treatment of burns is essential. The proper management of burns is the subject of many textbooks and is not discussed further. Management of hyperthermia includes turning off or removing the warming device from the patient and uncovering as much of the patient as is practical under the circumstances. Active cooling is rarely necessary if overzealous warming is the sole reason for the elevated temperature. If the temperature elevation is severe or refractory to passive cooling, other causes, such as infection, sepsis, or malignant hyperthermia, should be sought.

PREVENTION The best management for injury related to patient warming devices is prevention. The ASA closed claims analysis of such injuries found that in 17 of 28 cases, care was judged to be substandard. This was the finding in all but one case of burns resulting from the application of heated IV solution bags or bottles. These devices should never be used for patient warming; they are not intended for that purpose, they are inefficient, and they are associated with an unacceptably high risk of patient injury.

●

All devices should be maintained as recommended by the manufacturer. Any machine that fails safety testing during routine maintenance should be removed from service immediately. The anesthesia provider responsible for the patient’s care should personally check the settings of the machine used. The provider should be familiar with and adhere to the manufacturer’s recommendations for use of the device. No alterations in the device should be made unless they are approved by the manufacturer. Intraoperatively, constant vigilance must be maintained to ensure that portions of the heating devices not intended for direct patient contact, such as the tubing for a water blanket or the hose of a forced-air mattress, do not touch the patient. When possible, water blanket devices should be used on top of the patient rather than beneath. This should minimize the risk of poorly perfused tissue being in contact with the device. This should also enhance the efficacy of the device, because operating table mattresses already provide adequate insulation, and the primary loss of a patient’s heat is into the room. In fact, warming devices generally act by decreasing or eliminating the loss of the patient’s own metabolic heat rather than by adding extrinsic heat. Pressure (e.g., from positioning aids) should not be put on parts of the body in contact with warming devices. That is, water or forced-air warming blankets should not be applied until the patient has been properly positioned for the planned procedure. Warming devices should not be placed on any part of the body that is distal to a tourniquet or cross-clamp, because large device-tissue temperature gradients can develop, with resultant injury.

Further Reading Chaney FW, Posner KL, Caplan RA, Gild WM: Burns from warming devices in anesthesia: A closed claims analysis. Anesthesiology 80:806-810, 1994. Crino MH, Nagel EL: Thermal burns caused by warming blankets in the operating room. Anesthesiology 29:149-150, 1968. Hewitt FW: A lecture on the aethetics of anesthetics. Lancet 1:623-626, 1910. Moritz AR, Henriques FC Jr: Studies of thermal injury. II. The relative importance of time and surface temperature in the causation of cutaneous burns. Am J Pathol 23:695-720, 1947. Raphael DT, Ayoub N: Storage of plastic intravenous solution bags in operating room warmers. Anesth Analg 84:S203, 1997. Sessler DI: Temperature monitoring. In Miller RD (ed): Anesthesia, 3rd ed. New York, Churchill Livingstone, 1990, pp 1227-1242. US Food and Drug Administration: Manufacturer and User-Facility Device Experience database (MAUDE). Available at http://www.accessdata. fda.gov/scripts/cdrh/cfdocs/cfMAUDE/search.cfm?searchoptions=1.

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135

Rapid Fluid and Blood Delivery Systems S. Devi Chiravuri Case Synopsis A 65-year-old man is brought to the operating room for emergent repair of a ruptured abdominal aortic aneurysm. The patient is intubated, hypothermic (34.5°C), and hypotensive (blood pressure 85/60 mm Hg). Volume resuscitation is instituted with warmed intravenous (IV) fluids under pressure using a Level 1 System 1000 IV fluid warmer. Before skin incision, the blood pressure drops to 60/30 mm Hg, and the end-tidal carbon dioxide (ETCO2) drops precipitously from 35 to 10 mm Hg, suggesting a massive venous air embolus.

PROBLEM ANALYSIS Definition

● ● ● ● ● ●

Systemic hypotension Increased central venous or pulmonary artery pressures Arrhythmia Hypoxemia Acute decrease in ETCO2 Decrease in pulmonary compliance

HYPERVOLEMIA Hypervolemia can cause initial hypertension, but this may be followed by hypotension as left ventricular preload and end-diastolic volume increase and eventually drop off the Frank-Starling curve (forward left ventricular failure). If central monitoring is in place, elevated pulmonary artery pressures and pulmonary capillary wedge pressures are seen. HYPOTHERMIA

OR

HYPERTHERMIA

Recognition

Hypothermia occurs when transfusion is conducted without vigilant temperature monitoring or if the heating mechanism is faulty. This can cause coagulopathy, arrhythmias, or peripheral vasoconstriction. Hyperthermia can be as detrimental as hypothermia. Elevated temperature is detected with temperature monitoring. Core monitoring is more accurate than skin temperature monitoring. Hyperthermia can cause denaturing of molecules such as hemoglobin and cause hemoglobinemia and hemolysis. Clinically, it can manifest as sweating, vasodilatation, and hemoglobinuria.

VENOUS AIR EMBOLISM

ELECTRICAL SHOCK

Venous air embolism is a condition that is well described in anesthesia (see also Chapters 168 and 175). It occurs when air enters the venous system, either via entrainment at the operative site or inadvertently via IV catheters; this is more

Electrical shock is not unique to RFBD devices. It can occur with any electrical device that comes in contact with patients. Electrical shock may cause pain, tetanus, thermal injury, or transient arrhythmias.

● ● ● ● ● ●

Air embolism Hypervolemia or overtransfusion Overheating of fluids Hypothermia Hemolysis Electrical shock

553

EQUIPMENT & MONITORING

Rapid fluid and blood delivery (RFBD) devices are used when IV fluid or blood must be delivered at rates greater than those attainable with free-flow or IV pressure bag devices. Contemporary RFBD devices allow for flows of 750 mL/minute, with the ability to “dial in” flow rates. In addition to high flow, they allow one to select or set the temperature of the infusate. High flows are provided by pressure. RFBD pressurization can be achieved by two methods: external pneumatic pressurization and occlusive roller pumps. Heating is provided by either water bath conduction heat exchange or a magnetic induction heater. In addition to delivering high-volume flow rates and heating the fluids, RFBD devices must be able to detect or vent air. Air traps are able to extract small volumes of entrained air, but larger volumes may exceed the capacity of the trap. One model, the FMS2000 (Belmont Instrument Corporation, Billerica, Mass.), uses a reservoir from which the fluids are delivered, and it alerts the user when the reservoir is nearly empty (Fig. 135-1). Potential complications associated with the use or malfunction of RFBD devices include the following:

likely with central than with peripheral access. This air travels to the heart and can significantly decrease cardiac output. It can also travel via a patent foramen ovale to the left side of the heart and up to the cerebral circulation, potentially causing cerebral ischemia or stroke. Detection of air can be via echocardiogram, precordial Doppler, or a sudden drop in ETCO2. Signs of a venous air embolus include the following:

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● ● ● ●

Support blood pressure if hypotension occurs. Place the patient in a dependent or decubitus position. Turn off the nitrous oxide (if in use). If a central venous line is in place, attempt to aspirate air.

If hypothermia is present, a heating mattress and forced-air warming blanket can be used (see Chapter 134). Hyperthermia is treated by switching off any heating devices. Hemolysis has several causes: shear stresses from overpressurized infusion, overheating of blood and blood products, or transfusion reactions or mismatch. Treatment includes the following: ● ● ● ● ●

Discontinue the transfusion. Notify the blood bank and recheck the crossmatch. Maintain the urine output. Alkalinize the urine. Monitor for signs of disseminated intravascular coagulation.

Hypervolemia can present as pulmonary or circulatory collapse. Treatment includes the following: ● ● ● ● ●

Circulatory support Diuretics Vasodilator therapy Assisted ventilation or positive-pressure ventilation In extreme cases, phlebotomy

PREVENTION

MANAGEMENT

Vigilance is key to minimizing risk in the operating room. Meticulous venting of air before connecting IV lines and infusion devices is an important step. Careful monitoring of ETCO2 is a necessary precaution. Hyperthermia and hypothermia can be prevented by aggressive treatment and core body temperature monitoring. Skin temperature monitoring can give false information, especially when there is vasoconstriction. It is also important to pay close attention to the patient’s volume status. Urine output and central venous pressure should be monitored continuously when an RFBD system is used. The risk of electrical shock can be minimized with vigilance and proper maintenance of all electrical devices in the operating room. Quick checks of the insulation and ground fault detection alarms are a good start. Finally, the importance of familiarity with and proper use and maintenance of RFBD devices cannot be stressed enough. Attending in-service training programs related to such equipment and maintaining competency in its use should be a priority. RFBD systems may play a key role in surgery that requires large-volume resuscitation (e.g., major trauma, cardiovascular surgery, liver transplantation, major thoracic trauma), but only when it is used properly and with good judgment.

If a venous air embolus is suspected:

Further Reading

Figure 135–1 ■ FMS2000 rapid fluid delivery system. (Courtesy of Belmont Instrument Corporation, Billerica, Mass.)

Risk Assessment and Implications Vigilance is as imperative, as with any medical device. Fatal complications can result from machine malfunction or operator error.

●

●

Alert the surgeon in the event that the air is being entrained at the operative site. Stop the rapid infusion device.

Bedford RF: Air embolism. In Gravenstien N, Kirby RR (eds): Complications in Anesthesiology. Philadelphia, Lippincott-Raven, 1996, pp 271-280.

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Comunale ME: A laboratory evaluation of the Level 1 Rapid Infuser (H1025) and the Belmont Instrument Fluid Management System (FMS 2000) for rapid transfusion. Anesth Analg 97:1064-1069, 2003. Flacke WE, Flacke JW, Ryan JF, et al: Temperature: Homeostasis and unintentional hypothermia. In Gravenstein N, Kirby RR (eds):

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Complications in Anesthesiology. Philadelphia, Lippincott-Raven, 1996, pp 117-129. Smith CE: Principles of fluid warming in trauma. Semin Anesth Periop Med Pain 20:51-59, 2001.

EQUIPMENT & MONITORING

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Surgical Diathermy and Electrocautery

136

Ian Lewis Case Synopsis A 59-year-old man undergoes elective transurethal surgery for benign prostatic hypertrophy under spinal anesthesia. He had a pacemaker inserted 5 years ago for third degree heart block. It was programmed to ventricular-inhibited pacing with an adaptive rate response (i.e., VVIR mode). The device was programmed with a lower rate cutoff of 60 beats per minute and an upper rate cutoff of 130 paced pulses per minute. The initial electrocardiogram (ECG), before use of the unipolar diathermy device, revealed P waves at a rate of 100 beats per minute, with ventricular pacing at 60 pulses per minute. Each time the diathermy unit is activated, the paced ventricular rate gradually increases to a plateau of 130 pulses per minute. Each time the diathermy is stopped, the rate gradually returns to 60 beats per minute.

PROBLEM ANALYSIS Definition Surgical diathermy (cutting) and electrocautery (coagulating vessels) are similar processes whereby body tissues are heated as a consequence of their resistance to the passage of an electrical current. There are a number of potential hazards associated with its use during anesthesia and surgery, and the case synopsis illustrates one such phenomenon: interference with an implanted electronic device. The rapid ventricular pacing that occurred in this example may have resulted in a number of problems, including low cardiac output, myocardial ischemia, and pacemaker-mediated tachycardia, which could be misinterpreted and treated as ventricular tachycardia. Interference with pacemakers programmed to other modes may result in different problems, such as inhibition or reversion to an asynchronized mode. Owing to advances in pacemaker and internal cardioverter-defibrillator technology, it is no longer appropriate to manage patients with cardiac rhythm management devices (CRMDs) by placing a magnet over the CRMD pulse generator (see Chapter 97).

Recognition Recognition and prevention of the complications associated with any medical device require both an understanding of its underlying mechanisms and knowledge of the potential complications. This includes any features or associated warning signs or alarms that signal possible problems. With surgical diathermy, all operating room personnel should have a general awareness of the diverse but specific complications (e.g., skin burns, cardiac arrhythmias) associated with this device. These complications may result in significant morbidity and mortality to both patients and medical personnel. In the situation described in the case synopsis, there was an apparent lack of recognition that the use of surgical diathermy might be associated with heart rate changes 556

in a patient with a cardiac pacemaker. In this instance, there was no adverse outcome. However, with the illustrated upper rate behavior in response to sensed continuous electromagnetic interference (i.e., the “noise reversion mode”—ventricular pacing at 130 pulses per minute), paced QRS complexes would be widened, but pacing artifacts might be unapparent.1 If the supposed ventricular tachycardia were treated with drugs or electrical cardioversion, this might have produced an unfavorable outcome.

Risk Assessment Surgical diathermy is used frequently in the operating room. Problems are rare, but their incidence can be reduced or eliminated if anesthesia personnel are familiar with the operation of surgical diathermy. Programs must be in place for educating and training personnel in the proper use and servicing of this equipment. Additionally, there must be a reporting system for faulty equipment, complications, and “near misses.” In principle, diathermy uses the heating effect of passing an electrical current across a resistor. In practice, the “resistor” is the patient’s skin or other tissue being cauterized or cut. Alternating current (AC) is often used in clinical practice. The correct term for resistance with AC as opposed to direct current (DC) is impedance. A potential difference created by the diathermy device produces a current that passes through the patient to complete an electrical circuit. This circuit may be completed in two ways: 1. Unipolar diathermy. The cathode (−) is the cauterydiathermy (Bovie) tool tip, and the anode (+) is the ground or return plate. This is usually located on one of

1 This is especially true if the pacemaker lead configuration is bipolar, which greatly reduces the size of the pacing artifacts. However, many ECG monitors in use today have a feature that detects and amplifies small pacing artifacts, enabling clinicians to see them on the monitor.

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Figure 136–1 ■ Modes of current delivery from electrosurgical units: cutting, coagulation, and blend modes. (Courtesy of Valleylab, Inc., Boulder, Colo.)

PURE CUT

the patient’s buttocks or thighs. Unipolar diathermy-cautery configurations have the highest potential for complications with CRMDs, because the current pathway between the cathode and anode may pass near or across the CRMD pulse generator or leads. 2. Bipolar diathermy. Both the cathode (−) and the anode (+) are incorporated in a forceps and are therefore very closely spaced. Thus, a grounding plate is not required with bipolar diathermy-cautery, and the current pathway is very small. The risk of CRMD-related complications is much smaller (but not absent) because the current pathway is far less likely to pass near or across the CRMD pulse generator or leads. The exception is if cautery is applied directly to or very near (i.e., within a few centimeters) the pulse generator or leads.

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Mechanism of electrosurgical cutting mode.

Low frequency High voltage

BLEND 1 80% on 20% off

BLEND 2 60% on 40% off

BLEND 3 50% on 50% off

COAG 6% on 94% off

large surface area of a correctly placed ground electrode pad. In fact, the only significant point of resistance (i.e., heat production) should be at the electrode tip. Diathermy units often develop power levels between 50 and 400 watts and radiofrequency AC cycles from 300 kHz to 3 MHz. Current is delivered in varying waveform patterns or modes (Fig. 136-1). Continuous current is used for cutting, and pulses are used for coagulation. Because the pure cutting (diathermy) mode uses continuous current, it produces a series of sparks from the diathermy tool to the tissue. The pencil tip does not have to contact the tissue. The sparks generated cause intense local heating of cellular water, causing cellular explosion and destruction over a narrow band (Fig. 136-2). In contrast, coagulation (cautery) requires the direct application of the pencil tip; heat is thus dissipated over a wider area, causing the cells to shrink (crenate) and dry out (desiccate) rather than explode (Fig. 136-3). Bipolar diathermy is generally restricted to coagulation modes. In contrast, unipolar diathermy incorporates various coagulation and cutting modes (see Fig. 136-1). Argon gas, applied as a jet around the tip of the cathode, has been used to improve the safety and effectiveness of diathermy. This gas is heavier than air, inert, and noncombustible, and it displaces nitrogen and oxygen. It is also

Figure 136–3

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Mechanism of electrosurgical coagulation mode.

EQUIPMENT & MONITORING

The higher the resistance at a point in an electrical circuit, the higher the heating effect will be with the passage of current. Thus, W = I2R, where W is the power output in watts, which is proportional to the heating effect; I is the current in amps; and R is the resistance in ohms. Resistance and the heating effect are higher where the current passes over a narrow pathway. Thus, current density is very high at the point of the unipolar diathermy-cautery pencil tip and relatively low throughout the patient’s body and across the

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High frequency Low voltage

100% on

Figure 136–2

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readily ionized by the current and provides a medium for the passage of current, so that the pencil tip does not have to be in direct contact with tissue. Two types of complications associated with surgical diathermy or cautery are electrocution and electromagnetic interference (EMI). Electrocution may occur if the patient circuit becomes a route for the passage of electrical current from other sources to the diathermy or cautery ground plate. These are termed leakage currents. Current passing through the body at the AC outlet frequency (60 Hz) can cause serious problems in excitable tissue (e.g., arrhythmias and large muscle group contractions, which may be perceived by awake patients). However, the same current applied in the radiofrequency range allows diathermy-cautery to work without producing these untoward effects. Thus, diathermy-cautery units incorporate an isolating capacitor in their circuits. This allows the passage of relatively harmless (for excitable tissue) radiofrequency current but impairs the passage of more dangerous low-frequency leakage currents to the ground plate. The duration of the applied diathermy or cautery may also increase the probability of certain complications. For example, cardiac arrhythmias can be avoided if leakage current is prevented altogether or terminated rapidly (within a few microseconds) by line isolation circuitry. Major complications (e.g., ventricular fibrillation due to the passage of very small frequency currents across the heart) can also be minimized by line isolation monitors and ground fault circuit indicators (see Chapter 137). Finally, EMI is the tendency of electric current in one circuit or conductor (usually wires) to induce current in another, even though separated by a nonconducting material such as air. EMI may result in transient disturbances in patient monitoring equipment but can also cause transient malfunction, alter preset parameters, or cause permanent damage to implanted devices such as CRMDs.

Implications Many of the complications of surgical diathermy are predictable. Heat production may lead to the following: ●

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Burns may occur at the ground plate (also known as “return” or “anode”) site if there is poor contact of the ground plate with the patient’s skin surface. Localized burns via electrical pathways created by small surface area electrodes. These pathways may be created by application of ECG or other (e.g., bispectral index, patient state analyzer, neuromuscular function monitor) electrodes or the use of diathermy to an organ that has been temporarily suspended on a narrow vascular pedicle. Fires or explosions in association with alcohol-based skin preparations, colonic gas, explosive anesthetics (largely of historical interest), and oxygen-enriched environments (see Chapter 138). Inhalation of smoke and debris from vaporized tissue. Diathermy-vaporized tissue contains chemicals such as benzene, hydrogen cyanide, and formaldehyde, plus live cellular fragments and viruses. A suction port at the active electrode (cathode) can reduce the diffusion of smoke and debris.

ELECTROMAGNETIC INTERFERENCE EMI may enter an implanted electrical device through direct contact with the source of EMI or by exposure to an electromagnetic field, with the device leads serving as antennae. Devices that are most susceptible are CRMDs, phrenic nerve stimulators, and cochlear implants. Owing to CRMDs’ large antennae, unipolar lead configurations increase the susceptibility to device malfunction during exposure to EMI. EMI may interfere with other electrical equipment, including pulse oximeters and ECG monitors, by producing artifacts or noise. ELECTROCUTION

AND

MICROSHOCK HAZARDS

These complications can be serious, causing ventricular tachycardia or fibrillation or even cardiac standstill (asystole), and they are generally associated with electrical energy supplied by the main or leakage currents associated with faulty electrical apparatus.

MANAGEMENT AND PREVENTION Safety Precautions With unipolar diathermy or cautery, the full surface of the return (grounding) pad or plate must fully contact the patient’s skin surface to minimize the risk of burns. An alarm will sound if the resistance across the pad or plate increases, indicating a reduction in the contact area. Complete circuit disconnection is also sensed. The contact surfaces of diathermy-cautery grounding pads are already covered with electrolytic contact paste or gel to reduce resistance to current flow, but such electrolytic material must be manually applied to the surface of a grounding plate, taking care to ensure full coverage. It is necessary to check other parts of the cautery or diathermy circuits (e.g., for lead insulation defects), as well as to check any other electrical equipment (e.g., laparoscopic instruments) for their ability to induce or store (i.e., act as capacitors) leakage currents that could cause thermal injury or increase the risk for micro- or macroshock. Isolation capacitors permit the passage of radiofrequency current but impede dangerous 60-Hz main current. Electrical isolation of the main supply from the radiofrequency generator also reduces the risk for passage of leakage currents. Hand operation of the diathermy or cautery tool (versus using a foot pedal) reduces the risk of its inadvertent use. A noise should be emitted when the diathermy or cautery tool is activated. When not in use, active diathermy or cautery tools should be stored in an appropriate nonconductive holster. Jerry-rigged holsters (e.g., red rubber tubing) may not provide sufficient protection and may ignite under certain conditions. Use of different coagulation and cutting modes allows for the more efficient use of diathermy and can help minimize potential complications, such as smoke and debris production. As mentioned earlier, argon gas applied around the cathode tip can improve the safety and effectiveness of diathermy.

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The appropriate equipment should always be used. Interchanging parts from different devices may result in complications. The return (ground) electrode plate or pad should be placed on skin covering a well-vascularized muscle mass. Avoid irregularities, such as bony prominences, which may reduce the surface contact area and increase the risk for burns by creating air pockets and potential spark gaps. For children, appropriately sized grounding pads or plates should be used (refer to the manufacturer’s instructions). Pads or plates should be checked periodically during long cases. Contact with combustible fluids (e.g., alcohol-containing skin preparations) must be avoided. Oxygen should not be used in the vicinity of diathermy or cautery (e.g., when supplemental oxygen is being administered to the patient). There must be no direct contact with metal or other electrical conductors (e.g., fluids), as this may result in burns at points of contact and coincidentally act as pathways for leakage current.

Recommendations for Patients with Cardiac Rhythm Management Devices ●

● ●

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2 Generally, it is ill-advised to place a magnet over the CRMD pulse generator without knowing what the magnet response is. This information can be obtained from the manufacturer or hospital CRMD service. In some devices, the magnet response may be programmed off. In others, programming off the magnet response may not confer immunity to sensing or potential malfunction during the planned intervention, even after the patient has been discharged.

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some patients, prophylactic transvenous pacing is necessary. Regardless, chronotropic drugs should be available for all cases. In some high-risk cases (e.g., when atrioventricular synchrony is necessary to preserve cardiac output), a CRMD telemetry reprogramming device and a knowledgeable operator should be available during the case. Bipolar diathermy or an ultrasonic (harmonic) scalpel should be used when possible. If unipolar diathermy or cautery is used, the return (grounding) plate and active tip should be kept as far as possible from the pulse generator and leads. The duration of diathermy or cautery should also be as brief as possible. To the extent possible, the CRMD pulse generator and leads must be outside (not within) the current pathway between the diathermy-cautery tool and the return plate. A backup external cardioverter-defibrillator should be available should the internal one fail to deliver appropriate therapy for tachyarrhythmias (see Chapter 97). Postoperative care includes device interrogation to ascertain function, correction of settings, and reprogramming if necessary.

Further Reading American Society of Anesthesiologists Task Force on Perioperative Management of Patients with Cardiac Rhythm Management Devices: Practice advisory for the perioperative management of patients with cardiac rhythm management devices: Pacemakers and implantable cardioverter-defibrillators. Anesthesiology 103:186-198, 2005 (additional material available at http://www.anesthesiology.org). Atlee JL, Bernstein AD: Cardiac rhythm management Devices (part I). Anesthesiology 95:1265-1280, 2001. Atlee JL, Bernstein AD: Cardiac rhythm management Devices (part II). Anesthesiology 95:1492-1506, 2001. Epstein MR, Mayer JE Jr, Duncan BW: Use of an ultrasonic scalpel as an alternative to electrocautery in patients with pacemakers. Ann Thorac Surg 65:1802-1804, 1998. Kleinman B, Hamilton J, Heriman R, et al: Apparent failure of a precordial magnet and pacemaker programmer to convert a DDD pacemaker to VOO mode during use of the electrosurgical unit. Anesthesiology 86:247-250, 1997. Ozeren M, Dogan OV, Duzgun C, et al: Use of an ultrasonic scalpel in the open-heart reoperation of a patient with a pacemaker. Eur Cardiothorac Surg 21:761-762, 2002. Salukhe TV, Dob D, Sutton R: Pacemakers and defibrillators: Anaesthetic implications. Br J Anaesth 93:95-104, 2004. Valleylab (Pfizer) Web site: http://www.pfizer.com/valleylab/. Wong DT, Middleton W: Electrocautery induced tachycardia in a rateresponsive pacemaker. Anesthesiology 94:710-711, 2001.

EQUIPMENT & MONITORING

Preoperative assessment should include the indication for the device, identification of the device, the programmed mode, and the interference mode. Direct interrogation of the device is especially helpful. It may be necessary to consult a cardiologist or the CRMD follow-up service or clinic (see Chapter 97). A 12-lead ECG should routinely be obtained preoperatively. If diathermy-cautery will be used near the CRMD pulse generator or leads, the patient is at high risk for diathermy or electrocautery EMI. If the patient has an adaptiverate device or is mostly pacemaker dependent, the device must be reprogrammed to (1) an asynchronous operation (inactivate sensing), (2) disable any adaptive-rate features, and (3) inactivate antitachycardia pacing therapies or shocks (see Chapter 97). Reprogramming does not guarantee immunity against EMI-caused damage or altered CRMD function. Therefore, it is necessary to interrogate the CRMD and reprogram it after exposure to diathermy or cautery EMI. Alternatively, if the risk of EMI is high, the patient is pacemaker dependent, and the device does not deliver adaptive-rate or antitachycardia therapies, placement of a magnet or temporary cardiac pacing may be indicated.2 External cardiac pacing is not always effective, however; in

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Electrical Safety Jeffrey J. Schwartz Case Synopses Macroshock A 50-year-old man in good general health is undergoing laparoscopic cholecystectomy under general anesthesia. In the middle of the procedure, the anesthesiologist feels a tingle, and the patient develops ventricular fibrillation. Immediate resuscitation and defibrillation restore normal sinus rhythm. The case continues uneventfully after a faulty surgical light is removed from service. Microshock In an adjacent room, a 60-year-old man with a temporary pacemaker is undergoing lower extremity vascular bypass surgery. While the anesthesiologist is adjusting the pacemaker leads, the patient develops ventricular fibrillation. Immediate resuscitation and defibrillation restore normal sinus rhythm.

PROBLEM ANALYSIS Definition Electric shock occurs when a person becomes part of or completes an electrical circuit. To become part of the circuit, a patient must contact it at two points of different voltage. The contact need not be to a wire. Saline-soaked drapes conduct electricity, metal chassis can be energized due to faulty wiring, and leakage currents can flow between any two conductors. The mechanism of electric shock can be divided into two categories: ●

●

Macroshock refers to large amounts of current flowing through intact skin: 5 mA is accepted as the maximum harmless current; 10 to 20 mA causes sustained muscle contraction; 100 to 300 mA causes ventricular fibrillation. Microshock refers to relatively small currents applied directly to the myocardium. The current density is very high, and as little as 100 μA can cause ventricular fibrillation. This current is too small to be sensed as a tingle by the operator.

Risk Assessment All patients and personnel exposed to an environment with electrical equipment are at risk for macroshock. The OR is an especially hazardous place owing to the common use of saline solutions and the mechanical abuse to which electrical equipment is often subjected. Patients with an electrical connection to the heart, such as a saline-filled central venous catheter or pacemaker wires, are at increased risk for microshock. The most common cause of macroshock is damaged or faulty wiring in electrical equipment. Line voltages (110 to 220 V) provided by the utility company are kept out of contact by insulated wires. Insulation can wear down and come into contact with a metal chassis or directly with the patient. The use of numerous safeguards (see later) means that for an electric shock to occur, the safeguards must have failed, been ignored, or been absent.

Implications The implications of electric shock depend on the following: ● ● ● ●

Recognition Recognition of an electrical problem involves not only the realization that an electric shock has occurred but also the awareness that the potential for electric shock exists. Electric shock manifests in the operating room (OR) as sudden-onset ventricular fibrillation (VF) or ventricular tachycardia (VT). The anesthesiologist generally considers a cardiac origin for VF or VT, but the possibility of electric shock must always be kept in mind. Any perception of tingling represents a dangerous situation and must be investigated immediately. Microshock can be recognized only in an appropriate clinical setting, as there are often no premonitory findings. 560

Amount of current Frequency of current Duration of current Whether current is applied directly to myocardium

The voltage used in most OR equipment is 110 or 220 V. By Ohm’s law, the current that flows (amperes) when 120 V is applied is 120 V/resistance (Ω). The resistance of dry skin, about 120,000 Ω, allows 1 mA to flow. The resistance of wet skin, about 1200 Ω, allows 100 mA to flow, which is a potentially fatal shock. The frequency of electric power in the United States is 60 Hz, which, by coincidence, is the most dangerous frequency. Electric current affects electrically excitable tissue. Electric current flowing through a nerve or muscle causes pain and contraction, much as a peripheral nerve stimulator does. Electric current flowing through the heart can cause VT or VF and death.

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MANAGEMENT Management of electric shock itself consists of appropriate resuscitation, including cardiopulmonary resuscitation and defibrillation. If it can be identified, the source of current and faulty equipment must be removed. Electric shock, however, is often a diagnosis of exclusion.

Line Isolation Monitor In ORs that use isolated power (i.e., line isolation circuits), the line isolation monitor (LIM) gauges the integrity of such isolation. If the LIM alarm sounds, the power is no longer isolated, and electric current could flow in the event of another fault. The OR, however, is still safe, and all equipment will function normally. The usual cause of a LIM alarm is that faulty equipment has been plugged in. Nonessential electrical equipment should be unplugged, one piece at a time, until the faulty one is identified. Less commonly, many pieces of apparently flawless equipment, but all with small leakage currents, may be simultaneously connected to the same circuit.

Ground Fault Circuit Interrupters In ORs that use ground fault circuit interrupters (GFCIs), faulty equipment may cause the GFCI to interrupt current to all devices serviced by it. The GFCI has a reset button to restore current, but the faulty piece of equipment must be identified and removed, or the GFCI will trigger again.

PREVENTION Electric shock is an extraordinarily rare complication owing to the various safeguards undertaken by anesthesiologists, equipment manufacturers, and OR construction engineers.

Grounding

Power Isolation Many ORs use isolated power to decrease risk. The utility company supplies grounded power, which means that one of the wires that carries electricity is also connected to the earth via a large, buried conducting rod. This provides additional safety in the distribution of electric power. However, it also means that, to one degree or another, all patients are already directly connected to one part of an electrical circuit.

Electrical Safety

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Only one additional connection, due to faulty wiring, is necessary for the patient to complete the circuit. A line isolation transformer can convert the grounded power from the utility company to isolated power that has no direct connection to the ground. Two contacts with faulty equipment, which is an unlikely situation, would now be necessary to cause electric shock.

Line Isolation Monitor If isolated power is used, the integrity of the isolation must be monitored, or the system might accidentally become grounded without warning. The LIM continually measures the impedance between the power lines in the OR and the ground. The impedance should be (near) infinity. If it senses that the impedance is reduced and that the power is no longer isolated, an alarm sounds.

Ground Fault Circuit Interrupter Some ORs use GFCIs to decrease risk. GFCIs continually monitor the difference in current going to and returning from an appliance. If the difference exceeds a certain threshold (typically 5 mA), presumably because some current is being shunted through a patient, the GFCI cuts off the power before any injury can occur. The problem with GFCIs is that one piece of faulty equipment causes a loss of power to all equipment serviced by the GFCI, some of which may be vital.

Pacing Leads and Saline Monitoring Lines Central venous catheters and pacemaker wires should be manipulated only with gloved hands and while touching nothing else to minimize the likelihood of the flow of small leakage currents.

Inspection A program must be in place for regular inspection and testing of equipment by the biomedical engineering department, so that faulty wiring, worn wiring, or excessive leakage currents can be detected before they pose a hazard.

Further Reading Bruner JMR, Leonard PF: Electricity, Safety and the Patient. Chicago, Year Book Medical Publishers, 1989. Ehrenwerth J: Electrical safety. In Barash PB, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 3rd ed. Philadelphia, Lippincott-Raven, 1997, pp 137-155. Litt L, Ehrenwerth J: Electrical safety in the operating room: Important old wine, disguised new bottles. Anesth Analg 78:417-419, 1994. Schwartz JJ, Ehrenwerth J: Electrical Safety. In Lake CK (ed): Clinical Monitoring for Anesthesia and Critical Care. Philadelphia, WB Saunders, 1994, pp 35-42. Schwartz JJ, Ehrenwerth J: A case-oriented approach to electrical safety. In Morell RC, Eichhorn JH (eds): Patient Safety in Anesthetic Practice. New York, Churchill Livingstone, 1996, pp 55-70.

EQUIPMENT & MONITORING

Most electrical equipment in the OR is grounded. This means that the chassis, metal case, and other internal components are all connected to a common earth ground via the third prong on the device’s plug. This connection tends to shunt fault current safely to the ground rather than to a person in contact with the equipment.

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Paul E. Kazanjian and Anthony R. Doyle Case Synopsis A 2-year-old boy is undergoing inguinal herniorrhaphy as the first case of the day on a Monday. Inhalation induction is carried out with sevoflurane using a breathing system containing Baralyme carbon dioxide (CO2) absorbent. The Baralyme absorbent canisters had been changed the previous Wednesday evening. Fifteen minutes after induction of anesthesia, an explosion is heard in the vicinity of the anesthesia machine. The anesthesia circle system is damaged, and there is evidence of extreme heat in the CO2 absorber. Fortunately, the child is not injured.

PROBLEM ANALYSIS Definition A fire is a rapid, persistent, exothermic oxidation of a combustible substance (fuel) that releases heat and light energy; fire is usually accompanied by flame. Surgical fires are defined as the burning of materials on or in a surgical patient. This is in contrast to an operating room (OR) fire, which is defined as any fire that occurs in the OR and does not necessarily involve the patient. Examples of fires that occur in the patient include airway fires, such as ignition of an endotracheal tube by a laser, and intra-abdominal fires caused by sparks igniting bowel gas. An example of a fire occurring on the patient includes ignition of drapes, sponges, and other fuels by an electrosurgical instrument. Approximately 62% of surgical fires are located in the airway or on the face; 24% of surgical fires occur elsewhere on the patient, and 14% occur elsewhere in the patient. Though rare, surgical fires can cause serious injury or death. In most cases, they are preventable. Despite the use of nonflammable anesthetics, fires still occur in the OR, and they are caused by the same essential combination of an ignition source, oxidizer, and fuel (Table 138-1). Contributing factors include human error, lack of training, misconception, and the improper use of medical devices. Common ignition sources are electrosurgical

Table 138–1

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Causes of Fires and Explosions in the Operating Room

Electrocautery during facial, head, or neck surgery in an awake patient receiving supplemental O2 Laser surgery of the esophagus or trachea Ignition of flammable skin preparation solutions or bowel gas Electrosurgery in the area of an endotracheal tube, particularly during tracheostomy formation Exothermic reactions between potent inhaled anesthetics (e.g., sevoflurane) and desiccated CO2 absorbent (Baralyme) Interaction of static electricity or electrocautery in the presence of flammable or explosive anesthetic gases (rare)

562

equipment (68%), lasers (13%), and other heat sources, including electrocautery, hot wire cautery, fiberoptic light sources, defibrillators, and high-speed burs. Oxidizers are substances that support the combustion of fuels and cause fires to burn more intensely and vigorously than they would in the absence of an oxidizer. Although not explosive, air, oxygen (O2), and nitrous oxide (N2O) are the common oxidizers found in the OR environment. There are a number of potential fuels in the OR, including surgical drapes, gowns, sponges, endotracheal tubes, skin preparation solutions, hair, and skin. Some fuels are more likely to burn than others, and some fuels ignite only in the presence of an oxidizer. Fires in the OR are commonly associated with laser surgery of the airway. They usually result from ignition of an inadequately protected endotracheal tube (Fig. 138-1) or excessively long exposure of any combustible material placed in the airway (e.g., wet cotton pledgets) to a direct hit from the laser beam. The incidence of such fires is thought to be from 0.5% to 1%. Initially, most fires are located only on the external surface of the endotracheal tube; if unrecognized, they may lead to a blowtorch-like flame if the lumen of the tube is reached, allowing the O2-rich contents of the tube to enhance the combustion process. The risk of fire during surgery of the head, neck, and airway is increased because of the O2-enriched atmosphere created by the O2 and N2O building up beneath the surgical drapes or in the oropharyngeal cavity. Depending on the procedure, the O2-enriched atmosphere may be immediately adjacent to or encompass the operative site. There are several scenarios that can lead to the development of an O2-enriched atmosphere. During head and neck surgery that is performed under local anesthesia, a mask, nasal cannula, or other open breathing system can spill O2 near the patient’s mouth, nose, or airway, and O2 can collect under the drapes. O2 leaking from an uncuffed endotracheal tube can saturate the oropharynx during tonsillar surgery and similar procedures. Entering the trachea with an electrocautery device introduces an ignition source into the O2-enriched atmosphere of the patient’s tracheal airway. Fires can also result from a misdirected or reflected laser (laser light is reflected off metal surfaces) impinging any

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monitor the CO2 absorber for signs of excessive heat production and also monitor the relationship between the inspired sevoflurane concentration and the vaporizer setting. An unusually delayed rise or unexpected decline in the inspired sevoflurane concentration compared with the vaporizer setting may indicate exothermic sevoflurane degradation (see Table 138-4).

Risk Assessment

Figure 138–1 ■ Endotracheal tube damaged by a laser-induced airway fire. (Courtesy of Dr. Allan Brown, University of Michigan Medical Center.)

Recognition Sparks, pops, and flashes may indicate a situation conducive to ignition, combustion, or explosion. Most frank fires in the OR are heralded by flame and smoke. Anesthetists should

Implications Most surgical fires, if appropriately handled, result in little or no harm to the patient. However, inappropriate handling can have catastrophic consequences, including death or a prolonged period of ventilation in the intensive care unit consequent to pulmonary edema, sepsis, or multiple organ failure syndrome. A late complication of airway fire is tracheal stenosis.

MANAGEMENT OR staff should be educated about the nature, prevention, and extinguishing of surgical fires. Training, simulations, and drills should be used to familiarize staff with reactions and responses to surgical fires. Comprehensive training includes instruction in the rescue, alert, containment, and evacuation response to large fires. Staff should be familiar with the location and operation of firefighting equipment, medical gas supply shut-off valves, battery-powered portable lighting systems, ventilation systems, building alarms, and electrical systems. A small fire can often be extinguished safely and simply by patting the flame with a gloved hand or towel. The area should be carefully inspected to make sure that all the burning material has been extinguished. The OR team should assess the conditions that led to the fire and make efforts to prevent a recurrence.

EQUIPMENT & MONITORING

flammable material, such as the surgical drapes covering the patient. Many liquids used in the OR (e.g., skin preparations, tinctures, degreasers, solutions in suture packs) contain flammable volatile organic chemicals. Skin preparations may contain alcohol or acetone, and they are flammable until all the liquid has evaporated. Careless application may allow the solution to wick into the patient’s hair, pool on the patient’s skin, pool under the patient’s body, or soak into linens. If the patient is draped before the solution is completely dry, vapors can be trapped and channeled to the operative field, where they may be exposed to a heat source and ignite. Likewise, bowel gas may be ignited by surgical diathermy. Intestinal gases contain varying concentrations of nitrogen, CO2, hydrogen, methane, and O2. This combination of gases can be flammable in certain proportions. In addition, N2O can diffuse into the bowel and make the gas mixture even more flammable. Fires and explosions resulting from the interaction of an ignition source, such as static electricity, and flammable or explosive anesthetic gases (e.g., ether, cyclopropane) are of historical interest only. However, the interaction of potent inhaled anesthetics with desiccated CO2 absorbent can result in the production of carbon monoxide, extreme heat, smoke, fires, and explosions.

Whenever there is a high-energy source of ignition (e.g., laser or electrocautery), a potentially combustible material (e.g., endotracheal tube, alcohol-containing skin preparation, surgical drapes), and an oxidizer (O2, N2O, or both), there is the potential for combustion. Obviously, the risk of fire is greater if the concentration of oxidizer is higher, so it is advisable to keep the inspired O2 concentration as low as possible. Any patient undergoing airway surgery is at risk of the consequences of an airway fire, regardless of whether a laser is used. A high index of suspicion should be maintained at all times when anesthesia is being provided for laser surgery or during any airway surgery involving the use of electrocautery (e.g., tonsillectomy, tracheostomy). Risk of fire is also greater when surgery on the head and neck is performed under local anesthesia using an open breathing system (e.g., nasal cannula, facemask). Exothermic reactions between CO2 absorbents and sevoflurane are most likely to occur when the absorbent is desiccated. Most absorber fires occur during the first case on a Monday morning following a period of nonuse.

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Table 138–2

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Recommendations for Avoiding Laser-Induced Fires in the Operating Room

Minimize FiO2 and avoid N2O Use wet pledgets above the ETT cuff, but replace any string with wire Use colored saline in the cuff to allow early detection of ETT cuff rupture Place the ETT cuff as far distally as possible in the trachea Use an appropriately protected or specifically designed ETT Alternatively, use jet ventilation or intermittent apnea Be aware of the type of laser in use and the ETT’s susceptibility to a direct hit ETT, endotracheal tube; FiO2, fraction of inspired oxygen; N2O, nitrous oxide.

Large fires on the patient demand immediate action to extinguish the fire, protect the patient from (additional) thermal injury, and treat the patient, if injured. A comprehensive response requires the participation of the anesthesiologist, surgeon, and OR nursing staff. The anesthesiologist should stop the flow of O2 to the patient and be prepared to resume or assist ventilation with air. The surgeon or nurses should remove burning materials from the patient and extinguish them. This is especially important for paper drapes, which are impervious to water; dousing them with water may not extinguish a fire burning on the underside. It is also important to remove burned material from the

Table 138–3

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patient, even if it is extinguished, to prevent further burn injury from the hot material. The surgeon should assess and treat the patient’s injuries. Assistance from additional staff may be necessary. If the fire is large enough, extreme heat, fire, and smoke may force the OR team to evacuate the area. The team should attempt to evacuate or rescue the patient, but this may not be possible. In the event of an airway fire or explosion, the anesthesiologist, surgeon, and nursing staff must act quickly and decisively to reduce injury to the patient. The endotracheal tube or other source of ignition or fire should be removed immediately from the patient, and ventilation must be stopped to stem the supply of O2 to the flames. The endotracheal tube should be extinguished in a bucket of water, which should always be available during laser surgery. The airway should be inspected quickly via direct laryngoscopy to determine whether there is a remaining source of combustion. The patient should be mask ventilated with 100% O2 while anesthesia is continued. Rigid bronchoscopy should be performed to assess the damage and remove debris. This is followed by flexible fiberoptic bronchoscopy of the lower airways if the fire was of the interior blowtorch type. The latter results from a transluminal burn in an endotracheal tube during the inspiratory part of the respiratory cycle. If airway damage is detected, the patient should be reintubated; if there is appreciable upper airway damage, low tracheostomy may be indicated. Appreciable lower airway damage caused by smoke inhalation and heat damage may require prolonged intubation and ventilation, including the administration of high-dose steroids.

Precautions Regarding Ignition Sources in the Operating Room

Source

Management Guidelines

Electrosurgical unit (ESU)

Use bipolar cautery to limit ignition potential Exercise caution when using ESU near locations where O2 concentration is elevated (throat, mouth) Place ESU electrode probes in holster or away from patient and surgical drapes when not in use Do not use ESU to cut through tracheal rings; use scissors or scalpel instead Do not use red rubber catheter or other materials to sheathe long ESU electrode probes Avoid eschar buildup on electrode tip; clean buildup off as needed Use appropriate ESU modes for cutting; avoid arcing coagulation modes Soak gauze sponges in saline and wring them out when used near hot wire cautery Minimize supplemental O2 concentration Limit laser output to lowest acceptable power density and pulse duration Test-fire laser onto a safe surface Place laser in standby mode when not in use Activate laser only when tip is under surgeon’s direct vision Allow only the person using the laser to activate it Deactivate laser and place it in standby mode before removing it from the surgical site When performing laser surgery through an endoscope, pass the laser fiber through the endoscope before introducing it into the patient Use appropriate laser-resistant tubes during upper airway surgery Make sure all fiberoptic connections are complete before activating the light source Deactivate the light source before disconnecting the scope from the light cable Use according to the manufacturer’s instructions Avoid discharging in O2-enriched atmosphere Train operators in the use of defibrillation equipment Use disposable adhesive defibrillator pads instead of nondisposable paddles whenever possible Maximize contact between the patient and the surface of the pad or paddle When using paddles, use the appropriate conduction gel

Hot wire cautery Surgical lasers

Fiberoptic cables and light sources Defibrillators

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PREVENTION

Table 138–4

Anesthesiologists and other health care providers must consider the risk-benefit ratio of nasal O2 insufflation during monitored anesthesia care, particularly during a surgical procedure involving the head and neck. Supplemental O2 should be delivered as determined by clinical judgment, considering the patient’s preoperative O2 saturation as measured by pulse oximetry in room air. Avoidance of “luxury O2” should be considered. When higher concentrations of O2 are necessary to maintain O2 saturation, the surgeon should be informed about the potential for ignition and fire. Discontinue supplemental O2 for at least 1 minute before the use of an ignition source near the patient’s head, neck, or airway. Other strategies to avoid the creation of an O2enriched atmosphere include modified draping techniques, careful placement of expiratory hoses, and use of an active scavenging system. If an O2-enriched atmosphere is unavoidable, it should be isolated from the operative field by carefully applying a nonflammable incision drape. Also, the use of electrosurgical units should be minimized. The risk of airway fires resulting from use of the surgical laser can be reduced by avoiding misdirection of the laser, both within and outside the operative field, and accidental operation when directed at the drapes or the patient’s face (Table 138-2). The patient’s eyes should be covered with wet gauze pads and not taped closed, because tape is combustible. During laser airway surgery, the endotracheal tube must be protected from ignition, or a specially designed tube should be used; if metal foil wrap is used, it must be applied carefully. There are many commercially available endotracheal tubes for use with laser surgery, but none is completely impervious to ignition. An excellent review article by Rampil provides further details.

Table 138–5

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Fires in the Operating Room

565

Precautions Regarding Oxidizers (Oxygen and Nitrous Oxide)

In general, use air or O2 with an FiO2 less than 30% in open breathing systems Identify and ameliorate O2-enriched environments Tent drapes around the patient’s head and neck when supplying supplemental O2 in an open breathing system Discontinue supplemental O2 for 1 min before using ESU near the head and neck During oropharyngeal surgery, use wet gauze or sponges with uncuffed endotracheal tubes to minimize leak of O2 into oropharynx Turn O2 off when not in use Be aware that nitrous oxide (N2O) supports combustion as effectively as O2 does; a mixture of N2O and O2 is not less dangerous than pure O2 Diffusion of N2O into bowel gas introduces additional oxidizer to support combustion of hydrogen and methane ESU, electrosurgical unit; FiO2, fraction of inspired oxygen.

The surgeon must exercise great care during tracheostomy formation to avoid igniting the endotracheal tube with diathermy before its removal and replacement with a tracheostomy tube. Fires have resulted from the ignition of flammable skin preparations by electrosurgical units or other ignition sources (Table 138-3). Care must be taken to avoid pooling of the preparation solution around the patient. Allow sufficient time for the volatile material (usually alcohol) to evaporate before beginning surgery. Precautions regarding the use of oxidizers (e.g., O2, N2O) are summarized in Table 1384, and those for fuels and CO2 absorbers are given in Tables 138-5 and 138-6, respectively.

Precautions Regarding Fuel Sources in the Operating Room Management Guidelines

Volatile skin preparations (degreasers, ether, acetone, alcohol) and ointments (collodion, petroleum jelly, tincture of benzoin, aerosols, paraffin) Linens, drapes, gowns, masks, hoods, caps

Minimize use of alcohol-based skin preparations Apply skin preparations carefully; do not allow them to soak into hair or linens; avoid pooling on or under patient Wait for skin preparations to dry completely before draping patient Use incision drapes if possible All are flammable, even if labeled “flame resistant” Use wet drapes and towels adjacent to laser site Use incise drapes to isolate surgical field from fuels and oxidizers Use wet gauze sponges when possible Use cuffed tubes when possible Use laser-resistant tubes for upper airway laser cases Fill cuff with methylene blue-dyed saline for airway laser cases (to indicate breach in cuff) Protect cuff with wet pledgets for airway laser cases Cover hair near the operative site with sterile surgical lubricating jelly to prevent it from igniting Prepare the gastrointestinal tract when indicated Do not use mannitol-based bowel preparations Avoid nitrous oxide Dilute intestinal gases with an inert gas if indicated

Anesthesia components (endotracheal tubes, masks, nasal cannulas, tape, blood pressure cuffs)

Patient hair Intestinal gases

EQUIPMENT & MONITORING

Source

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Table 138–6

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Precautions Regarding Carbon Dioxide Absorbers and Halogenated Anesthetics in the Operating Room

Alert anesthesia personnel, including technicians and providers, to the nature of this hazard Develop anesthesia machine setup and maintenance protocols that ensure that absorbents do not become desiccated and are replaced regularly Avoid desiccation of absorbent; minimize or eliminate gas flow through absorber between uses, and turn anesthesia machine off at day’s end Replace CO2 absorbent every Monday before use; label canister with date that absorber should be replaced; replace absorbent if its hydration status is in question Periodically monitor temperature of CO2 absorbent canisters Monitor relation between inspired sevoflurane concentration and vaporizer setting; an unusually delayed rise or unexpected decline in inspired sevoflurane concentration compared with the vaporizer setting may indicate exothermic sevoflurane degradation Do not rehydrate absorbent by pouring water over it Consider using alternative absorbents that are free of strong alkali compounds

Further Reading Andersen K: Safe use of lasers in the operating room—what perioperative nurses should know. AORN J 79:171-188, 2004. Brechtelsbauer PB, Carroll WR, Baker S: Intraoperative fire with electrocautery. Otolaryngol Head Neck Surg 114:328-331, 1996. ECRI editorial staff: A clinician’s guide to surgical fires: How they occur, how to prevent them, how to put them out. Health Devices 32:5-24, 2003. ECRI editorial staff: Anesthesia carbon dioxide absorber fires. Health Devices 32:436-440, 2003. Hermans JM, Bennet MJ, Hirschmann CA: Anesthesia for laser surgery. Anesth Analg 62:218-229, 1983. Macdonald AG: A short history of fires and explosions caused by anaesthetic agents. Br J Anaesth 72:710-722, 1994. Olympio MA, Morell RC: Canister fires become a hot safety concern. Anesthesia Patient Safety Foundation Newsletter 18, 2003. Rampil IJ: Anesthetic considerations for laser surgery. Anesth Analg 74: 424-435, 1992. Van Der Spek AFL, Spargo PM, Norton ML: The physics of lasers and implications for their use during airway surgery. Br J Anaesth 60:709-729, 1988.

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Laser Complications Pattricia S. Klarr Case Synopsis A 75-year-old man with metastatic non–small cell carcinoma of the lung is scheduled for bronchoscopic laser tumor ablation under general anesthesia. He has a chronic nonproductive cough, and a computed tomography scan reveals tumor encroachment on the right bronchus.

PROBLEM ANALYSIS Definition Improved technology, better reliability, and reduced cost have led to an explosion in the applications for medical lasers over the past decade. Lasers deliver sterile, intense energy to tissue in both cutting and coagulation modes. Patients and operating room (OR) personnel are exposed to certain hazards with medical lasers, including atmospheric contamination, inadvertent perforation of a tissue structure or vessel, ignition of flammable material, and embolism. Although there are no federal safety requirements for medical lasers, there are national safety standards. The latter exist to decrease or prevent laser mishaps. Laser hazards are classified into four general risk categories, ranging from no risk to substantial risk. Medical lasers fall into the highest risk level. Therefore, proper use requires trained personnel and protective equipment for the operation of medical lasers.

types of lasers have their own unique risks. For example, the wavelength of the carbon dioxide (CO2) laser is in the far infrared region and is absorbed by the first surface it encounters, necessitating eye protection for both patient and OR personnel to prevent corneal damage. Argon, KTP:YAG, and Nd:YAG in both the visible and near infrared range are transmitted through clear material but absorbed by pigmented tissue. Therefore, they pass through the cornea but could damage retinal tissue. Laser hazards can be divided into beam-related and non-beam-related hazards. Nonbeam hazards include electric shock and laser-generated air contaminants. Beam-related hazards include perforation of a vessel or other structure, including the pilot balloon of an endotracheal tube. Delayed complications may appear after the use of certain lasers. In particular, the Nd:YAG laser can penetrate deeper than anticipated, causing bleeding or perforation to appear several hours to days later, when necrosis and edema are maximal.

Risk Assessment Recognition There are several types of medical lasers. Their differences are based on the medium used and the wavelength produced (Table 139-1). In addition to laser hazards in general, different

■

Commonly Used Lasers and Associated Hazards

Medium

Wavelength (nm)

Color

Features

Potential Hazard

CO2

10,600

Far infrared

Corneal damage

Holmium:YAG

2060 2140 (pulsed)

Infrared

Nd:YAG

1064

Near infrared

Ruby

694

Red

Helium-neon

632

Red

KTP:Nd:YAG

532

Green

Argon

488,514

Blue/ green

Readily absorbed by all biologic tissue; very precise, superficial penetration; not fiberoptically transmitted Precise cutting ability; minimal diffusion of thermal energy; good hemostasis; transmitted fiberoptically Can be transmitted fiberoptically; uses photocoagulation plus thermal necrosis; highest tissue penetration Absorbed by pigments except hemoglobin Used as an aiming beam for CO2 plus Nd:YAG lasers Fiberoptic transmission possible; some scatter and necrosis (less than Nd:YAG) Can be transmitted fiberoptically; absorbed by hemoglobin and pigmented tissue

EQUIPMENT & MONITORING

Table 139–1

Both patients and OR staff must be protected from laser hazards while the laser beam is on. Reflected beams can be aimed at an unintended site, causing eye damage, ignition of flammable material, or burns.

Corneal damage; can pierce metal More prone to late complications, delayed edema, tissue sloughing, retinal damage Retinal damage Harmless, unless directed toward eyes Similar to Nd:YAG (less retinal damage or tissue penetration) Retinal damage

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During laser airway surgery, airway fires are the most common serious complication and can cause severe morbidity and death. Should contact with a flammable endotracheal tube result in a fire, the blowtorch-like nature of the ignited fumes in an oxygen (O2)-rich environment can result in immense damage. If inhaled, smoke produced by the vaporizing of 1 g of tissue is equivalent to smoking six unfiltered cigarettes. This smoke, or the “laser plume,” can potentially be a vector for viral transmission, although there has been no documentation of a health care provider contracting a disease in this manner.

Implications Laser use has increased tremendously in the past few years. Lower cost and increased reliability have made medical lasers attractive for a variety of surgical applications. In addition to removing tumors, lasers are used to treat such conditions as benign prostatic hypertrophy and macular degeneration, to perform coronary angioplasty, and to treat various dermatologic and ophthalmic problems. Their increased utilization, however, results in the increased potential for complications. Lasers require a highly skilled staff trained in their use. They must be vigilant and able to anticipate associated risks and take measures to protect the patient and other medical personnel. If properly and promptly managed, complications are generally minor and treatable.

MANAGEMENT Airway fire is the most serious complication of laser use. To minimize damage, the OR team must act quickly and in a coordinated fashion, taking the following actions: ●

● ● ●

● ● ●

● ●

Disconnect the O2 source and remove the endotracheal tube or other object on fire. Douse any flames with normal saline. Resume anesthesia with mask ventilation, using l00% O2. Perform diagnostic laryngoscopy and rigid bronchoscopy to inspect the extent of damage. Remove any debris. Reintubate if airway damage is present. Consider a low tracheostomy if the damage is severe or if reintubation is unsuccessful. Use mechanical ventilation if required. Administer systemic steroids if necessary. Obtain and check the chest radiograph.

credentials in laser use and safety precautions should be allowed to operate the laser. While it is in use, everyone in the OR should be protected from known laser hazards.

Eye Protection Because the eye is most vulnerable to injury, all personnel must wear proper eye protection. Wraparound goggles with side protectors are advised, because standard eyeglasses do not protect the eyes from reflected beams that may glance off the side. Contact lenses are not protective. The protective lens must absorb the particular laser wavelength being used. Clear lenses are adequate for CO2 lasers, but for all other lasers, the lenses must be tinted. The patient’s eyes must be protected. Patients who are awake should also wear laser-safe goggles. If they are not the operative site, the eyes of anesthetized patients should be closed and covered with saline-soaked gauze or a nonshiny metal shield. Because all lasers other than CO2 lasers penetrate clear glass, windows must be protected. Signs must be placed prominently at all entrances to the OR warning of laser use, and spare goggles should be available at all entrances.

Perforation Risk When not directed at the target tissue, the laser beam should be turned off or set in a standby mode. Misdirected laser beams can cause inadvertent perforation of a vessel or viscus. Coronary arteries have been perforated during laser angioplasty, resulting in severe complications (e.g., tamponade, acute myocardial infarction, urgent coronary artery bypass surgery). Currently, the risk for such perforation approaches l%. Complications from perforation may not develop until several days postoperatively. Systemic air embolism with serious complications has also been reported with laser use.

Skin Damage Avoid prolonged laser exposure to nontargeted skin. All nearby skin should be protected with moist drapes. Compared with the cornea, the skin has a layer of dead cells that makes damage less likely.

Environmental Hazards

Surgical drapes are fire resistant, but if they are ignited, the flames are difficult to extinguish because the drapes are also water resistant. A fire extinguisher should be available when surgical drapes are in use. If any OR personnel are injured, they must be appropriately treated, and an incident report should be generated. The event should be investigated to prevent recurrences.

Laser plume (described earlier) can produce an unpleasant odor, cause tearing and bronchial irritation, and it may be a viral vector. Inhalation of this plume can be minimized with the use of a high-efficiency smoke evacuator and the use of special laser surgical masks. The Barrier Brand laser plume facemask (Molnlycke Health Care, Inc., Newton, Pa.) is a high-efficiency mask that filters plume particulate. However, such masks require periodic replacement when moist. Moreover, some laser plume facemasks may not provide complete protection from all laser-induced airborne debris.

PREVENTION

Airway Fire

Prevention depends on the particular complication to be avoided. Only personnel with the proper training and

No preventive measure guarantees that a fire will not occur. An insufflation technique or jet ventilation should be used

●

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for airway surgery, if possible, but the patient must be monitored for barotrauma and gastric dilatation. A laser-safe endotracheal tube, a conventional endotracheal tube wrapped in metal foil, or a commercially made laser tube or metal tube should be used. Foil-wrapped tubes can have rough edges that abrade tracheal tissue, however, and they may have gaps that expose flammable portions. Cuffs of metal tubes are flammable. These tubes are less flexible and have a reduced internal diameter that makes ventilation more difficult; they are also expensive. If a cuff is in the airway, it should be inflated with dyed saline to indicate if cuff rupture occurs. Use of moistened pledgets around the tracheal tube is also helpful. Keep the fraction of inspired O2 as low as possible—less than 30% or whatever is necessary to maintain adequate

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O2 saturation. Do not use nitrous oxide, because it can support combustion.

Further Reading Brown SG: Science, medicine, and the future: New techniques in laser therapy. BMJ 316:754-757, 1998. Kestenbaum A: New revision of ANSI Z136.1 (laser safety standards). LIA Today, May 8, 2000. Also available from Health Physics Society at http://hps.org/hpspublications/articles/ansiz136.1.html. Koster R, Kahler J, Brockhoff C, et al: Laser coronary angioplasty: History, present and future. Am J Cardiovasc Drugs 2:197-207, 2002. Laser Safety Information Bulletin, Laser Institute of America. Available at http://www.laserinstitute.org/publication/safety_bulletin/laser_safety _info. Rampil IJ: Anesthesia for laser surgery. In Miller RD (ed): Anesthesia, 5th ed. New York, Churchill Livingstone, 2000, pp 2199-2212.

EQUIPMENT & MONITORING

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Pulse Oximetry Mark D. Stoneham Case Synopsis A trauma victim is undergoing computed tomography of the head. His lungs are being ventilated with 100% oxygen. Monitoring consists of electrocardiogram (ECG), noninvasive blood pressure, and pulse oximetry, which displays an oxygen saturation (SpO2) of 100%. The breathing circuit becomes disconnected as the scan commences, but the ventilator disconnect alarm is faulty and fails to sound. Five minutes elapse before the patient’s SpO2 starts to drop; another minute passes before the oximeter low-saturation alarm sounds at 90%. The SpO2 then falls rapidly to 45% before the problem can be corrected.

PROBLEM ANALYSIS Definition and Recognition The arterial pressure of oxygen (PaO2) of a patient receiving 100% oxygen (O2) may reach as high as 600 mm Hg, as calculated from the alveolar gas equation.1 The O2 content of the body in this case equals the O2 in the lungs—perhaps 4 L—plus O2 bound to hemoglobin and other pigments, plus O2 dissolved in the plasma. Basal O2 consumption is about 250 mL/min–1. In an otherwise fit adult, these reserves provide enough O2 for several minutes. If ventilation stops for any reason, the PaO2 will start to decline. However, as can be seen from the oxygen-hemoglobin dissociation curve (Fig. 140-1), there will be no change in SpO2 until the PaO2 has fallen below 100 mm Hg. Thereafter, SpO2 will fall slowly until it reaches 90% (corresponding to a PaO2 of about 65 mm Hg), at which point an audible low-SpO2 alarm will sound. After this, desaturation occurs very rapidly. Thus, the pulse oximeter has been termed a lag monitor. In addition, there is a time lag between the true and displayed SpO2 due to signal averaging. This is an attempt to reduce the effects of artifact (electromagnetic interference) by averaging the detected signal over a variable period (often 5 to 30 seconds), rejecting sudden changes in SpO2. The implication of the lag effect is that a potentially life-threatening desaturation may go unnoticed for several minutes. For this reason, the pulse oximeter has been described as a “sentry standing on the cliff-edge of desaturation.” Other pulse oximetry complications are classified according to whether they are related to technologic limitations or the clinical interpretation of oximeter readings by the operator. TECHNOLOGIC LIMITATIONS

OF

PULSE OXIMETRY

gets smaller, it is amplified by the oximeter, but at the expense of amplifying background interference as well. At the highest amplification, the oximeter may generate SpO2 from the amplified noise signal itself. Thus, oximetry may be less effective in very ill patients with poor tissue perfusion, patients with vasoconstriction, or those who are hypothermic. Cardiac arrhythmias may also interfere with proper detection of the pulsatile signal by the oximeter and calculation of the pulse rate. Motion induces the movement of venous and capillary blood within tissue beneath the oximetry sensor (often the fourth or fifth digit of the hand), so that the pulsatile fraction of the SpO2 signal is no longer solely arterial blood. Shivering is the most common cause of motion artifact. Cardiac valvular defects, such as tricuspid regurgitation, also cause strong venous pulsations, in which case venous SpO2 may be recorded by the pulse oximeter. Intra-aortic balloon counterpulsation also generates artifact. Oximeter manufacturers have designed software algorithms to reject such artifact. These include the following: ●

●

●

●

Arterial Pulse Recognition. A pulsatile signal is required for an oximeter to measure surface SpO2. As the pulse signal 1 PaO2 = FiO2(PB − P*H2O) − PaCO2([1/R]), where PB is barometric pressure (760 mm Hg at sea level), FiO2 is the fraction of inspired O2, P*H2O is the vapor pressure of water at body temperature (47 mm Hg), and R is the respiratory quotient.

570

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Signal-averaging time manipulation. This was described earlier (often 5 to 30 seconds). Pulse oximetry linked to the ECG. Here, oximetry software assumes that for each “arterial” pulse detected by the oximeter, there must be a temporally linked ECG complex. Any pulsatile signal not associated with an ECG complex is rejected. Unfortunately, although the theory is good, in practice, it is not very effective. Time division multiplexing. The two LEDs are cycled (red on–infrared on), with both off many times per second. In this way, much background “noise” from extraneous sources, such as overhead lighting, is reduced. Quadrature division multiplexing. The red and infrared LED signals are separated in phase, rather than time, and subsequently recombined in phase. In this way, an artifact due to motion or electromagnetic interference may be eliminated, because it will not be in the same phase as the two LED signals once they are recombined. Signal extraction technology. Software analyzes the frequencies of all “pulsatile” signals and assumes that the frequency with the highest calculated SpO2 is arterial and rejects

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Pulse Oximetry

571

Figure 140–1 ■ Oxygen-hemoglobin dissociation curve.

all others (e.g., venous pulsations). This is an effective method of rejecting motion artifact, especially shivering.

Patient Safety Issues. There have been reports of babies suffering skin burns or pressure damage. These injuries occurred because early oximetry probes had a heater unit to ensure adequate skin perfusion or when probes and oximeters from different manufacturers were connected together. There have also been reports of oximeters causing burns in patients during magnetic resonance imaging due to current being induced in the cables by fluctuating magnetic fields. Low Oxygen Saturation Values. SpO2 values less than 70% are considered unreliable because there are few experimental or clinical values used to calibrate the device. The nomogram used by pulse oximeters to calculate SpO2 values (i.e., from the ratio of red to infrared, pulse-added absorbencies) is obtained from volunteers given increasingly hypoxic gas mixtures to breathe, but only down to SpO2 values of 70%. Despite this, directional changes in SpO2 are generally accurate.

Waveform Presence. All oximeters display some visible indicator of the pulse. This can be a plethysmographic waveform or a simple LED laddergram. If it is not visible, indicating that a pulse cannot be detected, any SpO2 values displayed cannot be considered valid. Bright overhead lighting, shivering, and motion artifact can produce apparently pulsatile waveforms and SpO2 values when no pulse is present. Sudden Changes in Oxygen Saturation Values. Physiologically, SpO2 is unlikely to change instantaneously (e.g., from 98% to 85%). If this happens, it should first be considered an artifact. One exception might be a patient with an intracardiac, bidirectional shunt and sudden changes in ventricular loading conditions (right or left ventricular preload or afterload). Oxygen Saturation Monitors Oxygenation, Not Ventilation. One case report highlighted the false sense of security that may be provided by pulse oximetry. An elderly woman in the postanesthesia care unit receiving O2 via facemask became increasingly drowsy due to carbon dioxide (CO2) narcosis, despite an SpO2 of 96%. Her respiratory rate and minute volume were low due to residual neuromuscular block and sedation. But because she was receiving a high inspired concentration of O2, her SpO2 was maintained. The arterial CO2 concentration reached 280 mm Hg (normal, 40 mm Hg), and she required postoperative mechanical ventilation for 24 hours. Thus, SpO2 gives a good estimation of adequate oxygenation but does not provide information about ventilation, especially when supplemental O2 is administered.

EQUIPMENT & MONITORING

Abnormal Hemoglobin and Dyes. Carboxyhemoglobin causes pulse oximeters to register artificially high SpO2 values. This is because carboxyhemoglobin absorbs very little light in the infrared range, but as much light as oxyhemoglobin in the red range. Thus, oximeters “see” carboxyhemoglobin as oxyhemoglobin and display the approximate sum of both hemoglobins as SpO2. This trends toward 100%. Methemoglobin has a high absorbency over a wide spectrum, causing SpO2 values to trend toward 85% when methemoglobin is greater than 10%. Circulating dyes, particularly methylene blue, may give transient, artificially low SpO2 values.

OPERATOR INTERPRETATION

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Risk Assessment Table 140-1 lists situations in which patients may be at increased risk for inaccurate oximetry readings.

Implications The most obvious adverse outcome with any monitor of oxygenation is a false-negative reading; namely, hypoxia is not detected by a pulse oximeter. Unrecognized hypoxia can lead to end-organ damage (e.g., myocardial ischemia, cerebral hypoxia, renal failure, blindness) or death. Fortunately, these are rare occurrences, partly because of a “redundancy” of multiple monitoring methods for unconscious patients. For example, the patient described in the case synopsis would not have become hypoxemic had there been a functioning capnograph, ventilator disconnect alarm, or spirometry. Any one of these would have sounded an alarm within seconds of the breathing circuit disconnection. Thus, it is possible for operators to rely too much on the pulse oximeter rather than on the clinical status of the patient. A pulse oximeter may also generate false-positive readings—in other words, hypoxia is reported when it does not exist. Such readings may lead to operator intervention, delays, or more invasive monitoring (e.g., arterial blood gas analysis) to confirm oximeter function and the patient’s clinical status. Table 140–1

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Sources of Errors and Complications in Pulse Oximetry

Effects of Dyshemoglobins and Dyes Carboxyhemoglobin: SpO2 displayed as sum of carboxyhemoglobin and oxyhemoglobin Methemoglobin: SpO2 values tend toward 85% with methemoglobin >10% Methylene blue: transiently, very low SpO2 values Indigo carmine: small decreases in SpO2 Indocyanine green: small decreases in SpO2 Nail polish: falsely low SpO2 values by 2%-3% SpO2 probe exposed to ambient light: falsely low SpO2 values by 1%-3%

MANAGEMENT Management of acute hypoxic complications must follow advanced cardiovascular life support guidelines. Securing the airway and administering 100% O2 to the patient should be followed by appropriate measures to remedy the cause of hypoxia. Clearly, knowledge of the effects of various dyshemoglobins and dyes on oximeter function can prevent the misinterpretation of SpO2 values under such circumstances. In cases in which there are problems with oximeter function or probe placement, it may be possible to select other sites for the probe (e.g., earlobe, nares, lip). In addition, an esophageal oximeter was recently described; I have used this device successfully in patients with extensive burns. There are also other methods of monitoring patients’ oxygenation, including transcutaneous partial pressure of oxygen monitoring, arterial blood gas analysis, and continuous mixed venous O2 saturation monitoring via an oximetric pulmonary artery catheter.

PREVENTION It is important to recognize the pulse oximeter for what it is— namely, another (albeit very useful) monitor of O2 delivery. Continued vigilance is required in the interpretation of oximeter readings under a wide variety of circumstances. Training of personnel is required to reduce observer misinterpretation of oximetry results. The pulse oximeter should not be relied on as the sole monitor of a patient’s welfare. In the case synopsis, a capnograph would have warned of the ventilator disconnection within a few breaths. Despite wide acceptance of pulse oximetry in anesthesia and critical care, there is no direct evidence that it has saved lives during anesthesia or in the postanesthesia care unit. Oximetry is a major advance in the noninvasive monitoring of the cardiorespiratory system. However, it should be used only in conjunction with other monitors by trained personnel, and it should not supplant clinical observation.

Clinical Conditions Causing Reduced Signal-to-Noise Ratio Mechanical: shivering and other motion artifact Hypovolemia: low cardiac output, shock, severe anemia Vasoconstriction: hypothermia, peripheral vascular disease Venous pulsations: tricuspid regurgitation; arteriovenous malformations, fistulas Circulatory support: cardiopulmonary bypass, intra-aortic balloon counterpulsation Light interference and radiant heaters: low SpO2 values of ⊕85%, inaccurate pulse rates

Oximeter Accuracy and Response Calibration by volunteer nomograms: accuracy of ± 2% over range 85% <SpO2 <100% Signal averaging: can cause spuriously low SpO2 values Low SpO2 values: no accurate clinical calibration <70% Penumbra effect: oximetry probe partially dislodged from its nominal (intended) position: low SpO2 values (85%-95%)

Complications Burns: mostly pediatric case reports and in magnetic resonance imaging Pressure necrosis: usually due to wraparound-type sensor SpO2, oxygen saturation.

Further Reading AHA/ACC/ILC guidelines 2000 for CPR and emergency CV care. Circulation 102:I158-I165, 2000. Atlee JL, Branotow N: Comparison of surface and esophageal oximetry in man. Anesthesiology 83:A455, 1995. Broome IJ, Harris RW, Reilly CS: The response times during anaesthesia of pulse oximeters measuring oxygen saturations during hypoxaemic events. Anaesthesia 47:17-19, 1992. Davidson JAH, Hosie HE: Limitations of pulse oximetry: Respiratory insufficiency—a failure of detection. BMJ 307:372-373, 1993. Dumas C, Wahr JA, Tremper KK: Clinical evaluation of a prototype motion artifact resistant pulse oximeter in the recovery room. Anesth Analg 83:269-272, 1996. Moller JT, Johannessen NW, Esperson K, et al: Randomized evaluation of pulse oximetry in 20,802 patients. II. Perioperative events and postoperative complications. Anesthesiology 78:445-453, 1993. Prielipp RC, Scuderi PE, Hines MH, et al: Comparison of a prototype esophageal oximetry probe with two conventional digital pulse oximetry monitors in aortocoronary bypass patients. J Clin Monit 16:201-209, 2000. Ralston AC, Webb RK, Runciman WB: Potential errors in pulse oximetry. I. Pulse oximetry evaluation. Anaesthesia 46:202-206, 1991.

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Ralston AC, Webb RK, Runciman WB: Potential errors in pulse oximetry. III. Effects of interferences, dyes, dyshaemoglobins and other pigments. Anaesthesia 46:291-295, 1991. Severinghaus JW, Kelleher JF: Recent developments in pulse oximetry. Anesthesiology 76:1018-1038, 1992. Tremper KK, Barker SJ: Pulse oximetry. Anesthesiology 70:98-108, 1989.

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Wahr JA, Tremper KK, Diab M: Pulse oximetry. Respir Care Clin N Am 1:77-105, 1995. Webb RK, Ralston AC, Runciman WB: Potential errors in pulse oximetry. II. Effects of changes in saturation and signal quality. Anaesthesia 46:207-212, 1991.

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Inspiratory and Expiratory Gas Monitoring Amit V. Chawla and Gauhar Sharih Case Synopsis A 23-year-old woman has laparoscopic surgery for evacuation of an ectopic pregnancy. She is under general endotracheal anesthesia (oxygen, nitrous oxide, isoflurane) and in the Trendelenburg position. She is mechanically ventilated. During introduction of pneumoperitoneum, her end-tidal carbon dioxide (ETCO2) initially rises from 32 to 45 mm Hg, but within a few minutes, it falls precipitously to 18 mm Hg. Her blood pressure falls from 100/70 to 70/50 mm Hg, and her heart rate increases from 80 to 100 beats per minute. Oxygen saturation falls from 98% to 87%. Inspired gas values are as follows: oxygen (O2) 40%, nitrous oxide (N2O) 53%, ETCO2 0 mm Hg, isoflurane 1.5%. Expired gas values are as follows: O2 37%, N2O 50%, ETCO2 18 mm Hg, isoflurane 1.2%

Recognition

PROBLEM ANALYSIS Definition Monitoring of inspired O2 concentrations in anesthetic or ventilator circuits is mandatory. In addition, inspiratory and expiratory monitoring for other gases (CO2, N2O) and volatile inhalational agents is vital to any anesthesia monitoring. The American Society of Anesthesiologists’ standards for basic patient monitoring strongly advise inspiratory and expiratory gas monitoring for all patients having general anesthesia. Gas monitoring is useful for both diagnosis and management.

The usefulness of inspiratory and expiratory gas monitoring for detecting complications of anesthesia and monitoring the affected parameters is illustrated in Table 141-1. Oxygen Analysis. Continuous O2 analysis in inspired gas mixtures allows the early detection of hypoxic gas delivery. These analyzers are not suitable for detecting disconnections within the breathing system.

C

40

OXYGEN PCO2 (mm Hg)

Inspired O2 monitoring will alert the anesthetist if a hypoxic O2 concentration is delivered to the patient’s airway. Machine-mounted (in-circuit) and in-line (between the circuit and the patient’s airway) analyzers provide the means for taking this measurement.

PETCO2

PACO2

30

20

B

EXPIRATION

D

10

CARBON DIOXIDE Altered ventilation (CO2 elimination), cardiac output (perfusion), distribution of pulmonary blood flow (e.g., embolism), and metabolic activity (CO2 production) are detected with expiratory CO2 monitoring. Capnometry is the measurement of CO2 concentrations during inspiration and expiration. Capnography is the continuous display of a patient’s capnogram during both these phases of ventilation (Fig. 141-1). VOLATILE ANESTHETICS

AND

NITROUS OXIDE

Monitoring of anesthetic vapors and N2O in the inspired and expired gases is useful during the induction of anesthesia, for closely observing and managing the depth of anesthesia, and finally for assessing recovery from volatile inhalation anesthesia. 574

A 0 0

1

2

3

Time (sec) Figure 141–1 ■ Expiratory capnogram depicting a normal carbon dioxide (CO2) waveform during expiration as a function of time. During inspiration, the CO2 tension is nearly 0 mm Hg. Note three distinct phases (A, B, and C) of the increasing partial pressure of CO2 (PCO2) during expiration before it decreases abruptly with inspiration (phase D). Anatomic dead-space gas is cleared during phase A. Because this gas contains little CO2, PCO2 remains near its inspiratory phase value. During phase B, PCO2 increases rapidly to approach its alveolar tension (PACO2). Remaining alveolar gas is washed out during phase C, which is termed the alveolar plateau phase, owing to little increase in PACO2. However, its slope may increase with high CO2 production (e.g., hypermetabolic states) or nonhomogeneous gas mixing (e.g., airway obstruction). Peak end-tidal CO2 (PETCO2) reached during the alveolar plateau is the end-tidal CO2. This has a somewhat lower value than systemic arterial CO2 (PaCO2) because of mixing of alveolar dead space and alveolar gas.

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Table 141–1 ■ Use of Gas Monitoring to Detect Complications Complication

Inspiratory Gas Monitoring

Expiratory Gas Monitoring

Patient disconnect

No effect

Esophageal intubation

No effect

Machine malfunction

O2, CO2, N2, N2O, VA† No effect VA (↑) No effect

O2, CO2, N2,* N2O, VA (all ↓) CO2 (↓), N2 (↓ or no effect) O2, CO2, N2, N2O, VA† CO2 (↓), N2 (↑)‡ VA (↑) CO2 (↓)

No effect No effect

CO2 (↑) CO2 (↓)

No effect

CO2 (↑)

Venous air embolism Anesthetic overdose Circulatory shock, cardiac arrest Hypermetabolic state Right-to-left shunt (CHD) Inadequate ventilation

*N2 would increase if air were sampled. † Parameters could go up or down or remain unchanged, depending on sampling site, flow rates, whether air or N2O was being administered, and so on. ‡ Rise in N2 is detectable only if a mass spectrometer or Raman scattering monitor is used. CHD, coronary heart disease; VA, volatile anesthetic.

Capnography. The capnograph is likely the most useful monitor in contemporary anesthesia practice. Capnography provides information about the mechanics of lung function (e.g., dead space, airway obstruction), gas exchange (e.g., ventilation-perfusion mismatch), metabolism (e.g., hypermetabolic versus hypometabolic states), and cardiovascular function (e.g., reduced blood flow to lungs with myocardial dysfunction, pulmonary embolism, or left-to-right shunt). Nonetheless, its most useful functions are to confirm correct endotracheal tube placement, detect airway obstruction or disconnections, and identify anesthesia-ventilator breathing circuit malfunction (e.g., incompetent valves, CO2 absorber exhaustion, leaks).

Infrared Absorption Spectrophotometry. Asymmetrical, polyatomic molecules absorb infrared light at specific wavelengths. Therefore, neither O2 nor nitrogen (N2) can be detected by this method. This modality is best suited for monitoring N2O, CO2, and volatile agents. Volatile agents, however, can complicate the analysis owing to interactions between specific gases and vapors and the close proximity of absorption spectra for volatile agents of interest. Optical filters and proprietary detection systems enhance the sensitivity for the detection of specific volatile agents. Paramagnetic Analyzers. O2 is unique among anesthetic gases in that it is strongly paramagnetic. Thus, if introduced into a nonhomogeneous magnetic field, O2 will move toward

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the stronger part of the magnetic field, while other diamagnetic gases move away. This principle is used in breathto-breath monitoring of O2 concentrations in inspired and expired gas. Mass Spectrometry. This modality is suitable for all anesthetic gases. Mass spectrometers use electrostatic and magnetic fields to spread these gases into a spectrum according to their mass-to-charge ratios. Ion current detectors are used for quantitative measurements. Raman Scattering. Gas sample molecules are scattered by coherent photons produced by a high-intensity argon laser (Raman scattering). After impact, the gas molecules are momentarily excited to unstable vibrational and rotatory states. After returning to their normal state, photons of a characteristic but lower frequency are emitted. The frequency shift between incidental and scattered light is specific for individual gases. Raman scattering detects most gases used in anesthetic practice (including O2 and N2), but not monoatomic gases such as helium and xenon. Owing to the size and cost of the equipment, mass spectrometry and Raman scattering monitoring are not routinely used, unlike infrared and paramagnetic analyzers.

Risk Assessment Similar to other devices used in medical practice, devices used for inspiratory and expiratory gas monitoring are prone to malfunction. This can occur as a result of the aging of component parts and systems, direct damage to the system or instrument, failure to properly calibrate the instrument, or interference by secretions or water accumulation in sampling lines, among other causes. This risk is reduced with regular inspection and preventive maintenance according to the manufacturer’s recommendations. The risk of direct injury (thermal, laser, electrical, explosive) to a patient from the malfunction of devices for monitoring inspiratory and expiratory gases is minimal, provided these devices are used as intended. Malfunction or failure of gas monitoring devices may cause indirect harm as a result of incorrect or missing information, misinterpretation of information, or an incorrect response to correct information.

Implications INCORRECT

OR

MISSING INFORMATION

As with any monitor, the information it provides must be considered in the context of the individual patients and circumstances. In the unlikely event that an erroneous value is reported (e.g., falsely high volatile agent concentrations due to miscalibration), the clinician must consider the value in light of the patient’s current status. Are there signs that the patient’s anesthesia is too deep? Similarly, a sudden fall in ETCO2 is not likely due to pulmonary embolism if the patient’s hemodynamic status remains unchanged. Rather, an air leak or a disconnection may have occurred. Finally, it is possible (but unlikely with properly maintained equipment) that a multiagent detection device will fail to provide information for one agent (i.e., agent “dropout” due to component or

EQUIPMENT & MONITORING

Monitoring of Anesthetic Agents. In-line and endtidal monitoring of anesthetic vapors is important for patient safety. It is used to detect vaporizer malfunction (e.g., due to calibration error). Such monitoring may also help prevent unintentional anesthetic overdose or underdose. Further, end-tidal agent monitoring may help detect the mixing of agents. Techniques commonly used for inspiratory and expiratory gas monitoring include the following.

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electronic circuitry failure) but report correct values for other agents. Again, the event must be viewed in light of the patient’s circumstances. Is there a reasonable explanation for the dropout? Are the other data plausible? MISINTERPRETATION

OF INFORMATION

It is possible that a clinician may misinterpret correct information supplied by a monitor. For example, an increase in ETCO2 of 5 to 10 mm Hg over 10 to 15 minutes might be misinterpreted as evidence of malignant hyperthermia when in fact it is due to hypoventilation or use of an exhausted CO2 absorber (in which case, the inspired CO2 will also rise). Again, individual data must be considered within the context of other patient data, such as vital signs, temperature, and inspired CO2 level. WRONG RESPONSE

TO

Oxygenation (Inspired Gas) ●

●

Ventilation (Expired Gas) ●

CORRECT INFORMATION

A monitor may provide correct information, but the clinician may not believe it or may respond inappropriately. As with misinformation or missing data, the clinician must consider individual patient data within a global context. Carefully consider other data and the patient’s condition before presuming device failure. Further, the clinician must know how to use gas monitoring data in diagnosis and management.

●

MANAGEMENT Inspiratory and expiratory gas monitoring is required or useful for the following aspects of perioperative patient diagnosis and management: ● ●

● ● ● ● ● ●

Assessment of oxygenation and ventilation Diagnosis of pulmonary embolism (e.g., gas, thrombus, amniotic fluid) Determination of anesthesia depth Diagnosis of circulatory insufficiency Confirmation of endotracheal intubation Diagnosis of patient–breathing system disconnection Assessment of recovery from volatile anesthetics Teaching of anesthetic pharmacokinetics

Returning to the case synopsis, the initial rise in ETCO2 is explained by absorption of CO2 in the blood from the insufflated gas in the peritoneum. The sudden drop in ETCO2 a few minutes later could be due to pulmonary gas embolism. This increases physiologic dead space, leading to impaired gas exchange and cardiovascular dysfunction.

PREVENTION The American Society of Anesthesiologists’ standards for basic anesthetic monitoring (effective October 15, 2003) are as follows1: 1 Under extenuating circumstances, the responsible anesthesiologist can waive any of these requirements. If so, this action and the reasons why should be recorded in the patient’s medical record.

During every administration of general anesthesia using an anesthesia machine, the concentration of O2 in the patient breathing system should be measured by an O2 analyzer with a low O2 concentration limit alarm. During all anesthetics, a quantitative method of assessing blood oxygenation, such as pulse oximetry, should be used. Adequate illumination and exposure of the patient are necessary to assess skin and/or mucosal color.

●

●

For every patient receiving general anesthesia, the adequacy of ventilation should be continually evaluated. Qualitative clinical signs such as chest excursion, observation of the reservoir breathing bag, and auscultation of breath sounds are useful. Continual monitoring for the presence of expired CO2 should be performed unless this is invalidated by the nature of the patient, procedure, or equipment. Quantitative monitoring of the volume of expired gas is strongly encouraged. When an endotracheal tube is inserted or a laryngeal mask is placed, its correct positioning should be verified by clinical assessment and by identification of CO2 in the expired gas. Continual ETCO2 analysis—from the time of endotracheal tube or laryngeal mask placement until extubation or removal, or until initiation of transfer to a postoperative care location—should be performed using a quantitative method such as capnography or capnometry. When ventilation is controlled by a mechanical ventilator, a device that is capable of detecting disconnection of the breathing system’s components should be in continuous use. The device must give an audible signal when its alarm threshold is exceeded. During regional anesthesia and monitored anesthesia care, the adequacy of ventilation should be evaluated, at least by continual observation of qualitative clinical signs.

Further Reading Dorsch JA, Dorsch SE: Understanding Anesthesia Equipment, 4th ed. Baltimore, William & Wilkins, 1999. Knopes KD, Hecker BR: Monitoring anesthetic gases. In Lake CL (ed): Clinical Monitoring and Anesthesia Care. Philadelphia, WB Saunders, 1994, pp 461-471. Pace NL: Why monitoring during anesthesia has unintended and undesirable consequences. In Anesthesia and Perioperative Complications. St. Louis, Mosby–Year Book, 1992, pp 173-202. Shulman D, Aronson HB: Capnography in early diagnosis of carbon dioxide embolism during laparoscopy. Can J Anaesth 31:455, 1984. Tremper KK, Barker SJ: Monitoring of oxygen. In Lake CL (ed): Clinical Monitoring and Anesthesia Care. Philadelphia, WB Saunders, 1994, pp 196-212. Vender JS, Gilbert HC: Monitoring the anesthetized patient. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 3rd ed. Philadelphia, Lippincott-Raven, 1997, pp 621-641.

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Transesophageal Echocardiography Patrick E. Benedict and Jack S. Shanewise Case Synopsis A 65-year-old woman undergoing emergency coronary artery bypass graft surgery for unstable angina has incomplete revascularization due to lack of a suitable conduit. Insertion of a transesophageal echocardiography (TEE) probe during cardiopulmonary bypass is difficult. After several attempts, the probe suddenly advances; however, its tip appears in the surgical field anterior to the heart, after perforating the pharynx. Subsequent discussion with the patient’s husband reveals that she has a 20-year history of dysphagia.

PROBLEM ANALYSIS Definition

Recognition Oropharyngeal trauma may be seen directly or may manifest as bleeding from the mouth. Gastrointestinal hemorrhage may be occult and present as hypovolemic shock or unexplained anemia. Insertion of a gastric tube should confirm the diagnosis. Perforation of the esophagus may be apparent to the surgeon or it may present later with sepsis or severe chest pain in a conscious patient. Buckling of the probe tip results in an inability to withdraw the probe from the esophagus.

Risk Assessment When possible, all patients should be asked about esophageal symptoms and diseases before insertion of the TEE probe. Three questions should always be asked: 1. Have you ever had any trouble with your esophagus? 2. Do you have any difficulty swallowing food? 3. Have you ever vomited blood? If the patient answers “no” to all three questions, it is safe to proceed. When the patient cannot be interviewed directly, a family member should be questioned. At a minimum, the medical record should be reviewed for esophageal problems. Contraindications to TEE are listed in Table 142-1. However, if TEE might provide important information and there is a history of esophageal disease, a preprocedure gastroenterologic evaluation with fiberoptic esophagoscopy is one option to consider. The mouth should be inspected before TEE probe insertion to look for loose teeth and EQUIPMENT & MONITORING

As TEE is used more frequently in operating rooms, anesthesiologists need to be aware of potential complications and their prevention. Most TEE complications are minor and are related to trauma to the oropharynx during probe insertion. More serious problems, such as pharyngeal perforation, esophageal perforation, and gastrointestinal bleeding, occur on rare occasions. A TEE complication unique to the operating room is laryngeal injury with vocal cord dysfunction. This can occur in patients having TEE monitoring during sitting craniotomy with prolonged periods of extreme neck flexion. TEE probe placement and manipulation can compress the bronchi or cause displacement of the endotracheal tube, especially in small children. In patients who are not intubated, the TEE probe may inadvertently be inserted into the trachea instead of the esophagus. Also, the tip of the TEE probe sometimes buckles back on itself in the esophagus, making its removal difficult and hazardous. Although esophageal burns due to transducer heat formation are theoretically possible, this complication has not been reported. Most TEE systems automatically shut down when the probe temperature exceeds a safe level. During TEE monitoring, anesthesiologists may be distracted from noticing more acute and important changes in vital signs. Also, without proper training and knowledge, TEE monitoring may be erroneously interpreted, leading to inappropriate management decisions.

It is associated with unusual imaging (upside-down orientation) and reduced control knob mobility.

Table 142–1 ■ Contraindications to Transesophageal Echocardiography Absolute Contraindications Esophageal obstruction Stricture Tumor Upper or lower sphincter hypertrophy Esophageal injury Perforation Recent esophageal surgery Fistula Esophageal diverticulum Unstable cervical spine

Relative Contraindications Undiagnosed dysphagia Esophageal varices Upper gastrointestinal tract bleeding

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preexisting injuries. TEE probes with stretched and loose steering cables may be more prone to buckle back on themselves in the esophagus and should be repaired before use. In most settings in which intraoperative TEE is used, other monitoring and interventional devices occupy the same pathway as the TEE probe or a nearby one. These devices include endotracheal tubes, temperature monitoring devices, gastrointestinal drainage tubes, and feeding tubes. Given the size and rigidity of TEE probes, displacement of any one of these devices is a distinct possibility. Potential complications from device dislodgment range from minor annoyances (e.g., improperly functioning gastric tube) to potentially life-threatening situations (e.g., displacement of the endotracheal tube into a main-stem bronchus, impairing the ability to ventilate the patient).

Implications Although rare, fatal complications from TEE can occur. As with all medical procedures, a risk-benefit analysis must be made before proceeding with the TEE examination. There is, however, a large experience with this procedure, indicating that the risk is minimal when performed on properly screened patients and using the proper technique.

PREVENTION The two cornerstones for preventing TEE complications are preprocedure assessment for esophageal disease and careful and gentle probe insertion and manipulation. Other devices occupying the same pathway must be carefully watched during placement and removal of the TEE probe. Excessive force should never be used to pass an apparent obstruction to TEE probe advancement. The probe should not be locked in a flexed position for prolonged periods, and it should never be advanced or withdrawn when the wheel locks are engaged. Patients with gastric pathology can safely undergo TEE examination, but the operator must not advance the TEE probe beyond the esophagus to avoid any potential problems with gastric insertion. Although not strictly a complication, damage to the TEE machinery is an extremely undesirable consequence of careless use. Typically, TEE systems are among the most expensive operating room devices, and repairs are extremely costly. This fact, along with the fragile nature of these complex electronic devices, underscores the need for gentle handling of TEE probes.

Further Reading MANAGEMENT Bleeding from the mouth after TEE should prompt careful, direct inspection of the mouth and pharynx to identify the location and extent of the injury. Minor trauma to the oropharynx often requires no specific treatment, but antibiotics may be indicated for more extensive injuries. Significant, persistent gastrointestinal bleeding after TEE should be evaluated with endoscopy. Besides permitting a diagnosis, endoscopy can provide a means of treatment, such as electrocautery. If perforation of the esophagus is suspected, it can be diagnosed by fluoroscopy with watersoluble contrast swallow. Perforation is usually treated as a surgical emergency. Pharyngeal perforation can be diagnosed by direct inspection and, if significant, warrants emergency consultation with an otolaryngologist for surgical drainage. Airway patency always takes precedence over TEE monitoring, and the probe should be removed immediately if airway problems occur. A TEE probe with its tip buckled back on itself should be advanced into the stomach to allow room for it to unflex before any attempt is made to remove it.

Benedict PE, Foley K: Transesophageal echocardiography not without pitfalls. J Cardiothorac Vasc Anesth 11:123, 1997. Daniel WG, Erbel R, Kasper W, et al: Safety of transesophageal echocardiography: A multicenter survey of 10,419 examinations. Circulation 83:817-821, 1991. Gilbert TB, Panico FG, McGill WA, et al: Bronchial obstruction by transesophageal echocardiography probe in a pediatric cardiac patient. Anesth Analg 74:156-158, 1992. Khandheria B, Tajik A, Freeman W: TEE examination: Technique, training, and safety. In Freeman W, Seward J, Khandheria B, et al (eds): Transesophageal Echocardiography. Boston, Little Brown, 1994, pp 49-51. O’Shea JP, Southern JF, D’Ambra MN, et al: Effects of prolonged transesophageal echocardiographic imaging and probe manipulation on the esophagus—an echocardiographic-pathologic study. J Am Coll Cardiol 17:1426-1429, 1991. Spahn DR, Schmid S, Carrel T, et al: Hypopharynx perforation by a transesophageal echocardiography probe. Anesthesiology 82:581-583, 1995. Urbanowicz JH, Kernoff RS, Oppenheim G, et al: Transesophageal echocardiography and its potential for esophageal damage. Anesthesiology 72:40-43, 1990. Woodland RV, Denney JD, Moore DW, et al: Inability to remove a transesophageal echocardiography probe. J Cardiothorac Vasc Anesth 8:477-479, 1994.

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Pema Dorje Case Synopsis A 48-year-old woman with a small build and a history of heavy smoking has a 20-gauge, 51-mm cannula placed atraumatically in her left radial artery for monitoring during aortobifemoral and right femoropopliteal bypass surgery. Two days after surgery, she complains of pain in her left hand, which is cold and shows discoloration of the fingers. A few blisters are seen on the radial side of the forearm proximal to the cannula.

PROBLEM ANALYSIS Definition The patient described in the case scenario has necrosis of the forearm skin proximal to the radial artery cannula, with ischemia of the fingers. Both of these complications of arterial blood pressure monitoring or sampling can occur independent of each other. Occlusion by the cannula or cannula-related thrombus of small endarteries emanating from the radial artery to the skin is the most likely cause of the skin necrosis (Fig. 143-1). A combination of thrombotic occlusion of the cannulated radial artery and inadequate collateral supply from an atherosclerotic ulnar artery likely resulted in the digital ischemia. The incidence of forearm skin necrosis is higher than that of hand or digital ischemia. Other complications of arterial cannulation and their risk factors are listed in Table 143-1.

Owing to the rich ulnar collateral flow, the risk of hand or digital ischemia is quite low, unless additional risk factors are present. The risk of occlusion leading to ischemia is increased by the following: ●

● ●

Advanced atherosclerosis or Raynaud’s or Buerger’s disease Low perfusion syndrome or shock Anatomic variation of the blood supply to the hand

Radial artery

Recognition

Risk Assessment

Superficial flexor muscles EQUIPMENT & MONITORING

Pain despite hand immobility and discolored and cold digits are highly suggestive of ischemia. The presence of a proximal pulse is not an indication of distal flow. The presence of such flow must be established with the use of a Doppler probe. The absence of radial and ulnar arterial flow in an individual with signs of hand or digital ischemia confirms the diagnosis. An absent digital pulse oximeter plethysmographic tracing on a hand with an arterial cannula at the wrist suggests inadequate flow and must be viewed with concern and treated as such. Ischemia of the skin in the forearm may present as patchy changes in coloration. These may progress to edema, blister formation, and skin ulceration.

Cutaneous endarteries

Reflected skin flap Base of first metacarpal

The risk of thrombotic occlusion of the radial artery by a 20-gauge needle is 10% to 30%, depending on the duration of arterial monitoring. Risk of thrombotic cannula occlusion is increased by the following: ● ●

●

Larger, longer, and non-Teflon cannulas Small radial arteries, as typically found in small women and children No heparin or pressure failure in the flush system

Figure 143–1 ■ Depiction of small endarteries arising directly from the radial artery, which are at risk of thromboembolic occlusion related to radial artery cannulation. (From Bedford RF: Radial arterial function following percutaneous cannulation with 18- and 20-gauge catheters. Anesthesiology 47:37-39, 1977.)

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Table 143–1 ■ Complications and Risk Factors Related to Arterial Cannulation Limb Ischemia Catheter material, size, length Advanced atherosclerosis or Raynaud’s or Buerger’s disease Small wrist circumference, which suggests a small vessel Accidental injection of medication into the arterial line

Neurologic Injury Needle injury to the nerve in close proximity to the cannulated artery Nerve injury because of prolonged wrist extension Nerve dysfunction from hematoma produced during repeated attempts at cannulation Stroke due to retrograde thrombus or air emboli with flushing (especially in infants or children)

Misinterpretation of Data “Acute hypertension”—transducer on the floor “Acute hypotension”—partial disconnection or pressure bag failure “Occult hemorrhage”—arterial line disconnection

Infection and Septicemia Aseptic cannulation Improper care of stopcocks Extended duration of cannulation

● ●

Use of vasoconstrictor infusions Ulnar artery cannulation if the patient had a recent ipsilateral radial artery cannulation

Small endarteries supplying the skin of the forearm may be blocked by a long cannula or a cannula-related thrombus. Hence, proximal skin ischemia is more common than hand or digital ischemia. Allen’s test is nonspecific. Therefore, it should be replaced by a digital plethysmographic tracing from a pulse oximeter in suspected high-risk cases. If the tracing disappears with digital occlusion of the radial artery before cannulation, the ipsilateral ulnar collateral supply is inadequate, and cannulation of that radial artery should be avoided. Routine testing in patients with no risk factors may be unnecessary owing to the very low incidence of complications. Risk factors for other complications are listed in Table 143-1.

Implications The low rate of complications with direct arterial blood pressure monitoring should not lead to a sense of complacency; when complications do occur, they can be severe. Awareness of the nature of and risk factors for complications related to direct arterial access can reduce their incidence and severity. In high-risk cases, consider avoiding arterial cannulation altogether; use an alternative site, or use the smallest cannula for the shortest possible time.

MANAGEMENT Monitor the hand for signs of ischemia if risk-benefit considerations justify direct arterial access in high-risk cases. With signs of finger, hand, or forearm skin ischemia, the

intra-arterial administration of local anesthetic or papaverine, along with temporary proximal venous occlusion, should be considered before the arterial cannula is removed. Vigorous aspiration of the cannula with proximal and distal digital pressure on the cannulated radial artery has been successful in removing some thrombi. Ipsilateral upper extremity sympathetic block of the affected extremity may also help. Importantly, a vascular surgeon should be consulted. Amputation of the hand or digits is considered after a line of demarcation becomes apparent. Skin grafting may be required for proximal skin necrosis.

PREVENTION Recognition of risk factors for the complications of peripheral arterial access is key to their prevention (see Table 143-1). Either avoid arterial cannulation altogether or consider an alternative site in high-risk cases. An arterial line should always be used for the shortest possible time and then removed. Thrombo-occlusion of the cannulated artery can be reduced with smaller (Fig. 143-2) and shorter cannulas, prior aspirin therapy, the addition of heparin in the flush solution, and the prevention of pressure failure of the flush. Recent cannulation of one of the arteries at the wrist contraindicates the cannulation of the other unless flow in the previously cannulated artery has clearly been reestablished. When in doubt, the adequacy of ulnar collateral flow should be confirmed by pulse oximeter tracings during digital compression of the radial artery. Wrist hyperextension should be corrected after radial artery cannulation to relieve stress on the nerves at the wrist.

100 Percent incidence of arterial occlusion

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60

40

20

0 0

20

40

60

80

100

Percent of vessel lumen occupied by catheter Figure 143–2 ■ Radial artery thrombosis during 24-hour cannulation. Small catheters in large vessels rarely produce thrombosis. (Adapted from Bedford RF: Invasive blood pressure monitoring. In Blitt CD [ed]: Monitoring in Anesthesia and Critical Care Medicine. New York, Churchill Livingstone, 1990, pp 93-134.)

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Further Reading Bedford RF: Radial arterial function following percutaneous cannulation with 18- and 20-gauge catheters. Anesthesiology 47:37-39, 1977. Bedford RF: Invasive blood pressure monitoring. In Blitt CD (ed): Monitoring in Anesthesia and Critical Care Medicine. New York, Churchill Livingstone, 1990, pp 93-134.

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Raju R: The pulse oximeter and the collateral circulation. Anaesthesia 41:784, 1986. Wyatt R, Glares I, Cooper DJ: Proximal skin necrosis after radial artery cannulation. Lancet 1:1135-1138, 1974.

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Peter J. Lee, William Prince, and James G. Ramsay Case Synopsis A 58-year-old man is taken to the operating room for elective repair of an infrarenal abdominal aortic aneurysm. During routine preparation and draping for surgery, a right internal jugular triple-lumen central venous catheter (CVC) is placed. The operation proceeds without complications. The patient is extubated in the operating room and taken to the intensive care unit in stable condition. On the fourth postoperative day, the patient develops fever and chills, has mental status changes, and becomes hypotensive.

PROBLEM ANALYSIS Definition Common complications of central venous pressure monitoring at the time of CVC insertion or while the catheter is in place are listed in Tables 144-1 and 144-2, respectively. Some of the more common complications, such as pneumothorax and inadvertent arterial puncture, can lead to serious consequences, including cardiac arrest, if not recognized early enough. Although fever and chills are not signs and symptoms of pneumothorax or arterial puncture, hypotension, mental status changes, or desaturation (due to airway compromise) may occur. Pneumothorax and inadvertent arterial puncture can largely be prevented with the use of a portable ultrasound-guided probe or a small “finder” needle. Table 144–1

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One of the most serious and insidious complications is CVC-related infection; this too is largely preventable. Elevated temperature, hypotension, and mental status changes should raise suspicion of a CVC-related sepsis syndrome. Although other infectious sources must be ruled out, any intravenous (IV) catheter is a potential route by which organisms can reach the bloodstream, leading to bacteremia. Diagnosis of CVC- or IV catheterrelated bloodstream infection is based on both clinical and laboratory criteria. Catheter-related bloodstream infection is most stringently defined as isolation of the same organism from semiquantitative or quantitative culture samples from both a catheter segment and blood (preferably from a peripheral venipuncture site) in a patient with signs or symptoms of infection but no obvious source for that infection.

Complications of Central Venous Pressure Monitoring during Catheter Insertion

Complication

Prevention

Recognition

Management

Air embolism

Use of Trendelenburg’s position during placement Meticulous occlusion of open needles and catheter hubs More common with subclavian approach Use of small “finder” needle Continuous aspiration with syringe More common with positive-pressure ventilation Avoidance of guidewire insertion >15 cm

Shortness of breath Desaturation Hypotension

Supplement with 100% O2 Cardiovascular support as indicated

Cough during needle insertion Desaturation, dyspnea Hypotension Chest radiographic findings Decreased breath sounds

Closed chest tube thoracostomy Observation if insignificant (<15%) Supplemental O2 Cardiovascular support as indicated

Pneumothorax

Arrhythmias Inadvertent arterial puncture

Pericardial tamponade

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Careful attention to landmarks Palpation of arterial pulse Use of small “finder” needle Use of manometer (extension tubing) or transducer pressure before dilating Use of portable ultrasound guidance Avoidance of overzealous manipulation of catheter guidewire and dilator Confirmation of proper placement by chest radiograph

Electrocardiographic findings Audible change in pulse regularity Bright red blood Pulsatile flow Expanding hematoma Airway compromise (with carotid puncture)

Withdraw guidewire Rarely, antiarrhythmic drug or external cardioversion Withdraw needle and hold direct pressure ≥10 min With dilator or introducer placement, obtain vascular surgeon consultation Airway support; intubation if indicated Cardiovascular decompensation Surgical evacuation Temporal association with catheter placement Echocardiogram

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Table 144–2

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Complications of Central Venous Pressure Monitoring during Catheter Residence Recognition

Management

Vascular erosion

Confirmation of correct catheter tip placement with chest radiograph (junction of superior vena cava and right atrium) More common in left subclavian and internal jugular than right Heparin-bonded catheters may reduce risk Use of catheter only as long as absolutely indicated Strict aseptic techniques Maximal barrier precautions Use of catheter only as long as absolutely indicated Consider antimicrobial catheters Daily inspection of insertion site Appropriate “zeroing” and leveling of transducers Education and training

Hydrothorax Cardiovascular decompensation (hemothorax, tamponade) Respiratory insufficiency

Surgical repair

May be “silent” Upper limb or shoulder edema or tenderness Pulmonary embolism may occur Fever without other source of infection Local redness, tenderness, purulence Positive cultures of both catheter segment and blood samples from separate venipuncture with same organism Correlation with clinical status Frequent zeroing and level checks of transducer

Consider thrombolytic drug or heparin Surgical thrombectomy if severe

Misinterpretation

Recognition Catheter-related bloodstream infection is recognized by the following:

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Infection

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Complication

Thrombosis

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Fever in a patient with an IV catheter or CVC No obvious source for infection Signs or symptoms of local infection at the IV catheter or CVC insertion site Positive catheter segment and peripheral blood cultures

results, but with evidence of local infection (erythema, tenderness, purulence) but not systemic infection, indicates catheter-related local infection. With evidence of sepsis, the diagnosis is catheter-related bloodstream infection. The most sensitive technique for diagnosing a catheterrelated infection is a quantitative culture. The catheter segment is either flushed and inserted into broth or placed in broth and sonicated. Quantitative cultures are performed on broth obtained by either of these methods. Growth of more than 10,000 colony-forming units in a sample from a catheter segment, but without signs of local or systemic infection, is indicative of catheter colonization. The same results with evidence of local infection but not systemic infection are indicative of a catheter-related local infection. With evidence of systemic infection, it is a catheter-related bloodstream infection. Quantitative blood culturing techniques were developed as a diagnostic alternative for patients in whom catheter removal is undesirable because of limited vascular access. This method relies on quantitative cultures of paired blood samples obtained from a CVC port and one peripheral venipuncture site. A colony count obtained from a catheter that is 5- to 10-fold greater than the colony count obtained from a peripheral blood culture is predictive of a catheterrelated bloodstream infection.

Risk Assessment The incidence of nosocomial bloodstream infection is estimated to be approximately 250,000 cases per year. Most of these infections are associated with the use of an intravascular device, and infection rates are much higher in patients with such devices than in those without. CVCs account for an estimated 90% of all catheter-related bloodstream infections. Between 1992 and 2003, the National Nosocomial Infection Surveillance Committee determined that in the United States, there were 2.9 to 8.5 bloodstream

EQUIPMENT & MONITORING

The sine qua non, although nonspecific, of catheterrelated bloodstream infection is typically a febrile episode. Therefore, fever in a person with a CVC should be attributed to the catheter until proved otherwise. A systematic approach should be used to rule out other sources of infection. This includes sputum and urine cultures, inspection of surgical wounds and skin integrity, and a thorough physical examination. Finally, all CVC or IV catheter insertion sites should be inspected for erythema, tenderness, and purulence. To obtain culture samples of catheter segments, the CVC or IV catheter must be removed. If there are no obvious signs of local infection, the site can be preserved by using “guidewire” exchange. Blood samples for culture should be obtained from a peripheral site at or near the time of CVC or IV catheter exchange for comparison. Isolation of the same organism from cultures of both the catheter segment and peripheral blood confirms the diagnosis of a catheterrelated bloodstream infection. Semiquantitative and quantitative catheter cultures have greater specificity than do traditional broth cultures. The most widely used semiquantitative technique was first described by Maki. It employs the roll plate method, in which the catheter segment is rolled across a sheep-blood agar plate and incubated for culture. Growth of more than 15 colony-forming units from a catheter segment by semiquantitative culture, but without signs of local or systemic infection, indicates catheter colonization. The same culture

Removal of infected catheter Antimicrobial therapy

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infections per 1000 catheter days (e.g., 100 catheters in use for 10 days each would total 1000 catheter days). The rate varies according to hospital size, patient population (higher incidence in immunocompromised and burn patients), frequency of catheter use, and practitioners’ adherence to strict definitions of catheter-related infections and proper diagnosis. The risk of infection increases with the duration of central venous catheterization, regardless of the number of catheter changes. Routine CVC changes do not lower the risk for a bloodstream infection; in fact, routine catheter changes increase the risk for mechanical complications and cause patient discomfort, without providing any benefit. Further, catheter changes increase the use of nurse and physician time and increase hospital costs. Any patient with a CVC is at increased risk for infection. However, certain practices may help reduce this risk. Skin colonization at the insertion site is one of the most powerful predictors of increased risk. It has been well documented that skin microorganisms gain access to the transcutaneous tract at the time of insertion or migrate from the skin surface sometime after catheter placement. Some studies have shown a higher infection rate with catheters inserted via the internal jugular versus the subclavian vein. This may be related to heavier cutaneous colonization at the internal jugular site or to greater difficulty maintaining an occlusive dressing. When choosing a site for prolonged (>48 hours) line placement, the subclavian approach, if practical, may be preferable.

are reported and sensitivities are known, the antibiotics can be tailored to the specific organism. Certain clinical situations, such as new sepsis in a critically ill patient or in a patient with a prosthetic heart valve, may dictate the need for catheter removal and replacement at a different site, even with a relatively low index of suspicion. In such situations, the risk of catheter-related bloodstream infection outweighs the benefit of preserving an existing catheter site and avoiding the risk of mechanical complications from new access. It is imperative that good clinical judgment be exercised when weighing the risks and benefits of new central access, including possible mechanical complications and increased patient discomfort. Flowcharts for diagnosing acute fever in a patient suspected of having nontunneled CVC infection and approaches to managing patients with nontunneled CVC-related bloodstream infections are provided in Figures 144-1 and 144-2, respectively.

PREVENTION The following precautions should be taken: ●

●

●

●

Implications Catheter-related bloodstream infections are associated with increased morbidity and mortality (10% to 20%), longer hospitalizations (>7 days), and increased medical costs (>$6000 per hospitalization). Moreover, these infections can be devastating in patients who have prosthetic implants (e.g., heart valves, vascular graft material), which can be seeded by bacteria in the bloodstream.

MANAGEMENT Once a catheter-related bloodstream infection is suspected, the catheter must be removed. If there is a low index of suspicion for a given catheter (e.g., recent placement; clean, noninflamed site), the catheter can be replaced using a guidewire-assisted exchange. However, the old catheter tip and intradermal segment should be sent for semiquantitative culture. Two sets of blood cultures should be obtained to confirm the diagnosis. Preferably, at least one should be from a peripheral site for comparison purposes. If the catheter culture results are negative, a newly placed catheter can be left in place. If the culture results are positive, the newly placed catheter should be removed and a new insertion performed at a different site. Broad-spectrum antimicrobial therapy can be instituted after catheter exchange and after blood cultures have been obtained. In some patients, this includes coverage for grampositive and gram-negative bacteria; in others, antifungal or narrower coverage may be indicated. Once culture results

● ● ●

Use a CVC only when a true indication exists, and remove it as soon as the indication no longer applies. Educate and train health care providers who insert and maintain CVCs. Practice strict adherence to hand-washing and aseptic technique during CVC placement and dressing changes. Use 2% chlorhexidine preparation for skin antisepsis. Use antiseptic- or antibiotic-coated CVC devices. Use maximal barrier precautions during CVC placement. Perform daily inspections of CVC insertion sites.

Any intravascular device is a conduit for microorganisms to the bloodstream (Fig. 144-3). The patient’s skin and the person inserting the catheter are the most likely sources of infecting microorganisms. Heavy skin colonization at the insertion site appears to be a predictor of increased risk of CVC infection. Therefore, strict adherence to hand washing and cutaneous antisepsis should be a high priority. A study that compared various antiseptics showed 2% chlorhexidine was associated with a lower incidence of CVC-related local infection and CVC-related bacteremia compared with 10% povidone-iodine or 70% alcohol. Currently, 10% povidone-iodine is the most widely used skin antiseptic in the United States. Maximal barrier precautions, including the use of a long-sleeved surgical gown, surgical mask, and large surgical sheet, have been shown to reduce the risk of pulmonary artery catheter infection (colonization) compared with less stringent precautions (sterile gloves, surgical mask, small fenestrated drape). Raad and colleagues showed a sixfold reduction in the incidence of long-term CVC-related bloodstream infection when maximal barrier precautions were used. The Centers for Disease Control and Prevention recommended maximal barrier precautions for all central line insertions in its most recently published guidelines. Insertion sites for all intravascular devices must be inspected and palpated daily. Early recognition of local catheter-related infection may help prevent progression

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Figure 144–1 ■ Diagnosis of acute fever in a patient with suspected nontunneled central venous catheter (CVC) infections. CFU, colony-forming unit. (Adapted from Mermel LA, Farr BM, Sheretz RJ, et al: Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 32:12491272, 2001.)

prospective, randomized study, Maki demonstrated a twofold decrease in catheter colonization and a fivefold decrease in bloodstream infections in CVCs impregnated with silver sulfadiazine and chlorhexidine versus standard CVCs among patients in a surgical intensive care unit. Similarly, Ramsay and colleagues showed a decrease in catheter colonization and bloodstream infections with the same catheters in hospital-wide application. Although the difference in catheter-related bloodstream infections between the two study groups was not statistically significant, the results suggest a benefit with antimicrobial catheter use. These studies also suggest that antibiotic-coated or -impregnated catheters may help reduce catheter site or catheter-related bloodstream infections. Catheters inserted by inexperienced personnel carry an increased risk of infection. Some hospitals use IV therapy teams for catheter insertion and follow-up care. Certainly, institutions can reduce their rate of catheter-related sepsis by

EQUIPMENT & MONITORING

to bloodstream infection. Dressing care is a controversial aspect of CVC maintenance. Apparently, there is no significant increase in catheter-related bloodstream infection with transparent versus more traditional gauze dressings. However, some studies found increased cutaneous colonization at catheter insertion sites covered with transparent dressings for longer than 48 hours. In contrast, more recent studies showed that transparent dressings are safe for up to 5 days. This difference may be due to the introduction of more permeable transparent dressings that prevent or minimize moisture buildup. Antimicrobial-coated or -impregnated catheters may be beneficial in reducing the risk of bloodstream infection. In a prospective, randomized trial, Kamal and colleagues showed the efficacy of antibiotic-bonded arterial catheters and CVCs in reducing intravascular catheter colonization. However, there were no catheter-related bloodstream infections in either the study group or the control group. In a

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Figure 144–2 ■ Management of patients with nontunneled central venous catheter–related bloodstream infection (CVC-RBI). TEE, transesophageal echocardiography. (Adapted from Mermel LA, Farr BM, Sheretz RJ, et al: Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 32:1249-1272, 2001.)

Figure 144–3 ■ Sources of intravascular cannula-related infection. The major sources are skin flora, contamination of the catheter hub, contamination of infusate, and hematogenous colonization of the intravascular device and its fibronectin-fibrin sheath. HCW, health care worker. (From Maki DG: Infections due to infusion therapy. In Bennett JV, Brachman PS [eds]: Hospital Infections, 3rd ed. Boston, Little, Brown, 1992, pp 849-898.)

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implementing catheter care protocols and better educating and training nurses and physicians in both sterile technique and practical skills.

Further Reading Cobb DK, High KP, Sawyer RG, et al: A controlled trial of scheduled replacement of central venous and pulmonary artery catheters. N Engl J Med 327P:1062-1068, 1992. Eyer S, Brummitt C, Crossley K, et al: Catheter-related sepsis: Prospective, randomized study of three different methods of long-term catheter maintenance. Crit Care Med 8:1073-1079, 1990. Guidelines for the prevention of intravascular catheter-related infections. MMWR Morb Mortal Wkly Rep 51(RR-10):1-32, 2002. Kamal GD, Pfaller MA, Rempe LE, et al: Reduced intravascular catheter infection by antibiotic bonding. JAMA 265:2364-2368, 1991. Keenan SP: Use of ultrasound to place central lines. J Crit Care 17:126-137, 2002. Kluger DM, Maki DG: The relative risk of intravascular device related bloodstream infections in adults. In Abstracts of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, American Society for Microbiology, 1999, p 514. Maki DG: Infections due to infusion therapy. In Bennett JV, Brachman PS (eds): Hospital Infections, 3rd ed. Boston, Little, Brown, 1992, pp 849-898. Maki DG: Yes, Virginia, aseptic technique is very important: Maximal barrier precautions during insertion reduce the risk of central venous catheter-related bacteremia. Infect Control Hosp Epidemiol 15: 227-230, 1994. Maki DG, Cobb L, Garmen JK: An attachable silver-impregnated cuff for prevention of infection with central venous catheters: A prospective randomized multicenter trial. Am J Med 85:307-314, 1988. Maki DG, Ringer M, Alvarado CJ: Prospective randomized trial of povidoneiodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet 338: 339-343, 1991.

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Maki DG, Stolz SM, Wheeler SJ, Mermel LA: A prospective, randomized, three-way clinical comparison of novel highly permeable polyurethane dressing with 442 Swan-Ganz catheters. In Program and Abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, October 1992, Chicago, Ill. Washington, DC, American Society for Microbiology, 1992, p 825. Maki DG, Weise CE, Sarafin HW: A semiquantitative culture method for identifying intravenous-catheter-related infection. N Engl J Med 296:1305-1309, 1977. Maki DG, Wheeler SJ, Stolz SM: Study of a novel antiseptic coated central venous catheter. Crit Care Med 19:S99, 1991. Mermel LA, Maki DG: Infectious complications of Swan-Ganz pulmonary artery catheters. Am J Respir Crit Care Med 149:1020-1036, 1994. Mermel LA, McCormick RD, Springman SR, et al: The pathogenesis and epidemiology of catheter-related infection with pulmonary artery Swan-Ganz catheters: A prospective study utilizing molecular subtyping. Am J Med 91(Suppl 3B):197S-205S, 1991. National Nosocomial Infections Surveillance System report: Data summary from January 1992 through June 2003, issued August 2003. Am J Infect Control 31:481-498, 2003. Pearson ML (for the Hospital Infection Control Practices Advisory Committee): Guideline for prevention of intravascular device-related infection. Am J Infect Control 24:262-293, 1996. Raad II, Darouiche R, Dupuis J: Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and blood stream infections: A randomized, double-blind trial. The Texas Medical Center Catheter Study Group. Ann Intern Med 127:267-274, 1997. Raad II, Hohn DC, Gilbreath JB, et al: Prevention of central venous catheter-related infections by using maximal sterile barrier precautions during insertion. Infect Control Hosp Epidemiol 15:231-238, 1994. Ramsay J, Nolte F, Schwartzman S: Incidence of catheter colonization and catheter related infection with an antiseptic impregnated triple lumen catheter. Crit Care Med 22:A115, 1994. Ruesch S, Walder B, Tramer M, et al: Complications of central venous catheters: Internal jugular versus subclavian access—a systematic review. Crit Care Med 30:454-460, 2002.

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Matthew D. Caldwell and Paul E. Kazanjian Case Synopsis A 74-year-old woman undergoes resection of a 7-cm aneurysm of the proximal descending thoracic aorta. Before induction of anesthesia, an oximetric pulmonary artery catheter (PAC) is introduced via the right internal jugular vein and wedged at 42 cm. A two-lumen endotracheal tube is positioned for one-lung ventilation. Deep, hypothermic circulatory arrest is used for aneurysmectomy and aortic repair. After cardiopulmonary bypass, the PAC is withdrawn 5 cm. After restoration of ventilation, the patient develops massive hemoptysis from the dependent right lung and hypoxemia. This resolves after protamine is administered. Two weeks later, a 1.5-cm nodular density is seen in the right lower lobe on portable chest radiography. Computed tomography confirms the clinical suspicion that the density is a pulmonary artery pseudoaneurysm.

PROBLEM ANALYSIS Definition PACs are commonly used by anesthesiologists to measure right atrial and ventricular and pulmonary artery pressures. Also, the pulmonary artery occlusion (wedge) pressure is used as a surrogate for left atrial pressure, and cardiac output is determined by thermodilution. These measurements aid in the diagnosis and management of many cardiovascular derangements. PAC placement requires the insertion of a large introducer sheath (8.0, 8.5, or 9.0 French), often in the left subclavian or right internal jugular vein. The PAC is then advanced through this sheath into the superior vena cava, its balloon is inflated, and blood flow directs its passage through the right atrium and right ventricle into the pulmonary artery. Simultaneous pressure monitoring is used as the PAC is advanced. Complications with PACs may occur during insertion or after positioning. The former complications are similar to those that occur with sheaths used for other central lines, except that the large size of the dilator and sheath can result in more serious vascular injuries. Complications related to central venous catheterization are discussed in Chapter 144. After PAC positioning, complications are due to erroneous PAC hemodynamic data or misinterpretation of correct data. Either can adversely affect decisions related to clinical management. Arrhythmias or Bundle Branch Block. Guidewire insertion or PAC passage often causes atrial or ventricular arrhythmias. Atrial or ventricular ectopic beats and nonsustained ventricular tachycardia occur in 13% to 70% of cases, usually while the balloon is passing through the right atrium and ventricle. Also, ventricular ectopy is often noted during withdrawal of PAC. In addition, ventricular arrhythmias can develop after the catheter has been in place for a few minutes to days. Most ventricular arrhythmias caused by catheter 588

manipulation are benign and self-limited. Hemodynamically significant sustained ventricular tachycardia or ventricular fibrillation is very infrequent but can develop, especially in patients with risk factors for these arrhythmias (e.g., prior or recent myocardial infarction, ejection fraction <25%, dilated cardiomyopathy). New right bundle branch block appears during 5% of PAC insertions. Development of new right bundle branch block in patients with preexisting left bundle branch block may cause complete heart block and hemodynamic instability. Malposition of the Catheter Tip. Obtaining accurate hemodynamic data from a PAC depends on positioning the catheter tip in a region of the pulmonary vasculature where the pulmonary artery pressure exceeds airway pressures. Errant catheter tip position can generate erroneous data and contribute to PAC-induced vascular injury. Minutes to hours after insertion, the tip may migrate distally as the catheter softens and is towed by the blood flow. A catheter with its tip located in a permanent wedge position can lead to pulmonary infarction or pulmonary artery rupture. Pulmonary Ischemia and Infarction. The incidence of ischemic injury is approximately 7%. It may be due to thromboembolism, endothelial damage, or ischemia distal to a catheter tip that completely occludes a small branch of the pulmonary artery. Pathologic and angiographic studies have revealed an unexpectedly high rate (53% to 66%) of thrombotic lesions in patients with PACs. The thrombus is often attached to the catheter at or near the site of insertion of the introducer sheath. Thrombus is also associated with traumatized endothelium or endocardial surfaces. Thromboses are usually small, but they can be massive and associated with pulmonary embolism. The thrombus can disrupt hemodynamic measurements by occluding the thermistor or infusion ports. Heparin bonding may not reduce mural and veno-occlusive thrombus formation. Pulmonary Artery Perforation or Rupture. Artery perforation and rupture are the most serious complications of PACs.

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Their exact incidence is unknown, but estimates range between 0.064% and 0.2%, with a mortality estimated at 41% to 70%. Barash and associates proposed possible mechanisms for PAC-related perforation or rupture based on postmortem study of isolated whole lung preparations: ●

●

●

A PAC tip that has been advanced too far distally can perforate the vessel. Eccentric balloon inflation can propel the tip of the catheter through the vessel wall. Balloon inflation can result in intraballoon pressures of 250 mm Hg, which can cause rupture of the pulmonary artery.

Catheter Knotting or Entanglement. PACs can become entangled around cardiac structures or knotted in the superior vena cava, right atrium, right ventricle, or pulmonary artery. Similarly, PACs have been entrapped by cardiac sutures during open-heart surgery and have become entangled with cardiac papillary muscles, pacing and defibrillator leads, and other central vascular access catheters. Knotted or entangled PACs are often discovered during attempts to withdraw or advance the catheter. Intracardiac Erosions or Hemorrhagic Lesions. These erosions or lesions may involve the vascular endothelium, right atrial or ventricular endocardium, tricuspid valve, chordae tendineae, and pulmonic valve, but they rarely lead to clinically important endocarditis. Such PAC-induced damage to the great vessels, heart, or pulmonary vessels can result in bleeding, hemoptysis, cardiac tamponade, or death. Catheter Colonization and Sepsis. Colonization and sepsis are more likely with multilumen catheters (e.g., PACs) than with single-lumen catheters. They underscore the need for strict adherence to aseptic technique during PAC insertion and dressing changes and when tending to transducers, stopcocks, and external tubing.

Recognition New arrhythmias or heart block should be easily detected by electrocardiogram (ECG). Changes in the ECG or pulse oximeter monitor tones may signal a rhythm disturbance and can alert the nursing staff or physicians to its presence. Unusual resistance to the advancement or withdrawal of a PAC suggests knotting or entanglement and should be

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evaluated by a chest radiograph before any further PAC manipulation. Pulmonary artery perforation by a PAC may go undetected but is often manifest by hemoptysis (sometimes massive), hemothorax, dyspnea, anxiety, and hypotension. The onset of these symptoms is often related to balloon inflation or flushing of a PAC that is in a wedged position. Until proved otherwise, any new hemoptysis in a patient with a PAC must be considered due to pulmonary artery rupture. Infectious complications are recognized by fever and erythema or pus at the PAC insertion site. Infection is confirmed by indicated laboratory studies and cultures at the insertion site.

Risk Assessment Risk factors for the development of arrhythmias during or after PAC insertion include the following: ●

●

● ●

Total time spent passing the PAC through the right atrium and ventricle Presence of previous myocardial infarction or ischemia or left bundle branch block Presence of hypoxemia or acidosis Electrolyte imbalance (especially hypokalemia or hypomagnesemia)

Low cardiac output syndrome may predispose to pulmonary infarction. Factors associated with increased risk of pulmonary artery rupture, infarction, or pseudoaneurysm are listed in Table 145-1. During cardiac surgery, manipulation of the heart or distal migration of a cold and stiff PAC from an empty heart predisposes to pulmonary artery perforation. Patients whose skin is heavily colonized with bacteria or yeast are at risk for catheter-associated infection, as are those who have had the same PAC in place for longer than 4 days. The incidence of thrombus formation increases with the duration of catheterization and the severity of the illness.

Implications As with all invasive procedures, PACs have associated risks and benefits. The incidence of serious complications is estimated to be 0.1% to 0.5% for anesthesiologists and <5% for other specialists. This risk must be weighed against the potential benefit of rapidly identifying and managing hemodynamic disturbances. The American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization recommends considering the patient, the surgical procedure, and the practice setting when deciding on the appropriateness of

Table 145–1 ■ Risk Factors for Pulmonary Artery Rupture, Infarction, or Pseudoaneurysm Advanced age Pulmonary hypertension Distal pulmonary artery catheter (PAC) migration Anticoagulation Hypothermia PAC balloon overinflation

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Inappropriate Use and Data Misinterpretation. The clinical benefits and utility of right-sided heart catheterization with PACs are unproved. In fact, a body of evidence and opinion exists that the risks and costs outweigh any benefits. Some observational studies suggest that the risk of death is higher in patients managed with PACs. One recent randomized study of PACs in high-risk surgical patients found no benefit in patients whose therapy was directed by PACs. Other studies have found serious flaws in the correct interpretation of PAC data, even by experienced physicians and critical care nurses. These flaws included the inability to correctly identify pulmonary artery wedge pressure and the determinants of oxygen transport, both of which are fundamental to the rational use of PACs.

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placing a PAC. In patients with clinically significant cardiopulmonary disease, renal insufficiency, or hemodynamic instability, the potential benefit of a PAC may be greater. Surgical procedures with a high risk of rapid hemodynamic changes and significant fluid shifts may also favor PAC placement. Finally, PACs are more likely to improve patient outcomes in practice settings where physicians and nurses have a sufficient level of training and familiarity with their use.

MANAGEMENT All patients should have ECG and pulse oximetry monitoring during PAC insertion. Most ventricular arrhythmias associated with PAC insertion are benign and self-limited. They usually terminate once the PAC is advanced into the pulmonary artery or withdrawn into the right atrium. Only rarely is antiarrhythmic therapy or external pacing necessary. Complete atrioventricular heart block is treated with temporary transcutaneous or transvenous pacing. Any suspected technical complication of pulmonary artery catheterization should immediately be investigated with chest radiography. Catheter malposition and kinking may be corrected by carefully repositioning the PAC with or without the assistance of fluoroscopy. The use of brute force is inappropriate and risks disastrous injury. A knotted or entrapped PAC may require angiographic or even surgical removal. Pulmonary artery rupture may require one or more of the following modes of therapy: ● ●

● ● ● ●

Positive end-expiratory pressure Lung isolation with a double-lumen endotracheal tube or endobronchial blocker Temporary unilateral occlusion of the pulmonary artery Direct repair of the lacerated artery Lung resection Embolization of a pseudoaneurysm

PACs that are suspected or proved to be infected must be removed, and the patient must be treated with appropriate antibiotic therapy.

PREVENTION It is important to remember that placement of a PAC is an elective, diagnostic procedure. It should be performed only after the patient’s medical condition has stabilized and physiologic imbalances (e.g., hypoxemia, electrolyte disturbance, acidosis, hypotension) have been corrected. Complications of vascular access may be reduced by ultrasound-guided cannulation and central venous pressure waveform confirmation during introducer sheath placement. Complete heart block is very infrequent and does not justify the prophylactic insertion of invasive pacing wires.

However, the means for temporary transcutaneous or transvenous pacing should be readily available during the insertion of PACs in patients with preexisting left bundle branch block. Prevention of pulmonary artery rupture requires careful technique during PAC insertion and manipulation. During initial insertion, once a pulmonary artery wedge pressure tracing is obtained, the catheter should be withdrawn 2 to 3 cm. Ideally, a PAC should be left with its tip 3 to 5 cm beyond the pulmonic valve. Typically, this translates to an insertion depth of 40 to 45 cm, but it depends on the patient and the insertion site. In addition, one should always consider the need to obtain a pulmonary artery wedge pressure in patients with risk factors for rupture (especially those receiving anticoagulants or with distal PAC migration). Radiographic or echocardiographic confirmation of proper position should be obtained whenever feasible. Routine chest radiography may alert the operator to inadvertent distal PAC migration or other technical complications. Competence in the placement and interpretation of data from PACs is mandatory. This requires formal training in right heart catheterization, along with supervised PAC placement. The minimum number of PAC placement procedures to ensure competence is debatable, but ongoing maintenance of skills is mandatory. Ideally, an institutional quality improvement program should be in place to ensure ongoing education and skill maintenance for all physicians and nursing personnel caring for patients with PACs.

Further Reading American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization: Practice guidelines for pulmonary artery catheterization. Anesthesiology 99:988-1014, 2003. Barash PG, Nardi D, Hammond G, et al: Catheter-induced pulmonary artery perforation: Mechanisms, management, and modifications. J Thorac Cardiovasc Surg 82:5-12, 1981. Connors AF, Castele RT, Farhat NZ, et al: Complications of right heart catheterization: A prospective autopsy study. Chest 88:567-572, 1985. Connors AF Jr, Speroff T, Dawson NV, et al: The effectiveness of right heart catheterization in the initial care of critically ill patients: SUPPORT investigators. JAMA 276:889-897, 1996. Damen J, Bolton D: A prospective analysis of 1400 pulmonary artery catheterizations in patients undergoing cardiac surgery. Acta Anaesthesiol Scand 30:386-392, 1986. Domino KB, Bowdle TA, Posner KL, et al: Injuries and liability related to central vascular catheters: A closed claim analysis. Anesthesiology 100:1411-1418, 2004. Ginosar Y, Thijs LG, Sprung CL: Raising the standard of hemodynamic monitoring: Targeting the practice or the practitioner? Crit Care Med 25:209-211, 1997. Mermel LA, McCormick RD, Springman SR, et al: The pathogenesis and epidemiology of catheter-related infection with pulmonary artery Swan-Ganz catheters: A prospective study utilizing molecular subtyping. Am J Med 91:197S-205S, 1991. Sandham JD, Hull RD, Brant R, et al: A randomized controlled trial of the use of pulmonary artery catheters in high risk surgical patients. N Engl J Med 348:5-14, 2003. Swan HJC, Ganz W, Forrester J, et al: Catheterization of the heart in man with the use of a flow-directed balloon-tipped catheter. N Engl J Med 283:447-451, 1970.

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Paul Smythe and Norah Naughton Case Synopsis An 18-year-old man has open long bone fractures and severe traumatic brain injury due to a motor vehicle accident. His Glasgow Coma Scale score is 6, and a computed tomography scan of the head reveals diffuse cerebral edema. An intraventricular monitor reveals a pressure of 30 mm Hg. Treatment for increased intracranial pressure is initiated, and the patient is transferred to the operating room for treatment of the long bone fractures.

PROBLEM ANALYSIS Definition

ICP monitoring can assist in the diagnosis and treatment of ICH. All ICP monitoring systems have certain characteristics in common, beginning with physical attachment to the system being monitored. This connection requires a watertight fluid interface between the ICP monitor and the intracranial compartment and consists of rigid tubing leading to a flexible membrane. Because ICP is being monitored, the compartment must be sealed. Any leakage would be indicative of serious underlying pathology that must be addressed. This could range from CSF leakage (best-case scenario) to cerebral herniation (worst-case scenario). With no leakage, any change in ICP leads to some degree of deformation of the flexible membrane contiguous with this space. CONSTRUCTION The deformed membrane is coupled to a transducer. Regardless of the coupling interface (i.e., rigid tubing), its role is to accurately transmit any membrane deformations occurring with each ICP pulsation. A transducer converts these coupled or transmitted pulsations to an electrical signal, which is then amplified to enhance the signal generated by the transducer for display purposes. The display is essentially a voltmeter. It may be connected to an oscilloscope or stylus recorder to display the ICP waveform and pressure changes. ICP monitoring systems differ mainly according to the type of coupling between the deformed membrane and transducer, and according to the anatomic location at which each system is placed. ZEROING All ICP monitoring devices must covert ICP to some voltage for electronic display. This relationship is expressed as the equation y = mx + b, where y is the voltage, x is the pressure, and m is the ICP curve slope. The characteristics of the transducer are such that there is a linear relationship between voltage and pressure, or m (discussed further under “Calibration”). It would be optimal for a monitor to read zero voltage when the pressure applied to the transducer is equal to zero. Adjusting the b term of the equation so that the relation becomes y = mx + b, with b equal to zero, accomplishes 591

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Intracranial pressure (ICP) is the pressure or force exerted within the rigid cranial vault by the intracranial contents. In normal adults, the intracranial contents comprise brain, 80%; blood, 10%; and cerebrospinal fluid (CSF), 10% of volume. Normal ICP is approximately 5 to 13 mm Hg (7 to 18 cm H2O). In patients who do not have intracranial pathology, the intracranial contents are considered to have normal elastance. This means that small increases in intracranial volume do not result in increased ICP. According to the Monro-Kellie hypothesis, this occurs because when the volume of one compartment increases, the volume of another compartment decreases by an equal amount, leaving the total volume unchanged. This type of compensation is necessary because all three elements of the intracranial contents are almost incompressible. Reduced elastance occurs when the intracranial volume approaches that of the intracranial space. In this case, a small increase in intracranial volume creates a dramatic and possibly life-threatening increase in ICP. The diagnostic and therapeutic use of ICP monitors has not changed appreciably in the last 5 years. Most centers consider 20 mm Hg the upper limit of normal for ICP, although others use 15 mm Hg for this cutoff. ICP above 15 to 20 mm Hg is considered intracranial hypertension (ICH; see Chapter 174). Beyond this level, treatment for ICH is initiated. Cerebral perfusion pressure (CPP) should be considered when managing patients with ICH. CPP is defined as mean arterial blood pressure minus ICP, and it is the physiologic variable that defines the pressure gradient driving cerebral blood flow and delivery of oxygen and metabolites. It is therefore closely related to cerebral ischemia. The optimal level at which CPP should be maintained is unclear, but several clinical studies suggest that keeping CPP greater than 70 mm Hg is associated with a substantial reduction in death rates and improved quality of survival. Further, it is likely to enhance ischemic brain perfusion after severe traumatic brain injury (TBI). In most cases of TBI, CPP is manipulated by normalizing intravascular volume or inducing systemic hypertension.

Recognition

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this and is called zeroing. Zeroing means that if the transducer produces a voltage when the pressure being measured is zero, it must be balanced or offset by an internally applied voltage of the opposite sign. The zero pressure of biologic pressure monitoring systems is always the ambient atmospheric pressure. Zeroing is achieved by opening a stopcock or valve on the transducer to sense the ambient or room air pressure as zero. Modern systems require pushing a zeroing button, and this setting is automatically remembered. Zeroing the transducer (ICP or any other pressure transducers) is important because an error in this step affects all subsequent pressure readings. TRANSDUCER LOCATION With ICP monitoring devices, the transducer can be located either externally or at the catheter tip inside the cranium. External transducers can be rezeroed at any time after placement of the ICP monitor. Monitors that have catheter-tip pressure transducers must be zeroed before placing the catheter into the intracranial compartment. Once placed, a catheter-tip pressure transducer cannot be rezeroed. CALIBRATION Calibration is accomplished by adjusting the m term, or slope, of the equation y = mx + b. The control on ICP amplifier systems that adjusts the slope is labeled “calibration,” “gain,” “amplification factor,” or “slope.” Most contemporary transducers have a small microprocessor incorporated within the transducer that is precalibrated. They produce a small constant voltage proportional to the degree of compression, termed the calibration factor. The most common calibration factor is 200. At 200 mm Hg, this means that the transducer may put out more or less voltage at a given pressure than it should. The calibration can be checked by applying a known pressure to the transducer and adjusting the monitor display to read the same as the known pressure applied. It is advised that calibration of all transducers be periodically cross-checked.

TRANSDUCER TYPES Two different types of transducers are used in contemporary ICP monitors. The first, the strain-gauge transducer, consists of a membrane physically attached to a magnet that moves with pulsations within a series of coils. As the magnetic flux changes across the coils, a current is induced that is proportional to the degree and frequency of magnet movement. This current is proportional to the pressure applied to the strain-gauge transducer. However, the most commonly used transducer is a highly specialized version of the strain-gauge transducer referred to as a piezoelectric transducer. This is a highly standardized ceramic crystal that generates voltage when a force is applied. In most piezoelectric systems, the transducer structure, analogous to the deformable membrane, is the crystal itself. The preset calibration factor is generally 200. The second class of transducers is the fiberoptic transducer. It uses a laser beam to couple membrane movement with the electrical component of the transducer. This system still depends on a membrane being distorted by intracranial compartment pressure variations. The transducer side of the membrane is reflective (mirrored), with the laser beam directed to this side of the membrane. When the membrane moves, it reflects the laser light beam at an angle that diverges from that of any incident light. This reflected light signal is related to the incident light signal to generate a quantitative estimate of the membrane distortion caused by altered ICP. A signal is generated for amplification and is proportional to the movement of the membrane. SOURCES

OF

ERROR

External transducers are accurate and can be recalibrated. They must be maintained at a fixed reference point relative to the patient’s head to avoid measurement error. Internal transducers (catheter-tip strain-gauge or fiberoptic) are calibrated before intracranial insertion and cannot be recalibrated once they are placed (i.e., without a separate intraventricular catheter). Therefore, if the device measures drift, there is the potential for inaccurate ICP measurements, especially if the ICP monitor is used for several days.

DRIFT

VENTRICULAR INTRACRANIAL PRESSURE MONITORING

When zero and gain settings change across time, this is referred to as drift. Because no transducer can be perfect, all transducer-amplifiers drift to some extent.

The intracranial spaces most frequently monitored are intraventricular, intraparenchymal, subarachnoid, subdural, and epidural (Table 146-1). Ventricular ICP monitoring is

Table 146–1

■

Intracranial Spaces Used to Monitor Intracranial Pressure

Space

Method of Pressure Transduction

Intraventricular

Fluid-coupled external strain gauge Fluid-coupled strain-gauge catheter tip Fluid-coupled fiberoptic catheter tip Strain-gauge catheter tip Fluid-coupled external strain gauge Strain-gauge catheter tip Fiberoptic catheter tip Fluid-coupled external strain gauge Fluid-coupled external strain gauge Pneumatic

Parenchymal Subarachnoid Subdural Epidural

+, possible or necessary; −, not possible or not necessary.

Cerebrospinal Fluid Drainage + + + − − − − − − −

Recalibration + + + − + − − + + +

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considered the gold standard for comparing the accuracy of ICP monitors in other intracranial compartments. It also has the therapeutic benefit of draining CSF for the treatment of ICH. ICP monitoring devices have been ranked based on their accuracy, stability, and ability to drain CSF. A ventricular catheter connected to an external strain-gauge transducer or catheter-tip pressure transducer device is the most accurate and reliable method of monitoring ICP and allows for therapeutic CSF drainage. Parenchymal cathetertip pressure transducer devices measure ICP similar to ventricular ICP pressure. Subarachnoid or subdural fluidcoupled devices and epidural ICP devices are less accurate.

●

●

● ●

●

With continuous ICP monitoring, three types of waveforms may be observed: A, B, and C. B and C waves are of limited clinical significance and correspond to changes in respiration and arterial blood pressure, respectively. A waves, referred to as plateau waves, are of clinical significance. These waves arise from an elevated baseline ICP and can reach magnitudes of 50 to 120 mm Hg for 2 to 20 minutes. These waves result from cerebral blood volume increases in response to CPP fluctuations and occur in vascular beds with overall intact autoregulation. These waves may signify impending limitation of the ICP volume compensation system.

Intracranial Pressure Monitoring

593

Limit the indiscriminate use of therapy to control ICP, which is potentially harmful Reduce ICP by CSF drainage and thus improve cerebral profusion Help in determining prognosis Improve outcomes

Comatose head-injured patients (Glasgow Coma Scale score 3 to 8) with abnormal computed tomography scans should have ICP monitoring. Comatose patients with normal scans should also have ICP monitoring if they have two or more of the following risk factors: ●

CONTINUOUS INTRACRANIAL PRESSURE MONITORING

■

●

Age older than 40 years Unilateral or bilateral motor posturing Systolic blood pressure less than 90 mm Hg

Routine ICP monitoring is not indicated for patients with mild or moderate head injury. The mortality rate for patients with an intracranial process associated with ICH increases 2- to 10-fold when patients have a disturbance in consciousness and are unable to follow commands. ICP monitoring may be recommended in these situations, which include subarachnoid hemorrhage (with and without hydrocephalus), intracerebral hemorrhage, hydrocephalus, encephalitis, meningitis, venous sinus thrombosis, ischemic infarct with swelling, and hepatic encephalopathy. Table 146-2 lists the advantages and disadvantages of ICP monitoring by device location.

Risk Assessment ICP monitoring has been used most extensively in patients with TBI (see also Chapter 174). In the TBI patient population, ICP monitoring may accomplish the following: ●

Help in the early detection of intracranial mass lesions

Table 146–2

■

Implications ICP monitoring complications include infection, hemorrhage, malfunction, obstruction, and malposition. Bacterial colonization is a more accurate term than infection because

Advantages and Disadvantages of Intracranial Pressure Monitoring by Device Location Advantages

Disadvantages

Waveform Quality

Intraventricular

Gold standard Accurate measurement of ICP Allows drainage or sampling of CSF Allows instillation of drugs or dyes directly into CSF Determines δP/δV Useful when unable to obtain ventricular access Accurate Requires zeroing only once No need to adjust transducer to patient position Ability to leave cerebral parenchyma undisturbed Quick to insert Useful to insert when unable to obtain ventricular access Useful after craniotomy Ease of placement Best when ICP relatively low Dura not penetrated Low risk of infection Ease of insertion

Catheter can become occluded by blood or tissue Risk of infection or hemorrhage May require frequent zeroing

Excellent

Potential for significant drift Breakage of fiberoptic cable Cannot be recalibrated once placed Does not provide for CSF sampling

Good

Lumen may be occluded by blood or tissue Tendency for dampened waveforms Less accurate at high ICPs Must be zeroed frequently CSF leakage a concern Risk for waveform dampening Underestimates ICP when high

Fair

Parenchymal

Subarachnoid

Subdural Epidural

Sensing membrane must remain coplanar to dura Risk of false or misleading readings Least understood of all ICP monitors

CSF, cerebrospinal fluid; ICP, intracranial pressure; δP/δV, change in pressure as a function of change in volume. Modified from Guidelines for the Management of Severe Head Injury. Brain Trauma Foundation, 1995.

Poor Poor

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Device Location

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there have been no reports in large prospective studies of clinically significant intracranial infections associated with ICP monitoring devices. Colonization of the ICP monitor increases significantly after 5 days of insertion. Irrigation of fluid-coupled ICP monitors significantly increases bacterial colonization. The average rate of bacterial colonization is 5% for ventricular, 5% for subarachnoid, 4% for subdural, and 14% for intraparenchymal devices, either catheter-tip strain-gauge or fiberoptic. However, clinically significant intracranial infections are uncommon. The overall incidence of hematomas associated with ICP devices is 1.4%. The incidence of malfunction or obstruction in fluid-coupled ventricular catheters, subarachnoid bolts, or subdural catheters has been reported as 6.3%, 16%, and 10.5%, respectively. When ICP measurements are greater than 50 mm Hg, obstruction and loss of signal and waveform can occur. Malfunction with parenchymal and ventricular pressure fiberoptic catheter-tip transduction devices ranges from 9% to 40%. This requires reinsertion of a new fiberoptic device.

MANAGEMENT Treatment of ICH is recommended when ICP is 20 mm Hg or greater or if there is significant brain swelling (see also Chapter 174). Treatments are generally classified according to the intracranial contents targeted for therapy and include the following: ● ● ● ●

Brain tissue volume CSF volume Cerebral blood flow Mass lesion

Brain tissue water content is 75% to 80%, and treatments designed to decrease brain tissue volume are aimed at decreasing brain tissue water. Hyperosmolar agents such as mannitol are used for this purpose. The administration of mannitol creates an osmolar gradient between cerebral blood and brain tissue, which favors the movement of water from the tissue space into the vascular space. Mannitol may also act initially to decrease cerebral blood volume by decreasing blood viscosity secondary to free water movement. Decreased blood viscosity results in increased cerebral blood flow, which prompts vasoconstriction in normally autoregulating brain areas. This decreases cerebral blood volume and, secondarily, ICP. Effective doses range from 0.25 to 1 g/kg of body weight. Euvolemia should be maintained, and serum osmolarity should not exceed 320 mOsm. Furosemide and other diuretics can be used to decrease brain tissue water by increasing blood osmolarity. This favors the movement of water from the brain tissue space into the cerebrovascular space. Corticosteroids have been reported to decrease brain tissue water content when vasogenic edema is the chief cause of increased water; however, they are not consistently helpful in the treatment of other forms of cerebral edema or in clinical conditions in which both vasogenic edema and other forms of edema are present. Corticosteroids are not recommended for the treatment of increased ICP in the management of acute head injury, because associated side effects may worsen outcomes. Adverse effects include decreased immune response in areas of the body other than

the brain, suppression of intrinsic steroid production, and hyperglycemia. Reduction in CSF volume may directly improve elevated ICP and increase the clearance of brain tissue water from edematous areas. The most direct means of decreasing CSF volume is through CSF drainage. This is usually accomplished via an intraventricular catheter or lumbar subarachnoid catheter. However, caution is advised when using the latter in patients with ICH, owing to the risk of acute brainstem herniation. CSF volume can also be reduced by promoting its movement from the intracranial space to the spinal subarachnoid space. Head elevation and repositioning relative to the subarachnoid space favor such movement. Methods to reduce cerebral blood volume include hyperventilation, the use of drugs known to cause cerebral vasoconstriction and the restriction of those that impair cerebral autoregulation, head elevation above the level of the heart, suppression of cerebral metabolism, and the minimizing of increased intrathoracic pressure with airway manipulation or mechanical ventilation. Hypocapnia with hyperventilation reduces cerebral blood flow and volume via cerebral vasoconstriction. The latter is mediated by acute increases in perivascular pH. However, hypocapnia may compromise cerebral perfusion due to cerebral vasoconstriction, especially in patients with severe TBI. In the absence of increased ICP, chronic prolonged hyperventilation therapy (to an arterial carbon dioxide tension of 25 mm Hg) should be avoided after severe TBI. Also, use of prophylactic hyperventilation therapy during the first 24 hours after severe TBI should be avoided because it may compromise cerebral perfusion at a time when cerebral blood flow is already reduced. Hyperventilation therapy may be required for short periods with acute neurologic deterioration or for extended periods if ICH is refractory to sedation, paralysis, CSF drainage, and osmotic diuretics. Sedative-hypnotic drugs (e.g., barbiturates, etomidate, propofol) are cerebral vasoconstrictors and decrease ICP. In extreme cases, barbiturate-induced coma may be necessary to control ICP. Drugs that impair cerebral autoregulation can increase cerebral blood volume and ICP. These include inhalation anesthetics and direct-acting vasodilators (e.g., nitroprusside, nitroglycerin, calcium channel blockers, prostacyclin, adenosine). Control of blood pressure with indirect-acting agents (e.g., labetalol, trimethaphan) prevents the increase in cerebral blood volume and ICP. Head elevation above the heart reduces cerebral blood volume by increasing cerebral venous outflow. Suppression of cerebral metabolism is accomplished by the use of hypothermia and barbiturate-induced coma. Space-occupying masses increase total intracerebral volume and therefore ICP. Treatment for mass lesions includes removal, chemotherapy or radiation therapy, and creation of additional space for normal intracranial contents, such as decompression or craniectomy.

PREVENTION There is no medical treatment for the prevention of increased ICP that is not part of the management of ICP covered in the previous section. Short of surgical intervention (in the case of intracranial hemorrhage, increasing

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tumor size, or hydrocephalus, for example), one prevents an increase in ICP by addressing the same three contents of the cranium, namely brain tissue volume, CSF volume, and cerebral blood volume. In summary: ●

●

●

Brain tissue volume ● Diuretics (mannitol) CSF volume ● Ventriculostomy ● Lumbar drain Cerebral blood flow ● Hyperventilation ● Head elevation and repositioning

●

● ●

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Discontinuation of inhalational anesthetics (and other cerebral vasoconstrictors) Barbiturate administration Sedation and paralyzing agents

Further Reading Albin MS (ed): Textbook of Neuroanesthesia with Neurosurgical and Neuroscience Perspectives. New York, McGraw-Hill, 1997, pp 61-117, 1137-1177. Fahy BG, Sivaraman V: Current concepts in neurocritical care. Anesth Clin North Am 20:441-462, 2002. Marik PE, Varon J, Trask T: Management of head trauma. Chest 122: 699-711, 2002.

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PERIOPERATIVE MANAGEMENT

Pediatric Laryngospasm Eric P. Wittkugel

147

Case Synopsis Following extubation at the conclusion of adenotonsillectomy, a 5-year-old boy develops high-pitched inspiratory stridor. Chest wall retractions are noted, and the breath sounds rapidly diminish until none are heard.

PROBLEM ANALYSIS Definition Among other functions, the larynx protects the upper airway and lungs from aspiration of foreign materials. The glottal closure reflex is most evident during swallowing. Laryngospasm is an exaggerated form of the glottal closure reflex in response to noxious stimuli. Partial or complete airway obstruction due to laryngospasm can persist even after removal of the stimulus. Laryngospasm is mediated by the vagus nerve. The afferent limb of this reflex is the superior laryngeal nerve, and the efferent limb is the recurrent laryngeal nerve. Laryngospasm consists of two phases: (1) adduction of the true vocal cords, causing partial airway obstruction via a “shutter” mechanism, followed by (2) constriction of the false vocal cords and supraglottic soft tissues, leading to complete obstruction by a “ball-valve” effect.

Risk Assessment Based on a sample of 136,929 patients studied over an 11-year period (1967-1978), Olsson and Hallen reported the incidence of laryngospasm to be 0.87%. The incidence doubled in pediatric patients 0 to 9 years of age (1.74%) and tripled in infants 0 to 3 months of age (2.82%); a further increase in the incidence of laryngospasm was seen in children with asthma or coexisting respiratory infection (9.58%). Factors specific to the practice of pediatric anesthesiology may help account for this higher incidence: ●

●

Other risk factors for laryngospasm include the following: ● ●

Recognition The following signs indicate laryngospasm: ● ● ● ●

Chest wall retractions: suprasternal, sternal, intercostal High-pitched inspiratory stridor Diminished or absent breath sounds Hypoxemia

● ●

“Light” levels of anesthesia Surgery associated with bleeding in the airway (e.g., tonsillectomy, adenoidectomy, nasal surgery, palatal surgery) Other noxious airway stimuli Exposure to secondhand cigarette smoke

Laryngospasm occurs during light levels of anesthesia. An animal model of acid-induced laryngospasm demonstrated that lighter levels of anesthesia increase the activity of laryngeal adductor neurons. Some anesthetic practices commonly used in children increase the likelihood of airway stimulation during light anesthesia. The duration of stage II (light) anesthesia is longer with inhalation versus intravenous induction and increases the period of vulnerability to laryngospasm. Stimulation of the glottis by secretions or airway management devices during this vulnerable period may trigger laryngospasm. Laryngospasm is especially likely when intubation without muscle relaxants is attempted before reaching an adequate depth of anesthesia. After extubation under deep anesthesia, patients are at risk for laryngospasm while passing through stage II with an unprotected airway. Surgical procedures on the airway are common in children, and the resulting oral secretions and blood can trigger laryngospasm. On average, children have six to eight upper respiratory infections (URIs) per year, making it unlikely that children presenting for surgery will be completely free of URI symptoms. Excess secretions and airway hyperreactivity may persist for 599

PEDIATRICS & NEONATOLOGY

Laryngospasm can be partial or complete. The case synopsis shows the progression from partial to complete laryngospasm. Differentiation of partial laryngospasm from other causes of upper airway obstruction may be difficult. Typically, partial laryngospasm presents with high-pitched “squeaking” sounds emanating from the apposed vocal cords. Obstruction due to the tongue or other soft tissues in the pharynx is associated with snoring, whereas obstruction due to secretions is usually accompanied by gurgling sounds. Prompt recognition and immediate treatment of complete laryngospasm are essential, because gas exchange is impossible with a closed glottis. During the evolution from partial to complete laryngospasm, signs of extrathoracic airway obstruction (chest wall retractions, nasal flaring, paradoxical breathing) intensify. Next, breath sounds weaken and then disappear.

Inhalation induction, deep intubation without muscle relaxants, and deep extubation increase the likelihood of stimulation of the glottis during light anesthesia. Upper respiratory infections, which increase airway irritability, are common in children.

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up to 6 weeks after URI, which increases the susceptibility to laryngospasm. Compared with children without URI symptoms, children with an active or recent URI (< 4 weeks) are more likely to experience breath holding, desaturation, or severe cough during or after anesthesia. However, laryngospasm occurs more often in children with active URIs, younger children, and those having airway surgery. A growing body of literature suggests that children exposed to secondhand tobacco smoke have a higher incidence of perioperative respiratory complications. There is a 10-fold increase in the relative risk of laryngospasm associated with exposure to secondhand tobacco smoke. Also, these patients are more prone to severe coughing in the postoperative period.

Implications Larygnospasm may progress to complete airway obstruction, which can lead to hypoxemia, hypercarbia, bradycardia, and cardiac arrest. Five of 1000 patients who develop laryngospasm experience cardiac arrest. Immediate recognition and intervention are essential if this progression is to be avoided. Laryngospasm has also been associated with the development of negative-pressure pulmonary edema. Markedly negative intrapleural pressures generated by the patient in an effort to

overcome the obstruction of the closed glottis lead to transudation of fluid into the alveoli.

MANAGEMENT The management of laryngospasm varies, depending on whether airway obstruction is partial or complete, the severity of the laryngospasm, and its cause. In all cases, prompt recognition and immediate aggressive management are essential to prevent or reverse hypoxemia, which has the potential to rapidly progress to bradycardia and cardiac arrest. If recognition and treatment are delayed, management can be complicated by depression of cardiac output, which reduces the effectiveness of drug therapy. Algorithms for managing complete or partial airway obstruction due to laryngospasm are presented in Figures 147-1 and 147-2, respectively. Initial management includes the following: ●

●

●

Monitoring with pulse oximetry, electrocardiogram, and precordial stethoscope Capnography to confirm the presence or absence of effective ventilation Delivery of 100% oxygen and positive pressure via a wellsealed facemask

Figure 147–1 ■ Algorithm for management of complete airway obstruction. CPR, cardiopulmonary resuscitation; IM, intramuscular; IV, intravenous.

Complete Airway Obstruction

Apply firm upward pressure behind angle of mandible Apply laryngospasm notch pressure Administer 100% oxygen by mask “Flutter the bag”

Listen and watch for oxygen entry

Eliminate noxious stimulus Suction airway No improvement No IV access

Improved No improvement with IV access

Succinylcholine + atropine IM or sublingual Ventilate with 100% oxygen Intubate if needed

Increase or decrease concentration of volatile anesthetic

Improved

No improvement

Continue 100% oxygen Apply gentle positive pressure to the airway

Succinylcholine + atropine Ventilate with 100% oxygen Intubate if needed

Failed intubation

Failed intubation Repeat laryngoscopy Spray cords with lidocaine Attempt intubation Call for help Failed intubation Start CPR Consider cricothyrotomy or tracheostomy

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Figure 147–2 ■ Algorithm for management of partial airway obstruction. IV, intravenous(ly).

■

Pediatric Laryngospasm

601

Incomplete Airway Obstruction

Apply gentle positive pressure with 100% oxygen

Eliminate noxious stimulus Suction airway

No improvement

Improved Increase or decrease concentration of volatile anesthetic

Deepen anesthesia with IV propofol Stabilize airway and resume anesthetic

No improvement Improved

No improvement

Stabilize patient and resume anesthetic

● ●

● ●

● ●

Anterior displacement of the mandible Removal of noxious airway stimuli (e.g., suctioning of blood and secretions, removal of airway devices) Lightening or deepening the anesthetic Continuous positive airway pressure for partial airway obstruction “Fluttering the bag” Administration of muscle relaxants for complete obstruction unresponsive to other measures

atrial flutter. Either of these techniques can provide the minimal air exchange needed to maintain oxygenation and facilitate deepening or lightening of the anesthetic to relieve laryngospasm. However, care must be taken to avoid excessive continuous positive airway pressure. This can lead to gastric distention, which can further compromise ventilation or cause regurgitation. With complete laryngospasm and ball-valve obstruction, the application of positive airway pressure can actually worsen airway obstruction by distending the piriform fossa on either side of the larynx and pressing the aryepiglottic folds more firmly against each other. Larson described a simple technique of pressure on the “laryngospasm notch” located behind the ear, bounded anteriorly by the ascending ramus of the mandible adjacent to the condyle and posteriorly by the mastoid process and cephalad by the base of the skull. In Larson’s technique, firm pressure is applied toward the base of the skull with both fingers, accompanied by anterior displacement of the mandible. Larson and others1 have successfully employed this maneuver to manage complete laryngospasm. If the preceding maneuvers do not improve airway obstruction, a muscle relaxant is indicated. Because of its rapid onset and short duration of action, succinylcholine is the most commonly used muscle relaxant to treat laryngospasm. Another advantage of succinylcholine is that it can be administered intramuscularly or sublingually if intravenous access is unavailable. However, owing to its vagotonic properties in children, succinylcholine should be given with atropine. Atropine is also indicated to treat bradycardia caused by 1 Including the editor and his colleagues at both the University of Wisconsin–Madison and the Medical College of Wisconsin–Milwaukee.

PEDIATRICS & NEONATOLOGY

Anterior displacement of the mandible (i.e., the jaw thrust-chin lift maneuver) lengthens the thyrohyoid muscle and unfolds the supraglottic tissues. This may be especially beneficial with complete laryngospasm. This also ensures that airway obstruction from laryngeal closure is not exacerbated by soft tissue obstruction. Laryngospasm is often precipitated by regurgitation or retained upper airway secretions. Pharyngeal suctioning, even during the acute event, prevents further stimulation of the superior laryngeal nerve. Because laryngospasm often occurs in light planes of anesthesia, deepening the anesthetic or awakening the patient may relieve it, depending on whether the spasm occurs during induction, maintenance, or emergence. Propofol may be useful for rapidly deepening the level of anesthesia to relieve laryngospasm. In most instances, partial laryngospasm is effectively managed with bag-mask positive-pressure ventilation. On inspiration, there is often a brief moment of relative relaxation of the larynx. A firm squeeze on the anesthesia bag in phase with this brief moment of relative laryngeal relaxation provides “pressure support” for the patient’s respiratory efforts. Alternatively, fluttering the bag is a technique of manual high-frequency ventilation; the anesthesia bag is rapidly squeezed and released in a staccato rhythm similar to

Succinylcholine + atropine IV Ventilate with 100% oxygen Intubate if needed

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persistent hypoxemia. Intravenous doses of succinylcholine range from 0.1 to 2 mg/kg. Higher doses (up to 4 mg/kg) are required for intramuscular administration. Smaller doses of succinylcholine can effectively treat laryngospasm, but larger doses are needed if emergency intubation is indicated. If laryngospasm is sustained and the child is in extremis due to prolonged hypoxemia, intubation without muscle relaxants may be necessary. If apposition of the vocal cords interferes with intubation, topical application of lidocaine may relax the larynx and facilitate intubation. If air exchange has not been restored after these measures and intubation proves impossible, cricothyrotomy or emergent tracheostomy is required. Negative-pressure pulmonary edema is managed supportively with supplemental oxygen and diuretics. Rarely, endotracheal intubation and positive-pressure ventilation with positive end-expiratory pressure are required for resolution of negative-pressure pulmonary edema.

●

During extubation, hold the breathing bag momentarily at end-inspiration with a positive pressure of 15 to 20 cm H2O to maintain a high lung volume as the endotracheal tube is removed. In animal models, such positive intrathoracic pressure inhibits the glottal closure reflex and laryngospasm. Also, extubation with the lungs inflated facilitates the expulsion of airway secretions along with the endotracheal tube, thereby reducing the likelihood of laryngospasm or aspiration of secretions.

It is important to identify children at increased risk for developing laryngospasm. Although it may not be possible to modify all preoperative risk factors, prudent choices of anesthetic techniques and agents can reduce the likelihood of laryngospasm. Additionally, increased vigilance will lead to faster recognition and expedited management should laryngospasm occur.

Further Reading PREVENTION Prevention is the best treatment for laryngospasm. Take the following measures: ●

●

●

● ●

Avoid noxious airway or surgical stimulation during light anesthesia. Intubate the trachea when conditions promoting laryngospasm cannot be avoided. Suction oropharyngeal secretions thoroughly before tracheal extubation. Extubate the trachea only when the patient is fully awake. Manage high-risk patients expectantly, especially during airway surgery.

In addition, the following measures may help prevent laryngospasm: ●

●

●

Lidocaine applied topically to the larynx suppresses laryngeal mucosal sensory nerve activity and may reduce the likelihood of laryngospasm during intubation and after extubation. Intravenous lidocaine given shortly before extubation may prevent or attenuate laryngospasm via central interruption of the reflex pathway or a direct peripheral action on sensory and motor nerve terminals. Before extubation, have the patient breathe 100% oxygen for 3 minutes to provide a margin of safety should airway obstruction or laryngospasm occur.

Afshan G, Shohan U, Qamar-Ul-Hoda M, et al: Is there a role for a small dose of propofol in the treatment of laryngeal spasm? Paediatr Anaesth 12:625-628, 2002. Badgwell JM: Clinical Pediatric Anesthesia. Philadelphia, Lippincott-Raven, 1997, pp 39-40. Johnstone RE: Laryngospasm treatment—an explanation. Anesthesiology 91:581-582, 1999. Lakshmipathy N, Bokesch PM: Environmental tobacco smoke: A risk factor for pediatric laryngospasm. Anesth Analg 82:724-727, 1996. Larson PC Jr: Laryngospasm—the best treatment. Anesthesiology 89:1293-1294, 1998. Lee KWT, Downes JJ: Pulmonary edema secondary to laryngospasm. Anesthesiology 39:347-349, 1983. Olsson GL, Hallen B: Laryngospasm during anaesthesia: A computer-aided incidence studying 136,929 patients. Acta Anaesthesiol Scand 28: 567-575, 1984. Roy WL, Lerman J: Laryngospasm in paediatric anaesthesia. Can J Anaesth 35:93-98, 1988. Sasaki CT: Development of laryngeal function: Etiologic significance in the sudden infant death syndrome. Laryngoscope 89:1964, 1979. Schreiner MS, O’Hara I, Markakis DA, et al: Do children who experience laryngospasm have an increased risk of upper respiratory tract infection? Anesthesiology 85:475-480, 1996. Skolnick ET, Vomvolakis MA, Buck KA, et al: Exposure to environmental tobacco smoke and the risk of adverse respiratory events in children receiving general anesthesia. Anesthesiology 88:1144-1153, 1998. Suzuki M, Sasaki CT: Laryngeal spasm: A neurophysiologic redefinition. Ann Otol Rhinol Laryngol 86:150-157, 1977. Tait AR, Malviya S, Voepel-Lewis T, et al: Risk factors for perioperative adverse respiratory events in children with upper respiratory tract infections. Anesthesiology 95:299-306, 2001.

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Case Synopsis A 3-year-old child is scheduled for tonsillectomy and adenoidectomy. The past medical history is significant for Treacher Collins syndrome (Fig. 148-1). After inhalation induction, an intravenous line is started and 0.6 mg/kg of rocuronium is administered. Attempts at laryngoscopy and intubation are unsuccessful.

PROBLEM ANALYSIS Definition A difficult airway is one in which there is moderate to severe difficulty in performing mask ventilation, direct laryngoscopy, or both. This situation may result from anatomic (congenital or acquired) or physiologic defects.

Recognition A thorough history and physical examination are the best means of recognizing and predicting a difficult pediatric airway. Understanding the significant differences between the pediatric and adult airways is mandatory for the successful management of a child with a difficult airway (Fig. 148-2). Anatomic differences exist in the size, shape, and position of the airway, as well as the airway epithelium and its supporting structures. Physiologic differences between the neonatal and adult respiratory systems are due to differences in anatomy and respiratory control mechanisms.

breathe and swallow simultaneously. Similarly, both the thyroid and the cricoid cartilages move caudad as the thyrohyoid and cricothyroid membranes develop. Airflow. Airflow in the upper airway is turbulent even during quiet respiration. Laminar flow begins at the level of the fourth and fifth bronchial divisions, where the rapid increase in airway cross-sectional area reduces airflow velocity. The resistance to turbulent gas flow is proportional to the fifth power of the radius of the airway. Thus, 1 mm of edema within the trachea (reduction in radius from 2.1 to 1.1 mm) increases resistance to gas flow about 25-fold. Respiratory Mechanics. The highly compliant chest wall in young infants reduces the work of breathing. Such increased compliance is attributed to the softer, noncalcified ribs, which articulate with the vertebral column and sternum at right angles. The diaphragm is the mainstay of ventilation in infants. The infant diaphragm has fewer type I (fast) muscle

Upper Airway. The upper airway of the newborn is unique. The tongue is relatively large and fully occupies the cavity of the mouth and oropharynx. This may make manipulation of the laryngoscope and endotracheal tube more difficult during attempted intubation. Most, but not all, neonates are obligate nose breathers. This is because the epiglottis, positioned high in the pharynx, almost meets the soft palate, making mouth breathing difficult. These features persist for 2 to 6 months.

PEDIATRICS & NEONATOLOGY

Lymphoid Tissue. Unlike older infants and children, neonates have almost no upper airway lymphoid tissue. The tonsils and adenoids appear during the second year of life and reach their maximal size by 4 to 7 years of age. After this, they gradually recede. Enlarged tonsils and adenoids may increase bleeding during attempted nasal intubation. Epiglottis. The epiglottis in infants is large and U-shaped, and it protrudes over the larynx at a 45-degree angle. The use of a straight blade facilitates vocal cord visualization because it requires direct lifting of the epiglottis. Larynx. In the newborn, the body of the hyoid bone is situated at the level of C3-C4. As the infant grows, the glottis moves caudally and reaches C5-C6 at maturity. The high position of the epiglottis and larynx enables the infant to

Figure 148–1 ■ Abnormalities pertinent to airway management in a patient with Treacher Collins syndrome (mandibulofacial dysostosis) include mandibular and malar hypoplasia, microstomia, and choanal atresia.

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Figure 148–2 ■ Comparison of the anatomy in adult and infant airways. (From Ho M: The pediatric airway. In Bell C, Hughes C, Oh T [eds]: The Pediatric Handbook. St Louis, Mosby-Year Book, 1991, p 130. Adapted from Coté CJ, Todres ID: The pediatric airway. In Ryan JF, Todres DI, Coté CJ [eds]: A Practice of Anesthesia for Infants and Children. Orlando, Fla., Grune & Stratton, 1986.)

fibers than the adult diaphragm does. Thus, contraction is less efficient, and diaphragmatic muscle tires faster in infants compared with adults.

Risk Assessment As mentioned earlier, successful management of a child with a difficult airway requires a thorough history and physical examination. The history should focus on the following:

airway emergency exists. Gas exchange must be restored immediately to avert the imminent threat of brain hypoxic injury and death.

MANAGEMENT Premedication

Features of the physical examination most pertinent to perioperative airway management are listed in Table 148-1. Occasionally, additional studies (e.g., awake laryngoscopy, radiologic imaging, flow-volume loops) may be necessary to adequately assess a potentially difficult airway.

Premedication should be individualized. The majority of children with compromised airways should not be given a sedative or a narcotic; these drugs can result in loss of muscle tone, worsening previous airway obstruction or causing respiratory depression. In some older children in whom awake intubation is contemplated, careful sedation by a practitioner experienced in difficult airway management is reasonable. Anticholinergic agents must be considered both for their antisialagogue effect and to protect against vagal responses during airway manipulation.

Implications

Induction

If the ability to ventilate by mask is absent or lost, and if it is determined that the patient cannot be intubated, a true

The technique chosen for the induction of anesthesia varies according to the severity of airway pathology and the degree of anticipated respiratory difficulty. Pediatric patients are divided into four categories that determine the appropriate methods for induction and intubation:

●

● ●

Review of prior records, especially anesthetic records for evidence of a difficult airway Evidence of congenital or acquired airway defects Evidence of airway obstruction or sleep apnea

Table 148–1

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Examination of the Pediatric Airway

Size and shape of the head Gross features of the face Size and symmetry of the mandible Size of the tongue Shape of the palate Prominence of the upper incisors Jaw, head, and neck range of motion

●

●

Type I. These children present with a normal respiratory rate and oxygen saturation, mild respiratory distress, a visually normal airway (external appearance), and minimal or no sternal retractions. An example would be a patient with minimal facial (orbital) trauma. Type II. These children may have significant airway disease and moderate airway distress, but their airways have been successfully managed by previous anesthesia or

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surgical teams. An example would be a patient who returns with the diagnosis of laryngeal papillomas. Type III. These patients may or may not be in respiratory distress, but the airway is abnormal on physical examination. The abnormality might be micrognathia, macroglossia, microstomia, tumors that displace the airway, prominent incisors, or a palatofacial deformity. Patients with Pierre Robin, Treacher Collins, or Down’s syndrome are included in this group. Also included are patients with lesions in the lower airway or with anterior mediastinal masses, which could obstruct the airway after induction of general anesthesia, regardless of neuromuscular blockade. Type IV. Patients in this group present for the first time with significant airway obstruction. They demonstrate symptoms of airway distress, sternal retractions, low oxygen saturation, and signs of fatigue. A patient with an aspirated foreign body in the airway would fall into this group.

For types I and II patients, anesthesia is induced with either halothane or sevoflurane by mask. Slowly, positive pressure (5 to 10 cm H2O) is applied. This confirms the possibility of ventilating and oxygenating the child and can also reduce soft tissue airway obstruction. Once ventilation and oxygenation are confirmed and satisfactory, a muscle relaxant (only if absolutely necessary) may be administered. Types III and IV patients need special preparation in anticipation of difficult direct laryngoscopy and endotracheal intubation. Personnel and equipment to establish an immediate surgical airway should be available. The vast majority of children with a difficult airway require general anesthesia. If possible, every effort should be made to keep patients breathing spontaneously during induction. This is important for two reasons: 1. Administration of a muscle relaxant may cause complete airway obstruction due to loss of tongue, pharyngeal, or laryngeal tone. Such obstruction may not be easily overcome with manual ventilation. 2. A spontaneously breathing patient provides a valuable sign to localize the glottis—namely, air bubbles during exhalation.

Airway Adjuncts Successful management of a difficult pediatric airway requires the necessary equipment and the know-how to use it. Standard equipment includes assorted sizes of facemasks, oropharyngeal and nasopharyngeal airways, laryngoscope blades, endotracheal tubes, and stylets. Additional equipment must be readily available (e.g., in a “difficult airway cart”).

ventilatory pressures and contains an inner tube for aspiration of gastric contents. Flexible Fiberoptic Bronchoscope. The flexible fiberoptic bronchoscope for children varies in external diameter from 2.2 to 4.0 mm. Those with 2.2- or 4.0-mm external diameters will pass through 2.5- and 4.5-mm endotracheal tubes, respectively. The 2.2-mm ultrathin fiberoptic bronchoscope has a flexible tip but lacks a suction port. It is invaluable for managing a child with a difficult airway. Bullard Laryngoscope. The Bullard laryngoscope, which is available in both pediatric and adult sizes, permits indirect visualization of the larynx with minimal mouth opening or movement of the neck. It does not require alignment of the oral, pharyngeal, and laryngeal axes. The pediatric blade is narrower and has more acute terminal angulation than does the adult version. The trachea is intubated by advancing a previously loaded endotracheal tube over an intubating stylet fastened to the laryngoscope blade. Light Wand. The light wand (lighted stylet) uses transtracheal illumination to guide insertion of the endotracheal tube. It is useful in the management of all types of difficult airways in children. Unlike with a fiberoptic bronchoscope, blood and secretions are not impediments to success. Smaller sizes are available for use with endotracheal tubes as small as 2.5 mm.

PREVENTION Studies have shown that children have a higher risk of anesthesia-related morbidity than adults do. Untoward respiratory events are the major reason for this morbidity. A thorough understanding of pediatric airway anatomy and physiology will help reduce this risk. Preoperative identification of a child with a difficult airway must be coupled with sufficient personnel and equipment to secure the airway without

PEDIATRICS & NEONATOLOGY

Laryngeal Mask Airway. The original laryngeal mask airway (LMA) is available in sizes 1, 1.5, 2, 2.5, and 3 for use in pediatric patients. It may be used as the sole airway of choice when endotracheal intubation or mask ventilation is undesirable or difficult. The LMA may also be used to facilitate either blind or fiberoptic intubation of the trachea (Fig. 148-3). The intubating LMA or Fastrack can be used in patients weighing more than 30 kg. It usually provides a better conduit for blind intubation. A Proseal LMA model is available in sizes 2 and 3; it has the advantage of allowing higher

Figure 148–3 ■ The laryngeal mask airway can be used to facilitate either blind or fiberoptic endotracheal intubation.

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life-threatening sequelae. Finally, the existence of a difficult airway can be communicated to future care providers via detailed notes in the chart, a letter given to the child’s parents, and a Medic-Alert bracelet.

Further Reading Bell C, Kain ZN, Hughes C: Respiratory physiology and disease processes. In Bell C, Kain ZN, Hughes C (eds): The Pediatric Anesthesia Handbook, 2nd ed. St. Louis, Mosby, 1997, pp 111-131. Brimacombe J, Keller C: The Proseal laryngeal mask airway. Anesthesiol Clin North Am 20:871-891, 2002. Brown RE, Vollers JM, Rader GR, et al: Nasotracheal intubation in a child with Treacher Collins syndrome using the Bullard intubating laryngoscope. J Clin Anesth 5:492-493, 1993.

Gregory GA, Riazi J: Classification and assessment of the difficult pediatric airway. Anesthesiol Clin North Am 16:729-741, 1998. Hagberg CA: Special devices and techniques. Anesthesiol Clin North Am 20:907-932, 2002. Lopez-Gil M, Brimacombe J, Alvarez M: Safety and efficacy of laryngeal mask airway: A prospective study of 1400 children. Anaesthesia 51:969-972, 1996. Lopez-Gil M, Brimacombe J, Brain AIJ: Preliminary evaluation of a new prototype laryngeal mask in children. Br J Anaesth 82:132-134, 1999. Muraika L, Heyman JS, Shevchenko Y: Fiberoptic tracheal intubation through a laryngeal mask airway in a child with Treacher Collins syndrome. Anesth Analg 97:1298-1299, 2003.

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Marnie Robinson and Joseph Previte Case Synopsis A 28-year-old gravida II, para I woman at 36 2/7 weeks of gestation presents with a fetus with a large neck mass. Ex utero intrapartum therapy is planned to establish an airway before delivery.

for uterine relaxation, it is now possible to maintain uteroplacental support for 60 to 90 minutes before delivery.

PROBLEM ANALYSIS Definition

Recognition

The rapidly growing field of fetal surgery encompasses many different procedures that can be divided into three broad categories: (1) fetoscopy, (2) open fetal surgery, and (3) ex utero intrapartum therapy (EXIT). Because fetoscopic, or minimally invasive, procedures (Table 149-1) involve manipulation of the placenta or umbilical cord through an endoscope, only local or regional anesthesia is required. Open fetal surgical procedures (Table 149-2) require complete uterine relaxation, usually with high concentrations of volatile anesthetics. Both fetoscopy and open fetal surgeries are performed in midgestation to allow for fetal growth after the procedure. In contrast, EXIT is performed if the fetus requires intervention at birth but before division of the umbilical cord. Consequently, the procedure is usually deferred until as late in gestation as possible, based on both the maternal and fetal condition. The particular intervention varies by indication (Table 149-3) and may involve securing the airway, resecting an intrathoracic mass, or inserting a cannula for extracorporeal membrane oxygenation. In the case synopsis, the large neck mass puts the fetus at risk for perinatal asphyxia if it proves difficult or impossible to intubate the trachea after conventional delivery. EXIT allows extended uteroplacental support while the airway is secured by direct laryngoscopy, rigid or fiberoptic bronchoscopy, or tracheostomy. With experience and the use of high concentrations of volatile anesthetics

Most fetal disease is initially detected by ultrasonography. Abnormal findings prompt further testing. An in-depth ultrasound examination is used to assess fetal weight and overall health. Amniocentesis provides amniotic fluid for analysis, including karyotype. Structural or functional cardiac defects can be identified using fetal echocardiography. Detailed images of fetal anatomy can be obtained with ultrafast magnetic resonance imaging. Although specific criteria for identifying a fetus that would benefit from an EXIT procedure vary by indication, some conditions have similar presentations. For example, cervical neck masses prevent the swallowing of amniotic fluid, resulting in polyhydramnios. Pulmonary amniotic fluid accumulation causes the lungs to appear large and echogenic. Chronic fetal disease from many causes can lead to hydrops fetalis, progressive ascites, pleural and cardiac effusions, and generalized edema that, without intervention, will ultimately lead to fetal demise.

Risk Assessment FETAL RISK The fetus is at risk for adverse events both during and after the EXIT procedure. During surgery, maintenance of

Table 149–1

■

Indications for Fetoscopic Surgery

Disease

Procedure

Twin-twin transfusion syndrome

Laser photocoagulation of placental vessels Coagulation of umbilical cord Division of amniotic bands

Twin reversed arterial perfusion Amniotic band syndrome

■

Indications for Open Midgestation Fetal Surgery

Disease

Procedure

Myelomeningocele Sacrococcygeal teratoma Intrathoracic masses Congenital diaphragmatic hernia with low lung-to-head ratio

Repair of neural canal defect Resection of teratoma Resection of mass Tracheal occlusion

607

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Table 149–2

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Indications for Ex Utero Intrapartum Therapy (EXIT)

Disease

Procedure

Congenital diaphragmatic hernia

Removal of tracheal clip or balloon that was placed in utero Tracheostomy

Congenital high upper airway obstruction syndrome Giant cervical neck mass Severe pulmonary hypoplasia from intrathoracic mass Anticipated difficult intubation

Resection of mass Resection of mass Obtain surgical airway

blood pressure and adequate oxygen (O2) delivery is essential, as is ensuring complete uterine atony and unobstructed umbilical cord blood flow. The greatest risk to the fetus is fetal demise or severe disability from the underlying disease process. To be considered for EXIT, the fetus must have a dismal prognosis without intervention. With intervention, in addition to the risks already mentioned, there are risks specific to the disease process and its treatment. For example, with a cervical neck mass, neck structures may be damaged during EXIT. If a tracheostomy is required, care of the neonate becomes more complex. Finally, depending on the timing of EXIT, the infant’s condition may be further complicated by premature birth. MATERNAL RISK

normothermia is hampered by exposure of the fetus, whose thin skin is inadequate to prevent heat loss. In a preterm fetus, the effects and duration of anesthetic agents are increased owing to immature organ function and incomplete myelination. Because of decreased contractility in the fetal heart, the fetus may not be able to compensate for hemodynamic changes. Changes in fetal heart rate, such as tachycardia with fetal incision or bradycardia from inadequate uteroplacental perfusion, may be tolerated for only a brief period. Hypoxia, increased systemic vascular resistance, or the negative inotropic effects of anesthetic agents may further compromise fetal cardiac function. Decreased cardiac preload from impaired venous return during surgical manipulation or blood loss can lead to fetal hypotension, bradycardia, shock, and cardiac arrest. During EXIT, the fetus remains on the sterile field until division of the umbilical cord, limiting monitoring options to detect physiologic derangements. Hemodynamic data are obtained from a sterile fetal pulse oximeter and intermittent fetal echocardiography. Ideally, the surgeon places a fetal intravenous catheter, permitting the administration of medications and fluids by the anesthesiologist. If fetal intravenous access is not available, resuscitation is limited to intramuscular injections by the surgeon and maternal interventions by the anesthesiologist. Maintenance of maternal

Table 149–4

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The mother is also exposed to significant risk during EXIT. Like any parturient, she has experienced the physiologic changes of pregnancy and is subject to the associated risks of general anesthesia (Table 149-4). She is also at risk for amniotic fluid embolism during labor or intra-abdominal surgery and for postoperative wound infection. Additional maternal risks unique to EXIT include the following: ●

●

●

Obligate cesarean section for all future deliveries. EXIT generally requires a larger incision than standard cesarean delivery, increasing the risk of uterine rupture during subsequent labor and vaginal delivery. Risks of invasive monitoring. Because the welfare of the fetus depends on uteroplacental perfusion, which in turn is dependent on maternal blood pressure, continuous monitoring of maternal blood pressure during EXIT is indicated. Increased risk of blood loss requiring transfusion. The profound uterine relaxation required to maintain uteroplacental support during EXIT increases the risk of uterine atony after the third stage of labor. Even if uterine tone is reestablished expeditiously, the likelihood of transfusion of blood products is greater with an EXIT procedure than with routine cesarean delivery.

Studies comparing maternal risk during fetal surgery and routine cesarean delivery have found only two major

Physiologic Changes of Pregnancy

Organ System

Changes in Pregnancy

Risk during Anesthesia

Neurologic

Decreased MAC Engorged epidural plexus Upper airway edema Decreased functional residual capacity and increased minute ventilation Inferior vena cava behind gravid uterus Plasma volume increased more than red cell volume Increased cardiac output and reduced peripheral vascular resistance Reduced lower esophageal sphincter tone and increased intra-abdominal pressure Decreased plasma proteins and albumin Reduced plasma cholinesterase

More sensitive to anesthetics More sensitive to neuraxial anesthetics Potentially difficult mask ventilation and intubation Faster desaturation with apnea

Respiratory Cardiovascular

Gastrointestinal Hepatic

MAC, minimum alveolar anesthetic concentration.

Supine aortocaval compression Relative anemia of pregnancy; little or no change in blood pressure More sensitive to anesthetics Increased risk of aspiration Increased risk of pulmonary edema Prolonged succinylcholine effect

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differences: increased blood loss and an increased incidence of wound infection. There have been no reports of long-term morbidity or decreased reproductive potential in women undergoing fetal surgery. The only reported maternal death associated with fetal surgery was from an amniotic fluid embolus during a fetoscopic procedure; there are no reports of maternal mortality associated with open fetal surgery or EXIT procedures.

Implications Fetal surgery is proposed only after a thorough evaluation by a fetal therapeutics committee and a careful consideration of the risks and benefits for both the mother and the fetus. Because fetal surgery involves substantial risk, it is considered appropriate only when the fetus is “sick” and the mother is “healthy.” Once a case is deemed appropriate for consideration of fetal intervention, a team meeting is held involving the mother, selected family members or friends, and the appropriate practitioners. A full explanation of the risks and benefits is presented by the pediatric surgeon, obstetrician, neonatologist, anesthesiologist, and other relevant medical specialists. Once the mother consents to proceed with EXIT, the complexity of the procedure requires close coordination of personnel and operating room resources.

MANAGEMENT Whereas cesarean delivery is performed under maternal regional or general anesthesia, with no anesthesia for the fetus, EXIT procedures require general anesthesia for both. Even a typical general anesthetic for cesarean delivery is unsuitable for an EXIT procedure. The goals of anesthetic management of an EXIT procedure include the following: ● ● ●

Anesthesia for the mother Anesthesia for the fetus Maintenance of uteroplacental perfusion until division of the umbilical cord

General endotracheal anesthesia for the mother with volatile anesthetics accomplishes these goals to some extent. The mother receives a complete anesthetic with a volatile agent that crosses the placenta and at least partially anesthetizes the fetus. High concentrations of volatile agents also decrease uterine tone, thereby supporting uteroplacental perfusion. However, additional drugs are required to supplement each of the listed goals during the course of the procedure.

Preinduction

Induction After adequate preoxygenation, a rapid-sequence induction is performed, and the airway is secured with a cuffed endotracheal tube. Following intubation, additional intravenous access is obtained, and intra-arterial and bladder drainage catheters are inserted. Before surgical incision, muscle relaxation is achieved with nondepolarizing neuromuscular blocking drugs.

Start of Surgery Ultrasonography is used just before surgical preparation to verify fetal well-being and identify the location of the placenta. Before uterine incision, complete uterine relaxation is induced using at least 2 MAC of volatile anesthetic, supplemented by small doses of nitroglycerin, if needed. As the volatile anesthetic concentration is increased, nitrous oxide is discontinued, and 100% O2 is administered to maximize O2 delivery to the fetus. High doses of volatile anesthetics invariably decrease maternal systemic vascular resistance and cardiac output. Thus, ephedrine and phenylephrine are titrated to maintain maternal systolic blood pressure within 10% to 20% of baseline. Reduced maternal blood pressure adversely affects the fetus, because uteroplacental perfusion is directly related to maternal blood pressure. Hysterotomy is planned to avoid placental injury. To minimize maternal bleeding, a special stapling device for fetal surgery is used. Also, warm uterine irrigation is performed to prevent fetal hypothermia and maintain uterine volume. Adequate uteroplacental blood flow is ensured by attention to complete uterine relaxation, maintenance of normal maternal blood pressure and oxygenation, and avoidance of kinking or compression of the umbilical cord. To monitor the fetus, a pulse oximeter probe is placed on an extremity and covered with foil to deflect ambient light. Supplemental fetal anesthesia is administered as an intramuscular “cocktail” consisting of a nondepolarizing muscle relaxant and a narcotic, with or without atropine. In the case of a cervical neck mass, the fetal head and torso are delivered into the surgical field for direct laryngoscopy and potential tracheostomy. Intermittently, sterile fetal echocardiography can monitor cardiac function, ductal patency, and volume status.

Post-EXIT Care Once the procedure is complete, umbilical, arterial, and venous catheters can be placed by the Seldinger technique while the umbilical cord is still engorged from uteroplacental blood flow. Before the umbilical cord is divided, adequate chest rise and an appropriate increase in pulse oximetry are confirmed. Fetal O2 saturation in utero is normally 55% to 65%. Ventilation with 100% O2 increases the hemoglobin O2 saturation to 95% to 100%. When the umbilical cord is divided, the delivery time is recorded, and the baby is taken from the sterile field for evaluation and resuscitation. If additional immediate surgery is indicated, the infant is usually taken to an adjacent operating room, where a second team of anesthesiologists, surgeons, and nurses awaits.

PEDIATRICS & NEONATOLOGY

Preoperatively, indomethacin may be given to the mother as a tocolytic if there are no fetal contraindications, such as a fragile fetal cardiac status. As for any pregnant patient requiring anesthesia, aspiration precautions include 8 hours of fasting and oral sodium citrate before induction. If postoperative maternal epidural analgesia is planned, the catheter is placed preoperatively, but it is not dosed during the procedure in order to avoid severe hypotension. Left uterine displacement is mandatory to prevent aortocaval compression.

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After delivery of the placenta, volatile anesthetic concentrations are reduced, and intravenous oxytocin (Pitocin) is given to restore uterine tone. At the same time, the anesthetic depth can be increased with nitrous oxide. Provided the mother is hemodynamically stable, analgesia can be provided with narcotics or by dosing the epidural catheter. Intramuscular methylergonovine or carboprost tromethamine may be required for cases of refractory uterine atony. As the hysterotomy and laparotomy incisions are closed, volume resuscitation is provided to the mother as indicated by vital signs and estimated blood loss. At the conclusion of surgery, muscle relaxants are reversed, and the mother is extubated when fully awake, followed by transport to the recovery area.

PREVENTION Although it is impossible to prevent all adverse outcomes, proper preparation for the anesthetic can help minimize any associated risks. For EXIT procedures, anesthetic preparation must include consideration of two patients—the mother and the fetus. Good communication among the specialist physicians and the nursing staff during the EXIT planning stages

can identify potential risks and problems and allow the best possible care for both patients.

Further Reading Adzick NS, Harrison MR: Fetal surgical therapy. Lancet 343:897-902, 1994. Gaiser RR, Cheek TG, Kurth CD: Anesthetic management of cesarean delivery complicated by ex utero intrapartum treatment of the fetus. Anesth Analg 84:1150-1153, 1997. Harrison MR, Keller RL, Hawgood SB, et al: A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia. N Engl J Med 349:1916-1924, 2003. Hirose S, Farmer DL, Lee H, et al: The ex utero intrapartum treatment procedure: Looking back at the EXIT. J Pediatr Surg 39:375-380, 2004. Liechty KW, Crombleholme TM, Timothy M, et al: Intrapartum airway management for giant fetal neck masses: The EXIT procedure. Obstet Gynecol 177:870-874, 1997. Lim BF, Crombleholme TM, Hedrick JL, et al: Congenital high airway obstruction syndrome: Natural history and management. J Pediatr Surg 38:940-945, 2003. Myers LB, Cohen D, Galinkin J, et al: Anaesthesia for fetal surgery. Paediatr Anaesth 12:569-578, 2002. Noah MM, Norton ME, Sandberg P, et al: Short-term maternal outcomes that are associated with the EXIT procedure, as compared with cesarean delivery. Am J Obstet Gynecol 186:1299-1303, 2002. Rychik J, Tian Z, Cohen MS, et al: Acute cardiovascular effects of fetal surgery in the human. Circulation 110:1549-1556, 2004.

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Liana Hosu and C. Dean Kurth Case Synopsis A 2.5-kg, 5-month-old male infant presents for ileostomy takedown. His history is significant for premature birth at 26 weeks’ gestation, intraventricular hemorrhage, and immature lung disease requiring mechanical ventilation for 3 weeks. He was discharged home at 3 months. He had a bowel resection and ileostomy at 1 month of age for necrotizing enterocolitis. A general anesthetic is administered for the ileostomy takedown, and an epidural catheter is placed for postoperative pain control. After 3 hours in the pediatric acute care unit, he is noted to have episodes of apnea. Intravenous caffeine is administered to prevent further apneic episodes.

PROBLEM ANALYSIS Definition Postoperative apnea is defined by periods of no ventilation during recovery after anesthesia and operation, usually in formerly premature infants or full-term neonates. This is distinguished from apnea of prematurity and apnea of infancy, which occur in premature and full-term infants, respectively, who have not had anesthesia or surgery. Postoperative apnea is characterized by duration and type. Brief apnea is longer than 6 but less than 15 seconds, whereas prolonged apnea is longer than 15 seconds. However, the latter can be less than 15 seconds if associated with bradycardia. In terms of type, apnea can be central, obstructive, or mixed (Fig. 150-1): ● ●

●

Central apnea occurs without respiratory effort. Obstructive apnea occurs with respiratory effort, but without ventilation. Mixed apnea is characterized by absent ventilation with occasional respiratory effort.

Recognition Postoperative apnea is diagnosed in the following situations: ●

●

Risk Assessment The incidence of postoperative apnea is influenced by patient, surgical, and anesthetic factors. Of these, premature birth history is the most important. Former preterm

Postconceptual Age. Postconceptual age (PCA), defined as the sum of postnatal age and gestational age, is the most important determinant of postoperative apnea. The incidence of postoperative apnea varies inversely with PCA (Fig. 150-2). The incidence is high in prematurely born infants younger than 40 weeks’ PCA. After this, the incidence decreases sharply until the infant is 50 weeks’ PCA. The incidence of postoperative apnea is low at that point and decreases gradually thereafter. Gestational Age. The gestational age of the infant modifies the incidence of postoperative apnea. Figure 150-2 displays the relationship of postoperative apnea incidence versus PCA for an infant born at 32 weeks’ gestation, with an approximate 85% incidence of postoperative apnea. The incidence-versusPCA curve shifts upward as the gestational age decreases; conversely, the curve shifts downward as gestational age approaches term. Thus, at any given PCA, the incidence of postoperative apnea is greater for infants born at 28 weeks’ gestation than at 32 weeks’ gestation. Anemia. The presence of anemia (hematocrit <30%) also modifies the incidence of postoperative apnea in formerly premature infants. The incidence-versus-PCA curve shifts upward with anemia (see Fig. 150-2). Thus, for a given PCA, the presence of anemia increases the incidence of postoperative apnea. Prematurity-Associated Comorbidity. Today, survival of extremely low-birth-weight infants (gestational age 24 to 28 weeks) is quite common. Bronchopulmonary dysplasia, retinopathy of prematurity, hydrocephalus, seizures, and cerebral palsy occur frequently in extremely low-birth-weight survivors. For a given PCA, the risk of postoperative apnea is greater in formerly premature infants with residual diseases of prematurity. 611

PEDIATRICS & NEONATOLOGY

●

No respiratory effort or ventilation is observed for more than 15 seconds (prolonged apnea). No respiratory effort or ventilation is observed for less than 15 seconds and the heart rate decreases to less than 80 beats per minute for more than 5 seconds (apnea and bradycardia). No respiratory effort or ventilation is observed for more than 6 seconds but less than 15 seconds (brief apnea).

infants are at increased risk for postoperative apnea, although full-term infants less than 4 weeks’ postnatal age are also at risk. In formerly premature infants, factors that influence the incidence of postoperative apnea include the following.

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A

B

250 Heart Rate 150 100 (bpm) 75 0.5 Impedance (Δohms)

0 −0.5 100

Thermistor (mvolts)

SpO2 (%)

0 −100 100

Figure 150–1 ■ Postoperative recording of heart rate, chest wall movement (impedance), nasal airflow (thermistor), and oxygen saturation (SpO2) from an infant after general inhalation anesthesia for inguinal hernia repair. A, Recordings obtained in the postanesthesia care unit depict brief central apnea. This is denoted by a lack of chest wall motion and airflow. Note mild arterial desaturation after the apnea. B, Another recording, also obtained in the postanesthesia care unit, illustrates mixed apnea. During the initial 6 seconds of apnea, there is no chest wall motion or airflow (brief central apnea), followed by 6 seconds of chest wall motion with no airflow (obstructive apnea). Note that arterial desaturation with the latter is more severe than with comparable central apnea in A.

80 60 10 sec

10 sec

Surgical Procedure. In premature infants, postoperative apnea is less frequently associated with minor surgical procedures (e.g., inguinal herniorrhaphy) than with major surgical procedures (e.g., laparotomy). Surgical factors appear to play a role in the pathogenesis of postoperative apnea. For example, premature infants undergoing cryotherapy for retinopathy of prematurity under topical anesthesia may experience postoperative apnea. Postoperative apnea may also begin hours after emergence from anesthesia, well after all anesthetic drugs have been cleared from the body. In fullterm infants, postoperative apnea can occur after pyloromyotomy and may be associated with severe desaturation.

100 Younger gestational age Anemia General anesthesia (?) Soluble inhalation anesthetics (?) Opioids (?) Epidural clonidine

90

Incidence of apnea

80 70 60 50 40 30 20 10 0 35

40

45

50

55

60

Postconceptual age Figure 150–2 ■ The incidence of postoperative apnea varies inversely with the postconceptual age in formerly premature infants. The incidence curve shifts upward for babies (1) born at younger gestational ages, (2) with postoperative anemia or residual diseases related to prematurity (e.g., bronchopulmonary dysplasia), (3) after general anesthesia versus pure regional anesthesia, and (4) following general anesthesia with soluble versus insoluble inhalational agents. Administration of clonidine epidurally or opioids intravenously may also shift the curve upward.

Anesthetic Management. Postoperative apnea may occur after general anesthesia, regional anesthesia, or combined general and regional anesthesia. A meta-analysis found no reliable evidence of a difference in the incidence of postoperative apnea, bradycardia, or oxygen desaturation in ex-preterm infants following hernia repair using general or regional anesthesia. However, spinal anesthesia has an appreciable failure rate, requiring the use of sedation or conversion to general anesthesia. Postoperative apnea may result from the addition of clonidine to local anesthetic solutions for caudal epidural analgesia. The incidence of postoperative apnea in infants undergoing general anesthesia may be lower following the use of less soluble inhalational agents (e.g., desflurane). For pyloromyotomy, new-onset postoperative apnea occurred less frequently after a remifentanil-based anesthetic compared with a halothane-based anesthetic. However, the incidence of postoperative apnea after regional anesthesia in which sedative drugs (e.g., ketamine, fentanyl, midazolam, nitrous oxide) were administered is similar to that after general anesthesia. Use of muscle relaxants as part of the general anesthetic regimen does not appear to alter the incidence of postoperative apnea. Of note, a history of apnea of prematurity is not predictive of postoperative apnea. Formerly premature infants with no history of apnea can develop postoperative apnea. Conversely, formerly premature infants with a history of apnea can undergo anesthesia and surgery without developing postoperative apnea. Sleep studies with pneumocardiography to document the presence or absence of apnea are often performed on premature infants to help determine whether the baby needs at-home monitoring. However, a normal sleep study (no apnea) before surgery does not guarantee that the baby will not develop postoperative apnea.

Implications Postoperative apnea can be life threatening. Cardiopulmonary arrest and death have been reported after postoperative apnea. The relationship between postoperative apnea and sudden infant death syndrome (SIDS) is unknown, as is the

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relationship between apnea in premature or full-term infants and SIDS. The risk of SIDS is increased for infants with apnea of prematurity or apnea of infancy. Most SIDS cases, however, occur in infants without a history of apnea. Postoperative apnea is characterized by its variable onset and offset in relation to emergence from anesthesia. Postoperative apnea begins in the postanesthesia care unit in about two thirds of affected infants. In the remaining infants, it begins between 2 and 12 hours after surgery. Usually, it is characterized by multiple events of variable duration that can continue for days after surgery. Apneic episodes are mostly self-limited and require close observation but no treatment. Occasionally, apneic infants require manual stimulation, such as flicking the soles of the feet, to restore ventilation. Sometimes they require bag and mask ventilation. Rarely, cardiopulmonary resuscitation must be instituted to revive the patient.

MANAGEMENT The anesthetic management of young infants at risk for apnea includes preoperative, intraoperative, and postoperative considerations.

Preoperative Considerations Nonemergency surgery should be postponed based on the PCA, because the risk of postoperative apnea decreases sharply between 40 and 50 weeks’ PCA and then gradually decreases until 70 weeks’ PCA. Depending on institutional practices, the risk for postoperative apnea is minimized by delaying nonemergency surgery until the infant is 50 to 60 weeks’ PCA. Elective surgery in full-term infants should be postponed until the infant is 4 weeks old. Blood hemoglobin concentration should be checked preoperatively in infants younger than 6 months. The risk of postoperative apnea is increased when the hematocrit is less than 30%. The cause of anemia should be elucidated and treated before surgery.

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Limitations for same-day surgery should be set. Some institutions use an algorithm to determine which infants must be monitored for postoperative apnea in the hospital overnight (Fig. 150-3).

Intraoperative Considerations General inhalation anesthesia, spinal anesthesia, caudal epidural anesthesia, or combined general and regional anesthesia may be administered to infants at risk for postoperative apnea. Less soluble inhalational anesthetics (desflurane) should be used in premature infants rather than more soluble agents (isoflurane). To decrease the incidence of postoperative apnea with general inhalation anesthesia, a caffeine base (10 mg/kg intravenously) should be administered intraoperatively shortly after anesthesia induction. Caffeine reduces the incidence and severity of oxygen desaturation with apnea. Although postoperative apnea may occur even if caffeine has been administered (caffeine’s effectiveness has been questioned), the risk-benefit ratio favors administration; caffeine has few side effects and has an excellent safety profile. Further studies are needed to determine which infants might benefit most from preemptive treatment with caffeine. Regional anesthesia (subarachnoid block or caudal epidural) may be suitable for lower extremity or inguinal surgery. It has been shown to decrease the incidence of postoperative apnea when compared with general inhalation anesthesia. Infants, however, may not be compliant during surgery with a pure regional anesthetic; they may not remain immobile in the upper extremities or trunk, or they may cry if they are hungry. Supplemental intravenous sedation or inhalation of nitrous oxide improves compliance but increases the risk of postoperative apnea to greater than that of general anesthesia. Surgical procedures are often difficult in young, formerly premature infants and may take longer than expected, making spinal anesthesia less advantageous than caudal epidural or general anesthesia. Caudal epidural clonidine should be avoided in premature infants and in term infants less than 4 weeks of age because it may cause respiratory depression.

Prematurely born? Preterm

Full term

Postconceptual age? <50 wk?

50–60 wk? Yes

Anemia? PS 3–4? Gestational age <28 wk?

>4 wk? No

Day surgery

<4 wk? Hospitalize overnight

Figure 150–3 ■ Day-surgery algorithm used for infants at Cincinnati Children’s Hospital. If the infant is full term and younger than 4 weeks, hospital admission for overnight monitoring is planned. If a term infant is older than 4 weeks, day surgery may be performed. If an infant was born prematurely, is older than 50 weeks’ postconceptual age, and there is no history of anemia or significant comorbidities, ambulatory surgery is planned. If the infant was born prematurely and is older than 60 weeks’ postconceptual age, regardless of anemia or comorbidities, day surgery is planned. All infants born prematurely and younger than 50 weeks’ postconceptual age are admitted to the hospital for overnight monitoring. PS, physical status.

PEDIATRICS & NEONATOLOGY

Hospitalize overnight

Postnatal age? >60 wk?

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Postoperative Considerations Cardiorespiratory monitoring is the most important postoperative treatment for infants at risk of postoperative apnea. Nurses must be familiar with how to respond to the cardiorespiratory alarm, including recognition of apnea in young infants, and how to treat apnea, from manual stimulation to cardiopulmonary resuscitation. The infant should be monitored in a location where a nurse will hear the cardiorespiratory alarm. Visual confirmation of breathing or apnea is important, because false-positive alarms are frequent. Cardiorespiratory monitors that employ impedance technology to detect respiratory rate and heart rate are sensitive and easily applied. These monitors have alarms for high and low heart and respiratory rates, as well as for apnea duration. For young infants, the apnea alarm is set to 15 seconds, and the low heart rate alarm is set to 80 beats per minute (relative bradycardia for young infants). For postoperative pain control, continuous caudal epidural analgesia with local anesthetic-opioid solutions is the mainstay of analgesic therapy. Clinical stability in preterm neonates who have received caudal epidural anesthesia with local anesthetic-opioid solutions is noted by a reduction in hypoxic episodes, improved hemodynamic stability, reduced mortality, and improved neurologic outcome. Continuous caudal epidural infusions are commonly used as an adjunct to neonatal general anesthesia. This allows earlier extubation and avoids the need for intravenous opioids. Further, the addition of opioids to local anesthetic in caudal epidural infusions may reduce the dose of local anesthetic needed for analgesia, thereby reducing the risk for local anesthetic toxicity and providing improved analgesia. However, young expremature infants are more susceptible to opioid-induced apnea. Therefore, the opioid dose must be reduced in the caudal epidural infusate. Even though continuous caudal epidural analgesia with opioids is the mainstay of analgesic therapy, there is a lack of properly controlled, randomized clinical trials that have evaluated postoperative regional analgesia versus more conventional (intravenous) analgesia strategies.

PREVENTION The following recommendations can reduce the risk of postoperative apnea: ●

Delay elective surgery until 50 to 60 weeks’ PCA in highrisk patients.

●

● ● ●

●

Administer a caffeine base (10 mg/kg intravenously) after anesthetic induction. Consider preoperative blood transfusion for anemia. Use an appropriate regional anesthesia-only technique. Avoid using caudal epidural clonidine, and reduce the dose of opioids with caudal epidural anesthesia or analgesia. Use less soluble inhalational agents when a general anesthetic is unavoidable.

Further Reading Anand KJS, Stevens BJ, McGrath PJ: Pain in Neonates, 2nd ed. Philadelphia, Elsevier, 2000. Andropoulos DB, Heard MB, Johnson KL, et al: Postanesthetic apnea in full-term infants after pyloromyotomy. Anesthesiology 80:216-219, 1994. Coté CJ, Zaslavsky A, Downes JJ, et al: Postoperative apnea in former preterm infants after inguinal herniorrhaphy: A combined analysis. Anesthesiology 82:809-822, 1995. Craven PD, Badawi N, Henderson-Smart DJ, et al: Regional (spinal, epidural, caudal) versus general anaesthesia in preterm infants undergoing inguinal herniorrhaphy in early infancy. Cochrane Database Syst Rev CD003669, 2003. Fellmann C, Gerber AC, Weiss M: Apnoea in a former preterm infant after caudal bupivacaine with clonidine for inguinal herniorrhaphy. Paediatr Anaesth 12:637-640, 2002. Galinkin JL, Davis PJ, McGowan FX, et al: A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. II. Perioperative breathing patterns in neonates and infants with pyloric stenosis. Anesth Analg 93: 1387-1392, 2001. Kurth CD, LeBard SE: Association of postoperative apnea, airway obstruction, and hypoxemia in former premature infants. Anesthesiology 75:22-26, 1991. Kurth CD, Spitzer AR, Broennle AM, et al: Postoperative apnea in preterm infants. Anesthesiology 66:483-488, 1987. Welborn LG, Hannallah RS, Fink R, et al: High-dose caffeine suppresses postoperative apnea in former preterm infants. Anesthesiology 71:347-349, 1989. Welborn LG, Hannallah RS, Luban NLC, et al: Anemia and postoperative apnea in former preterm infants. Anesthesiology 74:1003-1006, 1991. Welborn LG, Rice LJ, Hannallah RS, et al: Postoperative apnea in former preterm infants: Prospective comparison of spinal and general anesthesia. Anesthesiology 72:838-842, 1990. William JM, Stoddart PA, Williams SA, et al: Post-operative recovery after inguinal herniotomy in ex-premature infants: Comparison between sevoflurane and spinal anaesthesia. Br J Anaesth 86:366-371, 2001. Wolf AR, Lawson RA, Dryden CM, et al: Recovery after desflurane anaesthesia in the infant: Comparison with isoflurane. Br J Anaesth 76:362-364, 1996.

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Daniel D. Rubens and Jeremy M. Geiduschek Case Synopsis A 16-month-old boy, American Society of Anesthesiologists (ASA) class I, is having a bilateral inguinal herniorrhaphy with general anesthesia consisting of 2.5% sevoflurane with oxygen and nitrous oxide. He has a laryngeal mask airway in place. He is in the left lateral decubitus position with hips and knees flexed. A needle has been introduced into the caudal epidural space via the sacral hiatus. A 1.5-mL test dose of 0.25% bupivacaine with epinephrine 5 μg/mL is injected, with no change in the electrocardiogram (ECG) morphology, blood pressure, or heart rate. An additional 8.5 mL is administered over 1 to 2 minutes. ST segment changes are noted on the ECG waveform, followed by a rapid change in rhythm to coarse ventricular fibrillation, followed by asystole. The pulse oximetry and end-tidal carbon dioxide waveforms have disappeared. The patient has stopped breathing, and there is no palpable pulse.

PROBLEM ANALYSIS Definition Intraoperative cardiac arrest is defined by the need to begin cardiopulmonary resuscitation (CPR). This is generally an unplanned event, although it may be anticipated when dealing with critically ill patients. The need for CPR is apparent when palpable pulses and measurable blood pressure are absent or when there may be a palpable pulse but cardiac output is inadequate to provide acceptable organ perfusion (e.g., bradycardia with a heart rate of <30 beats per minute in an infant).

Recognition The first sign of patient deterioration under anesthesia is usually heralded by changes in the electronic monitoring signals. Unfortunately, electronic monitor alarms may activate falsely for any number of reasons. Nonetheless, when an alarm sounds, it is imperative to evaluate the patient before attributing the alarm to artifact. Loss of signal from the pulse oximeter, especially when associated with inaudible stethoscope heart sounds, is a harbinger of cardiac arrest. Similarly, until proved otherwise, loss of the end-tidal capnography waveform and the inability to measure blood pressure herald impending cardiac arrest.

All patients undergoing anesthesia are at risk for intraoperative cardiac arrest. In children, the most common arrhythmia seen before cardiac arrest is bradycardia. In 1954 Beecher and Todd reported higher anesthetic morbidity and mortality for children compared with adults. In 1961 Rackow and colleagues reported that this increase was due to a higher

615

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Risk Assessment

incidence of cardiac arrest in anesthetized children younger than 1 year old. Since then, other large series from Sweden and France have supported this finding. In 1990 Cohen and associates reported that the highest rate of anesthesia-related adverse events, including cardiac arrest, occurred in children younger than 1 month old. The majority of the aforementioned studies were published before the routine use of pulse oximetry and capnography, which makes comparison with current practices difficult. In 2000 the initial findings of the Pediatric Perioperative Cardiac Arrest Registry were presented after a review of 289 cases of cardiac arrest. Of these, 150 (52%) were judged to be related to the administration of anesthesia. Medication-related (37%) and cardiovascular (32%) causes were most common, together accounting for 69% of all cardiac arrests. In three cases, cardiac arrest was partly due to hyperkalemia following massive blood transfusion. Four cases occurred after caudal epidural local anesthetic injection. In all these patients, the local anesthetic test dose was negative, and all presented similarly to the patient described in the case synopsis. Anesthesia-related deaths occurred most often in infants younger than 1 year and in patients with severe underlying disease or having emergent surgery. Thirty-three percent of the patients were ASA status I or II. The most common identifiable cause for cardiac arrest without untoward respiratory events was hemorrhage or its therapy (8 patients). However, respiratory events accounted for 20% of all cardiac arrests. The most common respiratory cause was airway obstruction, due to either laryngospasm or anatomic obstruction. The most common technical problems were complications from the placement of central lines. Of the patients who suffered cardiac arrest, 26% died, 6% suffered permanent injury, and 68% had no residual injury. Congenital heart disease was present in 15 of the 75 patients who died, and all the patients who died had significant underlying systemic disease.

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Implications Cardiac arrest must be recognized and treated early, because delayed therapy can lead to severe morbidity or mortality. In a 2003 statement, the International Council of Resuscitation noted a need to change the way resuscitation instruction is given to trainees. It suggested that more time be dedicated to hands-on practice with lifelike manikins and training modules. Television and video-based instruction was also found to be extremely useful. Hands-on practice with frequent refresher sessions encourages skill retention and reduces the anxiety of trainees. Such models have been used by the commercial airline industry and in nuclear power plant safety programs for many years; only recently have they been adapted to medical emergencies.

MANAGEMENT Unanticipated cardiac arrest (such as that described in the case scenario) is best handled with formalized protocols for managing life-threatening events. Anesthesiologists should adhere to the current pediatric advanced life support (PALS) protocols: ● ●

●

●

●

● ●

●

● ● ●

Remain calm and focused. Maintain good communication with the surgical care team (surgeons, nurses, technologists). Explain in clear terms what you are witnessing on the monitors and by the patient’s vital signs. Ask if there has been any recent action that could explain the patient’s sudden hemodynamic deterioration. Call early for help. A system should be in place to call for and receive help rapidly. It is important to know how this system operates for each location. Examples are a “CODE” button on the wall or an internal emergency telephone system. Turn off anesthetic agents and deliver 100% oxygen via manual ventilation. Assess the patient for airway patency and breathing by listening for breath sounds with a stethoscope while the patient is manually ventilated. Place an endotracheal tube if one is not already in place. Assess the circulation. Brachial or femoral pulses are reliable sites in small children and infants, whereas the carotid is best in older children and adolescents. If the pulse is absent, begin chest compressions. It has been shown that consistent and adequate heart massage before and during defibrillation greatly improves the likelihood that spontaneous circulation will return. Determine the cardiac rhythm from the ECG. Treat arrhythmias according to the current PALS protocols. Designate someone to provide a written record of the events. Most anesthetic records are not designed to adequately document events and therapies during a cardiac arrest. Having a standardized recording form for intraoperative cardiac arrest (Fig. 151-1) is helpful, allowing the sequence and timing of events to be clearly noted and reviewed later.

Intraoperative cardiac arrest in children is rare (<3 per 10,000 anesthetics in all children, including ASA class IV and V patients). An organized response by all members of the anesthesia and surgery care team is needed to maximize the opportunity for a favorable outcome. To implement this

response, each participant’s part must be clearly defined and practiced. The following roles must be filled: (1) a team leader, or code coordinator (who directs the resuscitation effort but does not assume any specific task); (2) an airway manager (responsible for hand ventilation with 100% oxygen and endotracheal intubation, if necessary); (3) a person specifically designated to perform chest compressions; (4) someone to confirm patent intravenous (IV) access and to administer medications (according to PALS guidelines); and (5) a person delegated to obtain the code cart and defibrillator. The team leader or code coordinator also plays an important role in controlling the entry of outside responders into a code in progress, ensuring that all the designated code roles are filled. This system permits a clear understanding of each person’s role and direction at a time when panic, disorder, and lack of leadership can readily occur. Medications can be delivered via an endotracheal tube while IV access is established. For children younger than 7 years, if IV access is poor or unobtainable after 1 minute, placement of an interosseous needle is mandated (Fig. 151-2). This allows for the administration of emergency drugs and rapid fluid delivery, including blood. Early epinephrine administration can be lifesaving. Once the airway, breathing, and circulation have been assessed and appropriate therapy implemented, attention must be directed to determining the cause of cardiac arrest. Always consider tension pneumothorax in intubated patients. If this is suspected, perform left- and right-sided needle thoracentesis. A chest radiograph can be helpful and should be requested early during the resuscitation. Obtain blood for laboratory analysis as soon as possible, including arterial blood gases, electrolytes (sodium, potassium, chloride, bicarbonate, calcium), glucose, and hematocrit. The duration of CPR is handled on a case-by-case basis. Failure to reestablish perfusion should raise the following questions: ● ● ● ●

●

● ● ● ● ●

Have all anesthetic agents been discontinued? Is CPR being performed correctly? Are all team roles filled and being performed effectively? Does the patient have an underlying problem that could be contributory? Is the patient profoundly hypovolemic owing to fluid or blood loss? Has the patient had an anaphylactic reaction? Does the patient have a tension pneumothorax? Does the patient have cardiac tamponade? Is the patient hypothermic? Has there been a medication overdose or the wrong medication administered?

If perfusion is reestablished but lost again, consider the following iatrogenic causes: ●

●

●

Trauma related to closed-chest cardiac massage, including pneumothorax from rib fracture or splenic or hepatic rupture Pneumothorax or hemothorax from attempted central venous access or overinflation from mechanical ventilation Pericardial tamponade (if intracardiac medications were administered or a vascular cannula was placed into the right atrium)

Other

In situ

Site

Meds Dose Route

circle one

circle one

Include mg, μg, mEg/IV, ET, IO

Include μg/kg /min or mL / hr/ totals

Patientʼs response • Lab results • Procedures (Foley, taps, CXR) • Appearance/activity (color, mental status, neuro checks, pupils, seizures, etc.) • Urine output

Recorder RN___________________

Medication RN__________________

Charge MD____________________

Signatures:

Infusions

verified by____________________

NG tube inserted/placement

verified by____________________

Intubation and placement

Tube size____ Time___

Intubation: Oral____ Nasal___

Figure 151–1 ■ Example of a standardized institutional record for cardiac arrest (intraoperative or otherwise). Such a form can be used for most medical emergencies in which frequent interventions and the administration of medications occur.

Time

Vital Signs

Initial heart rhythm:

During code

CP R (Y es / He No) a rt Bl Card ra oo ia te d c p rh re yth ss m u r e/M AP Pu l s e s+ Sa /– t u V e nti ratio lat n ed Te mp rate e ra tur Ex De e t. f i o b rI /S nt. yn c p a cin h jou g les ( AB rate /M G Gl uc /Lab A) o s se /C sent h e Ep mstr S ip i n o e diu ph m rin b e A i c tro a rb pin on e at e / Co nc L . i d oc ain e Do p a m Ep ine ine_ _ p _ hr _ Lid ine_ mg/ _ _ o _ _ ca ine _mg ___m / _ _ L __ __ _m __ g /__ mL __ __ __ m _ g /__ mL __ _ __ _m g/_ _mL _ __ _m L

History of events prior to arrest:

Time placed

Ventilation: Bag/mask____ Time___

Airway:

Central line

Peripheral

IV access:

n Ri

S

Date_________________________________ Initial signs of arrest: Weight: Site of arrest__________________________ ❒ Apnea Est. time of arrest______________________ ❒ Bradycardia ❒ Cyanosis/Sats Pt. found by___________________________ ❒ Hypotension Observed arrest ❒ Yes ❒ No ❒ Absence of pulses Time CPR started______________________ ❒ Other_________________________

s/N ge r

d oo Bl

CODE 188 RECORD

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●

●

Debrief the code team. Make sure that team members have access to emotional support. Unanticipated intraoperative cardiac arrest with a poor outcome can be emotionally devastating to members of the code team, as well as to the patient’s family and friends. Notify the risk management office at the institution.

PREVENTION Femur

Tibia

Figure 151–2 ■ Schematic representation of an intraosseous needle inserted into the tibia to administer fluids and medications. In most children younger than 7 years, an 18-gauge styletted needle can be used. The insertion point is approximately 2.5 cm (1 inch) distal to the medial tibial tubercle on the flat portion of the tibial surface, with the needle oriented at right angles to the bony surface. A flange on the needle serves as a stop, which should prevent insertion beyond the bone marrow. During insertion, the hand not used to advance the needle into the bone should grasp the leg distal to the insertion site to minimize the potential for operator injury during insertion. Proper insertion allows easy administration of fluids and medications.

After resuscitation, it is extremely important to do the following: ●

● ●

●

●

●

●

Discuss the incident with the family, using language that they can understand. Explain what is known, but do not speculate on the cause if this is unclear. Inform the family what will occur next. Allow the family to ask questions. Allow the family to grieve alone or with designated support personnel. Sequester equipment and waste materials (especially opened medication vials) if an investigation is indicated. Do not reuse equipment (including the anesthesia machine) unless the cause of the intraoperative cardiac arrest has been determined. Enter a narrative of events in the progress notes section of the medical record. If the patient has died unexpectedly, in most instances the medical examiner should be notified.

Many pediatric intraoperative cardiac arrests are the result of the patients’ underlying conditions, and these may not be easily reversed. Others can result from any number of factors, including human error, errors in judgment or vigilance, equipment malfunction, and unexplained events. Vigilance throughout the intraoperative period and prompt investigation of any abnormalities in vital signs can lead to the early detection of problems and timely corrective intervention to reverse further patient deterioration before intraoperative cardiac arrest occurs.

Further Reading Beecher HK, Todd DP: A study of deaths associated with anesthesia and surgery. Ann Surg 140:1-35, 1954. Chamberlain DA, Hazinski MF, et al: Education in resuscitation. Resuscitation 59:11-43, 2003. Cohen MM, Cameron CB, Duncan PG, et al: Pediatric anesthesia morbidity and mortality in the perioperative period. Anesth Analg 70:160-167, 1990. Gaba DM, Fish KJ, Howard SK, et al: Crisis Management in Anesthesiology. New York, Churchill Livingstone, 1994. Hazinski MF (ed): Pediatric Advanced Life Support Provider Manual. Dallas, Tex., American Academy of Pediatrics–American Heart Association, 2002. Keenan RL, Shapiro JH, Kane FR, et al: Bradycardia during anesthesia in infants. Anesthesiology 80:976-982, 1994. Morray JP, Geiduschek JM, Caplan RA, et al: A comparison of pediatric and adult anesthesia closed malpractice claims. Anesthesiology 78:461-467, 1993. Morray JP, Geiduschek JM, Ramamoorthy C, et al: Anesthesia-related cardiac arrest in children: Initial findings of the Pediatric Perioperative Cardiac Arrest (POCA) Registry. Anesthesiology 93:6-14, 2000. Ollson GL, Hallen B: Cardiac arrest during anesthesia: A computerized study in 250,543 anesthetics. Acta Anaesthesiol Scand 32:653-664, 1988. Rackow H, Salatire E, Green LT: Frequency of cardiac arrest associated with anesthesia in infants and children. Pediatrics 28:697-704, 1961. Steen S, Liao Q, Pierre L, et al: The critical importance of minimal delay between chest compressions and subsequent defibrillation: A haemodynamic explanation. Resuscitation 3:249-258, 2003. Tiret L, Nivochey Y, Hatton F, et al: Complications related to anesthesia in infants and children. Br J Anaesth 61:263-269, 1988. Weick KE, Sutcliffe KM: Managing the Unexpected: Assuring High Performance in an Age of Complexity. San Francisco, Jossey-Bass, 2001.

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Sedation of Pediatric Patients Charles J. Coté Case Synopsis A 3-year-old child with enlarged tonsils and a history of sleep apnea is scheduled to undergo magnetic resonance imaging (MRI). At the direction of the radiologist, the technician administers 75 mg/kg of chloral hydrate for sedation. After falling asleep, the child is placed in the scanner. Ten minutes into the MRI scan, the child develops desaturation and is without respirations.

PROBLEM ANALYSIS Definition The entire process of sedating patients has changed in recent years. Work by the American Academy of Pediatrics (AAP), the American Society of Anesthesiologists (ASA), and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has resulted in unified definitions. For example, minimal sedation is equivalent to the older term anxiolysis, moderate sedation has replaced the oxymoron conscious sedation, and deep sedation is the same as previously defined. Expected patient responses to these new definitions of sedation are presented in Table 152-1. Because sedation is a continuum and patient responses to sedating medications are unpredictable, emphasis has been placed on practitioners’ ability to rescue patients if necessary. Thus, practitioners who administer drugs to achieve minimal sedation must have the skills to rescue a patient who becomes moderately sedated. Similarly, those who administer drugs for moderate sedation must have the skills required to rescue patients from deep sedation. Finally, practitioners who intend to achieve deep sedation must have the skills to rescue patients from a state of general anesthesia. Because most sedation-related adverse events in children are related to compromise or loss of respiratory effort,

Table 152–1

■

the most important skill is advanced airway management. Moderate sedation consists of alteration of consciousness to the point that patients are compliant, comfortable, and (theoretically) psychologically calm, but they retain intact reflexes (including reflex withdrawal from a painful stimulus) and the ability to respond appropriately to verbal or nonverbal stimuli. For practical purposes, most children require pharmacologic restraint consistent with deep sedation to gain their cooperation. Therefore, it is good practice to use the guidelines for deep sedation from the outset of the sedation process. The concept of deep sedation involves alterations of consciousness that are associated with partial or complete loss of protective reflexes and more profound changes in central nervous system and cardiopulmonary physiology. The JCAHO has recognized anesthesiologists as experts in sedation, analgesia, and anesthesia. That organization also agrees that deep sedation is virtually equivalent to a state of general anesthesia as far as safety is concerned. The JCAHO has mandated that departments of anesthesia lead the way in developing institutional policies regarding the sedation of all patients, whether adult or pediatric. The JCAHO is extensively involved in reviewing and ensuring the implementation of such sedation policies. The intention is to provide a uniform standard of care within each institution.

Expected Patient Responses with Minimal, Moderate, or Deep Sedation Moderate Sedation†

Deep Sedation‡

Responsiveness

Normal to verbal stimulation

Airway Spontaneous ventilation Cardiovascular function

Unaffected Unaffected Unaffected

Purposeful to verbal or light tactile stimulation No intervention required Adequate Usually maintained

Purposeful following repeated or painful stimulation May require intervention May be inadequate Usually maintained

*Drug-induced state equivalent to anxiolysis. † Drug-induced depression of consciousness equivalent to conscious sedation. ‡ Drug-induced depression of consciousness during which patients cannot be easily aroused. Modified from the American Society of Anesthesiologists, available at http://www.asahq.org/publicationsAndServices/standards/20.htm.

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Minimal Sedation*

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Recognition Recognition of complications related to sedation requires proper monitoring during the procedure by an independent observer whose only responsibility is to observe the patient. With the use of moderate sedation (rare in children), this individual could also assist with the procedure (Table 152-2). In patients undergoing MRI, who are generally out of reach and not easily visualized, expired carbon dioxide monitoring is useful for the early detection of airway obstruction, hypoventilation, or apnea. After a procedure requiring sedation, patients should be monitored in a fully equipped and staffed recovery area with strict and uniform discharge criteria identical to those used for patients recovering from general anesthesia.

Risk Assessment In reviewing sedation-related accidents reported to the Food and Drug Administration, it is clear that most cases involve one or more of the following factors: ●

●

●

●

The same person performing the procedure and sedating the child Residual drug effects combined with inadequate monitoring during recovery Lack of appreciation for drug-drug interactions and drug dosing errors Having parents administer a sedating medication at home and then having no one observe the child for signs of airway obstruction

The case synopsis raises a number of issues that are important when making decisions regarding the safety of sedation. In that case, the presedation assessment should have raised several red flags. First, it is known that children with tonsillar hypertrophy are at increased risk for developing further upper airway obstruction when sedation results in collapse of pharyngeal airway structures. Second, the child

Table 152–2

Monitoring

Charting

Personnel Equipment

■

already had a history of obstructive sleep apnea, so it is not surprising that sedating medications would exacerbate that problem. Apparently, neither of these issues was considered before sedation. This child would have benefited from expired carbon dioxide monitoring, because a loss of air exchange would have preceded the onset of desaturation and allowed more timely initiation of rescue interventions. Despite the lack of carbon dioxide monitoring, an independent observer was able to make the diagnosis of obstructive sleep apnea with the onset of desaturation, and appropriate interventions were initiated. It is also possible that the child received either an overdose (dispensing error) or a dose based on body weight rather than lean body mass (prescribing error). In the pediatric population, obesity is a major factor contributing to airway obstruction and obstructive sleep apnea. A study of sedation-related accidents conducted by the author found that approximately two thirds of children were younger than 6 years of age, and half received more than one sedating medication. There was equal representation of all classes of drugs (opioids, benzodiazepines, barbiturates, sedatives) associated with death or neurologic injury (N = 60). Chloral hydrate was associated with 13 neurologic injuries or death; in 8 cases, it was the only sedating medication. Thus, even chloral hydrate, a drug commonly thought to be extremely safe, can result in sufficient airway compromise to cause injury. This study also found that adverse outcomes were associated with all routes of drug administration (oral, rectal, nasal, intramuscular, intravenous, inhalation). Further, nearly every pediatric subspecialty service had an adverse event or outcome; 12 patients suffered an adverse event or outcome either on the way to the medical facility (2 patients) or after discharge from medical supervision (10 patients). All patients who suffered an adverse event after discharge had received long-acting medications, such as intramuscular DPT (Demerol, Phenergan, and Thorazine), oral or rectal chloral hydrate (half-life of approximately 10 hours in toddlers), or intramuscular pentobarbital.

Guidelines for Recognition of Complications Related to Sedation

Moderate Sedation

Deep Sedation

Pulse oximetry—continuous Heart rate—continuous Respiratory rate every 15 min Level of consciousness every 15 min Blood pressure every 15 min Pulse oximetry every 15 min Heart rate every 15 min Respiratory rate every 15 min Level of consciousness every 15 min‡ Blood pressure every 15 min Same individual may observe patient and assist with procedure Pulse oximeter Blood pressure measuring device

Pulse oximetry—continuous* Heart rate—continuous Respiratory rate every 5 min Level of consciousness every 5 min Blood pressure every 5 min† Pulse oximetry every 15 min Heart rate every 5 min Respiratory rate every 5 min Level of consciousness every 5 min Blood pressure every 5 min Dedicated patient observer may not assist with procedure Pulse oximeter Blood pressure measuring device Electrocardiograph and defibrillator immediately available

*Note whether and how oxygen is administered. † Blood pressure may be taken less frequently if other vital signs are stable and taking blood pressure would interfere with the procedure. ‡ Assessment of the level of consciousness may not be practical during some procedures, such as magnetic resonance imaging or computed tomography, if awakening the patient would prevent a successful scan.

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A study by Malviya and colleagues examined recovery in toddlers following chloral hydrate sedation for echocardiograms. They found that using discharge criteria based on the patient’s ability to remain awake for 20 consecutive minutes in a soporific environment and on the University of Michigan Sedation Scale resulted in a mean discharge time 75 minutes later than when using standard discharge criteria. This observation suggests that prolonged observation (perhaps in a step-down unit) may improve safety when long-acting medications are used for pediatric sedation. In summary, these and other studies clearly support the concept of uniform institutional sedation guidelines and the need for a systematic approach to children requiring sedation, with the goal of significantly reducing anesthetic-related morbidity and mortality.

Implications

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Sedation of Pediatric Patients

MANAGEMENT A systematic approach means organizing things in such a way that a number of checks and balances are in place so that vital pieces of information are not lost. For the sedation of pediatric patients, such an approach involves a number of important components: ● ●

●

●

●

●

All patients must be treated with the same degree of care. Presedation given at home before traveling to the site where the procedure will be performed is strictly prohibited. Children must be under medical supervision before being given any drugs. Adequate review of the patient’s history, physical examination (including a focused airway examination), current medications, allergies, and past medical and surgical records is essential. Uniform and rigorous screening procedures should be adopted and used by anesthesiologists and other specialists in airway management (e.g., emergency medicine physicians, pediatric intensivists) so that patients of high ASA status and those with unusual airway anatomy or cardiac or pulmonary problems receive the proper care. Compliance with preprocedure fasting guidelines for milk, formula, breast milk, and other solids and adequate hydration with clear fluids are essential (Table 152-3). Before sedation, ensure the availability of age- and sizeappropriate and functioning equipment to manage the airway; medications to effectively manage emergencies, including reversal agents for opioids and benzodiazepines; and adequate means of delivering positive-pressure ventilation with sufficient oxygen reserves for at least 1 hour.

PREVENTION It is essential to maintain a uniform level of safe care. In some institutions, the appointment of a “sedation team” is an effective method. It is of little importance who directs this team, but logic dictates that an anesthesiologist be intimately involved. If the sedation team is provided with appropriate resources and with a central procedure unit, the same sedation process can be used for patients undergoing a wide variety of procedures. Experienced sedation personnel need to be available for one to three shifts, depending on institutional needs. These persons, by virtue of their training and experience, work together to develop techniques unique to each institution to facilitate safe sedation and patient, parent, and

Table 152–3

■

Fasting Guidelines for Children Fasting Time (hr)

Age (mo)

Solids

<6 6-36 >36

4 (breast milk) 6 (formula or solids) 8 (solids)

*Apple juice, Pedialyte.

Clear Liquids* 2 3 3

PEDIATRICS & NEONATOLOGY

It is generally impossible to gain the cooperation of infants and young children for invasive or diagnostic procedures, necessitating pharmacologic control. Use of barbiturates, chloral hydrate, butyrophenones, opioids, and phenothiazines has been popular for decades, despite a paucity of information regarding pediatric safety and efficacy. The use of DPT, or the “lytic cocktail,” for cardiac catheterization and other invasive or painful procedures has traditionally enjoyed widespread acceptance. This use continues today, despite the availability of drug combinations with more favorable pharmacokinetics and pharmacodynamics. In recent years, the increasing use of ketamine and propofol by nonanesthesiologists has raised concerns regarding the skills of the individuals administering these medications. For many years, anesthesiologists have attempted to restrict the use of ketamine by nonanesthesiologists, but this appears to be changing. Ketamine is relatively safe in the hands of less skilled practitioners, because respiration is usually not depressed and airway patency is maintained (1% to 2% incidence of apnea or laryngospasm). Propofol is more commonly associated with airway obstruction, apnea, and unintended general anesthesia, making it a more problematic agent for use by nonanesthesiologists. The widespread use of sedation by nonanesthesiologists for the care of pediatric patients is not without complications. Safely sedating pediatric patients for radiology, gastroenterology, oncology, emergency room, dental, and cardiology procedures is a major issue. Because there are insufficient numbers of anesthesiologists to provide all this care, the majority of children requiring procedural sedation are sedated by nonanesthesiologists. It is up to our specialty to educate and train these individuals. The AAP has developed guidelines for the sedation of pediatric patients both inside and outside the hospital environment. The guidelines were revised in 1992, and since then they have been augmented by two ASA practice guidelines and an addendum to the AAP guidelines published in 2002. The AAP guidelines are currently undergoing further revisions that will likely expand on the indications for capnography in sedated children, further amplify the rescue skills needed by practitioners who sedate children, and suggest sedation teams and the use of patient simulators to maintain their skills.

■

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physician satisfaction. In some institutions, the pharmacy and therapeutics committee may be responsible for monitoring quality improvement activities with regard to overall institutional sedation practices. In other institutions, the ongoing monitoring of quality improvement activities may be a divisional, departmental, or hospital committee activity. It is incumbent on people dealing with infants and children to provide a safe environment for procedures requiring the use of sedation. The solution to the problem of sedating infants and children lies in broad-based education. Although anesthesiologists are uniquely qualified to provide such care, by virtue of their limited numbers their ability to do so is restricted. Thus, it falls on anesthesiologists and other appropriately trained people to provide information, training, support, and continuing surveillance for others who provide sedation services to infants and children.

Further Reading American Academy of Pediatric Dentistry: Guidelines for the elective use of conscious sedation, deep sedation, and general anesthesia in pediatric patients. ASDC J Dent Child 53:21-22, 1986. Committee on Drugs, American Academy of Pediatrics: Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures. Pediatrics 89:1110-1115, 1992.

Coté CJ: Sedation for the pediatric patient: A review. Pediatr Clin North Am 41:31-58, 1994. Coté CJ: Discharge criteria for children sedated by nonanesthesiologists: Is “safe” really safe enough? Anesthesiology 100:207-209, 2004. Coté CJ, Karl HW, Notterman DA, et al: Adverse sedation events in pediatrics: Analysis of medications used for sedation. Pediatrics 106:633-644, 2000. Coté CJ, Notterman DA, Karl HW, et al: Adverse sedation events in pediatrics: A critical incident analysis of contributory factors. Pediatrics 105:805-814, 2000. Dial S, Silver P, Bock K, et al: Pediatric sedation for procedures titrated to a desired degree of immobility results in unpredictable depth of sedation. Pediatr Emerg Care 17:414-420, 2001. Gross JB, Bailey PL, Caplan RA, et al: Practice guidelines for sedation and analgesia by non-anesthesiologists: A report by the American Society of Anesthesiologists Task Force on Sedation and Analgesia by Nonanesthesiologists. Anesthesiology 84:459-471, 1996. Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures: Addendum. Pediatrics 110:836-838, 2002. Litman RS, Kottra JA, Berkowitz RJ, et al: Upper airway obstruction during midazolam/nitrous oxide sedation in children with enlarged tonsils. Pediatr Dent 20:318-320, 1998. Malviya S, Voepel-Lewis T, Ludomirsky A, et al: Can we improve the assessment of discharge readiness? A comparative study of observational and objective measures of depth of sedation in children. Anesthesiology 100:218-224, 2004. Malviya S, Voepel-Lewis T, Prochaska G, et al: Prolonged recovery and delayed side effects of sedation for diagnostic imaging studies in children. Pediatrics 105:E42, 2000. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology 96:1004-1017, 2002.

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Muscle Relaxants Constance L. Monitto Case Synopsis A 2-year-old boy presents for inguinal herniorrhaphy. During mask induction with oxygen, nitrous oxide, and sevoflurane he develops laryngospasm, which is treated with intramuscular succinylcholine. A wide QRS tachycardia is subsequently noted on the electrocardiogram monitor.

PROBLEM ANALYSIS Definition There can be complications with all neuromuscular relaxant drugs; however, the potential for serious complications is greater with succinylcholine (SCh). Although these complications have limited its routine use, SCh retains a role in pediatric anesthesia because of the unparalleled speed with which it acts and its ability to be administered intramuscularly when intravenous access has not been achieved. Significant complications associated with SCh use in children include the following: ● ● ● ● ●

Cardiac arrhythmias Rhabdomyolysis Unanticipated prolonged duration of action Masseter spasm Malignant hyperthermia (see Chapter 162)

Complications with nondepolarizing muscle relaxants (NDMRs) include profound muscle weakness and impaired respiration with residual neuromuscular blockade (see Chapter 24). Prolonged myopathy after extended infusion of aminosteroid relaxants in the intensive care unit has been reported. Anaphylactic reactions can also occur. However, the most common side effects of NDMRs result from their histaminergic, cholinergic, and muscarinic effects. None of these reactions are unique to pediatric patients.

Rhabdomyolysis can be detected in a significant proportion of children following SCh administration. Although some patients may have detectable myoglobinuria, in the vast majority, rhabdomyolysis is a benign sequela of SCh. In some high-risk populations, however—most notably, patients with unrecognized congenital muscle disease or malignant hyperthermia sensitivity—SCh-induced rhabdomyolysis can be life threatening due to associated electrolyte disturbances, renal failure, or disseminated intravascular coagulation. Prolonged neuromuscular blockade lasting several hours can occur after giving SCh to patients with homozygous genetic abnormalities in plasma cholinesterase (pseudocholinesterase) (see Chapter 23). Because mivacurium is also metabolized by pseudocholinesterase, its use may produce this response as well. Although several medical conditions (e.g., hepatic failure) may result in striking reductions in the circulating concentrations of normal cholinesterases, reduced concentrations of normal enzyme have a far less dramatic impact than the presence of a genetically defective enzyme. Linking SCh-induced masseter spasm and malignant hyperthermia remains a matter of controversy. Careful investigations have shown that masseter muscle tone is commonly increased after SCh administration. Whether exaggerated masseter tone (i.e., masseter spasm) that prevents the mouth from being opened is a harbinger of malignant hyperthermia continues to be debated. Recognition and management of malignant hyperthermia are discussed in Chapter 162. NONDEPOLARIZING MUSCLE RELAXANTS

Recognition DEPOLARIZING MUSCLE RELAXANTS

●

●

Block of muscarinic receptors at the sinoatrial node (gallamine, pancuronium) Vagolytic action at the preganglionic or postganglionic nerve terminal (gallamine) 623

PEDIATRICS & NEONATOLOGY

Decamethonium, another depolarizing muscle relaxant (longer acting), is no longer available or used in the United States, so this discussion is limited to SCh. Arrhythmias frequently accompany the administration of SCh, with sinus bradycardia or junctional rhythm being most common. These arrhythmias may cause significant hypotension in infants and children whose cardiac output is largely heart-rate dependent or, in the case of junctional rhythm, dependent on properly timed atrial contractions to augment ventricular filling (e.g., hypertrophic, dilated, or restrictive cardiomyopathy or arrhythmogenic right ventricular dysplasia; see Chapter 166). Further, asystole has been reported in patients of all ages following SCh. Lifethreatening ventricular arrhythmias heralding severe rhabdomyolysis or malignant hyperthermia occur less frequently.

Although anaphylactic reactions are more commonly seen after SCh administration, they have been reported after both aminosteroid (especially rocuronium) and benzylisoquinoline NDMR (atracurium and cisatracurium) administration. Anaphylactic reactions to NDMRs may be difficult to diagnose, but clinical signs include flushing, hypotension, tachycardia, and bronchospasm following administration of the agent. Histamine release with benzylisoquinoline relaxants is recognized by skin flushing, hypotension, and tachycardia. The mechanisms for increased heart rate and blood pressure with gallamine and pancuronium are unclear but could involve some or all of the following:

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Catecholamine release (gallamine, possibly with extremely high concentrations)

Life-threatening episodes of bronchospasm (i.e., profound difficulty in ventilation with absent end-tidal carbon dioxide) and some deaths secondary to irreversible bronchospasm were reported after the introduction of rapacuronium bromide in 1999. Subsequent laboratory studies suggested that clinically relevant concentrations of rapacuronium may provoke bronchospasm due to muscarinic effects. Rapacuronium was subsequently withdrawn from the market.

Risk Assessment SUCCINYLCHOLINE Vagally mediated arrhythmias, including sinus or atrioventricular junctional bradycardia, sinus pause, and transient asystolic arrest, may occur in as many as 40% to 60% of children after a single intravenous dose of SCh. As in adults, repeated doses may elicit more frequent and more severe bradyarrhythmias. Malignant ventricular arrhythmias and even cardiac arrest after SCh may occur with exaggerated potassium release in patients with acute or progressive denervation injury (e.g., spinal cord transection, peripheral neuropathy, stroke), extensive tissue damage (e.g., burns, crush injury), prolonged immobilization, or neuromuscular disease. Historically, rhabdomyolysis after SCh was detected by serum myoglobin elevation in 40% of children anesthetized with halothane, and as many as 8% had associated myoglobinuria. Case reports also describe its occurrence in patients receiving enflurane, isoflurane, or sevoflurane. Although far more common in pediatric patients than in adults, rhabdomyolysis appears to be a benign process in the overwhelming majority of children. Nevertheless, a small population with myopathic processes (e.g., Duchenne’s muscular dystrophy) can exhibit life-threatening hyperkalemia,

Table 153–1

■

arrhythmias, acute renal injury, and disseminated intravascular coagulation. Because the underlying myopathy may be undiagnosed in young children (more commonly boys), cardiac arrest in apparently healthy children has been reported after SCh administration. Approximately 1 in 3000 patients presents with (frequently) occult genetic variants of pseudocholinesterase of the type that can result in markedly prolonged neuromuscular blockade following the administration of SCh or mivacurium. The diagnosis of masseter muscle spasm remains controversial. Some cite a 1% incidence rate, while others say that it never occurs. Because an increase in masseter tone often accompanies SCh administration, the determination of what constitutes clinically significant masseter spasm (i.e., a harbinger of malignant hyperthermia) is subjective. Of real concern, though, is the finding that in a select population of patients referred to the North American Malignant Hyperthermia Group, 50% of children with masseter spasm who were screened for malignant hyperthermia sensitivity by muscle biopsy tested positive. Of these patients, approximately 10% developed clinical signs of malignant hyperthermia perioperatively. Therefore, severe masseter spasm (i.e., an increase in masseter muscle tone sufficient to impede mouth opening) must be viewed with concern. NONDEPOLARIZING MUSCLE RELAXANTS Anaphylaxis is reported to occur in 1 in 10,000 to 20,000 anesthesias, and 50% to 70% of these episodes are related to neuromuscular blocking agents. A prior history of drug exposure is not necessary. Patients with an allergic history or a history of anaphylaxis may be more susceptible to histamine release from NDMRs that are associated with histamine release (Table 153-1). The initial data on rapacuronium suggested a 4% incidence of bronchospasm (versus <1% with other NDMRs).

Intubating Dose, Primary Clearance, and Side Effects of Muscle Relaxants in Children

Muscle Relaxant Intubating Dose (IV mg/kg)

Primary Method of Clearance

Cholinergic Effects

Histamine Release

Succinylcholine

Plasma cholinesterase

Stimulates

Rare

Plasma cholinesterase Ester hydrolysis; Hofmann degradation Ester hydrolysis; Hofmann degradation Hepatic

No No No No

+ (doses >3 × ED95) ++ (doses >3 × ED95) Minimal None

Hepatic

No effect

None

Renal Renal Renal Renal Renal Renal

No effect Blocks ++* No effect Blocks +++* No effect No effect

+++ None ++ None None None

Mivacurium Atracurium Cisatracurium Vecuronium Rocuronium

d-Tubocurarine Pancuronium Metocurine Gallamine Pipecuronium Doxacurium

2-3 (infants) 2 (children) 4 (IM) 0.2-0.4 0.3-0.5 0.15-0.2 0.1 0.4 (rapid sequence) 0.6 1.0 (rapid sequence) 1.0 IM (infants); 1.6 IM (children) 0.3-0.6 0.1 0.3-0.6 3.5 0.1 0.05

*Also causes sympathetic stimulation.

effect effect effect effect

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However, higher than expected rates of serious airwayrelated complications were reported after it was introduced into general clinical use. Associated risk factors for the development of bronchospasm in children following rapacuronium were rapid-sequence induction of general anesthesia and a prior history of reactive airway disease. However, neither of these factors alone was necessary or sufficient to cause bronchospasm.

Implications

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625

function returns. Absolute pseudocholinesterase activity and the dibucaine and fluoride numbers should then be determined. Masseter spasm usually requires no specific treatment because the spasm recedes within a few minutes. Reports suggest that it is safe to proceed with anesthesia and surgery. However, one must be alert for progression to malignant hyperthermia and be prepared to treat it. Known triggering agents should be discontinued, and the procedure should be aborted if signs of malignant hyperthermia develop. Further testing may be required.

SUCCINYLCHOLINE Bradyarrhythmias usually are benign and self-limited or respond to vagolytic therapy. However, if they are protracted and associated with hemodynamic compromise, temporary pacing may be required. In contrast, malignant ventricular arrhythmias and cardiac arrest seen with exaggerated potassium release after SCh have projected mortality rates as high as 60%. Rhabdomyolysis rarely has lasting consequences except in myopathic patients, in whom the consequences can be dire. Children with atypical pseudocholinesterase eventually recover neuromuscular function without sequelae. Consequently, the implications have more to do with genetic counseling and awareness of the condition. Masseter spasm usually has few immediate implications, because the spasm is localized to the masseter. If, however, the patient is at risk for malignant hyperthermia, the implications for future management of both the child and the family are substantial. NONDEPOLARIZING MUSCLE RELAXANTS Intraoperative anaphylaxis from NDMRs is a serious concern, with a mortality rate of approximately 3% to 6%. Owing to the potential for tachycardia, pancuronium (and gallamine, if still available) is best avoided in patients in whom tachycardia might be detrimental (e.g., severe mitral, tricuspid, or aortic stenosis; coronary strictures or anomalous left coronary artery; accelerated, juvenile coronary artery disease). Finally, NDMRs that release histamine are best avoided in patients with asthma, a significant right-to-left shunt, or valvular stenosis.

MANAGEMENT Succinylcholine

Routine management of anaphylaxis includes removal of the antigen source when possible, inhibition of mediator production and release (e.g., steroid administration), and interventions to modulate the effects of the mediators. These may include histaminergic blockade, treatment of bronchoconstriction with β2-agonists, and the administration of intravenous fluids and epinephrine to decrease bronchial hyperresponsiveness and support the circulation. Postoperative confirmatory laboratory data include elevated serum tryptase, histamine, and (drug-specific) immunoglobulin E levels at the time of the reaction and 6 weeks later. Hypotension due to histamine release is treated with intravenous fluids and vasopressors. In addition, use of a stereoselective NDMR (e.g., cisatracurium rather than atracurium) may result in a diminution of clinically significant histamine release. Treatment of symptomatic tachycardia not associated with hypotension may include a deepening of anesthesia, opioids, and a β-blocker.

PREVENTION Succinylcholine In light of reports of profound SCh-induced rhabdomyolysis, cardiac arrest, and death in apparently healthy children ultimately diagnosed with myopathic disease, drug manufacturers sought to ban routine SCh use in children in 1993. In response to protests from anesthesiologists who were aware of the drug’s benefits, the Food and Drug Administration held an open committee meeting from which compromise labeling for SCh emerged (Fig. 153-1). However, the fact that life-threatening hyperkalemia can be prevented only by avoiding SCh in high-risk patients—some of whom carry a diagnosis of myopathy, and some of whom do not—has discouraged the routine use of SCh in children. Given the uncertain association of masseter spasm with malignant hyperthermia, prudence dictates the avoidance of triggering anesthetic agents in untested patients with documented masseter spasm following SCh.

Nondepolarizing Muscle Relaxants Because rapacuronium was a low-potency NDMR with a rapid onset and short duration of action, it was initially hoped that it might provide a safer alternative to SCh for rapidsequence inductions and short procedures. However, after a

PEDIATRICS & NEONATOLOGY

Persistent or hemodynamically disadvantageous bradyarrhythmias are treated with atropine or pacing, particularly in infants. Arrhythmias with hyperkalemia are treated with alkalization, calcium, and glucose-insulin. Successful resuscitation may be prolonged, and extracorporeal circulation may be needed for extreme cases, at least until potassium is eliminated by excretion or dialysis. Rhabdomyolysis that goes undetected requires no specific therapy in most patients. For those with myopathy, full cardiac resuscitation and measures to promote myoglobin excretion (e.g., furosemide, mannitol) may be required. Children with clinically suspected pseudocholinesterase deficiency require ventilatory support until neuromuscular

Nondepolarizing Muscle Relaxants

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Figure 153–1 ■ Manufacturer’s warning concerning the association between succinylcholine and hyperkalemic cardiac arrest. (Adapted from Physicians’ Desk Reference. Montvale, NJ, Medical Economics, 1997, p 1062.)

number of deaths resulting from profound drug-related bronchospasm, the drug was removed from the U.S. market by its manufacturer in 2001. Atracurium and mivacurium undergo significant ester hydrolysis. Thus, prolonged neuromuscular blockade is possible with either of these NDMRs in patients with atypical pseudocholinesterase or cholinesterase deficiency.

Further Reading Bevan DR: Newer neuromuscular blocking agents. Pharmacol Toxicol 74: 3-9, 1994. Brandom BW, Fine GF: Neuromuscular blocking drugs in pediatric anesthesia. Anesth Clin North Am 20:45-58, 2002. Cook DR, Davis PJ: Pharmacology of pediatric anesthesia. In Motoyama EK, Davis PJ (eds): Smith’s Anesthesia for Infants and Children. St. Louis, Mosby, 1990, pp 157-200. Goudsouzian NG: Muscle relaxants in children. In Coté CJ, Ryan JF, Todres ID, et al (eds): A Practice of Anesthesia for Infants and Children. Philadelphia, WB Saunders, 1993, pp 151-170.

Gronert BJ, Brandom BW: Neuromuscular blocking drugs in infants and children. Pediatr Clin North Am 41:73-91, 1994. Jooste E, Klafter F, Hirshman CA, et al: A mechanism of rapacuronium-induced bronchospasm: M2 muscarinic receptor antagonism. Anesthesiology 98:906-911, 2003. Larach MG, Rosenberg H, Gronert GA, et al: Hyperkalemic cardiac arrest during anesthesia in infants and children with occult myopathies. Clin Pediatr (Phila) 36:9-16, 1997. Lebowitz PW, Ramsey FM: Muscle relaxants. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia. Philadelphia, JB Lippincott, 1989, pp 339-370. Martin LD, Bratton SL, O’Rourke PP: Clinical uses and controversies of neuromuscular blocking agents in infants and children. Crit Care Med 27:1358-1368, 1999. Physicians’ Desk Reference. Montvale, NJ, Medical Economics, 1997, pp 1062-1063, 1136-1139. Rajchert DM, Pasquariello CA, Watcha MF, et al: Rapacuronium and the risk of bronchospasm in pediatric patients. Anesth Analg 94:488-493, 2002. Sparr HJ, Beaufort TM, Fuchs-Buder T: Newer neuromuscular blocking agents: How do they compare with established agents? Drugs 61: 919-942, 2001.

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Delayed Emergence in Pediatric Patients Hector F. Nicodemus and John B. Rose Case Synopsis A 2-year-old, 12-kg girl with achondroplasia remains unresponsive and intubated in the pediatric postanesthesia care unit 45 minutes after undergoing cervical spine fusion and suboccipital craniectomy for atlanto-occipital instability and foramen magnum stenosis.

PROBLEM ANALYSIS Definition When agents used for general anesthesia are discontinued, the patient is expected to regain consciousness within a certain period, although the time it takes for this to occur is variable and depends on a number of factors. Delayed emergence is defined as the failure to recover consciousness after general anesthesia within a reasonable period. The determination of “reasonable” depends on the agents and techniques used, as well as the patient’s preoperative physical and mental status (see also Chapter 222).

Recognition EVALUATION

OF

PATIENTS

DRUG EFFECTS Prolonged anesthetic action is a likely cause if delayed emergence follows an otherwise uneventful operative procedure. Although inadvertent overdose of one drug may be responsible for delayed emergence, it is more often attributed to combined drug effects. Individually, drugs may be given in appropriate doses; however, relative overdose may occur owing to the potentiation of their hypnotic effects.

PHYSIOLOGIC IMBALANCE

OR

DISORDERS

OF

METABOLISM

The existence of various preoperative states (e.g., prolonged fasting, dehydration, malnutrition, renal or hepatic failure, diuretic or antacid therapy, severe anemia, sickle cell disease, diabetes, seizure disorder) or the occurrence of adverse intraoperative events (e.g., hypoventilation, hypotension, hypoperfusion, large blood loss with massive blood and fluid resuscitation) raises the possibility that physiologic imbalance or a metabolic disturbance is responsible for delayed emergence. The routine use of pulse oximetry and capnography has greatly enhanced the ability of anesthesiologists to detect and treat life-threatening conditions associated with hypoxemia and hypercarbia. Metabolic acidosis should be considered in 627

PEDIATRICS & NEONATOLOGY

The evaluation of patients with delayed emergence is summarized in Figure 154-1. Drug effects, physiologic imbalance, disorders of metabolism, central nervous system (CNS) injury, or undiagnosed preexisting CNS disease may cause delayed emergence from general anesthesia (Table 154-1). For the patient described in the case synopsis, first the airway was assessed. Then, adequate ventilation and oxygenation were assured by review of the patient’s vital signs, temperature, end-tidal carbon dioxide, and pulse oximetry readings. Adequate recovery of neuromuscular function was determined with a nerve stimulator. Subsequent review of the preoperative record revealed an excessive fasting time (>15 hours). Also, intraoperatively, non-glucose-containing intravenous (IV) solutions were used. Thus, hypoglycemia was suspected and confirmed by determination of the blood glucose concentration (42 mg/dL). Corrective therapy was instituted immediately, and the patient regained consciousness.

For example, oral midazolam (0.5 mg/kg) might be given for preoperative sedation. Then, toward the end of anesthesia, IV morphine is given for analgesia (0.15 mg/kg) and IV droperidol (0.075 mg/kg) is given to prevent postoperative nausea and vomiting. Reduced drug metabolism and elimination may contribute to delayed emergence, especially in premature and fullterm newborns. Respiratory depression and hypoventilation secondary to narcotics and sedatives can delay the elimination of inhalational agents and prolong emergence in spontaneously breathing infants or children. One recent investigation of the effects of oral midazolam premedication in 50 patients aged 10 to 18 years, American Society of Anesthesiologists status I and II, concluded that midazolam did not prolong emergence from general anesthesia. Further, it did not affect the expired concentrations of sevoflurane or nitrous oxide at emergence or the time required for discharge from the postanesthesia care unit. However, the investigators found that clinically detectable sedation before anesthetic induction, manifest in half of midazolam-treated patients, strongly correlated with delayed emergence. In infants and children, biologic variability in their response to the hypnotic effects of anesthetic drugs can be marked. If so, increased sensitivity to these effects may contribute to prolonged emergence in some children. However, this must be a diagnosis of exclusion in healthy children with no prior history of cognitive impairment or developmental delay.

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Unconscious patient after general anesthesia

Ensure adequate airway, ventilation, and oxygenation

Assess neuromuscular function: 1. Residual neuromuscular blockade (NMB) 2. Pseudocholinesterase deficiency

Paralysis?

No obvious impairment of neuromuscular function

1. Provide sedation and analgesia 2. Antagonize reversible NMB 3. Maintain airway and respirations

Rule out drug effects (see Table 154–1)

Volatile agent

Narcosis

Ventilation

Naloxone

Benzodiazepine excess

CNS depression due to: 1. Scopolamine 2. Ketamine 3. Phenothiazines 4. Tricyclic antidepressants

Flumazenil

Regains consciousness

1. Reassure family 2. Close observation 3. Consider need for a. Additional antagonist b. Ongoing correction of metabolic disturbance

Drug effect unlikely

Physostigmine

Failure to regain consciousness

Rule out metabolic disturbance (see Table 154–1)

1. Check patient temperature 2. Draw blood specimens: arterial blood gases, electrolytes, glucose, calcium, and magnesium

Metabolic abnormality found

Correct metabolic abnormality

No metabolic abnormalities identified

Failure to regain consciousness

Rule out CNS injury or undiagnosed preexisting CNS conditions (see Table 154–1)

Figure 154–1

■

Algorithm for evaluation of the patient with delayed emergence.

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Table 154–1

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Differential Diagnosis of Delayed Emergence

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from the conditions outlined earlier by careful assessment of neuromuscular function.

Risk Assessment

Drug Effects Drug overdose (accidental or error in judgment) Multiple CNS depressants or drug interactions Medication error (in preparation or administration) Impaired drug metabolism (reduced elimination or protein binding; increased sensitivity) Residual neuromuscular blockade

Physiologic Imbalance or Disorders of Metabolism Hypoxia; hypercarbia Electrolyte imbalance (hyponatremia, hypocalcemia, hypomagnesemia) Hypothermia or hyperthermia Sepsis Hypoglycemia

CNS Injury or Undiagnosed Preexisting Condition Intracranial hemorrhage or hypertension Cerebral ischemia, edema, or embolism (air or particulate) Seizure disorder (especially, postictal states) Brain tumor Stroke (e.g., in sickle cell disease, hypercoagulable states) CNS, central nervous system. Adapted and modified from Denlinger JK: Prolonged emergence and failure to regain consciousness. In Gravenstein N, Kirby RR (eds): Complications in Anesthesiology. Philadelphia, Lippincott-Raven, 1996, pp 441-450.

The incidence of delayed emergence is unknown. However, based on recent investigations of anesthetic complications in infants and children, its incidence appears to be low. In one study of anesthetic complications in 29,220 infants and children, there were no reported cases of delayed emergence or coma. In a review of complications in 40,240 infants and children, one case of coma was described; this occurred in a 13-year-old boy after nitrous oxide–opioid–neuroleptic anesthesia. In another study, 2 of 10,000 pediatric ambulatory surgery patients were hospitalized after surgery owing to excessive sleepiness. Underreporting of this complication may be a significant issue. The time required to emerge from general anesthesia is highly variable, so individual anesthesiologists must determine whether an emergence is delayed and report the complication. If most cases of delayed emergence are related to prolonged drug effects and the ultimate outcome is good, many practitioners are likely reluctant to report what appears to be an insignificant event.

Implications children who have experienced periods of hypotension or hypoperfusion or in those who have lost large amounts of blood necessitating massive fluid replacement with crystalloid, colloid, and blood products. Hypoglycemia should be suspected in children who (1) have fasted preoperatively for long periods, (2) have received non-glucose-containing IV fluids intraoperatively, or (3) are insulin-dependent diabetics and received insulin perioperatively. CENTRAL NERVOUS SYSTEM INJURY

OR

DISEASE

MANAGEMENT Management of delayed emergence entails the following steps: ● ● ● ● ●

Ensure adequate oxygenation and ventilation. Review the medical history and anesthetic management. Try drug antagonism. Rule out metabolic abnormalities. Rule out CNS injury.

The management of delayed emergence begins with ensuring that the patient has an adequate airway and that he or she is well oxygenated and ventilated. Next, the patient’s medical history and anesthetic management are reviewed to identify potential causes and determine what further actions are required. Frequently, opioid or benzodiazepine overdose cannot be ruled out, and a diagnostic and therapeutic trial of naloxone, flumazenil, or both is indicated (Table 154-2).

PEDIATRICS & NEONATOLOGY

CNS injuries during anesthesia in children are rare but may contribute to delayed emergence. Congenital heart lesions with right-to-left shunts place patients at risk for cerebral air embolism after even small amounts of air have been introduced via IV infusions. In addition, cerebral embolism with air or particulate matter can occur during cardiopulmonary bypass. Intracerebral or intraventricular hemorrhage can occur during awake laryngoscopy and endotracheal intubation in premature and term neonates and is also a complication of ventriculoperitoneal shunt revision and other neurosurgical procedures. Cerebral ischemia can occur with the delivery of hypoxic gas mixtures, prolonged hypotension with hypoperfusion, and carotid artery compression injury secondary to malpositioning. Undiagnosed, preexisting CNS conditions can also contribute to delayed emergence. Intracranial hypertension may exist in patients with malfunctioning ventriculoperitoneal shunts or in those with previously unrecognized brain tumors or foramen magnum stenosis; it can be exacerbated by hypercarbia, hypoxemia, or hyperextension of the neck. Seizures are difficult to detect in anesthetized and paralyzed patients. They can occur during general anesthesia, and the postictal state may present as delayed emergence. Finally, unrecognized muscle weakness or paralysis can make the patient appear to be unconscious. This must be distinguished

When delayed emergence results from prolonged drug action, long-term patient outcomes are good when proper measures are taken to support the airway and ensure adequate oxygenation, ventilation, and hemodynamic parameters. However, when delayed emergence is a consequence of metabolic abnormalities or CNS injury, it is imperative to recognize that there is a problem, determine the underlying cause, and institute corrective measures expeditiously to avoid a catastrophic outcome. Aside from its impact on patient outcome, delayed emergence can have a significant effect on operating room (OR) efficiency and the cost of operative procedures to families, institutions, and health care systems. Even small delays in emergence, if frequent, can disrupt the OR schedule, consume OR and recovery room time and personnel, and prevent an anesthesiologist from starting other scheduled cases on time.

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Antagonists to Reverse the Sedative Effects of Anesthetic Agents

Naloxone: 1-4 μg/kg IV titrated to effect; maximum dose, 10 μg/kg Flumazenil: 2.5-5 μg/kg IV titrated to effect; maximum dose, 10 μg/kg Physostigmine: 25-50 μg/kg IV; maximum dose, 2 mg

The nonspecific antagonist physostigmine may be beneficial when delayed emergence is due to volatile anesthetics, scopolamine, ketamine, phenothiazines, or tricyclic antidepressants. It should be emphasized that any of these antagonists may produce only a transient recovery of consciousness. If prolonged anesthetic drug effects are not suspected, blood should sampled to determine arterial blood gases, electrolytes, glucose, calcium, and magnesium concentrations. If no discernible cause is identified after the initial review, neurology consultation, CNS imaging studies, or electroencephalography may be indicated.

PREVENTION Delayed emergence is often preventable. Drug errors, inadequate patient surveillance or monitoring, and positioning injuries, especially when surgery involves the head and neck

or when patients are in the prone or lateral decubitus position, are some of the more common preventable causes of this complication.

Further Reading Brosius KK, Bannister CF: Oral midazolam premedication in preadolescents and adolescents. Anesth Analg 94:31-36, 2002. Cohen MM, Cameron CB, Duncan PG: Pediatric anesthesia morbidity and mortality in the perioperative period. Anesth Analg 70:160-167, 1990. Cook DR, et al: Pharmacology of pediatric anesthesia. In Motoyama EK, Davis PJ, Lerman J (eds): Smith’s Anesthesia for Infants and Children. St. Louis, Mosby, 1996, pp 159-209. Denlinger JK: Prolonged emergence and failure to regain consciousness. In Gravenstein N, Kirby PR (eds): Complications in Anesthesiology. Philadelphia, Lippincott-Raven, 1996, pp 441-450. Hinkle AJ: Neonatal sepsis presenting as delayed emergence from general anesthesia. Anesthesiology 57:412-414, 1982. Patel RI, Hannallah RS: Anesthetic complications following pediatric ambulatory surgery: A 3-year study. Anesthesiology 69:1009-1012, 1988. Seiber FE, Smith DS, Traystman RJ, et al: Glucose: A reevaluation of its intraoperative use. Anesthesiology 67:72-81, 1987. Tiret L, Nivoche Y, Hatton F, et al: Complications related to anaesthesia in infants and children: A prospective study of 40,240 anaesthetics. Br J Anaesth 61:263-269, 1988. Viitanen H, Annila P, Viitanen M, et al: Midazolam premedication delays recovery from propofol induced sevoflurane anesthesia in children 1-3 years old. Can J Anaesth 46:766-771, 1999. Welbourne LG, Hannallah RS, McGill WA, et al: Glucose concentrations for routine intravenous infusion in pediatric outpatient surgery. Anesthesiology 67:427-430, 1987.

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Postintubation Croup Mark I. Rossberg

155

Case Synopsis An otherwise healthy 3-year-old boy receives general endotracheal anesthesia for hypospadias repair. Shortly after arrival in the pediatric acute care unit, the child is noted to have a hoarse cry and mild inspiratory stridor.

PROBLEM ANALYSIS Definition Postintubation croup is a complication of general endotracheal anesthesia that is most commonly seen in children. Endotracheal intubation in children may cause traumatic injury to the tracheal epithelium, and postintubation croup is believed to be a manifestation of traumatic subglottic mucosal edema. Postintubation croup can vary in severity. Mild subglottic edema may be accompanied by hoarseness of the voice, a barking cough, and stridor when the patient is agitated or crying. With more significant subglottic swelling, tracheal narrowing occurs, and partial airway obstruction ensues, resulting in the patient’s use of accessory muscles of respiration. In its most severe form, postintubation croup can progress to total airway obstruction, requiring the establishment of an artificial airway. The signs of subglottic edema usually become evident within an hour of tracheal extubation. Respiratory compromise may progress until approximately 8 hours after extubation and usually resolves within 24 hours.

Recognition When postintubation croup occurs, it is important to assess the degree of airway compromise, monitor for progressive airway obstruction, and intervene if necessary. Pulse oximetry should be monitored. MILD POSTINTUBATION CROUP ● ● ● ●

Stridor when crying or agitated Mild retraction of respiratory muscles Good aeration of lungs No desaturation while breathing room air

● ● ● ●

Stridor at rest Moderate retraction of respiratory muscles Reduced aeration of lungs Desaturation while breathing room air

SEVERE POSTINTUBATION CROUP ● ●

Stridor at rest Deep retraction of respiratory muscles

●

●

Poor aeration of lungs Desaturation despite breathing an increased fraction of inspired oxygen Lethargy

Risk Assessment Mild postintubation croup (characterized by hoarse voice and stridor) remains a common problem, but the incidence of severe postintubation croup associated with significant airway compromise has declined. The reported incidence of postintubation croup in the 1960s varied from 1.6% to 6%; in 1977 it was 1%; and by 1991, it was reported to be 0.1%. Part of the reason for the apparent decline in incidence is the more stringent definition of croup used in more recent reports. Only patients with inspiratory stridor and retraction of accessory respiratory muscles for at least 30 minutes’ duration and severe enough to warrant therapy were considered to have postintubation croup. Thus, patients with transient postoperative stridor or an isolated hoarse voice or barking cough were excluded. However, a real decline in the incidence of significant subglottic edema has occurred as a result of changes in anesthesia practice and equipment. Previously, endotracheal tubes were rubber and were washed with a detergent and reused. They may have been both physically and chemically irritating to the trachea. With the advent of standardized, nonreactive, single-use polyvinyl chloride endotracheal tubes, these irritants are no longer a factor. Additionally, anesthesiologists are now more attuned to selecting endotracheal tubes of an appropriate size for children and replacing endotracheal tubes that fit too tightly within the patient’s trachea. Patients younger than 1 year rarely develop croup. The highest incidence seems to be between the ages of 1 and 4 years. Beyond 4 years, the risk diminishes. The most important factor associated with the development of postintubation croup is a tight-fitting endotracheal tube, as demonstrated by the absence of an air leak around the tube at 40 cm H2O pressure. There is no significant difference in risk between cuffed and uncuffed endotracheal tubes. Physical trauma or irritation of the airway is associated with postintubation croup. This may be related to difficult or multiple intubation attempts and patient coughing or head repositioning while an endotracheal tube is in place. The effect of the use of local analgesics and lubricants on endotracheal tubes is unclear. Patients with croup are more likely to have been intubated for longer than 1 hour, to have 631

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MODERATE POSTINTUBATION CROUP

●

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been in a position other than supine during surgery, or to have had neck surgery. There are conflicting data about whether preoperative upper respiratory tract infection correlates with the development of postintubation croup. Patients with a history of viral croup may be at a higher risk. Finally, postintubation stridor is more frequent in children with Down’s syndrome than in other children after cardiac surgical repair. This is probably because these children have a smaller-diameter cricoid ring and require smallerdiameter tracheal tubes than do normal children.

Implications It is wise to know the risk factors for postintubation croup and anticipate its occurrence. When subglottic edema does occur, it should be recognized, and the magnitude of airway compromise should be assessed and observed for signs of worsening. Appropriate therapy should be instituted promptly, and the response to therapy should be monitored closely, because unresolved airway obstruction may result in hypoventilation, hypoxemia, prolonged stay in the postanesthesia care unit, and unanticipated hospital admission.

MANAGEMENT Initial therapy consists of the administration of humidified oxygen by facemask, mist tent, or tubing directed at the child’s face. For mild croup, this is usually adequate. However, in the case of moderate to severe croup, or if a patient with mild croup is developing worse stridor and respiratory distress, further therapies are indicated. Nebulized racemic epinephrine may be given at a dose of 0.5 mL of 2.25% solution in 3 mL of normal saline. This usually relieves airway obstruction and alleviates symptoms through its vasoconstrictive effects on the tracheal mucosa. Improvement should be seen within 20 to 30 minutes. During the administration of racemic epinephrine, the cardiac rate and rhythm should be monitored for tachyarrhythmias with continuous electrocardiography. Many argue that any patient who has had sufficient airway compromise to warrant racemic epinephrine therapy should be admitted to the hospital for 12 to 24 hours of observation because of the potential for laryngeal edema to worsen again. Certainly any child who receives racemic epinephrine should be observed for at least 4 to 5 hours after therapy. Further, many of those treated with racemic epinephrine benefit from a repeat dose. Patients with significant ongoing or progressive respiratory compromise should be transferred to a pediatric intensive care unit for further therapy and observation. It should be recognized that racemic epinephrine, which consists of the d- and l-isomers of epinephrine, has traditionally been used instead of l-epinephrine. It was believed that racemic epinephrine was more effective at reducing tracheal edema and was less likely to provoke the side effects of l-epinephrine (tachycardia, hypertension, tremor). However, in a randomized study, l-epinephrine was found to be equally as efficacious as racemic epinephrine in the treatment of postintubation laryngeal edema, with neither of these drugs producing significant side effects. Although equipotent doses

of the drugs were used in this study, the doses were half those recommended earlier (0.25 mL of 2.25% solution of racemic epinephrine or 1% l-epinephrine in 3 mL of normal saline). However, the patients in the study were young (12 ± 10 months), possibly explaining why a reduced dose was chosen. Steroids are the most effective definitive therapy for croup (whether postintubation or viral) because of their ability to reduce tracheal edema and inflammation. Dexamethasone effectively reduces the risk of postextubation stridor in preterm infants. In young squirrel monkeys with experimental (traumatic) laryngeal edema, intravenous dexamethasone prevented the development of laryngeal edema and sped the resolution of existing experimental laryngeal edema. Based on evidence of the effectiveness of steroids and the seemingly low risk of short-course or single-dose steroid therapy, it seems prudent to administer a single dose of dexamethasone to patients who require nebulized racemic epinephrine. A dose of 0.25 to 0.5 mg/kg intravenously (to a maximum of 10 mg) is commonly used. In cases of mild croup, especially in ambulatory surgery patients, it may be prudent to administer a single dose of steroid either intravenously or orally. Clearly, for severe postintubation airway obstruction, the airway must be secured with an endotracheal tube. This is extremely unusual and is often associated with other issues, such as underlying subglottic stenosis or neurologic injury.

PREVENTION Take the following precautions to prevent postintubation croup: Avoid the use of excessively tight-fitting endotracheal tubes, especially if the patient has a history of croup. ● Check for leak pressure (the inspiratory pressure required to cause an audible escape of gas around the endotracheal tube) immediately after intubation, and consider changing the endotracheal tube to one half a size smaller if there is no leak at 40 cm H2O pressure. ● If a cuffed endotracheal tube is used, inflate the cuff only enough to maintain the desired leak pressure (<40 cm H2O pressure or, preferably, < −25 cm H2O pressure). ● During a long operation, if possible, intermittently check the leak pressure and adjust the volume of gas in the cuff to maintain the desired leak. Remember that nitrous oxide can diffuse into the endotracheal tube cuff and increase cuff pressure during surgery. ● Avoid multiple intubation attempts, especially in patients with upper respiratory tract infections or a history of croup. When using laryngoscopes that have been chemically sterilized versus heat sterilized, ensure that all chemicals have been thoroughly rinsed off. ●

Further Reading Bjornson CL, Klassen TP, Williamson J, et al: A randomized trial of a single dose of oral dexamethasone for mild croup. N Engl J Med 351:1306-1313, 2004. Cohen MM, Cameron CB, Duncan PG: Pediatric anesthesia morbidity and mortality in the perioperative period. Anesth Analg 70:160-167, 1990.

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Couser RJ, Ferrara TB, Falde B, et al: Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema. J Pediatr 121:591-596, 1992. Goddard JE, Phillips OC, Marcy JH: Betamethasone for prophylaxis of postintubation inflammation: A double blind study. Anesth Analg 46:348-353, 1967. Litman RS, Keon TP: Postintubation croup in children. Anesthesiology 75:1122-1123, 1991.

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Waisman Y, Klein B, Boenning D, et al: Prospective randomized doubleblind study comparing l-epinephrine and racemic epinephrine aerosols in the treatment of laryngotracheitis (croup). Pediatrics 89:302-306, 1992.

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Postobstruction Pulmonary Edema in Pediatric Patients

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Lynda J. Means Case Synopsis A 5-year-old obese child with developmental delay, asthma, and obstructive sleep apnea presents for a tonsillectomy. Inhalation induction is begun. The airway is partially obstructed intermittently until nasopharyngeal and oral airways are inserted. On completion of surgery, pink, frothy fluid is noted in the endotracheal tube. A chest radiograph (Fig. 156-1) is obtained, and the child is transferred to the intensive care unit for positive-pressure ventilation with positive end-expiratory pressure. The following morning the chest radiograph is normal (Fig. 156-2), and the child is extubated without incident.

PROBLEM ANALYSIS Definition Postobstruction pulmonary edema (POPE) is acute pulmonary edema that follows the relief of upper airway obstruction during which vigorous inspiratory efforts occurred (see Chapter 52 for POPE in adults). The obstruction may be acute and total, as occurs with laryngospasm in children or adults; alternatively, it can be partial and more prolonged, as occurs with

epiglottitis in children. POPE is often referred to as negativepressure pulmonary edema because the primary factor in its development is the generation of markedly negative intrathoracic pressure. This pressure, generated by forced inspiration against an obstructed upper airway (i.e., a modified Müller maneuver), ultimately leads to the transudation of fluid from pulmonary capillaries into the interstitium, and from there into alveoli. Hypoxia and acute left ventricular dysfunction may also play a role in the development of edema fluid.

Recognition Recognition of POPE involves an understanding of its pathophysiology. The pathogenesis of POPE is explained by

Figure 156–1 ■ Chest radiograph obtained at the completion of surgery. Note perihilar fluffy infiltrates in a butterfly pattern, consistent with pulmonary edema. Also present is left lower lobe atelectasis.

634

Figure 156–2 ■ Chest radiograph taken the following morning. Note resolution of the perihilar infiltrates.

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abnormal fluid flux across alveolar-capillary membranes. The abnormal fluid translocation results from a disruption in the balance between hydrostatic and colloid osmotic pressures in alveolar-capillary units, according to Starling’s equation. Normally, a balance exists among the forces maintaining fluid in the intravascular space and those moving fluid into the interstitium.

635

Airway obstruction

Negative intrathoracic pressure

Hypoxemia

(⇑ afterload) ⇑ Pulmonary blood flow

⇑ Sympathetic tone

(ventricular septum shift)

(⇑ afterload)

Fluid filtration rate = Kf [(Pc − Pi) − σ (πc − πi)] where Kf is capillary permeability, Pc is pulmonary capillary hydrostatic pressure, Pi is pulmonary interstitial hydrostatic pressure, σ is the reflection coefficient for proteins, πc is pulmonary capillary osmotic pressure, and πi is pulmonary interstitial osmotic pressure. The result is that only a small amount of fluid enters the pulmonary interstitium and, once there, is promptly removed by the pulmonary lymphatics. Patients who generate extremely negative intrathoracic pressures increase venous return to the right atrium. This increases pulmonary blood volume and capillary hydrostatic pressure. At the same time, a marked decrease in pulmonary interstitial hydrostatic pressure occurs, resulting in increased transfer of fluid into the interstitium. If lymph removal mechanisms are overwhelmed, signs and symptoms of pulmonary edema develop. The hypoxemia and increased sympathetic tone that frequently accompany airway obstruction also increase pulmonary vascular pressures and left ventricular afterload to facilitate edema formation (Figs. 156-3 and 156-4). Acutely, left ventricular dysfunction may contribute to the development of pulmonary edema. However, such dysfunction is typically extremely short-lived, as evidenced by normal or near-normal central venous, pulmonary artery, and pulmonary capillary wedge pressures when measured after the obstructive event. An example of the relative pressures maintaining a normal fluid filtration rate (assuming constant values for Kf and σ) is the following: Pc = 12 mm Hg, Pi = −4 mm Hg, πc = 23 mm Hg, πi = 9 mm Hg ≈ 2 mm Hg Relative pressures promoting an increased fluid filtration rate and the development of POPE are as follows: Pc = 22 mm Hg, Pi = −50 mm Hg, πc = 23 mm Hg, πi = 9 mm Hg ≈ 58 mm Hg Pc elevation reflects increased pulmonary capillary blood volume and left ventricular afterload; Pi elevation reflects decreased intrapleural pressure.

Left ventricular dysfunction Figure 156–4 ■ Proposed mechanisms leading to left ventricular dysfunction during airway obstruction.

POPE typically occurs in young, healthy individuals. The onset of edema is usually soon after relief of the obstruction, but it may be delayed for 3 to 4 hours. The patient exhibits an increased alveolar-to-arterial oxygen tension gradient, manifested by a requirement for supplemental oxygen; this, along with the pulmonary edema, typically resolves in less than 36 hours. Chest auscultation is consistent with pulmonary edema and may reveal rales and occasional rhonchi and wheezes. The chest radiograph and computed tomography scan show pulmonary edema, with peribronchial cuffing predominantly involving the perihilar and more central lung parenchyma. The peripheral lung regions remain remarkably free of alveolar edema, resulting in a “butterfly” pattern. The cardiac silhouette is normal. The following causes of pulmonary edema should also be considered and eliminated: ● ● ● ● ● ● ●

Aspiration pneumonia Iatrogenic volume overload Pulmonary embolus Primary cardiac abnormality Myocardial dysfunction secondary to ischemia Anaphylaxis Asthma

At least initially, aspiration pneumonia is the most difficult alternative diagnosis to eliminate. Massive aspiration of gastric contents can produce the same radiographic picture as POPE, but it more commonly involves the right upper lobe or posterior segments. Further, the clinical course is more protracted owing to the chemical injury to the lung parenchyma. Radiographic changes from acute aspiration of gastric contents typically lag behind the patient’s clinical course.

Hypoxia

Increased sympathetic tone

⇑ Pulmonary microvascular pressure

The incidence of POPE is unknown, despite clinical reports describing the phenomenon since the mid-1970s. Risk factors include the following: ● ●

⇑ Pulmonary microvascular permeability Figure 156–3 Role of hypoxia in the generation of postobstruction pulmonary edema. ■

● ● ●

Laryngospasm Obesity and obstructive sleep apnea Epiglottitis Croup Partial tracheal obstruction by a foreign body

PEDIATRICS & NEONATOLOGY

Risk Assessment Pulmonary microvascular vasoconstriction

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Upper airway pathology or surgical manipulation (e.g., tracheomalacia, vocal cord paralysis) Partial tracheal obstruction by an esophageal foreign body Obstructed endotracheal tube or laryngeal mask Difficult intubation

No specific anesthetic drugs have been shown to increase the incidence of POPE. However, anesthetic agents or techniques that increase the likelihood of laryngospasm or soft tissue upper airway obstruction have the potential to increase a patient’s risk for POPE.

Implications Profound hypoxia secondary to upper airway obstruction occurs rapidly in children. If it is not relieved, cardiac arrest can follow. Prompt and effective intervention to reestablish a patent upper airway and to maximize oxygenation is paramount. With recognition and appropriate management, the clinical course of POPE is usually self-limited.

MANAGEMENT Treatment of POPE involves reestablishing and maintaining a patent airway, followed by supportive care. Supplemental oxygen is necessary, and most patients require tracheal intubation for a period of time; this may be as short as several hours in some instances. Many patients receive positive airway pressure, either as continuous positive airway pressure or as positive-pressure ventilation with positive end-expiratory pressure. Rarely, hemoptysis and frank pulmonary hemorrhage have been reported after acute upper airway obstruction. Both require significant ventilatory and cardiovascular support. Aggressive, invasive hemodynamic monitoring, such as pulmonary artery catheterization, is not indicated except to rule out other causes of pulmonary edema. Use of diuretics is controversial because the edema is not due to excessive intravascular volume (as supported by normal pulmonary capillary wedge pressure measurements), and edema resolution is typically rapid. In addition to diuresis, furosemide increases venous capacitance, and it may have a role in the management of POPE. Corticosteroids and antibiotics have no role in the treatment of POPE unless

they are indicated for other reasons. Resolution of clinical symptoms and radiographic findings is usually rapid and typically occurs within 2 to 3 days.

PREVENTION Prevention of POPE involves (1) recognition of clinical scenarios in which upper airway obstruction is likely to occur and (2) the development of an anesthesia management plan to avoid potential obstruction. The latter includes the following: ●

●

●

●

Ensure an adequate depth of anesthesia during the use of a facemask or laryngeal mask airway. Consider the use of “bite blocks” to ensure patency of artificial airways during emergence from anesthesia. Perform tracheal extubation in fully awake patients to avoid laryngospasm or soft tissue airway obstruction. Use fiberoptic intubation in patients with known airway abnormalities.

Anesthesiologists are frequently faced with situations that cannot be avoided, such as anesthetizing a child with epiglottitis. In such cases, multiple strategies for avoiding the complications of airway obstruction, including surgical intervention, should be available if obstruction occurs.

Further Reading Broccard AF, Liaudet L, Aubert JD, et al: Negative pressure post-tracheal extubation alveolar hemorrhage. Anesth Analg 92:273-275, 2001. Devys JM, Balleau C, Jayr C, et al: Biting the laryngeal mask: An unusual cause of negative pressure pulmonary edema. Can J Anaesth 47:176-178, 2000. Guinard JP: Laryngospasm-induced pulmonary edema. Int J Pediatr Otorhinolaryngol 20:163-168, 1990. Herrick IA, Mahendran B, Penny FJ: Postobstructive pulmonary edema following anesthesia. J Clin Anesth 2:116-120, 1990. Lang SA, Duncan PG, Shepard DAE, et al: Pulmonary oedema associated with airway obstruction. Can J Anaesth 37:210-218, 1990. Oswalt CE, Gates GA, Holmstrom MG: Pulmonary edema as a complication of acute airway obstruction. JAMA 238:1833-1835, 1977. Ruffle J, Gleason M, Domino KB, et al: Pulmonary edema and transient cardiomyopathy in a previously healthy adolescent after general anesthesia. J Cardiothorac Vasc Anesth 8:463-470, 1994. Schwartz DR, Maroo A, Malhotra A, et al: Negative pressure pulmonary hemorrhage. Chest 115:1194-1197, 1999.

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157

Hypoxemia Lori A. Aronson Case Synopsis A 10-year-old boy undergoes general endotracheal anesthesia for elective repair of an undescended left testis. When he awakes from anesthesia, the trachea is extubated. The patient immediately coughs, becomes stridorous, and has chest wall retractions. Cyanosis, tachycardia, and percutaneous arterial oxygen saturation (SpO2) less than 60% are noted.

PROBLEM ANALYSIS Definition Hypoxemia is abnormally low oxygenation of the blood. It is distinguished from hypoxia, in which tissue oxygen (O2) delivery is inadequate to sustain normal cellular aerobic metabolism. Table 157-1 lists the normal age-related values of blood O2 tension, and Table 157-2 shows the change in the O2 affinity of hemoglobin with age.

Recognition Identifying hypoxemia is an integral part of anesthesia practice. The pulse oximeter has become the standard of care for monitoring oxygenation during anesthesia. A decrease in SpO2 is often the first and cardinal sign of hypoxemia. The clinical signs of hypoxemia vary with age. Preterm infants and neonates respond to hypoxemia with ventilatory depression, with or without bradycardia. Older infants and children respond with tachypnea and either tachycardia or bradycardia. Cyanosis, pallor, restlessness, or altered mental status may be evident, depending on the degree of hypoxemia. All these signs can be masked by anesthesia. Pulse oximetry has improved patient safety by allowing anesthetic providers to recognize and respond to an oxygenation problem sooner than would be possible based on clinical signs alone. Determining the cause of hypoxemia is critical to establishing a treatment strategy. One must use physical assessment skills (auscultation, percussion, palpation), monitors (pulse oximetry, end-tidal carbon dioxide, fraction of inspired O2 [FiO2], airway pressure), and tests such as chest radiographs and blood gas analysis to establish the cause of hypoxemia.

A systematic approach to ascertaining the underlying cause of hypoxemia should be taken. This includes an assessment of the O2 supply, the integrity of the anesthesia machine, the breathing circuit and airway, and the functioning of the patient’s pulmonary, cardiovascular, hematologic, and central nervous systems.

Risk Assessment The risk of hypoxemia in pediatric patients is related to many factors, including underlying disease and age-related anatomic and physiologic characteristics. The anesthesiologist must assess each factor’s contribution to the risk for hypoxemia in an individual patient. Table 157-3 lists the principal causes of hypoxemia. ANATOMY

AND

Knowledge of the unique anatomic and physiologic characteristics of infants and children is critical to their anesthetic management. These characteristics include the following: ●

●

●

Infants have relatively large heads, short necks, and large tongues, which make them prone to upper airway obstruction. In older children, enlarged tonsils may contribute to upper airway obstruction. An infant’s epiglottis is U-shaped and floppy. The larynx appears more anterior because it is higher than in adults (C3-C4 versus C4-C5). The vocal cords angle more cephalad. The narrowest part of the pediatric airway is the cricoid cartilage. Airway epithelium is easily traumatized, and tracheal cartilage is readily collapsible.

Age Preterm Full term 1 mo 1 yr 12 yr

■

■

Normal Arterial Oxygen Tension (PaO2) in Infants and Children PaO2 (mm Hg) 60 70 95 93 98

Age Neonates Infants (>3 mo) Adults (>18 yr)

Age-Related Oxygen Affinity for Hemoglobin at an Oxygen Saturation of 50% (P50O2)

PEDIATRICS & NEONATOLOGY

Table 157–2 Table 157–1

PHYSIOLOGY

P50O2 (mm Hg)* 30 20 27

*Oxygen affinity is highest in neonates and lowest in infants before reaching adult levels.

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Table 157–3

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Causes of Hypoxemia in Pediatric Patients Pulmonary edema Near-drowning Asthma, bronchospasm Pneumonia Pulmonary contusion Pulmonary embolus (air, fat, thrombus) Pulmonary fibrosis, cystic fibrosis Bronchiectasis

Central Nervous System and Respiratory Centers Apnea Head trauma Brain tumor Seizures Anesthetic agents Narcotic overdose Inhalational agents Barbiturates, sedatives Combinations of the above

Chest Wall and Pleura Pneumothorax Flail chest Pleural effusion Obesity Kyphoscoliosis Abdominal mass

Airway Epiglottitis, croup Tracheomalacia, laryngomalacia Retropharyngeal abscess Vascular ring Infantile stridor Laryngospasm Webs Mediastinal mass Foreign body, ETT obstruction Thermal airway injury (burns) Subglottic stenosis Upper respiratory infection

Cardiovascular Congenital heart disease Congestive heart failure Arteriovenous malformation Hypovolemia, hemorrhage

Hematologic Anemia Sickle cell disease or crisis Thalassemia

Respiratory Muscles Residual neuromuscular blockade Debilitation, malnutrition Myasthenia gravis Muscular dystrophy Phrenic nerve injury

Oxygen Delivery Main-stem bronchial intubation ETT kinking Low FiO2, hypoxic gas mixture Ventilator disconnection Anesthesia machine failure Esophageal intubation

Pulmonary: Physiologic Causes Ventilation-perfusion mismatch Shunt Dead-space ventilation Diffusion abnormality (rare)

Increased Oxygen Consumption Shivering (hypothermia) Malignant hyperthermia Hyperthermic states (sepsis) Hyperthyroidism

Pulmonary: Pathologic Causes Respiratory distress syndrome Bronchopulmonary dysplasia Primary pulmonary hypertension Aspiration pneumonitis Diaphragmatic hernia Tracheoesophageal fistula

●

●

●

An infant’s trachea is significantly shorter than an adult’s. Also, the angle of tracheal bifurcation (about 45 degrees) is nearly the same for both main-stem bronchi. Therefore, one must be diligent to avoid either right or left main-stem bronchial intubation. In contrast, in older patients, the angle of tracheal bifurcation is less for the right main-stem bronchus (about 30 degrees) than for the left, explaining the higher risk for right main-stem bronchial intubation in adults. Respiratory control is not well developed. Respiratory muscles (the intercostals and diaphragm) have fewer type I muscle fibers and tend to fatigue more easily. This may lead to hypoventilation. The newborn’s chest wall is very compliant and tends to move inward on inspiration. The rib angle is more horizontal, further limiting chest expansion on inspiration. Thus, infants often rely on their abdominal muscles during inspiration.

Miscellaneous Positioning Carbon monoxide Cyanide poisoning (sodium nitroprusside overdose) Hepatic failure

●

●

●

A distended abdomen due to aggressive positive-pressure ventilation can markedly impede diaphragmatic movement. Pulmonary development is incomplete at birth. Alveoli are present in adult numbers by 3 years, but they continue to grow in size until 7 to 8 years of age. Additionally, premature infants or sick newborns may have inadequate surfactant. This contributes to alveolar collapse, reduced compliance, and hypoxemia. O2 consumption and alveolar ventilation in infants are approximately double that in adults (7 versus 4 mL/kg per minute and 130 versus 60 mL/kg per minute, respectively). However, functional residual capacity is about half that of adults (25 versus 40 mL/kg). Infants also have higher lung closing volumes and faster respiratory rates. These combine to limit O2 reserve. With increased O2 consumption, hypoxia can occur rapidly. Newborns respond to hypoxia with transient tachypnea and then ventilatory depression.

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BREATHING PATTERNS Periodic breathing (apnea lasting <10 seconds) occurs in preterm and term infants. The frequency dramatically decreases by 12 months of age. Although periodic breathing is a benign respiratory pattern, central apnea is not. Central apnea of infancy (apnea lasting >15 seconds, or less if associated with bradycardia, cyanosis, or pallor) is common in preterm infants. It may be related to immature respiratory control mechanisms. Prematurity, anemia, and anesthesia are critical risk factors for life-threatening apnea in infants (see Chapter 150). Mild hypoxemia is common with respiratory infections in young infants, making them especially vulnerable to further desaturation. POSTANESTHESIA CARE UNIT A large percentage of healthy infants and children undergoing simple elective surgical procedures become hypoxemic in the postanesthesia care unit. Children younger than 1 to 2 years or those with upper respiratory infections are at greatest risk for hypoxemia. Airway obstruction, central hypoventilation (due to residual inhalational anesthetics or narcotics), atelectasis, and poor ventilation secondary to pain, dressings, shivering, or residual neuromuscular blockade may further contribute to hypoxemia. Therefore, pediatric patients should receive O2 during transport to and in the postanesthesia care unit.

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maintenance of monitors and equipment (see Section 6) is important for reducing the risk of life-threatening problems.

Implications Cardiac arrest may occur if hypoxemia is not promptly recognized and treated. Anaerobic metabolism leading to acidosis, end-organ injury, and death can follow. Thus, detection and treatment of hypoxemia are critical.

MANAGEMENT The initial management of hypoxemia is directed at improving the patient’s oxygenation by increasing the FiO2 to 1.0 and ensuring a patent airway and ventilation. This is done with mask ventilation and oropharyngeal or nasopharyngeal airways, endotracheal intubation, laryngeal mask airway, or cricothyrotomy or tracheotomy. Further management is directed at remedying the cause of hypoxemia. Rapid diagnosis of the cause of the problem allows the timely reversal of hypoxemia and the avoidance of further complications. If hypoxemia is prolonged, advanced life support may become necessary.

PREVENTION

The cardiovascular system is responsible for the delivery of O2 to the tissues. With the onset of respiration and altered blood flow patterns in newborns, pulmonary vascular resistance falls, while systemic vascular resistance increases. Increased afterload causes the foramen ovale to close, and this reverses the direction of shunt through the ductus arteriosus. Until these pathways close anatomically, reversion to a fetal-type circulation with hypoxemia may occur. Hypoxia and acidosis can increase pulmonary vascular resistance and cause right-toleft shunting and O2 desaturation. In congenital heart disease, anatomic shunting of blood through abnormal vascular pathways can result in right-toleft shunting with hypoxemia. Congestive heart failure may also contribute to hypoxemia. A true right-to-left shunt does not respond to O2 with an increase of SpO2. Fetal hemoglobin predominates at birth and causes a leftward shift of the oxygen-hemoglobin dissociation curve. Fetal hemoglobin has a high affinity for O2. This leads to less O2 released to the tissues at any given FiO2. The higher hemoglobin level, increased blood volume, and increased cardiac output per unit body weight compensate for increased tissue demands for O2. However, if anemia, hypovolemia, or low cardiac output occurs, the risk for hypoxemia is increased. Physiologic anemia occurs at 2 to 3 months of age, or earlier in premature infants. An increase in 2,3-diphosphoglycerate compensates for this and shifts the oxygen-hemoglobin dissociation curve to the right, allowing greater O2 delivery to tissues. Hypoxemia may occur due to failure of O2 supply equipment. Failure of oximetry monitoring delays the diagnosis of hypoxemia. Knowledge about the operation and

Prevention of hypoxemia and adverse outcomes begins with a careful patient evaluation, an understanding of the implications of the planned procedure, and a thorough check of all equipment before anesthesia and surgery. Preoperative evaluation includes assessing the patient’s medical status, recognizing the urgency and risks of the planned surgery, and determining whether further medical therapy before surgery could reduce patient risk. Some common anesthesia practices that may reduce hypoxemia include preoxygenation and denitrogenation before endotracheal intubation, increasing the FiO2 to 1.0 for several minutes before tracheal extubation, administering a higher FiO2 during anesthesia maintenance, use of supplemental O2 during patient transport, and utilization of pulse oximetry, capnography, and FiO2 monitoring. Although critical incidents may still occur despite the anesthesiologist’s vigilance, prompt recognition and treatment are critical to minimizing adverse outcomes.

Further Reading Coté CJ, Goldstein EA, Coté MA, et al: A single-blind study of combined pulse oximetry and capnography in children. Anesthesiology 68: 184-188, 1988. Coté CJ, Zaslavsky A, Downes JJ, et al: Postoperative apnea in former preterm infants after inguinal herniorrhaphy: A combined analysis. Anesthesiology 82:809-822, 1995. Kurth CD, LeBard SE: Association of postoperative apnea, airway obstruction, and hypoxemia in former premature infants. Anesthesiology 75:22-26, 1991. Liu LM, Coté CJ, Goudsouzian NG, et al: Life-threatening apnea in infants recovering from anesthesia. Anesthesiology 59:506-510, 1983.

PEDIATRICS & NEONATOLOGY

OXYGEN DELIVERY

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Motoyama E: Respiratory physiology in infants and children. In Motoyama E, Davis PJ (eds): Smith’s Anesthesia for Infants and Children. St. Louis, Mosby, 1996, pp 11-67. Pang LM, Mellins RB: Neonatal cardiorespiratory physiology. Anesthesiology 43:171-196, 1975.

Welborn LG, Hanallah RS, Luban NLC, et al: Anemia and postoperative apnea in former preterm infants. Anesthesiology 74:1003-1006, 1995. Xue FS, Huang YG, Tong SY, et al: A comparative study of early postoperative hypoxemia in infants, children, and adults undergoing elective plastic surgery. Anesth Analg 83:709-715, 1996.

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Mark Meyer and Joseph Previte Case Synopsis A 3-year-old girl with developmental delay, tracheomalacia, and reactive airway disease presents for laryngoscopy, bronchoscopy, and esophagogastroduodenoscopy. Despite a previous Nissen fundoplication, she continues to have episodes of pneumonia secondary to gastroesophageal reflux disease (GERD) and aspiration. Medications include albuterol for wheezing and pantoprazole for GERD.

PROBLEM ANALYSIS Definition Pulmonary aspiration is defined as the presence of bilious secretions or particulate matter in the tracheobronchial tree. It most commonly occurs from passive regurgitation of gastric contents or active vomiting, but aspiration of blood or pharyngeal secretions can also cause significant pneumonitis. Of pediatric patients who aspirate during anesthesia, 40% actively vomit, and the remainder passively regurgitate. When anesthetized patients aspirate, 80% do so during induction, 14% during emergence, 4% during the procedure, and 2% postoperatively.

Recognition After significant pulmonary aspiration, the physical examination may reveal fever, tachypnea, apnea, tachycardia, refractory laryngospasm, bronchospasm, wheezing, or cough. Rales and rhonchi can be heard, and cyanosis may be observed. A chest radiograph may reveal alveolar and, less commonly, reticular infiltrates. Radiographic findings may be localized but are more often extensive and frequently bilateral. The full extent of changes on the chest radiograph may not be demonstrated until 6 to 24 hours after pulmonary aspiration. Ninety percent of patients with significant pulmonary aspiration have symptoms within 1 hour, and almost all have symptoms within 2 hours. A pH determination of the aspirated material can be used to predict the severity of pulmonary damage.

on an extrapolation of unpublished experimental data in rhesus monkeys, the thresholds for gastric pH (<2.5) and residual gastric volume (>0.4 mL/kg) have been applied to humans. Based on these limits, the risk of pulmonary aspiration would be increased in children compared with adults, because 76% of pediatric patients have gastric contents whose pH is less than 2.5 and whose volume is greater than 0.4 mL/kg, versus 32% to 55% of adults who meet these criteria. Infants are at highest risk for pulmonary aspiration. GERD occurs in almost 50% of term neonates and is considered normal for the first 6 months of life. GERD can occur with intragastric pressures as low as 23 cm H2O. If the fundoesophageal angle decreases during tracheal intubation, GERD can occur at even lower intragastric pressures. Owing to a smaller stomach, air swallowing during crying, and diaphragmatic breathing, the resting intragastric pressure in infants is higher than in older children or adults, which contributes to an increased risk of GERD. The incidence of pulmonary aspiration with laryngeal mask airways may not be higher when used in healthy patients having elective surgery. However, the laryngeal mask airway does not form a tight seal around the larynx. Further, it causes reflex relaxation of the lower esophageal sphincter secondary to pharyngeal muscle distention, as during swallowing of a food bolus. The laryngeal mask airway may also increase the likelihood of pulmonary aspiration by contributing to gastric distention during positive-pressure ventilation and directing regurgitated gastric contents into

Table 158–1

Pulmonary aspiration occurs in 1 to 10 of 10,000 pediatric anesthetics. Pediatric patients may have a higher incidence of pulmonary aspiration associated with a greater risk of severe pulmonary damage compared with adults; however, the anesthesia literature is conflicting. Pediatric patients have some unique risks for pulmonary aspiration (Table 158-1) compared with adults (Table 158-2). Although the critical pH and volume of gastric contents that place a child at risk for aspiration are unknown, based

Transient pharyngeal weakness of the newborn Tracheoesophageal fistula (gastrointestinal reflux common after repair) Chronic pulmonary disease (asthma, croup, bronchopulmonary dysplasia, cystic fibrosis) Prematurity Cerebral palsy, developmental delay (swallowing dysfunction) Acute gastric distention in pediatric trauma patients

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PEDIATRICS & NEONATOLOGY

Risk Assessment

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Table 158–2

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Risk Factors for Pulmonary Aspiration in Adults and Children

ASA physical status III or IV Surgery outside regular working hours* Emergency surgery* Obesity, ascites, large abdominal mass Gastritis, history of ulcers Autonomic neuropathy (familial, acquired) Muscular disorders Long-lasting general anesthetics Vocal cord paralysis Diabetes mellitus Electrolyte, metabolic imbalance Insufficient anesthetic depth Airway difficulty Preexisting gastroesophageal reflux disease Esophageal and upper abdominal surgery Elevated intracranial pressure Degenerative neuropathies Opioids, methylxanthines, β-agonists Reduced level of consciousness Laryngeal malfunction or spasm Collagen vascular disease Renal, pelvic, bladder, or uterine distention *Increases risk by five- to sixfold. ASA, American Society of Anesthesiologists.

the larynx. Consequently, children at high risk for aspiration should have their airways secured with endotracheal tubes. Laryngeal competence, an important protective mechanism against pulmonary aspiration, is depressed by anesthetic induction agents, local anesthesia of the larynx and trachea, and greater than 50% concentrations of nitrous oxide. In adults, laryngeal competence is depressed for 2 to 8 hours after tracheal extubation, even in patients who appear alert. It is likely that a similar depression of laryngeal competence occurs in children. Depressed laryngeal competence is attributed to the mechanical effects of tracheal intubation and is distinct from residual anesthetic effects.

Implications The occurrence and severity of pneumonitis depend more on gastric pH than on volume. Low-volume aspirates with a pH less than 1.8 result in severe pneumonitis, whereas volumes as high as 2 mL/kg with a pH greater than 2.5 produce minimal pulmonary damage. Pulmonary aspiration leads to loss of the protective mucosal barrier of the trachea and major bronchi by causing edema and desquamation of epithelium. Damaged tissue is vulnerable to subsequent viral or bacterial infection. Highly acidic liquid aspirates produce pulmonary injury within 12 to 18 seconds and extensive atelectasis by 3 minutes. By 1 hour after pulmonary aspiration, pulmonary injury has progressed to bronchial epithelial degeneration, pulmonary edema, and hemorrhage. The consequent increased pulmonary capillary leak is followed by a neutrophil response. As a result of alveolar cell damage, fluid and protein move into the alveoli and interstitium and reduce pulmonary surfactant activity. Increased airway resistance and decreased pulmonary compliance due to reduced pulmonary surfactant activity lead to

severe hypoxia. Also, severe hypotension may occur due to a reduction in intravascular volume (from the transudation of fluid into the alveoli), along with impaired venous return caused by the high airway pressures required for adequate ventilation. With particulate aspiration, hypoxemia occurs earlier and is more severe. Although fluid shifts are less extensive than with acidic liquid aspiration, there is a greater increase in arterial carbon dioxide tension and a greater decrease in arterial pH. Mortality with clinically significant pulmonary aspiration is 5% or less.

MANAGEMENT Treatment includes immediate suctioning of the airway and administration of supplemental oxygen by nasal cannula or facemask. This is often sufficient, but tracheal intubation and mechanical ventilation may be required in severe cases. Bronchopulmonary lavage is not recommended for acidic aspirates because damage to the lungs occurs within 12 to 18 seconds. In addition, more extensive pulmonary damage may occur due to the spread of acidic aspirates to lower regions of the lung. An immediate danger of particulate aspiration is mechanical obstruction. Bronchoscopy to remove particulate material should be performed in this situation. Corticosteroids have not been shown to reduce morbidity or mortality after pulmonary aspiration and are not advised, because they can predispose the patient to gram-negative pneumonia. Antibiotics should be administered according to the results of cultures of tracheal aspirates. Empirical use is reserved for patients who have aspirated grossly contaminated material (e.g., feces, pus). Leukocytosis, pulmonary infiltrates, thick sputum, and fever are all nonspecific responses to chemical pneumonitis and are not sufficient reasons to institute antibiotic therapy. Postural drainage and respiratory therapy with bronchodilators may be useful. Most patients have resolution of clinical symptoms within 2 weeks.

PREVENTION Prevention and amelioration of pulmonary aspiration rely on the use of conventional antacids and drugs that promote gastric emptying and increase lower esophageal sphincter tone (prokinetic agents), reduce gastric volume (H2-blockers), or increase the pH of the gastric contents (H2-blockers, proton pump inhibitors). Doses, schedules, and principal actions of these agents are summarized in Table 158-3. There are well-defined fasting guidelines for healthy children undergoing surgery or procedures requiring anesthesia (Table 158-4). There are no published fasting guidelines for children considered to be at increased risk for pulmonary aspiration. Removal of gastric contents before induction is recommended for these patients. If gastric suctioning is not possible preoperatively, the gastric contents should be suctioned immediately after the airway has been secured after rapid-sequence induction to reduce the risk of pulmonary aspiration during emergence from anesthesia and extubation.

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Table 158–3

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Pharmacologic Agents Used for the Prophylaxis of Pulmonary Aspiration

Drug

Dose and Schedule

GV

pH LEST

2 tbsp/30 mL water (1 hr BS) 0.5-1 mL/kg (30 mL max; 1 hr BS)

↑

↑

0

↑

↑

0

7.5-10 μg/kg (1 hr BS)

?

?

0

7.5 mg/kg (PM/AM) 0.5 mg/kg (PM/AM) 1.5-2 mg/kg (1-2 hr BS)

↓ ↓ 0

↑ ↑ ↑

0 0 0

0.1 mg/kg IV or PO (1 hr BS)

↓

0

↑

1.5 mg/kg (PM/AM) 0.3 mg/kg (PM/AM) 1.4 mg/kg QID

↓ ↓ ↓

↑ ↑ ↑

0 0 0

Antacids Alka-Seltzer Sodium citrate

Anticholinergics Glycopyrrolate

H2 Blockers Cimetidine Famotidine Ranitidine

Prokinetic Agents Metoclopramide

Proton Pump Inhibitors Lansoprazole Omeprazole Pantoprazole

BS, before surgery; GV, gastric volume; LEST, lower esophageal sphincter tone; PM/AM, night before and morning of surgery.

To prevent regurgitation, rapid-sequence induction is used to minimize the vulnerable period between loss of consciousness and securing of the airway. Cricoid pressure is an integral part of rapid-sequence induction. Cricoid pressure, with or without the presence of a nasogastric tube, is an effective means of preventing passive regurgitation of gastric fluids in infants, children, and adults. Cricoid pressure with a force of 20 newtons (equivalent to a 2-kg mass acted on by the force of gravity) must be applied before the loss of consciousness. This amount of pressure is uncomfortable for awake patients. Loss of upper esophageal barrier pressure occurs before loss of consciousness in all age groups after the intravenous induction of anesthesia. The force of cricoid

Table 158–4

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pressure should be increased to 40 newtons (which is painful for awake patients) with unconsciousness. Higher pressures may distort or occlude the trachea. Cricoid pressure during active vomiting has the potential to cause esophageal rupture. Most episodes of aspiration during induction begin with coughing or gagging during airway manipulation as a result of inadequate anesthesia or the absence of muscle relaxation. Ensuring complete muscle relaxation before laryngoscopy reduces the likelihood of regurgitation. The use of cuffed endotracheal tubes in children during prolonged intubation (e.g., intensive care unit patients) has led to a reduction in the incidence of silent aspiration from passive regurgitation. In patients at high risk for pulmonary aspiration, extubation should be performed only when the patient is fully awake and has full return of neuromuscular function. Children should demonstrate mouth opening, hip flexion, and return of the sucking, cough, and gag reflexes. Patients should be in the lateral, 10- to 15-degree head-down (Trendelenburg) position so that any secretions or regurgitant material can accumulate in the cheek and drain passively. Finally, the application of 15 to 20 cm H2O positive endexpiratory pressure immediately before extubation induces a reflex cough, which pushes secretions or materials away from the larynx.

Further Reading Borland LM, Woelfel SK, Saitz EW, et al: Pulmonary aspiration in pediatric patients under general anesthesia: Frequency and outcome. Anesthesiology 83:A1150, 1995. Coté CJ, Goudsouzian NG, Liu LMP, et al: Assessment of risk factors related to the acid aspiration syndrome in pediatric patients: Gastric pH and residual volume. Anesthesiology 56:70-72, 1982. Goudsouzian N: Aspiration in children: Practical implications. Anesthesiol Rev 11:6-16, 1984. James CF: Pulmonary aspiration of gastric contents. In Gravenstein N, Kirby RR (eds): Complications in Anesthesiology. Philadelphia, Lippincott-Raven, 1996, pp 175-190. Orenstein DM: Aspiration pneumonias and gastroesophageal reflux-related respiratory disease. In Behrman RE, Kliegman RM, Arvin AM (eds): Nelson’s Textbook of Pediatrics. Philadelphia, WB Saunders, 1996, pp 1213-1217. Salem MR, Wong AY, Fizzotti GF, et al: Efficacy of cricoid pressure in preventing aspiration of gastric contents in paediatric patients. Br J Anaesth 44:401-404, 1972. Warner MA, Warner ME, Warner DO, et al: Perioperative pulmonary aspiration in infants and children. Anesthesiology 90:66-71, 1999.

Fasting Guidelines for Healthy Children Undergoing Elective Procedures Solids

0-6 mo 6 mo-2 yr >2 yr

6 hr 6 hr 6 hr (light meal)† 8 hr

Clear Liquids*

Formula

2 hr 2 hr 2 hr

6 hr 6 hr NA

2 hr

NA

*Some consider breast milk to be a clear liquid. † By American Society of Anesthesiologists guidelines, a light meal typically consists of toast and clear liquids. Meals that include fried or fatty foods or meat may prolong gastric emptying time. Both the amount and type of foods ingested must be considered when determining an appropriate fasting period. NA, not applicable.

PEDIATRICS & NEONATOLOGY

Age

>2 yr (chubby or obese)

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Senthilkumar Sadhasivam and Mehernoor F. Watcha Case Synopsis A 14-year-old, postpubertal girl with a history of motion sickness is scheduled for adenotonsillectomy. This will be her third surgery under general anesthesia. She had multiple episodes of postoperative nausea and vomiting (PONV) after the two previous procedures (dental rehabilitation, correction of strabismus), despite receiving intraoperative, prophylactic antiemetic therapy. Following the strabismus surgery, she was hospitalized with dehydration caused by refractory postoperative emesis. Both she and her parents are extremely anxious and wish to avoid a similar experience. They ask what can be done to prevent PONV.

PROBLEM ANALYSIS Definition Nausea, vomiting, and retching are common postanesthetic complications that may be considered relatively minor by some physicians. Patients, however, report that these sequelae are sometimes more debilitating than the surgery itself and the postoperative pain.

Implications Severe PONV causes patient discomfort and dissatisfaction and may also be associated with the following: ● ● ● ● ● ●

Recognition The overall incidence of PONV in many large pediatric studies is about 10% in the postanesthesia care unit (PACU) and 20% to 30% within the first 24 hours. However, rates of 40% to 80% have been reported in some high-risk groups. Recurrent emesis occurs in 0.1% of patients, and unanticipated hospital admission is required in 0.03% (1 in 3000).

Risk Assessment Patient-, anesthesia-, and surgery-related risk factors for PONV have been identified in adults and children (Table 159-1). However, the accuracy of proposed scoring systems for predicting which patients will develop PONV is 70% at best. The most important factors are patient gender, a history of prior PONV, nonsmoking status,1 and opioid use. Some patient- and surgery-related factors are beyond the anesthesiologist’s control. However, some strategies can be used to reduce the baseline risk (Table 159-2). Foremost among these are restricted use of perioperative opioids, infiltration of the surgical wound with local anesthetics, use of nonsteroidal anti-inflammatory drugs and acetaminophen, avoidance of nitrous oxide (N2O) and high-dose neostigmine, and adequate hydration. Use of high concentrations of oxygen during the perioperative period helps reduce PONV in some but not all patient populations. 1 This raises the question why nicotine patches are not used for the prevention of PONV.

644

●

● ●

Tension on suture lines Wound dehiscence and surgical bleeding Muscle fatigue and pulmonary aspiration of gastric contents Dehydration and electrolyte imbalance Increased intracranial and intraocular pressures Prolonged PACU stays Unanticipated hospital admission following ambulatory surgery Increased costs of anesthesia care Increased use of health care personnel and hospital resources

Although no anesthetics or other substances are known to act directly on the emetic center (located in the lateral reticular formation of the brainstem), it does receive stimuli from the pharynx, gastrointestinal tract, mediastinum, and afferent nerves from higher brain centers (Fig. 159-1), including the cortical visual center and the chemoreceptor trigger zone in the area postrema, as well as input from the vestibular portion of the eighth cranial nerve. There is no blood-brain barrier in the chemoreceptor trigger zone. Therefore, chemicals, drugs, and other substances found in the cerebrospinal fluid or blood can activate it. The chemoreceptor trigger zone is rich in dopamine, serotonin (5-hydroxytryptamine3 [5-HT3]), opioid, histamine, and muscarinic receptors. Blockade of these may be an important mechanism of action for antiemetics. Finally, there is also evidence that neurokinin-1 receptors are involved in the final common pathway of the emetic response.

MANAGEMENT There are far fewer studies on the management of PONV in the PACU than on its prevention (see later). The choice of drugs to treat PONV depends on which prophylactic antiemetics were used (Table 159-3). In general, patients should not

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Table 159–1

■

Risk Factors for Postoperative Nausea and Vomiting

■

Postoperative Nausea and Vomiting

Table 159–2

■

645

Strategies to Reduce Baseline Risk for Postoperative Nausea and Vomiting

Adult Patients Patient-specific risk factors Female sex* Nonsmoking status* History of PONV* History of motion sickness* Delayed gastric emptying Preoperative anxiety Anesthetic and PACU risk factors Volatile anesthetics Nitrous oxide Intraoperative and postoperative opioids* Neostigmine Preanesthetic medication Gastric distention Duration of anesthesia Mandatory fluids by mouth before discharge Surgical risk factors Longer duration of surgery High-risk surgery Laparoscopy Ear, nose, or throat surgery Neurosurgery Laparotomy Breast, strabismus, or plastic surgery

Pediatric Patients Vomiting incidence twice that of adults Risk increases as children age; decreases after puberty Sex differences not applicable before puberty Risk increases with specific pediatric procedures Adenotonsillectomy Strabismus repair Hernia repair Orchiopexy Penile surgery

Use regional anesthesia whenever feasible Use propofol for induction and maintenance of general anesthesia Use intraoperative supplemental oxygen Ensure adequate patient hydration Avoid use of nitrous oxide Avoid use of volatile inhalational anesthetics Minimize use of intra- and postoperative opioids Minimize use of neostigmine Modified from Gan TJ, Meyer T, Apfel CC, et al: Department of Anesthesiology DUMC: Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 97:62-71, 2003.

for reducing PONV versus placebo. However, the magnitude of effect is inconsistent, and many studies can be criticized for being underpowered or failing to standardize the perioperative regimen. Systematic reviews show that no single drug has sufficient efficacy to be considered a gold standard for PONV prevention. The relatively poor efficacy of antiemetics for preventing PONV has cast doubt on the benefit of using them prophylactically. With no adequately powered trials to resolve this controversy, a multidisciplinary panel examined the available literature to provide consensus guidelines for PONV management. The panel focused on identifying primary PONV risk factors in adults and children; determined how to reduce the baseline risks for PONV; and then made recommendations regarding the optimal choice, timing, and efficacy of mono- or combined

*Major risk factor. PACU, postanesthesia care unit. Modified from Gan TJ, Meyer T, Apfel CC, et al: Department of Anesthesiology DUMC: Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 97:62-71, 2003.

PEDIATRICS & NEONATOLOGY

receive a repeat dose of the same drug used for prophylaxis; they should receive one that acts at a different receptor site. In patients who were perceived to be at low risk and did not receive any prophylactic antiemetics, a low dose of a 5-HT3 antagonist (e.g., ondansetron 1 mg) can provide excellent control of symptoms for up to 24 hours. Data suggest that a second dose of a 5-HT3 antagonist for PONV in patients who failed prophylaxis is no more effective than placebo; however, the PONV consensus guidelines (discussed later) do allow a second dose of ondansetron to be given at least 6 hours after a prophylactic dose. A second dose of dexamethasone or transdermal scopolamine should not be given to patients who failed prophylaxis with these drugs. Figure 159-2 presents an algorithm for the prophylaxis and management of PONV.

PREVENTION Consensus Guidelines The literature is filled with numerous reports claiming that a particular intervention has statistically significant efficacy

Figure 159–1 ■ Physiology of emesis. Solid arrows represent afferent input; shaded arrow points to efferent targets. CTZ, chemoreceptor trigger zone.

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Drugs Used as Prophylaxis for Postoperative Nausea and Vomiting in Children

Class/Drug

Preferred Time of Administration

Dose (Route)

Relative Efficacy

Common Adverse Effects

Anticholinergic 1–1.5 mg q72h (transdermal patch)

Previous night

++

Sedation, dry mouth, visual disturbances, dysphoria, hallucinations

Dimenhydrinate

0.5 mg/kg (IV)

15-20 min before end of surgery

+++

Diphenhydramine

0.5 mg/kg (IV)

15-20 min before end of surgery

++++

Less sedation, extrapyramidal effects, dry mouth and restlessness (anticholinergic side effects) More sedation, extrapyramidal effects, dry mouth and restlessness (anticholinergic side effects)

0.15 mg/kg, but ≤10 mg total (IV)

Induction of anesthesia

+++

Cutaneous flushing, perineal itching

++++

Drowsiness, sedation, extrapyramidal effects

++

Sedation, extrapyramidal effects

++++

Extrapyramidal effects, sedation (< promethazine) Sedation (> perphenazine), extrapyramidal effects

Scopolamine

Antihistamines

Corticosteroid Dexamethasone

Dopamine Antagonists Metoclopramide

50–75 μg/kg up to 1.25 mg (IV) 0.1–0.25 mg/kg (IV)

Perphenazine

70 μg/kg (IV)

15-20 min before end of surgery Data unavailable

Promethazine

0.5–1 mg/kg (IV/IM)

Data unavailable

++++

350 μg/kg up to 12.5 mg (IV) 0.04 mg/kg (IV)

15-20 min before end of surgery 15-20 min before end of surgery 15-20 min before end of surgery

++++

Headache, dizziness

++++

Headache, abdominal pain, constipation, dizziness Headache, abdominal pain, constipation, dizziness

Droperidol

5-Hydroxytryptamine3 Receptor Antagonists Dolasetron Granisetron

50–100 μg/kg up to 4 mg (IV)

Ondansetron

++++

Evaluate risk of POV and its medical sequelae for individual patient

Low risk of POV Low risk of medical sequelae

NO prophylaxis Reduce baseline risk*

Low risk of POV High risk of medical sequelae

Reduce baseline risk* + prophylaxis with 5-HT3 antagonist

Rescue using 5-HT3 antagonist

Moderate risk of POV Any risk of medical sequelae

Reduce baseline risk* + prophylaxis with 5-HT3 antagonist + steroid

Rescue using different class antiemetic Phenothiazine or Antihistamine or Metoclopramide

High risk of POV Any risk of medical sequelae

Reduce baseline risk* + prophylaxis with 5-HT3 antagonist + steroid + propofol TIVA

Rescue using different class antiemetic Phenothiazine or Antihistamine or Metoclopramide

Rescue using different class antiemetic Phenothiazine or Antihistamine or Metoclopramide

Figure 159–2 ■ Algorithm for the prophylaxis and treatment of postoperative vomiting (POV) in children. *See Table 159-2; 5-HT3, 5-hydroxytryptamine3; TIVA, total intravenous anesthesia. (Modified from Gan TJ, Meyer T, Apfel CC, et al: Department of Anesthesiology DUMC: Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 97:62-71, 2003.)

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therapy for PONV prophylaxis and treatment in low-, moderate-, and high-risk patients (see Table 159-3). There was early consensus that low-risk patients should not receive prophylaxis and that those at high risk should receive multimodal prophylaxis. However, consensus could not be reached on the baseline risk that would qualify patients for these two categories.

Perioperative Prevention PREANESTHETIC SEDATION Opioid premedication (any route of administration) increases the risk for emesis. Benzodiazepine premedication may reduce this risk. INDUCTION Inhalation induction with diethyl ether and cyclopropane increases the incidence of PONV. The incidence is much lower with halothane, isoflurane, sevoflurane, or desflurane. Induction with ketamine or etomidate also increases the risk for PONV, whereas propofol reduces it. The latter’s effect is of short duration and is more pronounced when propofol is used for both induction and maintenance of anesthesia. Low-dose propofol infusions have been used for refractory PONV in the PACU, but the antiemetic action is short-lived, and the mechanism remains unknown. NITROUS OXIDE There is now good evidence (human volunteers) that N2O is associated with PONV. Although N2O omission appears to have no effect on early or late postoperative nausea, it does reduce early and late vomiting if the patient’s baseline risk is high. OPIOID AVOIDANCE The method of postoperative pain management has important implications for reducing the incidence of PONV, because both pain and opioids increase it. Even a single dose of morphine is associated with an increased risk for PONV. Regional nerve blocks, nonsteroidal anti-inflammatory drugs (e.g., ketorolac, high-dose acetaminophen), and local anesthetic wound infiltration reduce postoperative opioid analgesic requirements and PONV. NURSING PROTOCOLS

REVERSAL

OF

NEUROMUSCULAR BLOCKADE

Antagonism of residual neuromuscular blockade is often routine because of concerns about respiratory compromise.

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647

Anticholinesterase therapy (e.g., neostigmine) has gastrointestinal muscarinic actions that contribute to increased emesis; this effect is dose related (>2.5 mg of neostigmine). Giving atropine (rather than glycopyrrolate) with neostigmine or edrophonium reduces PONV. With the use of neuromuscular relaxants such as mivacurium, routine antagonism of neuromuscular blockade is avoided. However, avoidance of neostigmine after the use of intermediate-acting muscle relaxants (e.g., vecuronium, rocuronium, cisatracurium) can be associated with residual blockade in more than 70% of neuromuscular receptors, with the associated potential for respiratory compromise. PROPHYLACTIC ANTIEMETIC ADMINISTRATION Drugs used for PONV prophylaxis in children are listed in Table 159-3, along with their relative efficacy, dosages, preferred times and routes of administration, and adverse effects. Although ondansetron and other 5-HT3 antagonists are very effective against PONV, their high cost prohibits their use for routine prophylactic antiemetic therapy in many centers. Older drugs such as prochlorperazine, dimenhydrinate, and promethazine are similarly effective but have the potential for central nervous system side effects, such as drowsiness. In adults, low-dose droperidol (0.625 to 1.25 mg) is as effective as ondansetron 4 mg against PONV, and it does not cause excessive drowsiness. However, many no longer consider it to be a first-line prophylactic antiemetic owing to its potential to cause Q-Tc prolongation, torsades de pointes, and sudden death (see Chapter 81). The associated medicolegal implications after a “black box” warning by the U.S. Food and Drug Administration (2001) led many institutions to remove this clinically effective and cheap antiemetic from their formularies. Experts who examined the data on which the FDA based its advisory have raised major concerns about the justification of this warning. In patients at low risk for PONV, the use of prophylactic antiemetics is not cost-effective and exposes patients to the risk of adverse side effects for little or no benefit. For the few low-risk patients who do develop PONV, a low-dose 5-HT3 antagonist (e.g.,1 mg ondansetron) is effective. Patients at high and moderate risk for PONV should receive prophylactic antiemetic therapy, along with baseline risk-reduction strategies (see Table 159-2). For those at moderate risk for PONV, the optimal cost-effective approach differs for ambulatory patients and hospital inpatients. For the former, PONV prophylaxis with single or combined drugs is cost-effective. Evidence suggests that a 5-HT3 antagonist and a steroid provide excellent prophylaxis for the moderate- to high-risk group. Such combinations had been avoided until recently owing to concerns about enhanced adverse central nervous system effects (e.g., delayed emergence, drowsiness, extrapyramidal reactions). The ongoing debate on the relative merits of one antiemetic versus another may be irrelevant for patients at high risk for PONV. Data now suggest that combinations are more effective than any one antiemetic alone. In high-risk patients, a multimodal approach with double or even triple antiemetic combinations should be used. In one recent trial, multimodal prophylaxis resulted in a 98% complete response rate and a 0% incidence of vomiting before discharge.

PEDIATRICS & NEONATOLOGY

Nursing protocols are known to affect PONV. Frequent changes in position (e.g., from supine to sitting upright to walking) in children who have received opioids increase the likelihood of PONV. Thus, gentle handling and the avoidance of rapid positional changes are essential. In addition, the insistence that patients take fluids by mouth before being discharged from the day surgery center increases the likelihood of PONV. If children are permitted, but not required, to drink before discharge, the incidence of in-hospital emesis is reduced.

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CONCLUSIONS Based on our current knowledge about the factors affecting PONV, the following is a reasonable approach for the patient described in the case synopsis: ● ●

● ●

●

● ●

●

●

Preanesthetic anxiolysis with midazolam Total intravenous anesthesia with propofol (induction and maintenance) Avoidance of N2O and potent inhalational anesthetics Avoidance of neostigmine antagonism of nondepolarizing neuromuscular blockade No or minimal opioids; instead, use high-dose preoperative acetaminophen (40 mg/kg per rectum), local anesthetics, nonsteroidal anti-inflammatory drugs, and nerve blocks Avoidance of patient movement in the PACU Use of liberal perioperative intravenous fluids to replace fluid deficits, and discharge to home without insisting that the patient first drink fluids Administration of dexamethasone at the induction of anesthesia and ondansetron or another serotonin antagonist at the end of the adenotonsillectomy Early and aggressive treatment of PONV with an antiemetic from another class (e.g., antihistamine, phenothiazine)

Further Reading Apfel CC, Korttila K, Abdalla M, et al: An international multicenter protocol to assess the single and combined benefits of antiemetic interventions in a controlled clinical trial of a 2x2x2x2x2x2 factorial design (IMPACT). Control Clin Trials 24:736-751, 2003.

Apfel CC, Korttila K, Abdalla M, et al: A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 350:2441-2451, 2004. D’Errico C, Voepel-Lewis TD, Siewert M, et al: Prolonged recovery stay and unplanned admission of the pediatric surgical outpatient: An observational study. J Clin Anesth 10:482-487, 1998. Gan TJ, Meyer T, Apfel CC, et al: Department of Anesthesiology DUMC: Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 97:62-71, 2003. Gold BS, Kitz DS, Lecky JH, et al: Unanticipated admission to the hospital following ambulatory surgery. JAMA 262:3008-3010, 1989. Scuderi PE, James RL, Harris L, et al: Multimodal antiemetic management prevents early postoperative vomiting after outpatient laparoscopy. Anesth Analg 91:1408-1414, 2000. Tramer MR: A rational approach to the control of postoperative nausea and vomiting: Evidence from systematic reviews. Part I. Efficacy and harm of antiemetic interventions, and methodological issues. Acta Anaesthesiol Scand 45:4-13, 2001. Tramer MR: A rational approach to the control of postoperative nausea and vomiting: Evidence from systematic reviews. Part II. Recommendations for prevention and treatment, and research agenda. Acta Anaesthesiol Scand 45:14-19, 2001. Watcha MF: Postoperative nausea and emesis. Anesthesiol Clin North Am 20:709-722, 2002. Watcha MF, White PF: Postoperative nausea and vomiting: Its etiology, treatment, and prevention. Anesthesiology 77:162-184, 1992. White PF, Watcha MF: Postoperative nausea and vomiting: Prophylaxis versus treatment. Anesth Analg 89:1337-1339, 1999.

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Upper Respiratory Tract Infection Arjunan Ganesh, Susan C. Nicolson, and James M. Steven Case Synopsis A 4-year-old girl has a history of frequent upper respiratory infections (URIs). Following the resolution of symptoms from her most recent URI 10 days ago, she undergoes elective tonsillectomy and adenoidectomy. During induction of anesthesia with mask sevoflurane, laryngospasm occurs.

PROBLEM ANALYSIS

cancellation were severe URI, the presence of a lower respiratory tract infection, or bacterial infection.

Definition There is conflicting information regarding the outcome for children with active URIs who undergo anesthesia for elective surgical procedures. Some studies suggest that children with URIs are at increased risk for perioperative respiratory complications; others indicate that they have no increased risk (Table 160-1). Increased mortality has not been demonstrated in any controlled study. Study design flaws that prevent clinicians from drawing conclusions regarding the risk-benefit ratio of anesthetizing children with URIs include one of more of the following: ● ● ●

●

●

Mostly retrospective data acquisition Absence of well-defined criteria for URI Heterogeneous group of children with regard to age, type of surgery, and anesthetic technique Nonuniform definition and reporting of adverse patient occurrences Preselection bias

At least two of the following signs and symptoms must exist for a child to have a URI: 1. 2. 3. 4. 5. 6. 7.

Sore or scratchy throat Sneezing Rhinorrhea Congestion Nonproductive cough Fever less than 38.5°C Laryngitis

Combination of items 1 and 5, 2 and 3, 3 and 6, and 4 and 6 require the presence of at least one additional symptom to meet the criteria for a URI. Children with fever greater than 38.5°C and constitutional symptoms or signs of lower respiratory tract involvement do not have a simple URI; their ailment extends beyond localized involvement within the upper respiratory tract.

Risk Assessment The following caveats apply to the risk of anesthesia and surgery in children with URIs: ●

●

●

●

●

Children suffer five to eight URIs per year, with higher incidences for those in day care and whose parents smoke. Of pediatric anesthesia and surgery candidates, 6% present with active URIs. Pulmonary changes may last 4 to 7 weeks after the resolution of URI symptoms. The phase of the URI (onset, active, resolution) may influence the anesthesia risk. The type of surgery, the child’s age, the anesthetic plan (e.g., intubation), and coexisting medical conditions can affect outcome. 649

PEDIATRICS & NEONATOLOGY

Retrospective data indicate that children with recent URIs (within 2 to 6 weeks of anesthesia and surgery) have an increased risk of respiratory complications compared with those without recent URIs. The clinical impact of upper airway or pulmonary complications (see Table 160-1) also influences the decision to cancel surgery or proceed with anesthesia. For example, is an increased incidence of laryngospasm likely to be associated with a poor outcome, or can it be recognized and reversed early enough to prevent such an outcome? A recent prospective study suggested that although children with acute or recent URIs have a greater risk of respiratory complications, most of them can undergo elective procedures without a significant increase in adverse anesthetic outcomes. However, this study was not randomized, and the decision whether to proceed was left to the discretion of the attending anesthesiologist. Common reasons for

Recognition

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Incidence of Upper Airway and Pulmonary Complications in Children with Upper Respiratory Infection Undergoing General Anesthesia URI Status (%)

Outcome Measure

Active

Recent

None

Airway obstruction* Laryngospasm Bronchospasm Croup Hypoxemia

1.6 1.3 13.3 3.8 32 40 20

5.3 2.4

1.6 1.2 0.6 0.7 10 16 0

25

Number 3585 489 402 22,159 130 402 50

Intubated Most None Half Some None Half Most

Study Design R P P P P P P

*Includes laryngospasm and bronchospasm. P, prospective; R, retrospective; URI, upper respiratory infection.

Implications Potential URI-related respiratory complications related to increased secretions or irritable airways are as follows: ●

● ● ●

Laryngospasm (additional risk factors include young age, surgery on or within the airway, and an inexperienced anesthetist) Bronchospasm (intubated patients only) Postextubation stridor Perioperative arterial oxygen desaturation

Factors that affect the cost of these complications include a prolonged day-surgery stay, unexpected admission of an outpatient, unexpected admission to an intensive care unit, and medicolegal issues raised by URI-related respiratory complications. Costs of cancellation include those related to the need for an additional presurgery appointment, repeated laboratory testing or chest radiographs (if necessary), lost revenue from inefficient operating room use with short-notice cancellation, inconvenience to patient and family, and lost income to family.

MANAGEMENT When evaluating the potential for URI-related complications, be aware that not all patients are the same. When making a decision whether to proceed with anesthesia and surgery, take the following into consideration: ● ●

●

● ● ●

●

Age of the child Frequency of URIs (both in the individual and in agematched controls) Nature and urgency of surgery (e.g., is the procedure intended to alleviate or reduce the frequency of chronic nasal congestion or recurrent ear infections?) Coexisting medical problems Anesthesiologist’s skill and experience Miscellaneous issues (e.g., availability of surgeon, designated or autologous blood) Attitude of parents

If a decision is made to proceed, document on the chart that the risks have been discussed with the surgeon and the

family and that everyone has agreed to proceed. Then formulate an anesthetic plan that gives consideration to the following: ●

● ●

●

Preoperative administration of an anticholinergic agent (e.g., atropine, ipratropium nebulization) Use of bronchodilators for bronchospasm Use of smaller endotracheal tubes, laryngeal mask airways, or mask anesthesia Monitoring for arterial oxygen saturation intra- and postoperatively, and administering oxygen-enriched gas mixtures or supplemental oxygen when appropriate

PREVENTION Many preschool and early school-age children have or are recovering from a URI at any given time. Thus, it is impossible to postpone surgery for all children with URIs until 4 to 6 weeks after resolution of their symptoms. Such a strategy would lead to many children having a very narrow window for surgical intervention, or even none at all. Sound clinical judgment, documented informed consent, and experience of the anesthesiologist are important factors in deciding whether to proceed with an individual case.

Further Reading Cohen MM, Cameron CB: Should you cancel the operation when a child has an upper respiratory tract infection? Anesth Analg 72:282-288, 1991. Coté CJ: The upper respiratory tract infection (URI) dilemma: Fear of a complication or litigation? Anesthesiology 95:283-285, 2001. Rolf N, Coté CJ: Frequency and severity of desaturation events during general anesthesia in children with and without upper respiratory infections. J Clin Anesth 4:200-203, 1992. Schreiner MS, O’Hara IB, Markakis DA, et al: Do children who experience laryngospasm have an increased risk of upper respiratory tract infection? Anesthesiology 85:475-489, 1996. Tait AR, Knight PR: The effects of general anesthesia on upper respiratory tract infection in children. Anesthesiology 67:930-935, 1987. Tait AR, Knight PR: Intraoperative respiratory complications in patients with upper respiratory tract infection. Can J Anaesth 34:300-303, 1987. Tait AR, Malviya S, Voepel-Lewis T, et al: Risk factors for perioperative adverse respiratory events in children with upper respiratory tract infections. Anesthesiology 95:299-306, 2001.

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Latex Allergy Lucille A. Mostello Case Synopsis A 16-year-old boy with cerebral palsy is undergoing lengthening of an Achilles tendon. He has had 15 previous operations without complications. Thirty minutes after anesthetic induction, there is sudden hypotension along with bronchospasm.

PROBLEM ANALYSIS Definition Latex allergy is an immediate (type I) hypersensitivity reaction to the milky sap of cultured rubber trees (Hevea brasiliensis). With type I reactions, antigen enters the body to promote the genesis of immunoglobulin E (IgE) antibodies, which attach to mast cells. With subsequent exposures, the antigen bridges two mast cell IgE antibodies to initiate a biphasic reaction. In phase 1, preformed substances from intracellular granules (mostly histamine) are released. In phase 2, potent arachidonic acid metabolites (leukotrienes, prostaglandins) are generated. These cytokines act as catalysts to involve other cells and to activate kinin and complement systems to cause bronchoconstriction, vasodilatation, increased vascular permeability, and mucosal edema. Latex is the organic raw material for natural rubber products. Its proteins and polypeptides, but not its polymer backbone (cis-1,4-polyisoprene), are antigens. Other untoward reactions are due to residual chemicals from the rubber manufacturing process. Both irritation and contact dermatitis (type IV, or cell-mediated delayed hypersensitivity) are localized, uncomfortable, and deforming but not life threatening. They should not be confused with type I hypersensitivity to latex proteins (see also Chapters 27 and 53).

Recognition The manifestations of anaphylaxis under anesthesia include the following: ● ● ● ●

Hypotension or cardiovascular collapse (74% of cases) Bronchospasm or wheezing (44% of cases) Rash or urticaria (70% of cases) Angioedema and stridor (a small percentage of cases)

Risk Assessment Several subsets of children have higher sensitization rates than in the general population (estimated at 1%). Children at risk include those with the following: ● ●

●

●

Spina bifida (15% to 67% sensitization) Multiple surgeries, especially operations during infancy (25% to 55% sensitization) Urogenital malformations, particularly bladder exstrophy (70% sensitization) Fruit allergy (e.g., banana, kiwi, avocado, chestnut), atopy, or multiple allergies

Occupational exposure is the predominant risk factor in adults. For children with spina bifida (many of whom survive to adulthood), the high prevalence of antibodies has been postulated to be due to repeated latex exposure during surgery, urinary catheterization, and fecal disimpaction. Children who have undergone multiple surgeries for congenital defects, especially in infancy, now account for a large proportion of recent cases of intraoperative latex anaphylaxis. Latex antibodies can cross-react with an increasing list of fruits that have antigens similar to latex proteins. The presence of atopy or multiple allergies in other high-risk patient groups may increase sensitization or may be an independent risk factor.

Implications In adults, the estimated mortality from perioperative anaphylaxis for all antigens is about 4%. The rate for children is unavailable but may be the same or less. If less, this could be due to immunologic immaturity or naiveté. Regardless, anaphylaxis is life threatening and may require interruption or postponement of surgery and intensive care for complete resolution. Preoperative identification of latex-allergic patients and latex avoidance can reduce morbidity rates.

MANAGEMENT The treatment of anaphylaxis is as follows. 651

PEDIATRICS & NEONATOLOGY

The quantity and route of antigen exposure, and an individual’s sensitivity, partly determine the spectrum of manifestations. A patient’s reaction may range from mild to severe and involve single or multiple organ systems. Unfortunately, in the operating room (OR), the first sign may be cardiovascular collapse because general anesthesia and surgical drapes obscure earlier indicators. The time from latex exposure to symptoms is unpredictable and can range from 5 to 150 minutes. Over the past 15 years, latex allergy has become an important issue for pediatric patients and their health care providers. In the late 1980s one hospital reported a 500-fold increase in intraoperative anaphylaxis among patients with

spina bifida. In the early 1990s surveys from France and Belgium found that latex was the predominant cause of anaphylaxis during pediatric surgery (Fig. 161-1), in striking contrast to adults. Today, anaphylaxis in spina bifida patients has been reduced markedly, but severe reactions still occur in other high-risk patient groups.

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Figure 161–1 ■ Graphic results of separate surveys on the causes of intraoperative anaphylaxis in children and adults conducted in France and Belgium between 1990 and 1992. They indicate that latex allergy is the most common cause of intraoperative anaphylaxis in children. (Pediatric data from Murat I: Anaphylactic reactions during paediatric anaesthesia: Results of a survey by the French Society of Paediatric Anaesthetists 1991-1992. Paediatr Anaesth 3:339-343, 1993. Adult data (1990-1991) from Laxenaire MC, Mouton C, MoneretVautrin DA, et al: Drugs and other agents involved in anaphylactic shock occurring during anaesthesia: A French multicenter epidemiological inquiry. Ann Fr Anesth Reanim 12:91-96, 1993.)

Primary ● ● ●

Removal of the antigen Intravenous (IV) epinephrine bolus (1 to 10 μg/kg) Rapid IV volume expansion with a balanced salt solution (25 to 50 mL/kg)

Secondary ● ●

●

●

Epinephrine infusion (0.05 to 0.1 μg/kg per minute) Inhaled β-adrenergic receptor agonist (e.g., 0.15 mg/kg albuterol) IV diphenhydramine 0.5 to 1 mg/kg slowly plus IV ranitidine 1 mg/kg slowly Corticosteroids (e.g., IV hydrocortisone 5 to 10 mg/kg)

Because latex is ubiquitous in OR settings, it is very difficult to remove all sources of the antigen. In addition to obvious latex sources such as gloves and Foley catheters, the anesthesiologist must be concerned about latex in IV administration sets, drug vial stoppers, syringe plungers, facemasks, and adhesive tape. Unseen is the aerosolized cornstarch that carries adsorbed latex antigens from powdered gloves in the OR and on the clothes of OR personnel. The first line of therapy is IV epinephrine for vasoconstriction and specific reduction in the degranulation process. This is followed by massive IV fluid replacement. Higher epinephrine doses are needed if cardiovascular collapse has occurred. Additional pharmacologic therapy for bronchospasm and maintenance of vital organ perfusion is instituted secondarily. The role of antihistamines and corticosteroids has not been well documented. To confirm the diagnosis: ●

●

●

Send clotted blood for analysis to determine the serum tryptase level. Request consultation with a pediatric allergist or immunologist. Schedule antibody testing (immune globulins) 4 to 6 weeks after the event.

Serum tryptase is an excellent and stable marker of anaphylaxis and remains elevated for 1 to 4 hours following mast cell degranulation. Follow-up and testing are best managed by an allergist. Unfortunately, blood tests, such as the radioallergosorbent test, are not 100% sensitive. Currently, no standardized reagent for latex skin testing is commercially available in the United States. Because an anaphylactic episode can exhaust antibody stores, any testing should be delayed for 4 to 6 weeks. Even with latex antibodies, a complete evaluation is warranted because there may be concurrent allergies to other agents used intraoperatively.

PREVENTION Crucial to identifying patients at increased risk for latexrelated anaphylaxis is the screening of high-risk patients or subgroups. Ask every patient or parent about responses to latex products: ●

●

●

Is there swelling or itching of the hands or other body parts after contact with rubber gloves, toys, or other rubber products? Is there swelling or itching of the lips or mouth after inflating balloons or dental examinations? Has a previous, unexplained anaphylactic reaction occurred?

Preoperative latex testing is reserved for patients who respond in the affirmative to any of these questions or are otherwise considered to be at high risk. In addition, take the following steps to avoid latex-related reactions: ●

●

●

Develop latex-avoidance protocols for high-risk patients (e.g., use latex-free or low-protein latex gloves rather than powdered latex gloves for surgery in infants). Ensure that latex-allergic patients wear Medic-Alert bracelets and that they have autoinjectable epinephrine available at home and at school. Keep parents and patients informed about latex exposure.

Because desensitization therapy is experimental at this time, avoidance is the most effective prevention. The incidence

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of anaphylaxis in the OR has been reduced by protocols for latex avoidance in spina bifida patients. However, providing a latex-safe environment (“latex precautions”) is challenging, because the material is ubiquitous. It is an intimidating and sometimes impossible task to identify all latex-containing products, to substitute nonlatex items for those that contain latex, and to eliminate exposure to aerosolized latex or similar antigens. Technical advice is available from the support divisions of OR equipment and supply manufacturers. The U.S. Food and Drug Administration imposed labeling regulations in the fall of 1998, requiring all new medical equipment to denote its latex content. Both parents and physicians can obtain useful information about latex content and possible substitutions of medical and nonmedical items from the Spina Bifida Association (1-800621-3141) and on-line (http://latexallergylinks.tripod.com). Prophylactic premedication remains controversial because severe latex reactions have occurred despite its use. Some clinicians believe that a regimen of drugs known to attenuate reactions to radiocontrast media may reduce the severity of latex reactions, especially in patients at very high risk who are undergoing critical surgical procedures. A protocol combining antihistamines (both H1- and H2-blockers) and corticosteroids is begun the day before anesthesia and surgery and continued on the first postoperative day. The drugs used and the timing of their administration vary among institutions. However, in an emergency, a single dose of each of these drugs can be given 1 hour before surgery. Some continue the regimen for 12 hours after the procedure. Again, a pediatric allergist or immunologist should be consulted. Many institutions have protocols to prevent sensitization in children with spina bifida. From birth, no latex-containing

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Latex Allergy

653

items are used in the care of these patients. Whether other groups of children destined to undergo multiple surgeries, especially during infancy, should avoid latex-containing materials at home and in the hospital requires further evaluation. Some institutions now choose to be “latex-free” for the benefit of all patients and hospital personnel.

Further Reading Hepner DL, Castells MC: Latex allergy: An update. Anesth Analg 96: 1219-1229, 2003. Hollnberger H, Gruber E, Frank B: Severe anaphylactic shock without exanthema in a case of unknown latex allergy and review of the literature. Paediatr Anaesth 12:544-551, 2002. Holzman RS: Latex allergy: An emerging operating room problem. Anesth Analg 76:635-641, 1993. Hourihane JO, Allard JM, Wade AM, et al: Impact of repeated surgical procedures on the incidence and prevalence of latex allergy: A prospective study of 1263 children. J Pediatr 140:479-482, 2002. Kwittken PL, Sweinberg SK, Campbell DE, et al: Latex hypersensitivity in children: Clinical presentation and detection of latex-specific immunoglobulin E. Pediatrics 95:693-699, 1995. Landwehr LP, Boguniewicz M: Current perspectives on latex allergy. J Pediatr 128:305-312, 1996. Murat I: Anaphylactic reactions during paediatric anaesthesia: Results of the survey of the French Society of Paediatric Anaesthetists 1991-1992. Paediatr Anaesth 3:339-343, 1993. Murat I: Latex allergy: Where are we? Paediatr Anaesth 10:577-579, 2000. Poley GE, Slater JE: Latex allergy. J Allergy Clin Immunol 105:1054-1062, 2000. Sussman GL, Betschel SD, Beezhold DH: Latex allergy. In Leung DY, et al (eds): Pediatric Allergy, Principles and Practice. St. Louis, Mosby, 2003, pp 624-663. Tosi LL, Slater JE, Shaer CS, et al: Latex allergy in spina bifida patients: Prevalence and surgical implications. J Pediatr Orthop 13:709-712, 1993.

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Malignant Hyperthermia Karen M. Van Tassel and Scott R. Schulman

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Case Synopsis A healthy 12-year-old boy presents for reduction of a humerus fracture. Anesthesia is induced with sevoflurane. Fifteen minutes later, there is an abrupt increase in end-tidal carbon dioxide to greater than 70 mm Hg. He becomes tachycardic, with a heart rate of 150 beats per minute, and his temperature increases from 36.7°C to 39.4°C.

PROBLEM ANALYSIS Definition Malignant hyperthermia (MH) is a rare but potentially fatal subclinical myopathy. MH remains latent until susceptible individuals are exposed to triggering anesthetic agents, such as volatile inhalational anesthetics and succinylcholine. MH is characterized by an increase in myoplasmic calcium ions (Ca2+). Presenting signs include increased metabolism, muscle rigidity, and fever. Similarities were noted between human MH and the porcine stress syndrome, which occurs in one breed of pigs. Upon exposure to stress, including transport, fighting, vaccination, or preparation for slaughter, this breed experienced increased metabolism, acidosis, fever, and death. In 1966 Hall reported that succinylcholine and halothane induced MH in these pigs. They soon became the animal model for the disease. Subsequently, the genetic mutation responsible for porcine stress syndrome was found to be a single point mutation on chromosome 6, which entirely accounted for this homogeneous disease. Human MH, however, is a disease of significant genetic heterogeneity. Many different genetic abnormalities and predisposing conditions lead to a similar final pathway. Human MH is further complicated by incomplete penetrance and widely variable expression. The pathophysiology of MH lies in disordered excitationcontraction coupling in skeletal muscle. In normal muscle, an action potential is propagated along the sarcolemma and down the T tubule, leading to Ca2+ release from the sarcoplasmic reticulum. Ca2+ then binds troponin, exposing active actin binding sites, which leads to muscle contraction. This process is terminated by the active transport of Ca2+ back into the sarcoplasmic reticulum. The sarcoplasmic reticulum is the intracellular organelle responsible for Ca2+ regulation. As propagated action potentials cause voltage changes in the T tubule, a conformational change occurs in the α subunit of the dihydropyridine receptor. This activates the ryanodine receptor (RYR1). This activation leads to the opening of RYR1, causing Ca2+ efflux and muscle contraction. In MH, a defect in Ca2+ release is expressed upon exposure to a triggering agent. This defect results in a prolonged opening of RYR1 and enhanced Ca2+ efflux into the myoplasm, leading to prolonged interaction of actin and myosin (contracture) and increased muscle metabolism. Two known sites for this defect are the RYR1 and dihydropyridine receptors. 654

Recognition Understanding the underlying pathophysiology of MH leads to an appreciation of its clinical manifestations (Table 162-1). The increased muscle metabolism is initially aerobic, resulting in increased oxygen consumption, hypercarbia, respiratory acidosis, and heat production. As adenosine triphosphate (ATP) is depleted, metabolism becomes anaerobic, resulting in lactic acid production, metabolic acidosis, and further heat production. In the presence of hyperthermia, acidosis, and ATP depletion, the cell loses the ability to maintain the integrity of its membrane. Rhabdomyolysis leads to the release of potassium, myoglobin, and creatine kinase. Hypercarbia is the earliest and most sensitive sign of MH; generalized muscle rigidity is the most specific sign. Prompt diagnosis and treatment of MH are imperative and may avoid its associated complications (Table 162-2). However, other disease states must be considered in the differential diagnosis of MH (Table 162-3).

Risk Assessment Although precise estimates are difficult owing to the rarity of human MH, the incidence is thought to be 1 in 15,000 in children and 1 in 50,000 in adults. Determining a patient’s risk for MH includes careful questioning during the preoperative interview. A personal or family history of MH during a previous anesthetic should raise concerns. Further, a family history of unexpected intraoperative death or cardiac arrest should increase the suspicion for MH.

Table 162–1

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Clinical Manifestations of Malignant Hyperthermia

Early Tachycardia Tachypnea Muscle rigidity Arrhythmias Hypercarbia

Late Increased temperature Skin mottling Myoglobinuria Hyperkalemia Elevated creatine kinase Mixed acidosis

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Table 162–2

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Complications of Malignant Hyperthermia

Coagulopathy/disesminated intravascular coagulation Acute renal failure Hepatic dysfunction Severe muscle pain Weakness Arrhythmias Pulmonary edema Congestive heart failure Acute respiratory distress syndrome Seizures Coma Death

Although there are numerous case reports of patients with different diseases experiencing episodes of MH, the only diseases that are consistently associated with MH are central core disease, King-Denborough syndrome, and Duchenne’s muscular dystrophy. The current diagnostic test for confirming MH is the in vitro contracture test (IVCT), also known as the caffeine halothane contracture test. Although this test was developed in the 1970s, it remains the gold standard and has 97% sensitivity. The muscle biopsy must be performed at one of six designated IVCT centers, because the laboratory testing must be performed on freshly harvested tissue. Although the biopsy is performed on an outpatient basis, the dwindling number of testing sites in the United States may be an obstacle for some patients who need to have this test. For the IVCT, 2 g of muscle is harvested from the vastus lateralis or vastus medialis muscle and then longitudinally dissected into six strips. Small sutures are placed at both ends of the muscle, and the strips are placed into a tissue bath. One end is attached to a stationary hook, and the other to a force transducer. Halothane is added to the fresh gas flow via an in-line vaporizer in three of the baths, and caffeine is incrementally added to the other three baths. A patient is diagnosed with MH syndrome if a contracture or increase in the muscle’s baseline tension develops on exposure to these agents. Although the IVCT remains the gold standard for diagnosing MH, genetic testing may provide an alternative in the future. A significant international effort is now under way to clarify the molecular genetic basis of MH. Although multiple gene loci are involved, 50% of MH families can be linked to mutations in the RYR1 gene on chromosome 19.

■

Differential Diagnosis of Malignant Hyperthermia

Infection Sepsis Stimulant drugs Thyrotoxicosis Light anesthesia Neuroleptic malignant syndrome Pheochromocytoma Heatstroke

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More than 30 mutations have been described in this gene, along with two mutations in the α subunit of the dihydropyridine receptor gene. As new information on the genetic basis of MH is developed, genetic testing may provide the means for screening at-risk patients, avoiding the need for open muscle biopsy. Today, however, genetic testing is still only a research tool.

Implications MH is a grave and potentially fatal disease. Untreated, the mortality is as high as 70%. With the administration of dantrolene, however, this rate decreases to 4%. Thus, anesthesiologists have a critical role in diagnosing and appropriately treating MH patients to avoid its complications (see Table 162-2). As with any inherited disease, the diagnosis of MH carries implications for both the patient and his or her family members. The Malignant Hyperthermia Association of the United States (MHAUS) can be an invaluable resource for patients and physicians. Established in 1981, its goal is to provide information about MH to patients and health care providers and to help individuals cope with the diagnosis and reduce its associated morbidity and mortality. Its MH hotline (1-800-MH-HYPER) provides access to physician consultants 24 hours a day, 7 days a week. More information about the MHAUS can be found at www.mhaus.org. The North American Malignant Hyperthermia Registry, a division of the MHAUS, acquires and analyzes patientspecific clinical and laboratory data on MH. After diagnosing a suspected MH episode, a health care professional should report this information to the registry by completing an Adverse Metabolic Reaction to Anesthesia (AMRA) form. This information can then be relayed to future physicians caring for a registered patient. A recent topic of concern is the possibility of “awake triggering” of MH, occurring while a patient is not anesthetized or exposed to one of the known anesthetic triggers. Returning to the patient described in the case synopsis, the boy was diagnosed with MH intraoperatively, appropriately treated with dantrolene, and recovered uneventfully. Eight months later, however, he developed muscle weakness and stiffness after playing in a football game. His condition progressed to seizures and respiratory arrest. When paramedics arrived, the electrocardiogram showed sinus tachycardia, and intubation was unsuccessful secondary to jaw clenching. His temperature on arrival at the hospital was higher than 42.2°C, and he was successfully intubated. The patient developed ventricular fibrillation, and cardiopulmonary resuscitation was continued as he was treated for hyperkalemia and with dantrolene. Resuscitation was unsuccessful, and subsequent DNA studies identified an altered RYR1 sequence, consistent with the diagnosis of MH. It is known that hypermetabolic states can occur in individuals both with and without MH syndrome. Although rare, these episodes can be fatal. Health care professionals recommend that patients with MH syndrome limit their activity only if severe muscle cramps or symptoms suggestive of a hypermetabolic state develop. Although death due to awake triggering of MH may represent only a small percentage of patients presenting with heatstroke, MH

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Table 162–3

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should be considered in the differential diagnosis, and treatment with dantrolene may be indicated. Interestingly, mutations in the cardiac ryanodine receptor gene (RYR2) have been associated with sudden unexplained death in patients with catecholaminergic polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia type 2. RYR2 is the major Ca2+ release channel on the sarcoplasmic reticulum in cardiomyocytes, and mutations in RYR2 result in disordered Ca2+ regulation during exercise or stress-induced activation of the sympathetic nervous system. Thus, both RYR1 and RYR2 mutations cause disorders in Ca2+ metabolism in skeletal and cardiac muscle, respectively. Currently, no link between MH and sudden unexplained death has been established. However, further research may elucidate its pathophysiology.

MANAGEMENT Once the diagnosis of MH is made, the severity of the situation must be communicated to the surgical team, and additional help should be summoned to the operating room. Treatment includes the following: ● Discontinue triggering agents (any volatile inhalation anesthetic agent, succinylcholine). ● Hyperventilate with 100% oxygen. ● Administer dantrolene. ● Monitor arterial blood gases for pH, base excess, and serum potassium; check serial creatine kinase concentrations. ● Treat acidosis with sodium bicarbonate. ● Treat hyperkalemia with Ca2+, glucose, and insulin. ● Maintain diuresis with furosemide or mannitol. ● Institute core body cooling with ice packs, cold saline lavage of body cavities and the surgical site; consider cardiopulmonary bypass. ● Call the MH hotline (1-800-MH-HYPER). ● Complete an AMRA form. Dantrolene is a direct skeletal muscle relaxant that binds to the RYR1 receptor, thereby reducing its open-state probability and blocking Ca2+ release from the sarcoplasmic reticulum. It is administered as a 2.5 mg/kg intravenous bolus; this can be repeated every 5 minutes until the hypermetabolic state resolves, up to a maximum dose of 10 mg/kg. The maintenance dose of dantrolene is 1 mg/kg intravenously every 6 hours for 24 hours to prevent recurrence of the hypermetabolic state. For this reason, patients are monitored in the intensive care unit for at least 24 hours after an MH episode. If there is no change in the patient’s condition after giving large amounts of dantrolene, other diagnoses must be entertained (see Table 162-3). One possible drug interaction involves dantrolene and nondepolarizing muscle relaxants; dantrolene has been shown to potentiate neuromuscular blockade with vecuronium. Also, cardiovascular collapse has occurred in anesthetized swine when dantrolene and verapamil were administered simultaneously. Thus, calcium channel blockers are contraindicated.

Table 162–4

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Safe Drugs for Patients with Malignant Hyperthermia Syndrome

Benzodiazepines Opioids Propofol Ketamine Etomidate Local anesthetics Barbiturates Nitrous oxide Nondepolarizing muscle relaxants

PREVENTION When susceptible or high-risk patients present for surgery, the anesthesia team must make specific preparations. First, the anesthesia machine must be prepared with a new disposable circuit and new carbon dioxide absorbent. The vaporizers should be disabled, and the machine should be flushed with oxygen at 10 L/minute for 20 minutes. Although triggering agents should be avoided, there are many safe anesthetic medications that can be used in these patients (Table 162-4). Dantrolene prophylaxis is not recommended for these patients perioperatively. Postoperatively, patients should be monitored for a minimum of 4 hours with continuous electrocardiography, as well as temperature monitoring. If this recovery period is uneventful, it is safe to discharge patients to the floor or even home in the case of ambulatory surgery.

Further Reading Allen GC: Malignant hyperthermia susceptibility. Anesth Clin North Am 12:513-535, 1994. Hall LW, Woolf N, Bradley JW, Jolly DW: Unusual reaction to suxamethonium chloride. Br Med J 26:1305, 1966. Hall SC: General pediatric emergencies: Malignant hyperthermia syndrome. Anesth Clin North Am 19:367-381, 2001. Kaplan RF: Clinical controversies in malignant hyperthermia susceptibility. Anesth Clin North Am 12:537-549, 1994. Krause T, Gerbershagen MU, Fiege M, et al: Dantrolene: A review of its pharmacology, therapeutic use and new developments. Anaesthesia 59:364-373, 2004. Rosenbaum HK, Miller JD: Malignant hyperthermia and myotonic disorders. Anesth Clin North Am 20:623-664, 2002. Rosenberg H, Antognini JF, Muldoon S: Treatment for malignant hyperthermia. Anesthesiology 96:232-237, 2002. Sambuughin N, Holley H, Muldoon S, et al: Screening of the entire ryanodine receptor type 1 coding regions for sequence variants associated with malignant hyperthermia susceptibility in the North American population. Anesthesiology 102:515-521, 2005. Tobin JR, Jason DR, Challa VR, et al: Malignant hyperthermia and apparent heat stroke. JAMA 286:168-169, 2001. Wehrens XH, Marks AR: Sudden unexplained death caused by cardiac ryanodine receptor (RyR2) mutations. Mayo Clin Proc 79:1367-1371, 2004.

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163

Hypoglycemia and Hyperglycemia D. Ryan Cook Case Synopsis A healthy 4-year-old boy is scheduled for inguinal hernia repair. He has dinner at 5 PM the evening before surgery and has milk and cookies before going to bed at 9 PM. He is offered Jell-O water at 5:30 AM (2 hours before his scheduled surgery), which he refuses. Owing to a surgical emergency, the boy’s surgery is delayed 4 hours. Before induction of anesthesia, his vital signs are stable, but he is drowsy and somewhat fussy. His serum glucose concentration in the operating room after induction of anesthesia is 70 mg/dL.

PROBLEM ANALYSIS Definition Hypoglycemia is usually defined as a blood glucose concentration less than 55 mg/dL (3 mmol/L) in infants and older children and 35 mg/dL (2 mmol/L) in premature and term neonates. Normal values can be defined in several ways: (1) a statistical approach (such as that just stated; to convert mmol/L to mg/dL, simply multiply by 18); (2) a metabolic approach (the blood glucose concentration at which normal cell homeostasis is maintained); (3) a neurophysiologic approach (the blood glucose concentration at which impairment of neurologic function occurs); and (4) a neurodevelopmental approach (the relationship between chronic blood glucose concentrations and neurodevelopmental outcome). Hyperglycemia is usually defined as a blood glucose concentration greater than 200 mg/dL (11 mmol/L).

concentration might be viewed as a surrogate end point for inadequate analgesia. Hyperglycemia is not recognized clinically during anesthesia, except perhaps by the osmotic diuresis it may induce. A blood glucose determination is necessary to confirm any suspicion.

Risk Assessment The incidence of preoperative hypoglycemia in healthy infants and children who have fasted between 4 and 19 hours is quite low. Also, there appears to be no correlation between blood glucose concentration and the duration of fasting (hours) in this population. The risk of hypoglycemia has been virtually eliminated by allowing healthy children to ingest glucose-containing clear liquids up until 2 hours before the induction of anesthesia. The following patients, however, are at risk for preoperative hypoglycemia when fasting: ●

Recognition

●

HYPOGLYCEMIA

HYPERGLYCEMIA The stress response to surgery, and perhaps to anesthesia, may result in an intraoperative increase in blood glucose concentration. Intraoperative narcotics and regional analgesia reduce the stress response to surgery by reducing catecholamine release, which attenuates the increase in blood glucose concentration. Thus, an increase in blood glucose

●

● ● ●

●

●

Factors resulting in intraoperative hyperglycemia include the following: ●

●

● ●

Exogenous glucose administration at high maintenance rates (e.g., 20 mL/kg per hour) or massive transfusion Alteration of hormone levels affecting glucose control (e.g., stress) Decreased peripheral glucose utilization Continuation of 10% or 12.5% dextrose solution at the preoperative rate 657

PEDIATRICS & NEONATOLOGY

Most hypoglycemic children are asymptomatic; some are lethargic, irritable, or jittery. In infants and older children, lethargy may occur at a blood glucose concentration of 75 mg/dL, and unconsciousness at less than 35 mg/dL. In neonates, chronic low blood glucose concentrations can be associated with adverse changes in somatosensory evoked potentials and neurodevelopmental outcomes. Clinical signs of hypoglycemia (tachycardia, hypertension) may be masked by preoperative sedation or general anesthesia or attenuated by β-blockers.

Premature infants and small-for-gestational-age neonates Patients receiving hyperalimentation solutions or simple dextrose infusions (10% or 12.5%), especially when these infusions are discontinued acutely Newborns and infants born to diabetic mothers, and children with diabetes or insulinomas Malnourished patients Patients with severe hepatic failure Patients with abnormalities of lipolysis or amino acid metabolism Patients with myopathies, mitochondrial diseases, or glycogen storage diseases Those receiving certain drugs (e.g., propranolol, alcohol)

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Implications

dextrose infusion rates by one third or one half during surgery on septic infants.

HYPOGLYCEMIA Hourly and daily maintenance requirements for both water and calories can be determined for infants and children from standard formulas, the so-called 4-2-1 and 100-50-20 rules (Table 163-1). These formulas were developed from estimates of total caloric needs and based on the assumption that 100 mL of water is needed for each 100 calories. It is thus somewhat paradoxical that most clinicians avoid the routine use of solutions containing glucose, except perhaps for neonates, infants who are small for gestational age, and children with special problems. Unrecognized hypoglycemia can lead to neurologic injury. The absolute value at which hypoglycemia impairs neurologic function is unknown but is seemingly related to its duration measured in hours or days. Brain glucose metabolism increases markedly during development. Unlike the adult brain during ischemia, the neonatal brain is able to use alternative substrates such as lactate and glycogen for energy. HYPERGLYCEMIA Hyperglycemia can induce diuresis, dehydration, and electrolyte disturbances and may increase the incidence of cerebral hemorrhage in very small newborns. In adults, hyperglycemia existing before an ischemic or hypoxemic event may increase neurologic injury. It is postulated that in the presence of either insult, oxidative metabolism of glucose fails and glycolysis increases, producing excess lactate. With sufficient intracellular lactate accumulation, intracellular pH decreases, which may lead to compromised cellular function or cell death. In contrast to adults, moderate to profound hyperglycemia in neonates seems to protect the brain from ischemic damage by means of increased cerebral high-energy reserves and glycogen stores, increased glucose uptake, and enhanced lactate clearance. Thus, during pediatric cardiac surgery, the role of hyperglycemia (if any) in neurologic injury is unclear. The elimination of glucose solutions during cardiac surgery is associated with a 5% to 9% incidence of hypoglycemia, which may be an important contributor to adverse neurologic outcomes. Hyperglycemia is also associated with adverse outcomes in adults with sepsis. Glucose control in septic infants is poorly defined. However, most clinicians reduce 10% or 12.5%

Table 163–1

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Calculation of Maintenance Fluid Requirements for Infants and Small Children Fluid Requirements

Body Weight (kg)

Hourly Fluids*

Fluids over 24 Hours†

<10 11-20

4 mL·kg−1 40 mL + 2 mL·kg−1 >10 kg 60 mL + 1 mL·kg−1 >20 kg

100 mL·kg−1 1000 + 50 mL·kg−1 >10 kg 1500 + 20 mL·kg−1 >20 kg

≥20

*4-2-1 rule. † 100-50-20 rule.

MANAGEMENT The goals of intraoperative fluid management are to provide an appropriate amount of parenteral fluids (water plus electrolytes) to maintain adequate intravascular volume, cardiac output, and urine output and, in some instances, to provide sufficient glucose to prevent hypoglycemia or minimize the risk of perioperative hyperglycemia. To avoid both hypoglycemia and hyperglycemia during surgical procedures, some have suggested administering 2.5% dextrose in lactated Ringer’s (LR) solution at maintenance rates, along with a glucose-free fluid (e.g., LR or normal saline) for replacement of blood and third-space losses. Because 2.5% dextrose-LR solution is not commercially available, either the practitioner or a pharmacist must prepare it. Blood obtained from central venous or arterial catheters or from finger or heel sticks is used to monitor glucose concentrations. Glucose testing is usually available at the point of care. If not, concentrations are measured in the blood gas laboratory. Serial blood glucose determinations can be made, with the amount of intravenous glucose adjusted accordingly.

PREVENTION Prevention of hypoglycemia and hyperglycemia requires a case-specific risk-benefit analysis. Some caveats deserve special mention: ●

●

● ●

Be aware of patients at increased risk for hypoglycemia or hyperglycemia. Be judicious when administering glucose-containing solutions to patients at risk for hypoglycemia. Withhold glucose-containing solutions when appropriate. Frequently monitor blood glucose concentrations.

Further Reading Aun CD, Panesar NS: Paediatric glucose homeostasis during anaesthesia. Br J Anaesth 64:413-418, 1990. Bazaes RA, Salazar TE, Pittaluga E, et al: Glucose and lipid metabolism in small for gestational age infants at 48 hours of age. Pediatrics 111: 804-809, 2003. Ferranti SD, Gaureau K, Hickey PR, et al: Intraoperative hyperglycemia during infant cardiac surgery is not associated with adverse neurodevelopmental outcomes at 1, 4, and 8 years. Anesthesiology 100: 1345-1352, 2004. Leelanukrom R, Cunliffe M: Intraoperative fluid and glucose management in children. Paediatr Anaesth 10:353-359, 2000. Nishima K, Mikawa K, Maekawa N, et al: Effects of exogenous intravenous glucose on plasma glucose and lipid homeostasis in anesthetized infants. Anesthesiology 83:258-263, 1995. Pereira GR: Nutrition care of the extremely premature infant. Clin Perinatol 22:61-75, 1995. Welborn LG, Hannallah RS, McGill WA, et al: Glucose concentration in routine intravenous infusion in pediatric outpatient surgery. Anesthesiology 67:427-430, 1987. Welborn LG, McGill WA, Hannallah RS, et al: Perioperative blood glucose concentrations in pediatric outpatients. Anesthesiology 65:545-547, 1986.

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Pulmonary Hypertension Deborah A. Davis

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Case Synopsis A 4-month-old, formerly preterm infant with bronchopulmonary dysplasia presents for closure of a ventricular septal defect after failing to wean from mechanical ventilation. The surgical procedure is not difficult, but after weaning from cardiopulmonary bypass, the patient has suprasystemic pulmonary artery pressures.

PROBLEM ANALYSIS Definition Elevated pulmonary artery pressure (PAP) is due to increased pulmonary vascular resistance (PVR) or pulmonary blood flow. Pressure, resistance, and flow are related by Poiseuille’s adaptation of Ohm’s law: Ohm’s law: R = PAP − Pv/Q, where R is pulmonary vascular resistance, Pv is pulmonary venous pressure (approximately equal to left atrial pressure), and Q is flow. Poiseuille’s law: R = 8L/πr4,

Recognition The workup for secondary PAH entails serial physical examinations and laboratory and diagnostic testing (Table 164-3). In children without a predisposing condition,

Risk Assessment In lesions that involve a communication between the systemic and pulmonary circulations, some proportion of the systemic pressure is transmitted to the pulmonary circulation. Associated high pressure and increased blood velocities produce shear stress, causing structural and functional damage to the pulmonary vascular endothelium. In lesions with reduced pulmonary blood flow, there may be hypoplasia of the arteries themselves. The risk of

Table 164–1

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Cardiac Causes of Secondary Pulmonary Hypertension

Cardiac lesions that increase pulmonary flow (left-to-right shunt) Patent ductus arteriosus Atrial septal defect Ventricular septal defect (VSD) Atrioventricular canal Aorta-pulmonary window Arterial-pulmonary collaterals Transposition of great vessels with VSD Systemic-to-pulmonary shunts Cardiac lesions that decrease pulmonary flow Tetralogy of Fallot Ebstein’s anomaly Pulmonary atresia Tricuspid atresia Cardiac lesions that cause pulmonary venous hypertension Cor triatriatum Mitral stenosis Mitral atresia Interrupted aortic arch Cardiomyopathy Hypoplastic left ventricle Critical aortic stenosis Coarctation of aorta Veno-occlusive disease Endocarditis

PEDIATRICS & NEONATOLOGY

where R is pulmonary resistance, L is length of resistor, and r is radius of resistor. The latter suggests that the length of the pulmonary bed (and blood viscosity) has a direct impact on resistance, and that the effect of altered arterial radius is exponential. With increased PVR, higher perfusion pressures are needed to maintain constant pulmonary flow; otherwise, flow diminishes. Normal values for mean PAP (i.e., pulmonary artery – left atrial pressure) and PVR are 10 to 20 mm Hg and 4 Wood units, respectively. Either primary or secondary pulmonary artery hypertension (PAH) can occur in children. To diagnose the former, all other causes must be excluded (see Chapter 78). Persistent PAH of the newborn is one cause of primary PAH. It may be due to underdevelopment of the lung, pulmonary vascular maladaptation to extrauterine life, or maldevelopment of the pulmonary vascular bed in utero. With primary PAH, lung pathologic examination reveals a reduced number of arteries relative to the number of bronchioles. Secondary PAH typically develops in response to specific types of cardiac or pulmonary disease (Tables 164-1 and 164-2). Within the context of congenital heart disease, secondary PAH may be due to increased pulmonary artery blood flow, resistance, or both. Secondary PAH can result from advanced pulmonary disease, as well as from nonrespiratory causes (see Chapter 78).

early signs of secondary PAH are those of right ventricular failure, exercise limitation, and, possibly, hypoxemia if a patent foramen ovale is present. Neonates with a patent ductus arteriosus may exhibit differential upper and lower body systemic oxygen saturation as desaturated blood shunts right to left across the ductus to perfuse the lower body.

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Table 164–2

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Noncardiac Causes of Secondary Pulmonary Hypertension

Table 164–4

Respiratory Obstructed lung disease (rare) Restrictive lung disease Collagen vascular disease Bronchopulmonary dysplasia Respiratory distress syndrome Interstitial disease Infiltrative disease Pleural adhesions Neuromuscular disease Other Upper airway obstruction Pickwickian syndrome

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Classification of Structural Changes with Pulmonary Vascular Disease

Grade Structural Change

Status

I II III

Reversible Reversible

IV V VI

Medial hypertrophy Cellular intimal proliferation Intimal hyperplasia, luminal occlusion Pulmonary artery dilatation Pulmonary angiomatoid formation Pulmonary fibrinoid necrosis

Probably reversible Probably reversible Irreversible Irreversible

From Heath D, Edwards SE: The pathology of hypertensive pulmonary vascular disease. Circulation 18:533-547, 1958.

Nonrespiratory Juvenile rheumatoid arthritis Lupus erythematosus Pulmonary embolism (fat, thrombus, air, tumor) Sickle cell disease Scleroderma

developing increased PVR varies, depending on the cardiac malformation: ● ● ●

●

Ventricular septal defect, 15% Transposition of great arteries, 8% Transposition of great arteries with ventricular septal defect, 40% Complete atrioventricular canal defect, almost 100%

If the hematocrit is elevated, vascular thrombotic changes may exacerbate structural arterial changes. Secondary PAH

Table 164–3

■

Workup for Secondary Pulmonary Hypertension

Physical examination Irregular heart rhythms Elevated jugular venous pressure Loud P2, systolic ejection click, wide split P2 Diastolic murmur Chest radiograph (may be normal) Prominent pulmonary artery; enlarged heart Increased pulmonary vascular markings (congestive heart failure) Decreased pulmonary vascular markings (severe disease) Echocardiogram Define anatomy; estimate shunt flows Estimate right ventricular and pulmonary artery pressures Catheterization Further define anatomy Calculate pulmonary vascular resistance Test response to oxygen, nitric oxide, vasodilators Wedge angiography (pulmonary artery tapering and filling; circulation time) Other Electrocardiogram (right ventricular hypertrophy) Lung biopsy Elevated hematocrit

also occurs if left-sided lesions cause pulmonary venous hypertension, with increased venous pressure transmitted back to the pulmonary arteries. Heath and Edwards classified the structural changes that occur with pulmonary vascular disease (Table 164-4). Several factors contribute to secondary PAH with severe parenchymal lung disease: (1) hypoxia and polycythemia, (2) pulmonary endothelial injury, and (3) structural pulmonary artery damage. For example, along with the proliferation of vascular muscularis into nonmuscular peripheral pulmonary arteries, infants with bronchopulmonary dysplasia have excessive pulmonary interstitial water. This compresses the arterioles and further elevates PVR. Treatment of the primary lung disease helps reduce the impact of contributory causes of secondary PAH, allowing regression of some of the associated structural changes. Nonrespiratory diseases can also cause secondary PAH via inflammation (arteritis) or occlusion (thrombosis). Either reduces the pulmonary vascular cross-sectional area and elevates PVR. Also, vasoactive substances (e.g., prostaglandins, thromboxanes, leukotrienes) cause pulmonary vascular changes that increase PAP: ●

●

●

Pulmonary endothelium-derived von Willebrand’s factor increases platelet adhesion and the formation of microaggregates, along with the release of vasoconstrictive factors. Endothelium-derived relaxing factor (i.e., nitric oxide) relaxes vascular smooth muscle and is reduced in patients with lung injury and after cardiopulmonary bypass. Primary pulmonary hypertension can be triggered by almost any neonatal stress (e.g., hypoxemia, hemorrhage, hypoglycemia, hypothermia, aspiration, acidosis) via some of the aforementioned cellular mediators.

Paroxysmal increased PVR occurs on occasion, even with normal baseline PAPs (e.g., post–cardiac surgery patients with large left-to-right shunts or pulmonary venous obstruction). Such pulmonary hypertensive crises can arise when vascular endothelial cells are triggered by a particular stimulant. Consequent acute PAH is poorly tolerated, and

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circulatory collapse can be immediate. The following are more common triggers: ● ●

●

Hypoxia, hypercarbia, acidosis Aggressive suctioning, noxious stimuli, bronchoscopic procedures Pleural effusion, hemothorax, pneumothorax

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Sildenafil is a phosphodiesterase inhibitor that shows promise as an effective intravenous agent for reducing PAP. However, its use may be limited because of its potential to increase intrapulmonary shunt and worsen ventilationperfusion mismatch.

Invasive Measures

Implications

ATRIAL SEPTOSTOMY

High PVR increases right ventricular impedance and may lead to acute or chronic right ventricular failure. As a result, pulmonary blood flow decreases. Without direct pulmonary-systemic connections that allow right-to-left shunting (e.g., a patent foramen ovale), the systemic cardiac output will also fall.

If tissue oxygen delivery is unsatisfactory despite ventilatory and pharmacologic management, more invasive measures may be necessary. In children with low cardiac output due to right ventricular failure but without intracardiac connections, atrial septostomy may prove beneficial. The creation of an atrial septal defect enables systemic venous blood return to bypass the pulmonary circulation and augment left ventricular output, albeit at the cost of systemic hypoxia.

MANAGEMENT MECHANICAL CIRCULATORY SUPPORT Because the management of PAH due to increased pulmonary blood flow is surgical elimination of the left-to-right shunt, only the management of increased PVR is discussed here. The goal is to provide adequate systemic oxygen delivery. Initial therapy should focus on lowering PVR to optimize right ventricular performance. If this fails, intervention to bypass the pulmonary circulation may be necessary.

If low cardiac output persists despite atrial septostomy, or if systemic hypoxemia becomes life threatening, extracorporeal circulatory support is the final option. Because the pathophysiology resides in the pulmonary microcirculation, selective right ventricular assist devices usually do not provide sufficient benefit, necessitating the interposition of a membrane oxygenator.

Ventilatory Strategies

LUNG

Ventilatory strategies represent the most effective measures for selectively influencing PVR. Maintenance of a normal functional residual capacity optimizes PVR, because lung overdistention or underinflation can result in compression and distortion of the pulmonary microcirculation. Reactive pulmonary vasculature dilates in response to enriched oxygen mixtures and local alkalosis. The latter is achieved by hyperventilation or with sodium bicarbonate. When conventional ventilation cannot achieve satisfactory gas exchange without deleterious levels of intrathoracic pressure, jet ventilation may prove beneficial. Inhaled nitric oxide is a selective pulmonary vasodilator that may be effective in cardiac or noncardiac PAH.

Unless the pulmonary hypertensive crisis can be attributed to a finite and reversible cause (e.g., persistent pulmonary hypertension of the newborn), extracorporeal circulatory support must be regarded as a bridge to heart or heart-lung transplantation. Given the limited availability of these organs for children, both the patient’s family and medical providers must have realistic expectations before embarking on such heroic therapy.

Pharmacologic Agents A variety of intravenous drugs, listed here, can have a salutary effect on PVR. They vary in efficacy from patient to patient, and none is selective for the pulmonary circulation: ● ●

● ● ● ● ● ● ● ●

HEART-LUNG TRANSPLANTATION

PREVENTION Therapeutic options for primary and secondary PAH are limited in both scope and efficacy; therefore, prevention is vital. Children with PAH or medical histories that predispose to pulmonary hypertensive crises require meticulous anesthesia care. Preoperative measures directed at optimizing right ventricular function (e.g., digoxin, arrhythmia control) and intravascular volume status deserve special consideration and may provide some benefit. Most critical are precautions to preserve optimal ventilation and provide sufficient analgesia to blunt endogenous, catecholaminemediated responses to noxious stimuli. Also, children with intracardiac shunts and the potential for right-to-left shunting should receive drugs that substantially reduce systemic vascular resistance, even though this promotes systemic hypoxemia. Assuming that cardiac reserve is sufficient to tolerate the requisite doses of anesthetic agents, children with PAH should be managed similarly to those with other conditions in which endogenous responses to noxious stimuli

PEDIATRICS & NEONATOLOGY

●

Prostacyclin Isoproterenol Angiotensin-converting enzyme inhibitors Adenosine Nitroprusside Amrinone Acetylcholine Tolazoline Prostaglandin E1 Nitroglycerin Sildenafil

OR

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have a deleterious impact on the underlying circulatory pathophysiology.

Further Reading Avery GB (ed): Neonatology: Pathophysiology and Management of the Newborn. Philadelphia, JB Lippincott, 1987, p 1399. Davis DA, Russo PA, Greenspan J, et al: High frequency jet versus conventional ventilation in infants undergoing Blalock-Taussig shunts. Ann Thorac Surg 57:846-849, 1994.

Fishman AP: Hypoxia as the pulmonary circulation: How and where it acts. Circ Res 38:221-231, 1976. Haworth SG: Primary pulmonary hypertension. Br Heart J 49:517-521, 1983. Heath D, Edwards SE: The pathology of hypertensive pulmonary vascular disease. Circulation 18:533-547, 1958. Rabinovitch M, Andrew M, Thom H, et al: Abnormal endothelial factor VIII associated with pulmonary hypertension and congenital heart defects. Circulation 76:1043-1052, 1987. Schulze-Neick I, Hartenstein P, Li J, et al: Intravenous sildenafil is a potent pulmonary vasodilator in children with congenital heart disease. Circulation 108(Suppl II):167-173, 2003.

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Hypothermia in Pediatric Patients Kevin J. Sullivan Case Synopsis A 1-month-old, formerly premature (28-week) infant undergoes general anesthesia for magnetic resonance imaging of the brain and spine. At the conclusion of the imaging study, the patient is noted to have a core body temperature of 34.5°C and demonstrates delayed emergence from anesthesia and increased severity of apnea and bradycardia in the neonatal intensive care unit.

PROBLEM ANALYSIS Definition Central (core) body temperature is one of the most tightly regulated parameters in human physiology. Normal core body temperature in infants, children, and adults is about 37°C and seldom fluctuates more than 0.5°C above or below this setpoint. However, mild hypothermia (1°C to 3°C below normal) is commonly seen perioperatively. Anesthetic medications, environmental exposure, and critical illness may result in altered thermoregulation and hypothermia.

Recognition The minimum basic monitoring standards of the American Society of Anesthesiologists require that temperaturemonitoring capabilities be readily available to anesthesiologists. Temperature monitoring is especially important for detecting hypothermia in infants and children, because they are very susceptible to this complication. Sites for temperature monitoring are classified as central (nasopharyngeal, esophageal, axillary, rectal, or bladder) or peripheral (skin): ● ●

● ● ● ●

Nasopharyngeal—posterior to the soft palate Esophageal—posterior to the heart below the level of the carina Rectal Urinary bladder (less accurate with reduced urine output) Axillary—near the axillary artery with the arm abducted Skin surface (poor correlation with core body temperature) HEAT LOSS

IN

ANESTHETIZED INFANTS

The four mechanisms of heat loss in anesthetized patients are conduction, evaporation, convection, and radiation. An understanding of these mechanisms leads to a better understanding of the strategies to minimize heat loss in anesthetized children. Conduction is the direct transfer of heat energy between objects, as occurs with direct patient contact with a cold

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MECHANISMS OF AND CHILDREN

metal surface, irrigation of wounds with cold saline, and the intravenous administration of cold fluids. Evaporation results in heat loss when the latent heat of vaporization is expended to convert a liquid to a gaseous state. Evaporative heat loss in anesthetized patients comes from the skin (evaporation of sweat or surgical preparation solutions from the skin), respiratory tract, and wounds (especially exposed thoracic and peritoneal cavities). Convection occurs when molecules at different temperatures cause the net transfer of heat between objects, such as when cool air circulates over the surface of the patient’s skin. The rate of convective heat loss is proportional to the temperature difference between ambient air and skin and to the surface area of the patient’s skin exposed to that air. Finally, radiation heat loss occurs when infrared energy is exchanged between two solid objects that are not in contact. The magnitude of heat exchange is proportional to the fourth power of the temperature difference between the two objects. Body temperature is monitored by the hypothalamus through afferent sensory input from the skin, neuraxis, and deep body tissues. Under normal conditions, core body temperature is tightly regulated by the hypothalamus and remains within a narrow interthreshold range of 0.5°C above or below a recognized normal body temperature, or setpoint. When the hypothalamus detects a change in core body temperature beyond the acceptable interthreshold range, effector mechanisms are activated to bring core body temperature back to normal (Figs. 165-1 and 165-2). Central regulation of temperature is present in infancy but may be impaired in the elderly, in the critically ill, and in children with severe damage to the central nervous system. In response to hypothermia, effector mechanisms are activated. These mechanisms are classified as those that reduce heat loss (behavioral changes, vasoconstriction) and those that increase heat production (behavioral changes, nonshivering thermogenesis, shivering). Behavioral changes are not relevant in anesthetized patients, so cutaneous vasoconstriction is the primary response to hypothermia in this setting. Cutaneous blood flow can be reduced via norepinephrine secreted at presynaptic adrenergic terminals. This results in a 25% to 50% decrease in heat loss.

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Hypothalmus Other parts of brain Skin surface Spinal cord Deep central tissues

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Hypothalmus

Warm responses

PERIOPERATIVE THERMOREGULATION

Active vasodilation Sweating

Predictable changes in body temperature occur in infants and children after the induction of general anesthesia (Fig. 165-3). The first phase of heat redistribution begins when volatile anesthetics cause peripheral vasodilatation, effectively reducing core body (central compartment) perfusion. Central temperature declines as heat is lost to the peripheral tissues. During the second phase, there is reduced endogenous heat production and increased heat loss to the environment. During the third phase, metabolic heat production exceeds heat loss, causing the core temperature to stabilize (adults) or increase (greater in infants than in children). General anesthesia widens the thermoregulatory interthreshold range (≥2.5°C below the setpoint). This leads to passive core body temperature changes over a wider range of hypothermic temperatures before effector mechanisms become activated (see Fig. 165-2). A lower temperature threshold for effector mechanism activation has been demonstrated with halothane, enflurane, desflurane, sevoflurane, isoflurane propofol, and nitrous oxide–opioid anesthesia. Regional anesthesia techniques produce hypothermia as readily as general anesthesia does. The vasodilatation induced by neuraxial local anesthetics causes rapid redistribution of core heat to the periphery in a manner similar to that seen with the induction of general anesthesia. Effector mechanisms of shivering and vasoconstriction are absent below the level of block but remain intact above the level of block. Also, the interthreshold range for effector mechanisms appears to be widened in a manner similar to that seen with general anesthesia. It is postulated that the absence of cold afferent input from the tissues below the level of the block is interpreted as warm afferent input, which leads to

Interthreshold Vasoconstriction Nonshivering thermogenesis Shivering

range

Cold responses Figure 165–1 ■ Thermoregulatory model. Thermal afferent input is integrated and compared with the threshold temperature for heat and cold. The interthreshold range is the temperature range over which no regulatory effector responses occur. On either side of this interthreshold range are triggered thermoregulatory respononses. (From Bissonnette B: Thermoregulation and pediatric anesthesia. Curr Opin Anesthesiol 6:537-542, 1993.)

Under anesthesia

Awake

Heat production is augmented in anesthetized patients by nonshivering thermogenesis (NST) and shivering. NST is the production of heat in skeletal muscle and brown fat due to the catabolism of brown fat around the blood vessels of the neck, mediastinum, adrenal glands, and axillae. NST can be inhibited by ganglionic blockade, β-blockade, and inhalational anesthetics. Preterm infants, term neonates, infants, and children are capable of NST; however, recent reports have questioned the importance of NST in infants and small mammals during general anesthesia. Shivering is characterized by high-frequency, irregular muscle activity that begins in upper body muscles when vasoconstriction and NST have failed to maintain an adequate mean body temperature. Shivering is an important mechanism for thermoregulation in adults, but it has not been observed in children younger than 6 years.

NST Shivering

Active vasodilatation

NST Shivering >6 years

Sweating

35

Infants Children Adults

Sweating

Vasoconstriction Children Infants

33

38

Active vasodilatation

Vasoconstriction

37

39

Central temperature (°C)

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37

A

36

B

35

41°C

Figure 165–2 ■ Thermoregulatory thresholds and gains in awake and anesthetized infants and children. Thermoregulation appears to be an allor-none phenomenon. The threshold temperature triggering a thermoregulatory response to hypothermia during anesthesia—nonshivering thermogenesis (NST)—is about 2.5°C below the setpoint (about 37°C), whereas during hyperthermia, the temperature must increase approximately 1.3°C above the setpoint to activate an effector response. Within this temperature range, thermoregulatory responses are absent. Consequently, the patient’s body temperature changes passively in proportion to the difference between metabolic heat production and environmental heat loss. (From Bissonnette B: Thermoregulation and pediatric anesthesia. Curr Opin Anesthesiol 6:537-542, 1993.)

C

34 0

80

160

240

Elapsed time (min)

Figure 165–3 ■ Typical pattern of hypothermia during anesthesia. This occurs in three distinct phases in infants, children, and adults: internal redistribution of heat (A), heat loss to the environment (B), and thermal steady state or rewarming (C). Slopes for each stage vary as a function of age. (From Bissonnette B: Thermoregulation and pediatric anesthesia. Curr Opin Anesthesiol 6:537-542, 1993.)

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suppression of vasoconstriction, despite the fact that core body temperature is reduced. When combined with general anesthesia, the additional effects of regional anesthesia on thermoregulatory thresholds appear to be minimal.

Risk Assessment Infants and neonates are more likely than adults to develop perioperative hypothermia. Infants and small children have an increased surface area relative to their body mass. The prominence of the head and trunk and the small extremities of infants prevent the pooling of heat content in the peripheral compartment during anesthesia-related vasodilatation, while the increased surface area–to–body mass ratio diminishes the effectiveness of cutaneous vasoconstriction. Infants lose more heat through their thin skin and have a higher minute ventilation, which increases evaporative heat loss from the respiratory tract. Finally, although vasoconstriction and NST are present in infants and young children, small infants’ inability to shiver effectively limits their ability to optimally generate endogenous heat. These innate limitations in the conservation and production of endogenous heat render infants and children particularly vulnerable to the development of hypothermia in cool ambient environments.

Implications

Hypothermia in Pediatric Patients

665

MANAGEMENT AND PREVENTION The simplest and most effective method to treat or prevent heat loss is to warm the operating room to at least 26°C, and often to temperatures greater than 30°C when caring for term or preterm infants. Likewise, maintenance of relative humidity in the operating room minimizes evaporative heat losses from infants. Use of other heat conservation methods may allow the operating room to be cooled to ambient temperatures that are more comfortable for the health care team. During anesthesia induction, passive patient warming is accomplished by insulating as much of the skin surface as is practical. The amount of skin surface covered is more important than which part is covered, and no one material is superior to others for reducing radiation and convective heat loss from the skin. Passive insulation of the peripheral compartment limits the transfer of heat from the central compartment to the peripheral compartment during general anesthesia. Active patient warming can be used to minimize ambient heat loss during general anesthesia. Infrared radiant heaters are commonly used during anesthesia induction and patient preparation and positioning. Once the patient has been positioned and draped, convective air warming blankets or circulating warm water blankets are commonly used. The former circulate warm air at variable temperatures over the body surface outside the surgical field. Circulating warm water blankets are usually placed underneath the patient, with layers of cotton sheets between the blanket and the patient to prevent thermal injury. Convective blankets are more effective than warm water blankets for the prevention and treatment of perioperative hypothermia in infants. Care must be exercised to (1) monitor the patient’s skin for thermal injury, (2) ensure that warming devices are properly applied, and (3) use the minimal temperature required for gradual rewarming. This is especially important if surface blood flow is reduced (e.g., low cardiac output states, regions of pressure necrosis, procedures involving skin grafting or the creation of muscle flaps). Significant burn injuries have been reported with the use of warming devices. Efforts to reduce respiratory tract evaporative losses are more effective heat conservation measures in children than in adults owing to their higher minute ventilation. Airway humidification, whether active or passive, minimizes heat loss from the respiratory tree. Active humidifiers nebulize water particles in inspired gas mixtures and are most commonly used on ventilators in critical care settings. Care must be taken to monitor the temperature of the inspired gases to prevent tracheal mucosal thermal injury. Passive humidifiers (“artificial noses”) condense water contained in exhaled gases and return it to the patient during inspiration. Care must be taken to place the heat and moisture exchanger in close proximity to the airway to prevent condensation and “rain-out” of free water in the cool gas in the inspiratory limb of the ventilator circuit. Finally, attention to the temperature of intravenous and irrigation fluids is critical to prevent rapid conductive cooling during pediatric anesthesia. If large amounts of crystalloid and blood products are

PEDIATRICS & NEONATOLOGY

The primary disadvantages of hypothermia in awake patients are shivering and discomfort. Shivering increases heat production at the expense of a pronounced increase in oxygen consumption (up to 600%). Cardiac output increases to match increased oxygen demands, and although this is easily tolerated in healthy patients, it may be poorly tolerated in those with cardiovascular disease. Neutral thermal environment is the term used to describe the range of ambient temperatures at which metabolic expenditures for heat production are minimal. The critical temperature is the temperature below which heat must be produced by the patient to prevent a decrease in body temperature. Term newborns have a critical temperature of about 33°C, whereas preterm infants can have critical temperatures as high as 35°C. Because oxygen consumption for NST increases with larger skin surface–to– environmental temperature gradients, infants in cool ambient environments may expend considerable metabolic energy in pursuit of a stable body temperature. Hypothermia has deleterious effects on platelet function, immune function, nitrogen balance, and blood flow to surgical wounds. Surgical blood loss is increased when hip arthroplasty is performed during hypothermia, and surgical wound infection and prolonged hospital stays have been noted in patients having procedures performed under hypothermic conditions. Hypothermia depresses drug metabolism, prolongs the duration of action of muscle relaxants, and reduces the minimum alveolar concentration for volatile anesthetics. Severe hypothermia may impair cognitive function, but there is conflicting evidence about whether it delays anesthetic emergence. Finally, hypothermia often occurs with metabolic aberrations known to exacerbate central apnea in preterm infants (e.g., hypoglycemia, hypocalcemia, hypoxemia, acidosis).

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administered, precipitous declines in body temperature can occur if they are not warmed beforehand. Likewise, irrigation fluids that are not warmed to body temperature can cause rapid declines in body temperature, especially when used to irrigate the peritoneal and thoracic cavities.

Further Reading Bissonnette B: Thermoregulation and pediatric anesthesia. Curr Opin Anesthesiol 6:537-542, 1993. Bissonnette B, Ryan JF: Temperature regulation: Normal and abnormal (malignant hyperthermia). In Cote CJ, Todres ID, Ryan JF, et al (eds): A Practice of Anesthesia for Infants and Children. Philadelphia, WB Saunders, 2001, pp 610-635. Bissonnette B, Sessler DI: The thermoregulatory thresholds for vasoconstriction in pediatric patients anesthetized with halothane or halothane and caudal bupivacaine. Anesthesiology 76:387-392, 1992. Bissonnette B, Sessler DI, LaFlamme P: Intraoperative temperature monitoring sites in infants and children and the effect of inspired gas warming on esophageal temperature. Anesth Analg 69:192-196, 1989.

Dicker A, Ohlson KB, Johnson L, et al: Halothane selectively inhibits nonshivering thermogenesis: Possible implications for thermoregulation during anesthesia of infants. Anesthesiology 82:491-501, 1995. Kurz A, Kurz M, Poeschl G, et al: Forced-air warming maintains intraoperative normothermia better than circulating-water mattresses. Anesth Analg 77:89-95, 1993. Kurz A, Sessler DI, Lenhardt R: Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. N Engl J Med 334:1209-1215, 1996. Plattner O, Semsroth M, Sessler DI, et al: Lack of non-shivering thermogenesis in infants anesthetized with fentanyl and propofol. Anesthesiology 86:772-777, 1997. Schmied H, Kurz A, Sessler DI, et al: Mild hypothermia increases blood loss and transfusion requirements during total hip arthroplasty. Lancet 347:289-292, 1996. Sessler D: Temperature disturbances. In Gregory GA (ed): Pediatric Anesthesia, 4th ed. Philadelphia, Churchill Livingstone, 2002, p 67. Truell KD, Bakerman PR, Teodori MF, et al: Third-degree burns due to intraoperative use of a Bair Hugger warming device. Ann Thorac Surg 69:1933-1934, 2000. Zukowski ML, Lord JL, Ash K: Precautions in warming light therapy as an adjuvant to postoperative flap care. Burns 24:374-377, 1998.

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Cardiomyopathies Stephanie S. F. Fischer and B. Craig Weldon Case Synopsis A 6-month-old boy with Pompe’s disease (glycogen storage disease type II) presents for muscle biopsy and central venous catheter placement under general anesthesia. Mask induction with sevoflurane is followed by a maintenance propofol infusion. The patient develops signs of ischemia on the electrocardiogram (ECG) and hypotension. This quickly leads to ventricular fibrillation and cardiac arrest. The return of spontaneous circulation is achieved with external cardiac massage and two intravenous doses of epinephrine, and the surgery is canceled.

PROBLEM ANALYSIS Definition The World Health Organization defines cardiomyopathies (CMs) as myocardial diseases associated with cardiac dysfunction. They are classified by the dominant pathophysiology or, if known, by causative factors. Thus, CM may be dilated, hypertrophic, restrictive, or a special type called arrhythmogenic right ventricular cardiomyopathy (or arrhythmogenic right ventricular dysplasia). If the cause of a CM is known (i.e., secondary CM), it may be ischemic, valvular, hypertensive, inflammatory, metabolic, or peripartum in origin. CMs can also be associated with systemic disease, neuromuscular disorders, or exposure to toxins.

Recognition Primary CM (not caused by some other organ system disease or pathophysiologic state) and secondary CM (proven cause) can be dilated, hypertrophic, restrictive, or arrhythmogenic right ventricular, based on functional and anatomic presentations. Unclassified CMs consist of cases that do not fit readily into any of these groups, such as the following: ● ● ●

Fibroelastosis Noncompacted myocardium Mitochondrial disorders

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Dilated cardiomyopathy (DCM) is characterized by left ventricular chamber dilatation and impaired systolic function involving the left ventricle (LV), right ventricle (RV), or both. DCM may be viral or immunologic, idiopathic, or familial (genetic); it may be caused by alcohol or toxins or associated with other diseases involving the cardiovascular system. DCM may be asymptomatic or associated with severe functional impairment (New York Heart Association [NYHA] class III or IV heart failure). Patients with decompensated heart failure (NYHA class IV) present with low cardiac output and pulmonary edema (cor pulmonale). Also, all four cardiac chambers appear dilated on chest radiographs. The ECG in

acute cor pulmonale may resemble that of inferior myocardial infarction. However, differences include the following: (1) the pattern of lead II tends to follow that of lead I (no Q wave) as opposed to that of lead III (with Q waves); (2) the ECG changes may be fleeting or resolve over a period of hours or days, as opposed to weeks or months; (3) the ST-T abnormalities in the limb leads are slight, and those in the right precordial leads resemble the anteroseptal infarction pattern; (4) transient right bundle branch block may be present. In chronic cor pulmonale, the ECG is characterized by (1) a rightward shift of the QRS axis by greater than 30 degrees; (2) inverted, biphasic, or flattened T waves in leads V1 to V3; (3) ST segment depression in the inferior leads (II, III, aVF); and (4) right bundle branch block. Echocardiography confirms DCM as well as poor systolic function. Hypertrophic cardiomyopathy (HCM) may involve the LV, RV, or both and is often asymmetrical. Ventricular volumes may be normal or reduced. HCM is characterized by diastolic dysfunction, with preserved systolic function. HCM is a genetic condition and involves sarcomeric protein mutations. There is an autosomal dominant pattern of inheritance, with variable penetrance. Patients with HCM may be asymptomatic or present with exertional dyspnea, chest pain, and syncope. The ECG shows a progressive pattern, from septal hypertrophy to generalized left ventricular hypertrophy. A few other tendencies are also worth noting: (1) the ECG can be normal in up to 20% of cases; (2) many patients have ECG evidence of left ventricular hypertrophy; (3) some cases are associated with left axis deviation; (4) the pattern of bundle branch block (in reality, intraventricular conduction block) tends to be atypical, with notching and slurring of the QRS complex in the limb leads; (5) the P waves may be widened and notched, with evidence of left atrial enlargement; (6) in infants with HCM, the ECG pattern is commonly consistent with right ventricular hypertrophy; (7) possibly the most suggestive finding (25% to 30% of patients) is obviously abnormal Q waves, but dissimilar to those of myocardial infarction. Also, HCM is associated with an increased incidence of both supraventricular and ventricular arrhythmias. Finally, echocardiography reveals asymmetrical septal

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hypertrophy, with a septal–to–left ventricular wall ratio greater than 1.3. Restrictive cardiomyopathy (RCM) is characterized by restricted left or right (or both) ventricular filling due to reduced ventricular diastolic compliance. There may be normal or near-normal systolic function. RCM may be idiopathic, or it can be associated with endomyocardial fibrosis or the hypereosinophilic syndrome. Arrhythmogenic right ventricular cardiomyopathy (ARVCM) is characterized by fibrofatty replacement of right or left ventricular (or both) myocardium. ARVCM is a genetic cardiac disease with autosomal dominant inheritance and incomplete penetrance. Patients with ARVCM often present with dyspnea, fatigue, hepatomegaly, and ascites. The chest radiograph shows pulmonary venous congestion. The ECG may show impaired atrioventricular conduction. However, without histiologic confirmation (i.e., myocardial biopsy), ARVCM is diagnosed based on the presence of ventricular arrhythmias (most often sustained ventricular tachycardia) with a left bundle branch block configuration and wall motion abnormalities on echocardiography in the free wall of the RV. In addition, echocardiography may show atrial dilatation associated with near-normal ventricular dimensions and atrioventricular valve regurgitation.

Risk Assessment DCM is the most common form of CM in children; it has an equal prevalence in males and females. HCM usually does not present before adolescence. With HCM, morbidity and mortality are greatest in patients diagnosed at younger ages. Premature death is commonly due to ventricular fibrillation. RCM is uncommon in children but, when present, is often an end-stage finding with myocarditis or an infiltrative myocardial disease. ARVCM is uncommon but accounts for a high percentage of sudden cardiac deaths in children and adolescents. The prevalence in females is threefold grater than in males.

Implications In DCM, cardiac output is maintained by sympathetically mediated tachycardia and ventricular chamber dilatation with increased stroke volume. However, this leads to increased myocardial wall tension and oxygen utilization. In HCM, there is ventricular inflow obstruction secondary to diastolic dysfunction. Some 20% to 25% of patients also have dynamic obstruction of the left ventricular outflow tract. The systolic volume of the LV, the force of left ventricular contraction, and the transmural pressure gradient distending the outflow tract determine the severity of the obstruction. With RCM, the ejection fraction is maintained early in the process. However, as ventricular fibrosis progresses, left ventricular end-diastolic pressure increases, resulting in pulmonary hypertension and decreased stroke volume and cardiac output. With ARVCM, contractility is normal initially; however, the onset of ventricular arrhythmias (ventricular tachycardia) leads to slow deterioration of right ventricular function. Eventually, ventricular tachyarrhythmias (ventricular tachycardia or fibrillation) become resistant to antiarrhythmic therapy.

MANAGEMENT The perioperative management of children with known CM requires an understanding of normal cardiovascular physiology and an appreciation of the particular pathophysiology associated with the patient’s CM. Maintenance of cardiac output is the primary objective. As illustrated by the case synopsis, induction of anesthesia may cause myocardial depression or loss of systemic vascular tone, leading to abrupt circulatory collapse and, possibly, malignant arrhythmias and cardiac arrest. Two rather simple but crucial relationships illustrate the components that regulate cardiac output: 1. Cardiac output = Heart rate × Stroke volume. 2. Stroke volume is determined by preload, contractility, and afterload. Typically, the myopathic ventricle requires at least normal to increased preload to maintain adequate stroke volume. At the same time, intravenous volume loading may upset a delicate balance between sufficient preload and that which will dilate the ventricle and increase its end-diastolic pressure. The latter reduces endocardial perfusion to decrease rather than increase stroke volume. Invasive monitoring helps assess hemodynamic responses to intravenous fluid challenges, as well as intermittent positive-pressure ventilation. Patients who have been fluid-restricted preoperatively are most susceptible to severe hypotension in response to intermittent positive-pressure ventilation. Once preload has been optimized, contractility may need to be addressed. Except for patients with HCM, children with CM have compromised contractility and limited myocardial functional reserve. Anesthetic agents should be administered with this in mind. Inotropes (e.g., dopamine, dobutamine, epinephrine) or inodilators (e.g., milrinone) may be required perioperatively to maintain cardiac output. Augmented contractility improves stroke volume, but at the cost of increased myocardial oxygen consumption. Increased afterload, due to increased systemic or pulmonary vascular resistance, impedes the contraction of the LV and/or RV. Intramyocardial wall stress (a major determinant of afterload) increases directly with ventricular diameter according to Laplace’s principle. Thus, at the same level of arterial pressure, afterload encountered by an enlarged ventricle is higher than that for a ventricle of normal size. Children with end-stage CM may have pulmonary hypertension. Every effort should be made to avoid increases in pulmonary vascular resistance. This is done by minimizing mean airway pressures, maintaining normocapnea to hypocapnia, providing permissive metabolic alkalosis, and giving exogenous pulmonary vasodilator agents (e.g., nitric oxide, prostaglandins). Finally, a reduction in stroke volume often results in a sympathetically mediated increase in heart rate to compensate for the decrease in cardiac output. Maintenance of sinus or atrial-origin rhythms (e.g., wandering atrial pacemaker), and the associated atrial contribution to ventricular filling, is critical. Loss of sinoatrial rhythm with nonatrial, lower pacemaker escape rhythms (e.g., atrioventricular junctional or idioventricular rhythms or tachycardia) leads to inadequate diastolic filling and lower end-diastolic volumes. This aggravates any preexisting diastolic dysfunction.

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Management objectives for the specific CMs are as follows.

Dilated Cardiomyopathy ●

●

●

●

Preload: normovolemia ● Adequate fluids are required to maintain increased end-diastolic volume and cardiac output. Contractility: increase ● Inodilators (e.g., milrinone) are especially useful because they augment contractility and reduce afterload at the same time. Heart rate: normal or increase ● A mildly accelerated heart rate compensates for reduced stroke volume to help maintain cardiac output. Afterload: normal or decrease ● Afterload reduction helps unload a poorly contractile ventricle.

Hypertrophic Cardiomyopathy ●

●

● ●

Preload: increase ● Avoid hypovolemia due to inadequate fluid replacement or vasodilatation of the venous capacitance bed causing reduced venous return. Contractility: decrease ● Halothane is a useful anesthetic agent for reducing contractility and heart rate. ● Avoid light anesthesia and sympathetically mediated increases in contractility. ● β-Blockers can be used to control both the hyperdynamic myocardium and heart rate. Heart rate: normal or decrease Afterload: normal or increase ● Decreased systemic vascular resistance reduces coronary perfusion pressure. ● Reduced coronary perfusion pressure may lead to myocardial ischemia, with the potential to cause intraoperative cardiac arrest due to ventricular fibrillation or bradyasystole. ● Phenylephrine is the drug of choice to increase afterload.

Restrictive Cardiomyopathy ● ●

● ●

Preload: normovolemia Contractility: increase ● Inotropic support is frequently required. Heart rate: normal Afterload: do not increase or decrease

Arrhythmogenic Cardiomyopathy ● ●

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Preload: normovolemia Contractility: normal Heart rate: normal ● Maintain sinus rhythm and place defibrillator pads before the induction of anesthesia. Afterload: do not increase or decrease

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PREVENTION To avoid a catastrophic reduction in cardiac output during anesthesia and surgery in pediatric patients with CM, one must have a thorough understanding of the pathophysiology of the particular CM present. Obviously, elective or less urgent surgery in a patient known to have a CM requires extensive discussion with the child’s cardiologist, surgeon, and parents. This should allow complete medical preparation of the patient before the day of surgery and help reduce the risk of perioperative deterioration. When more urgent surgery is required, it may not be possible to optimize the patient’s medical condition before his or her arrival in the operating room. If so, the cardiologist should be immediately available for consultation with the anesthesia team. In general, preoperative preparation should follow the management objectives outlined earlier.

Further Reading Antman EM: Cardiovascular Therapeutics, 2nd ed. Philadelphia, WB Saunders, 2002. Atlee JL III: Perioperative Cardiac Dysrhythmias, 2nd ed. Chicago, Year Book Medical Publishers, 1990. Atlee JL: Arrhythmias and Pacemakers. Philadelphia, WB Saunders, 1996. Carvahlo JS: Cardiomyopathies. In Anderson RH, Baker EJ, Macartney FJ (eds): Pediatric Cardiology. Philadelphia, JB Lippincott–Williams & Wilkins, 2002, pp 1595-1643. Denfield SW, Gajarski RJ, Towbin JA: Cardiomyopathies. In Garson A, Bricker JT, Fischer DJ (eds): The Science and Practice of Pediatric Cardiology. Philadelphia, WB Saunders, 1998. Ing RJ, Cook DR, Bengur RA, et al: Anesthetic management of infants with glycogen storage disease type II: A physiological approach. Paediatr Anaesth 14:514-519, 2004. Kishnani PS, Howell RR: Pompe disease in infants and children. J Pediatr 144:35-43, 2004. Lipschultz SE, Sleeper LA, Towbin JA, et al: The incidence of pediatric cardiomyopathy in two regions of the United States. N Engl J Med 348:1647-1655, 2003. McKenzie IM: Cardiomyopathies. In Lake CL, Booker PD (eds): Pediatric Cardiac Anesthesia. Philadelphia, JB Lippincott–Williams & Wilkins, 2005, pp 530-535. Nugent AW, Daubeney PE, Chondros P, et al: The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med 348:1639-1646, 2003. Richardson P, McKenna W, Bristow M, et al: Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies. Circulation 93:841-842, 1996. Stockwell JA, Tobias JD, Greeley WJ: Noninflammatory, noninfiltrative cardiomyopathy. In Nichols DG, Cameron DE, Greeley WJ (eds): Critical Heart Disease in Infants and Children. St. Louis, Mosby, 1995, pp 1037-1051. Venugolapan P, Agarwal AK, Worthing EA: Chronic cardiac failure in children due to dilated cardiomyopathy: Diagnostic approach, pathophysiology and management. Eur J Pediatr 159:803-810, 2000. Weller RJ, Weintraub R, Addonizio LJ, et al: Outcome of idiopathic restrictive cardiomyopathy in children. Am J Cardiol 90:501-506, 2002.

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Case Synopsis An 8-year-old, previously healthy girl is admitted with respiratory distress, wheezing, and stridor. Her symptoms have been slowly progressive over 2 weeks and are associated with nocturnal fever and exercise intolerance. The chest radiograph demonstrates a widened mediastinum and a retrosternal mass (Fig. 167-1). A computed tomography (CT) scan of the chest confirms the presence of an anterior mediastinal mass (Fig. 167-2). A biopsy of the mass is scheduled.

PROBLEM ANALYSIS Definition Anterior mediastinal masses affect many intrathoracic structures. Most significant are those that compress the heart or major vessels within their respective compartments. Many reports describe sudden, progressive cardiopulmonary compromise due to these masses. Commonly, they involve the anterior mediastinum and, to a lesser extent, the middle and posterior mediastinum. The mediastinum is defined as that portion of the thorax between the medial aspects of the pleura, above the diaphragm, and below the thoracic inlet. It is bound anteriorly by the sternum and posteriorly by the thoracic vertebrae. A line between the fourth thoracic vertebra and the sternal angle subdivides the mediastinal space into inferior and superior compartments. The inferior space is further subdivided by the pericardium into anterior, middle, and posterior regions. The location of a mediastinal mass, whether benign or malignant, is characteristic. It provides the clinician with clues to the origin of the mass and determines what physiologic effects it will have on surrounding mediastinal and other thoracic structures.

Risk Assessment The best approach for the anesthetic management of patients with anterior mediastinal masses is still subject to debate. Some reports describe sudden death or severe cardiopulmonary compromise with the induction of anesthesia and, in some cases, emergence from anesthesia. Some authors suggest that these masses should be biopsied under

Recognition Adult patients with anterior or middle mediastinal masses present with a variety of signs and symptoms. Most, however, either are asymptomatic or have minimal to moderate symptoms, including cough, dyspnea on exertion, chest pain, fatigue, and vocal cord paralysis. Severe symptoms in a minority of adults include orthopnea, stridor, cyanosis, jugular vein distention, or superior vena cava syndrome. The presenting signs and symptoms of anterior mediastinal masses in pediatric patients can include the following: ● ● ●

Orthopnea or cough in the supine position Superior vena cava syndrome with jugular vein distention Wheezing or stridor; dyspnea on exertion; increased work of breathing

In pediatric patients, most anterior mediastinal masses are malignant, with lymphomas, germ cell tumors, mesenchymal tumors, and thymic lesions found in decreasing order of frequency. 670

Figure 167–1 ■ Lateral chest film of an 8-year-old girl later determined to have lymphoma. A large mass is seen in the anterior mediastinum. Treatment was initiated before biopsy.

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Figure 167–2 ■ Chest computed tomography scan revealing near-complete compression of the distal trachea and main-stem bronchi by a large anterior mediastinal mass. The mass measured approximately 7 by 7 cm and involved not only the trachea but also the great vessels and pericardium.

local anesthesia or, if lymphoma is suspected, they should be treated with chemotherapeutic agents or radiation therapy before biopsy. Others suggest that, given the importance of obtaining early tissue diagnosis, most patients can safely undergo general anesthesia, assuming proper preparation and anesthetic care. To better predict which patients are likely to have significant cardiopulmonary compromise while under general anesthesia, there have been attempts to correlate preoperative symptoms and CT and spirometry findings with anesthetic outcomes. Patients with a peak expiratory flow rate and tracheal area greater than 50% of predicted for age on CT appear to tolerate general anesthesia without incident. However, even with CT and spirometry, it is often difficult to predict which patients are likely to experience difficulties. A large case series of adult patients suggested that the most reliable predictors of cardiopulmonary compromise are the following: ● ●

● ●

Presence of symptoms on presentation Combined obstructive and restrictive pattern on pulmonary function testing Presence of pericardial effusion Tracheal compression with greater than 50% reduction in cross-sectional area on CT

In addition, the presence of severe preoperative symptoms (e.g., supine dyspnea) has been emphasized as an indicator of high-risk status.

Cardiopulmonary compromise in patients with mediastinal masses results from direct compression or, occasionally, invasion of adjacent pulmonary or vascular structures. The effects of anesthesia increase the impact of airway or vascular compression due to the loss of intrinsic thoracic muscle tone, resulting in reduced thoracic diameter and increased compression of vascular and pulmonary structures.

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The location of such compression is critical, because if airway compression occurs distal to the trachea or mainstem bronchi, patients may not benefit from airway stenting with endotracheal or endobroncial tubes. CT scanning can help localize any airway compression. Still, it must be recognized that airway compression following the induction of anesthesia may be more extensive than that seen on CT. Cardiovascular compromise can take the form of the superior vena cava syndrome owing to compression of venous structures within the superior mediastinum. If so, cardiac output may be compromised by the resulting reduction in preload or by direct compression of the right ventricle by the anterior mediastinal mass. Also, echocardiography has shown that masses of the posterior mediastinum may compress the left atrium and, to a lesser extent, the left ventricle. Children given general anesthesia for surgery on an anterior mediastinal mass are at risk for developing significant respiratory compromise and complete airway collapse intraoperatively or postoperatively. Some patients may not be able to be extubated after surgery and will require intensive care for the initiation of radiation or chemotherapy. Cardiovascular collapse and death, though rare, are potential complications of general anesthesia in these patients. An inflatable balloon in the anterior mediastinum has been used in animal models to simulate anterior mediastinal masses. In such models, cardiac output is equally reduced during controlled or spontaneous ventilation in direct proportion to the volume of the mass. This cardiac output reduction is due to increased right ventricular afterload, leading to right ventricular dilatation and septal encroachment on the left ventricle.

MANAGEMENT Based on the available evidence, it is clear that children with mediastinal masses, especially anterior masses, are at increased risk for cardiopulmonary compromise during the induction of general anesthesia. The question is: Is the risk sufficient for anesthesiologists to request that biopsies of such masses be performed under local anesthesia with monitored anesthesia care, or that radiation or chemotherapy be used preoperatively to shrink these masses? This question is difficult to answer. However, some recommendations can be made regarding the safe management of most, if not all, children with anterior mediastinal masses. Rather than defining those patients expected to experience cardiopulmonary compromise, existing reports allow us to predict those who are unlikely to have a complicated perioperative course. The following factors allow the anesthesiologist to make that prediction: ●

●

Anterior mediastinal masses are most likely to produce significant cardiopulmonary compromise during general anesthesia. A chest radiograph can provide sufficient information about the location and size of most of these masses to ascertain actual risk. Patients without cardiopulmonary symptoms at rest are unlikely to experience related compromise. Most reassuring is the absence of postural cough, stridor, or dyspnea.

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On CT scans, patients with a tracheal cross-sectional area greater than 50% of predicted are less likely to experience cardiopulmonary compromise. CT scanning should be routine for the evaluation of all patients with anterior mediastinal masses. Peak expiratory flow rates greater than 50% of predicted are reassuring and should be obtained whenever possible.

Older, more cooperative children thought to be at high risk of cardiopulmonary compromise can have their masses biopsied under local anesthesia. Fine-needle aspiration is sufficient to make an accurate diagnosis in more than 80% of cases. More problematic are children in whom it is impossible to perform such procedures under local anesthesia. An alternative may be a procedure at another site (e.g., bone marrow or lymph node biopsy, aspiration of pleural fluid) conducted under local anesthesia, possibly with intravenous ketamine for sedation. In those (rare) high-risk cases for which general anesthesia is required, the available reports suggest the following: ●

● ●

●

●

●

Use inhalational induction with spontaneous ventilation to maintain airway patency. If possible, avoid muscle relaxants. The sitting, lateral, or prone position may reduce the risk of airway obstruction. Rigid bronchoscopy should be available for immediate distal airway access (i.e., beyond the distal tracheal lumen of an endotracheal tube). Cardiopulmonary bypass standby has been advocated by some for extremely high-risk patients, including cannulation of the femoral vessels before the induction of anesthesia. Fiberoptic bronchoscopy, advocated by some, offers little advantage over endotracheal intubation under deep general anesthesia (without muscle relaxants) in most patients.

PREVENTION Prevention of acute airway compromise in patients with symptomatic mediastinal masses is achieved by avoiding

general anesthesia or deep sedation. Instead, biopsies should be performed with local anesthesia, or radiation therapy or chemotherapy should be administered to reduce the size of the mass before biopsy or before anesthesia and surgery. Although debates are ongoing, it appears that the ability to make a molecular diagnosis has greatly improved, even after radiation or chemotherapy. For the rare patient in which general anesthesia is mandatory, the anesthesiologist must proceed with extreme vigilance and caution.

Further Reading Bechard P, Letourneau L, Lacasse Y, et al: Perioperative cardiorespiratory complications in adults with mediastinal mass: Incidence and risk factors. Anesthesiology 100:826-834, 2004. D’Cruz IA, Feghali N, Gross CM: Echocardiographic manifestations of mediastinal masses compressing or encroaching on the heart. Echocardiography 11:523-533, 1994. Ferrari LR, Bedford RF: General anesthesia prior to treatment of anterior mediastinal masses in pediatric cancer patients. Anesthesiology 72:991-995, 1990. Johnson D, Hurst T, Cujec B, et al: Cardiopulmonary effects of an anterior mediastinal mass in dogs anesthetized with halothane. Anesthesiology 74:725-736, 1991. Keon TP: Death on induction of anesthesia for cervical node biopsy. Anesthesiology 55:471-472, 1981. Mullen B, Richardson JD: Primary anterior mediastinal tumors in children and adults. Ann Thorac Surg 42:338-345, 1986. Prakash US, Abel MD, Hubmayr RD: Mediastinal mass and tracheal obstruction during general anesthesia. Mayo Clin Proc 63:1004-1011, 1988. Pullerits J, Holzman R: Anaesthesia for patients with mediastinal masses. Can J Anaesth 36:681-688, 1989. Robie DK, Mustafa HG, Pokorny J: Mediastinal tumors—airway obstruction and management. Semin Pediatr Surg 3:259-266, 1994. Shamberger RC, Holzman RS, Griscom NT, et al: CT quantitation of tracheal cross-sectional area as a guide to the surgical and anesthetic management of children with anterior mediastinal masses. J Pediatr Surg 26:138-142, 1991. Shamberger RC, Holzman RS, Griscom NT, et al: Prospective evaluation by computed tomography and pulmonary function tests of children with mediastinal masses. Surgery 118:468-471, 1995. Sinner WN: Directed fine needle biopsy of anterior and middle mediastinal masses. Oncology 42:92-96, 1985.

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Air Emboli Lisa Wise-Faberowski and Christian Seefelder Case Synopsis An 8-week-old infant is undergoing a craniectomy for sagittal craniosynostosis. As the surgeon is excising the cranial bone segment, precordial Doppler sounds change, and the blood pressure rapidly declines (Fig. 168-1).

prone, or lateral position. The risk of such entrainment is increased by low venous pressure or negative intrathoracic pressure, as occurs during spontaneous respiration. Small children are at special risk for venous air emboli. Significant blood loss may occur rapidly, and a small amount of blood may constitute a large portion of a child’s blood volume. This is a particular concern during craniotomies, because the calvaria is very thin. Further, the head is relatively large in proportion to body size, frequently resulting in the surgical site’s being elevated above the heart level during a supine or prone craniotomy. Finally, owing to the high prevalence of intracardiac shunts, amounts of venous air emboli that might be insignificant in an adult can result in paradoxical air emboli and be disastrous for a neonate.

PROBLEM ANALYSIS Definition Gas bubbles within the vascular system are termed gas emboli or air emboli. When venous air emboli enter the arterial circulation, they are termed paradoxical air emboli. Venous air emboli or paradoxical air emboli from gases dissolved in solution are released through effervescence, or they may enter the bloodstream from outside through insufflation or entrainment. The amount of gas dissolved in a liquid is a function of temperature and pressure. A sudden increase in the temperature of a gas-containing liquid can release gas bubbles from solution through effervescence. This can occur during rapid rewarming following hypothermic cardiopulmonary bypass or by rapidly warming cold intravenous fluids or blood products. It also happens in divers who experience a too-rapid decompression (the “bends”). More commonly, gas is introduced into the bloodstream by insufflation (e.g., during laparoscopy, thoracoscopy, or arthroscopy) or delivered with fluids or blood products by pressurized delivery systems. Veins that do not easily collapse can also entrain air—for example, venous sinuses in bone; open, large central veins; and open veins that are well above the level of the heart. For entrainment to occur, the vein opening must be sufficiently above the level of the heart to exceed central venous pressure (e.g., sitting craniotomy). Venous and paradoxical air emboli can occur in the supine,

Blood Pressure

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(mm Hg)

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Heart Rate

Awake patients may experience dyspnea and coughing as a result of venous air emboli. During anesthesia, changes in vital signs occur late and usually only after the entrainment of large amounts of air. Monitoring methods to detect venous air embolism, in decreasing order of sensitivity, include the following: ● ●

● ● ●

Echocardiography or Doppler ultrasonography End-tidal carbon dioxide (ETCO2) decrease or new appearance of end-tidal nitrogen (ETN2) Pulmonary artery pressure elevation Central venous pressure elevation Blood pressure reduction

Figure 168–1 ■ Schematic trend recording of blood pressure, heart rate, oxygen saturation (SaO2), and end-tidal carbon dioxide (ETCO2) concentration in an 8-week-old infant during sagittal craniosynostosis repair. The dotted line marks the time at which Doppler sounds changed dramatically. Note the sudden decrease in blood pressure and ETCO2, tachycardia, but little change in SaO2.

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Electrocardiogram (ECG) changes (e.g., right ventricular strain, ischemia, arrhythmias) Audible cardiac or “mill-wheel” murmur

Echocardiography and Doppler monitoring are exquisitely sensitive. They can detect even microbubbles from routine intravenous injections and minor entrainment of air. Air emboli detected with echocardiography and Doppler monitoring should alert the clinical team but must be interpreted cautiously, taking into account the severity of detected air (amount, duration, and associated clinical signs) as well as the clinical situation (e.g., craniotomy). ECG changes are more ominous, and an audible cardiac or “mill-wheel” murmur is least sensitive; however, when associated with echocardiographic or Doppler evidence of venous air embolism, they suggest that a significant amount of air has been entrained.

A

ECHOCARDIOGRAPHY Transthoracic or transesophageal echocardiography (TEE) enables the recognition of discrete air bubbles and the relative quantification of larger volumes (i.e., the density of snowstorm pattern). Further, TEE localizes emboli to the right or left side of the heart and detects cardiac anomalies (septal defects) that increase the risk of paradoxical air emboli (Fig. 168-2). TEE has been used in neonates who weigh as little as 2.5 kg. Limitations to its widespread use include the following: ● ●

● ●

High cost Requirement for a separate, highly trained observer during anesthesia and surgery Risk of injury to the pharynx, larynx, and esophagus Possible displacement of the endotracheal tube, especially during manipulation in small infants

Consequently, although TEE is a very sensitive technique for detecting venous air emboli, it is currently not practical in many institutions and may not be necessary as a routine monitor. DOPPLER ULTRASONOGRAPHY

B Figure 168–2 ■ Transesophageal echocardiographic four-chamber view of the left atrium (LA), right atrium (RA), left ventricle (LV), and right ventricle (RV). A, View of the heart without venous air embolism (VAE). B, Arrows indicate the reflections produced by air bubbles in the RA during VAE.

can also be decreased because of reduced pulmonary blood flow from pulmonary thromboembolism, sudden large blood loss, decreased venous return, or reduced cardiac output due to cardiac dysfunction, bradycardia, or arrhythmia. A falsely low ETCO2 may occur with gas leakage or air entrainment around an uncuffed endotracheal tube or dilution of small tidal volumes with fresh gas flows, unless sampling occurs near the endotracheal tube tip. Even so, a sudden change in ETCO2 from a previously stable baseline is usually significant.

Precordial Doppler ultrasonography is as sensitive as TEE for the detection of venous air emboli. It enables semiquantitative assessment of air emboli but does not permit localization of air to the right or left side of the heart. The smaller distance between the heart and chest wall increases the sensitivity of Doppler ultrasonography in infants. The probe needs to be placed over the right side of the heart, generally at the nipple line, just to the right of the sternum. Minor movement may dislodge the probe, so it should be securely fastened to the chest. Correct positioning is confirmed by injecting a few milliliters of intravenous solution into an intravenous catheter while listening for a characteristic loud change in Doppler sounds. Doppler probes are easily dislodged and can cause pressure necrosis in prone patients. This can be avoided in small infants by placing the Doppler probe on the patient’s back. Electrocautery and echocardiography can interfere with Doppler ultrasonography.

Unless air is added to the inspired gases, N2 disappears from expired gas. Reappearance of N2 indicates a circuit leak or alveolar diffusion from venous air emboli. Without an air leak, the sudden reappearance of ETN2 is quite specific for venous air emboli but not very sensitive; even large venous air emboli increase ETN2 by only 1% to 2%.

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Significant venous air emboli reduce the ETCO2 concentration owing to increased dead-space ventilation. However, ETCO2

Pulmonary artery catheters reveal increased pulmonary artery pressure due to pulmonary vascular obstruction by air.

EXHALED NITROGEN

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Similar to low central venous pressure, low pulmonary artery wedge pressure may predispose to venous air emboli and paradoxical air emboli. However, pulmonary artery catheters in infants and small children are not practical or necessary in most situations.

● ●

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●

CENTRAL VENOUS CATHETER Central venous catheter placement is justified for high-risk procedures, such as craniotomy in the sitting position, even in a small child. It is rarely necessary for a healthy child when the bed is flat. A central venous catheter is useful for administering fluids and medications if peripheral venous access is difficult, as well as for monitoring central venous pressure. Low central venous pressure may indicate the need for fluid replacement to reduce the risk of venous air emboli; a sudden increase may signal major venous air emboli. A central venous catheter is sometimes effective for retrieving large venous air emboli, especially if the catheter has multiple orifices and the tip is near the junction of the superior vena cava and right atrium. This position is confirmed by radiograph or by recording a unipolar ECG with a right atrial ECG adapter. To do so, substitute the catheter lead for the V lead, and observe the characteristic P-wave changes (increased amplitude leading to tall, spiked P waves that may exceed R- or S-wave amplitudes) as the catheter is advanced into the right atrium. ARTERIAL BLOOD PRESSURE An arterial catheter allows continuous assessment of blood pressure and arterial blood gas determinations. Its use is justified in any procedure with a significant risk for bleeding or venous air emboli, especially in young children. PULSE OXIMETRY With significant venous air emboli, oxygen desaturation may be detected by pulse oximetry. Arterial blood gas analyses may reveal hypercarbia and an increased arterial-alveolar oxygen gradient.

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Angiography and cardiac catheterization Placement, use, and discontinuation of circuits for cardiopulmonary bypass or extracorporeal membrane oxygenation Hemodialysis, plasmapheresis, or central venous catheter insertion Barotrauma during positive-pressure ventilation Use of air to identify epidural space through loss of resistance

Implications Significant pulmonary air emboli can result in decreased cardiac output, arterial hypotension, and cardiovascular collapse as a result of one or more of the following: ● ● ● ●

● ●

Obstruction of peripheral pulmonary vessels by gas bubbles Air lock from gas in large pulmonary vessels or the heart Reflex pulmonary vasoconstriction Right ventricular failure secondary to pulmonary hypertension Electromechanical dissociation or arrhythmias Myocardial ischemia from reduced coronary perfusion pressure, coronary paradoxical air emboli, or hypoxemia

Impaired pulmonary function with carbon dioxide retention and arterial oxygen desaturation can result from the following: ●

●

●

Ventilation-perfusion mismatch from pulmonary vascular obstruction with increased dead-space ventilation Reactive bronchoconstriction with increased airway resistance Interstitial pulmonary edema

Gas bubbles enter the arterial circulation directly or through intracardiac communications. Most neonates have a patent foramen ovale, usually with left-to-right shunting. Although the foramen ovale may be probe-patent in 25% to 50% of infants and in 20% to 30% of adults, rarely is shunting demonstrated. However, increased right-sided pressures with venous air emboli may facilitate paradoxical air emboli across a patent foramen ovale. Paradoxical air emboli can result in myocardial or cerebral ischemia.

Risk Assessment Pediatric patients are at increased risk for venous air emboli during the following procedures: ●

●

●

● ●

● ●

Key to the successful management of venous air emboli during surgery is close communication between the anesthesiologist and surgeon. In addition, the following guidelines should be considered: ●

●

●

Doppler sounds should be audible to everyone. Intravenous injections likely to cause Doppler sound changes should be announced beforehand. If Doppler ultrasonography indicates venous air emboli unrelated to injections, the surgeon should use indicated measures (e.g., apply bone wax, flood the surgical field with saline or cover it with saline-saturated gauze) to reduce air entry. When venous air embolism is suspected, look for an associated decrease in ETCO2 or blood pressure, indicating a significant venous air embolus or blood loss. Reappearance of ETN2, if monitored, confirms the diagnosis of venous air emboli.

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Any surgical procedure in which the operative site is sufficiently above the heart, especially when sudden and severe blood loss is possible Craniotomy with a large craniectomy (e.g., craniosynostosis repair) Craniotomy with an operative site directly over large dural venous sinuses (e.g., posterior fossa exploration) Craniofacial procedures (e.g., frontal or midface advancement) with large bony excision and elevation of the head to minimize bleeding Certain orthopedic procedures (e.g., scoliosis surgery) General surgical procedures (e.g., liver surgery) with a high risk of entering large venous structures (e.g., hepatic veins, inferior vena cava) Liver transplantation surgery Any open-heart surgery

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Nitrous oxide, though not contraindicated for these procedures, should be promptly discontinued in the presence of venous air emboli. The patient is then ventilated with 100% oxygen to avoid further enlargement of gas bubbles and to treat hypoxemia. Change the table position so that the surgical site is below the level of the heart. Be sure that the patient is securely fastened to the operating table. Gentle compression of the jugular veins has been recommended to reduce air entry and to unmask possible entry sites, but care must be taken to avoid carotid artery compression. Although air may be aspirated through a central venous or pulmonary artery catheter, it does not usually allow removal of a significant amount of entrained air. Positioning the patient in the left lateral decubitus position has been suggested to aid in resuscitation, but it may not be practical during some procedures. Support cardiovascular function with additional intravenous fluids or inotropic agents (ephedrine, epinephrine) as indicated. Cardiopulmonary resuscitation is rarely required, especially if the embolus is detected quickly and appropriate measures are instituted.

PREVENTION A careful history and physical examination, as well as familiarity with the planned surgery, are essential to assess the risk

for venous air emboli or paradoxical air emboli. Use precordial Doppler ultrasonography as a sensitive and noninvasive monitor to detect venous air emboli early. Consider the use of filters or bubble traps when significant or rapid fluid or blood replacement is anticipated. For high-risk procedures, be prepared to use measures to reduce air entrainment and venous air emboli (e.g., positioning, use of bone wax, flooding the surgical field).

Further Reading Cucchiara RF, Bowers B: Air embolism in children undergoing suboccipital craniotomy. Anesthesiology 57:338-339, 1982. Eldredge EA, Soriano SG, Rockoff MA: Pediatric neurosurgical anesthesia. In Coté CJ, Todres ID, Goudsouzian NG, Ryan JF (eds): A Practice of Anesthesia for Infants and Children, 3rd ed. Philadelphia, WB Saunders, 2001, pp 493-521. Faberowski LW, Black S, Mickle JP: Incidence of venous air embolism during craniectomy for craniosynostosis repair. Anesthesiology 92:20-23, 2000. Harris MM, Strafford MA, Rowe RW, et al: Venous air embolism and cardiac arrest during craniectomy in a supine infant. Anesthesiology 65:547-550, 1986. Harris MM, Yemen TA, Davidson A, et al: Venous embolism during craniectomy in supine infants. Anesthesiology 67:816-819, 1987. Markhorst DG, Rothuis E, Sobotka-Plojhar M, et al: Transient foramen ovale incompetence in the normal newborn: An echocardiographic study. Eur J Pediatr 154:667-671, 1995. Sethna NF, Berde CB: Venous air embolism during identification of the epidural space in children. Anesth Analg 76:925-927, 1993.

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Lisa M. Montenegro and David R. Jobes Case Synopsis A 5-month-old infant presents to the operating room for exploratory laparotomy after being involved in a motor vehicle accident. He is tachycardic (heart rate 180 beats per minute) and normotensive (blood pressure 80/55 mm Hg), with a grossly distended abdomen on arrival to the operating room. On opening of the abdomen, the blood pressure falls to 50/30 mm Hg. Bleeding from a badly lacerated liver necessitates rapid and massive volume replacement.

PROBLEM ANALYSIS Definition For pediatric patients, massive transfusion is defined as the need to replace at least one blood volume; blood volume varies by age, being approximately 80 mL/kg at birth and 65 mL/kg at age 12 years. Although transfusion under any circumstances carries some risk (e.g., infection, transfusion reactions; see Chapters 49 and 50), massive transfusion involves a unique set of risks and complications, many of which require special consideration in the pediatric population.

Recognition Massive transfusion and related complications are the result of therapy for acute intravascular volume loss, which includes rapid repletion of intravascular volume with crystalloid, non–red blood cell (RBC) colloids, blood, and blood products. This can occur in the following situations: ● ● ● ● ● ● ● ●

Major trauma Gastrointestinal bleeding Major vascular surgery Cardiac surgery Hepatic surgery Craniofacial surgery Radical oncologic surgery Spinal instrumentation

● ●

Administration of anticoagulants or other drugs Clotting factor deficiencies ● Hereditary, dilutional, or acquired ● Due to clotting factor consumption ● Due to extracorporeal membrane oxygenation and circulatory assist devices

●

Hypothermia Use of a cell-saver or autotransfusion device

Loss of up to 30% of the blood volume is usually well tolerated in infants and children. Signs of hypovolemia may be subtle and include a small to moderate increase in heart rate and decrease in blood pressure. Such blood volume loss in otherwise healthy children can be replaced with crystalloid solutions without significant hemodynamic or cardiovascular compromise.

Risk Assessment Any patient who requires acute, massive intravascular volume replacement is at risk for complications related to massive transfusion. Infants and neonates appear to be at increased risk owing to the immaturity of their native coagulation systems. The following complications are more likely to occur in this patient subset: ● ● ● ●

Dilutional coagulopathy Hypothermia Hypokalemia or hyperkalemia Hypocalcemia

A more complete list of generally recognized complications is provided in Table 169-1.

Implications The hemostatic function of the coagulation system is normal at birth. However, quantities of many procoagulant and inhibitory proteins do not reach their adult concentrations until after puberty. Andrew and colleagues measured an extensive clotting profile, including prothrombin time (PT), partial thromboplastin time (PTT), and clotting factor concentrations, in healthy neonates, infants, and children (from 1 day to 16 years of age). Although most test results did not differ from normal values for adults, there was greater variability in PT, although mean PT values were not significantly different from those in adults. The PTT was significantly prolonged in neonates and infants; however, adult PTT values were attained by age 3 months. The concentrations of all clotting factors, including vitamin K–dependent factors (II, VII, IX, X), 677

PEDIATRICS & NEONATOLOGY

Anticipating the need for massive transfusion may allow the early recognition and aggressive treatment of its associated complications, thereby avoiding the risk of acute intravascular volume depletion. Some circumstances that enhance and may contribute to the development of transfusion-related complications include the following:

●

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Clinically Significant Complications of Massive Blood Transfusion

Dilutional coagulopathy Acid-base derangement Hypothermia Hyperkalemia Hypokalemia Citrate load (hypocalcemia) Microembolization or microaggregate formation: ARDS? Infectious (HIV, CMV, hepatitis, West Nile virus, bacterial) Hemolysis Anaphylaxis Change in RBC deformability Jaundice (long term) ARDS, acute respiratory distress syndrome; CMV, cytomegalovirus; HIV, human immunodeficiency virus; RBC, red blood cell.

plasminogen, and the plasma protease inhibitors (antithrombin 3, α2-antiplasmin, C1-esterase inhibitor, and α1-antitrypsin), were substantially reduced at birth. Although all clotting variables had independent maturation processes, the concentrations of factors II, VII, IX, and X were less than those for adults until age 16 years. In contrast, plasminogen and plasma protease inhibitors approached or reached adult levels by age 5 years. Each of the vitamin K–dependent factors also displayed its own age-related maturation process. Factor VII was the first to achieve near-adult values at 5 days of age. Neonates and infants have laboratory values that are outside the adult reference ranges for the integrity of coagulation (especially PT and PTT). As such, normal laboratory values for adults do not measure neonatal hemostatic competence, and comparisons must be made with caution.

MANAGEMENT Management goals are to maintain the quantitative and qualitative integrity of intravascular volume. Oxygen carrying capacity and hemostasis are of primary importance. In the face of massive volume loss, these goals can be met only by transfusing whole blood or components of fractionated whole blood. The intravenous administration of any blood product, especially pooled components, is associated with a substantial risk of complications. This risk is amplified and multiplied during massive transfusion (see Table 169-1).

Dilutional Coagulopathy The most common complication of massive transfusion is dilutional coagulopathy. Dilution of hemostatic blood elements occurs from substances used for volume expansion (crystalloid, colloid, hetastarch, albumin), transfused blood, and blood products. The administration of nonblood substances begins the dilutional process. Component therapy may also result in the dilution of hemostatic blood elements, because each lost component is not precisely replenished. When replacement approaches or exceeds approximately one blood volume, continued dilution of remaining platelets and clotting factors results in impaired hemostasis.

Component Replacement Therapy Controversy exists regarding the timing of replacement of non-RBC blood products. Some suggest that products other than RBCs should not be administered until a coagulopathy or specific factor deficiency is documented. This approach is intended to limit transfusion risk and seems plausible when the loss and replacement are expected to be about one blood volume. However, when the loss is expected to or does exceed one blood volume, or bleeding is not controlled, early administration of non-RBC products is necessary to prevent enhanced blood loss from coagulopathy. Coté’s group demonstrated an exponential decline in the number of available platelets versus the number of blood volumes replaced. However, the absolute decline is not as great as one would expect based on blood loss and replacement. This may be due to platelet recruitment. Qualitative platelet function is further reduced by hypothermia, with only 12% of the original platelet function remaining after 24 hours of storage at 4°C. The same concept likely applies to other clotting factors as well. With the exception of thrombocytopenia (platelet counts <100,000/mm3), the existence of a coagulopathy can rarely be documented in a timely fashion. Therefore, platelets and fresh frozen plasma must be administered during a massive transfusion without waiting for a documented coagulopathy to develop. Although no differentiation is made between infants and adults, some recommended transfusion protocols include the following: ●

●

0.3 unit/kg platelets when the platelet count is less than 100,000 mm3 or when more than 1.5 blood volumes have been transfused One unit of fresh frozen plasma and 4 units of platelets for every 5 units of packed RBCs transfused

Indications for component replacement and the positive and negative attributes of specific component therapy are listed in Table 169-2. Because infants and neonates have lower plasma clotting factor concentrations than adults do, dilutional coagulopathy with massive transfusion develops more quickly. Therefore, the threshold for replacement of coagulation factors in infants is lower.

Recombinant Factor VIIa Recombinant factor VIIa has been used to treat microvascular bleeding when replacement therapy has been judged adequate but the bleeding continues. Originally developed to treat hemophilia, recombinant factor VIIa promotes hemostasis at the site of injury by interacting with tissue factor. It is beginning to be incorporated into trauma management protocols, although controlled clinical trials for this application are currently lacking. Case reports describe dramatic cessation of bleeding after its administration, and it should be considered as a lifesaving measure in pediatric patients with continued microvascular bleeding despite adequate replacement therapy. Recombinant factor VIIa has a short half-life and requires redosing (90 units/kg) every 2 hours until bleeding is controlled. Other drugs, such as aprotinin, are increasingly reported in the cardiac and orthopedic surgical literature as adjuncts to reduce blood loss and transfusion requirements.

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Indications for Component Replacement and Anticipated Hemostatic Attributes

Product

Indication

Positive Attributes

Negative Attributes

Packed RBCs

Hypovolemia associated with anemia

Dilutional coagulopathy; hemolytic reaction; infection; rare blood types may be unavailable

Fresh whole blood

Anemia; hypovolemia with anemia; massive transfusion (neonates)

Fresh frozen plasma

Dilutional coagulopathy

Readily available (autologous, homologous, cell saver blood); more efficient than blood substitutes; maintains or ↑O2 transport capacity and BV Less donor exposure, especially neonates; platelets and clotting factors functional; maintains or ↑O2 transport capacity and BV Replaces all protein clotting factors at presumed normal adult concentrations; available universally in frozen state

Cryoprecipitate

Dilutional coagulopathy; factor VIII deficiency

High concentrations of fibrinogen and factor VIII

Platelets

Platelet dysfunction; thrombocytopenia

Increases platelet count

Limited availability; hemolytic transfusion reaction

Timing of administration; infection; concentration of specific factors may be inadequate in some cases (e.g., fibrinogen); availability (minimum of 30 min to thaw) Pooled product; risk of infection; timing of administration; availability (not stored in all blood banks) Hypotension; single donor vs multiple donors; infection; brief functional half-life

BV, blood volume; RBCs, red blood cells.

Laboratory Testing Repetitive laboratory tests to identify the development and correction of coagulopathy are necessary. However, massive transfusion may alter normal tests of hemostasis. Murray and colleagues reported that in the absence of thrombocytopenia, PT and PTT values in adult surgical patients may be increased to 1.5 times control values without clinical evidence of increased or unusual blood loss. Because all blood and blood derivatives are obtained from adult donors, when massive transfusion occurs in a pediatric patient, all laboratory tests of hemostatic function should be interpreted in light of the adult donor pool. A platelet count of more than 100,000/mm3 is necessary after massive volume replacement because of qualitative changes in platelet function. Some variation exists in the dilution of individual clotting factors. When more than 1.5 blood volumes are replaced, concentrations of

Table 169–3

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fibrinogen, factor V, and factor VIII become inadequate (20% of normal), whereas other clotting factor concentrations are less affected. In acute situations, laboratory measurement of specific clotting factor concentrations is not helpful, because the test results are not immediately available.

Autotransfusion and Cell-Saver Devices The use of blood salvage devices to return lost RBCs has become commonplace. Processing washes the salvaged blood and returns concentrated RBCs suspended in normal saline. Although these devices reduce the need to administer homologous RBCs, they contribute to the dilution of all hemostatic elements. Thus, when transfusion approaches or surpasses 1.5 blood volumes, laboratory assessment of hemostasis is essential, regardless of the replacement strategy used (Table 169-3).

Laboratory Assessment and Treatment Indications when Transfusion Approaches or Surpasses 1.5 Estimated Blood Volumes Treatment Indication

Metabolic Arterial blood gases: pH, PO2, PCO2, base excess, hematocrit Electrolytes K+, Ca2+, Mg2+, Na+, Cl− Hemostasis Prothrombin time Partial thromboplastin time Fibrinogen Platelet count

Deviation from normal laboratory values Deviation from normal laboratory values Continued gross hemorrhage or microvascular bleeding present ≥1.5 × normal value ≥1.5 × normal value ≤100 mg/dL ≤100,000/mm3

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Laboratory Assessment

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Biochemical Changes for Blood Stored in CPD and CPDA-1 CPD

Biochemical Change Days of storage % Viable cells 24 hr after transfusion pH (37°C) 2,3-DPG (% of initial value) Plasma K+ (mmol/L) Plasma Na+ (mmol/L) ATP (% of initial value)

CPDA-1

Whole Blood 0 100 7.2 100 3.9 168 100

21 80 6.84 86 21.0 156 86

Whole Blood 0 100 7.6 44 4.2 169 100

35 79 6.98 <10 27.3 155 56 ± 16

RBCs 0 100 7.55 100 5.1 169 100

35 71 6.71 <10 78.5* 111 45 ± 12

*The plasma K+ concentration appears to be unusually high in RBC units stored for 35 days because the total plasma in these units is only about 70 mL. ATP, adenosine triphosphate; CPD, citrate phosphate dextrose; CPDA-1, citrate phosphate dextrose adenine; DPG, diphosphoglyceride; RBC, red blood cell. From Vengelen-Tyler V (ed): Technical Manual, 12th ed. Bethesda, Md., AABB, 1996, p 138.

Fresh Whole Blood Not all patients are optimally managed by component therapy for massive volume loss. The administration of fresh whole blood (24 to 48 hours old) to children younger than 2 years undergoing repair of complex congenital cardiac lesions significantly reduces postoperative hemorrhage compared with reconstituted blood (with fresh frozen plasma and platelets) or component therapy. However, the use of fresh whole blood is impractical for emergencies and is difficult to provide logistically. Additionally, nucleic acid testing of donated blood for human immunodeficiency virus (HIV) may not be accomplished in less than 48 hours, making fresh whole blood less safe than banked blood. Despite its theoretical advantage in massive transfusion, this technique has not been studied outside the infant cardiac surgery population.

Metabolic Derangement Acid-base alterations may occur simply from the blood collection and preservation process. The pH of freshly collected blood added to CPD (citrate phosphate dextrose) solution decreases to 7.0; over the next 21 days of storage, it decreases to 6.84 (Table 169-4). The majority of this decrease is due to an increase in the partial pressure of carbon dioxide, because storage containers do not permit its egress.

Hypothermia Hypothermia commonly occurs with massive transfusion and can be a cause of coagulation dysfunction. The trauma literature supports a 100% mortality rate if a patient’s core temperature falls below 32°C, regardless of the severity of injury.1 Large volumes of unwarmed crystalloid, non-RBCcontaining colloids, blood, and blood products can produce cardiac arrest, especially when administered directly into the central circulation in small children.

Hyperkalemia Hyperkalemia can develop with the rapid transfusion of stored RBCs. The potassium concentration in stored blood increases

over time as cells lyse (see Table 169-4). Although patients with normal renal function rarely display hyperkalemia or its hemodynamic consequences, neonates and infants with immature renal function, or patients with renal dysfunction, should receive washed RBCs. Occasionally, seeming paradoxical delayed hypokalemia may be seen after the transfusion of stored RBCs ceases.

Hypocalcemia Hypocalcemia, or functional hypocalcemia, occurs after the rapid administration of blood stored with citrate. The citrate chelates the calcium and other covalent cations, such as magnesium. Hypotension can result from overly rapid transfusion, especially of platelet concentrates or fresh frozen plasma. Correction with intravenous calcium is immediate. Calcium replacement in asymptomatic patients is controversial, because ionized calcium levels return to normal after acute blood administration ceases.

Pulmonary Dysfunction Microaggregate formation and pulmonary deposition are believed to be mechanisms by which acute respiratory distress syndrome develops after massive transfusion. The incidence of acute respiratory distress syndrome has been reduced with the use of 10-μm filters for blood administration. In addition, this complication is seen predominantly in patients with preexisting or acute lung injury, suggesting that other factors also are involved.

Infection The risk of infection escalates with massive transfusions, either by the transmission of infectious agents or by the depression of immune responses. Although the risk for transmission of HIV, viral hepatitis, West Nile virus, and cytomegalovirus is low, each donor exposure increases a patient’s likelihood of contracting a potentially fatal disease. Rarely, bacterial contamination of a blood product may occur.

Hemolysis 1 Assuming such hypothermia has not been deliberately imposed (e.g., cardiopulmonary bypass).

Hemolysis, usually due to an ABO incompatibility, can be catastrophic. Currently, the most common cause of this

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Algorithm for the management of massive transfusion. ABG, arterial blood gas; FFP, fresh frozen plasma; RBC, red blood cell.

complication is administrative error. Antibodies found in the Kell, Kidd, and Lewis systems also may precipitate a hemolytic response. Therefore, whenever possible, a complete type and crossmatch should be carried out before administering any blood products.

Additional personnel are essential to track multiple details, facilitate communication, and transport specimens and supplies. Development of an institutional protocol for massive transfusion (Fig. 169-1) is suggested.

Further Reading PREVENTION Successful preventive management of patients with acute, massive hemorrhagic volume loss requires the following: ● ● ● ● ●

Blood bank support Laboratory support Adequate personnel Body temperature control Warming of all intravenous and surgical irrigation fluids

PEDIATRICS & NEONATOLOGY

The prevention of complications requires the immediate availability of adequate blood bank resources, appropriate administration equipment, and rapid laboratory turnaround time. Careful recording and reporting of the quantity and type of all volume infused (including crystalloid, colloid, and blood products), along with timely communication of anticipated needs to the blood bank, are critical.

Andrew M, Paes B, Milner R, et al: Development of the human coagulation system in the full-term infant. Blood 70:165-172, 1987. Andrew M, Vegh P, Johnston M, et al: Maturation of the hemostatic system during childhood. Blood 80:1998-2005, 1992. Coté CJ, Liu LM, Szyfelbein SK, et al: Changes in serial platelet counts following massive blood transfusion in pediatric patients. Anesthesiology 62:197-201, 1985. Hardy JF, De Moerloose P, Samama M: Groupe d’interet en Hemostase Perioperatoire: Massive transfusion and coagulopathy: Pathophysiology and implications for clinical management. Can J Anaesth 51:293-310, 2004. Jurkovich GL, Greiser WB, Luterman A, et al: Hypothermia in trauma victims: An ominous predictor of survival. J Trauma 27:1019-1024, 1987. Levi M, Peters M, Buller HR: Efficacy and safety of recombinant factor VIIa for treatment of severe bleeding: A systematic review. Crit Care Med 33:883-890, 2005. Manno CS, Hedberg KW, Kim HC, et al: Comparison of the hemostatic effects of fresh whole blood, stored whole blood, and components after open heart surgery in children. Blood 77:930-936, 1991. Murray DJ, Olson J, Strauss R, et al: Coagulation changes during packed red cell replacement of major blood loss. Anesthesiology 69:839-845, 1988.

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Zeev N. Kain Case Synopsis A 4-year-old boy presents for inguinal hernia repair. In the preoperative holding area, he appears scared and agitated and refuses to leave his mother’s lap. On separation, he cries and tries to escape from the anesthesiologist. One week after surgery, the mother reports major behavioral changes in the boy since his operation, including nightmares and temper tantrums.

PROBLEM ANALYSIS Definition The perioperative period is frequently an extremely traumatic time for both children and parents. Subjective feelings of tension, apprehension, and worry characterize preoperative anxiety in children. Preoperative anxiety stimulates sympathetic, parasympathetic, and endocrine systems, leading to increases in heart rate, blood pressure, and cardiac excitability. These reactions reflect the child’s fear of separation from parents and the home environment, loss of control, and fear of unfamiliar routines, surgical instruments, and hospital procedures. Thus, it is no surprise that up to 65% of all children undergoing anesthesia and surgery develop extreme anxiety and fear during the perioperative period. Of perhaps greater importance than the child’s behavior in the preoperative holding area is the child’s behavior after the surgery. Clinicians and investigators have long recognized postoperative psychological reactions such as general anxiety, nighttime crying, enuresis, separation anxiety, and temper tantrums. These behavioral changes are of particular concern if they persist for an extended period and negatively affect the child’s responses to subsequent medical care or interfere with his or her emotional and cognitive development.

Recognition Children having anesthesia and surgery express many forms of anxiety. Some explicitly verbalize their fears, whereas others express their anxiety behaviorally. Many children look scared, become agitated, breathe deeply, tremble, stop talking or playing, or begin to cry. Others may wet themselves unexpectedly, have increased motor tone, and actively attempt to escape from medical personnel. The specific maladaptive behaviors in any particular child can vary widely. However, the most common ones are separation anxiety, eating problems, increased fear of doctors and hospitals, bad dreams or nightmares, and temper tantrums. Perioperative anxiety is associated with increased levels of serum cortisol, epinephrine, growth hormone, and adrenocorticotropic hormone. Reports show a significant correlation between increased heart rate and blood pressure and behavioral ratings of anxiety. Preoperative anxiety is 682

often associated with a relative vagal predominance in sympathovagal-mediated heart rate variability.

Risk Assessment The incidence of preoperative anxiety in young children is reported to range from 40% to 60%. Children of anxious parents, shy and inhibited children, children with a history of previous surgery, children with a history of previous poorquality medical encounters, and children aged 4 to 7 years are at increased risk for the development of preoperative anxiety. Postoperative maladaptive behavioral responses, such as general anxiety, nighttime crying, enuresis, separation anxiety, and temper tantrums, occur in 13% to 40% of children 2 weeks after surgery; 3% to 20% of these children continue to demonstrate maladaptive behaviors 6 months after surgery (Fig. 170-1). More significant behavioral changes, such as newonset enuresis, are rare and present in only 0.8% of children. It is important to emphasize that although a large number of young children develop negative behavioral responses in the immediate postoperative period, the magnitude of these changes is limited, and only a minority of children have persistent, long-term maladaptive behavioral responses. The child’s age, baseline temperament, number of siblings, enrollment in day care, and preoperative anxiety are all independent predictors for postoperative maladaptive behaviors in multivariate models (Tables 170-1 and 170-2). Genitourinary surgery is associated with the highest incidence of postoperative behavioral changes. Pressure-equalizing myringotomy and tympanic membrane tube placement have the lowest incidence of postoperative negative behavioral changes.

Implications Preoperative anxiety may be a hardship on both the child and the parents and lead to immediate postoperative negative behavioral responses. Long-lasting psychological effects that influence the child’s response to subsequent medical care and interfere with normal development have been described. Although reports are conflicting, they suggest that preoperative anxiety may delay gastric emptying and increase gastric acidity; therefore, some practitioners consider this response to be a risk factor for aspiration pneumonitis.

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Behavioral Modification Parental presence during the induction of anesthesia has been suggested as an alternative to preanesthetic medication. The potential benefits of parental presence include the following: ● ● ●

Avoidance of screaming and struggling (separation anxiety) Reduction in the child’s anxiety during induction Potential reduction of the long-term behavioral effects of surgery

Common objections to parental presence include the following: ● ● ● ●

Figure 170–1 ■ Changes over time in the prevalence of negative behavioral responses based on the Posthospitalization Behavior Questionnaire. Separation anxiety was the most common maladaptive behavior reported by parents at both 2 weeks (40.3%) and 6 months (6.3%). The prevalence of behaviors in all six categories decreased significantly from 2 weeks to 6 months and 1 year (numbers in bars represent percentages of total subjects). *P <.05. (From Kain ZN, Mayes LC, O’Connor T: Preoperative anxiety in children: Predictors and outcomes. Arch Pediatr Adolesc Med 150:1238-1245, 1996.)

Preoperative anxiety is also associated with an increased risk of symptoms of emergence delirium upon awakening from anesthesia, as well as altered cortisol and epinephrine responses over the first 24 hours after surgery.

MANAGEMENT Behavioral modification and pharmacologic agents are the two preoperative interventions directed toward reducing perioperative anxiety.

Table 170–1

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Disruption of the operating room routine Compromise of operative sterility Crowded operating rooms Additional stress on the anesthesiologist

Experimental data do not support the routine use of this intervention. Although earlier studies suggested reduced anxiety, more recent reports indicate that routine parental presence during the induction of anesthesia is not always beneficial. Children who benefit are the following: ● ● ●

Generally, those older than 4 years Those with a shy and inhibited personality Those with a calm parent

Most parents prefer to be present during the induction of anesthesia, regardless of the child’s age or previous surgical experience (even those whose children received sedative premedication at a previous surgery). Among parents present during the induction of anesthesia, the vast majority believe that they were of some assistance to the child and the anesthesiologist. However, more than 90% of parents report feeling some degree of anxiety during induction. Although this is clinically significant, it is not sufficiently debilitating to cause concern for the parents’ health. Parental presence during the induction of anesthesia is increasing in the United States, even though available data indicate that it is

Risk Factors for Negative Behavioral Changes Two Weeks after Surgery Outcome

4 vs 6 years of age

Separation anxiety General anxiety Separation anxiety Apathy and withdrawal Sleep anxiety Separation anxiety Eating anxiety

9.4 3.3 6.6 6.6 3.9 3.4 4.2

Separation anxiety General anxiety

3.5 (1.3-9.6) 2.7 (1.1-6.8)

Not enrolled vs enrolled in a day-care facility Very anxious mother vs calm mother in the holding area∗ Child who is very anxious on separation vs one who is calm on separation† No siblings vs siblings Child who is very impulsive vs one who is not very impulsive‡

Relative Risk (95% CI) (1.2-39) (1.1-7.8) (1.2-29) (1.6-19.1) (1.1-14) (1.2-6.7) (1.3-8.7)

∗“Very anxious” is defined as an anxiety score in the upper 25th percentile on the State-Trait Anxiety Inventory (STAI) state subscale; “calm” is defined as a score in the lower 25th percentile on the same scale. † Measured by the Clinical Anxiety Rating Scale. ‡ “Very impulsive” is defined as an impulsivity score in the upper 25th percentile on the Emotionality, Activity, Sociability, Impulsivity Instrument; “not very impulsive” is defined as a score in the lower 25th percentile on the same instrument. CI, confidence interval. From Kain ZN, Mayes LC, O’Connor T: Preoperative anxiety in children: Predictors and outcomes. Arch Pediatr Adolesc Med 150:1238-1245, 1996.

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Predictor Variables

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Risk Factors for Negative Behavioral Changes Six Months after Surgery

Predictor Variables

Outcome

Relative Risk (95% Cl)

No siblings vs siblings

General anxiety Separation anxiety Aggressiveness Eating anxiety Sleep anxiety

3.0 (1.4-6.9) 2.0 (1.1-3.5) 2.0 (1.1-4.1) NA† 4.8 (1.2-20.4)

Very anxious child vs calm child in the holding area∗ Very anxious mother vs calm mother in the holding area‡

∗“Very anxious” is defined as an anxiety score in the upper 25th percentile on the Venham Picture Test; “calm” is defined as a score in the lower 25th percentile on the same test. † Not applicable; relative risk cannot be calculated because of a 0 value—0% vs 17% (P =.04). ‡ As measured with the State-Trait Anxiety Inventory (STAI) state subscale. CI, confidence interval. From Kain ZN, Mayes LC, O’Connor T: Preoperative anxiety in children: Predictors and outcomes. Arch Pediatr Adolesc Med 150:1238-1245, 1996.

beneficial for only some children. All factors and circumstances should be considered whenever the question of parental presence arises. Research in this area is now focusing more on what parents do during induction of anesthesia rather than their mere presence or absence.

population at high risk for preoperative anxiety and use preoperative sedatives only for those children.

Pharmacologic Agents

Preoperative behavioral preparation programs are available, but increasingly fewer U.S. hospitals routinely offer them. These programs consist of child and family preoperative teaching, an orientation tour, and role-playing using dolls to allow the child to become familiar with a new and anxietyprovoking environment. This familiarity may enhance cooperative behavior and lessen anxiety in the preoperative holding area and operating room. Although most studies suggest that behavioral preparation of children reduces stress and enhances coping mechanisms, other reports indicate that such programs may actually “sensitize” younger children.

Sedative premedication before surgery is an effective and widely used method for decreasing anxiety in young children. The primary goal of such premedication is to facilitate smooth and anxiety-free parental separation. A detailed discussion of preanesthetic medication in children is beyond the scope of this chapter. Only the most commonly used agents are discussed. Midazolam is by far the most commonly used agent for premedication. It has a rapid onset and offset of action and has predictable effects, without causing cardiorespiratory depression. It can be given by any route, depending on the clinical setting. However, when used for preoperative anxiety, it is most commonly administrated orally (0.5 mg/kg) or nasally (0.2 mg/kg). When the drug is mixed with flavored syrup or Tylenol and administered orally, midazolam provides excellent sedation and anxiolysis in 20 to 30 minutes. Despite the high incidence of crying on nasal instillation, this provides predictable effects within 10 minutes. Midazolam can also be given per rectum (0.3 to 0.4 mg/kg), although older children may object to this route. Ketamine is especially useful as a premedication or induction agent for uncooperative patients. When mixed with a cola-flavored soft drink and given orally (6 mg/kg), ketamine provides predictable sedation in 20 to 25 minutes. The nasal route provides good sedation at similar doses. Fentanyl’s lipid solubility makes it ineffective as an oral premedication. However, oral transmucosal absorption in the form of a fentanyl lollipop can produce effective preoperative sedation and facilitate the inhalational induction of anesthesia. Transmucosal fentanyl (10 to 15 μg/kg) has been reported to cause facial pruritus, and perioperative nausea and vomiting occur in a significant number of children. Finally, it is important to emphasize that routine preoperative administration of sedatives to all children may result in increased pharmacy costs and the need for additional nursing staff and appropriately equipped bed space in the holding area. It is therefore important to identify the

PREVENTION

Further Reading Brophy CJ, Erickson MT: Children’s self-statements and adjustment to elective outpatient surgery. J Dev Behav Pediatr 11:13-16, 1990. Kain ZN, Caldwell-Andrews AA, Maranets I, et al: Preoperative anxiety, emergence delirium and postoperative maladaptive behaviors: Are they related? A new conceptual framework. Anesth Analg 99: 1648-1654, 2004. Kain ZN, Caldwell-Andrews AA, Mayes LC, et al: Parental presence during induction of anesthesia: Physiological effects on parents. Anesthesiology 98:58-64, 2003. Kain ZN, Caldwell-Andrews AA, Wang SM, et al: Parental intervention choices for children undergoing repeated surgeries. Anesth Analg 96:970-975, 2003. Kain ZN, Mayes LC: Anxiety in children during the perioperative period. In Borestein MH, Genevro JL (eds): Child Development and Behavioral Pediatrics. Mahwah, NJ, Lawrence Erlbaum, 1996, pp 85-103. Kain ZN, Mayes LC, Caramico L: Preoperative preparation in children: A cross sectional study. J Clin Anesth 8:508-514, 1996. Kain ZN, Mayes LC, Caramico LA, et al: Parental presence during induction of anesthesia: A randomized controlled trial. Anesthesiology 84: 1060-1067, 1996. Kain ZN, Mayes LC, O’Connor T: Preoperative anxiety in children: Predictors and outcomes. Arch Pediatr Adolesc Med 150:1238-1245, 1996. Lumley MA, Melamed BG, Abeles LA: Predicting children’s presurgical anxiety and subsequent behavior changes. J Pediatr Psychol 18: 481-497, 1993. Melamed BG, Dearborn M, Hermecz DA: Necessary considerations for surgery preparation: Age and previous experience. Psychosom Med 45:517-525, 1983. Vernon DT, Schulman JL, Foley JM: Changes in children’s behavior after hospitalization. Am J Dis Child 111:581-593, 1966.

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Case Synopsis An otherwise healthy 4-year-old boy undergoes general anesthesia for circumcision. The surgery proceeds without incident until the child arrives in the postanesthesia care unit (PACU), where he is noted to be restless, irritable, crying, and not responsive to calming measures. His agitated behavior escalates to incoherent screaming, thrashing of his extremities, and intermittent combativeness.

PROBLEM ANALYSIS

appear to lessen the risk for emergence agitation. However, preanesthetic sedation appears to offer some risk reduction.

Definition

PREEXISTING MENTAL DISTURBANCES

Emergence agitation in young children is characterized by crying, restlessness, and irritability during the emergence from anesthesia. It is unclear whether a continuum exists between emergence agitation and emergence delirium, an acute confusional state in which the patient manifests extreme agitation, hyperkinesis, and, occasionally, combativeness.

Children and adolescents with autism, mental retardation, bipolar disorder, or disruptive behavior (e.g., those with oppositional defiant, attention deficit-hyperactivity, or conduct disorders) may have more behavioral problems in the postoperative period. These patients should receive their regular psychotropic medications on schedule on the day of surgery. They may also benefit from the oral administration of a preanesthetic sedative.

Recognition Emergence agitation is a common event after even minor surgery in toddlers, preschoolers, and young school-aged children. An episode of emergence agitation may last 20 to 30 minutes and may not respond to routine comforting measures. Between 5% and 10% of children manifest severe symptoms that resemble delirium. Adolescents and young adults seem to have a higher incidence of delirium versus simple agitation in the PACU (also see Chapter 223).

Risk Assessment DEVELOPMENTAL FACTORS Young children lack mature coping mechanisms. Therefore, they are less able to tolerate being separated from their parents in a strange place, the psychological stress associated with medical illness or surgery, and the altered mental state associated with emergence from anesthesia. Parental anxiety or the parents’ lack of understanding about what to expect in the perioperative period may also have a negative effect on their child’s behavior. PREOPERATIVE ANXIETY

AND

BASELINE TEMPERAMENT

Unrecognized postoperative pain is likely the single most common cause of emergence agitation in all age groups. It is difficult to assess preverbal and developmentally delayed infants and children with subjective pain scoring systems. Also, most young children are notoriously poor self-reporters of pain intensity. Those who emerge from anesthesia in pain often show agitated or delirious behavior but do not indicate their pain to caregivers. Other causes for discomfort, including gastric or urinary bladder distention, surgical drains, or overly tight bindings and dressings, must be ruled out. UNDERLYING MEDICAL CONDITIONS The following are potentially life-threatening medical conditions that may present in the PACU as emergence agitation or delirium: ● ●

● ● ●

Hypoxemia or hypercapnia Reduced cerebral blood flow with shock states or severe hypotension Hypoglycemia, hyperthyroidism, or hyperparathyroidism Hyponatremia Seizures or elevated intracranial pressure

These diagnoses are considered within the proper clinical context if a cause for emergence agitation or delirium cannot be rapidly identified or if the period of agitation is prolonged or accompanied by a decreasing level of consciousness. ANTICHOLINERGICS Scopolamine and, to a lesser extent, atropine have been associated with postoperative mental disturbances. These agents 685

PEDIATRICS & NEONATOLOGY

Children with high levels of preoperative anxiety are less able to cooperate during mask induction, have a higher incidence of emergence agitation in the PACU, and have more severe episodes of emergence agitation. Likewise, children who are highly distressed during mask induction of anesthesia tend to be more agitated during emergence. Also, the child’s baseline temperament affects his or her postoperative behavior, and parents can frequently predict whether a child is going to have trouble dealing with events on the day of surgery. Parental presence during induction of anesthesia does not

INADEQUATE POSTOPERATIVE ANALGESIA

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cross the blood-brain barrier to cause a central anticholinergic crisis (or syndrome). This is due to block of acetylcholinemediated neuroinhibitory pathways in the brain. Full-blown central anticholinergic syndrome is characterized by warm, flushed, dry skin; visual disturbances; fever; and delirium. Some ophthalmic preparations used for mydriasis, as well as numerous antihistamines and nonproprietary drugs, have central anticholinergic effects that may contribute to disturbed behavior in patients emerging from anesthesia. Many of these drugs are tertiary versus quaternary amines and thus cross the blood-brain barrier more easily. ANESTHETIC AGENTS Low-blood-soluble gaseous or volatile anesthetics (cyclopropane, desflurane, sevoflurane) have been associated with emergence agitation in children. The mechanism for such emergence agitation is unknown, but it could be related to the more rapid emergence from anesthesia with these agents. Children who emerge rapidly from anesthesia may suddenly become aware that they are in an unusual place surrounded by strangers and therefore become distressed. Also, rapid loss of analgesic effects (greater with desflurane than sevoflurane) might contribute to inadequate postoperative analgesia and provoke or aggravate agitated behaviors. Ketamine has long been associated with dysphoria and disturbing psychological reactions in adolescents and adults. Postoperative behavioral disturbances may occur when ketamine is used to “rescue” a difficult (contentious) mask induction in an already terrified child.

other vascular access lines adequately secured. This must be accomplished quickly and may require physically restraining the child. Children with severe agitation or delirium should be given repeated doses of a rapid-onset IV opioid such as fentanyl if there is any doubt about the adequacy of their analgesia. This may be followed by small doses of midazolam if the agitation persists and if the child did not receive midazolam preoperatively. Physostigmine 0.025 mg/kg is the treatment of choice to counter the central anticholineric effects of atropine, scopolamine, and other drugs with similar effects. If postoperative pain has been sufficiently treated or ruled out and midazolam fails to reduce the severity of agitation, repeated doses of 0.1 to 0.2 mg/kg of propofol should be administered until the child is unconscious. This state can be maintained with a low-dose propofol infusion until the child can be allowed to slowly re-emerge. As a last resort, a severely agitated or delirious child or adolescent who has lost IV access can be quickly sedated with 1 to 2 mg of haloperidol administered intramuscularly.

PREVENTION ● ●

●

●

Implications The most immediate concern for a child suffering from emergence agitation is the increased risk of self-harm. Children with severe emergence agitation can accidentally injure themselves or their caregivers as a result of combativeness or hyperkinesis. Displacement of intravenous (IV) or monitoring lines, surgical drains, and dressings further complicates the postoperative care of these patients. In the tumult that often surrounds these children in the PACU, the nurses and anesthesiologist may be required to turn their attention from other patients for a prolonged period, possibly leading to reduced monitoring and care for nonagitated PACU patients. Care for a delirious patient is very laborintensive; it prolongs PACU stays and increases costs. Most parents of severely agitated children find the experience frightening and emotionally draining.

MANAGEMENT The initial approach to a child with mild to moderate emergence agitation includes the following: (1) reduce environmental stimuli other than those required for routine comfort, (2) involve the child’s parents in his or her care as soon as possible, and (3) seriously consider the possibility of inadequate analgesia and administer an IV opioid. Children with severe agitation who are thrashing about must be protected from bodily harm and have their IV and

●

●

●

●

Consider the developmental level of the patient. Allay parental anxiety with preoperative education before the day of surgery. Assess the child’s level of preoperative anxiety on the day of surgery. Administer preanesthetic sedation to high-risk pediatric age groups (1to 6 years) and children with high levels of preoperative anxiety. Implement a multimodal analgesia plan and maintain a high degree of suspicion for the inadequacy of postoperative analgesia. Avoid overly rapid emergence from low-solubility volatile inhalation anesthetics. Consider administering IV opioids, midazolam, propofol, dexmedetomidine, or clonidine before emergence in patients who have received low-solubility volatile anesthetics. Rapidly reunite the child with his or her parents in the PACU.

Further Reading Aono J, Ueda W, Marniya K, et al: Greater incidence of delirium during recovery from sevoflurane anesthesia in preschool boys. Anesthesiology 87:1298-1300, 1997. Cohen IT, Finkel JC, Hannallah RS, et al: Rapid emergence does not explain agitation following sevoflurane anaesthesia in infants and children: A comparison with propofol. Paediatr Anaesth 13:63-67, 2003. Cravero J, Surgenor S, Whalen K: Emergence agitation in paediatric patients after sevoflurane anaesthesia and no surgery: A comparison with halothane. Paediatr Anaesth 10:419-424, 2000. Kain ZN, Caldwell-Andrews AA, Weinberg ME, et al: Sevoflurane versus halothane: Postoperative maladaptive behavioral changes: A randomized, controlled study. Anesthesiology 102:720-726, 2005. Kain ZN, Wang SM, Mayes LC, et al: Distress during the induction of anesthesia and postoperative behavioral outcomes. Anesth Analg 88:1042-1047, 1999. Lerman J, Davis PJ, Welborn LG, et al: Induction, recovery and safety characteristics of sevoflurane in children undergoing ambulatory surgery. Anesthesiology 84:1332-1340, 1996.

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Olympio MA: Postanesthetic delirium: Historical perspectives. J Clin Anesth 3:60-63, 1991. Welborn LG, Hannallah RS, Norden JM, et al: Comparison of emergence and recovery characteristics of sevoflurane, desflurane and halothane in pediatric ambulatory patients. Anesth Analg 83:917-920, 1996.

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Weldon BC, Bell M, Craddock T: The effect of caudal analgesia on emergence agitation in children after sevoflurane versus halothane anesthesia. Anesth Analg 98:321-326, 2004.

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Adenotonsillectomy Lynne R. Ferrari Case Synopsis A 2-year-old boy with obstructive sleep apnea presents for tonsillectomy and adenoidectomy. In the postanesthesia care unit, his respiratory rate is 40 breaths per minute, and his heart rate is 140 beats per minute. A small amount of blood is noted in the oropharynx, and he has bilateral rales on auscultation. Oxygen saturation by pulse oximetry is 86%.

PROBLEM ANALYSIS Definition Tonsillectomy, with or without adenoidectomy, is performed so frequently that associated medical abnormalities and the potential for complications are often overlooked. The vast majority of children do well after surgery. However, complications can be serious and, at times, life threatening. The proper selection of patients and attention to anesthetic technique can reduce the risk of death and complications related to the following factors: ● ● ● ● ● ●

Bleeding Young age Postoperative pulmonary edema Postoperative vomiting Postoperative pain Obstructive sleep apnea

Recognition Bleeding. Postoperative hemorrhage occurs in 0.1% to 8.1% of patients. In 75% of cases, bleeding occurs within 6 hours of surgery; in the remaining 25%, it can occur as late as the eighth postoperative day. Most bleeding is noted by blood-stained sputum or the vomiting of “coffee grounds” material. Young Age. In the past, all children were admitted to the hospital for tonsillectomy. This approach was justified by reports of vomiting, dehydration, bleeding, pain, and apnea. The advent of cost containment, along with a trend toward ambulatory surgery, has changed this practice. Today, only children aged 3 years or younger are routinely admitted to the hospital for tonsillectomy. Pulmonary Edema. Pulmonary edema may present as frothy pink fluid in the endotracheal tube, decreased oxygen saturation, wheezing, dyspnea, or increased respiratory rate after tracheal extubation. The differential diagnosis of postobstruction pulmonary edema (see Chapter 156) includes aspiration of gastric contents, respiratory distress syndrome, congestive heart failure, volume overload, and anaphylaxis. A chest radiograph illustrating diffuse, usually bilateral, interstitial pulmonary infiltrates, combined with an appropriate clinical history, confirms the diagnosis. 688

Postoperative Pain and Vomiting. Pain is minimal after adenoidectomy but often severe after tonsillectomy. The combined effects of irritant blood in the stomach, interference with the gag reflex caused by edema, and stimulation of receptors in the chemoreceptor trigger zone contribute to postoperative vomiting, which can occur in up to 60% of tonsillectomy patients. Obstructive Sleep Apnea. Hypertrophied tonsils may obstruct the upper airway during sleep, causing obstructive sleep apnea (OSA) in approximately 3% to 12% of children. The highest incidence is in children younger than 5 years. The diagnosis of OSA is confirmed by polysomnography, which is a graphic record of respiratory activity during natural sleep. A positive sleep study is an indication for tonsillectomy, especially if related systemic abnormalities are present. The clinical presentation of OSA is quite varied. Some patients have significant limitations, whereas others are minimally affected (Table 172-1).

Risk Analysis Bleeding. The tonsillar fossa, nasopharynx, or both are the sites for 67%, 27%, or 6% of postoperative bleeding, respectively. Young Age. Age younger than 3 years is the most significant risk factor for the development of respiratory compromise after adenotonsillectomy. Respiratory compromise is defined as oxygen saturation less than 90%, with an obstructive

Table 172–1

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Clinical Presentation of Obstructive Sleep Apnea

Young age (<6 yr) Snoring during sleep Failure to thrive Recurrent respiratory tract infections Craniofacial dysmorphism Cardiac arrhythmias Apnea during sleep Somnolence while awake Developmental delay Obesity Behavioral difficulty Cor pulmonale

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breathing pattern or acute respiratory distress requiring intervention. Pulmonary Edema. Factors that increase venous return and preload in either ventricle, or those that reduce the ability of the pulmonary lymphatic system to acutely remove large amounts of fluid, increase the risk of postobstruction pulmonary edema. Postoperative laryngospasm and breathing against a closed glottis cause negative transpulmonary pressures, leading to an increased hydrostatic gradient and subsequent pulmonary edema. Postoperative Pain and Vomiting. Significant differences in the degree of postoperative pain are related to the surgical technique of tonsil removal. Increased pain medication requirements, otalgia, and irritability have been observed in patients undergoing tonsillectomy with electrocautery and laser excision compared with sharp dissection. Vomiting is multifactorial and may be due in part to the stimulation of vagal mediators in the hypopharynx as well as systemic serotonin release. Obstructive Sleep Apnea. The degree of tonsillar hypertrophy does not correlate with the severity of upper airway obstruction with OSA. Children with only slightly enlarged tonsils may have severe OSA, whereas those with very enlarged tonsils may not have OSA at all. The risk for OSA increases with changes in the nasopharyngeal airway and obesity. Children with OSA have a narrowed aperture of the nasopharyngeal airway, so posterior displacement of the tongue causes hypopharyngeal obstruction. Two thirds of children affected with OSA are obese. Fatty infiltration of the neck, along with relaxation of the pharyngeal muscles, compounds obstruction, because the collapsing force of negative inspiratory pressure exceeds the expanding force of pharyngeal muscular contraction.

Implications Bleeding. Post-tonsillectomy bleeding may be controlled by the application of topical agents to promote coagulation. However, most episodes require surgical exploration and treatment. Large volumes of blood may be swallowed but not appreciated by the patient, parents, or surgeon. Therefore, all post-tonsillectomy patients with tonsillar hemorrhage are considered to have a full stomach, and appropriate anesthetic precautions must be taken. Because the amount of swallowed blood is usually underappreciated, examination for orthostatic hypotension as a measure of intravascular volume adequacy is required.

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transpulmonary pressure gradient of this magnitude can disrupt the integrity of the pulmonary capillary walls. Concurrently, increased pulmonary blood flow and hydrostatic pressure facilitate transudation of fluid into the alveolar space. To counteract this, positive intrapleural and alveolar pressure is generated during exhalation (similar to the expiratory grunt or Valsalva’s maneuver). This reduces pulmonary venous return and blood volume. Relief of airway obstruction after tonsillectomy reduces airway pressure, but it also increases venous return and pulmonary hydrostatic pressure. This can lead to hyperemia and, ultimately, pulmonary edema. Bear in mind that the counterbalancing effect of the expiratory grunt to limit pulmonary venous return is lost with relief of airway obstruction. Postoperative Pain and Vomiting. Uncontrolled pain, swallowed blood, and poor oral intake contribute to nausea and vomiting after tonsillectomy. Dehydration occurs in 1% of patients and can be prevented by intravenous hydration to restore intravascular volume. Hospital admission for rehydration with intravenous fluids is warranted. Obstructive Sleep Apnea. Central neurologic dysfunction contributes to a worsening of cardiopulmonary function in many children with OSA. Persistent hypercapnia, hypoxemia, and right ventricular dysfunction contribute to arrhythmias and cor pulmonale. Pulmonary artery pressure increases progressively, perhaps because vascular reactivity is increased with OSA.

MANAGEMENT Bleeding. Bleeding is controlled with pharyngeal packs, topical agents, or both. If this approach fails, patients are returned to the operating room for exploration and surgical hemostasis. Both intravenous and inhalational anesthetic techniques are appropriate, but patients should be responsive at the end of surgery and should be extubated awake. A rapid-sequence induction, accompanied by cricoid pressure and a styletted endotracheal tube, is suggested. Finally, surgical procedures for control of bleeding are usually quite brief, so anesthesia should be planned accordingly. Young Age. In the absence of evidence of post-tonsillectomy complications, otherwise healthy children older than 3 years can be discharged home after 4 hours of observation.

Pulmonary Edema. Pulmonary edema can occur when airway obstruction is relieved by tonsillectomy. It has been suggested that increased negative inspiratory pressure consequent to airway obstruction increases venous return and pulmonary blood volume (Fig. 172-1). Peak negative inspiratory intrapleural pressure, which is normally 2.5 to 10 cm H2O, increases to 30 cm H2O with airway obstruction. A negative

Postoperative Pain and Vomiting. Intraoperative administration of corticosteroids may reduce edema formation and subsequent patient discomfort. Infiltration of the peritonsillar space with a local anesthetic and epinephrine can reduce intraoperative blood loss and provide immediate and protracted postoperative pain relief.One explanation for the latter may be that neural blockade prevents nociceptive impulses

PEDIATRICS & NEONATOLOGY

Young Age. Children younger than 3 years are at increased risk for inadequate oral intake and subsequent dehydration immediately following surgery. They are also at increased risk for postoperative respiratory compromise.

Pulmonary Edema. Treatment is supportive: maintain a patent airway and administer oxygen and diuretics if needed. Tracheal intubation and mechanical ventilation with positive end-expiratory pressure may be required in severe cases. Resolution is usually rapid, sometimes within hours of surgery. Many cases resolve without treatment within 24 hours.

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Figure 172–1 ■ Physiologic changes leading to pulmonary edema after treatment for upper airway obstruction. (Adapted from Galvis AG, Stool SE, Bluestone CD: Pulmonary edema following relief of acute upper airway obstruction. Ann Otol 89:124-128, 1980.)

from entering the central nervous system during and immediately after surgery, thus suppressing the formation of a sustained hyperexcitable state, which facilitates pain perception. Local anesthetic and epinephrine infiltration is not without danger, however; intravascular (especially intra-arterial) injection can be lethal. Small, repeated doses of narcotic are effective for pain relief. Nonsteroidal anti-inflammatory agents should be avoided; their potential to interfere with coagulation could be disastrous. Antiemetic agents, gastric decompression with an orogastric tube (a nasogastric tube is contraindicated after adenoidectomy), and adequate pain control are indicated for post-tonsillectomy vomiting. Obstructive Sleep Apnea. Before extubation after tonsillectomy, patients with OSA should be breathing spontaneously and able to protect their airways; therefore, cautious use of sedatives and analgesics is advised. A small dose of a benzodiazepine may be administered, especially preoperatively, to very anxious or hard-to-manage children. With regard to

postoperative narcotics, a balance must be struck between the need for analgesia and the risk of respiratory depression. Keep in mind that residual central nervous system dysfunction, hypercarbia, and hypoxemia may persist after tonsillectomy, despite relief of airway obstruction. For this reason, children with OSA should be hospitalized for apnea monitoring postoperatively (Table 172-2). Most OSA patients have normal carbon dioxide tension (PCO2) levels and are extubated after anesthesia; however, patients with severe OSA (i.e., cor pulmonale, resting PCO2 >50 mm Hg) should remain intubated and be mechanically ventilated until PCO2 has normalized. They are then extubated and observed carefully.

PREVENTION Bleeding. Before anesthetic induction, a tilt test is performed to assess orthostatic changes due to hemorrhage, intravenous

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access is established, volume replacement is begun, hematocrit is measured, and a blood sample is sent for type and crossmatch. Assorted laryngoscope blades, handles, and endotracheal tubes should be on hand, and at least two suction apparatuses should be available in case the suction tube becomes plugged with blood clots during attempted airway visualization. Young Age. Postoperative morbidity after tonsillectomy is well documented in younger children; therefore, the American Academy of Otolaryngology guidelines recommend overnight hospitalization for children younger than 3 years or those meeting other criteria (see Table 172-2).

Table 172–2

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Criteria for Hospital Admission of Patients after Adenotonsillectomy

Patients must be admitted if they meet any of the following criteria of the American Academy of Otolaryngology’s Head and Neck Surgery–Pediatric Otolaryngology Committee: Abnormal coagulation values, with or without a known bleeding disorder in the patient or family Evidence of an obstructive sleep disorder or apnea due to tonsil or adenoid hypertrophy Systemic disorders that put the patient at increased postoperative cardiopulmonary, metabolic, or general medical risk Presence of craniofacial or other airway abnormalities, including but not limited to the following: Treacher Collins syndrome Crouzon’s syndrome Goldenhar’s syndrome Pierre Robin anomaly CHARGE association defects* Achondroplasia Down’s syndrome Isolated airway abnormality Choanal atresia Laryngotracheal stenosis Procedure performed for acute peritonsillar abscess Extended travel time, weather, or home social conditions are not consistent with close observation, cooperation, and ability to return to the hospital quickly at the discretion of the attending physician ∗ CHARGE association defects consist of colobomatous malformation sequence (ranging from isolated iris coloboma to clinical anophthalmos), heart defects (e.g., tetralogy of Fallot, atrial or ventricular septal defects, patent ductus arteriosus), atresia of choanae, retarded growth and development or central nervous system anomalies, genital anomalies or hypogonadism (males), and ear anomalies or deafness.

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Pulmonary Edema. There is no reliable method to predict which patients will experience postobstructive pulmonary edema after surgery. Moderate, continuous positive airway pressure during anesthesia allows time for circulatory adaptation to take place. This is similar to the approach to acute upper airway obstruction secondary to epiglottitis or laryngospasm. Postobstructive pulmonary edema is not common in children with long-standing airway obstruction, but unfortunately, it is unavoidable in some children after their tonsils are removed. Postoperative Pain and Vomiting. Antiemetic agents, oral gastric decompression, adequate pain relief, and quiet emergence from anesthesia can help diminish the frequency of post-tonsillectomy vomiting. Obstructive Sleep Apnea. Digitalization and surgical removal of the tonsils and adenoids can reverse the progressive cardiovascular changes that occur in most patients with OSA. The occurrence of OSA in children is usually not preventable.

Further Reading Blum R, McGowan F: Chronic upper airway obstruction and cardiac dysfunction: Anatomy, pathophysiology and anesthetic implications. Pediatr Anesth 14:75-83, 2004. Brown OE, Cunningham MJ: Tonsillectomy and adenoidectomy: Inpatient guidelines: Recommendations of the AAO-HNS Pediatric Otolaryngology Committee AAO-HNS Bull 13-15, 1996. Carithers JS, Gebhart DE, Williams JA: Postoperative risks of pediatric tonsilloadenoidectomy. Laryngoscope 97:422-429, 1987. Colclasure JB, Graham SS: Complications of outpatient tonsillectomy and adenoidectomy: A review of 3340 cases. Ear Nose Throat J 69:155-160, 1990. Feinberg AN, Shabino CL: Acute pulmonary edema complicating tonsillectomy and adenoidectomy. Pediatrics 75:112-114, 1985. Ferrari L: Anesthesia for pediatric ENT surgery, routine and emergent. Am Soc Anesthesiol Refresher Course Lect 24:57-69, 1996. Galvis AG, Stool SE, Bluestone CD: Pulmonary edema following relief of acute upper airway obstruction. Ann Otol 89:124-128, 1980. Marcus CL, Ward SD, McColley SA: American Academy of Pediatrics clinical practice guideline: Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 109:704-712, 2002. McColley S, April M, Carroll J, et al: Respiratory compromise after adenotonsillectomy in children with obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 118:940-943, 1992. Tom LWC, DeDio RM, Cohen DE, et al: Is outpatient tonsillectomy appropriate for young children? Laryngoscope 102:278-280, 1992.

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Scott D. Cook-Sather Case Synopsis A 5-year-old girl with no prior ophthalmic history has a thyroglossal duct cyst excision under general anesthesia. On awakening, she complains that “something hurts in my eye.” Although there is no obvious foreign body in the eye, excessive tearing is noted. Her eyes had been taped closed following tracheal intubation. Corneal abrasion is suspected, and an ophthalmology consultation is obtained.

INTRODUCTION For nonocular surgery, the incidence of anesthesia-related eye injury is estimated at 0.06%; this accounts for 3% of the American Society of Anesthesiologists (ASA) nondental closed claims cases. Risk factors for perioperative ocular injury include general anesthesia, long procedures, head and neck procedures, and lateral positioning. For ocular surgery, anesthesia-related eye injury is exceedingly rare. When it occurs, it may be related to perioperative coughing or severe postoperative vomiting, with a related sudden increase in intraocular pressure (IOP). Important ophthalmic complications and issues relevant to pediatric anesthesia include corneal abrasion, postoperative visual loss, retinopathy of prematurity, penetrating ocular trauma, oculocardiac reflex, and postoperative nausea and vomiting. The last occurs in 40% to 90% of children after strabismus surgery and is discussed in Chapter 159.

exophthalmos place patients at higher risk. General anesthesia increases the risk, in part owing to lost protective corneal reflexes, abolished Bell’s phenomenon (in which the globe turns upward during sleep), and diminished tear production and stability.

Implications The majority of children sustaining intraoperative corneal abrasion have a full recovery within 24 hours with appropriate treatment. Extensive injury or delayed treatment results in a 16% incidence of permanent injury. Permanent scarring is usually related to secondary corneal infection or abrasions that are chronic.

MANAGEMENT Patients with corneal abrasion should be evaluated by an ophthalmologist to document the extent of injury and

CORNEAL ABRASION PROBLEM ANALYSIS Definition Corneal abrasion is the most common perioperative ophthalmic complication, with an incidence of 0.1% to 44%. A higher incidence was reported in the 1970s for anesthetized patients without eye protection or lubrication. Most corneal abrasions result from corneal drying associated with lagophthalmos during general anesthesia.

Recognition Symptoms of corneal abrasion include photophobia, pain, and foreign body sensation. Excessive tearing and miosis are characteristic physical findings. Staining with fluorescein reveals the abraded zone in green under a cobalt blue light (Fig. 173-1).

Risk Assessment Although the inciting event for corneal abrasion is not always clear, factors such as prone or lateral positioning and 692

Figure 173–1 ■ The opacified zone overlying the iris at the 2 o’clock position is a corneal abrasion with surrounding edema. These lesions are most easily seen with fluorescein staining. (Courtesy of Dr. Katrinka Heher.)

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initiate treatment. Usual recommendations include lubrication, application of a topical antibiotic or cycloplegic agent (or both), and patch closure.

PREVENTION To prevent corneal abrasion, ocular contact with masks, stethoscopes, name tags, intubation equipment, sheets, and padding material must be avoided. Eye protection should be established early, before laryngoscopy. Tape should be used to keep the eyelids closed, with ophthalmic lubricants used for longer procedures. Petroleum-based ophthalmic ointments are more likely to cause foreign body sensation and blurred vision postoperatively than are aqueous solutions. Placement of a disposable pulse oximeter probe on the child’s ring finger as opposed to the index finger may lessen the chance of inadvertent eye contact and potential corneal injury in the postoperative period.

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surgery in the prone position, two for scoliosis and one for reconstruction of the cranial vault. Intraoperative events included large blood loss and episodes of hypotension. One proposed mechanism of injury involves the complex interaction of transient anemia, arterial hypotension, increased central venous pressure, and increased IOP in the prone position, which results in decreased optic perfusion pressure and limited hemodynamic reserve in the optic pathways. Adult patients with hypertension, smoking, diabetes, or peripheral vascular disease appear to be at increased risk for ION. Direct orbital compression (e.g., from patient malposition on a headrest) is not required for ION to occur. However, such compression can result in POVL via central retinal artery occlusion, in which case POVL can be attributed to ION. POVL may also be consequent to perioperative cortical ischemia.

Implications Most postoperative visual deficits do not improve significantly over time. Those who experience complete absence of light perception are unlikely to regain vision.

MANAGEMENT

PROBLEM ANALYSIS Definition Postoperative visual loss (POVL) is the most catastrophic perioperative ophthalmic complication and may manifest as either partial visual field loss or total blindness. The incidence of POVL in the general, nonocular surgical population is 1 in 61,000 to 1 in 125,000, but following spinal surgery in the prone position, it is estimated to be 1 in 1100. There is also a higher relative incidence after open-heart and head and neck surgeries. From the inception of the ASA Postoperative Visual Loss Registry in July 1999 until July 2004, there were three reported pediatric cases of POVL in patients ranging in age from 5 to 18 years.

Early ophthalmology consultation must be obtained for unequivocal vision deficits (absence of light perception, unilateral visual loss), periorbital ecchymosis or obvious trauma, and milder visual symptoms that do not improve in the first few hours after anesthesia and surgery. Visual acuity tests, funduscopic examination, and head magnetic resonance imaging are often required to establish a diagnosis; however, few (if any) therapies are currently available. Thus, ensuring adequate hemodynamics, hemoglobin concentration, and oxygenation in the postoperative period cannot be expected to reverse the initial injury but may prevent further damage.

PREVENTION Recognition

Risk Assessment Ischemic optic neuropathy (ION) associated with spinal surgery in the prone position accounts for the majority of cases in the ASA POVL Registry. Three pediatric patients developed bilateral ION following prolonged (>8 hours)

Although direct pressure is not a common cause of POVL, protecting the eyes from external compression is vital. Anesthesia providers must carefully position patients and then monitor their positioning, because patients may shift in relation to headrests and other equipment during surgery. Special headrests with mirrors allow instant assessment of the periorbital area in prone patients. Slight reverse Trendelenburg’s position may reduce orbital venous pressure and promote better perfusion for any given mean arterial pressure. Although deliberate hypotension may help reduce operative blood loss, it may increase the risk for POVL. Deliberate hypotension has been used in tens of thousands of uneventful cases, but two of the three pediatric cases in the ASA POVL Registry involved deliberate hypotensive techniques. The current practice at my institution is to avoid deliberate hypotension for posterior spinal fusion surgery, because somatosenory and motor evoked potentials are better preserved with normotension.

PEDIATRICS & NEONATOLOGY

Visual changes may be appreciated in the immediate postoperative period, but delays in diagnosis may occur when such changes are incorrectly attributed to “normal recovery” after anesthesia and instilled ophthalmic lubricants. In one study of 28 POVL cases, visual changes were recognized in 50% of patients in the recovery room and in 80% by postoperative day 2. Some patients initially had normal vision but experienced symptoms 1 to 12 days later. Younger pediatric patients may have difficulty expressing symptoms. When there is local ecchymosis around the affected eye or periorbital numbness, compression injury should be suspected.

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Precise transfusion parameters for reducing POVL risk are not well defined, but significant anemia should be avoided. Current recommendations also include minimizing the time the patient is in the prone position. Staged procedures should be considered if total operative time is expected to exceed 8 hours.

RETINOPATHY OF PREMATURITY PROBLEM ANALYSIS Definition Retinopathy of prematurity (ROP) occurs in more than 50% of premature infants weighing less than 1500 g at birth. It is caused by abnormal proliferation of vascular tissue, with destruction of the retinal capillary bed. ROP ranges in severity from reversible regional neovascularization to complete retinal detachment with permanent blindness. Although multiple, interrelated factors predispose to ROP, the immature retina appears to be more susceptible if exposed to high oxygen (O2) concentrations and accompanying free radicals.

MANAGEMENT AND PREVENTION ROP is primarily a concern in neonatal intensive care units, where prolonged O2 exposure may place infants at risk; however, efforts to reduce intraoperative O2 concentrations also may be beneficial. Older studies indicated that an arterial O2 tension (PaO2) of 150 mm Hg for 1 to 2 hours could affect the immature retina. More recent data suggest that even lower PaO2 values may contribute to ROP. Consistent damage occurs after only several days of hyperoxia. Prudent preventive management thus includes the lowest fraction of inspired O2 (FiO2) required to achieve a percutaneous arterial O2 saturation of 90% to 95% (PaO2 ≈70 mm Hg). However, neonates with severe pulmonary pathology who require a high FiO2 to maintain adequate tissue oxygenation should receive it.

PENETRATING OCULAR TRAUMA AND VITREOUS EXTRUSION PROBLEM ANALYSIS

Recognition

Definition

Ophthalmologic examination can document the development or exacerbation of ROP. The stages of ROP are as follows:

Penetrating ocular trauma, with the concomitant risk of extrusion of ocular contents, is a classic management challenge for pediatric anesthesiologists. Patients present emergently, are often uncooperative, and usually require rapid anesthetic induction to minimize the risk of pulmonary aspiration of gastric contents. However, sudden increases in IOP during anesthesia, especially during induction, may increase the risk of vitreous humor extrusion. Loss of ocular contents solely due to anesthetic management is exceedingly rare, relegated to a few anecdotal reports.

●

● ● ● ●

Linear separation of posterior vascular retina from the anterior avascular portion Elevation of the demarcation line and ridge formation Extraretinal neovascular tissue proliferation Partial retinal detachment Complete retinal detachment—also known as retrolental fibroplasia

Recognition Risk Assessment ROP is associated with low birth weight (<1500 g), young gestational age (≤32 weeks), hemorrhagic shock at birth, anemia and transfusion, and prolonged exposure to high O2 tensions. The temporal portion of the retina does not mature until 40 to 44 weeks’ postconceptual age. Neonates up to 44 weeks’ postconceptual age who require surgery are therefore presumed to be at risk for the development of ROP or for worsening of existing pathology.

Implications Although approximately 85% of acute ROP cases undergo spontaneous regression, outcomes depend on the stage, with fibrous tissue traction and retinal detachment having worse prognoses. Laser photocoagulation is the treatment of choice in 90% of cases. Cryotherapy, scleral buckle, or vitrectomy may be required.

The patient’s history may include either handling or being struck by a sharp object, with subsequent eye pain, swelling, erythema, obvious ocular rent, or an in situ foreign body. Poor eye turgor and exposed vitreous are signs of vitreous extrusion.

Risk Assessment Penetrating eye injury is more likely to result in vitreous extrusion in children with large defects and in those who continue to cry, cough, retch, or vomit.

Implications Extrusion of ocular contents is catastrophic and requires immediate wound closure and possible posterior sclerotomy to release suprachoroidal blood. The prognosis is extremely poor—most victims lose all vision in the affected eye.

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MANAGEMENT AND PREVENTION Evaluation and management strategies for children with penetrating ocular trauma are summarized in Table 173-1. The most important concerns are preventing the aspiration of gastric contents and preventing a sudden increase in IOP, as occurs with coughing. Coughing can transiently increase IOP by 30 to 40 mm Hg and may cause vitreous extrusion, iris or lens prolapse, or choroidal hemorrhage. Smaller increases in IOP may also cause extrusion of vitreous, although the absolute minimum increase in IOP required to do so is unknown; it is clearly dependent on the degree of baseline injury. Succinylcholine administered during a rapid-sequence intubation may increase IOP by 6 to 8 mm Hg for 5 to 10 minutes via the depolarization of extraocular, facial, and smooth orbital muscles. There are no credible case reports of vitreous extrusion following succinylcholine administration, however; concern stemmed from a single anecdotal report. Defasciculating doses of nondepolarizing muscle relaxants (NDMRs) may attenuate the rise in IOP associated with succinylcholine. Priming doses of NDMRs may hasten the achievement of adequate intubation conditions after the induction of anesthesia, but there are reports of intervening weakness, difficulty breathing, agitation, and even aspiration. In general, pediatric patients poorly tolerate the potential difficulties associated with NDMR priming; also, in theory, these

Table 173–1

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Anesthetic Evaluation and Management of Patients with Penetrating Eye Injuries

Nature of Injury, Urgency, and Expected Duration of Procedure Small defects: less risk of extrusion Simple injury: short-duration procedures Complex injury: prolonged retinal reattachment Copper: causes early vitreous clouding Protruding foreign body: true ophthalmic emergency Nonviable eye: can wait several hours

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would increase the risk of further injury to the eye. Large doses (two to three times the ED95) of NDMRs such as cisatracurium, mivacurium, rocuronium, or vecuronium may permit intubation within 60 to 90 seconds, but recovery from the block may be prolonged. Finally, throughout the operation, one should maintain adequate neuromuscular relaxation and administer sufficient opioid to mimimize coughing on emergence.

OCULOCARDIAC REFLEX PROBLEM ANALYSIS Definition Decreased heart rate associated with pressure on the globe or traction on the extraocular muscles is common in children. The reported incidence of the oculocardiac reflex (OCR) is 20% to 90% during strabismus surgery. The afferent OCR limb is via the long ciliary nerve and the short ciliary nerves. The latter first come together at the ciliary ganglion; these two inputs then converge to form the ophthalmic division of the trigeminal nerve (Fig. 173-2). The efferent limb of the OCR is vagal via the cardiac depressor nerve.

Recognition The OCR results in a slowed or irregular heart rate. It can be detected by precordial heart sounds, pulse oximetry, or electrocardiographic monitoring. Sinus bradycardia is the most common rhythm disturbance. Sinus pause, transient asystole, wandering atrial pacemaker, atrioventricular junctional rhythm, atrioventricular heart block, and ventricular arrhythmias (extrasystoles, bigeminy, escape beats) may also occur. Although ventricular tachycardia and fibrillation have been reported, they are most likely to occur after prolonged asystole (presumably due to myocardial hypoxia) or treatment with anticholinergics or β-adrenergic agonists, especially in patients anesthetized with sensitizing inhalational anesthetics such as halothane.

Risk of Pulmonary Aspiration Recent full meal Impaired gastrointestinal function Severity of trauma Opioid administration Gastroesophageal reflux, hiatal hernia

Airway Evaluation Difficult: consider a fiberoptic approach Normal or not anticipated to be difficult: rapid-sequence induction

Anesthetic Management Options

NDMR, nondepolarizing muscle relaxant; SCh, succinylcholine.

Younger patients, because of a relative increase in vagal tone, are most predisposed to the OCR during strabismus surgery. Although sudden, forceful traction on any of the extraocular muscles is the most common provocative stimulus, there can be others (Table 173-2). Prophylactic atropine and other chronotropic agents do not abolish the OCR but may reduce its incidence and the severity of associated bradycardia. However, as just noted, prophylaxis with anticholinergics or β-adrenergic agonists has the potential to cause worse arrhythmias, especially with older inhalational anesthetics such as halothane. Hypercarbia and hypoxia augment the potential for arrhythmias with the OCR, as does inappropriate anesthetic depth.

Implications The OCR is usually transient and relieved with release of traction. There is a significant association between intraoperative

PEDIATRICS & NEONATOLOGY

Possible delayed start: 8 hr after solids; 2 hr after clear liquids Rapid-sequence induction variants: Lidocaine 1.5-2 mg/kg; remifentanil 1 μg/kg or fentanyl 1-2 μg/kg; thiopental 4-6 mg/kg or propofol 2-3 mg/kg; SCh 1.5-2 mg/kg (± defasciculating NDMR dose); high-dose NDMR (rocuronium 1.2 mg/kg) in place of SCh if surgery will be prolonged Monitoring: train-of-four to determine earliest time for intubation and ongoing muscle relaxation

Risk Assessment

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Figure 173–2 ■ Oculocardiac reflex (OCR). The ophthalmic division of the trigeminal nerve (afferent limb) is stimulated via the long and short ciliary nerves. Afferent impulses are transmitted to the gasserian ganglion and main trigeminal sensory nucleus. From there, they are relayed to the efferent (motor) nucleus of the vagus nerve. The efferent pathway includes the vagus nerve and the cardiac depressor nerve. (From Vassallo SA, Ferrari LR: Anesthesia for ophthalmology. In Coté CJ, Ryan JF, Todres ID, et al [eds]: A Practice of Anesthesia for Infants and Children, 2nd ed. Philadelphia, WB Saunders, 1993, p 325.)

OCR and postoperative nausea and vomiting. Indeed, children with OCR episodes in the operating room are two to three times more likely to experience postoperative nausea and vomiting than are those without such episodes.

should relax tension on the eye muscle. Administering a chronotropic agent before the stimulus is removed and normal rhythm is restored is not advised; this only increases the risk for more serious arrhythmias. In general, the OCR fatigues with repetitive and more gentle traction, making treatment with chronotropic drugs unnecessary.

MANAGEMENT Although the OCR is a common cause of arrhythmias during strabismus surgery, it is important to investigate and treat other primary causes, including hypoxia, hypercarbia, and inadequate anesthesia. All these have the potential to worsen the OCR. However, if arrhythmias persist, the surgeon

Table 173–2

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Perioperative Stimuli for Oculocardiac Reflex

Traction on any extraocular muscle Traction on conjunctiva or orbital structures Ocular trauma or retrobulbar hematoma Pressure on globe or tissue in orbital apex∗ Performance of retrobulbar block ∗After enucleation of the eye.

PREVENTION Recommendations include the use of controlled, mild hyperventilation to prevent hypercarbia during strabismus surgery. Compared with halothane, sevoflurane can reduce OCR incidence and the magnitude of bradycardia in children during both spontaneous and controlled ventilation. Although intravenous atropine given 30 minutes before eye muscle traction may reduce OCR incidence or attenuate its magnitude, it does not guarantee protection against significant arrhythmias. Because atropine is not universally effective for OCR prophylaxis, and because of the generally low incidence of severe OCR leading to hemodynamic compromise, routine anticholinergic prophylaxis is no longer recommended. Retrobulbar block with 1 to 3 mL of 1% to 2% lidocaine may prevent the OCR in adults but is rarely used in pediatric practice.

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Acknowledgments Special appreciation is extended to Dr. Monte D. Mills, chairman of the Department of Ophthalmology, Children’s Hospital of Philadelphia and the University of Pennsylvania, for reviewing and improving this chapter.

Further Reading Allison CE, De Lange JJ, Koole FD, et al: A comparison of the incidence of the oculocardiac and oculorespiratory reflexes during sevoflurane and halothane anesthesia for strabismus surgery in children. Anesth Analg 90:306-310, 2000. Blanc VF, Hardy JF, Milot J, et al: The oculocardiac reflex: A graphic and statistical analysis in infants and children. Can Anaesth Soc J 30:360-369, 1983. Gild WM, Posner KL, Caplan RA, et al: Eye injuries associated with anesthesia: A closed claims analysis. Anesthesiology 76:204-208, 1992. Gregory GA: Anesthesia for premature infants. In Gregory GA (ed): Pediatric Anesthesia, 4th ed. Philadelphia, Churchill Livingstone, 2002, pp 352-353.

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Haberer JP: Ophthalmic surgery: Anesthetic considerations and postoperative management. In Bissonette B, Dalens B (eds): Pediatric Anesthesia Principles and Practice. New York, McGraw-Hill, 2002, pp 1277-1290. Lee LA, Lam AM: Unilateral blindness after prone lumbar spine surgery. Anesthesiology 95:793-795, 2001. Myers MA, Hamilton SR, Bogosian AJ, et al: Visual loss as a complication of spine surgery: A review of 37 cases. Spine 22:1325-1329, 1997. Roth S, Thisted RA, Erickson JP, et al: Eye injuries after nonocular surgery. Anesthesiology 85:1020-1027, 1996. Siffring PA, Poulton TJ: Prevention of ophthalmic complications during general anesthesia. Anesthesiology 66:569-570, 1987. Vachon CA, Warner DO, Bacon DR: Succinylcholine and the open globe. Anesthesiology 99:220-223, 2003. Vassallo SA, Ferrari LR: Anesthesia for ophthalmology. In Coté CJ, Ryan JF, Todres ID, et al (eds): A Practice of Anesthesia for Infants and Children, 2nd ed. Philadelphia, WB Saunders, 1993, pp 323-335. Warner ME, Warner MA, Garrity JA, et al: The frequency of perioperative vision loss. Anesth Analg 93:1417-1421, 2001. White E, Crosse MM: The aetiology and prevention of peri-operative corneal abrasions. Anaesthesia 53:157-161, 1998.

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Intracranial Hypertension Rosemary Hickey

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Case Synopsis A 64-year-old man presents with progressive personality changes, memory disturbances, and urinary incontinence. The physical examination is remarkable for depressed consciousness and papilledema. The computed tomography scan reveals a large frontal mass consistent with a meningioma.

Recognition

PROBLEM ANALYSIS Definition Intracranial hypertension exists when there is a sustained elevation in intracranial pressure (ICP) of more than 15 to 20 mm Hg. It results when the three intracranial components—blood, brain, and cerebrospinal fluid (CSF)—are no longer able to compensate for volume changes occurring within the cranium. CSF translocation from the head into the spinal subarachnoid space and its reabsorption via the arachnoid villi are the major compensatory means of accommodating intracranial volume increases. Spatial compensation can also be achieved through compression of the venous system and, ultimately, capillary collapse, leading to cerebral ischemia. Changes in ICP that occur with changes in intracranial volume can be described by the intracranial elastance curve (Fig. 174-1). The shape of the curve may be influenced by the type of lesion causing the increase in volume; for example, slower-growing lesions may be better tolerated than rapidly growing ones.

C ICP

The signs and symptoms most frequently associated with intracranial hypertension include headache, nausea, vomiting, papilledema, unilateral pupillary dilatation, and oculomotor or abducens nerve palsies. Changes in consciousness and irregular ventilatory patterns indicate advanced stages of intracranial hypertension. Headache is typically present on awakening, or it may awaken the patient from sleep. It is related to traction and distortion of pain-sensitive cerebral blood vessels and the dura mater. Vomiting may be due to direct stimulation of the vomiting centers by local compression. Papilledema is the only reliable sign of an increase in ICP, although intracranial hypertension may be present without it. Oculomotor palsies are secondary to herniation or compression of the nerve, and abducens palsies result from stretching of the nerve as the brainstem is displaced inferiorly by the increased pressure. A general slowing in mentation occurs from continuously increased ICP and a diffuse decrease in cerebral blood flow. Further deterioration in the level of consciousness indicates progressive transtentorial herniation. Alterations in vital signs (bradycardia, hypertension, depression of respiration) also may occur from increased ICP and brainstem compression. Computed tomography scanning, magnetic resonance imaging, or angiography provides indirect evidence of elevated ICP. These studies may reveal a mass lesion accompanied by a midline shift of at least 0.5 cm, encroachment of the CSF cisterns by the expanding brain, or both.

Risk Assessment

B A Volume added Figure 174–1 Intracranial elastance curve. A, Normal elastance. B, Reduced elastance (small increase in intracranial pressure [ICP] with increasing intracranial volume). C, Poor elastance (large ICP increase with minimal increase in cerebral volume). (From Mahla ME: Neurologic surgery. In Kirby RR, Gravenstein N [eds]: Clinical Anesthesia Practice. Philadelphia, WB Saunders, 1994, pp 1283-1311.) ■

The three major mechanisms of increased ICP are (1) increased intracranial volume due to an intracerebral mass lesion (e.g., tumor, massive infarction, trauma, hemorrhage, abscess), extracerebral mass lesion (e.g., tumor, hematoma, abscess), or acute brain swelling (e.g., anoxic states, acute hepatic failure, hypertensive encephalopathy, Reye’s syndrome); (2) high venous pressure resulting from heart failure, superior mediastinal obstruction, or cerebral or jugular venous obstruction, which increases blood volume in the pial veins and dural sinuses and may interfere with CSF absorption; and (3) obstruction to the flow (hydrocephalus) or absorption (pseudotumor cerebri) of CSF. 701

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Implications The danger of intracranial hypertension lies in the potential for cerebral ischemia and herniation of brain tissue. If ICP, either locally or globally, reaches levels exceeding mean arterial pressure, cerebral ischemia will develop. Cerebral perfusion pressure is calculated as mean arterial pressure minus ICP. The likelihood of permanent tissue damage from cerebral ischemia depends on the severity and duration of the ischemia. If ICP is sufficiently high to obstruct venous outflow from the brain, arterial inflow also may be compromised. Brain herniation can occur around any fixed structure in the skull. In open head trauma, injured brain may herniate through the fractured skull. In the intact skull, herniation sites include the falx cerebri, under which the cingulate gyrus of the frontal lobe can herniate; temporal lobe (uncal) herniation through the tentorium cerebri; and classic herniation of the cerebellum through the foramen magnum, compressing the medulla and resulting in cardiovascular and respiratory collapse.

MANAGEMENT Therapeutic interventions to lower elevated ICP are categorized according to its intracranial determinant (Table 174-1). Parenchymal volume may be reduced in several ways. Mannitol results in an osmotic reduction of brain water content. It may also improve blood rheology and microcirculatory flow. Loop diuretics (furosemide) provide intracranial decompression through a diuresis-mediated brain dehydration, reduced CSF formation, and resolution of cerebral edema via improved cellular water transport. Corticosteroids reduce peritumoral edema but are not useful for treating intracranial hypertension secondary to head trauma. Surgical excision of mass lesions reduces the volume of the intracranial space occupied by parenchymal components and thus improves intracranial elastance. Techniques to reduce CSF volume include ventricular or lumbar puncture, drains, and shunts. Cerebral blood flow and volume and ICP are reduced by hyperventilation; however, such a reduction in cerebral blood flow may be poorly tolerated.

Table 174–1

■

Jugular venous oxygen saturation monitoring is used to guide the level of hyperventilation in head trauma. Values greater than 75% indicate hyperemia, so induced vasoconstriction associated with hyperventilation may be valuable; values less than 50% indicate cerebral ischemia, so attempts to induce further cerebral vasoconstriction may be harmful. Measurement of brain tissue oxygen tension can also provide information about the safety of hyperventilation. Some intravenous anesthetic drugs (e.g., lidocaine, thiopental, etomidate, propofol) are beneficial for decreasing ICP. A continuous infusion of propofol combined with a low-dose inhalational agent is another useful anesthetic technique. Venous drainage is maximized by keeping the head elevated 15 to 30 degrees, but without excessive rotation or flexion.

PREVENTION Prevention of intracranial hypertension centers on avoiding factors that are known to increase ICP. Intravenous fluid management is directed toward achieving a euvolemic state. Therapy should avoid the use of intravenous solutions that decrease plasma osmolality (5% dextrose in water, 0.45% sodium chloride, lactated Ringer’s solution). The factor in administered fluid that most affects brain edema is the osmolality. An acute drop in osmolality affects brain water content and ICP more than an acute drop in oncotic pressure. Glucose-containing solutions are avoided because hyperglycemia may aggravate ischemic brain injury. Other factors that increase ICP and should be avoided include compression of jugular veins by improper head positioning, coughing and straining on the endotracheal tube, seizure activity, hypercarbia, and hypoxia. Increased body temperature raises cerebral metabolic oxygen consumption and should be avoided. Volatile anesthetic agents may cause an increase in cerebral blood flow, cerebral blood volume, and ICP. In the presence of intracranial hypertension, these agents should be used in moderation and in combination with hyperventilation and intravenous anesthetics with favorable effects on ICP (e.g., thiopental, etomidate, propofol, fentanyl). If used at a minimum alveolar concentration (MAC) of 1.2 in combination with hyperventilation,

Determinants of Intracranial Pressure and Therapeutic Techniques to Lower It

Determinant

Therapeutic Intervention

Mechanism

Duration of Effect

Volume of parenchyma

Mannitol infusion Corticosteroids

Osmotic reduction of brain water content Reduction of peritumoral or peri-inflammatory edema Volume reduction Increased craniospinal compliance Volume reduction Volume reduction Volume reduction Cerebral vasoconstriction due to decreased PCO2 Cerebral vasoconstriction

Hours to days Days to weeks

Cerebrospinal fluid volume Cerebral blood volume

Excision of mass Craniectomy Ventricular or lumbar puncture Ventriculostomy or lumbar drain Ventricular or lumbar shunt Hyperventilation Barbiturates

Indefinite Indefinite Hours Days Indefinite Hours Hours to days

Revised from Broaddus WC, Delashaw JB, Park TS: Anatomic, physiologic, and neurosurgical considerations in neuroanesthesia. In Sperry RJ, Stirt JA, Stone DJ (eds): Manual of Neuroanesthesia. Toronto, BC Decker, 1989.

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desflurane and isoflurane have similar effects on cerebral perfusion pressure, mean arterial pressure, and lumbar CSF pressure. Nitrous oxide is cerebrostimulatory and increases cerebral blood flow and cerebral metabolic oxygen consumption, especially when combined with volatile anesthetics. Use of nitrous oxide should be avoided with pneumocephalus (e.g., recent craniotomy) because of its potential to diffuse into and expand intracranial and other air-containing spaces.

Further Reading Adams RD, Victor M: Disturbances of cerebrospinal fluid circulation, including hydrocephalus and meningeal reactions. In Adams RD, Victor M (eds): Principles of Neurology. New York, McGraw-Hill, 1993, pp 539-553. Bedell E, Prough DS: Anesthetic management of traumatic brain injury. Anesthesiol Clin North Am 20:417-439, 2002. Bendo AA, Luba K: Recent changes in the management of intracranial hypertension. Int Anesthesiol Clin 38:69-85, 2000.

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Coles JP, Minhas PS, Fryer TD, et al: Effect of hyperventilation on cerebral blood flow in traumatic head injury: Clinical relevance and monitoring correlates. Crit Care Med 30:1950-1959, 2002. Diringer M: Hyperventilation in head injury: What we have learned in 43 years. Crit Care Med 30: 2142-2143, 2002. Dutton R, McCunn M: Traumatic brain injury. Curr Opin Crit Care 9: 503-509, 2003. Hickey R: Neurosurgical emergencies. Am Soc Anesthesiol Refresher Courses 24:97-110, 1996. Imberti R, Bellinzona G, Langer M: Cerebral tissue PO2 and SjvO2 changes during moderate hyperventilation in patients with severe traumatic brain injury. J Neurosurg 96: 97-102, 2002. Kaye A, Kucera IJ, Heavner J, et al: The comparative effects of desflurane and isoflurane on lumbar cerebrospinal fluid pressure in patients undergoing craniotomy for supratentorial tumors. Anesth Analg 98:1127-1132, 2004. Shapiro HM: Anesthesia and intracranial pressure. In Sperry RJ, Johnson JO, Stanley TH (eds): Anesthesia and the Central Nervous System. Dordrecht, Netherlands, Kluwer Academic Publishers, 1993, pp 119-138.

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Venous Air Embolism Jennifer E. Souders and Maurice S. Albin

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Case Synopses Gravitational Pressure Gradient of 7.5 cm H2O During a repeat lumbar laminectomy in the prone position with an orthopedic frame, a 55-year-old man suddenly develops severe hypotension, rapidly goes into electromechanical dissociation, has cardiac arrest, and cannot be resuscitated after 1 hour of effort. Gravitational Pressure Gradient of 20 cm H2O A 42-year-old woman with acromegaly secondary to pituitary adenoma undergoes transsphenoidal resection of the tumor in the semisitting position (head elevated 30 degrees). Severe hypotension (60 mm Hg systolic) occurs when surgical manipulations are carried out in the area of the sella.

PROBLEM ANALYSIS Definition Air can enter the venous circulation when there is a negative gravitational gradient between the right atrium and the upper area of incision or the air’s point of entrance. Albin and coworkers reported that a 5 cm H2O gravitational gradient was sufficient to entrain air in a neurosurgical case. The entry of a bolus of 100 mL of air into the venous circulation can be fatal, and it has been calculated that this amount of air can pass through a 14-gauge needle with a gradient of 5 cm H2O in a matter of seconds. Factors modifying air entrainment include body position, depth of ventilation, volume of air entering the vessel, rate of gaseous entry, and composition and concentration of gases in the inhaled anesthetic mixture. Animal studies and human cases have shown that the transpulmonary passage of air can occur without a patent foramen ovale. Reduced central venous pressure due to a contracted blood volume or hemorrhagic hypovolemia, or decreased intrathoracic pressure due to the use of a table or frame to reduce abdominal compression, can help increase the gravitational pressure gradient and enhance the entrainment of air. The fate of entrained air is illustrated in Figure 175-1. In the first case synopsis, the gravitational gradient was probably less than 7.5 cm H2O but was enhanced by blood loss and use of an orthopedic frame, which reduced abdominal pressure, allowing the development of negative intrathoracic pressure with expiration. Because 50% nitrous oxide (N2O) was used, this increased the air bubble size by a factor of about two.1 Autopsy revealed air in the coronary vessels, heart, spinal cord, and cerebral and mesenteric vessels, despite a non-probe-patent foramen ovale. In the second case synopsis, more than 150 mL of air was aspirated from the central line after the hypotensive episode. The gravitational pressure gradient was at least 20 cm H2O, 1 Increased gas bubble volume with N2O is approximated as 100/(100 – FiN2O) = 100/(100 – 50) = 2.

704

and the air bubble volume was approximately doubled, because 50% N2O again was used. Postoperatively, a technetium lung scan revealed a peripheral decortication pattern in the posterosuperior portion of the right and left lung fields and an abrupt decrease in perfusion to the right middle lobe, all due to the entrance of air into the pulmonary system. These cases show that venous air embolism (VAE) can occur in any position, as long as a pressure gradient allows the ingress of air between the procedural area and the heart (Table 175-1). Evidence has accumulated that VAE is far from rare in patients undergoing procedures in the prone position, especially spinal procedures; there have been at least 22 cases reported, with a total of 13 deaths, 10 of which were in the pediatric age group. In addition to neurosurgery, VAE has been reported with virtually all surgeries and endoscopy. It also occurs with catheterization for cardiac or central vascular access, arteriovenous shunts, and intravenous infusions and transfusion therapy.

Recognition Physical signs and symptoms include gasping respiration in spontaneously breathing patients, increased central venous and pulmonary artery pressures, cardiac arrhythmias, electrocardiographic (ECG) changes, hypotension, abnormal heart sounds, changes in heart rate, decreased peripheral resistance, reduced cardiac output, cyanosis, a mill-wheel murmur, and cardiac arrest. Increased pulmonary artery pressure is the most prominent physical sign of VAE during controlled ventilation, irrespective of the volume or rate of air entrainment. The more rapidly air enters the pulmonary circulation, the more rapidly and severely the pulmonary artery pressure will rise. If it rises dramatically over the systemic pressure, a rightto-left shunt can occur through a septal defect (i.e., patent foramen ovale) and cause paradoxical embolism of air into the left heart. ECG changes with air embolism are quite variable and include tachyarrhythmias, varying degrees of atrioventricular block, right ventricular strain, and ST segment changes. Very large volumes of entrained air may cause such

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Air Veins sinuses Right atrium Large bolus

Pulmonary artery

Reverse transatrial gradient PFO

Air lock Pulmonary capillaries

Vented

Left heart?

Figure 175–1

Brain ■

Coronaries

■

Brain

Coronaries

Fate of entrained air after venous air embolism. PFO, patent foramen ovale.

severely increased right ventricular afterload that the right ventricle becomes ischemic and fails acutely. Right heart failure is the primary cause of acute hypotension, reduced cardiac output, and cardiac arrest after massive air embolism. A mill-wheel murmur indicates that a significant volume of air has entered the right heart chambers. If so, cardiac arrest may be imminent. Air causes this churning sound and is one of the last signs observed. Besides physical signs and symptoms, the other methods for detecting intraoperative air embolism, in order of sensitivity, are transesophageal echocardiography (TEE), precordial Doppler ultrasonography, end-tidal carbon dioxide (CO2), pulmonary artery catheter, pulse oximetry, and direct observation of the surgical site. TEE can detect both venous and paradoxical embolism consisting of as little as 0.02 mL/kg of air. However, it is expensive and may be inaccessible in some surgical locations; it has no audible alarms and may be difficult for solo practitioners to use when they are occupied with urgent patient care duties. A well-positioned precordial Doppler probe detects 0.05 mL/kg of intravascular air, is noninvasive, and alerts both the anesthesiologist and the surgeon simultaneously. As mentioned earlier, although pulmonary artery catheters can show early and Table 175–1

Left heart Lungs

Decreased venous return

prominent signs of air embolism, they are highly invasive and less sensitive than precordial Doppler. A sudden reduction in end-tidal CO2 concentration is the most convenient and widely used noninvasive method for detecting air embolism. The magnitude and duration of the decrease in end-tidal CO2 correlate positively with the volume of air entrained, and detection is possible during any general anesthetic. In contrast, pulse oximetry is relatively insensitive, because decreases in arterial oxygen saturation often occur late with a decrease in arterial oxygen tension. Further, the surgical field is often overlooked. Especially in high-risk surgery, it may be easy to see whether there is a lack of venous oozing, indicating subatmospheric venous pressure. In high-risk procedures, combined precordial Doppler ultrasonography and end-tidal CO2 monitoring should be used. Doppler tone activation and reduced end-tidal CO2 signal air entrainment. VAE is confirmed if gas bubbles can be aspirated from a central line.

Risk Assessment The incidence of VAE is uncertain, largely because the criteria for VAE vary. Nevertheless, we have a general idea about

Incidence of Air Embolism in Neurosurgery by Position

From Albin MS, Carroll RG, Maroon JC: Clinical considerations concerning detection of air embolism. Neurosurgery 3:380-384, 1978.

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the incidence of VAE and the associated morbidity and mortality rates for neurosurgical procedures performed with the patient in the sitting position. The overall incidence is about 25%, ranging from 2% to 60%. In 10 studies of more than 5000 patients, the mortality rate did not exceed 1% in any individual report. Morbidity data, even in neurosurgical sitting cases, are more difficult to ascertain. Albin and coworkers reported 100 cases of VAE in 400 patients operated on in the sitting position. These patients were considered to have VAE only if both Doppler activation and visual aspiration of air from a central line occurred. Under these conditions, 25 of the 100 patients with recognized VAE developed symptoms ranging from severe hypotension to cardiac arrest. Paradoxical air embolism (air entering the left side of the heart via a patent foramen ovale or transpulmonary passage) caused significant mortality in the small number of cases reported. Somewhat surprisingly, most VAE-related mortality appears to occur in non-neurosurgical cases, possibly because anesthetists fail to appreciate that it can occur in these cases and the patient is not monitored adequately for VAE. Adding to this lack of appreciation is the medicolegal “fear factor,” which likely leads to underreporting of VAE in the medical literature. There is a significant risk of VAE in cesarean section, spinal surgery, and total hip arthroplasty.

Implications Because of coalescence and filming of bubbles at the bloodbubble interface, the passage of air into the right atrium can impede or even halt venous return to the right side of the heart. The consequences are hypotension, arrhythmias, and even circulatory arrest, because cardiac output can be severely compromised. The occurrence of an “airlock” in the right ventricle has been postulated as the cause for hemodynamic collapse with massive VAE. However, more recent studies indicate that right ventricular dysfunction is more likely the result of an acute increase in afterload. Continuous entrainment and passage of large volumes of air may lead to the inability of the lungs to adequately vent air from the pulmonary circulation. This results in the liberation of vasoactive substances from the blood-air interface, leading to pulmonary perfusion deficits. Ventilation-perfusion inhomogeneity is due to the redistribution of pulmonary perfusion. Areas of dead space and high ventilation-perfusion ratios reduce end-tidal CO2 and increase arterial CO2 tension. Hypoxia results from altered intrapulmonary shunt, mixed venous oxygen saturation, and redistribution of pulmonary blood flow to regions that are relatively overperfused and underventilated (low ventilation-perfusion ratio). These ventilation-perfusion defects can be variable, because the distribution of air in the pulmonary vessels is a function of both buoyancy and regional pulmonary perfusion. Although ventilation-perfusion inhomogeneities may resolve in as little as 30 minutes after VAE, they can also become progressively worse as a result of the inflammatory response to air in the vascular space. Continuous entrainment of large volumes of air can lead to progressive pulmonary compromise, pulmonary capillary leak, and acute respiratory distress syndrome. Such volumes of air may also reach or exceed the threshold for transpulmonary passage of air, so that it enters the left side of the

heart and coronary sinuses and moves into the brain. This can lead to coronary occlusion and cardiac arrest, as well as cerebral air embolization, with stroke and associated dysfunction.

MANAGEMENT AND PREVENTION Given the severity of VAE sequelae, prevention and early detection are far preferable to management after the fact. The key to preventing VAE is a greater appreciation of risk factors. Patients who will undergo procedures in which a gravitational gradient will be present, blood loss may be significant, or the surgical site is in a highly vascular area are predisposed to air entrainment and VAE. Good examples from the literature include radical retropubic prostatectomy and repeat lumbar or thoracic laminectomies in the prone position. Monitoring for VAE should include ECG, blood pressure, pulse oximeter, end-tidal CO2, precordial Doppler, and a multiorificed catheter with its tip 1 to 2 cm past the junction of the right atrium and superior vena cava (Fig. 175-2). Although the last is important for treatment, the ability to aspirate air from this catheter leaves no doubt about the diagnosis. Further, the transducer of the right atrial catheter can be placed at the level of the surgical site to determine whether a negative pressure gradient exists. In patients thought to be at risk for VAE and in whom invasive monitoring is contemplated, the use of an indwelling catheter for arterial blood gas and pressure monitoring is also advised. 200-

FAP (torr) 0-

RAP (torr) 5-

25-

0-

PAP (torr) 5 sec.

ECG Doppler

I mL saline flush

I mL air

0-

ETCO2 Figure 175–2 ■ Monitoring for venous air embolism. ECG, electrocardiogram; ETCO2, end-tidal CO2; FAP, femoral artery pressure; PAP, pulmonary artery pressure; RAP, right atrial pressure.

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Preventive measures for VAE are few and may be contraindicated in certain patients. Hydration can be used to decrease the pressure gradient between the right heart and the surgical site, provided the patient can tolerate increased right ventricular preload. Many patients with intracranial pathology are not suitable candidates. Although the use of positive end-expiratory pressure to increase intrathoracic pressure has been proposed, it may increase right ventricular preload and is also controversial because it may increase the transatrial gradient and open a patent foramen ovale, thus allowing air to egress into the left heart and brain. For intracranial surgery, bilateral manual jugular venous compression temporarily elevates cerebral venous pressure, thereby preventing ongoing cerebral air embolism; it may also help localize the source. This maneuver is safe and effective, but only if applied gently and transiently in patients without preexisting carotid artery disease. With Doppler activation, a decrease in end-tidal CO2, or both, the central line must be aspirated immediately (using a 50-mL syringe attached to a stopcock). A delay of even a few seconds might allow the entrance of large volumes of air. At the same time, inspired N2O or air should be replaced with 100% oxygen, and the surgeons should be notified to flood the field with water and look for any open veins. Any resulting hypotension or cardiac arrhythmias should be treated symptomatically with positive inotropes and vasopressors to improve contractility and support the circulation. Epinephrine is the drug of choice for resuscitation from massive VAE. If recovery to pre-VAE physiologic levels does not occur in a very short time, or if air continues to be aspirated, the patient should be returned to a position in which there is no gradient present. In the event VAE is suspected and the patient remains comatose after surgery or has a neurologic deficit that is thought to be unrelated to the surgical procedure, neurology or neurosurgery consultation is in order, and magnetic resonance imaging should be performed to diagnose the presence of intra-axial air. If air is visualized, a course of hyperbaric oxygen therapy should be considered.

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Further Reading Adornato DC, Gildenberg PL, Ferrario CM, et al: Pathophysiology of intravenous air embolism in dogs. Anesthesiology 49:120-127, 1978. Albin MS: Air embolism. In Albin M (ed): Textbook of Neuroanesthesia with Neurosurgical and Neuroscience Perspectives. New York, McGraw-Hill, 1997, pp 109-125. Albin MS, Carroll RG, Maroon JC: Clinical considerations concerning detection of venous air embolism. Neurosurgery 3:380-384, 1978. Albin MS, Wills J, Schwend RM: Patent foramen ovale and unexplained stroke. N Engl J Med 354:1753-1755 (Letter to the Editor), 2006. Black S, Cucchiara RF, Nishimura RA, et al: Parameters affecting occurrence of paradoxical air embolism. Anesthesiology 71:235-241, 1989. Chang JL, Albin MS, Bunegin L, et al: Analysis and comparison of venous air embolism detection methods. Neurosurgery 7:135-141, 1980. Drummond JC, Prutow RJ, Scheller MS: A comparison of the sensitivity of pulmonary artery pressure, end-tidal carbon dioxide, and end-tidal nitrogen in the detection of venous air embolism in the dog. Anesth Analg 64:688-692, 1985. Fong J, Gadalla R, Pierri MK, et al: Are Doppler-detected venous emboli during cesarean section air emboli? Anesth Analg 71:254-257, 1990. Geissler MJ, Allen SJ, Mehlhorn U, et al: Effect of body repositioning after venous air embolism: An echocardiographic study. Anesthesiology 86:710-717, 1997. Matjasko J, Petrozza P, Cohen M, et al: Anesthesia and surgery in the seated position: Analysis of 554 cases. Neurosurgery 17:695-702, 1985. Newfield P, Albin MS, Chestnut JC, et al: Air embolism during transphenoidal pituitary operations. Neurosurgery 2:39-42, 1978. Souders JE: Pulmonary air embolism. J Clin Monit Comput 16:375-383, 2000. Souders JE, Doshier JB, Polissar NL, Hlastala MP: Spatial distribution of venous gas emboli in the lungs. J Appl Physiol 87:1937-1947, 1999. Toung T, Ngeow YK, Long DL, et al: Comparison of the effects of positive end-expiratory pressure during continuous venous air embolism in the dog. Anesthesiology 64:724-729, 1986. Verstappen FT, Bernards JA, Kreuzer AF: Effects of pulmonary gas embolism on circulation and respiration in the dog. I. Effects on circulation. Pflugers Arch 386:89-96, 1977. Verstappen FT, Bernards JA, Kreuzer AF: Effects of pulmonary gas embolism on circulation and respiration in the dog. II. Effects on respiration. Pflugers Arch 386:599-604, 1977. Wills J, Schwend RM, Paterson A, Albin MS: Intraoperative visible bubbling may be the first sign of venous air embolism during posterior surgery for scoliosis. Spine 30:E629-E635, 2005.

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Posterior Fossa Surgery Donald S. Prough and Eric Bedell

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Case Synopsis A 28-year-old woman undergoes posterior fossa craniotomy for removal of a brainstem tumor. Preoperative symptoms included headache, facial asymmetry, and difficulty swallowing. The intraoperative course is complicated by periods of bradycardia sufficient to reduce blood pressure and a brief episode of asystole. At the conclusion of the case, the patient opens her eyes and follows simple commands, but she has no spontaneous respiratory efforts and only a weak cough and gag.

PROBLEM ANALYSIS Definition The most important aspect of posterior fossa surgery is location. A review of posterior fossa anatomy demonstrates that lesions, stimulation, or damage to small areas associated with the brainstem or cerebellum can profoundly influence the operative course and long-term outcome of neurosurgical patients. Anatomically, the posterior fossa is defined posteriorly by the occipital bone; laterally by the occipital, temporal (petrous and mastoid portions), and parietal (posteroinferior angle) bones; anteriorly by the sphenoid (clivus), temporal (petrous), and occipital (clivus) bones; superiorly by the tentorium cerebelli; and inferiorly by the foramen magnum. Important structures located within the posterior fossa include the cerebellum, cerebral aqueduct, fourth ventricle, midbrain, pons, medulla, and proximal spinal cord. Located within these structures are the nuclei for all cranial nerves and important afferent and efferent tracts. The oculomotor nerve (3rd cranial nerve) originates in the rostral midbrain, acquires parasympathetic fibers from the Edinger-Westphal nucleus, and courses ventrally through the midbrain. The trochlear nerve (4th cranial nerve) arises from the contralateral caudal midbrain and decussates before traveling ventrally. Other midbrain structures include the corticospinal and corticobulbar tracts, substantia nigra, red nuclei, and decussation of the superior cerebellar peduncles. The pons contains the nuclei for the trigeminal (5th), abducens (6th), facial (7th), and auditory (8th) cranial nerves. The medulla contains the remaining cranial nerves: glossopharyngeal (9th), vagus (10th), spinal accessory (11th), and hypoglossal (12th). The medulla also contains the decussation of the corticospinal tracts ventrally and the inferior cerebellar peduncles posteriorly. From the perspective of intraoperative and postoperative management, one of the most important considerations is that critical respiratory and cardiovascular control centers reside in the brainstem. Involuntary respiratory control is a complex process involving multiple structures, including the pneumotaxic center (upper pons), which is involved in the transition from inspiration to exhalation; the apneustic center (lower pons), which is involved in the control of 708

inspiration; and the medullary respiratory center (dorsal and ventral respiratory groups), which influences both inspiration and exhalation and coordinates those functions with extracranial nerve input. Vasomotor and cardiac centers, located predominantly in the medulla, powerfully influence resting vascular tone, blood pressure, and heart rate. Lesions of the posterior fossa can generate diffuse or localized signs and symptoms, depending on the structures where the lesions are located or the structures compressed by mass lesions. A small lesion impinging on the cerebral aqueduct may result in obstructive hydrocephalus (producing symptoms such as headache and altered mental status). Similarly, a small lesion located in the lateral pons may result in isolated cranial nerve dysfunction. Therefore, important clinical data include the anatomic location of any posterior fossa lesion and the presence and magnitude of associated neurologic or systemic compromise. Intraoperative stimulation, retraction, or damage to structures located within the posterior fossa may activate or inhibit nearby nuclei, leading to rapid and dramatic systemic responses. Intraoperative damage to adjacent structures may result in postoperative alterations in neuronal function (either activation or inhibition), leading to a wide array of clinical problems for postsurgical patients and for those providing postoperative care. The typical presentation of complications related to postoperative edema or bleeding may differ in important respects from that seen after supratentorial surgery. In general, supratentorial lesions lead to a rostral-to-caudal progression of signs and symptoms. This progression may include headache, mental status changes, respiratory alterations, pupillary and oculomotor changes, hemodynamic changes, and, finally, motor abnormalities. In posterior fossa lesions, deterioration may be rapid, may fail to demonstrate a pattern of deterioration, and may present with localized cranial or brainstem deficits. Finally, the surgical approach to the posterior fossa must be considered. The three general approaches are sitting, prone, and lateral (either routine or exaggerated, such as the three-quarter prone–park bench position). Each position has its own risks and benefits and will influence anesthetic management. Because of the significant risk of venous air entrainment (as high as 30%), posterior fossa craniotomies in the sitting position are being performed less frequently. However, even with horizontal positioning,

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venous air embolism—with the attendant risk of cardiovascular collapse and paradoxical air embolism—is a possibility that should be considered in all posterior fossa surgery (also see Chapters 168 and 175).

Recognition Special care is required when evaluating and managing patients with posterior fossa lesions. Mass lesions located within the posterior fossa or that compress posterior fossa structures can generate diffuse or localized signs and symptoms. A thorough preoperative evaluation, with attention to signs and symptoms produced by such lesions, is mandatory. Intraoperatively, vigilance for signs and symptoms of possible stimulation of or damage to critical portions of the brainstem and cerebellum is paramount. This extends to the postoperative period as well. Owing to the risks of hydrocephalus, cranial nerve dysfunction, and alterations in respiratory function, extreme caution must be used when administering any form of sedative, hypnotic, or analgesic medications. Even small doses of benzodiazepines or narcotics may produce unacceptable respiratory depression. Therefore, they should be administered only when patients are directly monitored. For lesions involving the pons and medulla, airway maintenance and protective reflexes may be impaired by bulbar dysfunction, making aspiration and airway compromise a significant risk. Monitoring should include frequent evaluation of the level of consciousness, airway maintenance and protection, oxygenation (e.g., pulse oximetry), ventilation (capnography), heart rate, and blood pressure. The importance of frequent neurologic examination and assessment of ventilation and cardiovascular function cannot be overemphasized. Intraoperative monitoring during posterior fossa surgery can be complex and must be tailored to the brain regions at highest risk during surgery. The cerebellum, though important for the patient’s coordination and longterm function, has relatively little impact on intraoperative anesthetic management. Lesions in other areas may have more intraoperative impact. They often require other techniques, which can be roughly divided into (1) monitoring for nerve function and (2) monitoring for other dangerous conditions (e.g., hemodynamic instability, airway compromise, respiratory insufficiency). Intraoperative monitoring for nerve integrity and function is often accomplished through provocative testing. Common techniques include somatosensory evoked potentials and facial nerve monitoring. In each case, specific monitoring modalities are used in an attempt to assess the integrity and function of the nerve or nerve pathways at risk. These techniques often have anesthetic implications (e.g., stable, low concentrations of potent inhalational agents to avoid excessive attenuation of somatosensory evoked potentials) and thus require appropriate anesthetic management to provide the best monitoring conditions. Failure to appreciate the specific monitoring needs for the proposed surgery may result in inadequate patient monitoring and suboptimal outcomes. Intraoperative monitoring for hemodynamic instability and postoperative monitoring for neuronal dysfunction, hemodynamic instability, airway compromise, or respiratory

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insufficiency are important mandates for anesthesiologists. Stimulation of or damage to brainstem cardiac and vasomotor centers can lead to rapid and unpredictable hemodynamic changes. Extreme heart rate and blood pressure alterations are common with surgical manipulation, and rapid diagnosis and treatment are required. Consideration of the manner of treatment is also important, for neurosurgeons often rely on hemodynamic changes to guide the extent of surgical exploration. Thus, prophylactic treatment of heart rate (i.e., with vagolytic agents) and blood pressure is generally discouraged. In practice, it is more important to recognize when a critical portion of the brainstem is stressed than to blunt all hemodynamic responses. The risk of venous air embolism is also a consideration in all posterior fossa surgery, and there should be a plan in place for diagnosis and management. Finally, there are no adequate intraoperative monitors for a large number of important brainstem functions, such as airway maintenance and protection, swallowing, and respiratory control. Thus, anesthetic management must be planned and executed to provide rapid and clear emergence with tight hemodynamic control. Close communication between the anesthesiologist and the neurosurgeon is vital. Specifically, hemodynamic parameters, expected neuronal or bulbar dysfunction, and anticipated alterations in airway protection and respiratory function should be discussed. Postoperative ventilatory support, intubation, or diagnostic studies (e.g., angiography, computed tomography, magnetic resonance imaging) must be discussed before emergence, and appropriate plans must be developed in light of those discussions.

Risk Assessment Knowledge of the anatomic location of the lesion of interest, the planned surgical procedure, and the actual structures involved in the surgery is a critical element of posterior fossa surgery. Risk assessment is possible only after a review of the individual patient’s history and physical examination, an evaluation of radiologic studies, and a discussion with the neurosurgeon. The greatest risks are associated with tumors directly involving the brainstem (e.g., pons and medulla), lesions with direct involvement of the cranial nerves required for airway maintenance and protection, lesions involving the facial nerve, and surgeries conducted with the patient in the sitting position. The actual events encountered during surgery are impossible to predict, which contributes to the challenge of providing anesthesia for neurosurgery in general and for posterior fossa surgery in particular. At a minimum, plans for the diagnosis and management of hemodynamic instability, respiratory dysfunction, alterations in cranial nerve function, and venous air embolism should be made before starting any posterior fossa surgery.

Implications The risks to patients undergoing posterior fossa surgery can be divided into preoperative, intraoperative, and postoperative complications. Before surgery, patients must be carefully monitored, and sedative-hypnotic and analgesic drugs must be titrated with extreme care. Intraoperative risks are

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predominantly hemodynamic instability and cardiovascular collapse. Especially with surgery involving the pons and medulla, extreme hemodynamic variability in heart rate and blood pressure may result in patient instability. This instability is usually limited to periods of direct surgical retraction and manipulation, but it can be clinically important. Hemodynamic collapse and cardiac arrest have resulted from venous air entrainment, and both are a constant risk during all posterior fossa (and skull base) surgery, even in patients who are horizontally positioned. Important postoperative risks include alterations in respiratory function, rapid development of increased posterior fossa pressure (e.g., from hematoma formation), development of hydrocephalus, and alterations in cranial nerve function. Because there are limited intraoperative methods of monitoring for these possibilities, rapid and clear emergence from anesthesia with limited respiratory depression and tight hemodynamic control is of primary importance and should be a major determinant in the choice of anesthetic technique.

MANAGEMENT A full understanding of the patient’s condition and anticipated surgical requirements represents an important part of management. Failure to understand the specific location and effect of the posterior fossa lesion severely limits the delivery of optimal therapy. Support and protection of oxygenation and ventilation should be the primary focus when managing complications associated with posterior fossa surgery. Hemodynamic monitoring and modification of heart rate and blood pressure through the use of vasoactive medications

Table 176–1

■

are common requirements during posterior fossa surgery. However, remember that prophylactic treatment of heart rate and blood pressure is not indicated, because the surgeon often depends on the development of hemodynamic alterations to guide ongoing surgery. Postoperatively, to determine the need for ongoing monitoring and support, all cranial nerve and brainstem functions associated with the site of surgery should be specifically evaluated once the patient is awake. This requires that the anesthetic technique permit neurologic examination at the conclusion of surgery, preferably in the operating room before transport to the intensive care unit. Black and coworkers reported their experience with 579 posterior fossa craniotomies performed in 1981 through 1984. During this period, the number of sitting position craniotomies performed at the Mayo Clinic markedly decreased, while the number of horizontal position craniotomies markedly increased. Overall, there were no significant differences in mortality or other postoperative outcomes between patients undergoing surgery in the two positions (Table 176-1). The incidence of important complications was substantial after surgery in either position. The time course and presenting signs and symptoms of posterior fossa deterioration may be different from those associated with supratentorial surgery. With supratentorial lesions, deterioration (usually due to an expanding mass or hydrocephalus) generally progresses over time, so serial monitoring is appropriate. For posterior fossa surgery, rapid localized deterioration may occur, leading to a loss of bulbar function, respiratory arrest, or hemodynamic collapse. Thus, vigilance and a high index of suspicion must be maintained into the postoperative period.

Postoperative Outcomes Not Affected by Position Sitting (N = 333)

Outcome

No.

Mental status deteriorated Mental status improved Eye injury Seizures Motor deficit new or worse Motor deficit improved Sensory deficit new or worse Sensory deficit improved Complete loss of facial nerve function Perioperative myocardial infarction Respiratory complications Coma (>1 wk) Cerebrovascular accident Congestive heart failure Hemodynamic instability Pulmonary embolus Re-exploration for bleeding Re-exploration for infection Acute mortality (within 30 days) Quadriparesis Symptomatic pneumocephalus Peripheral nerve injury Laryngeal or lingual edema

14 7 8 6 17 29 6 19 23 1 7 6 8 1 5 0 6 2 9 0 0 0 0

Horizontal (N = 246) %

4 2 2 2 5 9 2 6 7 0.3 2 2 2 0.3 1.5 1.8 0.6 2.7

No. 9 12 12 2 16 9 5 4 26 4 8 3 8 0 10 2 6 2 5 0 0 0 0

% 4 5 5 1 6 4 2 2 11 1.6 3 1 3 4 1 2.4 0.8 2

From Black S, Ockert DB, Oliver WC Jr, Cucchiara RF: Outcome following posterior fossa craniectomy in patients in the sitting or horizontal positions. Anesthesiology 69:49-56, 1988.

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PREVENTION Careful evaluation of the patient and discussion with the surgeon about location, impact, and proposed surgical approach are required for the optimal management of patients undergoing posterior fossa surgery. Anticipation of the more common severe complications, such as postoperative venous air embolism and airway or respiratory dysfunction, is a critical part of anesthetic management, as is recognition of the need for specialized monitoring techniques. Although serious complications associated with posterior fossa surgery are uncommon with current surgical procedures, a high index of suspicion and constant vigilance are the most important aspects of perioperative care.

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Further Reading Black S, Ockert DB, Oliver WC Jr, Cucchiara RF: Outcome following posterior fossa craniectomy in patients in the sitting or horizontal positions. Anesthesiology 69:49-56, 1988. Endo T, Sato K, Takahashi T, Kato M: Acute hypotension and bradycardia by medulla oblongata compression in spinal surgery. J Neurosurg Anesth 13: 310-311, 2001. Nolte J: The Human Brain: An Introduction to Its Functional Anatomy, 5th ed. St. Louis, Mosby–Year Book, 2002. Plum F, Posner JB: The Diagnosis of Stupor and Coma, 3rd ed. Philadelphia, FA Davis, 1982. Williams DL, Umedaly H, Martin IL, Boulton A: Chiari type I malformation and postoperative respiratory failure. Can J Anaesth 47:1220-1223, 2000.

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Pituitary Tumors: Diabetes Insipidus Melissa A. Laxton and Patricia H. Petrozza Case Synopsis A 58-year-old man undergoes transsphenoidal hypophysectomy for resection of a prolactin-secreting pituitary adenoma with suprasellar extension. Ten hours after surgery, urine output exceeds 3 L/hour, and the serum sodium level is 150 mEq/L.

PROBLEM ANALYSIS Definition Diabetes insipidus is a syndrome characterized by polyuria, thirst, and polydipsia triggered by plasma hyperosmolarity. Neurogenic diabetes insipidus results from insufficient antidiuretic hormone (ADH) secretion, secondary to damage to the hypothalamic-neurohypophysial axis. Loss of approximately 75% of ADH-secreting neurons is needed for the development of clinically relevant polyuria. In contrast, nephrogenic diabetes insipidus is characterized by renal resistance to the action of ADH. An absolute deficiency of ADH results in impaired urine concentrating ability, polyuria, and a tendency toward dehydration. Most patients have incomplete neurogenic diabetes insipidus and retain a limited ability to concentrate urine and conserve free water. However, if access to water is impaired (e.g., unconsciousness, perioperative nothing-bymouth status), hypertonic dehydration and hypernatremia may develop. Signs and symptoms of hypernatremia include psychomotor agitation, neuromuscular irritability, lethargy, coma, and seizures.

Recognition Diabetes insipidus occurs in as many as 20% of adult patients after transsphenoidal pituitary surgery. The syndrome is usually transient in this setting, and perioperative glucocorticoid replacement may facilitate the development of polyuria. Often, polyuria appears on or before the first postoperative day. The polyuria of diabetes insipidus is characterized as follows: ● ● ●

A 24-hour urine volume greater than 50 mL/kg Urine osmolarity greater than 300 mOsm/kg H2O Urine specific gravity less than 1.010

Chronic polyuria causes the hypertonic renal medullary concentration gradient to be “washed out.” Additional urine concentrating mechanisms become impaired, so that polyuria increases. Alternative causes of polyuria must be eliminated to make the diagnosis of primary neurogenic or nephrogenic diabetes insipidus with confidence (Table 177-1). 712

Risk Assessment As noted earlier, transient diabetes insipidus occurs in up to 20% of patients after transsphenoidal hypophysectomy. However, it becomes permanent in about 2% of cases. A macroadenoma with suprasellar extension is associated with a higher risk for postoperative diabetes insipidus than is a lesion confined to the sella. Recent data suggest that an endoscopic transsphenoidal approach for resection of pituitary tumors may decrease both the short- and long-term incidence of diabetes insipidus compared with the traditional, direct transsphenoidal approach. The secretory type of tumor appears to have no effect on the postoperative occurrence of diabetes insipidus. Postoperative diabetes insipidus is usually recognized within 12 to 24 hours of the initial insult, but delays of days to weeks have been recorded. In approximately 50% to 60% of cases, diabetes insipidus is transient, lasting only 3 to 5 days. More rarely, it may last several weeks, followed by gradual resolution. This pattern is more common after resection of pituitary adenomas confined to the sella. After transcranial approaches to pituitary macroadenomas with suprasellar extension, or procedures in which proximal damage to the pituitary stalk is likely, both complete and partial diabetes insipidus have been observed; in some cases, it takes several years for this condition to improve or resolve. A small group of patients (5% to 10%) exhibits a classic triphasic response to injury. This pattern most commonly Table 177–1

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Causes of Polyuria Other Than Primary Neurogenic or Nephrogenic Diabetes Insipidus

Chemical diuresis Mannitol Urea Radiocontrast agents Hyperglycemia Furosemide, thiazides, ethacrynic acid Acute renal failure Drug-induced nephrogenic diabetes insipidus (e.g., cisplatin, lithium) Postobstructive diuresis Postresuscitation diuresis

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follows hypophysial stalk injury due to severe head trauma or the resection of extensive suprasellar tumors. The initial phase is characterized by an abrupt cessation of ADH release. This is followed by polyuria, which begins within 12 to 24 hours after injury and lasts for 4 to 8 days. An antidiuretic phase, lasting 5 to 6 days, follows. It is characterized by concentrated urine, with plasma hyposmolarity and hyponatremia as a result of free water reabsorption. Profound hyponatremia and its attendant complications may develop if there is a delay in recognizing this phase. Excessive release of stored ADH from degenerating neurohypophysial tissues is the likely explanation for this antidiuretic phase. Once this stored ADH release is complete, diabetes insipidus frequently recurs. Although usually persistent, sometimes it may improve or resolve.

Implications A patient with diabetes insipidus is unable to concentrate urine and retain water. Without treatment, intravascular volume depletion results, cardiac stroke volume declines, and heart rate increases in an effort to maintain cardiac output. Hypoperfusion may be signaled by weak peripheral pulses; orthostatic hypotension; cold, clammy skin; rapid, shallow respirations; and a reduced level of consciousness. Hypernatremia may manifest as seizures and hyperreflexia.

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Although desmopressin is clearly the drug of choice for the chronic treatment of diabetes insipidus, its duration of action is 12 to 18 hours. Some clinicians prefer aqueous vasopressin if diabetes insipidus is likely to be transient. Aqueous vasopressin is formulated as 20 pressor units/mL of solution. The peak effect occurs by 1 to 2 hours, and the duration of action is 4 to 8 hours. The usual starting dosage is 2 to 5 units subcutaneously or intramuscularly every 4 to 6 hours as needed. Careful assessment of fluid intake; urine output, osmolarity, and specific gravity; plasma osmolarity; serum sodium concentration; and body weight should guide therapy with vasopressin or desmopressin. Clinicians must be alert to the possible development of an antidiuretic phase of hormonal dysfunction, complicated by water intoxication.

PREVENTION Meticulous surgical resection is the best means of preventing perioperative diabetes insipidus. Anesthesiologists should maintain a high index of suspicion for the development of diabetes insipidus, especially when there is suprasellar extension of a pituitary tumor or other endocrine abnormalities in a neurosurgical patient.

Further Reading MANAGEMENT Owing to the predominantly transient nature of perioperative diabetes insipidus, some mild cases are managed with oral fluid replacement, especially if the patient is cooperative and the thirst mechanism is intact. However, if the patient is unable to cooperate, and there is associated hypokalemia and concern about “wash-out” of the renal medullary concentration gradient, more aggressive therapy may be warranted. Exogenous replacement of ADH is with either desmopressin or aqueous vasopressin. After transsphenoidal resection, desmopressin is usually administered subcutaneously in a dosage of 1 to 2 μg every 8 to 12 hours. Desmopressin lacks the vasoconstrictor effects of vasopressin and is less likely to cause hypertension or abdominal cramping. For patients requiring long-term ADH replacement, both intranasal and oral preparations are available. However, the dose must be titrated individually.

Arafah BM, Nasrallah MP: Pituitary tumors: Pathophysiology, clinical manifestations and management. Endocr Relat Cancer 8:287-305, 2001. Barker FG II, Klibanski A, Swearingen B: Transsphenoidal surgery for pituitary tumors in the United States, 1996-2000: Mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab 88:4709-4719, 2003. Carrau RL, Kassam AB, Snyderman CH: Pituitary surgery. Otolaryngol Clin North Am 34:1143-1155, 2001. Fukuda I, Hizuka N, Takano K: Oral DDAVP is a good alternative therapy for patients with central diabetes insipidus: Experience of five-year treatment. Endocr J 50:437-443, 2003. Rajaratnam S, Seshadri MS, Chandy MJ, et al: Hydrocortisone dose and postoperative diabetes insipidus in patients undergoing transsphenoidal pituitary surgery: A prospective randomized controlled study. Br J Neurosurg 17:437-442, 2003. Singer PA, Sevilla LJ: Postoperative endocrine management of pituitary tumors. Neurosurg Clin N Am 14:123-138, 2003. Vance ML: Perioperative management of patients undergoing pituitary surgery. Endocrinol Metab Clin North Am 32:355-365, 2003. Verbalis JG: Management of disorders of water metabolism in patients with pituitary tumors. Pituitary 5:119-132, 2002.

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Philippa Newfield Case Synopsis A 64-year-old man undergoing craniotomy for clip-ligation of a right anterior communicating artery aneurysm 12 hours after initial subarachnoid hemorrhage becomes acutely hypertensive and experiences bradycardia during the induction of anesthesia.

PROBLEM ANALYSIS Definition Subarachnoid hemorrhage (SAH) from the rupture of an intracranial aneurysm (ICA) occurs with a frequency of 6 to 8 per 100,000 persons in most Western populations. Rates of ICA rupture are 0.05% to 6% per year, depending on the size and location of the aneurysm. The risk of rupture is 11 times greater in patients with previous SAH than in those with symptomatic aneurysms. Rebleeding is the occurrence of further hemorrhage after the initial SAH. Such episodes can be catastrophic, with high mortality and chronic morbidity rates. If untreated, 50% of ruptured ICAs rebleed within 6 months of the initial SAH. The incidence of rebleeding is highest within 24 hours of SAH (4%); it then declines to 1% to 2% per day for the next 13 days. About 20% to 30% of ruptured ICAs rebleed within 30 days of the initial SAH. Another 10% to 15% of patients rebleed during the ensuing 5 months. ICA rerupture produces neurologic deterioration by raising intracranial pressure (ICP) and impairing cerebral perfusion. Many complications may ensue (Table 178-1). Hydrocephalus can develop acutely, because sudden clot deposition throughout the subarachnoid space blocks the passage of cerebrospinal fluid (CSF) through the basal subarachnoid cisterns. Late-onset hydrocephalus is due to obstruction of CSF drainage pathways by organized subarachnoid clot. Brain infarction also occurs due to direct, hematomainduced brain destruction or shifts in the intracranial contents, along with vascular compromise. The larger the volume of subarachnoid blood and the greater the ICP, the Table 178–1

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more likely it is that cerebral blood flow (CBF) will be reduced and the patient’s neurologic condition will worsen. SAH also impairs autoregulation, the ability of the brain to maintain CBF fairly constant over mean arterial pressures between 50 and 150 mm Hg, and it reduces the cerebral metabolic rate of oxygen (O2) consumption. The incidence of intraoperative ICA rupture ranges from 6% to 8%. It varies among institutions and depends on the size and location of the aneurysm. Causes of ICA rupture and rebleeding during surgery, in decreasing order of frequency, are dissection, brain retraction, hematoma evacuation, and opening of the dural and arachnoid membranes.

Recognition Signs of rebleeding with reruptured ICAs are largely due to intracerebral hemorrhage. The risk of such bleeding is higher with subsequent episodes of ICA rupture. This is because adhesions from the prior SAH seal off the aneurysm from the subarachnoid space and deflect any new bleeding into the brain parenchyma. After ICA rebleeds, the level of consciousness deteriorates, and patients develop focal neurologic deficits (aphasia, hemiplegia), abnormal vital signs (hypertension, bradycardia, arrhythmias, irregular respirations), and temperature elevation. They also have fluid and electrolyte imbalance (especially hyponatremia), and retinal hemorrhage may be evident on ophthalmologic examination (Table 178-2). If ICA rebleeding occurs during or immediately after the induction of anesthesia, the patient’s blood pressure will increase, and the heart rate may or may not decrease. It is important to realize that the ICP will also increase. At this

Complications of Subarachnoid Hemorrhage

Early

Late

Hematoma, ↑ ICP, rebleeding, seizures, hydrocephalus Nerve palsy, hemiparesis, reduced LOC Cardiac arrhythmias Transient ↑ BP Impaired vision Fluid and electrolyte imbalance

Rebleeding, hydrocephalus, vasospasm, infarction, epilepsy Permanent hemiparesis, cognitive disabilities Myocardial infarction, pneumonia, hepatic and renal dysfunction Persistent ↑ BP Vitreous hemorrhage Neurologic deterioration, death

BP, blood pressure; ICP, intracranial pressure; LOC, level of consciousness.

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juncture, ICA rupture is diagnosed by intracranial Doppler ultrasonography, and the efficacy of management is monitored thereafter. Intraoperative rupture of an ICA is readily apparent. Rebleeding after completion of the operation is signaled by failure to awaken from anesthesia or by further neurologic deterioration after awakening (e.g., decrease in level of consciousness, development of new focal neurologic deficits or aphasia).

Once the ICA has bled, the risk of rebleeding is greatest within the first 24 hours (4%); this is because clot sealing the aneurysmal rent is tenuous, and systemic blood pressure is usually at its highest. The cumulative rebleed rate for ruptured ICAs is 19% at 14 days and about 40% at 179 days. Patients whose ruptured ICAs remain untreated continue to rebleed at a rate of 3% per year for up to 15 years. Late rebleeding is fatal in 67% of cases. The International Subarachnoid Aneurysm Trial compared operative aneurysmal clip-ligation with endovascular coiling in 2143 patients with ICA-related SAH. At 1-year follow-up, results of the randomized study showed a low risk of rebleeding in both groups (2.4% for coil versus 1.0% for clip repair). However, even after accounting for effects of rebleeding, the relative risk for death or significant disability was 22.6% lower for endovascular versus surgical repair, an absolute risk reduction of 6.9%. Most of these patients were in good condition after SAH (World Federation of Neurosurgical Societies grades I and II) and had small anterior ICAs (92% <11 mm in size). For such ICAs, endovascular and surgical repairs are considered equivalent therapies.

Risk Assessment

Implications

ICA rerupture is one of the major causes of neurologic deterioration after initial SAH (Table 178-3). Risk of rebleeding begins immediately after the initial ICA hemorrhage and is the major threat early after SAH. The likelihood of rebleeding is directly related to the patient’s systolic blood pressure in the post-SAH period. For patients who have already had multiple rebleeding episodes, the likelihood of further rupture and death is much greater. Other risk factors include poor neurologic status (owing to initial SAH parenchymal injury), shorter time since initial SAH, female gender (twice the incidence of rebleeding versus males), poor medical condition, older age, posterior ICA, higher rates of intracerebral or intraventricular hematoma, and abnormal clotting parameters. During pregnancy, the risk of rebleeding from an unsecured ICA is 33% to 50%. Although this is fatal in 50% to 68% of patients, there is no evidence that the rebleeding rate in pregnant patients is different from that in the general population.

Pathophysiologic sequelae and complications of rebleeding after initial aneurysmal SAH are considerable. Because a recurrent hemorrhage is usually more severe than the initial one, mortality with recurrent hemorrhage doubles to 80%, with significant associated morbidity in the surviving patients. The size of the hematoma is the most critical factor in determining outcome (Table 178-4). Patients with large subdural hematomas and more of a midline shift on computed tomography scanning have a poorer prognosis, as do those with associated intracerebral or intraventricular hemorrhage. Because the majority of rebleeding takes place within the first 6 to 24 hours after the initial SAH, early intervention to secure the aneurysm (whether by surgical clipping or endovascular coiling) has become the mainstay of treatment for rebleeding. Thus, diagnosis and treatment of rebleeding must be accomplished quickly and efficiently. Further, because increased experience with SAH, its sequelae, and its treatment improves patient care, collaborative relationships between community hospitals and centers specializing in the surgical and endovascular treatment of ICAs are mandatory.

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Effects of Aneurysmal Rebleeding

Direct brain destruction Disturbance of CSF flow → hydrocephalus ↑ ICP from hematoma, intracerebral hemorrhage, intraventricular hemorrhage Cerebral infarction from ↓ CBF Fluid and electrolyte imbalance Cardiac arrhythmias, ↑ BP Respiratory impairment BP, blood pressure; CBF, cerebral blood flow; CSF, cerebrospinal fluid; ICP, intracranial pressure.

Table 178–3

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Causes of Neurologic Deterioration after Subarachnoid Hemorrhage

Rebleeding—intracranial hypertension Hematoma Hydrocephalus Cerebral edema Seizures Meningitis Disordered autoregulation Disordered carbon dioxide responsiveness Acid-base disturbances Fluid and electrolyte disturbances Vasospasm Delayed ischemic deficit Cerebral infarction—secondary cerebral insults Hypotension Hypoxemia Hyperglycemia Intracranial hypertension (beyond initial hemorrhage)

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Predictors of Mortality after Acute Subarachnoid Hemorrhage

Poor clinical status or grade on admission—directly related to size of hematoma Decreased level of consciousness Elevated blood pressure Rebleeding Delayed ischemic deficit (vasospasm) Thickness of subarachnoid clot on initial computed tomography scan Basilar aneurysm Older age Preexisting medical illness

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MANAGEMENT Therapy for rebleeding after an initial SAH is designed to maintain cerebral perfusion, reduce intracranial hypertension and volume, control systemic blood pressure, and decrease transmural pressure (mean arterial pressure minus ICP) across the aneurysm wall. Within this context, optimization of brain O2 delivery depends on total arterial O2 content and necessitates the maintenance of normal hemoglobin concentrations and arterial O2 saturations. Specific therapy varies according to the stage of ICA therapy at which rerupture occurs (Table 178-5). If the aneurysm bleeds before, during, or after the induction of anesthesia, the patient is hyperventilated with 100% O2. Thiopental, which also affords some amount of cerebral protection, or intravenous sodium nitroprusside or nicardipine1 will lower blood pressure, although excessive lowering of blood pressure at this juncture can be detrimental if it interferes with cerebral perfusion. Nitroprusside also causes cerebral vasodilatation, which may further raise ICP and impair cerebral perfusion, thereby increasing the ischemic penumbra.2 Immediate craniotomy for “rescue clipping” after ICA rupture during induction has been successful. Intraoperative rupture of an ICA mandates rapid achievement of surgical control. The mean arterial pressure may be reduced briefly to 50 mm Hg to facilitate temporary proximal and distal occlusion of the parent vessel in preparation for clip-ligation of the aneurysmal neck. Once the parent vessel is occluded, blood pressure is increased to normal to enhance collateral circulation during the period of temporary occlusion. This may be superior to the use of controlled hypotension after rupture. Alternatively, the ipsilateral carotid artery can be manually compressed for 3 minutes to produce a bloodless field. Also, if the bleeding is sufficient to cause hypovolemia, induced hypotension may not be an option. Any blood loss is replaced immediately with whole blood, blood products, colloid, or crystalloid. It is essential to maintain normal blood volume while the blood pressure is lowered. Although barbiturates and etomidate have been advocated to protect against focal brain ischemia, the clinical efficacy is unproved. Also, with hypovolemia, the associated hypotension can be detrimental. Stable patients can receive thiopental or etomidate before temporary occlusion. For all patients, temperature is maintained in the lownormal range (34°C to 35°C). Even moderate hypothermia confers some cerebral protection by reducing the release of excitatory neurotransmitters and the cerebral metabolic rate of O2 consumption (by 7% to 8% per 1°C). However, results of the recent International Hypothermia for Aneurysm Surgery Trial suggest that intraoperative hypothermia (33°C) does not improve neurologic outcomes compared with maintaining normothermia (target temperature 36.5°C). Any increase in temperature above normal should be promptly reduced.

1 2

The latter may be more effective for reducing associated vasospasm. Zone of ischemic brain surrounding nonviable brain tissue.

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Aneurysmal Rupture: Management Priorities

During or After Induction Hyperventilation 100% oxygen Blood pressure control Barbiturates

During Dissection Induced hypotension Proximal vascular or carotid occlusion with high normal blood pressure 100% oxygen Pharmacologic metabolic suppression Volume resuscitation

Patients who do not awaken as expected following the operation, or who awaken and then deteriorate neurologically, require timely diagnosis of the cause. Emergent computed tomography scans can help differentiate ICA rebleed, rupture of another ICA, postsurgical bleeding, pneumocephalus, acute hydrocephalus, and acute cerebral infarction as the cause of deterioration. If there is intracranial hypertension postoperatively, the patient requires intracranial volume-reducing measures such as hyperventilation with 100% O2, mannitol, cerebral vasoconstricting drugs (e.g., thiopental, propofol), and augmentation of cerebral perfusion through maintenance of systemic blood pressure in the patient’s high-normal range. Emergency reoperation may be necessary for rescue clipping of the ruptured ICA, evacuation of hematoma, control of bleeding, or ventricular drainage. In an emergency, an external ventricular drain may be inserted in the postanesthesia care area or intensive care unit to decompress the ventricular system.

PREVENTION The only definitive measure to prevent ICA rebleeding is early surgical clip-ligation or endovascular obliteration of the aneurysm. Once the ICA has been secured, the risk of rebleeding is reduced to practically zero, with late rebleeding occurring more often after endovascular than neurosurgical intervention. After securing the ICA, the patient can receive prophylaxis against or treatment for cerebral vasospasm, such as hypertensive hypervolemic hemodilution (“triple H therapy”), without fear of ICA rerupture. Short of securing the ICA by mechanical means, preoperative measures to prevent rebleeds include maintenance of blood pressure in the patient’s normal range, maintenance of euvolemia (Table 178-6), and avoidance of seizures (which may be associated with hypertension). Blood pressure control is achieved with analgesics and short-acting antihypertensive drugs (e.g., labetalol) that do not affect the cerebral vasculature. Lowering blood pressure has not been shown to reduce the risk of rebleeding in any controlled trial, but prospective studies have correlated rebleeding with higher systolic blood pressures. Beyond the first few days after initial SAH, the risk of lowering the blood pressure increases,

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Prevention of Aneurysmal Rebleeding

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Induction of Anesthesia: Aneurysmal Clip-Ligation

Preoperative BP control: sedatives, short-acting antihypertensive drugs Maintain adequate cerebral perfusion pressure (70 to 80 mm Hg) Analgesic drugs Cautious HHH therapy for vasospasm Early aneurysmal clip-ligation or endovascular obliteration

Intraoperative Induction Maintain normal BP Maintain direct BP monitoring Avoid surges in systolic BP Ensure adequate depth of anesthesia Provide optimal oxygenation Maintain normocapnia Craniotomy Osmotic diuretic with craniotomy CSF drainage after craniotomy Aneurysmal manipulation Proximal temporary occlusion High-normal BP Hypotension Osmotic diuretics CSF drainage Hyperventilation Venous drainage Normoglycemia Hypothermia Adequate analgesia Maintain normovolemia Monitor central venous pressure, urine output, blood loss

Emergence Avoid surges in systolic BP Adequate analgesia

Postoperative Avoid surges in systolic BP Maintain intravascular volume Avoid hypotension Adequate analgesia BP, blood pressure; CSF, cerebrospinal fluid; HHH, hypertensive hypervolemic hemodilution; ICP, intracranial pressure.

because the patient is now susceptible to vasospasm. At this point, it is best to let the patient’s blood pressure self-adjust, although pain should be treated appropriately to prevent associated increases in blood pressure. If the patient deteriorates neurologically from cerebral vasospasm before the ICA is secured, triple H therapy (see earlier) must be instituted with caution. To avoid rebleeding, the systolic pressure is increased modestly from 120 to 150 mm Hg, central venous pressure from 10 to 12 mm Hg, and pulmonary capillary wedge pressure from 12 to 16 mm Hg. Avoidance of lumbar puncture and rapid ventricular drainage before ICA clip-ligation may also protect against rebleeding. However, these measures are sometimes used to lower ICP (as a calculated risk) when cerebral perfusion is seriously compromised by intracranial hypertension. The antifibrinolytics ε-aminocaproic acid and tranexamic acid can reduce the likelihood of ICA rebleeding. However, associated cerebral vasospasm limits their usefulness and may double mortality rates due to delayed ischemia. Thus, there is little if any indication for the use of these drugs after SAH.

Optimal head position Deep level of anesthesia Propofol (1-2 mg/kg) Thiopental (3-5 mg/kg) Fentanyl (3-5 μg/kg) Sufentanil (0.5-1 μg/kg) Vecuronium (0.1 mg/kg) Low-dose inhalation anesthetic Controlled ventilation 100% O2 Normal PaCO2 (35-40 mm Hg) Before laryngoscopy Lidocaine (1.5 mg/kg) Thiopental (2-3 mg/kg) Propofol (0.5 mg/kg) Brief, gentle laryngoscopy Intubation

During the induction of anesthesia for craniotomy for ICA clip-ligation, it is essential to maintain transmural pressure across the ICA wall in the patient’s preoperative range by the judicious use of drugs and meticulous technique (Table 178-7). Certainly, one must prevent sudden increases in systemic blood pressure and decreases in ICP. Direct blood pressure monitoring provides beat-to-beat information about the immediate effects of anesthetic or neurosurgical interventions (e.g., laryngoscopy, application of pin headholders). Anticipation of a blood pressure increase with these maneuvers can facilitate the timely use of drugs such as propofol and thiopental to deepen anesthesia. Avoiding sudden increases in transmural pressure from a decrease in ICP before the bone flap is turned is also important. Ventilation is adjusted to maintain normocapnia (arterial carbon dioxide tension 35 to 40 mm Hg) and intracranial volume until the dura is opened. However, if the patient has a large subdural hematoma, hyperventilation and other maneuvers to improve intracranial compliance are indicated during induction. The volume-reducing effect of mannitol also may decrease ICP before the skull is opened. To avoid consequent increased transmural pressure and the potential for ICA rerupture, mannitol is not administered until after the craniotomy has been performed, when the intracranial contents are at atmospheric pressure. Lumbar drainage of CSF also facilitates ICA access by relaxing the brain, but this too increases transmural pressure by reducing ICP if it is performed before the cranium has been opened. Interventions to prevent rebleeding are also necessary during ICA manipulation for clip-ligation. Temporary proximal occlusion of the parent vessel is used to decrease the turgor of the ICA sac, and the blood pressure is maintained in the patient’s high-normal range to enhance distal and collateral perfusion. Of course, if the temporary clip is removed before the aneurysm has been secured, blood pressure must be quickly returned to the patient’s low-normal range to prevent aneurysmal rupture. Hypotension with isoflurane or nitroprusside to a mean arterial pressure of 50 mm Hg in normotensives and 60 mm Hg or higher in hypertensives was once used to increase the safety of aneurysmal manipulation. This is no longer done,

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however, because hypotension to lower CBF may adversely affect patients with or in the process of developing cerebral vasospasm. Although there are no controlled human studies of the protective effects of intravenous drugs during ICA surgery, the ability to quickly institute prophylactic protective measures before the onset of ischemia is desirable. A number of intravenous drugs, alone and in combination, have been administered to extend the safe duration of temporary vascular occlusion. High-dose mannitol (2 g/kg) enhances the microcirculation and increases regional CBF in areas of ischemia. Because the production of free radicals may contribute to neuronal damage from ischemia, vitamin E and dexamethasone are used to augment mannitol’s effects in some protocols. To the regimen of normotension, normovolemia, and mannitol, some neurosurgeons have added electroencephalographic burst suppression (with etomidate or barbiturates), with reported benefit. Propofol, if administered to provide burst suppression before temporary ICA occlusion, may also confer cerebral protection. Normoglycemia and relative hypothermia to 35°C may also reduce the ischemic risk with temporary occlusion of cerebral vessels. Control of blood pressure is essential during emergence from anesthesia, because patients are at risk for rebleeding during this time as well. This may be due to multiple ICAs, whether diagnosed or not. If one has been clipped, another unsecured one may bleed on emergence. Hypertension with emergence also threatens surgical hemostasis and may produce intracranial hemorrhage. Finally, wrapping the ICA (versus clipping) does not necessarily protect against rebleeding during emergence from anesthesia.

Further Reading Chang HS, Hongo K, Nakagawa H: Adverse effects of limited hypotensive anesthesia on the outcome of patients with subarachnoid hemorrhage. J Neurosurg 92:971-975, 2000. Cross DT, Tirschwell DL, Clark MA, et al: Mortality rates after subarachnoid hemorrhage: Variations according to hospital case volume in 18 states. J Neurosurg 99:810-817, 2003. Egge A, Waterloo K, Sjoholm H, et al: Prophylactic hyperdynamic postoperative fluid therapy after aneurysmal subarachnoid hemorrhage:

A clinical, prospective, randomized, controlled study. Neurosurgery 49:593-606, 2001. Eng CC, Lam AM: Cerebral aneurysms: Anesthetic considerations. In Cottrell JE, Smith DS (eds): Anesthesia and Neurosurgery, 3rd ed. St. Louis, Mosby–Year Book, 1994, pp 376-405. Fridriksson S, Saveland H, Jakobsson KE, et al: Intraoperative complications in aneurysm surgery: A prospective national study. J Neurosurg 96:515-522, 2002. Gianotta SL, Oppenheimer JH, Levy ML, et al: Management of intraoperative rupture of aneurysms without hypotension. Neurosurgery 28:531-536, 1991. Haley EC Jr, Kassell NF, Torner JC, et al: The International Cooperative Study on Timing of Aneurysm Surgery: The North American experience. Stroke 23:205-214, 1992. Kett-White R, Hutchinson PJ, Al-Rawi PG, et al: Adverse cerebral events detected after subarachnoid hemorrhage using brain oxygen and microdialysis probes. Neurosurgery 50:1213-1222, 2002. LeRoux P, Winn HR: Management of the ruptured aneurysm. In LeRoux P, Winn HR, Newell DW (eds): Management of Cerebral Aneurysms. Philadelphia, WB Saunders, 2004, pp 303-333. Molyneux A, Kerr R, Stratton I, et al: International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: A randomized trial. Lancet 360:1267-1274, 2002. Murayama Y, Song JK, Uda K, et al: Combined endovascular treatment for both intracranial aneurysm and symptomatic vasospasm. AJNR Am J Neuroradiol 24:133-139, 2003. Newfield P: Anesthetic management of intracranial aneurysms. In Newfield P, Cottrell JE (eds): Handbook of Neuroanesthesia, 3rd ed. Philadelphia, JB Lippincott–Williams & Wilkins, 1999, pp 175-194. Qureshi AI, Suri MF, Yahia AM, et al: Risk factors for subarachnoid hemorrhage. Neurosurgery 49:607-613, 2001. Rabinstein AA, Pichelmann MA, Friedman JA, et al: Symptomatic vasospasm and outcomes following aneurysmal subarachnoid hemorrhage: A comparison between surgical repair and endovascular coil occlusion. J Neurosurg 98:319-325, 2003. Sluzewshi M, Bosch JA, van Rooij WJ, et al: Rupture of intracranial aneurysms during treatment with Guglielmi detachable coils: Incidence, outcome, and risk factors. J Neurosurg 94:238-240, 2001. Smith MJ, Le Roux PD, Elliott JP, Winn HR: Blood transfusion and increased risk of vasospasm and poor outcome after subarachnoid hemorrhage. J Neurosurg 101:1-7, 2004. Solenski NJ, Haley EC Jr, Kassell NF, et al: Medical complications of aneurysmal subarachnoid hemorrhage: A report of the Multicenter Cooperative Aneurysm Study. Crit Care Med 23:1007-1017, 1995. Todd MM, Hindman BJ, Clarke WR, et al: Mild intraoperative hypothermia during surgery for intracranial aneurysm. N Engl J Med 352:135-145, 2005. Treggiari-Venzi MM, Suter PM, Romand JA: Review of medical prevention of vasospasm after subarachnoid hemorrhage: A problem of neurointensive care. Neurosurgery 48:249-261, 2001.

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Intracranial Aneurysms: Vasospasm and Other Issues Philippa Newfield Case Synopsis A 47-year-old woman underwent craniotomy for clip-ligation of a middle cerebral artery aneurysm. The procedure was successful, and the patient was alert and neurologically intact until postoperative day 4, when her level of consciousness decreased and she developed a new hemiparesis.

PROBLEM ANALYSIS Definition Vasospasm is the transient, self-limited narrowing of intradural subarachnoid arteries that occurs several days after subarachnoid hemorrhage (SAH). It is a result of sustained contraction of arterial smooth muscle. The subsequent delayed ischemic deficit and infarction caused by cerebral vasospasm are a major cause of disability and death after SAH, accounting for 30% of SAH-induced morbidity and mortality. Cerebral vasospasm is associated with a deterioration in clinical status in 30% of patients after SAH. Up to 10% of patients die, and another 10% have permanent neurologic deficits. This reactive narrowing of the subarachnoid arteries occurs after rupture of an intracranial aneurysm because these vessels are bathed by spasmogenic breakdown products of red blood cells (especially hemoglobin) released into the cerebrospinal fluid.

Recognition Angiographic vasospasm begins 3 to 5 days after SAH. The narrowing is maximal at 6 to 8 days and gradually resolves 12 to 14 days after a single episode of SAH. Angiographically severe vasospasm is defined as a decrease of 50% or greater in arterial diameter. The diagnosis of cerebral vasospasm (Table 179-1) is based on clinical signs of progressive impairment in mental status and level of consciousness or the appearance of new focal neurologic deficits more than 4 days after the initial SAH that cannot not attributed to any other structural or metabolic cause. The onset of SAH may be sudden or insidious and is often accompanied by increased headache, meningismus, and fever. Although some evidence of vasospasm is apparent on angiography in 70% to 80% of cases, only one third of patients develop full clinical expression. It is important to rule out other causes of neurologic deterioration with suspected SAH, including rebleeding, intracerebral hemorrhage, hydrocephalus, subdural hematoma, cerebral infarction, cerebral edema, meningitis,

seizures, electrolyte and acid-base disturbances, and adverse drug reactions. Cerebral angiography is the most reliable test for diagnosing and evaluating vasospasm. On angiography, vasospasm may be focal, diffuse, or segmental. Clinical signs and symptoms of decreased cerebral blood flow (CBF) usually develop when there is greater than 50% reduction in the diameter of the arterial lumen. Angiography is indicated for patients suspected of having cerebral vasospasm who do not improve after the administration of intravenous fluids and induced hypertension. It is also used for those who cannot tolerate the aforementioned therapy to rule out vasospasm as a cause of deterioration. Computed tomography (CT)–angiography can detect severe or no cerebral vasospasm in proximal cerebral arteries. It is less reliable for assessing cerebral vasospasm in more distal arteries and intermediate degrees of vasospasm. Methodologies for measuring CBF are positron emission tomography (PET), single photon emission computed tomography (SPECT), and xenon-enhanced CT. PET studies have revealed a fall in the cerebral metabolic rate for oxygen following SAH. Angiographic vasospasm, delayed ischemic deficits, and increased transcranial Doppler velocities are associated with regions of cerebral hypoperfusion on SPECT. Xenon-enhanced CT is a fairly inexpensive technique and can reveal and quantify reductions in regional CBF in patients with clinical vasospasm; it can also be

Table 179–1

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Diagnosis of Cerebral Vasospasm

Clinical appearance of new neurologic signs and symptoms Decrease in level of consciousness Focal weakness Angiography Positron emission tomography (PET) Single photon emission computed tomography (SPECT) Computed tomography (CT)–angiography Xenon cerebral blood flow measurement Transcranial Doppler (TCD)

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repeated within 20 minutes. Further, it is possible to fuse regional CBF data with conventional CT anatomy and distinguish ischemia from other causes of neurologic deterioration after SAH. Transcranial Doppler (TCD) ultrasonography is also used to diagnose cerebral vasospasm. Either a sharp increase (e.g., middle cerebral artery velocity >120 cm/second) or a rapid rise in TCD blood flow velocity (e.g., >50 cm/second in 24 hours) is indicative of a reduction in the caliber of the vessels. Peak TCD flow velocity of 140 to 200 cm/second is associated with moderate cerebral vasospasm; values greater than 200 cm/second indicate severe vasospasm. CBF velocities become maximal 7 to 20 days after SAH. Critical TCD blood flow velocities (>120 cm/second) correlate strongly with vasospasm on angiography. As such, TCD is a better corroborative tool than a predictive one. Either a reduction in TCD velocity or a return to normal often indicates abatement of vasospasm and can be used to determine the efficacy and duration of treatment. Because TCD is operator dependent and involves other technical factors (e.g., intracranial pressure [ICP], cardiac output, the artery being assessed), it is important to correlate any TCD results with sequential neurologic examinations and other monitoring modalities, including ICP, blood pressure, and cardiac output. Jugular bulb venous oximetry detects changes in cerebral oxygen extraction. In one study, patients who developed clinical vasospasm were noted to have a significant rise in cerebral oxygen extraction approximately 1 day before the onset of signs of neurologic deficits. When these patients were treated with hypertensive hypervolemic hemodilution, their deficits resolved, and there was a significant improvement in cerebral oxygen extraction. There was no increase in cerebral oxygen extraction in patients who did not have clinical vasospasm; therefore, increases in this parameter may be predictive of the impending onset of clinical vasospasm.

in 5% to 17% of patients after SAH. Modifiable risk factors that affect the progression from ischemia to infarction include a premorbid history of hypertension and smoking. Transfusion of packed red blood cells intraoperatively is a risk factor for poor outcome. Also, postoperative transfusion is correlated with the development of angiographically proven cerebral vasospasm. The mechanism may involve depletion or inactivation of nitric oxide, an endogenous vasodilator that transfused red blood cells appear to lack. Transfused cells may also have proinflammatory effects or may induce immune system dysfunction. If so, before transfusion, one must determine whether SAH patients are symptomatic from any associated anemia.

Implications Cerebral vasospasm appreciably worsens patient outcomes after SAH. It is believed to be the cause of 28% and 39% of all associated deaths and disability, respectively. Thus, it is responsible for extensive utilization of limited health care resources. Owing to the high mortality, and because survivors of SAH with vasospasm are more likely to have serious permanent neurologic deficits, considerable research efforts and dollars are being expended to identify pharmacologic and other measures to prevent, ameliorate, or eradicate the devastating sequelae of SAH-related cerebral vasospasm. The presence of cerebral vasospasm has implications for anesthetic management as well. Cerebral perfusion pressure is maintained at higher-than-normal levels to enhance cerebral perfusion. Hypotension, including controlled hypotension during aneurysmal dissection, should be avoided. Because autoregulation and carbon dioxide responsiveness are impaired to varying degrees with cerebral vasospasm, blood pressure stability and normocapnia are maintained.

MANAGEMENT Risk Assessment After clip-ligation of cerebral aneurysms, and regardless of clinical status, all patients have a 50-50 chance of developing cerebral vasospasm. Vasospasm is directly related to the severity of the hemorrhage from aneurysmal rupture, which correlates well with the location and volume of blood noted on the initial posthemorrhage CT scan. The risk is increased by the presence of cerebral dysautoregulation and abnormal carbon dioxide responsiveness after SAH. Elderly patients may be at less risk for developing vasospasm, but they do not tolerate ischemia as well as younger ones do and therefore develop cerebral infarction more frequently. The timing of surgery has no effect on the subsequent development of angiographic cerebral vasospasm, nor does surgical versus endovascular occlusion have an effect. Other indicators of increased risk for the development of vasospasm include an admission Glasgow Coma Scale score less than 14 (see Table 182-1), an early increase in mean middle cerebral artery flow velocity on TCD, and anterior cerebral or internal carotid artery aneurysms. Angiographic vasospasm (>30% reduction in cerebral vessel diameter) is a significant risk factor for the development of infarction. Death from vasospastic infarction occurs

Pharmacologic and other modalities used to treat cerebral vasospasm after SAH are listed in Table 179-2. Early operation for clip-ligation of the ruptured aneurysm after SAH secures the aneurysm and permits the removal of fresh clot by irrigation and suction. The surgeon may also apply tissue plasminogen activator (tPA) directly into the subarachnoid space to dissolve remaining clot. Although this fibrinolytic drug can reduce vasospasm, it also has the potential to cause rebleeding by dissolving normal clot. Thus, only patients at high risk for clinically significant vasospasm are candidates for tPA treatment. Early obliteration of the aneurysm by endovascular coils also facilitates the subsequent treatment of vasospasm.

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Pharmacologic and Other Modalities Used to Treat Cerebral Vasospasm

Hypertensive hypervolemic hemodilution Volume expansion with crystalloids and colloids Vasopressors (e.g., dopamine, dobutamine, phenylephrine) Transluminal balloon angioplasty

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Both hypervolemia and hypertension are used to increase cardiac output and augment cerebral perfusion in vasospastic areas of the brain with impaired autoregulation. Early institution of these measures can mitigate or avoid the progression of vasospasm-induced ischemia to infarction. Hemodilution alone is unlikely to be beneficial and may reduce cerebral oxygen delivery. However, a hematocrit of 30% to 35% is likely adequate. Complications of induced hypervolemia and hypertension include rebleeding, hemorrhagic infarct transformation, cerebral edema, hypertensive encephalopathy, intracranial hypertension, myocardial infarction, heart failure, pulmonary edema, coagulopathy, and dilutional hyponatremia, as well as complications related to central vascular catheterization. Expansion of intravascular volume is necessary because total circulating blood and red blood cell volumes are reduced in most patients after SAH. This is secondary to supine diuresis, peripheral pooling, negative nitrogen balance, reduced erythropoiesis, iatrogenic blood loss, and increased natriuresis. Limits for crystalloid and colloid volume expansion are central venous and pulmonary capillary wedge pressures of 10 to 12 and 12 to 16 mm Hg, respectively. There is a suggestion that albumin may improve the clinical outcome at 3 months and reduce hospital costs when normal saline alone has failed to increase the central venous pressure to at least 8 mm Hg. Vagal and diuretic responses to intravascular volume augmentation might dictate the need for a drug such as vasopressin to reduce urine output to less than 200 mL/hour. Hydrocortisone has also been used to attenuate excessive natriuresis and hyponatremia in patients with SAH, as well as to prevent the associated decrease in total blood volume. It appears to have no serious side effects. Vasopressors, including dopamine, dobutamine, and phenylephrine, might also be required to increase blood pressure and augment cardiac output. Invasive hemodynamic monitoring (e.g., direct arterial, central venous, or pulmonary artery pressure; cardiac output) is required for patients with induced hypertension. Before the aneurysm is secured, systolic blood pressure is maintained between 120 and 150 mm Hg. Once secured, it can be increased to 160 to 200 mm Hg. Transluminal balloon angioplasty is also used to relieve cerebral vasospasm. The inflatable intravascular balloon mechanically dilates the segmental zone of vasospastic narrowing. This may improve the patient’s level of consciousness by relieving focal ischemic deficits. However, early intervention is critical. Another treatment is serial papaverine angioplasty. This improves cerebral circulation times, but serial infusions are required for recurring cerebral vasospasm.

PREVENTION Cerebral Vasospasm The prevention of cerebral vasospasm requires a high level of vigilance and care, maintenance of normovolemia, careful monitoring, and prevention of secondary cerebral insults and medical complications (Table 179-3). Early occlusion of the aneurysm facilitates subsequent efforts to prevent and

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Pharmacologic and Other Modalities Used to Prevent Cerebral Vasospasm after Subarachnoid Hemorrhage

Administer nicardipine (IV) Administer nimodipine (orally or via gastric feeding tube) Maintain normal electrolyte balance Provide adequate analgesia Maintain normovolemia Maintain normothermia Maintain normotension

treat vasospasm. Monitoring in an intensive care unit or a transitional area is indicated until after the peak time for the development of vasospasm has passed. The purpose of such care is to avoid hypovolemia, hyponatremia with inappropriate diuresis, arrhythmias, hyperthermia, pulmonary edema, hypoxia, hypercarbia, and intracranial hypertension. Any of these has the potential to exacerbate cerebral vasospasm. After SAH, adults need 3 to 4 L of fluid a day to maintain normovolemia. Hypotonic solutions (e.g., lactated Ringer’s) are avoided. Hyponatremia is treated with either normal or hypertonic saline as necessary. However, Egge and colleagues showed that prophylactic hypertensive hypervolemic hemodilution after aneurysmal SAH neither prevents vasospasm nor improves outcomes when compared with controls treated with normovolemia. In addition, costs were higher and complications were more frequent in patients receiving hyperdynamic therapy. In the International Subarachnoid Aneurysm Trial, patients with better clinical grades (World Federation of Neurosurgical Societies grades I to III on admission) whose aneurysms were occluded with endovascular coils rather than surgical clipping were less likely to have symptomatic vasospasm. However, there was no difference in clinical outcome between the groups at the end of the follow-up period. Although blood pressure is controlled before the aneurysm is secured, it is not treated thereafter, unless elevations are critically high. ICP is maintained in the normal range with mannitol, ventricular drainage, and mild ventilation. The goal is to keep cerebral perfusion pressure above 60 to 70 mm Hg. Use of the dihydropyridine calcium channel blocker1 nimodipine within 96 hours of SAH in good- and poorgrade patients has been shown to reduce the morbidity and mortality associated with aneurysmal cerebral vasospasm. It is now a standard of care after SAH. Nimodipine improves the poor outcome associated with vasospasm in all grades of patients, improves the chance of a good to fair outcome, and reduces the chance of infarction after SAH. However, the incidence of symptomatic vasospasm is not affected by nimodipine. Because it has a limited effect on the angiographic caliber of vessels, it is postulated that nimodipine 1 Dihydropyridine calcium channel blockers are selective for vascular smooth muscle versus cardiac muscle, in contrast to non-dihydropyridines such as verapamil and diltiazem. Intravenous nicardipine, a dihydropyridine calcium channel blocker, is increasingly used for the treatment of vasospasm in aneurysmal SAH, although long-term outcomes are not yet known.

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confers cerebral protection by reducing the influx of calcium in marginally ischemic neurons. Alternatively, it may increase CBF by dilating pial collateral vessels not seen on angiography. Nimodipine also reduces blood pressure; however, it does so by reducing systemic vascular resistance, not preload. Treatment with subcutaneous low-molecular-weight heparin (enoxaparin 20 mg/day) for 3 weeks after SAH also appears to improve overall outcomes at 1 year. Apparently, this is due to a reduction in delayed ischemic deficits and cerebral infarction. Patients who received enoxaparin also had fewer intracranial bleeding events and a lower incidence of severe (i.e., shunt-dependent) hydrocephalus. Other drugs have been investigated for the prevention of vasospasm. Tirilazad, an antioxidant and free radical scavenger, showed mixed clinical results. Nicaraven, a free radical scavenger, showed a trend toward improved survival, good outcome, and smaller infarct size at 3 months. Ebselen, an antioxidant and anti-inflammatory drug, has neuroprotective properties and appears to be effective in acute ischemic stroke. Intra-arterial fasudil, a kinase inhibitor, has been used to treat clinical vasospasm. However, there was no difference in neurologic outcome versus placebo, and patients treated with fasudil had more pneumonia and hypotensive episodes. Owing to increased endothelin (an endothelial-derived vasoconstrictor peptide) with cerebral vasospasm, an endothelin antagonist has also been investigated. Intracisternal tPA prevents vasospasm but does not improve outcome because of increased bleeding associated with its use. Finally, although antifibrinolytics reduce rebleeding, they increase delayed cerebral ischemia and therefore are rarely used.

Hydrocephalus Chronic hydrocephalus occurs in 10% of patients after SAH. It is due to obstructed pathways for cerebrospinal fluid drainage (i.e., subarachnoid venous granulations). Development of arachnoid adhesions also prevents the reabsorption of cerebrospinal fluid. If the blockage is incomplete, the problem persists only for several weeks. Hydrocephalus that either causes intracranial hypertension or reduces CBF can adversely affect the outcome following SAH. Whether the aneurysm is occluded using surgical or endovascular techniques does not affect the subsequent risk for hydrocephalus. Acute hydrocephalus is associated with a poor clinical grade and thickened subarachnoid or intraventricular hemorrhage on admission CT scans. It occurs in 15% to 20% of SAH patients. Other associations are alcoholism, female sex, older age, larger aneurysms, pneumonia, meningitis, and hypertension. It is recognized by the onset of lethargy and coma within 24 hours of SAH. Development of acute ventricular dilatation soon after SAH is a cause of sudden deterioration in neurologic status and may require external ventricular drainage to normalize ICP. External ventricular drainage is used only when the patient’s level of consciousness becomes depressed. Good results have been achieved when this is done along with early aneurysm occlusion. Ventricular drainage should be used with caution, however, to avoid changes in the transmural pressure that may precipitate aneurysmal rebleeding. Because acute hydrocephalus is often associated with

vasospasm, early aneurysm occlusion allows the use of hyperdynamic therapy and angioplasty. Half of patients who develop acute hydrocephalus require a ventriculoperitoneal shunt, but the need for a permanent shunt is reduced by external ventricular drainage. Predictors of the need for permanent shunting include poor grade on admission, rebleeding, and intraventricular hemorrhage. Chronic hydrocephalus, seen in 25% of patients who survive SAH, is an important cause of the subsequent slow physical decline of patients who were originally in good condition. Symptoms include an increasingly impaired level of consciousness and the development of dementia, gait disturbances, and incontinence. A CT scan is indicated within a month after SAH to ascertain ventricular size.

Abnormalities of Cerebral Autoregulation The central nervous system is directly affected by SAH and the resultant hematoma, vascular disruption, and edema. SAH interferes with cerebral autoregulation, which is the ability of the cerebral vasculature to maintain normal (unchanged) CBF over a wide range of cerebral perfusion pressures (mean arterial pressure minus ICP), from 50 to 150 mm Hg. Importantly, this range is higher (shifts to the right) in patients with chronic hypertension. Intracranial aneurysms (especially giant aneurysms) and SAH-induced hematoma and cerebral edema can cause intracranial hypertension, with a consequent decrease in the patient’s level of consciousness and the potential for brainstem herniation and death. Patients with intracranial hypertension also have reduced CBF and cerebral metabolic rate for oxygen. The extent of such impairment correlates with the patient’s clinical grade. The response of the cerebral vasculature to changes in arterial carbon dioxide tension is preserved after SAH. A decline in carbon dioxide reactivity usually does not occur until there is extensive disruption of cerebral homeostasis.

Seizures The seizure incidence after SAH is from 3% to 26%. Early seizures occur in 1.5% to 5% of patients, and late ones in 3%. Seizures are detrimental after SAH because they increase CBF and cerebral metabolic rate for oxygen and also may cause rebleeding, owing to increased blood pressure. Patients at highest risk for seizures have either thick cisternal blood on CT scan or lobar intracerebral hemorrhage. Other risk factors are rebleeding, vasospasm with delayed ischemic neurologic deficits, middle cerebral artery aneurysm location, subdural hematoma, and chronic central nervous system impairment. Use of prophylactic antiepileptics is controversial, because most seizures occur within the first 24 hours after SAH, often before hospitalization. Therefore, neurosurgeons use seizure prophylaxis (e.g., phenytoin, fosphenytoin, levetiracetam) for only 1 to 2 weeks after SAH. Patients with one or more intracerebral hemorrhages or early seizures receive anticonvulsants for at least 6 months.

Cardiac Disturbances Electrocardiographic changes occur in 27% to 100% of patients with SAH. Most common are T-wave inversion or ST

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segment depression. Others are new U or Q waves and Q-T interval prolongation. Rhythm disturbances occur in 30% to 80% of patients and include premature ventricular beats (most common), sinus bradycardia and tachycardia, lower escape rhythms, atrial fibrillation, and tachyarrhythmias (atrial or ventricular in origin). Arrhythmias commonly occur within 7 days of SAH, with the peak occurrence between the second and third days. The extent of myocardial dysfunction correlates with the severity of neurologic injury after SAH. The cause of this dysfunction is believed to be related to hypothalamic injury, with consequent autonomic imbalance and release of catecholamines, causing myocardial ischemia and infarction. Increased adrenergic tone may persist for the first week after SAH. These SAH-related cardiac abnormalities are similar to those seen with acute coronary syndromes (myocardial ischemia, infarction, and reperfusion injury) and may predispose patients to life-threatening arrhythmias. Associated Q-T interval prolongation makes patients more vulnerable to ventricular tachyarrhythmias (see Chapter 81). This risk is increased with low serum potassium or magnesium levels and with drugs that prolong the Q-T interval. The routine measurement of Q-T intervals may identify patients at risk for potentially lethal arrhythmias. Often, the question for the neurosurgeon and anesthesiologist is whether to proceed with surgical or endovascular intervention to secure an aneurysm emergently, even if a delay might put the patient at increased risk for rebleeding and compromise the treatment for vasospasm. Serial cardiac isozymes and ventricular function assessment by echocardiography may indicate the magnitude of ischemia. Use of a pulmonary artery catheter to measure pulmonary capillary wedge pressure and cardiac output can both facilitate the management of cardiac dysfunction and monitor the response to hyperdynamic therapy for the treatment of cerebral vasospasm. The presence of severe arrhythmias (about 5% of patients with arrhythmias) or significant cardiogenic pulmonary edema may necessitate postponing surgical or endovascular intervention until treatment has begun. Prophylactic β-adrenergic blockade can improve the cardiac outcome in some patients.

Further Reading Chang HS, Hongo K, Nakagawa H: Adverse effects of limited hypotensive anesthesia on the outcome of patients with subarachnoid hemorrhage. J Neurosurg 92:971-975, 2000.

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Cross DT, Tirschwell DL, Clark MA, et al: Mortality rates after subarachnoid hemorrhage: Variations according to hospital case volume in 18 states. J Neurosurg 99:810-817, 2003. Egge A, Waterloo K, Sjoholm H, et al: Prophylactic hyperdynamic postoperative fluid therapy after aneurysmal subarachnoid hemorrhage: A clinical, prospective, randomized, controlled study. Neurosurgery 49:593-606, 2001. Eng CC, Lam AM: Cerebral aneurysms: Anesthetic considerations. In Cottrell JE, Smith DS (eds): Anesthesia and Neurosurgery, 3rd ed. St. Louis, Mosby–Year Book, 1994, pp 376-405. Fridriksson S, Saveland H, Jakobsson KE, et al: Intraoperative complications in aneurysm surgery: A prospective national study. J Neurosurg 96:515-522, 2002. Gianotta SL, Oppenheimer JH, Levy ML, et al: Management of intraoperative rupture of aneurysms without hypotension. Neurosurgery 28:531-536, 1991. Haley EC Jr, Kassell NF, Torner JC, et al: The International Cooperative Study on Timing of Aneurysm Surgery: The North American experience. Stroke 23:205-214, 1992. Kett-White R, Hutchinson PJ, Al-Rawi PG, et al: Adverse cerebral events detected after subarachnoid hemorrhage using brain oxygen and microdialysis probes. Neurosurgery 50:1213-1222, 2002. Le Roux P, Winn HR: Management of the ruptured aneurysm. In Le Roux P, Winn HR, Newell DW (eds): Management of Cerebral Aneurysms. Philadelphia, Elsevier Science, 2004, pp 303-333. Molyneux A, Kerr R, Stratton I, et al: International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: A randomized trial. Lancet 360:1267-1274, 2002. Murayama Y, Song JK, Uda K, et al: Combined endovascular treatment for both intracranial aneurysm and symptomatic vasospasm. AJNR Am J Neuroradiol 24:133-139, 2003. Newfield P: Anesthetic management of intracranial aneurysms. In Newfield P, Cottrell JE (eds): Handbook of Neuroanesthesia, 3rd ed. Philadelphia, JB Lippincott–Williams & Wilkins, 1999, pp 175-194. Qureshi AI, Suri MF, Yahia AM, et al: Risk factors for subarachnoid hemorrhage. Neurosurgery 49:607-613, 2001. Rabinstein AA, Pichelmann MA, Friedman JA, et al: Symptomatic vasospasm and outcomes following aneurysmal subarachnoid hemorrhage: A comparison between surgical repair and endovascular coil occlusion. J Neurosurg 98:319-325, 2003. Sluzewshi M, Bosch JA, van Rooij WJ, et al: Rupture of intracranial aneurysms during treatment with Guglielmi detachable coils: Incidence, outcome, and risk factors. J Neurosurg 94:238-240, 2001. Smith JS, Le Roux PD, Elliott JP, et al: Blood transfusion and increased risk of vasospasm and poor outcome after subarachnoid hemorrhage. J Neurosurg 101:1-7, 2004. Solenski NJ, Haley EC Jr, Kassell NF, et al: Medical complications of aneurysmal subarachnoid hemorrhage: A report of the Multicenter Cooperative Aneurysm Study. Crit Care Med 23:1007-1017, 1995. Treggiari-Venzi MM, Suter PM, Romand JA: Review of medical prevention of vasospasm after subarachnoid hemorrhage: A problem of neurointensive care. Neurosurgery 48:249-261, 2001.

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Shailendra Joshi and William L. Young Case Synopsis A 39-year-old woman is given general anesthesia for resection of a right superior temporal gyrus arteriovenous malformation (AVM) measuring 3 by 3 by 2 cm (Figs. 180-1 and 180-2). After surgery, her mean arterial pressure increases to 100 mm Hg when phenylephrine is used to confirm surgical homeostasis (Fig. 180-3). The patient emerges from anesthesia without neurologic deficits. Six hours later, she complains of a severe headache, vomits, and becomes lethargic. The right pupil is dilated. Immediate computed tomography scan reveals a large hemorrhage into the operative site and a midline brain shift (Fig. 180-4). After surgery to evacuate the clot, there is no residual AVM, the feeding artery is thrombosed, the surrounding brain is lax, and a vessel on the anterior rim of the AVM bed is identified as the source of bleeding. Postoperative neurologic examination reveals an appropriate response to painful stimuli and recovery of pupillary reaction. Four hours later, the patient’s intracranial pressure suddenly increases from 10 to 80 mm Hg and her pupils become fixed and dilated. Immediate repeat exploration reveals the source of hemorrhage to be an arterial vessel on the posterior rim of the AVM bed. The brain is edematous and adheres to the dura. The postoperative neurologic evaluation shows no improvement. Subsequent examination shows no evidence of brainstem function, and serial electroencephalograms are isoelectric. The patient dies. At autopsy, there is no residual AVM.

PROBLEM ANALYSIS Definition Normal perfusion pressure breakthrough (NPPB) after AVM resection is a catch-all term that describes unexplained intraoperative brain swelling or diffuse bleeding from the AVM bed or unexplained postoperative brain swelling or intracranial hemorrhage (ICH). NPPB is a diagnosis of exclusion. Although much has been written about NPPB, the lack of a rigorous definition makes interpretation of the existing literature difficult. The proposed pathophysiology of NPPB is as follows: High blood flow through the arteriovenous fistula creates a region of chronic cerebral hypotension in the neighboring vascular territories. Chronic cerebral hypotension may lead to a state of near-maximal vasodilatation and vasoparalysis that impairs the vessels’ ability to constrict or even dilate effectively. Excision of the low-resistance AVM shunt restores perfusion in the formerly hypotensive regions of brain. However, owing to the inability of these beds to effectively vasoconstrict, normalization of cerebral perfusion pressure results in cerebral hyperemia (“luxury perfusion”), 724

with the potential for cerebral edema formation and ICH. Although this is an attractive hypothesis, the pathophysiology has not been proved. Abnormal vascular reactivity, such as an impaired vasodilator response to acetazolamide, has been observed in regions adjacent to cerebral AVMs that show marked hyperperfusion after resection. Possibly, NPPB shares certain similarities to cerebral hyperemia after carotid endarterectomy or transluminal angioplasty and stenting of extracranial cervical arteries. Some observations argue against a “hydraulic hypothesis” to explain the pathophysiology of NPPB. First, hypotensive vascular beds in proximity to the AVM retain the ability to vasoconstrict. Also, pressure autoregulation can be shown in these hypotensive beds, although the cerebral autoregulation curve is shifted to the left. Second, severe cerebral hypotension (feeding artery pressure <50% of systemic blood pressure) in normal, functional vascular beds is often seen in proximity to an AVM (approximately half of cases), although NPPB is a rare complication of AVM surgery. Third, NPPB hyperemia is not limited to hypotensive areas near the AVM; it appears to be global. Alternative mechanisms for unexplained hemorrhage or swelling have been suggested, such as (1) unrecognized

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Figure 180–1 ■ Lateral arteriogram showing a moderate-sized arteriovenous malformation (AVM), with a large arterial supply (closed arrow) and abundant venous drainage (open arrows). These are indicative of very large, high-flow AVM shunts. (From Young WL, Prohovnik I, Ornstein E, et al: The effect of arteriovenous malformation resection on cerebrovascular reactivity to carbon dioxide. Neurosurgery 27:257-267, 1990.)

Figure 180–3 ■ Operative photograph after surgical resection of the arteriovenous malformation (AVM). This depicts a dry surgical bed and surrounding dilated arteries (arrows). These became enlarged after interruption of the AVM. (From Young WL, Prohovnik I, Ornstein E, et al: The effect of arteriovenous malformation resection on cerebrovascular reactivity to carbon dioxide. Neurosurgery 27:257-267, 1990.)

technical complications at the time of surgery; (2) vascular disturbances due to abnormal autonomic activity, resulting in the release of vasoactive peptides from innervated cerebral vessels; (3) hemorrhage from a structurally deficient capillary vessel bed adjacent to the AVM, perhaps secondary to overexpression of angiogenic factors such as vascular endothelial growth factor or angiopoietin-2; and (4) venous occlusion after resection of the AVM. With regard to the third hypothesis, Sato and colleagues recently described markedly dilated capillary networks in the perinidal AVM region. Vessel diameters were 10 to 25 times those of normal capillaries and vascular connections to the nidus, including feeding arteries and arterioles, drainage veins and venules, and the normal capillary network. With regard to the fourth hypothesis, severe global hyperemia (i.e., increased cerebral blood flow) that occurs immediately after AVM resection

appears to be associated with NPPB later in the postoperative course. In the case synopsis, cerebral blood flow significantly increased immediately after AVM resection, although ICH or cerebral edema and ICH did not occur until several hours later.

Figure 180–2 ■ Operative photograph showing the surface of the temporal lobe, with prominent arterial supply (closed arrows) and venous drainage (open arrows). (From Young WL, Prohovnik I, Ornstein E, et al: The effect of arteriovenous malformation resection on cerebrovascular reactivity to carbon dioxide. Neurosurgery 27:257-267, 1990.)

Figure 180–4 ■ Computed tomography scan taken 6 hours postoperatively showing massive hemorrhage into the arteriovenous malformation (AVM) bed. The hemorrhage was under tension, with a major shift of intracranial structures. It was evacuated, but the patient died after further hemorrhages. (From Young WL, Prohovnik I, Ornstein E, et al: The effect of arteriovenous malformation resection on cerebrovascular reactivity to carbon dioxide. Neurosurgery 27:257-267, 1990.)

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Recognition NPPB is a controversial entity, and the diagnosis carries a certain degree of subjectivity. The incidence of NPPB after AVM resection is about 2.5%. NPPB is a diagnosis of exclusion, after more common causes of cerebral edema or hemorrhage have been ruled out. Causes of cerebral edema after AVM resection include hypoxia, increased venous pressure, decreased serum osmolality, systemic hypertension, and surgical trauma. After AVM resection, ICH may be due to the presence of residual AVM, poor control of systemic blood pressure, or uncorrected coagulopathy.

Risk Assessment Predictors of NPPB after AVM ablation remain controversial. Some have proposed that large (≥4 cm) AVMs with high blood flow through the shunt and evidence of decreased perfusion in the neighboring regions may predict an increased likelihood for NPPB. Intraoperative monitoring of cerebral blood flow with laser Doppler or near-infrared spectroscopy may also reveal patients at risk of developing postoperative hyperemia. A sudden increase in laser Doppler blood flow in cortical regions adjacent to the AVM, after temporary clipping of the feeding arteries, is often seen in patients at risk for developing NPPB. Intraoperative near-infrared spectroscopy permits measurements of tissue oxygen saturation and blood volume. An increase in pre- to post-resection oxygen saturation and a blood volume ratio greater than 2 might indicate an increased risk for NPPB. Postoperative blood flow mapping by positron emission tomography (PET) or single photon emission computed tomography (SPECT) may help predict NPPB. There is no evidence that the choice of anesthetic agent influences the development of NPPB.

Implications Although NPPB represents a class of complications without a clearly defined cause, it has been suggested that staged surgical resection or endovascular embolization could reduce the likelihood of NPPB. Staged resection or embolization permits vessels to adapt to increased perfusion pressure by gradually normalizing cerebral perfusion pressure (or it may permit adaptation to as yet unidentified pathophysiologic changes). Changes in cerebral blood flow after ablation of the AVM, however, may not be related to the preintervention feeding artery pressure. Despite the lack of precise pathophysiologic information, preoperative endovascular embolization may serve other useful purposes, such as facilitating surgery by minimizing intraoperative blood loss or by defining the location and extent of the AVM. Embolization may also reduce the size of the AVM, making it more amenable to surgery or radiosurgery. It might also alleviate neurologic symptoms by decreasing the AVM mass effect and reducing tissue perfusion in adjacent areas. Recent evidence suggests that another technique used for AVM removal might affect the incidence of subsequent rebleeding, at least for small (< 3 cm) AVMs located in critical or eloquent areas of the brain (e.g., sensorimotor, language,

or visual cortex; hypothalamus or thalamus; internal capsule; brainstem; cerebellar peduncles; deep cerebellar nuclei), where rebleeding often results in disabling neurologic defects. Stereotactic (gamma knife) radiosurgery is often used to remove such small AVMs and provides radiographic evidence of AVM “cure” (obliteration) in 80% to 95% of patients after a latency period of 3 to 5 years. At issue was how bleeding during the latency period would compare with bleeding in patients with similar but untreated AVMs. It was found that the risk of hemorrhage from small AVMs was significantly reduced after radiosurgery (but before angiographic obliteration) and was even lower after angiographic obliteration. Whether radiosurgery for larger AVMs would reduce the incidence of rebleeding compared with surgical resection is unknown, but it might be tested; surgical AVM resection is recommended for less strategically located, larger AVMs amenable to surgery, but some patients choose radiosurgery instead because it seems less invasive.

MANAGEMENT Unexplained cerebral edema or ICH after AVM resection is managed using standard cerebral resuscitative guidelines. Treatment of cerebral edema requires careful management of fluid and electrolyte imbalances, judicious use of osmotic and loop diuretics, and attention to cerebral perfusion pressure. Severe symptomatic swelling may necessitate controlled ventilation and, rarely, barbiturate coma. If NPPB is suspected, blood pressure is empirically maintained within 10% of the baseline. Cerebral outflow pressure (i.e., central venous or intracranial pressure) must be maintained at levels consistent with adequate cerebral perfusion and cardiac preload. If deliberate systemic hypotension is used, assessment should include whether it is necessary to maintain collateral perfusion in any cerebral territories that might have their primary feeding supplies interrupted during AVM resection. Surgical intervention may be required for removal of intracranial blood clot or for institution of intracranial pressure monitoring.

PREVENTION In the absence of a clearly defined explanation of NPPB, the empirical strategy is to prevent cerebral edema and hemorrhage after AVM resection by careful control of systemic blood pressure to avoid hypertension. The use of intraoperative embolization of the AVM nidus via the ligated feeding arteries while the patient is under general anesthesia has been noted to prevent NPPB in high-risk cases. Mild systemic hypertension is sometimes used to test surgical homeostasis before dural closure. Once this has been achieved, however, the systemic blood pressure must be maintained as close to the patient’s baseline blood pressure as feasible. After resection of an AVM, strict maintenance of normotension may serve two purposes. First, prevention of blood pressure increases may be important for the prevention of postoperative hematoma. This could be caused by

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rupture of cauterized stumps of dysplastic feeding vessels to the AVM or an unidentified residual nidus. Second, avoidance of hypertension prevents the cerebral hyperemia and edema that result from exceeding the upper limit of the flow-pressure autoregulation curve. This can be explained as follows: Functionally normal but chronically hypotensive cerebral beds in proximity to the AVM show a leftward shift in the cerebral autoregulatory curve. It is generally believed that in intact human cerebral circulation, cerebral hyperemia and edema occur whenever cerebral perfusion pressure increases beyond the upper limit of autoregulation. If the cerebral autoregulation curve shifts to the left, it may be that the upper limit of pressure autoregulation also shifts to a lower pressure. Ablation of the AVM shunt increases the regional perfusion pressure in the hypotensive areas, even at normal systemic arterial pressures. The magnitude of increase in the regional perfusion pressure is difficult to predict. In the absence of means to monitor regional cerebral perfusion in the perioperative period, it is reasonable to maintain strict normotension. In selected high-risk cases, mild systemic hypotension might minimize the chances of post-resection hyperemia and edema. Decreasing systemic perfusion pressure, however, might jeopardize brain regions that depend on collateral pathways for the maintenance of perfusion. Therefore, induced systemic hypotension to any significant degree should be considered carefully within the context of the patient’s overall circulatory status.

727

Further Reading Brown AP, Spetzler RF: Intracranial arteriovenous malformations. In Batjer HH, Caplan L, Friberg L, et al (eds): Cerebrovascular Hemodynamics, Cerebrovascular Disease. Philadelphia, Lippincott-Raven, 1997, pp 833-842. Hashimoto T, Lam T, Boudreau NJ, et al: Abnormal balance in the angiopoietin-2 system in human brain arteriovenous malformations. Circ Res 89:111-113 2001. Joshi S, Ornstein E, Young WL: Cerebral and spinal cord blood flow. In Cottrell JE, Smith DS (eds): Anesthesia and Neurosurgery, 4th ed. St. Louis, Mosby, 2001, pp 19-68. Kader A, Young WL: The effects of intracranial arteriovenous malformations on cerebral hemodynamics. Neurosurg Clin North Am 7:767-781, 1996. Kader A, Young WL: Arteriovenous malformations: Considerations for perioperative critical care monitoring. In Batjer HH, Caplan LR, Friberg L, et al (eds): Cerebrovascular Disease. Philadelphia, Lippincott-Raven, 1997, pp 857-869. Ko N, Achrol A, Gupta D, et al: Cerebral blood flow changes after endovascular treatment of cerebrovascular stenoses. AJNR Am J Neuroradiol 26:538-542, 2005. Sato S, Kodama N, Sasaki T, et al: Perinidal dilated capillary networks in cerebral arteriovenous malformations. Neurosurgery 54:163-170, 2004. Young WL, Ornstein E, Baker KZ, et al: The Columbia University AVM Project: Cerebral hyperemia after AVM resection is related to “breakthrough” complications but not to feeding artery pressure. Anesth Analg 80:S573, 1995. Young WL, Ornstein E, Baker KZ, et al: Neuroanesthesia considerations for surgical and endovascular therapy of arteriovenous malformations. In Batjer HH, Caplan LR, Friberg L, et al (eds): Cerebrovascular Disease. Philadelphia, Lippincott-Raven, 1997, pp 843-855. Young WL, Prohovnik I, Ornstein E, et al: The effect of arteriovenous malformation resection on cerebrovascular reactivity to carbon dioxide. Neurosurgery 27:257-267, 1990.

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181

Case Synopsis A previously healthy 14-month-old child is admitted to the emergency department following a motor vehicle accident in which he sustained a closed head injury associated with loss of consciousness and a large scalp laceration. A grand mal–type seizure occurs on arrival at the hospital. Physical examination reveals a lethargic, tachypneic, hypotensive, and tachycardic child. His pupils are equal and reactive, and there is no evidence of papilledema. Computed tomography scan of the head reveals diffuse cerebral swelling and subdural hematoma. He undergoes anesthesia for a craniotomy to evacuate the subdural hematoma, repair the scalp laceration, and place an intracranial pressure (ICP) monitor.

Recognition PROBLEM ANALYSIS Definition Surgical procedures in children with central nervous system (CNS) pathology are performed to correct pathologic entities (e.g., evacuation of hematoma, excision of tumors or seizure foci, closure of meningomyelocele) and to facilitate monitoring (e.g., ICP monitoring). Brain tumors are the most common solid tumors in children and are the second most common malignancy after the leukemias. Trauma is the leading cause of death in children older than 1 year, and traumatic brain injury (TBI) is the major cause of morbidity and mortality. Outcome is determined by the extent of primary and secondary brain injury. The former is the biomechanical injury that occurs with trauma; it is irreversible. Management must focus on preventing the sequelae of primary brain injury, termed secondary brain injury (Table 181-1); these management goals include reducing cerebral edema, preventing cerebral hypoxia, maintaining cerebral perfusion, avoiding increases in the cerebral metabolic rate for oxygen, and avoiding damage to neuronal membranes. Similarly, prevention of secondary brain injury is the focus of treatment for nontraumatic CNS lesions.

Table 181–1

■

The most reliable signs of TBI severity are degree of change in level of consciousness and impaired CNS function. The Glasgow Coma Scale score (see Chapter 182 and Table 182-1) adapted for pediatric patients provides a tool to assess the severity of primary and secondary brain injury and trends. The major cause of secondary brain injury involves failure of perfusion, leading to tissue hypoxia and brain edema. Associated brain swelling impairs tissue perfusion, leading to further CNS functional deterioration. The failure of cerebral oxygenation arises from hypoxemia, hypotension, hypovolemia, hyperemia, and acidosis. When the pathologic process evolves slowly (e.g., expansion of solid tumors), physiologic compensation may occur. However, in the event of TBI, cerebral edema evolves quickly, and any compensatory mechanisms are easily overcome. The intracranial contents in children are less compliant than in adults. Thus, comparable increases in ICP are more likely to produce ischemia and herniation in children than in adults. Although hyperemia and increased cerebral blood flow in response to TBI were once considered common in children, recent data suggest that hyperemia may not be so common. Open fontanelles do not automatically exclude brain injury from increased ICP.

Prevention of Secondary Brain Injury

Maneuver

Expected Effect

30-degree head-up tilt (waist up) Mechanical ventilation Systemic steroids

Increases cerebral venous drainage while maintaining CPP Maintains normocapnia to slight hypocapnia to prevent cerebral vasodilatation and ↑ ICP Improves outcome with spinal cord injury; reduces vasogenic cerebral edema with tumors; stabilizes neuronal membrane; may act as free radical scavengers Avoids coughing, straining, or other movement that might increase ICP Reduces ICP Prevents further cerebral edema or hemorrhage leading to further ischemia, especially when due to cerebral vasospasm Prevents seizures and associated increase in ICP and CMRO2 Reduces CMRO2 and cerebral glucose consumption Reduces CBF and CMRO2 and may have membrane-stabilizing effect

Muscle paralysis Ventricular drainage Antihypertensive drugs∗ Anticonvulsants Mild hypothermia Barbiturate coma

∗For example, dihydropyridine calcium channel blockers. CMRO2, cerebral metabolic rate for oxygen; CBF, cerebral blood flow; CPP, cerebral perfusion pressure; ICP, intracranial pressure.

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Table 181–2

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Neurophysiologic Effects of Commonly Used Anesthetic Agents

Agent

MAP

Nitrous oxide Halothane Enflurane Isoflurane Sevoflurane Desflurane Thiopental Propofol Etomidate Ketamine Benzodiazepines Opiates Droperidol

0 or ↓↓ ↓↓ ↓↓ ↓↓ ↓↓ ↓↓ ↓↓↓ 0 or ↑↑ 0 or 0 or ↓↓

↓

↓ ↓ ↓

CBF ↑ or ↑↑ ↑↑↑ ↑↑ ↑ ↑ ↑ ↓↓↓ ↓↓↓ ↓↓↓ ↑↑↑ ↓↓ ↓ ↓

CPP

ICP

↓ ↑ or ↑↑ ↑↑ ↑↑ ↑↑ ↑↑ ↑↑ ↑ ↑ ↑ ↑ ↑ ↑↑↑ ↓↓↓ ↑↑ ↓↓ ↑↑ ↓↓↓ ↓ ↑↑↑ ↑ 0 or ↓ ↑ or ↓ 0 or ↓ ↑ ↓

CMRO2 ↓ or ↑ ↓↓ ↓↓ ↓↓↓ ↓↓↓ ↓ ↓↓↓ ↓↓↓ ↓↓↓ ↑ ↓↓ ↓ 0 or ↓

CSF (Synthesis) ↑ ↑ ↑ ↓ ? ↓ ↑ ? ↑ ↑ ↑ ↑ ↑

CSF (Absorption)

or ↓ or ↓ or ↑ or ↓ or or or or or

↓ ↓ ↓ ↓ ↓

↑ or ↓ 0 or ↓ ↓ ↑ ? ↓ ↑ ? ↑ ↓ ↑ ↑ ?

SEP (Amplitude) ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↑ ↑ ↑ ↑ ↓ ?

SEP (Latency) ↑ or 0 ↑ ↑ ↑ ↑ ↑ ↑ ↑ ↑ 0 0 or ↑ ↑ ?

CBF, cerebral blood flow; CMRO2, cerebral metabolic rate for oxygen; CPP, cerebral perfusion pressure; CSF, cerebrospinal fluid; ICP, intracranial pressure; MAP, mean arterial pressure; SEP, somatosensory evoked potential.

The presence of cervical spine trauma should always be assumed in children with TBI. Infants and young children are more likely to experience cervical spine trauma than are older children, owing to their large heads and relatively weak necks. Ligamentous injury is common in this age group. In contrast, bony injury is extremely rare. Therefore, unless there is radiologic evidence of odontoid displacement or spinal cord edema, cervical spine injury is diagnosed based solely on the clinical examination. Because this is often not possible when TBI presents, cervical spine trauma is presumed to exist. Also, neurologic signs from spinal cord injury may be absent initially.

Risk Assessment Risk assessment relates to the likelihood of death or permanent CNS functional impairment. TBI that involves or is immediately adjacent to vital structure is more likely to be compounded by the need for surgical intervention; thus, it is associated with higher morbidity. Evidence of primary cortical brain injury (e.g., intracranial hematoma, seizures) and the presence of risk factors for secondary brain injury (e.g., hypovolemia, impaired ventilation) indicate more severe TBI as well as increased morbidity and mortality. Classic signs of intracranial hypertension seen in adults (e.g., papilledema, pupillary dilatation, cranial nerve palsies, headache on awakening, vomiting) may be absent in children, even when ICP approaches fatal levels. The presence of intracranial hematomas with acute TBI indicates a significant force of impact. Seizures after TBI also indicate significant parenchymal injury. Spinal cord injury is assumed to be present in all cases of head trauma, at least until a definitive diagnosis can be made.

Implications The danger of intracranial pathology is that expansion in an enclosed space leads to brain compression, causing ischemia, swelling, and loss of function that can be permanent and possibly fatal. Seizures greatly increase the cerebral metabolic

rate for oxygen. They are also associated with regional ischemia that can lead to cell death and loss of cognitive and functional abilities. Compromised integrity of the membranes covering the CNS (e.g., meningomyelocele) presents a significant risk for infection, as well as cerebrospinal fluid loss and hypothermia. Many children who present for surgical removal of tumors are malnourished and debilitated due to nausea, vomiting, and neurologic dysfunction with increased ICP. Acid-base, electrolyte, and endocrine abnormalities may be present. Patients with paralysis of an extremity of greater than 24 hours’ duration are at risk for an exaggerated hyperkalemic response to succinylcholine. Obtunded patients are at increased risk for aspiration, airway obstruction, and hypoventilation. Anesthetic management can influence the outcome and long-term prognosis in pediatric neurosurgical patients (Table 181-2). Therefore, conducting a thorough preoperative assessment, with indicated laboratory and radiographic studies; maintaining a stable intraoperative course (e.g., preserving cerebral perfusion while preventing increased ICP); and providing this same level of care throughout the postoperative period are critical.

MANAGEMENT In TBI, immediate attention is directed to establishing the airway, ventilation, and circulation. Supplemental oxygen, a secure airway, and intravenous (IV) cannulation are required. A Glasgow Coma Scale score of 9 or less is an indication for tracheal intubation, because the patient will be unable to protect his or her airway. A history is taken and a comprehensive physical examination is performed as soon as possible to evaluate medical comorbidities and the extent and severity of other physical injuries. Spinal cord injury precautions are taken. Any obvious bleeding should be controlled. Blood should be sent for complete blood count, coagulation studies, clinical chemistry, and type and crossmatch. Radiographic investigation includes computed tomography scans of the

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head, neck, and chest. Other investigations are performed based on the history and clinical findings. Anesthetic management is geared toward preventing further increases in ICP and maintaining cerebral perfusion pressure. Anxiolytic premedication is often unnecessary in neurologically compromised children. If the child is crying and agitated, however, small doses of IV midazolam or rectal barbiturates may be given, provided airway patency and adequacy of ventilation are ensured. After preoxygenation, anesthesia is usually induced with an IV induction agent (e.g., sodium thiopental). Ketamine and methohexital are generally contraindicated; the former increases ICP, and the latter lowers the seizure threshold. Rapid-sequence induction is indicated in patients who have not fasted or in whom there is an aspiration risk. If inhalation induction is desired, moderate hyperventilation is used to counter any vasodilatory effects of volatile anesthetics on the cerebral vasculature. Once effective mask ventilation is established, generous doses of opiates are given to obtund the sympathetic response to laryngoscopy and tracheal intubation. IV lidocaine also blunts the stimulus of laryngoscopy and tracheal intubation. Muscle relaxation with succinylcholine and atropine is used to facilitate endotracheal intubation. If succinylcholine is contraindicated, a large dose of a nondepolarizing drug (e.g., rocuronium) is used. The airway should be secured as efficiently as possible to ensure optimal ventilation and to avoid hypoxia and hypercarbia. The necessary equipment to deal with a difficult airway should be on hand in the event of unanticipated difficult intubation. If there is doubt about the ability to secure the airway in a timely fashion, tracheostomy should be considered. In-line neck traction with direct laryngoscopy and fiberoptic-guided intubation are equally effective at minimizing cervical spine injury associated with intubation. The former is the more usual approach in small children, but practitioners should use the technique with which they are most facile. Moderate hyperventilation (arterial carbon dioxide tension 30 to 35 mm Hg) is indicated to prevent cerebrovascular vasodilatation and the subsequent increase in cerebral blood flow and edema formation. Hyperoxia is unnecessary, and hypoxia must be avoided. Anesthesia is maintained with opioids and IV infusions of barbiturates or propofol, or with volatile anesthetic agents. Nitrous oxide is contraindicated in the presence of pneumocephalus, which can be present up to 3 weeks after previous craniotomy. Muscle relaxation is maintained to facilitate mechanical ventilation, prevent involuntary patient movement (e.g., coughing, bucking), and avoid increases in ICP. The drugs used for anesthetic induction and maintenance are chosen based on their effects on cerebral perfusion pressure and the patient’s overall condition (see Table 181-2). Hemodynamic stability is maintained using blood, crystalloid infusions, and vasopressors, as required. Osmotic pressure gradients are more important in avoiding cerebral edema than are oncotic pressure gradients. Thus, crystalloid rather than colloid infusions are the mainstay of fluid therapy. Hypertonic solutions (e.g., 3% saline) are reserved for refractory increased ICP. They are not advised in the perioperative period. Fluid maintenance is usually with 0.9% saline or balanced salt solutions with a physiologic

osmolality (285 to 290 mOsm/L). Because 0.9% saline is slightly hypertonic (306 mOsm/L), it can be given with a relatively hypotonic salt solution if large volumes of fluid are required. However, infused volumes are limited to the replacement of deficits and surgical losses, and they are maintained to avoid the exacerbation of coexisting cerebral edema. Blood should be given early in cases associated with hemorrhage to prevent anemia, which can increase CNS morbidity. Glucose-containing solutions should be used only to maintain serum glucose in the normal range. Patient monitoring includes the following: pulse oximetry, capnography, electrocardiography, invasive blood pressure, central venous pressure, urine output, temperature, precordial Doppler, and ICP monitoring if available. Cannulation of the femoral vein may be preferable to use of the internal jugular vein to avoid accidental neck trauma, which may aggravate already increased ICP. Hyperthermia must be avoided, as this increases the cerebral metabolic rate for oxygen. Normal body temperature or mild hypothermia is desirable. However, deep hypothermia should be avoided, because it is associated with disorders of coagulation and glucose control as well as arrhythmias. Also, shivering on awakening increases the cerebral metabolic rate for oxygen and should be avoided. If surgery involves or is proximate to the sensory or motor cortex, sensory and motor evoked potentials can be measured. However, motor evoked potentials cannot be monitored in denervated limbs or in the presence of neuromuscular blocking drugs. The electroencephalogram is monitored in patients undergoing surgery for seizures and some neurovascular lesions. Careful positioning to avoid injury to soft tissues (e.g., eyes, nose, ears, joints, peripheral nerves) is required. Headup tilt (15 to 30 degrees) improves cerebral venous drainage but increases the risk for venous air embolism. Smooth emergence and extubation are important to prevent increases in ICP due to cerebral venous congestion. This is facilitated by sufficient analgesia and antiemesis. Ondansetron is a popular choice because of its lack of sedation. Except after certain neurovascular procedures, the patient should be awake before tracheal extubation and should exhibit good muscle strength and ventilatory drive. Consequently, muscle relaxation should always be reversed. When there is any doubt whether the patient will maintain adequate spontaneous ventilation, he or she should be sedated and left intubated and ventilated. Such patients are cared for in the pediatric intensive care unit postoperatively. Postoperative complications include impaired ventilation in earlier extubated patients and intracranial bleeding. Diabetes insipidus may also occur. Intracranial bleeding is usually signaled by a diminishing level of consciousness or increasing ICP in an unconscious patient. Emergent head computed tomography is indicated to confirm the diagnosis and guide further management. Diabetes insipidus is characterized by the passage of copious volumes of dilute urine, with increased serum sodium concentrations and osmolality. It often occurs after surgery for hypothalamic tumors and TBI. Treatment consists of (1) replacing urine volume with dilute crystalloid, (2) infusing aqueous vasopressin (1 to 10 mU/kg per hour), and (3) monitoring serial serum electrolyte concentrations.

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Diabetes insipidus is often transient. Rebound volume overload and water intoxication can occur if vasopressin is not stopped and the fluid regimen is not adjusted when diabetes insipidus resolves. Finally, antibiotic and anticonvulsant therapy is continued through the perioperative period, both for prophylaxis and for treatment.

PREVENTION Prevention of primary TBI is best achieved through sociopolitical interventions and public education (e.g., use of appropriate child restraints in motor vehicles, obeying speed limits). Secondary brain injury is prevented by meticulous management of brain-injured patients, both in the field and in health care facilities. Aggressive resuscitation to maintain adequate oxygenation, ventilation, stable hemodynamics, and cerebral perfusion pressure, while minimizing intracranial hypertension, is the mainstay of therapy. Other therapeutic or prophylactic interventions are instituted after initial resuscitation and stabilization. New technologies (e.g., stereotactic-guided excision of intracranial tumors) have helped reduce the adverse impact of iatrogenic brain injury in pediatric neurosurgery.

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Further Reading Adelson PD, Bratton SL, Carney NA, et al: Guidelines for the acute medical management of severe traumatic brain injury in infants, children and adolescents: Use of hyperosmolar therapy in the management of severe pediatric traumatic brain injury. Pediatr Crit Care Med 4(3 Suppl): S40-S44, 2003. Alderson P, Roberts I: Corticosteroids in acute traumatic brain injury: Systematic review of randomized controlled trials. BMJ 314:1855-1859, 1997. Berger S, Schwarz M, Huth R: Hypertonic saline solution and decompressive craniectomy for treatment of intracranial hypertension in pediatric severe traumatic brain injury. J Trauma Injury Infect Crit Care 53:558-563, 2002. Bullock R, Chesnut RM, Clifton G, et al: Guidelines for the management of severe head injury: Brain Trauma Foundation, American Association of Neurosurgical Surgeons, Joint Section on Neurotrauma and Critical Care. Eur J Emerg Med 3:109–127, 1996. Carli P, Orliaguet G: Severe traumatic brain injury in children. Lancet 363:584-585, 2004. Hammer GB, Krane EJ: Perioperative care of the neurosurgical pediatric patient. Int Anesthesiol Clin 34:55-71, 1996. Johnson JO, Jimenez DF, Tobias JD: Anaesthetic care during minimally invasive neurosurgical procedures in infants and children. Paediatr Anaesth 12:478-488, 2002. Rekate HL: Head injuries: Management of primary injuries and prevention of secondary damage. A consensus conference on pediatric neurosurgery. Childs Nerv Syst 17;632-634, 2001. Vavilala MS, Lam AM: Perioperative considerations in pediatric traumatic brain injury. Int Anesthesiol Clin 40:69-87, 2002.

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182

Head Injury Arthur M. Lam and M. Sean Kincaid Case Synopsis A 22-year-old previously healthy man sustained a head injury and an open right femur fracture in a motorcycle accident. His initial Glasgow Coma Scale score was 9, and his right pupil was dilated and unreactive. Tracheal intubation was performed at the scene, and he was transported to the trauma center. A computed tomography scan revealed a large right epidural hematoma with a midline shift. Initial hematocrit was 32 after the administration of 2 L of crystalloid. His blood pressure was 130/80 mm Hg, and his heart rate was 120 beats per minute. He was scheduled for emergent evacuation of the epidural hematoma, followed by open reduction and internal fixation of the femur.

PROBLEM ANALYSIS Definition Head injury is a common problem, with an annual incidence of approximately 200 per 100,000 persons in the United States. Many of these injuries are minor, with few sequelae, but some are devastating. Car and motorcycle crashes are the most common cause of traumatic brain injury (TBI), followed by injuries from firearms, falls, and sports. Severe TBI is defined as any injury that results in a Glasgow Coma Scale (GCS) score of 8 or less after adequate cardiopulmonary resuscitation. Damage to neural tissue directly related to trauma is considered the primary injury and includes cerebral contusion, diffuse axonal injury, hemorrhage into the epidural or subdural space, and intraparenchymal hemorrhage. Secondary injury is any insult to the brain occurring after the initial TBI that causes further neuronal damage. Although cerebral ischemia or hypoxia is the ultimate cause of secondary brain injury after TBI, systemic or local insults often contribute to such injury. Among these are elevated intracranial pressure (ICP), systemic hypotension, and hypoxemia. Neuronal death is likely mediated by complex biochemical processes involving the release of excitatory amino acids (e.g., glutamate) and the cellular influx of calcium. Actual cell death may be necrotic or apoptotic in nature. Preventing or reducing secondary brain injury is the focus of most medical management of TBI in both the intensive care unit (ICU) and the operating room. TBI is often associated with other injuries (as illustrated in the case synopsis). Thus, anesthesiologists may care for a patient during surgical intervention for TBI (e.g., evacuation of subdural hematoma, decompressive craniectomy) and for laparotomy or fracture fixation, as well as in the ICU.

Recognition PRIMARY TRAUMATIC BRAIN INJURY Clinical Signs. TBI is suspected when head trauma is associated with mental status changes. Severity of TBI is 732

commonly assessed by the GCS, which assigns a score to the patient’s best motor, verbal, and eye-opening abilities (Table 182-1). A total score of 8 or less indicates severe TBI. Use of the GCS to evaluate patients with TBI reduces interobserver variability and allows for the comparison of serial examinations to evaluate disease resolution or progression. However, use of the GCS as a prognostic indicator is controversial. Further, assignment of a GCS score is appropriate only after adequate cardiopulmonary resuscitation, especially if severe hypotension or hypoxia is present. Along with the GCS, pupil evaluation is important. TBI may manifest as alterations in pupil size, symmetry, and reactivity to light. With acute unilateral mass lesions, an ipsilateral dilated and unreactive pupil suggests uncal herniation. In contrast, bilateral fixed and dilated pupils suggest severe intracranial hypertension (ICH) that may result in brain herniation, Vital signs may reflect the patient’s overall clinical status aside from any TBI. For example, hypotension and tachycardia may be due to concealed hemorrhage with a femur fracture, and hypertension may be due to pain. Vital signs also

Table 182–1

■

Glasgow Coma Scale Score

Eye Opening Spontaneous To speech To pain None

4 3 2 1

Verbal Response Oriented Confused Inappropriate Incomprehensible None

5 4 3 2 1

Motor Response Obeys commands Localizes to pain Withdraws to pain Flexes to pain Extends to pain None

6 5 4 3 2 1

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provide significant insight into the nature of TBI. Severe hypertension may be compensatory (i.e., to preserve cerebral perfusion pressure [CPP] in severe ICH; CPP is mean arterial pressure [MAP] minus ICP). Severe systemic hypertension with bradycardia is an ominous sign (Cushing’s reflex). It signifies impending brain herniation and requires immediate therapeutic intervention. Computed Tomography Findings. Cranial computed tomography (CT) is highly sensitive for detecting intracranial hemorrhage and acute mass lesions. CT findings that support a significantly elevated ICP include the following: ● ● ● ●

Mass lesion greater than 25 mL Midline shift of 5 mm or more Compression of the basal cisterns or lateral ventricles Medial displacement of the uncus

SECONDARY BRAIN INJURY Secondary brain injury is due to systemic or cerebral factors (Table 182-2). Among these, hypoxia and ischemia are most likely to have an adverse impact on TBI outcome. However, the neurologic defects of primary TBI may obscure the signs of secondary injury due to cerebral hypoxia or ischemia. Although the calculation of CPP (which requires an arterial line and ICP monitor) is useful with abnormal head CT findings, even a normal CPP does not preclude secondary ischemia or cerebral hypoxia. Other monitors are used to assess cerebral blood flow (CBF) and brain perfusion. A jugular venous bulb oximetric catheter (JBC) continuously measures brain venous oxygen saturation (SjvO2). Low brain perfusion increases oxygen extraction, causing a drop in SjvO2, while nonfunctioning brain extracts little oxygen to cause high SjvO2 values. SjvO2 less than 55% or greater than 75% is associated with a poor prognosis. SjvO2 catheters are especially useful to monitor cerebral metabolic rate (CMR) when deliberate hyperventilation is used in TBI to reduce global CBF. JBC lactate concentrations may also reveal anaerobic brain metabolism if they are higher than simultaneously drawn arterial lactate concentrations. A limitation of JBC is that it monitors only global CBF-CMR balance. SjvO2 values can be normal despite small regional areas of ischemia. Two other devices may provide greater sensitivity for monitoring regional brain ischemia than the JBC: brain tissue oxygen tension (PbrO2) monitors and microdialysis catheters.

Table 182–2

■

■

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Neither is as widely used as the JBC, but the PbrO2 monitor is readily available for clinical application. It provides a continuous measurement of brain parenchymal oxygen tension. This reflects the balance between local brain supply and demand for oxygen. Doppenberg and coworkers showed close correlation between PbrO2 and CBF. A PbrO2 of 26 mm Hg was about equivalent to a CBF of 18 mL/100 g per minute (i.e., ischemic threshold). Also, a PbrO2 of approximately 39 mm Hg is correlated with a good outcome, whereas one of 19 mm Hg correlates with a bad outcome, thus offering some guidance for therapeutic intervention. The normal PbrO2 is greater than 20 mm Hg. Microdialysis catheters are placed in brain parenchyma, where they continuously perfuse the brain with a perfusate and sample small volumes of fluid (the dialysate), which is tested for lactate and pyruvate concentrations to estimate the balance between anaerobic and aerobic metabolism. In addition, glutamate, glucose, and glycerol can be measured. However, a fairly long lag time is needed to analyze samples, which hinders real-time clinical decision making. Thus, microdialysis catheters are predominantly a research tool in their present form.

Risk Assessment and Implications Hypoxia and Hypercapnia. TBI patients are at increased risk for airway obstruction and hypoventilation. These lead to hypoxia and hypercapnia, which cause cerebral vasodilatation. The latter may aggravate any ICH. Elevated Intracranial Pressure. An acute mass lesion increases ICP and reduces CPP. Increased ICP can lead to brain herniation, with catastrophic consequences. Systemic Hypotension and Hypovolemia. Adults usually do not become hypovolemic and hypotensive as a result of blood loss from TBI alone. In contrast, small children can lose enough blood with TBI to become hypotensive. Other injuries (e.g., splenic rupture, femur fracture) can make TBI patients hypotensive and further compromise CPP in those with increased ICP. Compensatory hypertension and bradycardia (Cushing’s reflex) with elevated ICP may further complicate the clinical picture. Thus, in patients with TBI, normotension and tachycardia can still be compatible with severe hypovolemia, with the latter “concealed” by increased systemic vascular resistance (Cushing’s reflex). Thus, ample blood pressure may give clinicians a false sense of security

Risk Factors for Secondary Brain Injury

Cerebral Factors

Systemic Factors

Increased intracranial pressure Expanding mass lesions Hypercapnia Hypoxemia Venous obstruction (cervical collar, poor positioning) Systemic hypotension (compensatory cerebral vasodilatation) Excessive hyperventilation Post-traumatic vasospasm (patient with traumatic subarachnoid hemorrhage) Seizures

Hypotension Hypoxemia Anemia Hypovolemia Hyperglycemia Hyponatremia Hypo-osmolar state Coagulopathy

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human studies have linked brain infarct size and fever in ischemic brain injury.

Blood Pressure

CPP

autoregulation

Vasodilation

ICP

poor compliance Cerebral blood volume Figure 182–1 ■ Vasodilator cascade, showing the potential interaction between systemic hypotension and intracranial hemodynamics when autoregulation is intact. A cascade in the opposite direction also occurs when blood pressure is increased. CPP, cerebral perfusion pressure; ICP, intracranial pressure.

regarding the progress of resuscitation. Should ICH be relieved by decompressive craniectomy or evacuation of an intracranial hematoma, profound hypotension or cardiac arrest may occur. Of all the factors associated with secondary brain injury, systemic hypotension is likely the most significant. With impaired cerebral autoregulation, it invariably leads to reduced CPP. Patients with intact autoregulation but reduced intracranial compliance are also at risk for impaired CPP with hypotension. Reduced MAP dilates cerebral vasculature to increase cerebral blood volume and ICP. This increase in ICP further compromises CPP, leading to further compensatory cerebral vasodilatation. This vicious circle is referred to as the vasodilator cascade (Fig. 182-1). Impaired Autoregulation. Cerebral autoregulation is a homeostatic mechanism that maintains near-constant perfusion of the brain over a wide range of MAPs. In normal adults, this range is 60 to 160 mm Hg. Autoregulation may be impaired in patients with TBI, and although the frequency of impaired autoregulation is higher in patients with severe TBI, it is clinically impossible to predict which patients will be affected. Even minor TBI may impair autoregulation. If so, CBF becomes directly proportional to blood pressure. Loss of cerebral autoregulation is associated with worse outcomes with TBI. Coagulopathy. Severe TBI liberates enough thromboplastin from damaged neurons to cause coagulopathies, which may be mild to severe. They can increase surgical morbidity and mortality, can preclude or delay extracranial surgical procedures, and are associated with poorer outcomes. Pyrexia. Fever raises the CMR, increasing the risk for ischemia and neural injury, especially when cerebral perfusion is marginal. Cerebral blood volume increases with pyrexia owing to flow-metabolism coupling, exacerbating any ICH. Although human studies do not conclusively link body temperature to outcome in TBI, both animal and

Hyperglycemia. Hyperglycemia in TBI and stroke is associated with a poor prognosis, although a cause-effect relationship has not been clearly established. In experimental cerebral ischemia, detrimental effects of hyperglycemia have consistently been shown. Further, in one prospective trial, van den Berghe and colleagues found that patients with lax glucose control had worse outcomes than those with tight control. Fluid and Electrolyte Abnormalities. Acute fluid and electrolyte disturbances occur in TBI patients, often due to inappropriate fluid administration. They can also be caused by diabetes insipidus. Hyponatremia and excessive free water may worsen cerebral edema, thereby increasing ICP. Associated Injuries. As many as 10% of patients with TBIs also have spine injuries. Spinal evaluation is often delayed if the patient requires emergent neurosurgical intervention (e.g., evacuation of epidural or subdural hematoma). For this reason, spine precautions should be taken when moving or positioning patients before the completion of a spine injury workup. TBI patients may also have undiagnosed extremity injuries.

MANAGEMENT Secure the Airway Immediate tracheal intubation is necessary for severely head-injured patients, particularly those with GCS scores of 8 or less and without protective airway reflexes. Both propofol and thiopental are used as induction agents because they decrease CMR and lower ICP. However, either may cause hypotension, especially in inadequately fluid-resuscitated TBI victims, which negates their benefit. Because of a lower risk of untoward hypotension in TBI patients, etomidate may be a better choice. Ketamine is avoided because it increases ICP. A short-acting muscle relaxant should be used. Succinylcholine is preferred, and rocuronium is used when succinylcholine is contraindicated.

Maintain Adequate Cerebral Perfusion Pressure The updated Brain Trauma Foundation guidelines (2003) advise keeping CPP between 60 and 70 mm Hg (in patients without cerebral ischemia); the trend today is to maintain CPP above 60 mm Hg. To maintain CPP, there must be good intravenous access, and fluid resuscitation must replete intravascular volume as needed. Fear of worsening cerebral edema should never dissuade one from providing adequate fluid resuscitation. Hypotonic fluids should be avoided, however (Table 182-3). Hypertonic fluids (e.g., 3% saline) may be used, although evidence is lacking to justify their routine use. Vasopressors and inotropes are often used along with fluid resuscitation to maintain CPP. However, they should be used with caution, because they may increase the risk for acute respiratory distress syndrome. Without ICP monitoring, MAP should be maintained at greater than 70 mm Hg.

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Fluids Plasma Crystalloid 0.9% NS 0.45% NS 3% NS 7.5% NS LR D5LR D5W∗ D5 NS∗ D50.45% NS∗ Normosol Mannitol (20%) Colloid Hetastarch (6%) Albumin (5%) Plasmanate

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Intravenous Fluids Osmolality (mOsm/kg)

Oncotic Pressure (mm Hg)

Na+ (mEq/L)

Cl− (mEq/L)

289

21

141

103

308 154 1030 2400 273 527 252 586 406 295 1098

0 0 0 0 0 0 0 0 0 0 0

154 77 515 1200 130 130

310 290 270-300

31 19 ?

K+ (mEq/L)

Ca2+/Mg2+ (mEq/L)

4-5

5/2

154 77 515 1200 109 109

4 4

3/0 3/0

154 77 140

154 77 98

5

0/3

154

154

145

100

Glucose (g/L)

50 50 50 50

0.25

∗The osmolality of these dextrose solutions decreases as glucose enters the cells. D5W, 5% dextrose in water; LR, lactated Ringer’s; NS, normal saline.

Ischemia is likely the final pathway in secondary brain injury. Therefore, the hematocrit is kept at 30% to provide adequate oxygen delivery. If Cushing’s reflex is present in patients with acute subdural or epidural hematoma, blood pressure may decline precipitously with surgical decompression. This is anticipated based on clinical findings (e.g., low GCS score, significant midline shift on CT, abnormal pupils), and preemptive intravenous fluid resuscitation should be undertaken. Prompt treatment of hypotension after surgical decompression with intravenous fluids and vasopressors or inotropes is essential.

Reduce Intracranial Pressure To optimize CPP, one must try to reduce ICP. Recent data suggest that better physiologic parameters are maintained (e.g., SjvO2, arterial-venous difference in oxygen saturation) in patients with ICP of 20 mm Hg or less. CPP is maintained in the 60 to 70 mm Hg range. Mannitol (0.25 to 1 g/kg) is useful for reducing brain bulk and may decrease the production of cerebrospinal fluid; both these effects reduce ICP. Mannitol is given after volume repletion. Patients refractory to mannitol may respond to hypertonic saline (3% or 7.5%). Cerebral blood volume is reduced with acute hyperventilation, and CBF decreases by about 3% for each 1 mm Hg decline in arterial carbon dioxide tension. There is the potential for cerebral ischemia with excessive hyperventilation. Arterial carbon dioxide tension is not decreased to less than 30 mm Hg, except for brief periods (e.g., impending herniation). Otherwise, normocapnia or slight hypocapnia (35 to 40 mm Hg) is desirable when ICP is less than 20 mm Hg. Barbiturates or propofol given to suppress CMR can reduce ICP. Effects are maximal with electroencephalogram burst suppression or an isoelectric electroencephalogram. Vasopressors may be required to support blood pressure with maximal CMR suppression. Low-dose propofol is often used in TBI, because it allows effective ICP control while

permitting prompt neurologic evaluation. However, metabolic syndromes characterized by myocardial dysfunction and lactic acidosis have been observed after prolonged propofol infusions, especially in children. Other techniques to reduce ICP are slight head-up and neutral neck positions. Both facilitate venous drainage. Many TBI patients have cervical collars in place, and it is important to inspect the collar to ensure that it does not impede venous drainage; a collar that is too tight can increase ICP. Circumferential endotracheal tube ties should be avoided for the same reason. In patients with increased ICP that is refractory to medical management, a decompressive craniectomy is indicated.

Correct Coagulopathies Coagulopathies increase the morbidity associated with any surgery in TBI patients. Coagulation should be followed closely, and any deficient factors should be replaced aggressively. Some surgeons advocate early replacement of platelets and clotting factors based solely on clinical observations.

Treat Hyperglycemia Dextrose-containing intravenous solutions are avoided during fluid resuscitation. They may cause hyperglycemia and worsen cerebral ischemic injury. Current ICU guidelines advise keeping blood glucose at 80 to 110 mg/dL. Some may be uncomfortable with such tight glucose control in anesthetized patients, because signs of hypoglycemia may be masked. Insulin infusions are titrated by frequent glucose determinations to keep glucose levels at less than 120 mg/dL.

Restore Normothermia Clearly, hyperthermia is harmful to patients at risk for ischemic brain injury. Any beneficial effects of hypothermia

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are less clear. Despite animal studies showing a neuroprotective effect, no clinical trial has shown that hypothermia improves the outcome in TBI. Although reducing body temperature decreases the CMR, theoretically reducing ischemic risk, the potential disadvantages may outweigh any potential benefits. Importantly, hypothermia may cause coagulopathy, which is undesirable in patients who are already prone to such disorders. Hypothermia also increases the risk of infection, and cooling patients to less than 35°C may lower PbrO2 owing to a leftward shift of the hemoglobin-oxygen dissociation curve. Given the inconclusive evidence for hypothermia, we advise keeping temperature in a low-normal range (35°C to 36°C). One setting in which hypothermia might be considered is in a TBI patient with refractory ICH, because hypothermia is known to reduce ICP. Hypothermia may be used in conjunction with other techniques to reduce ICP (e.g., mannitol, propofol, barbiturate coma). Whether outcomes are improved is uncertain, and the prognosis for this patient population remains grim.

Use Appropriate Anesthetic Agents There are many options with regard to anesthetic agents and techniques in TBI patients. A combination of an opioid and a volatile anesthetic is appropriate if the concentration of the volatile agent is kept at significantly less than 1 minimum alveolar concentration (MAC). Higher concentrations may cause cerebral vasodilatation, or “luxury perfusion.” Total intravenous anesthesia is another option. Thiopental and propofol are potent cerebral vasoconstrictors, but vasopressors may be needed to support blood pressure. Nitrous oxide is best avoided because it can increase the CMR and worsen ischemia; also, it may exacerbate pneumocephalus.

Delay Nonemergent Medical Procedures In general, the benefits of other procedures must be weighed against the risk of further injury to the brain. Nonemergent procedures should be delayed in unstable TBI patients. Instead, these patients should be taken to the ICU, where they can be resuscitated, their coagulation parameters can be normalized, and ICP can be brought under control.

PREVENTION Treatment of acute TBI aims to prevent secondary injury while allowing the brain to recover from the primary injury. For those with mass lesions, definitive therapy is surgical intervention. Anesthesiologists must understand the pathophysiology and nature of TBI, anticipate any complications, and treat

these appropriately and in a timely manner. Optimal patient care also depends on good communication among surgeons, anesthesiologists, and the nursing staff. For example, the nursing staff should ensure that blood and indicated blood products are available. Also, for the decompression of mass lesions, the surgeon must notify the anesthesiologist just before cranial decompression occurs. In turn, the anesthesiologist must have intravenous fluid and vasopressors ready to treat any hypotension that follows. With careful planning and anticipation, patient care and outcome can be optimized, even if a good outcome is not ensured.

Further Reading Clifton GL, Miller ER, Choi SC, et al: Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med 344:556-563, 2001. Coles JP, Fryer TD, Smielewski P, et al: Incidence and mechanisms of cerebral ischemia in early clinical head injury. J Cereb Blood Flow Metab 24:202-211, 2004. Doppenberg EM, Zauner A, Bullock R, et al: Correlations between brain tissue oxygen tension, carbon dioxide tension, pH, and cerebral blood flow—a better way of monitoring the severely injured brain? Surg Neurol 49:650-654, 1998. Gopinath SP, Cormio M, Ziegler J, et al: Intraoperative jugular desaturation during surgery for traumatic intracranial hematomas. Anesth Analg 83:1014-1021, 1996. Hlatky R, Furuya Y, Valadka AB, et al: Dynamic autoregulatory response after severe head injury. J Neurosurg 97:1054-1061, 2002. Junger EC, Newell DW, Grant GA, et al: Cerebral autoregulation following minor head injury. J Neurosurg 86:425-432, 1997. Kawaguchi M, Sakamoto T, Ohnishi H, et al: Preoperative predictors of reduction in arterial blood pressure following dural opening during surgical evacuation of acute subdural hematoma. J Neurosurg Anesth 8:117-122, 1996. Lam AM, Mayberg TS: Anesthetic management of patients with traumatic head injury. In Lam AM (ed): Anesthetic Management of Acute Head Injury. New York, McGraw-Hill, 1995, pp 181-221. Lam AM, Winn HR, Cullen BF, et al: Hyperglycemia and neurological outcome in patients with head injury. J Neurosurg 75:545-551, 1991. Management and Prognosis of Severe Traumatic Brain Injury. New York, Brain Trauma Foundation, 2003. Marion DW, Penrod LE, Kelsey SF, et al: Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med 336:540-546, 1997. Marion DW, Puccio A, Wisniewski SR, et al: Effect of hyperventilation on extracellular concentrations of glutamate, lactate, pyruvate, and local cerebral blood flow in patients with severe traumatic brain injury. Crit Care Med 30:2619-2625, 2002. Matta BF, Lam AM, Mayberg TS, et al: A critique of the intraoperative use of jugular venous bulb catheters during neurosurgical procedures. Anesth Analg 79:745-750, 1994. Rosner MJ, Rosner SD, Johnson AH: Cerebral perfusion pressure: Management protocol and clinical results. J Neurosurg 83:949-962, 1995. Valadka AB, Hlatky R, Furuya Y, et al: Brain tissue PO2: Correlation with cerebral blood flow. Acta Neurochir Suppl 81:299-301, 2002. van den Berghe G, Wouters P, Weekers F, et al: Intensive insulin therapy in the critically ill patient. N Engl J Med 345:1359-1367, 2001.

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Tod B. Sloan

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183 4

Spinal Cord Injury Case Synopsis A 32-year-old man presents to the emergency department following a motorcycle accident in which he was thrown to the roadside. He is mildly obtunded, smells of alcohol, and is difficult to examine neurologically, but he appears to have loss of sensation and motor activity below the C5 dermatome. Lateral neck films fail to identify bony injury or subluxation. Vital signs reveal hypotension (90/40 mm Hg), bradycardia (50 beats per minute), respiratory difficulty, and an oral temperature of 36.2°C. He is taken to the operating room emergently for repair of an open tibial fracture.

PROBLEM ANALYSIS Definition Spinal cord injury (SCI) is defined as injury to the spinal cord with neurologic dysfunction, with or without spinal column disruption. Anesthesia care is often required shortly after injury, for resuscitation or surgical intervention. Later, anesthesia care may be required for surgery in patients with chronic SCI or for the management of patients who have recently sustained iatrogenic SCI (e.g., corrective surgery for scoliosis, aortic reconstructive surgery). Acute SCI occurs most frequently with trauma. Most of the problems accompanying SCI are a result of the neurologic loss, and they evolve over time. Early recognition of SCI is important if devastating late complications are to be reduced or prevented. Acutely, the spinal cord distal to the level of injury is nonfunctional (e.g., areflexia, vasodilatation, muscle flaccidity). Loss of thoracic sympathetic outflow leads to the spinal shock syndrome; this is characterized by hypotension and bradycardia due to unopposed sacral and vagal parasympathetic tone. After several days to 6 to 8 weeks, the uninjured cord becomes functional (i.e., spinal reflexes are intact), but it is isolated from higher neural input (i.e., cephalad spinal cord, brainstem, brain). This leads to uncontrolled spinal reflexes, muscle spasticity, and, ultimately, contractures. Such changes distinguish acute from chronic SCI and explain the attendant neurophysiologic differences between the two types of injury.

However, an unstable cervical spine may be missed in as many as 30% of cases. Thus, computed tomography or magnetic resonance imaging may be required to identify all cervical spine injuries. Acute SCI can also occur without ligamentous or bony injury, especially in children; this is called spinal cord injury without radiographic abnormality. SCI is evaluated according to the following parameters: ● ● ● ●

Level of injury Time since injury Presence of spinal instability Degree and type of neurologic impairment

The level of injury is usually related to the mechanism of injury and the site of trauma. It is inferred by the neurologic examination and confirmed by any of the aforementioned radiographic procedures. The SCI level defines the potential complications and has implications for management. The time since injury is usually apparent from the trauma event itself or the onset of neurologic findings. Early recognition of acute SCI is important, because early treatment may reduce the degree of irreversible injury. As time progresses, the spectrum of residual injury changes (see later). Recognition of spinal instability (especially in the cervical spine) is important for patient positioning and movement, especially during airway management and tracheal intubation. However, spine injury can occur without bony or ligamentous instability (e.g., spinal hematomas and abscesses; intraoperative injuries; trauma in children). Finally, the degree and type of neurologic impairment define the potential neurologic sequelae.

Recognition All patients with multiple trauma should be evaluated for acute SCI, especially those with neck complaints or neurologic abnormalities; those who are comatose, with hypotension and absent reflexes; and any trauma patient with apparent hypovolemic shock but without the expected compensatory tachycardia. Most traumatic acute SCI occurs in the more flexible cervical and lumbar regions, but especially in the cervical spine. Radiographic films of the lateral cervical spine (C1-C7) and anteroposterior open-mouth (“swimmer’s view”) films usually confirm any bony injury.

Risk Assessment Certain surgical procedures are associated with a recognized risk of acute SCI. The neurologic risk in spinal column correction procedures is approximately 1% to 4%; however, the risk approaches 75% for the correction of severe kyphosis. Surgery involving the thoracic aorta also has a high risk (see Chapter 94). In surgical patients, early detection of the injury by intraoperative monitoring may allow correction before the injurious process (often ischemia) causes irreversible injury. 737

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Acute SCI should be suspected in all trauma victims. Major trauma victims have a 2.6% risk of acute SCI, and patients with head trauma have a 4% to 5% risk of associated cervical spine injury. Traumatic acute SCI is thought to occur in 12 to 53 persons per million yearly, more often in males (4:1 predominance), and most commonly at C4-C6. The second most commonly injured spine region is T11 to L2. The most frequent cause is motor vehicle accidents, often associated with alcohol or drug consumption. Falls in elderly persons and diving accidents are among the other important causes. Of patients with cervical spine injuries, about 25% become quadriplegic, and 40% have no residual neurologic impairment. That leaves about 35% with some degree of residual neurologic impairment. Patients with acute SCI who show no resolution of neurologic impairment progress to chronic SCI. In obtunded patients, a careful history and neurologic examination may be needed to distinguish chronic SCI from cerebral injury. A better understanding of the mechanisms of SCI and its management has reduced overall mortality from 80% (World War I era) to less than 2% by the early 1980s.

Implications The complications of SCI depend on the level of injury and the particular syndrome of injury, defined by the zone of injury in the spinal cord. The greatest number of complications occur with neurologically complete acute SCI (comparable to spinal cord transection). This is characterized by loss of all neurologic function at and below the level of injury. With high spinal cord injury (C4-C6), pulmonary function studies usually reveal reduced total lung capacity, vital capacity, expiratory reserve volume, and forced expiratory volume and increased residual lung volume. Vital capacity is an excellent measure of pulmonary compromise; patients with a vital capacity less than 15 mL/kg often require tracheal intubation and ventilatory support. A variety of factors contribute to ventilatory compromise, which occurs in 67% of acute SCI patients within the first few days after injury (Table 183-1). Acute SCI patients ventilate better when supine, because the abdominal contents tent the diaphragm, allowing for better mechanical action (except when distended bowel or stomach hinders

Table 183–1

■

Factors Contributing to Ventilatory Compromise in Acute Spinal Cord Injury

Limitation of diaphragmatic motion by gastric distention and ileus Aspiration pneumonitis Reduced expiratory reserve and ability to cough, secondary to loss of abdominal (T2-L1) and intercostal (T1-T11) muscle control Fat emboli with long bone fractures Chest trauma (rib fractures, pulmonary contusion, pneumothorax, hemothorax) Loss of spinal input to the phrenic nerve (C3-C5) and control of the diaphragm Depressed consciousness from head injury, alcohol, or drugs Neurogenic edema from head injury Pulmonary edema secondary to cardiovascular dysfunction

diaphragmatic movement). Retained airway secretions and atelectasis are common. Ventilation may improve with chronic SCI due to strengthening of the chest wall and abdomen by intercostal and abdominal muscle contractures. Cardiovascular function is markedly altered in acute SCI by the associated loss of sympathetic control of the heart and vasculature. Consequent venodilatation leads to relative hypovolemia and reduced preload. This is aggravated by traumatic or surgical blood loss. Peripheral vasodilatation reduces systemic vascular resistance. The reduction in both preload and systemic vascular resistance contributes to a hypotensive state known as spinal shock. Loss of cardiac sympathetic innervation leads to the inability to increase contractility and heart rate in response to hypovolemia or blood loss. Resulting unopposed vagal tone enhances the potential for bradycardia and escape rhythms. Either may occur with sudden increased blood pressure (i.e., hyperactive carotid sinus reflex) or airway manipulation and may necessitate atropine or temporary or permanent pacing. In addition to the potential for bradycardia and hypotension, patients with acute SCI are at risk for acute heart failure and pulmonary edema. Experimental evidence suggests that myocardial injury may occur at the time of SCI due to a catecholamine surge with an acute and transient increase in afterload. There is greater cardiovascular stability with chronic SCI. However, with lesions above T7, sensory stimuli below the level of SCI may provoke exaggerated sympathetic spinal reflexes (i.e., autonomic hyperreflexia), causing intense vasoconstriction and acute hypertension (see Chapter 114). In addition to cardiovascular dysfunction, there are other types of injury or defects associated with acute SCI (Table 183-2). Impaired temperature regulation, caused by loss of sympathetic-mediated changes in vascular tone, leads to vasodilatation and the inability to control sweating. Denervation of skeletal muscle leads to neuromuscular junction hypersensitivity, so that depolarizing muscle relaxants (e.g., succinylcholine) cause exaggerated potassium release. This begins within 24 to 48 hours of acute SCI and lasts until muscle atrophy with chronic SCI abolishes the effect. Succinylcholine is generally considered safe 1 year after the onset of acute SCI. In traumatic acute SCI, patients may have associated injuries (e.g., head trauma with increased intracranial pressure; chest, abdominal, or orthopedic injuries).

Table 183–2

■

Injuries or Defects Associated with Acute Spinal Cord Injury

Cardiovascular dysfunction (spinal shock) Impaired temperature regulation Neuromuscular junction hypersensitivity Head injury (raised intracranial pressure) Chest trauma (pneumothorax, cardiac contusion) Myocardial injury Aspiration pneumonitis Pneumothorax, pneumomediastinum Hematoma compromise of airway in neck trauma Long bone fractures with blood loss and fat emboli Renal failure Muscle contractures Deep venous thrombosis and pulmonary thromboembolism

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Other conditions associated with chronic SCI include the following: ●

●

●

Renal failure (from recurrent urinary tract infection or amyloidosis) Drug or alcohol abuse or dependence (owing to depression or pain syndromes) Decubitus ulcers

Also with chronic SCI, spinal reflex action below the lesion may lead to uncontrolled muscle contractures (i.e., the “mass reflex”). Patients with both acute and chronic SCI are prone to develop deep venous thrombosis (up to 80% to 85% in cervical injuries). Thus, pulmonary thromboembolism is a common cause of death in patients with acute SCI and may prompt the placement of a vena cava filter.

MANAGEMENT Initial priorities in acute SCI victims are securing the airway, ensuring adequate oxygenation and ventilation, and providing circulatory support. Further medical management is for coexisting injuries and the prevention of ischemic SCI. The unstable spine should be stabilized in a neutral position, with traction deferred until the neurologic evaluation is complete. Traction can lead to further injury, including disk herniation, C1-C2 ligamentous laxity, or ankylosing spondylitis. The first priority is to secure the airway. Ideally, a controlled, awake intubation allows neurologic observation during intubation. However, if immediate tracheal intubation using direct laryngoscopy is necessary, midline stabilization (not traction) can minimize the degree of cervical spine movement. If facial trauma prohibits oral intubation, a surgical airway (tracheostomy or cricothyrotomy) or transtracheal ventilation may be needed. In patients with head trauma, nasal intubation should be avoided, if possible, until a basilar skull fracture has been ruled out. After establishment of the airway, adequate oxygenation and ventilation must be confirmed. Any hypotension, which could be secondary to loss of sympathetic tone from acute SCI, hypovolemia, and trauma, should be treated with intravenous fluids to restore adequate cardiac output and blood pressure. Pulmonary artery catheterization may be needed, especially with quadriplegia, because excessive fluids may cause pulmonary edema. Vasoconstrictors (e.g., dopamine, ephedrine, phenylephrine1) are used to augment cardiovascular dynamics when volume alone is ineffective. Myocardial inotropic support may also be necessary, because acute SCI may cause myocardial injury from brief, explosive autonomic discharge with hypertension due to mechanical compression of the descending sympathetic nerves. Transient bradycardia is treated with atropine or β-adrenergic agonists, with provision for pacing in patients with persistent bradycardia or escape rhythms. High-dose methylprednisolone is thought to improve outcome (see later).

1 Phenylephrine may be advantageous. It is primarily an α-adrenergic agonist. Thus, it increases both systemic vascular resistance and preload via constriction of the venous capacitance bed.

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Sudden changes in position may cause postural hypotension (head-up tilt) or pulmonary edema (headdown tilt) due to reduced cardiovascular compensation. The clinician should monitor the patient’s temperature and use warming blankets or adjust the ambient temperature as needed. Unexplained hypotension may also be due to previously unrecognized intra-abdominal or retroperitoneal bleeding. Associated major injuries occur in about two thirds of patients with traumatic acute SCI. Of special concern are thoracoabdominal injuries, which may be nonapparent owing to sensory loss or head injury. Thoracoabdominal injuries occur in as many as 25% to 50% of patients with acute SCI. Other aspects of postinjury care relate to complications of acute SCI, such as gastric erosions, deep venous thrombosis, and pulmonary embolism. Emergency surgery in cases of traumatic acute SCI is usually for injuries other than those to the spinal cord. However, emergency spinal cord surgery may be required if vertebral bony alignment cannot be achieved by traction (e.g., due to “locked” facets) or when bone fragments or protruding disk material is impinging on the spinal cord. Anesthetic management for such surgery involves maintaining adequate spinal cord perfusion. Outcomes are improved if mean blood pressure is greater than 85 mm Hg, central venous pressure is 5 to 10 mm Hg, arterial oxygen tension is greater than 100 mm Hg, and normoglycemia and normocarbia are maintained. Extubation should be delayed until adequate unsupported ventilatory function is ensured. Postoperative mechanical ventilatory support may be needed. Emergency reintubation is undesirable in patients with acute cervical spine injury due to the need for additional neck manipulation. If acute SCI is related to recent spinal or aortic surgery, time is of the essence if deleterious effects are to be reversed. Many surgeons use steroids, such as methylprednisolone or dexamethasone, at this time. Removal of spinal instrumentation or exploration of the spinal canal for hematomas may be required within a few hours. If so, electrophysiologic monitoring (i.e., sensory or motor evoked potentials) may be necessary to warn of further SCI. Anesthesia for surgery in patients with chronic SCI is often for decubitus ulcers or kidney stones. Local, regional, or general anesthesia may be sufficient, depending on the site of surgery and the degree of neurologic impairment. However, many chronic SCI patients (85%) with lesions above T7 are prone to autonomic hyperreflexia and associated hypertension, which can occur when local anesthesia alone is used; both regional and general anesthesia can block this. Although less successful than subarachnoid block for urologic or general surgery, epidurals have been used successfully during labor. Positioning problems may be anticipated in chronic SCI patients due to either contractures or positions that compromise ventilation. In patients with chronic SCI, the blood volume is often contracted (60 mL/kg), making them prone to orthostatic hypotension. Other procedures that may require anesthesia care and are common in patients with chronic SCI are placement of pulse generators for phrenic nerve or spinal cord stimulation (i.e., to improve ventilatory mechanics or for pain control, respectively) and intrathecal baclofen for the management of spasticity.

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PREVENTION Once acute SCI has occurred, efforts should be directed toward reducing additional injury due to secondary causes (e.g., hypoxemia, impaired spinal cord perfusion). Although methylprednisolone (30 mg/kg intravenous bolus, then 5.4 mg/kg per hour for 23 hours), when started 3 to 8 hours after acute SCI, appears to reduce the neurologic injury score, it may not improve function. Such steroid use is not advised with penetrating abdominal injuries because of the probable or assumed contamination of the spinal canal with bowel flora. Prompt intervention for acute SCI related to spinal cord surgery, or to relieve compression, can also reduce the degree of injury. Intraoperative measures that help reduce acute SCI include maintaining normal blood pressure, arterial carbon dioxide tension, and glucose concentrations throughout surgery and the immediate postoperative period. Finally, spinal cord function monitoring with evoked sensory and motor potentials may reduce any additional (iatrogenic) injury, especially during spinal decompression and fusion.

Further Reading Bracken MB, Shepard MJ, Holford TR, et al: Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury: Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA 277:1597-1604, 1997. Chiles BW, Cooper PR: Acute spinal injury. N Engl J Med 334:514-520, 1996. Gronert GA, Theye RA: Pathophysiology of hyperkalemia induced by succinylcholine. Anesthesiology 43:89-99, 1975. Hambly PR, Martin B: Anaesthesia for chronic spinal cord lesions. Anaesthesia 53:273-289, 1998. Kirshblum SC, Groah SL, McKinley WO, et al: Spinal cord injury medicine. 1. Etiology, classification and acute medical management. Arch Phys Med Rehabil 83(3 Suppl 1):S50-S57, S90-S98, 2002. Lambert DJ, Deane RS, Mazuzan JE: Anesthesia and the control of blood pressure in patients with spinal cord injury. Anesth Analg 61:344-388, 1982. Lee TT, Green BA: Advances in the management of acute spinal cord injury. Orthop Clin North Am 33:311-315, 2002. Mackensie CF, Geisler FH: Management of acute cervical spinal cord injury. In Albin MS (ed): Textbook of Neuroanesthesia with Neurosurgical and Neuroscience Perspectives. New York, McGraw-Hill, 1996, pp 1083-1136. Sloan TB, Hickey R, Albin MS: Anesthesia management of the patient with acute spinal cord injury. Adv Anesth 8:55-90, 1991. Woodring JH, Lee C: Limitations of cervical radiography in the evaluation of acute cervical trauma. J Trauma 34:32-39, 1993.

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184

Corneal Injury Lois L. Bready and Stacey L. Allen Case Synopsis A 25-year-old woman in the postanesthesia care unit complains of pain and a foreign body sensation in her left eye. She had received general endotracheal anesthesia for nasal polypectomy earlier that day. Physical examination reveals residual petroleum-based ointment containing mascara particles around both eyes and left-sided conjunctival erythema, marked tearing, photophobia, and diminished visual acuity. A pulse oximeter probe is attached to her left index finger.

PROBLEM ANALYSIS Definition Corneal injury occurs infrequently during anesthesia, but it can be painful. A corneal abrasion may progress to corneal ulceration and erosion, with loss of visual acuity. Exposure of the cornea to a variety of chemicals may cause burns, with subsequent scarring.

Recognition A patient with corneal trauma typically experiences tearing, foreign body sensation, photophobia, diminished visual acuity, and eye pain. Bedside examination may reveal an abraded site (Fig. 184-1). Ophthalmologic examination with fluorescein staining and an ultraviolet lamp or (preferably) a slit lamp reveals areas of denuded cornea within the interpalpebral area (Fig. 184-2A) or linear defects from mechanical abrasion (Fig. 184-2B). Chemical corneal toxicity usually leads to chemosis (i.e., marked swelling of the conjunctiva), with various corneal epithelial defects, including punctate keratitis (Fig. 184-3).

database (Table 184-1). Of these, 25 were corneal abrasions, and 16% resulted in permanent injury. Chemical injury or direct trauma was identified as the mechanism of corneal injury in only 20% of corneal abrasions. A 1996 study by Roth and coworkers suggested that older patients and lengthier procedures are associated with a higher risk of injury to the eyes. CHEMICAL INJURY Exposure to a variety of disinfectant solutions can result in chemical burns to the cornea (Table 184-2), with the potential to cause blindness. Most skin antiseptic solutions are toxic to the cornea, as documented in animal models. If the solution accidentally splashes or runs into the tear film (e.g., during preparation for surgery on the head and neck), intense toxic effects may result. Hibiclens (chlorhexidine gluconate 4% and detergent) has been reported to cause permanent corneal scarring. The toxicity of other antiseptic solutions may be less profound, but these solutions should be avoided if possible. The solution least toxic to the cornea is 10% povidone-iodine. Because both the concentration of the solution and the contact time are critical factors in corneal toxicity, it is prudent to

Risk Assessment A number of risk factors associated with general anesthesia may predispose to corneal trauma. Numerous manipulations occur around the patient’s face and head during the course of routine surgery with anesthesia. The corneal epithelium is delicate; even gentle tactile contact may cause trauma. Pain perception is reduced by narcotics and is blocked during general anesthesia. Protective corneal reflexes are obtunded, and tear production is diminished. Foreign bodies may be present and are an additional risk factor for corneal abrasion. When surgical procedures are performed on the head and neck, antiseptic solutions are applied to the skin near the eyes, and inadvertent contact with the cornea can occur.

Implications Eye injuries account for 71 of 2046 cases (3%) in the American Society of Anesthesiologists closed claims

Figure 184–1

■

Corneal abrasion.

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A

B

Figure 184–2 Staining patterns of the cornea and conjunctiva. A, Interpalpebral abrasion (indicating exposure due to incomplete eyelid closure). B, Linear defects (suggesting mechanical abrasion). ■

immediately irrigate the conjunctival sac with saline, balanced salt solution, or water if exposure to a chemical disinfectant occurs. The great majority of reported cases of severe keratitis due to exposure to surgical preparation solutions occurred during operations performed by nonophthalmologists on or around the head and neck, suggesting that failure to recognize the exposure and the consequent lack of irrigation may have played a role in the adverse outcomes. Also, be aware that surgical preparation solutions can flow in a retrograde fashion from the nasal cavity into the conjunctival sac via a patent nasolacrimal duct. Exposure to acidic gastric secretions can also cause a chemical burn to the cornea. If such exposure is recognized or suspected, once again, irrigation of the conjunctival sac is advised.

or other nearby objects can abrade the corneal surface. Corneal abrasion may occur during the induction of anesthesia, during mask airway management or instrumentation of the airway, upon application of ophthalmic lubrication (if the tip of the eye lubricant tube contacts the cornea rather than being at least 3 to 4 mm away from its surface), during the procedure (pressure on the eye by the surgeon’s or anesthetist’s hands or elbows, instruments, or other causes), or at emergence (due to causes similar to those during induction or if the patient rubs his or her eyes for any reason). If the pulse oximeter probe is positioned on the patient’s index finger, particularly on the dominant hand, the risk of selfinduced corneal abrasion or laceration is increased. Foreign bodies in and around the eye (e.g., mascara, contact lenses, false eyelashes) also increase the risk of corneal abrasion.

CORNEAL ABRASION Direct pressure on the eye by the facemask and head strap; the hand, arm, or elbow of the anesthesiologist or surgeon;

MANAGEMENT When a patient’s postoperative complaints suggest corneal injury, it is absolutely necessary to obtain an ophthalmologic consultation as soon as possible. Examination with a slit lamp can confirm the diagnosis of corneal injury. If perforation has occurred, prompt repair can then be accomplished. For abrasions, antibiotic ointment followed by patching can lessen the patient’s pain. The ophthalmologist determines the need for follow-up.

PREVENTION

Figure 184–3 ■ Grade I chemical burn with punctate keratitis (the mildest form).

Awareness of the risk for ophthalmic injury is paramount to prevent such occurrences. With proper planning, it is possible to eliminate most manipulations and potentially damaging objects that may be injurious to the eyes. Although the first report of corneal abrasion during induction of anesthesia was published in 1987, such injuries continue to occur. The recommendation by Watson and Moran to protect the patient’s eyes before laryngoscopy (or, for that matter, any maneuvers or manipulations related to airway management) is strongly supported. Intraoperatively, simple manual eyelid closure can be effective in supine patients for brief procedures distant from the head and neck. However, not all patients have complete

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Table 184–1

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Mechanism of Injury

Total No. (%) of Eye Injuries (N = 71)

Patient movement Chemical injury Direct trauma Pressure on eye Other Unknown

21 9 6 2 3 30

No. (%) of Corneal Abrasions (n = 25)

(30) (13) (8) (3) (4) (42)

0 1 (4) 4 (16) 0 0 20 (80)

From Gild WM, Posner KL, Caplan RA, Cheney FW: Eye injuries associated with anesthesia: A closed claims analysis. Anesthesiology 76:204-208, 1992.

Table 184–2

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Causes of Chemical Damage to the Cornea

Hibiclens (chlorhexidine gluconate, 4% isopropyl alcohol with a detergent) pHisoHex (3% hexachlorophene and a detergent) Lavacol (70% ethanol) Betadine surgical scrub (7.5% povidone-iodine scrub with a detergent) Tincture of iodine (2% iodine, 2.35% sodium iodate, 46% ethanol) Detergent-containing iodine-based products From MacRae SM, Brown B, Edelhauser HF: The corneal toxicity of presurgical skin antiseptics. Am J Ophthalmol 97:221–232, 1984.

lid closure at rest, and any exposed cornea is at risk for desiccation and abrasion. Instillation of methylcellulose drops or petroleum-based ointment in the conjunctival sac below the lower eyelid is protective against corneal abrasion (Fig. 184-4). However, petroleum-based ointments may not afford protection against other ophthalmic complications, such as postoperative loss of visual acuity or blurred vision. Siffring and Poulton reviewed four comparable groups of patients in their study of eye care techniques to prevent ophthalmic complications during general anesthesia (Table 184-3). Blurred vision and reduction in visual acuity (both self-limited) were noted in the two groups that received eye ointment and tape. In contrast, those receiving

Frontal sinus Levator palpebrae muscle

Orbital fat

Gland of Krause

Orbicularis oculi muscle

Gland of Wolfring

Orbital septum Levator palpebrae aponeurosis Skin

Superior tarsal muscle

Meibomian gland in tarsal plate

Conjunctiva

Eyelash

Lower eyelid retractors

Figure 184–4

■

Schematic cross section of the orbit and eyeball.

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Table 184–3

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Eye Care Routines and Postoperative Ophthalmic Complications

Group A. Lacri-Lube and tape B. Duratears ointment and tape C. Isopto Alkaline drops (methylcellulose) and tape D. Hypoallergenic paper tape alone

% Corneal Abrasions

% Blurred Vision (Hours)

0 0 0

75 (7.4) 55 (4.5) <3

0

<3

Visual Acuity (by Lines Decreased) −1.9 −1.3 0 0

% Sensation of Foreign Body (Hours) 62.5 (5.2) 42 (3.5) <3 <3

From Siffring PA, Poulton TJ: Prevention of ophthalmic complications during general anesthesia. Anesthesiology 66:569-570, 1987.

eye tape only or methylcellulose drops plus eye tape rarely experienced these complications. In the study by Boggild-Madsen and colleagues, methylcellulose proved to be superior to a paraffin-based ointment. However, in almost all patients whose eyes were protected with methylcellulose, their eyelids were virtually “glued” closed, making periodic intraoperative evaluation of pupil signs difficult. Manecke and associates reported corneal injury in one patient, which was attributed to a preservativecontaining eye lubricant. The application of tape to close the eyelid can protect the cornea. However, this measure obscures pupillary signs and may leave adhesive residue on the periocular tissues and eyelashes.1 Also, removing the tape may remove a ribbon of eyelid epithelium. If the tape is not removed in a downward fashion (so that the eyelids remain closed during tape removal), there is a risk of stripping off the corneal epithelium and abrasion. In addition, allergy to adhesives is not uncommon. Gauze eye pads or protective eye goggles are indicated if the head is not supine and visible to the anesthesiologist (e.g., lateral or prone positioning, head or neck surgery with drapes covering the head, use of a head wrap, upper airway surgery). Although some clinicians advocate the routine use of eye goggles, a good fit can be challenging owing to interpatient variability in head size, interpupillary

1 This is likely less of a risk with synthetic (clear or slightly opaque) tape than with cloth adhesive tape.

distance, and so forth. Also, such eye goggles must be disposable or disinfected. Finally, patients should not use mascara on the morning of surgery or should be assisted in its removal before the induction of general anesthesia. Those who wear contact lenses must remove them if general anesthesia is planned, to avoid damage to the cornea or lenses. Finally, placement of the pulse oximeter probe on a finger other than the index finger (e.g., the fourth or fifth digit) is recommended to prevent self-inflicted corneal abrasion during the patient’s emergence from anesthesia.

Further Reading Boggild-Madsen NB, Bundgaard-Nielsen P, Hammer U, et al: Comparison of eye protection with methylcellulose and paraffin ointments during general anesthesia. Can Anaesth Soc J 28:575-578, 1981. Gild WM, Posner KL, Caplan RA, et al: Eye injuries associated with anesthesia: A closed claims analysis. Anesthesiology 76:204-208, 1992. Glasser DB, Edelhauser HF: Toxicity of surgical solutions. Int Ophthalmol Clin 29:179-187, 1989. MacRae SM, Brown B, Edelhauser HF: The corneal toxicity of presurgical skin antiseptics. Am J Ophthalmol 97:221-232, 1984. Manecke GR, Tannenbaum DP, McCoy MD: Severe bilateral corneal injury attributed to a preservative-containing eye lubricant. Anesthesiology 93:1545-1546, 2000. Roth S, Thisted RA, Erickson JP, et al: Eye injuries after nonocular surgery: A study of 60,965 anesthetics from 1988 to 1992. Anesthesiology 85:1020-1027, 1996. Siffring PA, Poulton TJ: Prevention of ophthalmic complications during general anesthesia. Anesthesiology 66:569-570, 1987. Watson WJ, Moran RL: Corneal abrasion during induction. Anesthesiology 66:440, 1987.

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Stacey L. Allen and Ellen Duncan

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Open Globe Injury Case Synopsis A 12-year-old boy presents to the emergency department after being hit in the left eye by a BB from a BB gun. He had eaten a full lunch 1 hour before the accident.

PROBLEM ANALYSIS Definition By the history, this patient has an open globe injury. Blindness can be a disastrous consequence of such an injury and may result from an elevation of intraocular pressure (IOP) and extrusion of the contents of the globe.

30 to 40 mm Hg. Poorly applied cricoid pressure may block venous drainage from the eye.

Implications Following induction of anesthesia, the administration of succinylcholine can increase IOP in the intact eye by 6 to 8 mm Hg within 4 minutes. IOP returns to baseline in 5 to 7 minutes. In the open globe, however, the IOP is atmospheric pressure.

Recognition Generally, the diagnosis of open globe injury can be surmised from the history of a penetrating injury to the globe. This may involve a BB shot, wood pieces, or an industrial accident, or it may be the result of blunt or multiple trauma. In any patient who sustains trauma to the head, the globe and vision must be evaluated. Conversely, when open globe injury is present, other coexisting injuries should be ruled out, such as skull fracture, intracranial trauma, neck injury, and thoracic or abdominal bleeding.

Risk Assessment The most common risk associated with open globe injury is a full stomach. This risk involves not only the possibility of aspiration of gastric contents but also the fact that drugs or maneuvers used to manage the patient can cause an increase in IOP (Table 185-1) and extrusion of the ocular contents, with subsequent loss of vision. Hypoxemia may raise IOP via vasodilatation of the choroidal arteries. Sustained hypertension may increase IOP, and induced hypotension may decrease IOP. Vomiting, coughing, or “bucking” causes the most dramatic increase in IOP by causing congestion in the venous system, impeding the outflow of aqueous humor, and increasing the volume of choroidal blood. This increase in pressure may be as high as

Table 185–1

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Drugs or Factors That May Increase Intraocular Pressure

Hypoxemia, hypercarbia, acidosis Hypertension Coughing, vomiting, laryngoscopy, tracheal intubation Excessive cricoid pressure Ketamine, succinylcholine Increased extraocular muscle tone Increased extraocular contents (tumor, hemorrhage)

MANAGEMENT Preoperatively, a detailed history of previous medical conditions should be obtained. The clinician should take measures to decrease or avoid increasing IOP (Table 185-2). Large doses of narcotics should be avoided because they can cause nausea and vomiting. Prophylaxis against aspiration may include a nonparticulate antacid, metoclopramide to enhance gastric emptying, and an H2-receptor antagonist to elevate gastric fluid pH and reduce gastric acid production. Periocular local anesthesia with intravenous sedation may be considered, depending on the patient’s status, the surgeon’s willingness, associated injuries, and the severity of the open globe injury. General anesthesia is usually preferred, however. The patient should be preoxygenated, and pressure on the eye by the facemask should be avoided. Although the use of succinylcholine is controversial, the rise in IOP can be lessened by pretreatment with a nondepolarizing drug and an induction dose of propofol or thiopental. Rapid-sequence induction can be accomplished without succinylcholine, using a nondepolarizing agent after preoxygenation, cricoid pressure, and induction with propofol or sodium pentothal. Rocuronium 1.2 mg/kg can be used for rapid-sequence induction (thereby shortening the time to relaxation to approximately 60 seconds). Alternatively, vecuronium 0.25 mg/kg provides intubating conditions in 60 to 90 seconds, and pancuronium 0.2 mg/kg in 90 seconds.

Table 185–2

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Drugs or Factors That May Decrease Intraocular Pressure

Hypothermia Inhalational anesthetics Hyperventilation (hypocarbia, alkalosis) Central nervous system depressants Reduced extraocular muscle tone

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Pancuronium may actually decrease IOP. A disadvantage of vecuronium and pancuronium, however, is the prolonged duration of neuromuscular blockade. Further, a priming dose of any nondepolarizing muscle relaxant can be used to hasten the onset of effect of the subsequent intubating dose of the same agent.1 Ketamine’s effect on IOP is controversial; however, it may cause nystagmus and blepharospasm and therefore should not be used in ophthalmologic surgery. Etomidate may decrease IOP, but it can cause unpredictable myoclonus, with consequent elevation of IOP. Postoperatively, before extubation, the stomach should be decompressed, the oropharynx suctioned, and an antiemetic such as a serotonin antagonist administered. Intravenous lidocaine (1.5 mg/kg) may be given to reduce coughing during emergence.

PREVENTION ●

●

●

●

Take the necessary precautions to prevent coughing, straining, bucking, and vomiting. Try to minimize hypercarbia, hypoxia, and increases in blood pressure. Attempt to minimize the risk of aspiration while ensuring the patient’s safety. Provide prophylaxis for postoperative nausea and vomiting with H2-receptor antagonists, metoclopramide, and nonparticulate antacids.

1 The editor has done this with rocuronium. Relaxation sufficient for endotracheal intubation is achieved in about 60 seconds, and sometimes in less than 45 seconds.

Further Reading Berry JM, Merin RG: Etomidate myoclonus and the open globe. Anesth Anal 69:256-259, 1989. Cook JH: The effect of suxamethonium on intraocular pressure. Anesthesia 36:359-365, 1981. Cunningham AJ, Barry P: Intraocular pressure: Physiology and implications for anesthetic management. Can Anaesth Soc J 33:195-208, 1986. Konchiergeri HN, Lee YE, Venugopal K: Effect of pancuronium on intraocular pressure changes induced by succinylcholine. Can Anaesth Soc J 26:479-484, 1979. Libonati MM, Leahy JJ, Ellison N: The use of succinylcholine in open eye surgery. Anesthesiology 62:637-640, 1985. Mehta MP, Choi WW, Gergis SD, et al: Facilitation of rapid endotracheal intubations with divided doses of nondepolarizing neuromuscular blocking drugs. Anesthesiology 62:392-395, 1985. Naguib M, Abdulatif M, Gyasi HK, et al: Priming with atracurium: Improving intubating conditions with additional doses of thiopental. Anesth Analg 65:1295-1299, 1986. Peuler M, Glass DD, Arens JF: Ketamine and intraocular pressure. Anesthesiology 5:575-578, 1975. Schwarz S, Ilias W, Lackner F, et al: Rapid tracheal intubation with vecuronium: The priming principle. Anesthesiology 62:388-391, 1985. Scott IU, McCabe CM, Flynn HW, et al: Local anesthesia with intravenous sedation for surgical repair of selected open globe injuries. Am J Ophthalmol 134:707-711, 2002. Taboada JA, Rupp SM, Miller RD: Refining the priming principle for vecuronium during rapid-sequence induction of anesthesia. Anesthesiology 64:243-247, 1986.

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Wendy B. Kang

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Retrobulbar Block Case Synopsis Monitored anesthesia care is provided for an active 70-year-old patient undergoing extracapsular cataract extraction and intraocular lens implantation. The patient has stable hypertension, coronary artery disease, mild emphysema, and renal insufficiency. Sedation with 1 mg midazolam and 50 μg fentanyl is administered, along with verbal reassurance, while the ophthalmologist performs a retrobulbar block. Surgery is uneventful, and vital signs are stable. After 30 minutes in the darkened operating room, the surgical drapes are removed to reveal a patient who cannot be awakened.

PROBLEM ANALYSIS Definition Cataract surgery is likely the most frequently performed surgical procedure in industrialized nations. Yet many anesthesiologists are unaware of the potential complications associated with the use of regional anesthesia in ocular surgery, either from a lack of technical familiarity or from a lack of follow-up in predominantly same-day surgical patients. Anesthesiologists must be aware of the consequences of local anesthetic injections into a patient’s eye, whether performed by the anesthesiologist or by the surgeon. In 2001 the Royal College of Anaesthetists and Royal College of Ophthalmologists issued guidelines encouraging the involvement of physician anesthetists in the administration of local anesthesia, rather than merely providing monitored anesthesia care. A review of the literature reveals a continuing and pervasive use of retrobulbar blocks along with newer techniques, such as peribulbar, episcleral, or sub-Tenon’s capsule local anesthetic injections, as well as the use of topical anesthesia in the eye. The goals of ocular regional anesthesia are akinesia and analgesia, both for patient comfort and for safety. Retrobulbar block combined with facial nerve block has been the standard regional anesthetic technique for more than a century. It provides superior akinesia, anesthesia, and analgesia compared with other regional techniques. Indications for retrobulbar block are as follows: ●

●

●

Avoidance of general anesthesia in elderly patients, who may have multiple medical comorbidities Achievement of optimal surgical conditions for extracapsular cataract extraction, phacoemulsification, intraocular lens implantation, and open globe surgery (e.g., vitrectomy, glaucoma treatment, repair of retinal detachment) Prolonged, difficult surgeries (e.g., in a patient who has had previous eye surgery) or in patients with hard cataracts or nystagmus Contraindications to retrobulbar block are as follows:

● ●

True allergy to local anesthetic drugs Patient refusal, despite explanations regarding the use of intravenous sedation and lack of intraoperative awareness

●

Patient inability to cooperate (e.g., severe restless leg syndrome)

The operating room team must determine its own level of comfort concerning contraindications to local anesthetic blocks. The diverse spectrum of “uncooperative” patients (e.g., impaired mental status, youth, dementia, deafness, severe emphysema or congestive heart failure, inability to keep still, excessive anxiety) can often be managed safely with regional anesthesia and monitored anesthesia care. Coagulation abnormalities must also be considered, and there is considerable variation among institutions regarding what is acceptable. Available evidence suggests that patients who take nonsteroidal anti-inflammatory drugs, aspirin, or warfarin can undergo eye surgery safely. The question of whether a patient with uncontrolled glaucoma or recent surgery on the same eye should undergo regional anesthesia is best answered by a discussion among the surgeon, the anesthesia care provider, and the patient, rather than relying on rigid adherence to institutional policies.

Recognition COMPLICATIONS Complication rates with regional anesthesia vary and range from 1 in 1300 to 1 in 16,000 for globe perforation and 1 in 300 to 1 in 500 for brainstem anesthesia (Table 186-1). The reported incidence for ocular perforation is 0.114%. In one retrospective review, there was a 0.25% incidence of anesthesia-related diplopia, with retrobulbar block accounting for 0.39% of cases.

Table 186–1

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Complications of Retrobulbar Block

Retrobulbar or peribulbar hemorrhage Globe penetration or perforation Optic nerve damage leading to visual changes, including blindness Central nervous system depression leading to brainstem anesthesia Severe symptomatic activation of oculocardiac reflex Diplopia and eye muscle imbalance

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With retrobulbar block, hematomas can occur subconjunctivally or as hyphemas in the anterior chamber of the eye. Although visually striking, these are not as dangerous as more hidden retrobulbar hemorrhages within the extraocular muscles. These can cause edema or paresis and result in vertical or horizontal ophthalmoplegia, diplopia, strabismus, or hyper- or hypotonia. Bleeding within the extraocular muscles or damage to the central retinal artery or vein increases intraocular pressure, which may lead to optic nerve compression, ischemia, and subsequent loss of vision. Penetration of the optic globe sufficient to cause perforation results in loss of vitreous humor. Mild eye compression is used after retrobulbar block. A sudden loss of firmness to palpation may signal the loss of vitreous humor. This can progress to optic neuropathy. Mental status changes (as in the case synopsis) may result from direct injection of local anesthetic into the dural cuff along the optic nerve or into a blood vessel. Depending on the amount of local anesthetic reaching the subarachnoid space, the patient may exhibit drowsiness, obtundation, vomiting, convulsions, or contralateral blindness. If the local anesthetic reaches the optic chiasm, complete respiratory and cardiac arrest may occur (i.e., the ultimate “high spinal”). Activation of the oculocardiac reflex may trigger bradycardia, asytole, or other arrhythmias. Ocular injection; pressure on the globe; or traction on the extraocular muscles, conjunctiva, or globe transmits signals through the ophthalmic branch of the trigeminal nerve to the vagus nerve. Young children who have not received atropine pretreatment are especially prone to the oculocardiac reflex. Anecdotal case reports describe severe orbital cellulitis in immunocompromised patients, myopic staphylomas, chemosis, and acute pulmonary edema concurrent with trigeminal nerve block as complications associated with retrobulbar block.

oculomotor, abducens, and optic nerves run within the cone behind the globe, along with the central retinal artery and vein. Importantly, the dural cuff surrounds the optic nerve. The ophthalmic division of the intracranial trigeminal nerve divides into the lacrimal, frontal, and nasociliary nerves. Extraconal and conjunctival sensations are supplied by the first two of these nerves. Branches of the nasociliary provide innervation to the intraconal portion, cornea, sclera, iris, and ciliary body of the eye. Block of the anterior ethmoidal nerve, another branch of the nasociliary nerve, results in nasal stuffiness. The ciliary ganglion of the nasociliary nerve lies near the apex of the retrobulbar cone; therefore, it is associated with the optic nerve and artery. Parasympathetic fibers from the Edinger-Westphal nucleus accompany the oculomotor nerve and synapse in its ganglion, whereas sensory and sympathetic fibers from T1 continue through the ganglion. Its efferent nerve, the short ciliary nerve, travels anteriorly to provide sensation to the globe and autonomic motor function to the iris.

ANATOMIC CONSIDERATIONS

The following are risk factors for complications associated with retrobulbar block:

To understand how complications occur with retrobulbar block and other regional anesthesia techniques used for ophthalmic surgery, a brief review of the ocular anatomy is necessary (Fig. 186-1). The extraocular muscles surround the globe and form the cone. The lateral rectus is supplied by the abducens (sixth cranial) nerve, the superior oblique by the trochlear (fourth cranial) nerve, and the other muscles by the oculomotor (third cranial) nerve. The nasociliary,

TECHNIQUE All sensory and motor nerves can be blocked by injection into either the optic cone (retrobulbar block) or the orbital fat (peribulbar block). For retrobulbar block, the needle is placed from the inferolateral orbital rim to past the equator of the globe, before turning medially and inward. Ideally, the needle enters between the inferior and lateral rectus muscles, behind the globe, and within the space bounded by the extraocular muscles. Upon injection, the pulsatile ocular blood flow decreases, even in the absence of changes in intraocular pressure.

Risk Assessment

●

●

● ●

Technical inexperience on the part of the surgeon or anesthesiologist Use of a sharp needle and an insertion depth greater than 25 mm Long axial length of a myopic eye (long, thin globe) Left inferior rectus muscle injection by a right-handed physician

Cross section of the eye

Superior rectus muscle Choroid layer

Cornea

Bone Superior oblique muscle

Eyelid Vitreous body

Iris

Medial rectus muscle

Macula Retina Optic nerve to brain

Lens

Inferior oblique Muscles of the eye muscle

Sclera Figure 186–1

Lateral rectus muscle Inferior rectus muscle

■

Anatomy of the eye relevant to the performance of retrobulbar block.

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Use of excessive volume (≥4 to 5 mL) of local anesthetic, which may lead to “compartment syndrome” ● An uncooperative patient It is unclear how the type of local anesthetic used or the inclusion of hyaluronidase affects the risk of complications. Inadequate blockade of the extraocular muscles can result in increased pain and squinting. For extracapsular cataract extraction or phacoemulsification, complete akinesia is seldom necessary for the safe performance of surgery. ●

Implications Owing to the serious sequelae of retrobulbar hemorrhage and globe perforation, alternative regional anesthesia techniques continue to be developed. A peribulbar deposition technique was described by Davis and Mandel in 1986. It is theoretically extraconal, going no deeper than the globe equator. However, there is no assurance against accidental intraconal injection. Also, larger volumes of local anesthetic, with up to two injections at the superomedial and inferolateral quadrants, raise intraocular pressure, with potential adverse sequelae. The sub-Tenon’s, or episcleral, space is the cavity formed by Tenon’s capsule (a fascial layer surrounding the globe and extraocular muscles) and the sclera. Stevens in 1992 described medial quadrant infiltration of local anesthetic with a blunt-tipped cannula. In contrast to retrobulbar or peribulbar block, sub-Tenon’s block is relatively painless. The local anesthetic diffuses through the fenestrated posterior Tenon’s capsule into the retrobulbar cone and periorbital tissues, causing akinesia of the globe and eyelid; such akinesia may be incomplete, however. There have also been case reports of complications similar to those associated with retrobulbar and peribulbar block. The use of subconjunctival and topical anesthesia with intravenous sedation has increased since the mid-1990s. Ease of administration, rapid placement, lack of painful injections, and minimal complications have made this technique popular. Unfortunately, the eye is not akinetic, and the patient must be able to cooperate during the procedure. Patients have also experienced pain with the superior rectus fixation suture and during cautery of scleral vessels.

MANAGEMENT An anesthesiologist’s presence continues to be vital to the well-being of any patient undergoing ophthalmic surgery. Maintaining communication with the patient (through intermittent hand squeezes) is as important as monitoring the blood pressure, electrocardiogram, capnography, and pulse oximetry. In the event of extensive ocular hemorrhage or global perforation, the opinion of the ophthalmologist should guide further treatment. Surgery may be deferred or changed (e.g., progressed to a scleral buckle procedure).

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Cardiopulmonary sequelae are easily managed by an alert anesthesiologist. Airway management and circulatory support with vagolytic or anticonvulsive medications may be used until the patient returns to his or her preoperative status.

PREVENTION Knowledge of ocular anatomy and its proximity to intracranial structures and a continuing dedication to improving one’s regional anesthesia skills can help reduce the incidence of serious complications. The use of short, 2.5- to 3-cm blunt needles and small volumes (3 to 4 mL) of local anesthetics is prudent. A minimal needle insertion depth (< 25 mm) and stopping the insertion if the patient complains of severe pain can lower the likelihood of touching the globe or the dura. The eye should remain in the primary neutral gaze or in a slightly down and outward gaze during local anesthetic injection. Judicious amounts of oral or intravenous sedatives can relieve anxiety and hypertension before injection. The patient must be cooperative, which is facilitated by providing verbal reassurance.

Further Reading Bellucci, R: Anesthesia for cataract surgery. Curr Opin Ophthalmol 10:36-41, 1999. Canavan KS, Dark A, Garrioch MA: Sub-Tenon’s administration of local anaesthetic: A review of the technique. Br J Anaesth 90:787-793, 2003. Davis DB, Mandel MR: Posterior peribulbar anesthesia: An alternative to retrobulbar anesthesia. Cataract Refract Surg 12:182-184, 1986. Edge R, Navon S: Scleral perforation during retrobulbar and peribulbar anesthesia: Risk factors and outcomes in 50,000 consecutive injections. J Cataract Refract Surg 25:1237-1244, 1999. Gómez-Arnau JI, Yangüela J, González A, et al: Anaesthesia-related diplopia after cataract surgery. Br J Anaesth 90:189-193, 2003. Jacobi PC, Dietlein TS, Jacobi FK: A comparative study of topical vs retrobulbar anesthesia in complicated cataract surgery. Arch Ophthalmol 228:1037-1043, 2000. Kallio H, Paloheimo M, Maunuksela E-L: Haemorrhage and risk factors associated with retrobulbar/peribulbar block: A prospective study in 1383 patients. Br J Anaesth 85:708-711, 2000. Kwinten FA, de Moor GP, Lamers R: Acute pulmonary edema and trigeminal nerve blockade after retrobulbar block. Anesth Analg 83:1322-1324, 1996. Nouvellon E, L’Hermite J, Chaumeron A, et al: Ophthalmic regional anesthesia: Medial canthus episcleral (sub-Tenon) single injection block. Anesthesiology 100:370-374, 2004. Ripart J, Lefrant J-Y, Vivien B, et al: Ophthalmic regional anesthesia: Medial canthus episcleral (sub-Tenon) anesthesia is more efficient than peribulbar anesthesia: A double-blind randomized study. Anesthesiology 92:1278-1285, 2000. Rüschen H, Bremner FD, Carr C: Complications after sub-Tenon’s eye block. Anesth Analg 96:273-277, 2003. Stevens JD: A new local anesthesia technique for cataract extraction by one quadrant sub-tenon’s infiltration. Br J Ophthalmol 76:670-674, 1992. Taylor G, Devys JM, Heran F, et al: Early exploration of diplopia with magnetic resonance imaging after peribulbar anaesthesia. Br J Anaesth 92:899-901, 2004. Thind GS, Rubin AP: Local anaesthesia for eye—no room for complacency. Br J Anaesth 86:473-476, 2001.

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Laryngoscopy and Microlaryngoscopy

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Susan H. Noorily Case Synopsis A 50-year-old man with a vocal cord lesion is undergoing microlaryngoscopy with possible biopsy or laser excision of the lesion. The patient is hemodynamically stable until the surgeon exposes the larynx with the operating laryngoscope and applies the suspension apparatus. At this time, the patient becomes hypertensive (blood pressure 200/118 mm Hg) and has multiform ventricular bigeminy on the intraoperative electrocardiogram (ECG) (Fig. 187-1).

PROBLEM ANALYSIS Definition Cardiovascular complications (e.g., myocardial infarction, ischemia, arrhythmias) have been reported with increasing frequency in patients having laryngeal microsurgery. Stimulation caused by laryngeal instrumentation or manipulation can result in adrenergic stress responses, leading to hypertension, tachycardia, and arrhythmias. Pressure of the laryngoscope blade and stretching of laryngeal structures during suspension laryngoscopy stimulate deep sensory receptors in the larynx and provoke cardiac arrhythmias. Because these sensory receptors are deep within the laryngeal musculature, they are not blocked by topical anesthesia. The reflex pathway believed to be responsible for the arrhythmias includes the afferent fibers of the superior laryngeal nerve and the cardioinhibitory fibers of the vagus nerve. Patients undergoing laryngoscopy and microlaryngoscopy are at risk for other complications as well. Abnormal airway anatomy places some patients at risk for difficult tracheal intubation. Also, they are at risk for airway compromise both during and after the procedure. Some who met extubation criteria in the operating room require reintubation in the postanesthesia care unit (PACU), especially

II

V

Figure 187–1 ■ Intraoperative electrocardiogram (leads II and V). Note the frequent premature ventricular contractions (beats).

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those who required extensive airway manipulation or laryngeal biopsy. Patients having bronchoscopy and esophagoscopy are at risk for pneumothorax and esophageal perforation. Finally, those undergoing airway laser surgery are at risk for airway and facial burns. A recent prospective study of complications during suspension laryngoscopy concluded that this was a relatively safe procedure because no life-threatening complications occurred in 339 consecutive patients. The most common complications were minor mucosal injuries (75% of patients), dental injuries (6.5%), and injuries to the lingual (2.6%) or hypoglossal (1.1%) nerve.

Recognition Diligent monitoring is required to diagnose early hemodynamic or ECG changes before irreversible myocardial injury occurs. In most cases, such changes appear minutes after the surgeon exposes and suspends the larynx. Constant vigilance is also required to diagnose airway compromise perioperatively. Maximal laryngeal edema occurs 1 hour after extubation, so patients must be closely observed in the PACU during that period.

Risk Assessment The patient’s physical status influences the incidence of complications. In particular, patients with preoperative cardiovascular disease are at increased risk for cardiac complications during laryngoscopy and microlaryngoscopy. Further, hypoxia and hypercarbia make the heart more susceptible to insult, as does the presence of excess endogenous catecholamines. Some patients are at high risk for airway complications. Risk factors include a history of chronic pulmonary disease, smoking, radiation therapy, and previous head and neck surgery. Other risk factors are the presence of an advanced tumor involving the upper airway, extensive surgical airway

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manipulation, and laryngeal biopsy, any of which can increase bloody secretions. Patients undergoing airway laser surgery are at greatest risk for airway and facial burns when the laser is exposed to flammable inhaled gases or materials (e.g., oxygen, nitrous oxide, nonmetallic endotracheal tubes; see Chapters 138 and 139).

●

Implications

PREVENTION

Hypertension and arrhythmias occurring in response to laryngoscopy are often transitory and are usually without sequelae. In some patients, however, these changes persist and can be associated with myocardial ischemia, myocardial infarction, and even death. Airway compromise can result in hypoxia, hypercarbia, pulmonary edema, respiratory arrest, and death. Laser-related complications can result in burns, airway obstruction, pulmonary injury, and death.

MANAGEMENT Cardiovascular Complications When hypertension or arrhythmias occur during suspension laryngoscopy, ask the surgeon to release the laryngoscope pressure for a few minutes. During that time, anesthesia can be deepened and adequate oxygenation and ventilation confirmed. Antiarrhythmic drugs (e.g., lidocaine, atropine, β-blocker) may be indicated, but only if arrhythmias persist and are associated with circulatory insufficiency (see Chapter 79). If cardiovascular complications persist, consider terminating the procedure and rescheduling it, at which time preoperative superior laryngeal nerve blocks can be placed as a preemptive measure. Also, a postoperative 12-lead ECG should be obtained, along with evaluation by a cardiologist, if indicated. This cardiac evaluation can take place outside the hospital or ambulatory surgery PACU. If there are new or previously undiscovered but relevant cardiovascular findings, these must be addressed before the rescheduled procedure.

● ●

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Ventilate the patient by mask before reintubation for bronchoscopy. Use bronchoscopy to assess the extent of airway injury. Admit the patient to an intensive care unit for observation and supportive care.

Cardiovascular Complications The risk of cardiovascular complications can be minimized by ensuring adequate oxygenation and ventilation at all times. The patient must be well anesthetized before surgical manipulation. Small doses of a narcotic (e.g., 1 to 2 μg/kg fentanyl) may attenuate circulatory responses to microlaryngoscopy. Lidocaine and β-blockers may offer some benefit. Pediatric patients are often pretreated with anticholinergics. Consideration should be given to preoperative placement of a superior laryngeal nerve block in high-risk patients. Surgical manipulations should be as gentle as possible, and the procedure should be abandoned if refractory cardiac complications occur.

Airway Complications The risk of airway complications can also be minimized. The surgeon must be present in the operating room during the induction of anesthesia. Awake intubation should be performed on patients with suspected difficult airways. Glycopyrrolate is administered as a drying agent to improve surgical exposure and thereby limit airway manipulation. Steroids (e.g., 10 mg intravenous dexamethasone) are administered intraoperatively to limit edema formation. Obstructive airway tumors are debulked. In some patients, a tracheotomy may have to be performed. Patients are extubated awake and observed closely in the PACU for at least 1 hour. Again, a tracheotomy set should be readily available. Vigilance throughout the perioperative period is extremely important.

Airway Complications

Laser Airway Fire

If a difficult intubation is encountered unexpectedly, follow the American Society of Anesthesiologists algorithm for difficult intubation (see Chapters 40 and 41). At times, establishing a surgical airway can be lifesaving. All patients require supplemental oxygen in the recovery room, and close monitoring is essential for at least 1 hour. Patients with postoperative stridor should be treated with racemic epinephrine and steroids. The surgeon must be notified if a patient shows signs of airway compromise. An emergency tracheotomy setup must be available, and some patients require tracheal reintubation. The need for this is usually apparent within 1 hour of extubation. Supportive care is continued as necessary.

Laser Airway Fire

Several precautions may help prevent laser airway fires. The patient and operating room personnel must wear eye protection. Areas of tissue that might come into contact with the carbon dioxide laser beam (e.g., eyes, skin) are covered with moist pads or towels. Anesthesia can be administered without an endotracheal tube (e.g., jet ventilation). Nonmetal endotracheal tubes are combustible and can ignite, but special metal laser endotracheal tubes are available and safe. The endotracheal tube cuff is filled with saline and surrounded by moist cottonoids. Ideally, the inspired oxygen concentration is kept at or below 30%, and nitrous oxide is avoided. Either air (nitrogen) or helium can be mixed with the oxygen. The laser should be used with the minimum required power. Muscle relaxants are often used to prevent patient movement during use of the laser.

A laser airway fire is managed according to the following protocol:

Further Reading

● ●

Discontinue oxygen and extubate the patient. Douse any flames with saline or water.

Hendrix RA, Ferouz A, Bacon CK: Admission, planning and complications of direct laryngoscopy. Otolaryngol Head Neck Surg 110:510-516, 1994.

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Hill RS, Koltai PJ, Parnes SM: Airway complications from laryngoscopy and panendoscopy. Ann Otol Rhinol Laryngol 96:691-694, 1987. Klussmann JP, Knoedgen R, Wittekindt C, et al: Complications of suspension laryngoscopy. Ann Otol Rhinol Laryngol 111:972-976, 2002. Sosis M: Anesthesia for laser surgery. Int Anesth Clin 28:119-131, 1990. Strong MS, Vaughan CW, Mahler DL, et al: Cardiac complications of microsurgery of the larynx: Etiology, incidence and prevention. Laryngoscope 84:908-920, 1974.

Wenig BL, Raphael N, Stern JR, et al: Cardiac complications of suspension laryngoscopy: Fact or fiction? Arch Otolaryngol Head Neck Surg 112:860-862, 1986. Werkhaven JA: Microlaryngoscopy-airway management with anaesthetic techniques for CO2 laser. Pediatr Anesth 14:90-94, 2004.

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Scott Holliday and Mary Ann Gurkowski

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NEUROSURGERY, OPHTHALMOLOGY, ENT

Foreign Body Aspiration Case Synopsis A 5-year-old girl was eating a candy bar containing peanuts when she began to choke. The mother firmly patted the child on the back, and she stopped choking. The next day the mother noted that the child’s breathing was fast and noisy. Her temperature was 100.8°F, and she had an unremitting cough.

PROBLEM ANALYSIS Definition Foreign body aspiration (FBA) is the introduction of solid matter into the airway at the level of the glottal opening, larynx, trachea, or bronchi. Complications associated with FBA can be either immediate or delayed. Immediate complications usually occur when the foreign body becomes lodged in the glottal opening, larynx, or trachea, partially or completely obstructing the movement of air to both lungs. Immediate complications include respiratory arrest, negative-pressure pulmonary edema, pneumothorax, pneumomediastinum, subcutaneous emphysema, hypoxic neurologic damage, and cardiac arrest. Delayed complications usually occur when the foreign body lodges in one of the main or distal bronchi, obstructing airflow to the lung distal to the blockage (Fig. 188-1). Delayed complications include recurrent pneumonia, bronchiectasis, and pyelopneumothorax.

Recognition FBA can occur in any age group, but it occurs most commonly in children younger than 4 years, with those younger

Figure 188–1

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Tooth in the left mainstem bronchus.

than 1 year accounting for the greatest percentage. In these young children, the most common foreign bodies apirated are food particles, such as vegetable matter (e.g., peanuts, sunflower seeds, other nuts). Processed food products (e.g., hot dogs, candy, gum), metallic objects (e.g., coins, jacks, pins), and plastic products (e.g., beads, small toy parts) constitute the majority of the remaining foreign bodies aspirated. The most recent national mortality data for choking in children (aged 14 years and younger) are from the year 2000. It was reported that 41% of deaths were from food matter, and 59% from other materials. The most recent data on unintentional, nonfatal choking episodes are from the U.S. Consumer Product Safety Commission, published in 2001. These data verified earlier data that in children younger than 14 years, food items (68.6%) were a more common cause of nonfatal choking than were nonfood items (31.4%). In adults, FBA is more common in older persons. Organic materials (e.g., fish bones, meat), medications (e.g., pills), and inorganic objects (e.g., artificial teeth) have all been reported. In adults, the occurrence of sudden death at restaurants caused by the aspiration of food was frequent enough that an article appeared in JAMA in the 1960s that coined the term “café coronary.” The type, size, shape, and location of the foreign body and the duration of time before FBA is diagnosed determine the clinical expression. A foreign body can migrate distally, which alters the signs, symptoms, and radiographic and clinical findings. Partial obstruction of a bronchus creates unilateral air trapping (emphysema) by means of a ballvalve mechanism, whereas complete obstruction causes atelectasis. The most commonly used diagnostic tools are the clinical history, physical examination, chest fluoroscopy, and plain, forced-expiratory, inspiratory-expiratory, and lateral neck films. The chest radiograph may be normal if the recently aspirated article is radiolucent. Consequently, a positive clinical history is often the most useful tool for diagnosing FBA. FBA symptoms include choking, irritative cough, shortness of breath, aphony, hoarseness, hemoptysis, and odynophagia or dysphagia. Clinical signs include reduced breath sounds on lung auscultation and dullness to percussion, cyanosis, wheezing, dyspnea, fever, rales, stridor, and subcutaneous emphysema. A conscious adult may use the universal distress signal for choking—grabbing the neck with one hand—when a foreign body has been aspirated and prevents vocalization. 753

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Risk Assessment

Choking Infants

As noted earlier, the incidence of FBA is greater in children than in adults. In 2001 the Centers for Disease Control and Prevention analyzed data from the National Electronic Injury Surveillance System—All Injury Program and reported that an estimated 17,537 children (aged 14 years or younger) were treated for choking-related episodes. The high rate of FBA among children was attributed to their tendency to put inappropriate foods and small objects (e.g., coins, toys) in their mouths. Also, children often run, laugh, and play while eating or holding objects in their mouths. Of nonfood objects, coins are the most common ones aspirated. There is also a gender difference, with a slightly higher incidence in males (50% to 60%) than in females. Both adults and children who do not adequately chew their food are at increased risk. Reports have cited aspiration of food as being the sixth most common cause of accidental deaths in all age groups, causing from 2500 to 3900 deaths per year in the United States. It has been hypothesized that children are at greater risk than adults for FBA because of the immaturity of the mechanisms that coordinate swallowing and respiration. Such coordination relies on a complex neuromuscular mechanism to ensure laryngeal closure during chewing and swallowing. This, as well as the neural control mechanisms for laryngeal closure, appear to be more efficient in adults than in young children. It has also been speculated that vegetable matter (e.g., peanuts, seeds) is so frequently aspirated because it can “float” over the laryngeal vestibule; it is thus likely to be aspirated on inspiration. In contrast, candies tend to adhere to the pharyngeal mucosa and pass into the esophagus more easily. Adults with a preexisting dysfunctional swallowing mechanism, such as stroke victims or those with nervous system degeneration (e.g., amyotrophic lateral sclerosis), have an increased risk of food aspiration.

If the infant is conscious:

Implications FBA carries a significant degree of morbidity and mortality. The latter is usually immediate due to sudden respiratory arrest, followed by cardiac arrest. Delayed mortality is not common but may result when the initial hypoxic insult leads to brain death or from an associated pulmonary infection, respiratory distress, and sepsis. Morbidity is more common than mortality and includes complications related to bronchoscopy to diagnose and remove the object, prolonged hospital stay, and need for surgical intervention. Further, delayed diagnosis can lead to prolonged treatment for nonresolved pneumonia or problems such as hemoptysis, pyelopneumothorax, or bronchiectasis.

MANAGEMENT Management for out-of-hospital FBA involves immediate remedial treatment for the choking victim. Recommended protocols have been developed by the American Heart Association.

1. Place the infant prone, resting on the rescuer’s forearm. Support the infant’s head by holding the jaw. 2. Use the heel of the hand to deliver five back blows between the shoulder blades. 3. Place the free hand and forearm on the infant’s back. Support the head and neck. Turn the infant supine. 4. With the infant supine, draped on the thigh, deliver five quick, downward chest thrusts, using two fingers placed one fingerbreadth below the nipple line. 5. Repeat the process until the object is expelled or the infant becomes unconscious. If the infant is unconscious: 1. Open the airway. Lift the chin using a tongue-jaw lift. Remove the foreign body only if it is visible in the mouth. 2. Attempt rescue breathing. If unsuccessful, reposition the head and reattempt ventilation. 3. If unable to ventilate, give five back blows and chest thrusts. Repeat steps 1, 2, and 3. 4. After approximately 1 minute, notify emergency medical services and resume efforts.

Choking Child or Adult If the person is conscious, with poor or no air exchange: 1. Apply the Heimlich maneuver (subcostal, upward abdominal thrusts) while the victim is standing or sitting. 2. Continue abdominal thrusts until the foreign body is expelled or the patient loses consciousness. If the person is unconscious: 1. Place the victim supine, and open the airway using a tongue-jaw lift. If the foreign body is visible, remove the object with a finger sweep. 2. Attempt rescue breathing. If unsuccessful, reposition the head and reattempt ventilation. 3. If there is no ventilation, kneel beside or straddle the hips of the victim. Place the heel of one hand on the abdomen above the navel and below the xiphoid process. Place the other hand on top of the first hand. 4. Press both hands into the abdomen with a quick upward thrust five times. 5. Open the airway with a tongue-jaw lift. If the foreign body is visible, remove it. If not, repeat steps 2 through 4 until ventilation is successful. 6. After approximately 1 minute, notify emergency medical services and resume efforts. Once in the hospital, if the foreign body lies in the supraglottic or glottic region, immediate removal is necessary to prevent total airway occlusion. In both adults and children, this is usually performed under general anesthesia with laryngoscopy or bronchoscopy. For adults, intravenous access is placed before induction. In children, intravenous access is established after induction to avoid agitating the

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child, which could dislodge the foreign body, creating total airway obstruction and respiratory arrest. The most common method for induction of anesthesia in both adults and children with FBA is inhalational induction with spontaneous ventilation. Positive-pressure ventilation poses a risk for dislodging the object, again creating the potential for complete airway obstruction. However, one retrospective case review suggested that even though this risk was present, there was no difference in morbidity between positive-pressure ventilation and spontaneous ventilation. The removal of a foreign body lodged in a bronchus usually requires urgent surgery. This involves nothing-bymouth status, prophylaxis for aspiration, and intravenous line placement. The urgency is greater if the object is more proximal than distal. Theoretically, in the former circumstance, coughing could dislodge the object and move it to the carina, where it has the potential to obstruct both mainstem bronchi. Most often, a rigid ventilating bronchoscope is used to remove the foreign body. Induction of anesthesia can be via either an inhalational or an intravenous technique. Nebulized racemic epinephrine may be used to decrease swelling around the object to allow easier removal. Thoracotomy and direct surgical removal may also be necessary. Postoperatively, depending on the location of the object and the duration of aspiration, racemic epinephrine, bronchodilators, antibiotics, steroids, and chest physiotherapy may be indicated. Postoperative hospitalization for monitoring is prudent.

PREVENTION The majority of FBA cases are preventable in both children and adults. The key to prevention in children is public education. Parents, caretakers, and manufacturers or suppliers of food and food products must be more aware of the causes of choking. With the development of federal consumer product safety standards regulating the minimum size of

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toys and toy parts for young children and product safety labeling, the incidence of FBA has decreased. The home is now the most common site for such occurrences. Vigilance on the part of those caring for children is important, as are methods of making the home environment safer. For example, children must be taught not to put things in their mouths and never to eat and run at the same time. Proper chewing habits for both children and adults can help prevent aspiration of large chunks of food. Finally, parents and caregivers should take courses to learn how to provide basic life support in the event that a choking episode occurs.

Further Reading Black RE, Johnson DG, Matlak ME: Bronchoscopic removal of aspirated foreign bodies in children. J Pediatr Surg 29:682-684, 1994. Centers for Disease Control and Prevention: Nonfatal choking-related episodes among children—United States, 2001. JAMA 288:2400-2402, 2002. Emergency Cardiac Care Committee and Subcommittees: American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiac care. II. Adult basic life support JAMA 268:2191-2194, 1992. Emergency Cardiac Care Committee and Subcommittees: American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiac care: V, VI, VII. JAMA 268:2251-2281, 1992. Gurkowski MA: Foreign body aspiration. In Bready LL, Mullins R, Noorily SH, et al (eds): Decision Making in Anesthesiology, 4th ed. Philadelphia, BC Decker (in press). Hoeve LJ, Rombout J, Pot DJ: Foreign body aspiration in children: The diagnostic value of signs, symptoms and pre-operative examination. Clin Otolaryngol 18:55-57, 1993. Litman RS, Ponnuri J, Trogan I: Anesthesia for tracheal or bronchial foreign body removal in children: An analysis of ninety-four cases. Anesth Analg 91:1389-1391, 2000. Reilly JS: Airway foreign bodies: Update and analysis. Int Anesth Clin 30:49-55, 1992. Schwartz AJ, Campbell FW: Cardiopulmonary resuscitation. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 2nd ed. Philadelphia, JB Lippincott, 1992, pp 1633-1642. Tan HKK, Tan SS: Inhaled foreign bodies in children—anaesthetic considerations. Singapore Med J 41:506-510, 2000. Wolach B, Raz A, Weinberg J, et al: Aspirated foreign bodies in the respiratory tract of children: Eleven years’ experience with 127 patients. Int J Pediatr Otorhinolaryngol 30:1-10, 1994.

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OBSTETRICS AND GYNECOLOGY

Hypertensive Disorders of Pregnancy

189 OTHER SURGICAL SUBSPECIALTIES

Curtis L. Baysinger Case Synopsis A 27-year-old woman, gravida 1, presents with 4 cm cervical dilatation and a fetus whose estimated gestational age is 38 weeks. Her blood pressure is 160/110 mm Hg; and she has 4+ patellar reflexes, right upper quadrant tenderness, and 4+ proteinuria. Her platelet count on admission was 145,000/mm3 but has decreased to 110,000/mm3. She is receiving 1 g/hour of intravenous magnesium sulfate (MgSO4) and oxytocin (Pitocin) augmentation. She and her obstetrician have requested epidural analgesia for labor.

PROBLEM ANALYSIS Definition The American College of Obstetricians and Gynecologists recognizes four categories of hypertension associated with pregnancy (Table 189-1): gestational hypertension, preeclampsia, eclampsia, and chronic hypertension. Gestational hypertension occurs in 6% to 17% of pregnancies, and 50% of women with gestational hypertension before 30 weeks of pregnancy develop preeclampsia. Preeclampsia presents after 20 weeks’ gestation, can be either mild or severe, and is diagnosed by hypertension with proteinuria (Table 189-2). It can also be associated with coagulopathies and liver dysfunction. Edema is no longer a diagnostic criterion, but it is often severe. Eclampsia is defined as the occurrence of convulsions unrelated to a preexisting neurologic disorder that occur in women who are preeclamptic. Preeclampsia superimposed on chronic hypertension or transient hypertensive disorders of unknown cause may also occur. The HELLP syndrome requires the presence of intravascular hemolysis, elevated liver enzymes, and low platelet count; it usually manifests earlier during pregnancy compared with other types of preeclampsia.

Table 189–1

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Classification of Hypertensive Disorders in Pregnancy

Gestational hypertension Preeclampsia Mild Severe Eclampsia Chronic hypertension with or without superimposed preeclampsia or eclampsia

Recognition Preeclampsia becomes severe with blood pressure greater than 160/100 mm Hg and evidence of end-organ damage, including the following: ● ●

●

●

●

Pulmonary edema Renal dysfunction—proteinuria of 4+ on dipstick testing or greater than 5 g in a 24-hour urine collection, or oliguria (< 500 mL in 24 hours) Cerebral manifestations, including headache, visual changes, or seizures (eclampsia) Elevated liver enzymes with right upper quadrant pain (secondary to hepatic capsular distention) Severe thrombocytopenia, with a platelet count less than 100,000/mm3

The last in association with the HELLP syndrome may occur with modest levels of blood pressure elevation. Also, parturients with acute cocaine intoxication may present with signs and symptoms of preeclampsia, including seizures, pulmonary edema, proteinuria, and thrombocytopenia.

Risk Assessment Preeclampsia occurs in 3% to 7.5% of all pregnancies, primarily in young primigravidas, and especially in those who do not receive prenatal care. It accounts for 20% of all maternal deaths. Maternal and neonatal morbidity increases with maternal age, gestational age of onset (especially when preeclampsia develops before 32 weeks’ gestation), and preexisting maternal diabetes, renal disease, or thrombophilia. The risk of preeclampsia is also increased in patients with uterine overdistention (e.g., multiple gestations, polyhydramnios), trophoblastic disease, obesity, and abnormal uterine artery Doppler studies between 18 and 24 weeks’ gestation. Parturients who develop preeclampsia in the second trimester have worse outcomes compared with those who develop it after 34 weeks’ gestation. These patients are also at 759

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Definition of Preeclampsia

Measure

Findings

Blood pressure (BP)

Increase in systolic or diastolic BP of 30 or 15 mm Hg, respectively Systolic, mean, or diastolic BP of 140/105/90 mm Hg taken at least 6 hr but <7 days apart 300 mg in 24 hr or 1+ (30 mg/dL) on two clean dipstick tests taken at least 6 hr but <7 days apart Fluid collection in nondependent part of the body or weight gain >5 pounds in 1 wk

Proteinuria Edema

greater risk for chronic hypertension and underlying renal disease or collagen vascular disease. Headache, visual disturbances, epigastric pain, severe refractory hypertension, progressive thrombocytopenia or liver function abnormalities, oliguria, and a poor fetal environment (determined by nonstress testing or biophysical profile, with estimated fetal weight below the 5th percentile) are ominous signs. Currently, there is no single cost-effective screening test that reliably predicts preeclampsia. Early in pregnancy, the vasculature becomes more sensitive to vasoconstrictors, perhaps owing to abnormally high levels of thromboxane compared with prostacyclin. Normal increases in renin, angiotensin II, and aldosterone, with reduced vascular sensitivity to catecholamines, fail to develop in patients with preeclampsia. This may be explained by endothelial cell injury, which reduces the synthesis of prostacyclin and nitric oxide. Plasma fibronectin levels, an indicator of endothelial damage, become elevated early in gestation in those who develop preeclampsia. The generalized pathophysiology suggests widespread endothelial damage in the face of general vasoconstriction. This is believed to cause end-organ damage and activation of the coagaulation system, including consumption of coagulation factors and platelets. Edema is attributed to salt and water retention, which is aggravated by decreased colloid osmotic pressure in the presence of proteinuria. Blood volume is reduced in most patients with preeclampsia compared with normotensive parturients. Sympathetic system activation most often leads to a hyperdynamic state in patients with severe preeclampsia, with increased cardiac output and normal to slightly increased systemic vascular resistance. However, pulmonary artery catheter studies have revealed a subset of patients with reduced blood volume, depressed left ventricular function, and markedly increased systemic vascular resistance.

Implications Edema of the airway, including the larynx, may occur. The risk of pulmonary edema is greatest after delivery, when colloid osmotic pressure is lowest. Thrombocytopenia secondary to consumptive coagulopathy occurs in 11% to 50% of patients with severe preeclampsia. Reduction in the platelet count to less than 100,000/mm3 is associated with other coagulation abnormalities and occurs more often with the HELLP syndrome. Intrinsic platelet dysfunction may also occur. Oliguria may result from low cardiac filling pressures and often responds well to fluid challenge. Less often, oliguria is associated with depressed cardiac function and very

high systemic vascular resistance. If so, afterload reduction is the treatment of choice. Uteroplacental blood flow decreases as a result of uterine artery vasospasm. Exaggerated reductions in uteroplacental blood flow may occur when vasopressors are used to treat hypotension, which may accompany the onset of regional blockade.

MANAGEMENT Obstetric Management Obstetric management includes judicious fetal delivery, prevention of eclampsia (seizures), fluid status optimization, and treatment of excessive increases in blood pressure (especially diastolic blood pressure >110 mm Hg). Delivery is indicated in mild preeclampsia with a gestational age greater than 37 weeks, fetal lung maturity, a favorable cervix, and increasing maternal blood pressure. Delivery is mandatory if hypertension is uncontrolled after 24 to 48 hours of therapy or with progressive renal dysfunction or thrombocytopenia, fetal stress, impending eclampsia, liver function values twice the upper limit of normal, or cardiopulmonary compromise. If possible, delivery is delayed for 48 hours after glucocorticoid administration to accelerate fetal lung maturity. With a preterm fetus, expectant management is safe if the blood pressure is well controlled, laboratory parameters stabilize, and the fetal environment is reassuring. Several studies have documented the effectiveness of MgSO4 for the prevention of seizures. For example, the British Eclampsia Trial Collaborative Group study found a 52% reduction in seizure activity with MgSO4. In this trial, MgSO4 was superior to diazepam or phenytoin for seizure prevention, although the use of phenytoin continues outside the United States. MgSO4 does not appear to alter the duration of labor or maternal coagulability or significantly affect uterine blood flow in parturients with epidural blockade. It is given as a 4- to 6-g bolus, with an infusion of 1 to 2 g/hour. Magnesium serum levels are checked every 8 hours to ensure therapeutic concentrations of 4 to 7 mg/dL. Loss of deep tendon reflexes precedes respiratory compromise with MgSO4 toxicity (see also Chapter 15). MgSO4 is ineffective as an antihypertensive agent because its vasodilatory effects are weak and transient. Instead, intravenous hydralazine is the more traditional therapy for hypertension during pregnancy, at a dose of 5 to 10 mg every 15 minutes. One recent study suggests that

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Anesthetic Management LABOR

AND

VAGINAL DELIVERY

Epidural analgesia provides superior pain relief and also has beneficial effects on placental blood flow. It can rapidly be converted to anesthesia for emergent cesarean delivery. Judicious volume loading and incremental dosing of local anesthetics reduce the risk of significant hypotension. Thrombocytopenia occurs in 15% to 20% of patients with severe preeclampsia. One should obtain a platelet count before performing regional anesthesia. Acute-onset thrombocytopenia is more ominous than the chronic variety. However, specific platelet count values that increase the risk for epidural hematoma are unknown. Platelet activity may be abnormal in severe preeclamptics with counts less than 100,000/mm3. Therefore, it is prudent to consider tests for platelet activity (platelet function analysis, thromboelastography) when the platelet count is less than 100,000/mm3, especially in patients with the HELLP syndrome. Again, the degree of abnormality that increases the risk for untoward events (e.g., central neurologic sequelae due to bleeding) is unknown. One retrospective study suggests that platelet counts less than 75,000/mm3 are relatively insensitive for untoward events but more specific for prolonged bleeding times. Therefore, in patients with thrombocytopenia one should consider the risk of epidural block versus the benefits of epidural analgesia, including pain relief, salutary blood pressure effects, and the ability to expeditiously convert analgesic to anesthetic blocks for cesarean delivery. It seems prudent to place epidural catheters early in labor, before platelet counts fall below 100,000/mm3. CESAREAN DELIVERY If general anesthesia is used for cesarean delivery, airway edema may make endotracheal intubation difficult. A variety of small endotracheal tubes should be available, and management of a difficult airway should be anticipated. Measures to reduce the blood pressure increase accompanying tracheal intubation or light anesthesia should be available. Sodium nitroprusside (SNP) is effective but must be titrated carefully owing to the potential for severe hypotension; SNP affects both preload and afterload, and patients with eclampsia (like any hypertensive patient) are preload restricted. Direct arterial pressure monitoring is usually required when using SNP. Similarly, the effects of nitroglycerin are unpredictable (it is a primary venodilator, with a consequent drop in preload). Labetalol may be the drug of choice. It has a slower onset of action, is longer acting, and is administered incrementally up to a total intravenous dose

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of 1 mg/kg.1 Intravenous nicardipine (15 to 30 μg/kg) may also be effective. Because it is arterioselective (i.e., has no effect on venous capacitance or preload), nicardipine is less likely to produce rapid declines in blood pressure compared with SNP or nitroglycerin. Finally, at least one report suggests that an intravenous bolus of MgSO4 (30 to 45 mg/kg) given immediately after anesthesia induction is also effective. However, MgSO4 has the potential to augment the effects of nondepolarizing muscle relaxants; cause uterine relaxation, increasing the need for postpartum oxytocin; and increase the risk of uterine atony and postpartum hemorrhage. Spinal (subarachnoid) block has been used safely in severely preeclamptic patients after judicious volume loading. Recent evidence-based reviews and prospective cohort studies comparing subarachnoid and epidural blocks in severely preeclamptic patients show that blood pressure effects and the need for vasopressors are similar or better with subarachnoid blocks. However, subarachnoid block for cesarean delivery is associated with statistically greater (but probably clinically insignificant) neonatal umbilical artery base deficit and lower pH values versus parturients who receive general anesthesia. The smaller needles used for subarachnoid block convey less risk of spinal hematoma than the larger needles used for epidural anesthesia. However, epidural anesthesia with judicious incremental dosing may reduce the volume of fluid administration and the need for vasopressors. Combined spinal-epidural anesthesia with hyperbaric bupivacaine (7.5 mg) with fentanyl (25 μg) may offer the advantage of rapid onset, with the ability to extend the anesthetic level and duration of block, if necessary. Furthermore, it may reduce the risk of adverse hemodynamic changes compared with subarachnoid block with higher doses of local anesthetic. The use of vasopressor-containing local anesthetic solutions is controversial. Some studies advocate their safety, but severe hypertension after their use has been reported.

PREVENTION Therapy with MgSO4 reduces the risk of neonatal intraventricular hemorrhage in preterm infants of preeclamptic mothers. There is no evidence that colloid is preferable to crystalloid for volume expansion; in fact, colloid for this purpose has been reported to increase maternal mortality. Antepartum dexamethasone increases the platelet count, which allows the use of regional analgesia or anesthesia in some patients with the HELLP syndrome. Pulmonary artery pressure monitoring does not appear to improve maternal outcome and in most cases is not needed for the management of preeclampsia. Young and Johanson reviewed routine pulmonary artery pressure monitoring in severely preeclamptic patients and concluded that the data provided by such monitoring did not alter clinical management. Nonetheless, patients with cardiopulmonary compromise or other indications should be considered for

1 This bolus dose of intravenous labetalol is very high. With such doses, α-adrenergic blocking effects are expected to be more prominent, with β-blocking effects near the maximum.

OTHER SURGICAL SUBSPECIALTIES

intravenous labetalol or oral nifedipine is as effective as hydralazine and has fewer side effects. Labetalol given incrementally to a cumulative dose of 0.5 to 1 mg/kg has no significant effects on neonatal heart rate or uterine blood flow. Dihydropyridine calcium channel blockers (e.g., nicardipine, nifedipine) also appear to be effective, with little or no effect on labor and neonatal outcome. However, they have the potential to produce untoward hypotension if used in patients also receiving MgSO4.

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Indications for Pulmonary Artery Catheter Monitoring in Patients with Preeclampsia

Pulmonary edema Congestive heart failure Low urinary output despite adequate fluid challenges or normal central venous pressure Concomitant maternal disease Amniotic fluid embolism Valvular heart disease Congenital heart disease Peripartum cardiomyopathy New York Heart Association class III or IV myocardial function

pulmonary artery pressure monitoring (Table 189-3). Alone, central venous pressure monitoring may not be helpful. Indeed, central venous pressure–to–pulmonary capillary wedge pressure gradients can vary by as much as 10 mm Hg in severe preeclampsia.

Further Reading Allen RW, James MFM, Uys PC: Attenuation of the pressor response to tracheal intubation in hypertensive proteinuric pregnant patients by lignocaine, alfentanil, and magnesium sulphate. Br J Anaesth 66:216-223, 1991. American College of Obstetricians and Gynecologists: Diagnosis and management of preeclampsia and eclampsia. Obstet Gynecol 99:159-167, 2002. Aya AGM, Mangin R, Hoffet M, Eledjam JJ: Intravenous nicardipine for severe hypertension in preeclampsia: Effects of an acute treatment on mother and foetus. Intensive Care Med 25:1277-1281, 1999. Aya AGM, Mangin R, Vialles N, et al: Patients with severe preeclampsia experience less hypotension during spinal anesthesia for elective cesarean section than healthy parturients: A prospective cohort comparison. Anesth Analg 97:867-872, 2003. Beilin Y, Zahn J, Comerford M: Safe epidural analgesia in thirty parturients with platelet counts between 69,000 and 98,000. Anesth Analg 85:385-388, 1997. Brimacombe J: Acute pharyngolaryngeal oedema and preeclamptic toxaemia. Anaesth Intensive Care 20:97-98, 1992. Cotton DB, Lee W, Huhta JC, Dorman KF: Hemodynamic profile of severe pregnancy-induced hypertension. Am J Obstet Gynecol 158:523-529, 1988. Cunningham FG, Gant NF, Levine LJ, et al: Hypertensive disorders in pregnancy. In Cunningham FG, Gant NF, Leveno KJ, et al (eds): Williams Obstetrics, 21st ed. New York, McGraw-Hill, 2001, pp 567-618. deJong CL, Dekker GA, Sibai BM: The renin-angiotensin-aldosterone system in preeclampsia: A review. Clin Perinatol 18:683-711, 1991. Dekker GA, Sibai BM: Pathogenesis and etiology of preeclampsia. Am J Obstet Gynecol 179:1359-1375, 1998. Dyer RA, Els I, Farbas J, et al: Prospective, randomized trial comparing general with spinal anesthesia for cesarean delivery in preeclamptic patients with a nonreassuring fetal heart trace. Anesthesiology 99:561-569, 2003. Eclampsia Trial Collaborative Group: Which anticonvulsant for women with preeclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 345:1455-1563, 1995. Fawcett WJ, Haxby E, Male DA: Magnesium: Physiology and pharmacology. Br J Anaesth 83:302-320, 1999. Gambling DR: Hypertensive disorders. In Chestnut DH (ed): Obstetric Anesthesia: Principles and Practice, 3rd ed. Philadelphia, Mosby, 2004, pp 794-835. Harnett MJP, Datta S, Bhavani-Shankar K: The effect of magnesium on coagulation in parturients with preeclampsia. Anesth Analg 92:1257-1260, 2001.

Hood D, Curry R: Spinal versus epidural anesthesia for cesarean section in severely preeclamptic patients: A retrospective study. Anesthesiology 90:1276-1282, 1999. Hood D, Dewan D, James FI, et al: The use of nitroglycerin in preventing the hypertensive response to tracheal intubation in severe preeclampsia. Anesthesiology 63:329-332, 1985. Jouppila P, Jouppila R, Hollmen A, Koivula A: Lumbar epidural analgesia to improve intervillous blood flow during labor in severe preeclampsia. Obstet Gynecol 59:158-167, 1982. Leduc L, Wheeler JM, Kirshon B, et al: Coagulation profile in severe preclampsia. Obstet Gynecol 79:14-18, 1998. Lewis R, Sibai BM: Recent advances in the management of preeclampsia. J Matern Fetal Med 6:6-15, 1997. McDonagh RJ, Ray JG, Burrows RF, et al: Platelet count may predict abnormal bleeding time among pregnant women with hypertension and preeclampsia. Can J Anaesth 48:563-569, 2001. Moore TR, Key TC, Reisner LS, et al: Evaluation of the use of continuous lumbar epidural anesthesia for hypertensive pregnant women in labor. Am J Obstet Gynecol 152:404-411, 1985. Morgan MA, Silavin SL, Dormer KJ, et al: Effects of labetalol on uterine blood flow and cardiovascular hemodynamics in the hypertensive gravid baboon. Am J Obstet Gynecol 168:1574-1579, 1993. Newsome W, Bramwell RS, Cosling PE: Severe preeclampsia: Hemodynamic effects of lumbar epidural anesthesia. Anesth Analg 65:31-36, 1986. Ramanathan J, Bennett K: Preeclampsia: Fluids, drugs and anesthetic management. Anesthesiol Clin North Am 21:145-163, 2003. Ramanathan J, Vaddadi A, Areheart KL: Combined spinal-epidural anesthesia with low doses of intrathecal bupivacaine in women with severe preeclampsia. Reg Anesth Pain Med 26:46-51, 2001. Rasmus KT, Rottman RL, Kotelko DM, et al: Unrecognized thrombocytopenia and regional anesthesia in parturients: A retrospective review. Obstet Gynecol 73:943-946, 1989. Saleh AA, Bottoms SF, Welch RA, et al: Markers for endothelial injury, clotting, and platelet activation in preeclampsia. Arch Gynecol Obstet 251:105-110, 1992. Sibai BM: Prevention of preeclampsia: A big disappointment. Int J Obstet Gynecol 179:1275-1278, 1998. Sibai BM: Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol 102:181-192, 2003. Sibai BM: Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol 103:981-991, 2004. Silver HM, Seebeck M, Carlson R: Comparison of total blood volume in normal, preeclamptic, and nonproteinuric gestational hypertensive pregnancy by simultaneous measurement of red blood cell and plasma volumes. Am J Obstet Gynecol 179:87-93, 1998. Sinatra RS, Philip BK, Naulty JS, Ostheimer GW: Prolonged neuromuscular blockade with vecuronium in a patient treated with magnesium sulfate. Anesth Analg 64:1220-1222, 1985. Sipes SL, Chestnut DH, Vincent RD, et al: Does the intravenous infusion of ritodrine or magnesium sulfate alter the hemodynamic response to hemorrhage in gravid ewes? Am J Obstet Gynecol 159:1467-1473, 1988. Szal S, Croughan-Minnihane MS, Kilpatrick SJ: Effect of magnesium prophylaxis and preeclampsia on the duration of labor. Am J Obstet Gynecol 180:1475-1479, 1999. Towers CV, Person RA, Nanette MP, et al: Cocaine intoxication presenting as preeclampsia, eclampsia. Obstet Gynecol 81:545-547, 1993. Vermillion ST, Scardo JA, Newman RB, Chauhan SP: A randomized, double-blind trial of oral nifedipine and intravenous labetalol in hypertensive emergencies of pregnancy. Am J Obstet Gynecol 181:858-861, 1999. Vincent RD, Chestnut DH, Sipes SL, et al: Magnesium sulfate decreases maternal blood pressure but not uterine blood flow during epidural anesthesia in gravid ewes. Anesthesiology 74:77-82, 1991. Wang Y, Walsh SW, Kay HH: Placental lipid peroxides and thromboxane are increased and prostacyclin is decreased in women with preeclampsia. Am J Obstet Gynecol 167:946-949, 1992. Young P, Johanson R: Haeomodynamic, invasive, and echocardiographic monitoring in the hypertensive parturient. Best Pract Res Clin Obstet Gynecol 15:605-622, 2001. Zinaman M, Rubin J, Lindheimer MD: Serial plasma oncotic pressure levels and echoencephalography during and after delivery in severe preeclampsia. Lancet 1:1245-1250, 1985.

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Preterm Labor Craig M. Palmer Case Synopsis

PROBLEM ANALYSIS Definition Preterm labor is defined as regular uterine contractions occurring at least once every 10 minutes and resulting in cervical dilatation or effacement before 37 weeks’ gestation. A preterm infant is any infant delivered before 37 weeks’ gestation. Any infant weighing less than 2.5 kg or 1.5 kg at birth is a low-birth-weight or very-low-birth-weight infant, respectively, regardless of gestational age. At 29 weeks’ gestation, more than 90% of fetuses weigh less than 1.5 kg. Prematurity is the leading cause of perinatal morbidity and mortality in the United States, accounting for 60% to 80% of infant deaths in those without congenital anomalies. Advances in neonatology have decreased mortality for verylow-birth-weight infants; survival at 23 weeks’ gestation may be as high as 25%. However, such neonates usually have difficult courses following delivery. Very-low-birth-weight infants are at risk for significant morbidity from respiratory distress syndrome, necrotizing enterocolitis, and intraventricular hemorrhage, and many survivors have significant long-term neurologic impairment, chronic pulmonary problems, and visual disturbances. Delaying delivery from 23 to 31 weeks’ gestation improves the neonatal survival rate from just over 25% to 96%. Thus, current obstetric practice focuses on delaying delivery in patients with preterm labor.

Recognition and Risk Assessment The initial assessment of a patient with preterm labor consists of a thorough physical examination to eliminate treatable medical conditions that may have precipitated premature labor and a pelvic examination to rule out premature rupture of membranes. Bed rest, intravenous hydration, continuous fetal heart rate monitoring, and tocodynamometry are almost universally indicated. Bed rest and hydration alone are effective in a large number of patients, but if these conservative measures fail, ultrasonography and occasionally amniocentesis are undertaken to establish gestational age and fetal maturity (especially if there is any ambiguity with regard to these parameters). Once the diagnosis of preterm labor is established, the obstetrician must decide whether to institute pharmacologic tocolytic therapy. This decision is based on the estimated gestational age, the fetal weight, and the presence or absence of a reassuring fetal heart rate. In general, a gestational age

OTHER SURGICAL SUBSPECIALTIES

A 29-year-old woman, gravida 1, presents with new-onset, regular uterine contractions and a fetus whose estimated gestational age is 28 weeks. Following intravenous hydration, she is admitted to the hospital to begin tocolytic therapy.

between 20 and 34 weeks and a fetal weight less than 2.5 kg in the presence of a reassuring fetal heart rate, without evidence of fetal distress, are indications for tocolytic therapy. However, tocolytic agents in current use have the potential to interact adversely with commonly used inhalational anesthetics and depolarizing or nondepolarizing muscle relaxants.

Implications Prematurity may have implications for the route of delivery (vaginal versus cesarean section). Although the processes that initiate labor are incompletely understood, much is known about the physiology of uterine contractions. The interaction of myosin and actin filaments generates contractile forces in the myometrium. Myometrial pacemaker cells initiate spontaneous contractile activity, which propagates throughout the myometrium via gap junctions between cells. Calcium also plays a critical role. Before contraction, the intracellular calcium concentration increases due to the release of calcium from the sarcoplasmic reticulum or via sarcolemmal influx. Calcium then interacts with calmodulin, activating myosin light-chain kinase. In turn, this kinase phosphorylates myosin, which subsequently binds with actin. Adenosine triphosphate (ATP) is hydrolyzed by myosin to adenosine triphosphatase (ATPase), resulting in movement of the actin-myosin elements and myometrial contraction. A reduction in intracellular calcium concentration, or the dephosphorylation of myosin, inhibits the actin-myosin interaction, causing relaxation. This cascade offers several opportunities for pharmacologic intervention. Activation of β2-adrenergic receptors within the myometrium activates adenylyl cyclase, converting ATP to cyclic adenosine monophosphate (cAMP). Increased cAMP decreases intracellular calcium, inhibiting myosin light-chain kinase and decreasing contractile activity. Magnesium sulfate (MgSO4) reduces uterine activity, probably by decreasing intracellular free calcium concentration through competition for binding sites. It may also activate adenylyl cyclase, increasing the synthesis of cAMP. By blocking voltage-dependent calcium channels in the cell membrane (or altering intracellular uptake and release mechanisms), calcium channel blocking agents decrease the concentration of free calcium within the myometrium. Prostaglandins F2α and E2α are potent stimulators of uterine activity. During labor, their concentration increases in 763

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maternal blood and amniotic fluid. The nonsteroidal antiinflammatory agents that inhibit prostaglandin synthetase can inhibit the production of these prostaglandins.

MANAGEMENT

further administration of muscle relaxants. If this becomes necessary, very small doses should be used (especially with nondepolarizing muscle relaxants) because of the potential for exaggerated or prolonged effects. Finally, although Mg2+ at therapeutic concentrations is known to reduce the minimum alveolar concentration of halothane, this is probably not clinically significant.

The most commonly used tocolytic agents are as follows: ● ● ● ●

MgSO4 β2-Adrenergic agonists Prostaglandin synthetase inhibitors Calcium channel blockers

No single agent is uniformly successful for tocolytic therapy, and it is difficult to compare the efficacy of these agents. Each agent possesses side effects that can further limit its usefulness.

Magnesium Sulfate MgSO4 is the intravenous tocolytic agent of choice in most centers owing to its low cost and relatively low incidence of serious side effects. At the neuromuscular junction, Mg2+ inhibits the release of acetylcholine and reduces the sensitivity of the postsynaptic end plate to acetylcholine. Normal serum Mg2+ concentrations range from 1.3 to 2.9 mg/dL. Therapy is initiated with intravenous bolus MgSO4 (4 to 6 g), followed by continuous infusion. The infusion is titrated to maintain a serum concentration of 5 to 8 mg/dL. Although these concentrations are usually sufficient to inhibit uterine activity, such therapy is not always successful. Increasing the serum concentration is usually not more effective, and this may increase side effects. MgSO4 causes peripheral vasodilatation, and parturients often experience warmth, flushing, and nausea, particularly with the onset of therapy. Maternal tachycardia and hypotension may result, but these are usually transient. At higher serum concentrations, other effects are observed. QRS complex widening and P-R interval prolongation are uncommon with Mg2+ concentrations less than 10 mg/dL, but such effects may be seen even at therapeutic levels. At Mg2+ concentrations above 12 mg/dL, deep tendon reflexes are absent. Mg2+ concentrations greater than 18 mg/dL can result in respiratory arrest, and those greater than 25 mg/dL may cause cardiac arrest. Although untoward fetal effects are infrequent, decreased fetal heart rate and reduced biophysical profile score have been reported. Respiratory depression, hyporeflexia, and reduced muscle tone have also been observed in neonates following prolonged maternal MgSO4 therapy. As a result of MgSO4-caused vasodilatation, there is an increased potential for hypotension in these patients with neuraxial blockade. Careful attention to maternal blood pressure permits the use of either epidural or spinal anesthesia, but the slower onset of epidural blocks may make them preferable. Parturients receiving MgSO4 are more susceptible to the effects of neuromuscular relaxants if general anesthesia becomes necessary. Following the administration of succinylcholine, the train-of-four response must be closely monitored with a peripheral nerve stimulator to guide

β2-Adrenergic Agonists Both ritodrine and terbutaline are used as tocolytic agents, but only ritodrine is approved by the Food and Drug Administration for this use. Ritodrine is administered by continuous intravenous infusion and titrated in response to the uterine contraction pattern. Terbutaline is administered as a single intravenous or subcutaneous dose for prompt but temporary inhibition of uterine activity; it may be continued as oral therapy. Although β2-agonist activity is responsible for their tocolytic effects, both ritodrine and terbutaline have significant β1-adrenergic effects as well, which accounts for many of the side effects. β2-Adrenergic activity can cause vasodilatation, hypotension, and hyperglycemia. Direct β1-adrenergic activity increases myocardial contractility and heart rate, leading to increased cardiac output, which may help offset any potential for hypotension with spinal or epidural blocks. The most significant side effects of β-agonist therapy are cardiac. Either cardiogenic or noncardiogenic pulmonary edema may occur in up to 4% of patients. Fortunately, it usually resolves with discontinuation of therapy. Myocardial ischemia has also been reported, manifesting as chest pain and electrocardiographic changes. This too resolves with discontinuation of therapy. Tachyarrhythmias (both maternal and fetal) may also occur. Finally, hyperglycemia and hypokalemia are frequently observed in these patients, but glucose levels frequently return to baseline in nondiabetic patients, and total body potassium remains unchanged. If anesthesia is required, ideally, one should allow at least 60 to 90 minutes between the discontinuation of β2-adrenergic agonist tocolysis and the administration of anesthesia. Unfortunately, such a delay may jeopardize the fetus. Aggressive hydration is avoided because of the risk of pulmonary edema. Aggressive vasopressor therapy is used instead to maintain maternal blood pressure.

Prostaglandin Synthetase Inhibitors Prostaglandins E2α and F2α are potent stimulators of uterine activity. They also soften the cervix near term (“ripening”). Prostaglandin synthetase inhibitors prevent the conversion of arachidonic acid into active prostaglandins. Although all drugs in this class possess this capability, only indomethacin is widely used for tocolysis in preterm labor. It can be given either orally or rectally and is continued for several weeks. In contrast to MgSO4 and β-agonists, indomethacin has few maternal side effects. It may affect maternal coagulation, but this is not of major clinical importance. In an otherwise healthy parturient without clinical evidence of impaired hemostasis, further evaluation of maternal coagulation status is generally not indicated.

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Calcium Channel Blockers By inhibiting transmembrane calcium flux, calcium channel blockers reduce myometrial contractility. Nifedipine is the most widely used calcium channel blocker for tocolysis, but the use of nicardipine is becoming more common owing to safety concerns related to nifedipine, especially for treating hypertension.1 Nifedipine has a rapid onset following sublingual administration, and therapy is maintained via the oral route. Maternal side effects with nifedipine therapy are generally mild. The drug has few cardiac effects, but vasodilatation with untoward hypotension are often observed.1 These effects may be associated with reflex tachycardia, headache, and nausea. Oral nicardipine may be a better choice and has generally been shown to be a safe and well-tolerated tocolytic agent. In one prospective trial, patients randomly assigned to receive oral nicardipine had arrest of preterm labor more rapidly than did those assigned to receive parenteral MgSO4. Also, those receiving MgSO4 were more likely to have adverse drug-related effects and recurrent preterm labor. However, one recent case report and another case series (five patients) observed acute pulmonary edema during oral nicardipine therapy for tocolysis. However, in one instance, fluid overload and concurrent use of betamethasone (a corticosteroid) were believed to be possible contributing factors. A review published in 2001 concluded that when calcium channel blockers are used for tocolysis, they have fewer maternal side effects than other tocolytics, with no adverse effect on fetal outcome.

PREVENTION Although the intraoperative anesthetic considerations related to each of the tocolytics have been discussed, it is important to remember that the properties of these agents do not cease with delivery. Depending on the duration of tocolytic therapy and the half-life of the agent used, all may contribute to uterine atony. Vigorous therapy may be necessary to restore uterine tone to prevent significant maternal

1 In 1985 the Food and Drug Administration advised that sublingual nifedipine should not be used in hypertensive emergencies because it was neither safe nor efficacious. Variable absorption with suboptimal effects often led to early repeat sublingual dosing in patients with hypertensive emergencies. This caused untoward hypotension, myocardial infarction, and even death in some patients.

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blood loss. Also, despite aggressive tocolytic therapy, labor often progresses. When delivery becomes inevitable, a choice regarding the best route (vaginal versus cesarean) must be made. Some obstetricians advocate routine cesarean delivery for all infants with an estimated gestational weight below 1500 g, to reduce head trauma and subsequent intracranial hemorrhage, but there is little evidence to support this position. In this group of very-low-birth-weight infants, with vertex presentation, there is no difference in outcome between those delivered vaginally or by cesarean section. Likewise, there is no evidence that the routine use of outlet forceps provides protection against head trauma. The advantages of cesarean delivery for the fetus must be weighed against the increased morbidity for the mother. Whenever vaginal delivery is planned for a very-low-birth-weight infant, good pelvic relaxation (which can be accomplished with regional anesthesia) has theoretical value. Currently, the lower limit of viability hovers around 24 to 25 weeks’ gestational age. When planning for the delivery of a very premature infant, it is most important to ensure the presence of personnel trained in neonatal resuscitation and access to a neonatal intensive care unit for subsequent care. Access to this expertise is one of the best predictors of neonatal survival and is largely responsible for lowering the age of viability.

Further Reading ACOG Practice Bulletin: Management of preterm labor. Obstet Gynecol 101:1039-1047, 2003. Bal L, Thierry S, Brocas E, et al: Pulmonary edema induced by calciumchannel blockade for tocolysis. Anesth Analg 99:910-911, 2004. Childress CH, Katz, VL: Nifedipine and its indications in obstetrics and gynecology. Obstet Gynecol 83:616-624, 1994. Economy KE, Abuhamad AZ: Calcium channel blockers as tocolytics. Semin Perinatol 25:264-271, 2001. Goldenberg RL: The management of preterm labor. Obstet Gynecol 100:1020-1037, 2002. Hack M, Fanaroff AA: Outcomes of children of extremely low birthweight and gestational age in the 1990s. Early Hum Dev 53:193-218, 1999. Huddleston JF, Sanchez-Ramos L, Huddleston KW: Acute management of preterm labor. Clin Perinatol 30:803-824, 2003. Larmon JE, Ross BS, May W, et al: Oral nicardipine versus intravenous magnesium sulfate for the treatment of preterm labor. Am J Obstet Gynecol 181:1432-1437, 1999. Lumley J: Method of delivery for the preterm infant. Br J Obstet Gynaecol 110(Suppl 20):88-92, 2003. Palmer CM: Complications of labor. In Palmer CM, D’Angelo R, Paech MJ (eds): Handbook of Obstetric Anesthesia. Oxford, BIOS Scientific Publishers, 2002, pp 163-173. Vaast P, Dubreucq-Fossaert S, Houfflin-Debarge V, et al: Acute pulmonary oedema during nicardipine therapy for premature labour: Report of five cases. Eur J Obstet Gynecol Reprod Biol 113:98-99, 2004. Wilkins IA, Lynch L, Mehalek KE, et al: Efficacy and side effects of magnesium sulfate and ritodrine as tocolytic agents. Am J Obstet Gynecol 159:685-689, 1988.

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However, prostaglandin synthetase inhibitors may have significant fetal effects, such as resulting in premature closure of the fetal ductus arteriosus in utero. This appears to be related to gestational age and is of less concern before 32 weeks’ gestation. Indomethacin may cause decreased fetal urine excretion, leading to oligohydramnios and, rarely, neonatal renal failure. Finally, an increased incidence of necrotizing enterocolitis, intracranial hemorrhage, and bronchopulmonary dysplasia has been reported in neonates following indomethacin therapy.

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Case Synopsis A 29-year-old woman, gravida 1, at 24 weeks’ gestation presents with a fetus in cardiac failure secondary to a giant cystic thoracic mass. The maternal history is otherwise noncontributory. Fetal surgery with fetal thoracotomy and resection of the lung mass is planned.

Fetal surgery is a field of rapid growth. Ex utero intrapartum therapy (EXIT), fetoscopic procedures, and open midgestation procedures (e.g., myelomeningocele repair, congenital cystic adenomatoid lung malformation or sacrococcygeal teratoma resection) are now done at many centers worldwide. Surgical intervention is considered for a fetus with a congenital lesion or condition that compromises or disturbs cardiovascular function or may cause severe postnatal morbidity. Surgery is performed only when the risk to the mother is low and the risk of fetal death or severe disability outweighs the potential poor outcome with no intervention. Contraindications for these procedures include maternal medical conditions precluding such surgery and lethal or severely disabling fetal genetic defects. Fetal surgery is based on extensive animal investigation and clinical research. In contrast, anesthesia for fetal surgery is based mostly on clinical experience, case reports, and translation of responses to anesthesia from pregnant sheep models. Discussed here are maternal and fetal anesthetic considerations for specific fetal surgical interventions.

intervention and returned to the uterus to mature. Correction of the lesion is expected to improve fetal survival or enhance postgestational quality of life. Untreated, these lesions are expected to result in severe disability or death during infancy. EXIT involves procedures done at or near term on fetuses that are expected to have immediate airway or oxygen compromise at birth. Fetal surgery is performed after hysterotomy and just before cord clamping. The surgeon assesses the infant’s airway with bronchoscopy and, if necessary, secures it with an endotracheal or tracheostomy tube before clamping the cord, thereby reducing the risk of complete airway obstruction or postpartum ventilatory failure. Up to actual delivery, the fetus is oxygenated via placental transfer of oxygen. Fetoscopic surgery is minimally invasive. For uterine access, percutaneous small-diameter trocars and laparoscopes are used. This technique is most commonly used to evaluate and treat the twin reversed arterial perfusion sequence, twin-twin transfusion syndrome, amniotic band syndrome, and bladder outlet obstruction. Surgical electrocautery and lasers are used to ablate or cauterize affected vessels or tissue during these procedures. Fetoscopic surgery is considered when fetal demise or severe fetal morbidity is imminent and more conservative measures (e.g., amnioreduction) have failed.

Recognition

Risk Assessment and Implications

Fetal surgery involves three distinct procedural groups (Table 191-1): midgestational open hysterotomy, EXIT, and fetoscopic surgery. Midgestational (18 to 26 weeks) open hysterotomy is performed on fetuses with well-defined congenital lesions. After hysterotomy, the fetus is exteriorized for surgical

MATERNAL ANESTHETIC CONSIDERATIONS

PROBLEM ANALYSIS Definition

Table 191–1

■

Regional anesthesia is the preferred technique for most obstetric cases. However, because uterine relaxation is required for hysterotomy-based fetal surgery and is best provided by high

Surgical Approaches to Fetal Lesions: Timing and Reason for Treatment

Surgical Approach

Fetal Lesion or Anomaly

Reason for Treatment

Gestational Age

Midgestational open hysterotomy

Congenital cystic adenomatoid malformation Myelomeningocele Sacrococcygeal teratoma Congenital or iatrogenic high airway obstruction Giant fetal neck mass Twin-twin transfusion Twin reversed arterial perfusion sequence Bladder outlet obstruction

Hydrops fetalis, lung hypoplasia

18-25 wk

Aminotic fluid neurotoxicity Hydrops fetalis Secure airway

22-26 wk 18-25 wk Near term

Secure airway, resect mass Impending fetal demise, hydrops fetalis Impending fetal demise, hydrops fetalis Hydronephrosis, renal hypoplasia

Near term Midgestation Midgestation Midgestation

Ex utero intrapartum therapy (EXIT) Fetoscopic surgery

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Fetal Intrauterine Surgery

767

100

Adult 80

% Stroke volume

60

Neonate

40

Fetus

0

5

0

10

15

20

25

30

End-diastolic pressure (mm Hg) Figure 191–1

■

Starling curves for adult, neonate, and fetus.

concentrations of volatile inhalational anesthetics, general anesthesia is the technique of choice for fetal surgery. Maternal physiologic changes during pregnancy contribute to an increased anesthetic risk for both the mother and the fetus. Pregnant patients are at increased risk for aspiration pneumonitis. Therefore, a rapid-sequence induction is always performed for endotracheal intubation. Pregnancy also affects maternal pulmonary function. Cephalad movement of the gravid uterus reduces lung functional residual capacity, especially lower lobe volumes. Also, oxygen consumption increases to meet the greater demands of both mother and fetus. All these factors increase the risk for maternal hypoxemia during rapid-sequence induction. Further, reduced capillary oncotic pressure and increased capillary permeability increase the maternal postoperative risk for pulmonary edema, especially when magnesium sulfate (MgSO4) is used for tocolysis. Pregnancy also affects the cardiovascular system. Reduced preload due to vena cava compression by the gravid uterus may cause maternal hypotension in the supine position (supine hypotensive syndrome) and fetal hypoxemia. Left uterine displacement is important to reduce this risk. Anesthetic requirements are also affected by pregnancy. The minimum alveolar concentration (MAC) of anesthetics is significantly reduced during pregnancy. Thus, lower concentrations of volatile anesthetics are required for surgery. Moreover, sensitivity to nondepolarizing skeletal muscle relaxants is increased.

pressure (Fig. 191-1). Thus, cardiac output is more dependent on heart rate. Also, owing to high vagal tone and low baroreceptor sensitivity, the fetus responds to stress with a decrease in heart rate. The circulating fetal blood volume is low. The midgestational fetus has an estimated blood volume of 50 to 70 mL/kg, versus 110 mL/kg for the placenta. Therefore, small surgical blood losses can precipitate fetal hypovolemia. Inhalational anesthetics can also destabilize fetal cardiovascular dynamics by causing systemic vasodilatation, direct myocardial depression, and altered arteriovenous shunting. Also, because of incomplete myelination and reduced synaptic transmission, the fetus is more sensitive to the effects of volatile anesthetics. This results in a reduced MAC requirement compared with a pregnant adult. Further, sensitivity to analgesics and muscle relaxants is greater for a fetus compared with a neonate. Fetal cutaneous and evaporative heat losses necessitate warm ambient temperatures during fetal exposure. Limiting fetal surgical time and using warm irrigation fluids can prevent fetal hypothermia. Finally, altered coagulation predisposes to bleeding and difficulty achieving surgical hemostasis during fetal surgical manipulation. Relatively small fetal blood volumes compound this problem. Fetal hemoglobin can be assessed intraoperatively via central or percutaneously obtained fetal blood samples. UTEROPLACENTAL ANESTHETIC CONSIDERATIONS

FETAL ANESTHETIC CONSIDERATIONS In addition to maternal safety, a major concern for anesthetic management is to preserve placental perfusion and fetal cardiovascular stability. The combination of fetal immature organ function and maternal cardiovascular compromise predisposes the fetus to anesthetic-related circulatory compromise. The cardiovascular system of a fetus is less able to compensate for hypoxia and hypovolemia than that of a full-term infant. Lacking a functional pulmonary system to increase oxygen tension, the fetus relies instead on increased maternal umbilical blood flow and cardiac output, as well as fetal blood flow redistribution to improve oxygen delivery to vital organs. The Starling curve is shifted downward for a fetus compared with a neonate, resulting in a lower percentage stroke volume for a given end-diastolic

Uterine and umbilical arterial blood flow and placental barriers to diffusion influence fetal oxygen delivery. Maternal systemic blood pressure and myometrial tone directly correlate with uterine artery blood flow. Volatile anesthetics decrease myometrial tone and tend to reduce maternal blood pressure and placental blood flow as well. This can result in decreased fetal oxygenation. Umbilical arterial blood flow is determined by maternal and fetal cardiac output and vascular resistance and by extrinsic factors (e.g., extrinsic compression by a “nuchal cord”). Thus, maintaining maternal arterial pressure within 10% of baseline values and umbilical artery patency is critical. Relaxation of myometrial tone by inhalational anesthetics is required for optimal exposure during open fetal surgery. Epidural anesthesia alone does not provide adequate uterine

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relaxation, but it may help prevent premature labor in the early postoperative period. Tocolytics (MgSO4, terbutaline, nifedipine, indomethacin) are used alone or in combination to ensure uterine quiescence.

MANAGEMENT AND PREVENTION Open Fetal Surgery PREOPERATIVE EVALUATION

AND

PREPARATION

Before surgery, the operating room is warmed to 80°F (26.7°C). Type-specific packed red blood cells must be available for the mother, and O-negative packed red blood cells for the fetus. Monitoring includes maternal and fetal pulse oximetry and maternal direct arterial pressure. Before anesthesia and surgery, prepare several sterile 1-mL syringes with fentanyl 10 to 20 μg/kg, vecuronium 0.2 mg/kg, epinephrine 10 μg/kg, and atropine 20 μg/kg. These may be needed for the fetus. After assuring the mother’s nothing-by-mouth status, one large-bore intravenous (IV) catheter is placed. Metoclopramide and bicitrate are given to reduce the risk for aspiration pneumonitis. An indomethacin suppository is used for postoperative tocolysis. After lumbar epidural catheter insertion and testing, the mother is positioned in the left lateral decubitus position, or the operating table is tilted to the left to reduce the risk of supine hypotensive syndrome. INTRAOPERATIVE MANAGEMENT Rapid-sequence induction using IV sodium thiopental and succinylcholine is performed, followed by endotracheal intubation. General anesthesia is maintained with 0.5 MAC volatile anesthetic (isoflurane or desflurane) and 50% nitrous oxide (N2O) in oxygen. A radial arterial catheter, second IV access catheter, nasogastric tube, and Foley catheter are placed. Fetal status is monitored by sterile intraoperative echocardiography. IV fluid administration is restricted to 500 mL (total) to reduce the risk of postoperative pulmonary edema. Open hysterotomy procedures require low uterine tone to maintain fetal perfusion and optimize fetal exposure. Before maternal skin incision, N2O is discontinued to improve fetal oxygenation,1 and the inhalational agent is increased to 2.0 MAC to provide uterine relaxation and fetal anesthesia before uterine and fetal incisions. IV ephedrine (5 to 10 mg) or phenylephrine (1 to 2 μg/kg) is given as necessary to maintain maternal systolic blood pressure within 10% of baseline. Fetal anesthesia and analgesia are provided by both placental transfer of volatile anesthetic and intramuscular opioids. After maternal-fetal equilibration, fetal concentrations of isoflurane and desflurane are about 70% and 50% of maternal levels, respectively, by 1 hour. Before fetal incision, the fetus receives intramuscular fentanyl (20 μg/kg) to supplement anesthesia and provide postoperative analgesia. Fetal well-being is assessed by direct and indirect methods. For procedures in which a fetal extremity is available (e.g., congenital cystic adenomatoid malformation and sacrococcygeal

1 This also helps reduce maternal bowel distention, thereby improving surgical exposure.

teratoma resection), fetal arterial saturation is monitored by pulse oximetry. The pulse oximeter probe is placed on the fetus’s hand, which is then wrapped with sterile foil to reduce exposure to ambient light. Normal fetal arterial saturation is 60% to 70%. During surgery, values greater than 40% indicate adequate fetal oxygenation. To monitor fetal heart rate and stroke volume, echocardiography is used. Fetal distress manifests as bradycardia, along with reduced oxygen saturation or stroke volume. Often, this is due to partial umbilical cord occlusion. Fetal arterial or venous blood gas samples are used to guide therapy during periods of fetal stress; these samples are obtained by the surgeon percutaneously or from the umbilical artery or central vessel. Warm, fresh O-negative blood is used to correct fetal anemia intraoperatively via fetal venous access. Near the end of uterine closure, the volatile anesthetic is reduced, and the epidural catheter is dosed with an opioid and local anesthetic. Tocolysis is begun with IV MgSO4 (6 g), followed by infusion at 2 to 3 g/hour. After tracheal extubation, the patient is transferred to the obstetric floor for postoperative care. POSTOPERATIVE MANAGEMENT Key for postoperative management are the prevention of premature labor and adequate maternal pain control. MgSO4 is the tocolytic of choice for the first 18 to 24 hours. Along with tocolysis, good pain control with epidural analgesia helps prevent preterm labor.

Ex Utero Intrapartum Therapy PREOPERATIVE MANAGEMENT Anesthesia for EXIT procedures is similar to that for open procedures, except that tocolytic therapy is unnecessary (EXIT procedures end with delivery of the fetus). In addition, a second operating room with neonatal resuscitation equipment and a neonatologist must be available for care of the neonate. INTRAOPERATIVE MANAGEMENT The risk of aspiration and supine hypotensive syndrome is increased in full-term mothers, owing to the larger gravid uterus. Thus, after epidural catheter placement, a rapidsequence induction is performed, followed by orotracheal intubation. Then a nasogastric tube and Foley catheter are placed, along with a second IV catheter in case the patient requires volume resuscitation for acute blood loss after fetal delivery. If the fetus has end-stage disease (e.g., fetal hydrops), the maternal blood pressure may be very labile. If so, direct arterial pressure monitoring may be required for beat-to-beat assessment of blood pressure and frequent blood sampling. Sub-MAC concentrations of a volatile anesthetic are used before maternal skin incision, and higher concentrations thereafter. Desflurane is preferred by many, not only because it maintains heart rate and allows rapid induction but also because emergence is faster than with sevoflurane and other agents. The latter is explained by its lower fat partition coefficient compared with sevoflurane and other agents. Vasopressors are used to maintain maternal blood pressure if necessary. During hysterotomy, the surgeon only partially exposes the fetus. This keeps the uterine volume near normal and

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Table 191–2

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Fetal Depression

769

Uteroplacental Blood Flow

Uterine Relaxation

– +

– +/–

– +/–

++

++

++

maintains placental perfusion. Maternal hyperventilation is avoided because of the risk of placental vasoconstriction and fetal hypoxemia with hypocapnia. Fentanyl 20 μg/kg is given to the fetus intramuscularly to supplement analgesia (via placental transfer) and for postoperative analgesia. Fetal status is closely monitored by pulse oximetry, sterile echocardiography, and visual inspection. Fetal blood gases are obtained if needed, and fresh O-negative blood is administered if necessary. Fetal orotracheal intubation is performed by the surgeon or anesthesiologist. If the fetus cannot be intubated, resection of an obstructive lesion or tracheotomy is performed by the surgeon. After securing the airway and ensuring adequate fetal oxygenation with manual ventilation, the umbilical cord is clamped, and the fetus is delivered. After delivery, one must quickly reverse uterine relaxation. Anesthetic depth is reduced after cord clamping, and the epidural catheter is dosed for anesthesia and postoperative opioid analgesia. Owing to anesthetic-induced uterine relaxation, uterine atony and large blood losses are known risks. The timing of cord clamping with respect to the use of oxytocin, methylergonovine maleate (Methergine), and 15-methyl prostaglandin F2α is coordinated by the anesthesiologist and surgeon. Blood loss is closely monitored, and blood is transfused if needed. The trachea is extubated after uterine closure. The epidural is used for wound closure and postoperative analgesia. POSTOPERATIVE MANAGEMENT

After surgery and delivery, the mother is transferred for postpartum care. The immediate disposition of the newborn is based on whether further surgery is required (e.g., excision of a cervical teratoma). If not, a neonatology team resuscitates and transports the infant to the neonatal intensive care unit.

Fetoscopic Surgery PREOPERATIVE MANAGEMENT Patients scheduled for fetoscopic surgery are admitted to the hospital on the day of surgery. The operating room is prepared as for an open procedure, in the rare event that hysterotomy is required for surgical access. In the preoperative area, the mother receives “full-stomach” prophylaxis and, if she is at high risk for preterm labor, indomethacin by rectum. Standard monitoring per American Society of Anesthesiologists guidelines is applied, and a lumbar epidural catheter is inserted and tested. Left uterine displacement is used to prevent supine hypotension.

INTRAOPERATIVE MANAGEMENT Choice of anesthesia is guided by the implications of various anesthetic techniques for fetoscopic surgery (Table 191-2). Epidural anesthesia is used in the majority of these cases because of its minimal effect on fetal hemodynamics and uteroplacental blood flow. Disadvantages include the lack of uterine relaxation and fetal anesthesia; fetal movement may make it difficult to manipulate the uterus and cord, especially with difficult cord positions. Although a balanced anesthetic technique allows uterine manipulation with an immobile, anesthetized fetus, there is greater fetal cardiovascular depression than with epidural anesthesia. General endotracheal anesthesia also eliminates concerns related to an awake patient (e.g., anxiety, combativeness, nausea, aspiration of gastric contents). Deep inhalation anesthesia has the advantage of providing profound uterine relaxation for externalizing the uterus during hysterotomy-based fetal procedures. However, associated risks are fetal cardiovascular depression and reduced uteroplacental blood flow. POSTOPERATIVE MANAGEMENT As with open hysterotomy, tocolysis is the most important aspect of postoperative management. Epidural catheters are removed in the immediate postoperative period unless the patient will have a hysterotomy-based procedure based on findings at fetoscopy. MgSO4 (with or without nifedipine or terbutaline) is the mainstay of tocolytic therapy. Discharge from the hospital on postoperative day 1 or 2 is expected after fetoscopy.

Further Reading Bianchi DW, Crombleholme TM, D’Alton ME: Fetology: Diagnosis and Management of the Fetal Patient. New York, McGraw-Hill, 2000. Fisk NM, Gitau R, Teixeira JM, et al: Effect of direct fetal opioid analgesia on fetal hormonal and hemodynamic stress response to intrauterine needling. Anesthesiology 95:828-835, 2001. Gaiser RR, Cheek TG, Kurth CD: Anesthetic management of cesarean delivery complicated by ex utero intrapartum treatment of the fetus. Anesth Analg 84:1150-1153, 1997. Galinkin JL, Gaiser RR, Cohen DE, et al: Anesthesia for fetoscopic fetal surgery: Twin reverse arterial perfusion sequence and twin-twin transfusions syndrome. Anesth Analg 91:1394-1397, 2000. Galinkin JL, Schwarz U: Anesthesia for fetal surgery. In Smith’s Anesthesia for Infants and Children, 7th ed. St. Louis, Mosby, 2004. Motoyama EK, Rivard G, Acheson F, et al: Adverse effect of maternal hyperventilation on the foetus. Lancet 1:286-288, 1966. Palahniuk RJ, Shnider SM, Eger EI 2nd: Pregnancy decreases the requirement for inhaled anesthetic agents. Anesthesiology 41:82-83, 1974. Tame JD, Abrams LM, Ding XY, et al: Level of postoperative analgesia is a critical factor in regulation of myometrial contractility after laparotomy in the pregnant baboon: Implications for human fetal surgery. Am J Obstet Gynecol 180:1196-1201, 1999.

OTHER SURGICAL SUBSPECIALTIES

Regional anesthesia Balanced general anesthesia with or without epidural Deep general anesthesia with epidural

AND

Fetal Intrauterine Surgery

Implications of Anesthetic Technique for Fetoscopic Surgery

Type of Anesthesia

POSTDELIVERY

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Fetal Distress Brenda A. Bucklin Case Synopsis An 18-year-old, 150-kg primigravida presents at 27 weeks’ gestation with severe preeclampsia. Her worsening condition necessitates induction of labor. During uterine contractions, the electronic fetal heart rate monitor demonstrates ominous changes (Fig. 192-1).

PROBLEM ANALYSIS Definition Fetal distress is a widely used clinical term that is imprecise and nonspecific. In 1998 the American College of Obstetricians and Gynecologists (ACOG) published a committee opinion that suggested replacing the term fetal distress with nonreassuring fetal heart rate tracing because the former term has a low predictive value and is frequently associated with the delivery of infants who turn out to be in good condition. The ACOG went on to recommend that a nonreassuring fetal heart rate tracing be accompanied by a further description of the findings (e.g., fetal bradycardia, repetitive variable decelerations). Still, obstetricians continue to use the term fetal distress to describe a wide range of fetal heart rate abnormalities that, if not corrected or circumvented, will result in decompensation of physiologic responses and cause permanent central nervous system or other damage or death. Anesthesiologists must consider the severity of the fetal heart rate abnormality when determining the urgency of delivery and the type of anesthesia to be administered.

Recognition Consistent, accurate diagnosis of true fetal distress (i.e., intrauterine hypoxia or asphyxia) is a clinical challenge because of the questionable reliability of electronic fetal heart rate monitoring for predicting adverse neonatal outcomes. Still, electronic fetal heart rate monitoring is the primary screening tool. Additional support for the diagnosis may be obtained from the presence of meconium in the amniotic fluid, deteriorating fetal acid-base status, lack of a fetal heart rate response to acoustic or scalp stimulation, and umbilical artery Doppler velocimetry. The most sensitive indicators of fetal cerebral oxygenation are heart rate variability or accelerations. Gradual decreases in fetal oxygenation produce a variety of fetal heart rate patterns (Fig. 192-2). Early signs of transient hypoxemia in a neurologically intact fetus may include tachycardia, persistent sinusoidal fetal heart rate pattern, and periodic changes consisting of late and variable decelerations. Although these changes alone do not preclude the delivery of a healthy neonate, they should alert the clinician that the fetus is at risk. In extreme cases, the fetus will lose all central influence over its heart rate and develop a straight-line tracing 770

devoid of accelerations, variability, and even decelerations. Abrupt and profound decreases in fetal oxygenation often result in severe fetal bradycardia, usually less than 90 beats per minute. Ominous signs suggesting that both fetal acidosis and hypoxia are present include the following: ● ● ● ●

Loss of fetal heart rate accelerations Increase in baseline fetal heart rate Persistent absent variability, unresponsive to stimuli Absent variability with late or variable decelerations

The challenge for obstetricians is to judiciously consider the electronic information within the clinical context to ensure the best possible neonatal outcome. Emergency cesarean delivery is indicated when the condition is life threatening to the mother or fetus. In these situations, communication between obstetric and anesthesia care providers is essential for maternal and fetal well-being.

Risk Assessment The true incidence of fetal distress is difficult to quantify, largely because of the lack of clearly defined diagnostic criteria. However, it is a diagnosis that is likely overused by physicians. In 1991 U.S. birth certificate statistics revealed that fetal distress was a confounding factor in 4.3% of live births. More recently, rates of cesarean delivery for fetal distress ranged from 2% to 8.7%. Fetal distress may result from interference of oxygen transport at the level of the mother, the placenta, the umbilical cord, or the fetus itself (Table 192-1). Sometimes the cause is multifactorial, but more often a primary cause is identifiable. Common high-risk obstetric conditions that increase the risk of fetal distress include the following: ● ● ● ● ● ●

Preeclampsia or eclampsia and chronic hypertension Diabetes mellitus Intrauterine growth retardation Oligohydramnios Fetal prematurity or postmaturity Chorioamnionitis

Implications Severe and sustained hypoxia in the fetus will eventually lead to profound acidosis, neurologic sequelae (e.g., seizures, coma, hypotonia), and ultimately, death.

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Figure 192–1 ■ The fetal heart rate tracing (top) demonstrates no beat-to-beat variability, with late decelerations evident after each uterine contraction in the uterine activity (UA) tracing (bottom).

MANAGEMENT When clinical signs suggest intrauterine hypoxia, the obstetrician and anesthesiologist should initiate in utero fetal resuscitation. Obstetric management includes supplemental oxygen administration, maternal repositioning (e.g., left or right lateral decubitus, Trendelenburg’s, or knee-chest position), assessment of maternal circulation, treatment of maternal hypotension, and discontinuation of oxytocin, tocolytic administration, and amnioinfusion. Although a distressed fetus may occasionally be delivered vaginally, the diagnosis of fetal distress significantly increases the likelihood of cesarean delivery. The anesthesiologist should be prepared to assist in either situation and must consider the following factors: ● ● ●

Urgency of delivery Anesthetic risk factors in the mother Direct and indirect effects of anesthesia on the distressed fetus

Emergent cesarean delivery is performed when the maternal or fetal condition is considered to be life threatening (e.g., massive maternal hemorrhage, catastrophic uterine rupture, evidence of sustained and severe fetal bradycardia). Communication between the obstetrician and anesthesiologist is imperative in cases of emergent cesarean delivery. In this situation, anesthesia care providers should determine

the diagnosis and how expeditiously the fetus must be delivered. Fetal heart rate monitoring via a scalp electrode should be continued following transfer to the delivery room and, if possible, until delivery. This information helps guide the choice of anesthetic. The relative risks of general and regional anesthesia must be carefully considered in each patient. General anesthesia is associated with a higher incidence of fatal maternal complications. Therefore, if the fetal heart rate tracing improves, there may be time to extend epidural analgesia to anesthesia or even for de novo induction of spinal or epidural anesthesia. When a preexisting epidural catheter is in place and the mother is hemodynamically stable, surgical epidural anesthesia can easily be established. With administration of either 2% alkalinized lidocaine with 1:200,000 epinephrine or 3% alkalinized 2-chloroprocaine in 5-mL increments (total volume of 15 to 20 mL) over a 2- to 3-minute period, the interval between injection and delivery is about 10 to 12 minutes. Although the addition of freshly prepared epinephrine to the lidocaine and bicarbonate solution hastens the onset of epidurally administered lidocaine, 3% 2-chloroprocaine with bicarbonate is the agent of choice when time is of the essence. Spinal anesthesia is also acceptable for urgent or emergent cesarean delivery. However, the skill of the anesthesiologist, the patient’s body habitus, and the acceptance of neuraxial anesthesia by the patient and obstetrician must all be considered before the use of either epidural or spinal techniques. Although a non-dextrose-containing crystalloid

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Figure 192–2 ■ Electronic fetal heart rate monitoring. Characteristics of progressive fetal deterioration are superimposed above a uterine activity (UA) tracing showing two uterine contractions. (1) Healthy fetus exhibiting accelerations and moderate variability. (2) Late decelerations, indicating transient hypoxemia. The presence of accelerations signifies a normal pH. (3) Loss of accelerations, which occurs with evolving hypoxia. (4) Decreasing variability and shortened latency period with worsening acid-base status. (5) Increased latency period consistent with fetal myocardial depression. (6) Intermittent decelerations, indicating progression of acidosis or hypoxia. (7) Absent variability and loss of decelerations in a moribund fetus. (From Dellinger EH, Boehm FH: Emergency management of fetal stress and distress in the obstetric patient. Obstet Gynecol Clin North Am 22:225, 1995.)

solution should be administered as rapidly as possible before spinal anesthetic administration, fluid preloading does not justify delaying spinal anesthesia when it is the most appropriate method for the patient. Emergent cesarean delivery is not the time to strengthen one’s regional anesthesia skills, and even an experienced anesthesiologist may have to accept less-than-perfect regional anesthesia; injection of local anesthetic into the incision by the obstetrician can obviate the need for general anesthesia. When a preexisting epidural block cannot be extended safely or there is inadequate time to place a spinal anesthetic, rapid induction of general anesthesia is usually the most expeditious technique. However, significant maternal morbidity or even mortality is associated with failed endotracheal intubation or pulmonary aspiration. Because emergency surgery has been identified as a risk factor for anesthesia-related maternal mortality, the mother’s life should not be endangered for the sake of the fetus. Obstetricians should consult with an anesthesiologist for all parturients at increased risk for operative delivery, especially those with potential airway problems. In such patients, early initiation and maintenance of epidural analgesia can facilitate the extension to surgical anesthesia if cesarean delivery

becomes necessary. A history or suspicion of difficult intubation should prompt an awake intubation or regional anesthesia, despite severe fetal distress. Some urgent and emergent cesarean deliveries require the administration of general anesthesia. Failed or difficult intubation is the leading cause of anesthetic-related maternal mortality. Failed intubation has been reported to occur with a frequency of 1 in 300 obstetric patients, compared with 1 in 2000 general surgical patients. In cases of unrecognized difficult airway and failed intubation, the absence of sustained, severe fetal bradycardia may allow the anesthesiologist to safely awaken the patient and attempt an alternative technique. However, if fetal bradycardia persists, the anesthesiologist may choose to proceed with inhalation anesthesia with a facemask or laryngeal mask ventilation when maternal oxygenation and ventilation can be maintained. Although the use of laryngeal mask ventilation is limited to “cannot intubate, cannot ventilate” situations in obstetrics, it can be lifesaving and is an important part of emergency airway management. In many urgent cases of fetal distress, cesarean delivery can be performed safely using skillfully administered regional anesthesia. As clinical expertise has increased, the

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Causes of Fetal Distress

Maternal

Placental Abruption Infection Infarction

Umbilical Cord Compression Prolapse

Fetal Sepsis Hydrops Anemia (both acute and chronic) Anomalies Preexisting neurologic injury

theoretical objections to the use of regional anesthesia— namely, a delay in delivery and significant maternal hypotension—have proved to be less consequential than previously feared.

PREVENTION Early diagnosis of fetal distress is important if the sequelae of intrauterine hypoxia and asphyxia are to be minimized. The anesthesiologist’s expertise in this setting and his or her ability to effectively communicate with the obstetrician are critical to ensuring the best maternal and fetal outcomes.

Fetal Distress

773

Further Reading American College of Obstetricians and Gynecologists Committee on Obstetric Practice: Inappropriate Use of the Terms Fetal Distress and Birth Asphyxia (ACOG Committee Opinion No. 197). Washington, DC, ACOG, 1998. American College of Obstetricians and Gynecologists Committee on Obstetrics: Anesthesia for Emergency Deliveries (ACOG Committee Opinion No. 104). Washington, DC, ACOG, 1992 (reaffirmed in 1998). Campbell C: Fetal distress. In Atlee JL (ed): Complications in Anesthesia. Philadelphia, WB Saunders, 1999, pp 807-810. Chestnut DH: Anesthesia for fetal distress. In Chestnut DH (ed): Obstetric Anesthesia: Principles and Practice, 3rd ed. St. Louis, Mosby–Year Book, 2004, pp 447-471. Dellinger EH, Boehm FH: Emergency management of fetal stress and distress in the obstetric patient. Obstet Gynecol Clin North Am 22:225, 1995. Eskew PN Jr, Saywell RM Jr, Sollinger TW, et al: Trends in the frequency of cesarean delivery: A 21-year experience, 1970-1990. J Reprod Med 39:809-817, 1994. Parer JT, Livingston EG: What is fetal distress? Am J Obstet Gynecol 162:1421-1427, 1990. Paul RH, Miller DA: Cesarean birth: How to reduce the rate. Am J Obstet Gynecol 172:1903-1907, 1995. Spielman FJ, Mayer DC: Clear head, steady hands: Anesthesia for emergency cesarean delivery [editorial]. Am J Anesthesiol 28:328-330, 2001.

OTHER SURGICAL SUBSPECIALTIES

Chronic and pregnancy-induced hypertension Diabetes mellitus Cardiovascular disease Pulmonary disease Substance abuse Trauma or shock Anemia

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Case Synopsis A 33-year-old woman, gravida 3, para 2, presents at 28 weeks’ gestation with vaginal bleeding. Estimated blood loss is greater than 1000 mL. The patient underwent an emergent cesarean delivery for the birth of her first child 4 years ago. Ultrasound examination confirms a breech presentation with placenta previa.

PROBLEM ANALYSIS Definition Vaginal bleeding occurs in 24% of diagnosed pregnancies. Most often, it is associated with minimal blood loss and limited pathology. In contrast, major antepartum bleeding may occur at any time during pregnancy and is the leading cause of antepartum maternal death worldwide. It is also a leading cause of perinatal morbidity and mortality. The distinction between bleeding and hemorrhage is one of semantics. What is more important is the recognition that with any bleeding, blood loss and physiologic deterioration may occur rapidly. If so, both fetal and maternal outcomes depend on a cogent plan of investigation and an appropriate response. Antepartum hemorrhage is commonly associated with certain causes. Bleeding during early pregnancy (before 20 weeks’ gestation) can result from abnormal embryo implantation (e.g., placenta previa, placenta accreta, placental abruption, or vasa previa), miscarriage, ectopic pregnancy, gestational trophoblastic disease, dysfunctional uterine bleeding, and benign and malignant tumors of the reproductive tract. Among pregnancies complicated by bleeding in the first trimester, less than 50% progress normally beyond 20 weeks’ gestation; 10% to 15% are ectopic pregnancies, 0.2% are hydatidiform moles, and more than 30% result in miscarriage. Bleeding during late pregnancy (beyond 20 weeks’ gestation) complicates 2% to 5% of pregnancies. The most common causes are placental abruption (31%) and placenta previa (22%). Miscarriage, ectopic pregnancy, placenta previa, placental abruption, uterine rupture, and vasa previa are the most common causes of significant antepartum hemorrhage. Unclassified bleeding may occur at any time during 47% of pregnancies. Causes are marginal placental sinus bleeding, “bloody show” during labor, cervicitis, trauma, genital tract tumor and infection, and vasa previa.

do not result in a viable pregnancy. Miscarriages may be threatened, inevitable, complete, incomplete, septic, recurrent, or missed. Typically, the presentation includes a history of vaginal spotting or mild bleeding. When vaginal bleeding during the first 12 weeks of pregnancy is as heavy as normal menstrual blood loss, the pregnancy is rarely successful. Larger amounts of blood loss are observed with intrauterine fetal demise, especially at greater gestational ages. However, severe hemorrhage with disseminated intravascular coagulation (DIC) does not usually occur until approximately 4 weeks after fetal demise. ECTOPIC PREGNANCY Approximately 2% of pregnancies do not implant normally in the uterus, and the incidence appears to be increasing. Although ectopic pregnancies classically present as pelvic pain with intraperitoneal bleeding, they can also masquerade as a number of other entities, including appendicitis, ovarian cyst torsion, endometriosis, and pelvic inflammatory disease. Major blood loss with sudden death has been described. However, the risk of bleeding and the outcome correlate with the implantation site (e.g., isthmic or interstitial portion of the fallopian tube, ovary, cervix, abdomen) and the timing of diagnosis. Ectopic pregnancies may resolve spontaneously, be treated medically, or require laparoscopic or open surgery. Surgery is indicated in the presence of peritoneal signs, hemodynamic instability, or failed conservative management. PLACENTA PREVIA Placenta previa is implantation of the placenta in the lower uterine segment. It is classified by the degree to which the cervical os is encroached on or covered (Fig. 193-1). As the lower uterine segment elongates during gestation, the amount of placental encroachment on the cervical os (and therefore the risk of bleeding) may lessen. Placenta previa occurs in up to 1% of third-trimester pregnancies.

MISCARRIAGE The definition of spontaneous abortion (miscarriage) varies, depending on the accepted age of fetal viability. Typically, it is defined as the spontaneous termination of pregnancy before 22 to 24 weeks of gestation. Between 15% and 20% of all clinically diagnosed pregnancies result in miscarriage, but the actual incidence may be higher. This is so because up to 60% of “chemical pregnancies” (i.e., those diagnosed by changes in β-human chorionic gonadotropin) 774

PLACENTA ACCRETA On occasion, the placenta can adhere to the implantation site with an absent decidua, an abnormality that produces an absence of the physiologic line of cleavage through the decidual layer. Furthermore, the placenta can invade the myometrium (placenta increta) or can extend through the myometrium and adhere to surrounding structures (placenta percreta).

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Figure 193–1 ■ Types of placenta previa. (From Ricci JM: Antepartum hemorrhage. In Hacker NF, Moore JG [eds]: Essentials of Obstetrics and Gynecology, 2nd ed. Philadelphia, WB Saunders, 1992, p 156.)

OTHER SURGICAL SUBSPECIALTIES

PLACENTAL ABRUPTION Placental abruption—also referred to as abruptio placentae or placental separation—is defined as the premature separation of a normally situated placenta from its attachment to the placental decidua basalis before the birth of the fetus. Such separation is thought to result from a rupture of placental arteries or veins. In 20% to 35% of cases, the bleeding site is “concealed”; that is, there is no obvious vaginal bleeding. Placental abruption occurs in 0.5% to 1.8% of all pregnancies, with approximately 40% of cases occurring after the 37th week of gestation, 40% occurring between the 34th and 37th weeks, and less than 20% occurring before the 32nd week. UTERINE RUPTURE Uterine rupture is defined as a defect in the uterine wall associated with fetal distress or maternal hemorrhage sufficient to require cesarean delivery or postpartum laparotomy. Rupture of the gravid uterus occurs in less than 1% of pregnancies, most often in patients with prior uterine trauma. Uterine scar dehiscence does not require surgical intervention. Although it is more common than true uterine rupture, most cases are asymptomatic and are not likely to cause maternal or fetal mortality. However, uterine scar dehiscence

can result in significant morbidity, especially if it causes extension of the placenta laterally into major uterine vessels or there is abnormal placentation (placenta accreta, increta, or percreta). Cesarean scar rupture is more likely to occur with vaginal birth if labor has been induced or augmented. VASA PREVIA Although the umbilical cord typically is attached to the placenta, in about 1% and 9% of single and twin gestations, respectively, it attaches to the chorioamniotic membranes. Such atypical or velamentous insertion exposes the umbilical vessels to trauma or compression as they traverse between the amnion and chorion to reach the placenta. Vasa previa exists when the velamentous umbilical vessels present ahead of the fetus, placing them at even greater risk with rupture of membranes. Fetal exsanguination and demise often result. UNCLASSIFIED BLEEDING Unclassified bleeding accounts for almost half of antepartum bleeding (vasa praevia is sometimes included in this category). It usually occurs in late pregnancy, and its cause either is unknown or does not become apparent until later. This type of bleeding, though typically mild with spontaneous resolution, is associated with high perinatal mortality

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Assessment of Obstetric Hemorrhage

Shock Severity

Findings

None Mild

None Tachycardia (<100 bpm), mild hypotension, peripheral vasoconstriction Tachycardia (100-120 bpm), hypotension (SBP 80-100 mm Hg), restlessness, oliguria Tachycardia (>120 bpm), hypotension (SBP <60 mm Hg), altered consciousness, anuria

Moderate Severe

Blood Loss (%) 15-20 20-25 25-35 >35

bpm, beats per minute; SBP, systolic blood pressure.

(3.5% to 15.7%). This may be due to placental dysfunction and higher rates of preterm labor in patients with unclassified bleeding.

Recognition Hemorrhage during pregnancy can be masked by physiologic adaptations that begin early in pregnancy. As early as 6 to 8 weeks’ gestation, there is a progressive increase in plasma volume, reaching near-maximal volume (4700 to 5200 mL) by 32 weeks. This volume, which represents a 45% increase over that in nonpregnant women, is further augmented with multiple gestations and appears to be correlated with fetal weight. Placental chorionic somatomammotropin, progesterone, erythropoietin, and prolactin act in concert to increase red cell mass by 250 to 450 mL at term, an increase of 20% to 30% over pregestational values. The disproportionate increase in plasma volume versus red cell mass accounts for relative hemodilution and the maximal decreases in hematocrit seen by the middle of the third trimester. The resulting decrease in blood viscosity is believed to improve intervillous perfusion, reducing the risk for thromboembolic events. It also serves to reduce red cell loss during delivery. The changes in hematocrit and blood volume help increase maternal cardiac output (heart rate times stroke volume). The heart rate increases from the fifth week of gestation to a maximal increment of 15 to 20 beats per minute by 32 weeks. This is in response to the relative anemia, reduced vagal control, and increased sympathetic tone. Increased stroke volume, which is primarily responsible

Table 193–2

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for the early increase in cardiac output, is related to increased myocardial muscle mass in the first trimester and end-diastolic volume in the second and early third trimesters. Overall, there is a 30% to 50% increase in cardiac output during pregnancy. Half the increase occurs during the first 8 weeks of gestation. The greatest increase is seen immediately post partum. These physiologic alterations allow the pregnant patient to tolerate 1000 to 1500 mL of blood loss without major hemodynamic changes. However, because nearly 600 to 700 mL of blood flows through the placental intervillous spaces each minute, obstetric hemorrhage can rapidly result in severe signs of shock (Table 193-1). Also, owing to the potential for severe blood loss with antepartum bleeding, the characteristics of the common causes of such bleeding should be reviewed to assist in early diagnosis and treatment (Table 193-2).

Risk Assessment The risk of antepartum hemorrhage for any one patient cannot be predicted precisely. This risk is affected by many factors, including the presence of any obstetric pathology, medical conditions, or fetal anomalies (Table 193-3).

Implications In addition to the risk of postpartum hemorrhage, antepartum hemorrhage may have important sequelae. These include coagulopathy, acute renal failure, pituitary necrosis,

Characteristics of Early and Late Antepartum Hemorrhage Diagnoses

Diagnosis

Early Pregnancy (< − 20 wk) Miscarriage

Ectopic pregnancy

Late Pregnancy (< − 20 wk) Placenta previa

Placental abruption Uterine rupture Vasa previa Unclassified bleeding

Characteristics Vaginal bleeding (± pain) >8 wk after last menstrual period; slight tenderness to uterine exam; no adnexal mass Possibly, no vaginal bleeding; pain <8 wk after last menstrual period; unilateral tenderness; possibly shock and normal-sized uterus Painless vaginal bleeding (< − 10% have painful abruption); malpresentation of fetus (35%); difficulty palpating the presenting fetal part Painful vaginal bleeding; uterine irritability or tetany; coagulopathy; fetal distress or demise Vaginal bleeding (± pain); hypotension; cessation of labor; fetal distress Painless vaginal bleeding; fetal hemoglobin present in shed blood Painless vaginal bleeding; mild bleeding (often resolves spontaneously); often >37 wk gestation

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Risk Factors Associated with Antepartum Hemorrhage

Cause

Risk Factor

Early Pregnancy (£ 20 wk) Miscarriage

Late Pregnancy (≥ 20 wk) Placenta previa Placental abruption Uterine rupture

Vasa previa

Increased parity or maternal age; prior placenta previa or cesarean delivery Trauma; ruptured membranes; cocaine, methadone, tobacco use; preeclampsia; fibroid uterus Previous uterine surgery; trauma; history of intrauterine manipulations, including placental extraction, curettage, version, forceps use; grand multiparity; uterine anomaly; placenta percreta; tumor; fetal issues (e.g., macrosomia, malposition, anomaly); induced or augmented labor Multiple gestation; low-lying placenta; pregnancy after in vitro fertilization; velamentous umbilical cord insertion; bilobed and succenturiate placentas

shock, and both maternal and fetal mortality. Perinatal morbidity and mortality are primarily the result of poor placental perfusion or preterm delivery. Coagulopathy, which is initially dilutional from ongoing loss of blood components and rapid volume replacement, may be accompanied by DIC. Although DIC is an ongoing concern with all cases of antepartum hemorrhage, it most commonly occurs with placental abruption (up to 20% of cases). Laboratory findings supporting the diagnosis of DIC are prolonged prothrombin time and partial thromboplastin time, hypofibrinogenemia, thrombocytopenia, and elevated fibrin degradation products. Although treatment for DIC is controversial, restoration of clotting factors, especially fibrinogen, is required. For a 70-kg adult, 4 g of fibrinogen is required to increase fibrinogen levels by 100 mg/dL. Fibrinogen is found in a 3- to 10-fold greater concentration in cryoprecipitate than in fresh frozen plasma; treatment requires 13 to 16 bags of cryoprecipitate. A fibrinogen level of 150 to 200 mg/dL appears to be optimal for obstetric patients. Keep in mind that it may take 20 to 40 minutes to thaw 1 unit of cryoprecipitate, which is stored at –18°C to –20°C. Acute renal failure, with or without associated DIC, occurs in about 10% of patients with severe antepartum hemorrhage. Acute renal failure is related to hypotension, renal ischemia, fibrin deposition, microvascular clotting, and myoglobinuria. It is most common with placental abruption and may be prevented by aggressive blood transfusion and volume resuscitation. Hemodynamic monitoring with pulmonary artery or central venous catheters or with transthoracic or transesophageal echocardiography may assist in assessing volume status and the need for inotropes or vasopressors. Ischemic pituitary necrosis (Sheehan’s syndrome) may accompany severe hemorrhage or even delivery without significant blood loss. Enlargement of the pituitary gland, small sella size, DIC, or autoimmunity may also contribute to Sheehan’s syndrome. Most commonly it presents as mild pituitary dysfunction, such as the failure to lactate or to resume menses. Acute hyponatremia and hypoglycemia may also accompany Sheehan’s syndrome.

MANAGEMENT Hemodynamic Management Underestimation of blood loss and inadequate volume resuscitation are common in patients with antepartum hemorrhage and likely contribute to associated maternal mortality. In one report, substandard care was considered a contributing factor in 79% of maternal deaths associated with antepartum hemorrhage. Rapid volume replacement to maintain tissue perfusion and oxygenation is more important than the type of fluid given. Colloids and blood products should be administered early, along with a request for assistance, placement of a second large intravenous line, and use of pressurized transfusion equipment. Although many centers require blood typing and screening for parturients at high hemorrhagic risk having vaginal deliveries and all those having cesarean sections, it is prudent to crossmatch and have 2 to 4 units of packed red blood cells available whenever there is a potential for significant blood loss. Such cases include known placenta previa or partial abruption and placenta accreta, increta, or percreta. If crossmatched blood is unavailable, type O, Rh-negative blood should be used. Continued blood loss with hemodynamic instability, despite blood and volume replacement, mandates more invasive monitoring. However, restoration of circulating blood volume takes precedence. Even noninvasive measures (e.g., urine output, heart rate, blood pressure) can help assess the adequacy of volume resuscitation. In such situations, the need for blood component therapy other than red cell mass may be less than previously thought. After delivery, uterine perfusion and oxygenation are less relevant, and otherwise healthy parturients can usually tolerate severe blood loss. The American Society of Anesthesiologists Task Force on Blood Component Therapy advised that transfusions of packed red blood cells, platelets, and fibrinogen component therapy are rarely indicated unless there is microvascular bleeding, the hemoglobin

OTHER SURGICAL SUBSPECIALTIES

Ectopic pregnancy

Previous miscarriage; increased maternal age; genetic aberrations; uterine abnormalities; endocrine abnormalities; infection; thrombophilic disorders; immune response abnormalities; tobacco, alcohol, drugs Endometriosis; infertility; infection; past tubal sterilization or reconstruction; intrauterine contraceptive device

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is less than 6 g/dL, the platelet count is less than 50 × 109/L, and fibrinogen is less than 80 to 100 mg/dL. Platelet transfusion may be indicated with a normal platelet count (>100 × 109/L) and known platelet dysfunction with microvascular bleeding. Finally, there is now interest in the use of erythropoietin to boost red cell production, autologous blood donation, intraoperative salvage, and acute normovolemic hemodilution in patients at high risk for antepartum hemorrhage. Further study is needed to determine the utility of such therapies.

“double setup” may be required. This involves digital examination of the vaginal fornices in the operating room, with the patient prepared for emergent cesarean delivery. This is now done only for patients with active bleeding, known fetal well-being, and equivocal imaging studies. Alternatively, interventional radiologists can place balloon occlusion catheters in the uterine arteries of very high-risk parturients, permitting rapid control of bleeding should this become necessary.

Further Reading Anesthetic Management Hemorrhaging parturients should be prepared for surgery simultaneously while optimizing hemodynamic status. Full replacement of blood loss before surgery is unrealistic, because the bleeding will continue until the cause is removed. Although regional anesthesia may be considered, other more pressing concerns may rule in favor of general endotracheal anesthesia. These include ● ● ● ● ●

Active bleeding Hemodynamically unstable patient Ongoing, labor-intensive blood and volume resuscitation Possible loss of consciousness with an unprotected airway Associated coagulopathy and increased risk for subdural or epidural hematoma

Etomidate may be the preferred induction agent in parturients with shock. Hypotension commonly occurs with thiopental, propofol, and even ketamine. After left uterine displacement, preoxygenation, and rapid-sequence induction and intubation, potent inhalational agents are relatively contraindicated because they promote uterine relaxation. Instead, oxygen and nitrous oxide, benzodiazepines, and short-acting narcotics are titrated as tolerated. Urine output should be checked often, and the need for additional intravenous lines or invasive monitoring should be assessed frequently. Following removal of the fetus and placenta, uterotonic agents (oxytocin, methylergonovine, 15-methyl prostaglandin F2α) should be administered as necessary. However, underlying uterine pathology may not permit restoration of normal uterine tone or cessation of bleeding. If so, a gravid hysterectomy may be required. This does not require general anesthesia if an epidural catheter is present, functional, and has been controlled.

PREVENTION Prevention of complications related to severe antepartum hemorrhage requires a high index of suspicion based on the patient’s history and symptoms, evaluation by ultrasonography or magnetic resonance imaging, and an expedited team response. Imaging, especially with color Doppler blood flow enhancement, has greatly improved the diagnosis of placenta previa, placental invasion of the uterine wall (placenta accreta, increta, percreta), and vasa praevia and the maternal and fetal outcomes. Even so, there are limits to the diagnostic sensitivity and specificity of these imaging methods, as well as limited access in some places. Therefore, a

Anderson FW, Hogan JG, Ansbacher R: Sudden death: Ectopic pregnancy mortality. Obstet Gynecol 103:1218-1223, 2004. Bick RL: Syndromes of disseminated intravascular coagulation in obstetrics, pregnancy, and gynecology: Objective criteria for diagnosis and management. Hematol Oncol Clin North Am 14:999-1044, 2000. Bick RL: Disseminated intravascular coagulation: A review of etiology, pathophysiology, diagnosis, and management: Guidelines for care. Clin Appl Thromb Hemost 8:1-31, 2002. Birnbach DJ, Browne IM: Anesthesia for obstetrics. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 2307–2344. Carretti N, La Marca A: Maternal serum levels of human chorionic somatotropin correlates with transferrin and erythropoietin in pregnancy. Gynecol Obstet Invest 53:28-31, 2002. Chan CC, To WW: Antepartum hemorrhage of unknown origin—what is its clinical significance? Acta Obstet Gynecol Scand 78:186-190, 1999. Chestnut DH, Dewan DM, Redick LF, et al: Anesthetic management for obstetric hysterectomy: A multi-institutional study. Anesthesiology 70:607-610, 1989. Coste J, Bouyer J, Ughetto S, et al: Ectopic pregnancy is again on the increase: Recent trends in the incidence of ectopic pregnancies in France (1992-2002). Hum Reprod 9:2014-2018, 2004. Duvekot JJ, Cheriex EC, Pieters FA, et al: Maternal volume homeostasis in early pregnancy in relation to fetal growth restriction. Obstet Gynecol 85:361-367, 1995. Gilson GJ, Samaan S, Crawford MH, et al: Changes in hemodynamics, ventricular remodeling, and ventricular contractility during normal pregnancy: A longitudinal study. Obstet Gynecol 89:957-962, 1997. Gonik B: Intensive care monitoring of the critically ill pregnant patient. In Creasy RK, Resnik R (eds): Maternal-Fetal Medicine. Philadelphia, WB Saunders, 1994, pp 865-890. Guise JM, McDonagh MS, Osterweil P, et al: Systematic review of the incidence and consequences of uterine rupture in women with previous caesarean section. BMJ 329:19-25, 2004. Hansch E, Chitkara U, McAlpine J, et al: Pelvic arterial embolization for control of obstetric hemorrhage: A five-year experience. Am J Obstet Gynecol 180:1454-1460, 1999. Hunter S, Robson SC: Adaptation of the maternal heart in pregnancy. Br Heart J 68:540-543, 1992. Kelestimur F: Sheehan’s syndrome. Pituitary 6:181-188, 2003. Koonin LM, MacKay AP, Berg CJ, et al: Pregnancy-related mortality surveillance—United States, 1987-1990. MMWR CDC Surveill Summ 46:17-36, 1997. Lund CJ, Donovan JC: Blood volume during pregnancy: Significance of plasma and red cell volumes. Am J Obstet Gynecol 98:394-403, 1967. Paterson ME: The aetiology and outcome of abruptio placentae. Acta Obstet Gynecol Scand 58:31-35, 1979. Pritchard JA, Brekken AL: Clinical and laboratory studies on severe abruptio placentae. Am J Obstet Gynecol 97:681-700, 1967. Rosevear S: Bleeding in early pregnancy. In James DK, Steer PJ, Weiner CP, Gonik B (eds): High Risk Pregnancy Management Options. London, WB Saunders, 1999. Why Mothers Die 1997-1999: Confidential Enquiries into Maternal Deaths in the United Kingdom. London, Department of Health, HMSO, 2001, pp 36-37. Williams MA, Mittendorf R, Lieberman E, Monson RR: Adverse infant outcomes associated with first-trimester vaginal bleeding. Obstet Gynecol 78:14-18, 1991.

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Case Synopsis

former placental site. Failure of this mechanism can result in massive and rapid blood loss. Predisposing factors are any that result in overdistention of the uterus or reduce the ability of the myometrium to contract, including

PROBLEM ANALYSIS Definition Every delivery is associated with some blood loss. Postpartum hemorrhage has been defined as blood loss greater than 500 mL in the first 24 hours after delivery. However, because blood loss at the time of normal vaginal or cesarean delivery may approximate or even exceed 500 mL, this definition is not useful clinically. For most cases of postpartum hemorrhage that cause morbidity or mortality or that present management problems, blood loss is significantly greater than 500 mL. Most of these cases occur immediately after birth or within the first hour after delivery.

● ● ● ● ● ● ● ● ● ● ●

Recognition Postpartum hemorrhage occurs in as many as 10% of deliveries. Postpartum blood loss is difficult to quantitate and is often underestimated. Bleeding may be obvious, such as per vagina or into the surgical wound; however, it can also be concealed and contained within the uterus, soft tissues, or peritoneum. The patient often has hypotension, tachycardia, and oliguria. In addition, there may be ongoing volume requirements.

Risk Assessment Causes of postpartum hemorrhage and predisposing factors are listed in Table 194-1. The most common cause is uterine atony. At term, blood flow through the placental vasculature is approximately 600 mL/minute. After delivery, the primary mechanism by which blood loss is controlled is contraction of the uterine myometrium to constrict severed vessels at the

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OTHER SURGICAL SUBSPECIALTIES

A 32-year-old woman, gravida 5, para 4, has continuous labor epidural analgesia and an uneventful vaginal delivery of a 4500-g infant. The anesthesiologist is called 10 minutes after delivery of the placenta when the patient is noted to be hypotensive, tachycardic, pale, and nauseated. On arrival, the anesthesiologist notices a pool of blood at the foot of the bed, a steady flow of blood per vagina, and the obstetrician vigorously massaging the uterus through the abdominal wall.

Multiple gestation Macrosomia Polyhydramnios Chorioamnionitis Prolonged labor Precipitous labor Augmented labor High parity Tocolytic agents Inhalational anesthetics at high concentrations History of uterine atony (increased likelihood of recurrence)

Retained placenta is also a common cause of both early and delayed postpartum hemorrhage, although not all cases result in significant blood loss. Retained placental fragments may be unrecognized; thus, bleeding might be insidious and cause delayed postpartum hemorrhage. Patients who have had a prior retained placenta or who deliver well before term are predisposed to retained placenta. Trauma associated with delivery represents another cause of postpartum hemorrhage and should be considered in all postpartum patients with continued blood loss despite a firm, contracted uterus. Traumatic postpartum hemorrhage can be categorized as follows: ● ● ● ●

Vaginal Cervical Perineal laceration Episiotomy

Postpartum Hemorrhage: Causes and Predisposing Factors

Cause

Predisposing Factors

Uterine atony

Multiple gestation, macrosomia, polyhydramnios, chorioamnionitis, prolonged labor, precipitous labor, augmented labor, multiparity, use of tocolytics, use of potent inhalational anesthetics, prior uterine atony Prior history of retained placenta, second-trimester delivery, abnormal placentation Precipitous delivery, instrumented delivery, macrosomia Uterine atony, inappropriate umbilical cord traction, uterine anomalies, abnormal placentation

Retained placenta Trauma to genital tract Uterine inversion

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Traumatic laceration of blood vessels, whether occurring during vaginal or cesarean delivery, can result in pelvic hematoma. Uterine rupture, especially in patients who give birth vaginally after a previous cesarean delivery, is another potential cause of postpartum bleeding. In addition to the use of instrumentation for delivery, many cases of postpartum hemorrhage occur with precipitous delivery or delivery of macrosomic infants. Uterine inversion is a rare cause of postpartum hemorrhage but can be catastrophic. It should be suspected in any case of postpartum hemorrhage when significant hypotension coexists. Most cases of uterine inversion are obvious owing to the associated vaginal mass. Risk factors for uterine inversion include uterine atony, inappropriately applied fundal pressure or umbilical cord traction, uterine anomalies, and abnormal placentation.

Implications Patient outcome depends on the severity and rate of blood loss, as well as the need for additional anesthetic or obstetric interventions. Postpartum hemorrhage is a major cause of morbidity and remains one of the top five causes of maternal death in both developed and developing countries.

MANAGEMENT Basic Management Similar to any case of hemorrhage, basic resuscitative measures are required. Blood pressure, heart rate, respiration, and level of consciousness should be assessed quickly whenever one is called to evaluate a patient with postpartum bleeding. Adequate intravenous access should be obtained if it is not already present. General supportive measures are instituted, including oxygen by facemask and Trendelenburg positioning. Appropriate blood products should be requested and, depending on the situation, additional anesthesia help should be summoned. For all categories of anesthetic management, one must remember that immediately post partum, all patients continue to have delayed gastric emptying. Therefore, an oral nonparticulate antacid should be administered before any anesthetic intervention is performed.

Obstetric and Anesthetic Management Analgesia or anesthesia may be required, depending on the need for surgical intervention. Manual extraction of the placenta is usually a brief procedure, but in most cases of retained placenta, some form of analgesia or anesthesia is necessary. If an epidural catheter is in place and functional, it may be possible to perform manual extraction without further anesthesia. Alternatively, a bolus of local anesthetic can be administered epidurally if the patient’s volume status is adequate. If a catheter is not in place or not functioning, it may be possible to perform a manual extraction using small amounts of intravenous opioids, anxiolytics, or ketamine. Forty percent to 50% nitrous oxide by facemask can also be administered as an adjunct to provide some

degree of analgesia. If this proves inadequate, a low spinal anesthetic may be administered, provided that the patient has received adequate volume resuscitation. If general anesthesia is required, rapid-sequence induction with cricoid pressure and tracheal intubation is necessary. If the cause of hemorrhage is uterine atony, obstetric treatment initially involves external uterine massage and administration of uterotonic agents. If bleeding continues, laparotomy and ligation of uterine, hypogastric, or ovarian arteries, or even hysterectomy, may be necessary. These may be prolonged surgical procedures with massive blood loss. Regional anesthesia can be used, especially if an epidural catheter is already in place; however, this should be considered only when there are adequate anesthesia personnel to perform the multiple simultaneous tasks required. Because patients with epidural catheters (or single or continuous spinal blocks) are often awake, it may be difficult to manage ongoing volume resuscitation while also establishing arterial or central access. Further, sympathetic block with central neuraxial techniques may complicate the management of ongoing hemorrhage, especially if block reinforcement is required. Repair of vaginal or perineal lacerations can sometimes be performed with local anesthetic infiltration by the obstetrician. However, most patients with significant postpartum hemorrhage from these causes require spinal or epidural anesthesia, and some require general anesthesia. The obstetrician often needs excellent exposure to repair a cervical laceration, necessitating the use of spinal, epidural, or general anesthesia with muscle relaxants. Evacuation of pelvic or retroperitoneal hematomas usually requires laparotomy, and central neuraxial block or general anesthesia is needed for such procedures. TOCOLYTIC AGENTS Management of retained placenta and uterine inversion involves the administration of tocolytic medications to allow the obstetrician to perform manual extraction or replace the inverted uterus. In normovolemic patients, intravenous nitroglycerin (50 to 100 μg) provides uterine relaxation in about 45 seconds and lasts approximately 60 seconds. Nitroglycerin spray is also used as an alternative to intravenous administration for uterine relaxation. Each spray delivers about 400 μg of nitroglycerin sublingually; therefore, careful attention to the patient’s blood pressure is essential. If nitroglycerin is ineffective or the cervical os has closed (i.e., does not permit a transvaginal or other operative procedure), deep general anesthesia may be needed. After rapid-sequence induction and tracheal intubation, a potent volatile agent provides uterine relaxation, but the agent should be discontinued as soon as possible after the intervention. OXYTOCIC AGENTS The primary treatment for uterine atony is the use of uterotonic medications. Oxytocin is the first choice for both the treatment and prophylaxis of uterine atony. Prophylactic oxytocics reduce the risk of postpartum hemorrhage by about 60%. Oxytocin is typically administered by intravenous infusion, with 20 to 40 units added to 1 L of carrier fluid.

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successful use of recombinant factor VIIa (20 to 40 μg/kg) in patients with severe, refractory postpartum hemorrhage.

PREVENTION Postpartum hemorrhage usually occurs without warning. Prevention of associated morbidity and mortality requires vigilance, a high index of suspicion, and preparedness for a rapid response.

Further Reading Boehlen F, Morales MA, Fontana P, et al: Prolonged treatment of massive postpartum haemorrhage with recombinant factor VIIa: Case report and review of the literature. Br J Obstet Gynaecol 3:284-287, 2004. Crowley M: Postpartum hemorrhage. In Atlee JL (ed): Complications in Anesthesia. Philadelphia, WB Saunders, 1999, pp 817-819. El-Refaey H, Rodeck C: Post-partum haemorrhage: Definitions, medical and surgical management: A time for change. Br Med Bull 67:205-217, 2003. Mayer D, Spielman F, Bell E: Antepartum and postpartum hemorrhage. In Chestnut DH (ed): Obstetric Anesthesia Principles and Practice, 3rd ed. Philadelphia, Elsevier Mosby, 2004, pp 668-682. Papp Z: Massive obstetric hemorrhage. J Perinat Med 31:408-414, 2003.

OTHER SURGICAL SUBSPECIALTIES

It can cause vasodilatation and hypotension if administered by bolus. If this alone is unsuccessful, ergot alkaloids are second-line medications for the treatment of uterine atony. Both ergonovine and methylergonovine produce tetanic uterine contractions, most likely mediated by α-adrenergic receptors. The usual dose is 0.2 mg intramuscularly. Effects are observed within a few minutes and last several hours. These agents may cause extreme hypertension, especially in hypertensive patients or those receiving concomitant vasopressor therapy. Such ergot-induced hypertension may be severe enough to cause intracranial hemorrhage, stroke, or seizures. If these methods fail to relieve uterine atony, 15-methyl prostaglandin F2α can be used to treat refractory cases. However, it may cause bronchospasm and alter lung ventilation-perfusion ratios, causing hypoxemia. The usual dose is 250 μg administered intramuscularly or intramyometrially. It can be repeated every 15 to 30 minutes, but the total dosage should not exceed 2 mg. Misoprostol, another prostaglandin, has been investigated for safety and efficacy in the treatment of postpartum hemorrhage. A dose of 1000 μg per rectum has been shown to be effective for severe postpartum hemorrhage unresponsive to standard uterotonic agents. Recently, several case reports have described the

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Pulmonary Aspiration in the Parturient Nollag O’Rourke and William R. Camann Case Synopsis A 32-year-old woman, gravida 2, para 1, with a full-term pregnancy undergoes general anesthesia for emergency cesarean delivery owing to prolonged fetal bradycardia. The patient receives a rapid-sequence induction using thiopental and succinylcholine. The trachea is intubated using a 3.0 MacIntosh blade, cricoid pressure, and a styletted 7.5 endotracheal tube. After cesarean delivery, the patient is extubated and transferred to the postanesthesia care unit. She is breathing spontaneously with supplemental oxygen. Vital signs include blood pressure of 110/78 mm Hg, heart rate of 96 beats per minute, and arterial oxygen saturation of 88% on 6 L of oxygen by facemask. On physical examination, the patient is noted to have bilateral wheezing, and the chest radiograph reveals a right lower lobe infiltrate.

PROBLEM ANALYSIS Definition Pain relief during childbirth has long been of interest to anesthesiologists. As the quest for optimal analgesia and anesthesia for childbirth continues, so does that for the prevention and management of one of the most important peripartum complications: pulmonary aspiration of gastric contents. Hall first noted an increased incidence of this complication in obstetric patients in 1940. The term used to describe such pulmonary aspiration, chemical pneumonitis, soon gained popularity. In 1946 Mendelson more completely defined this condition. Parturients belong to a special category of patients at increased risk for difficult or failed intubation and aspiration. The incidence of failed intubation in obstetric patients is estimated to be 8 to 10 times greater than that in the general surgical population. Aspiration pneumonitis most often occurs with difficult or failed intubation. However, there are pregnancy-specific factors that contribute to the increased risk of aspiration, including the following: ● ● ● ●

Increased levels of progesterone Reduced sphincter tone at the gastroesophageal junction Elevation of the gravid uterus against the stomach Mechanical obstruction of the duodenum by the latter

The gravid uterus further compromises esophageal sphincter tone due to distortion of the gastroesophageal angle. Also, “pushing” during the second stage of labor, manual pressure on the lower abdomen, and the lithotomy position act in concert to increase intra-abdominal pressure and decrease gastric emptying (Table 195-1). The production of motilin, a hormone that speeds gastric emptying, is depressed throughout pregnancy and returns to near normal by 1 week post partum. Nevertheless, gastric emptying appears to be normal in early pregnancy. 782

The cause of delayed gastric emptying during advanced labor, despite satisfactory epidural analgesia, is unknown. However, recent work suggests that gastric volume and acidity at term gestation are no different from those parameters in the nonpregnant state, during early pregnancy, or in the postpartum period. Iatrogenic factors that may increase the risk of gastric aspiration include parenteral or epidural opioids and the use of anticholinergic drugs (e.g., glycopyrrolate). Opioids slow gastric motility, and anticholinergics reduce esophageal sphincter tone.

Recognition Signs and symptoms of chemical pulmonary aspiration are quite variable and are largely a function of volume and pH (Table 195-2); however, such aspiration may also be “silent.” Further, the anesthetist may be unable to see aspirate in the posterior oral pharynx. Coughing and bronchospasm may

Table 195–1

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Aspiration Risk Factors Related to the Parturient

Cause

Effect

Gastric volume and acidity Increased levels of progesterone Reduced levels of motilin

No change at term or during early pregnancy Reduced gastroesophageal sphincter tone Delayed gastric emptying in advanced labor Mechanical compromise of esophageal sphincter Decreased gastric motility and sedation Decreased esophageal sphincter tone

Gravid uterus Parenteral or epidural opioids Anticholinergic drugs

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Signs and Symptoms of Chemical Pulmonary Aspiration

also be infrequent symptoms. Often, radiographic changes provide the first evidence of aspiration; such changes are found in dependent parts of the lung, often in the right lower lobe. The outcome for patients with chemical pulmonary aspiration can be categorized as follows: Roughly 10% to 15% of patients have rapid clinical deterioration, with hypoxia and early circulatory shock. Of the remaining patients, approximately two thirds improve rapidly within 1 to 4 days; they may require ventilatory support. The other one third develop bacterial lung infections necessitating antibiotic therapy. Most lung injuries eventually resolve.

Risk Assessment The actual incidence of maternal chemical aspiration is unknown. It is likely that minor degrees of aspiration often go unnoticed, and only maternal deaths from aspiration are reported. In a retrospective review of 185,000 anesthetic inductions, Olsen and colleagues found that the incidence of aspiration was 1 in 2131 (0.047%) for nonobstetric inductions and 1 in 661 (0.15%) for inductions before cesarean delivery (i.e., a threefold increase in aspiration risk during pregnancy). Warner and colleagues found the incidence to be 1 in 3216 (0.031%) for general anesthesia and 1 in 895 (0.11%) for emergency operations. Although Warner’s group evaluated all types of emergency cases, cesarean delivery is often emergent. More recently, Ezri and colleagues retrospectively studied patients having general anesthesia around the time of delivery (e.g., manual extraction of placenta) or immediately after delivery (e.g., repair of lacerations) from 1979 to 1993. They found a 0.05% incidence of aspiration (1 in 1870 cases). All patients were breathing spontaneously, were not intubated, and had general anesthesia induced and maintained with intravenous agents. The lower incidence of aspiration in this group compared with the general surgical population might be related to reduced intra-abdominal pressure. Also, many cases of chemical pulmonary aspiration occur with difficult or failed intubations that require mask ventilation. Even more recently, Han and coworkers reported the use of laryngeal mask airway for elective cesarean delivery in 1060 patients. Although there were no reported cases of aspiration, this success may be attributed to careful patient selection. Among the patients excluded were those with symptoms of gastric reflux, an American Society of Anesthesiologists (ASA) classification higher than II, a known difficult airway, or a prepregnancy body mass index greater than 30, as well as those who had fasted for less than

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6 hours. Also, antacid prophylaxis was used preoperatively, and cricoid pressure was applied. However, in practice, almost all parturients requiring general anesthesia are those with obstetric emergencies, especially the unexpected need for cesarean delivery. We believe that such nonfasting patients require a rapid-sequence induction and tracheal intubation. Finally, anesthesia-related maternal mortality has decreased in recent years due to the increased use of regional anesthesia. Even so, Hawkins and coworkers reported that 23% of all anesthesia-related deaths in obstetric patients were a direct result of aspiration. Although data on maternal morbidity with perioperative aspiration are generally not reported, several studies now indicate that there is still significant morbidity associated with this condition in obstetric patients. Although all parturients are at increased risk for chemical pulmonary aspiration, the timing and nature of peripartum surgery, as well as the circumstances under which general anesthesia is performed, must be considered when interpreting studies of the incidence of peripartum pulmonary chemical aspiration.

Implications The volume, content, and character of any gastric aspirate determine the severity of pneumonitis after pulmonary aspiration. Many believe that gastric pH is more critical for determining the severity of lung injury after pulmonary aspiration than is the actual volume (provided it is < 25 mL). Others, notably James and associates, believe that regardless of volume, lower pH correlates with higher mortality. Particulate matter increases the risk of lung injury after aspiration, because large particles can lodge in major bronchi, causing asphyxiation within minutes. However, nonacid aspirates may produce only mild, transient hypoxia, with no evidence of parenchymal injury; such hypoxia may be due to bronchospasm and microatelectasis. As the acidity of the aspirate increases, the potential for parenchymal injury and pulmonary hemorrhage increases. Amplification of this response may lead to the acute respiratory distress syndrome, which is characterized by persistent lung inflammation with radiologic evidence of bilateral pulmonary infiltrates. These infiltrates are due to increased vascular permeability and reduced arterial oxygen tension (irrespective of the fraction of inspired oxygen or the use of positive endexpiratory pressure), with no increase in left atrial pressure. Survival has improved with better supportive care and ventilatory strategies, but mortality from gastric aspiration and associated acute respiratory distress syndrome is still very high, with current estimates ranging from 35% to 40%.

MANAGEMENT Immediately after aspiration, airway management is critical (Table 195-3). Any aspirate identified in the posterior oral pharynx should be quickly evacuated, and the airway should be secured. Although several authors recommend a headdown tilt or left lateral decubitus position to minimize the spread of aspirate, this position has not been proved to reduce such spread. Tracheal suctioning without saline

OTHER SURGICAL SUBSPECIALTIES

None Gastric contents in oropharynx Cough Bronchospasm Oxygen desaturation Circulatory shock Infiltrates on chest radiograph

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Indicated Therapy after Suspected Pulmonary Aspiration

Secure airway; provide supplemental oxygen and positive end-expiratory pressure Place patient in head-down position and turn head to one side Alternatively, place patient in left lateral decubitus position Provide tracheal suctioning (intubate to protect airway, if not already done) Once airway is protected, consider gastric decompression with oro- or nasogastric tube Initiate β-agonist therapy for bronchospasm Consider systemic steroids (dexamethasone 1 mg/kg or methylprednisolone 30 mg/kg) Institute conservative fluid management

lavage is advised for removal of the aspirate. Saline lavage may disseminate the aspirate to more distal airways and worsen the situation. The pH of the aspirate may be measured to help identify the nature of the gastric contents. The most important factors for reducing morbidity are quick identification of aspiration, expeditious airway intubation, and ventilation with supplemental oxygen and positive end-expiratory pressure. Bronchospasm may be relieved by the administration of an intravenous β-agonist. Although acid-injured lungs are more susceptible to bacterial infection, there is no evidence that prophylactic antibiotic administration alters the incidence of infection, nor does it affect the outcome. Prophylactic antibiotics may even facilitate the development of infection with resistant organisms. Similarly, the administration of systemic glucocorticoids is controversial. Several animal models suggest a reduction in pulmonary damage if steroids are given immediately after the insult. Other data suggest that any benefit may be outweighed by steroid-caused reduction of macrophage activity and subsequent increased susceptibility to gram-negative pneumonia. Although it is not uncommon to administer methylprednisolone (30 mg/kg) or dexamethasone (1 mg/kg), current thinking does not advocate this practice. The use of fluids must be restricted. Damaged pulmonary endothelium exudes protein-rich edematous fluid, and patients may be further compromised by pulmonary edema from the overly aggressive use of intravenous fluids.

PREVENTION Perhaps the single most important treatment measure is prevention. Preventive measures include the following: ●

● ● ● ● ●

Implementation of ASA fasting guidelines in patients in labor Regional anesthesia Cricoid pressure Administration of nonparticulate antacid Metoclopramide administration H2-receptor antagonist administration

Prevention approaches can be categorized as pharmacologic and nonpharmacologic. The nonpharmacologic approach includes implementing ASA fasting guidelines in

patients in labor and minimizing their exposure to general anesthesia with the appropriate use of regional techniques. However, emergencies may arise that require general anesthesia under conditions that are less than optimal for intubation. In these situations, prevention is often a combination of pharmacologic and classic full-stomach precautions. Recent national trends encourage the oral intake of fluids during labor, and the ASA Task Force on Obstetrical Anesthesia supports this practice. Owing to the adverse metabolic consequences of prolonged starvation during labor, modest amounts of clear fluids, including isotonic “sports drinks,” are now recommended for patients with uncomplicated labor. However, in patients with additional risk factors for aspiration (e.g., morbid obesity, diabetes, difficult airway) or an increased risk of operative delivery, more restricted oral intake may be required; this should be decided on a case-by-case basis. Solid food should be avoided in all patients in active labor and those who have received opioid-containing analgesics. Cricoid pressure is a simple technique that may help prevent passive regurgitation during induction of general anesthesia. Pressure must be maintained until the trachea is intubated, the endotracheal cuff is inflated, and intubation is confirmed. In approximately 5% to 7% of obstetric patients, intubation is difficult to perform. If a difficult airway is anticipated, an awake intubation may be appropriate. Just as these patients are at risk for aspiration during induction, similar precautions must be observed during extubation. Extubation should occur only when the patient is conscious and able to follow commands appropriately. It is important to differentiate between the excitement phase of recovery and actual emergence. Airway assessment, management of failed intubation, and alternative techniques of airway management should be reviewed before the induction of general anesthesia. Pharmacologic approaches to reducing the risk of aspiration often begin with the administration of a nonparticulate antacid. Antacids are one of the most effective and practical means of altering gastric pH. However, the maximal effects of nonparticulate antacids are limited to approximately 30 minutes’ duration. Similarly, the administration of 10 mg intravenous metoclopramide is beneficial. Although metoclopramide does not directly affect gastric pH, it possesses antiemetic properties, increases lower esophageal sphincter tone, and decreases gastric emptying time. A reduction in gastric volume can be observed after about 20 minutes of intravenous administration. H2-receptor antagonists, such as cimetidine, ranitidine, and famotidine, are effective in reducing hydrochloric acid production by the gastric parietal cells. With histamine blockers, timing is important; effects can be seen 30 minutes after intravenous administration, but 60 to 90 minutes are required for maximal effect. This delay in onset limits their efficacy during an emergency. In addition to histamine and gastrin, acetylcholine is an endogenous secretagogue. Administration of anticholinergic medications can inhibit gastric fluid production, with variable results. Of the anticholinergics, glycopyrrolate has the most profound effect on gastric secretion and pH. However, this benefit is outweighed by concurrent reduction of lower esophageal sphincter tone and delayed

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gastric emptying. Consequently, these medications are not recommended for aspiration prophylaxis.

Further Reading

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Hawkins JL, Koonin L, Palmer SK, et al: Anesthesia-related deaths during obstetric delivery in the United States, 1979-1990. Anesthesiology 86:277, 1997. James CF, Modell JH, Gibbs CP, et al: Pulmonary aspiration effects of volume and pH in the rat. Anesth Analg 63:665, 1984. King TA, Adams AP: Failed tracheal intubation. Br J Anaesth 65:400, 1990. Kubli M, Scrutton MJ, Seed PT, et al: An evaluation of “isotonic sports drinks” during labor. Anesth Anal 94:404, 2002. Malinow AM, Ostheimer GW: Anesthesia for the high-risk parturient. Obstet Gynecol 69:951, 1987. Mendelson CL: Aspiration of stomach contents into lungs during obstetric anesthesia. Am J Obstet Gynecol 53:191, 1946. Olsen GL, Hallen B, Hambraes-Johnson K: Aspiration during anaesthesia: A computer-aided study of 185,358 anesthetics. Acta Anaesthesiol Scand 30:84, 1986. O’Sullivan G, Scrutton M: NPO during labor: Is there any scientific validation? Anesthesiol Clin North Am 21:87, 2003. Schwartz DJ, Wynne JW, Gibbs CP, et al: The pulmonary consequences of aspiration of gastric contents at pH values greater than 2.5. Am Rev Respir Dis 121:119, 1980. Warner MA, Warner ME, Webber JG: Clinical significance of pulmonary aspiration during the perioperative period. Anesthesiology 78:56, 1993.

OTHER SURGICAL SUBSPECIALTIES

American Society of Anesthesiologists Task Force on Obstetric Anesthesia: Practice guidelines for obstetric anesthesia. Anesthesiology 90:600, 1999. Downs JB, Chapman RL, Modell JH, et al: An evaluation of steroid therapy in aspiration pneumonitis. Anesthesiology 40:129, 1994. Ezri T, Szmuk P, Stein A, et al: Peripartum general anesthesia without tracheal intubation: Incidence of pulmonary aspiration. Anaesthesia 55:421, 2000. Gibbs CP: Gastric aspiration prevention and treatment. Clin Anesth 4:47, 1986. Hall GC: Aspiration pneumonitis as an obstetric hazard. JAMA 114:728, 1940. Han TH, Brimacombe J, Lee EJ, et al: The laryngeal mask airway is effective (and probably safe) in selected healthy parturients for elective cesarean section: A prospective study of 1067 cases. Can J Anaesth 48:1117, 2001.

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Embolic Events of Pregnancy Cheryl DeSimone Case Synopsis A 32-year-old woman, gravida 2, para 0, undergoes cesarean delivery of twins under spinal anesthesia. After delivery of the neonates, the patient complains of chest pain; oxygen saturation subsequently decreases to 75%, and blood pressure falls to 60/40 mm Hg.

PROBLEM ANALYSIS Definition Embolic events during pregnancy are the leading cause of maternal mortality in the United States, accounting for 20% of all maternal deaths. Such events are the most common causes of acute hemodynamic and respiratory collapse during pregnancy. Embolism results from blood clots, fat particles, tumor cells, air, amniotic fluid, or foreign material entering the circulatory system. Most emboli originate from venous thromboses, amniotic fluid, or air. The clinical presentation of embolic events in pregnancy varies from no symptoms to cardiovascular collapse. Variation in the initial presentation of such events is due to the size and type of embolus, as well as its location.

Recognition PULMONARY EMBOLISM Symptoms of pulmonary embolism are listed in Table 196-1. In the case of a massive embolism, defined as obstruction of more than 50% of the pulmonary circulation, hypotension, syncope, or cardiovascular collapse may be the presenting symptom. If pulmonary embolism is clinically suspected, a chest radiograph, electrocardiogram (ECG), and arterial blood gas analysis may assist in the diagnosis. However, the primary screening tool for diagnosis is a ventilation-perfusion scan. A normal scan precludes the presence of pulmonary embolus. A high-probability scan indicates the need for therapy. An indeterminate scan may require further study, including spiral (helical) computed tomography or pulmonary angiography. AMNIOTIC FLUID EMBOLISM Whereas the classic presentation of amniotic fluid embolism is the sudden onset of dyspnea, cyanosis, and hypotension followed by cardiovascular collapse, signs and symptoms are often vague, nonspecific, and similar to those of other types of pulmonary embolism (Table 196-2). Twenty percent of patients initially present with a seizure, and 40% develop consumptive coagulopathy and profuse hemorrhage. 786

Primarily, the diagnosis is made by the clinical presentation. Because many patients are hemodynamically unstable, it may be difficult to perform specific testing. In acute cases, the ECG may show a right ventricular strain pattern, with typical ST-T changes and tachycardia. Transthoracic or transesophageal echocardiography confirms severe left ventricular failure. The chest radiograph may be normal or show effusions, an enlarged cardiac silhouette, or pulmonary edema. Pulmonary scans may show multiple filling defects. Identification of fetal squamous cells in the pulmonary artery was once considered pathognomonic for amniotic fluid embolism, but this is no longer the case, because such cells may be recovered from the pulmonary circulation of pregnant women without amniotic fluid embolism. The term anaphylactoid syndrome of pregnancy is often used to describe the clinical manifestations of amniotic fluid embolism. It presents similarly to toxic reactions involving multiple organ systems. Anaphylactoid syndrome of pregnancy has three distinct phases, which may occur separately or together. After embolism, respiratory distress with cyanosis occurs. This leads to hemodynamic compromise, pulmonary edema, and cardiovascular shock. Ultimately, seizures, coma, or both result from cerebral hypoperfusion. VENOUS AIR EMBOLISM Symptoms and signs of venous air embolism are listed in Table 196-3. In patients under general anesthesia, an abrupt reduction in end-tidal carbon dioxide may be the initial sign. The clinical presentation depends on the volume, rate, and duration of air entrainment, as well as where it is deposited. Air in the coronary circulation may cause cardiac arrhythmias,

Table 196–1

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Signs and Symptoms of Pulmonary Embolism

Sudden onset of tachypnea Dyspnea Pleuritic chest pain Apprehension Nonproductive cough Hemoptysis Cyanosis Accentuated second heart sound

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Table 196–2

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Signs and Symptoms of Amniotic Fluid Embolism

chest pain, and myocardial infarction. Cerebral air embolism is associated with seizures, unconsciousness, paralysis, or visual disturbances. Hypotension and cardiac arrest may result from air in the pulmonary outflow track. Disseminated intravascular coagulation and endothelial damage result from air within the microcirculation; these are later manifestations. Capnography appears to be the most sensitive means of detecting venous air embolism. A sudden decrease in endtidal carbon dioxide occurs, followed by reduced arterial oxygen saturation. Precordial Doppler ultrasonography may confirm the diagnosis. Transesophageal echocardiography is more sensitive and specific, but use of this test is limited in obstetric practice. Finally, air aspiration from a central venous pressure catheter is diagnostic.

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787

during vaginal or cesarean delivery, as well as in the immediate postpartum period. It has been reported after abdominal trauma and with termination of pregnancy. Further, amniotic fluid embolism may occur without uterine contractions or manipulation. Risk factors are inconsistent, and the condition does not appear to be preventable. VENOUS AIR EMBOLISM Venous air embolism is quite common, occurring in 52% of cesarean deliveries. It is speculated that partial placental separation allows the ingress of air into the uterine sinuses. Air embolism has been reported to occur during manual extraction of retained placenta previa or accreta, during placental abruption, and with forceps or vacuum deliveries. It has also occurred following uterine rupture or after breech delivery. During cesarean delivery, both ruptured membranes and a protracted interval between uterine incision and delivery of the fetus are known risk factors for air embolism.

Implications PULMONARY EMBOLISM Although fatal pulmonary embolism is rare, it is the leading cause of pregnancy-related mortality in the United States.

Risk Assessment

AMNIOTIC FLUID EMBOLISM

PULMONARY EMBOLISM

Amniotic fluid embolism is a rare, unpredictable, and nonpreventable obstetric complication. It is responsible for 5% to 18% of maternal deaths in the United States. Overall maternal mortality ranges from 26% to 86% with amniotic fluid embolism. Up to 50% of fatalities occur within the first hour, and fetal survival is only 39%. Noncardiogenic pulmonary edema develops in 70% of patients who survive the initial amniotic fluid embolism. Neurologic impairment and acute renal failure may also occur.

The incidence of thromboembolism during pregnancy is from 0.5 to 3 per 1000 patients. Of these, pulmonary embolism occurs in up to 24%, with a mortality rate of 15%. This incidence is five times greater than in nonpregnant patients and is due to increased lower extremity venous stasis and hypercoagulability associated with pregnancy. Thromboembolism occurs with equal frequency during the antepartum and postpartum periods. Risk factors include prolonged bed rest, operative delivery (either instrument-assisted or cesarean), hemorrhage, sepsis, multiparity, obesity, and advanced maternal age. AMNIOTIC FLUID EMBOLISM The actual incidence of amniotic fluid embolism is unknown, but the reported incidence ranges from 1 in 8000 to 1 in 80,000 deliveries. A recent study reported an incidence of 1 in 20,046 deliveries. Amniotic fluid embolism can occur

Table 196–3

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Signs and Symptoms of Venous Air Embolism

Gasping Dyspnea Chest pain Hypotension Mill-wheel murmur Cyanosis Increase in central venous pressure Reduction in end-tidal carbon dioxide Electrocardiographic changes Cardiac arrest

VENOUS AIR EMBOLISM Venous air embolism causes significant hemodynamic compromise in only 0.7% to 2% of parturients at delivery. However, even small amounts of air can result in ventilationperfusion mismatch, hypoxemia, right ventricular failure, arrhythmias, and hypotension. Larger volumes (>3 mL/kg) may be fatal, usually as a result of right ventricular outflow tract obstruction.

MANAGEMENT Pulmonary Embolism Treatment for pulmonary embolism includes both cardiovascular and respiratory support. It focuses on maintaining adequate maternal and fetal oxygenation, maternal circulatory support, and immediate anticoagulation. Two thirds of patients who ultimately die from pulmonary embolism do so within 30 minutes of the acute event. If the clinical picture strongly suggests pulmonary embolism, anticoagulation therapy should be initiated to

OTHER SURGICAL SUBSPECIALTIES

Dyspnea Cyanosis Hypotension Seizures Cardiovascular collapse Consumptive coagulopathy with profuse hemorrhage

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prevent further embolic events before any diagnostic studies are obtained. When anticoagulation is contraindicated or ineffective, interruption of the inferior vena cava by transvenous placement of a Greenfield filter is considered safe and effective. Thrombolytic therapy is relatively contraindicated in pregnancy but may be useful for the prevention of re-embolization in parturients who are hemodynamically unstable and hypoxic. If pulmonary embolism is life threatening, emergency embolectomy is indicated.

Amniotic Fluid Embolism Treatment is primarily symptomatic and is aimed at the restoration of oxygenation, blood volume, and cardiac output and the correction of coagulopathy. If there is cardiopulmonary arrest, cardiopulmonary resuscitation, endotracheal intubation, and mechanical ventilation with 100% oxygen should be initiated immediately. Because of high early maternal mortality, delivery should be expedited, and the obstetrician must be prepared to perform postmortem cesarean section. Early delivery of the infant allows more effective cardiopulmonary resuscitation of the mother. The parturient’s circulating blood volume and cardiac output can be augmented by infusions of crystalloid and vasopressors. Direct arterial pressure monitoring and pulmonary artery catheters are used to guide resuscitative efforts. Communication with the blood bank is important to facilitate the availability of large quantities of blood products, which may be required during resuscitation or treatment of associated coagulopathies. Patients who survive delivery require intensive care management.

Venous Air Embolism Successful treatment for venous air embolism lies in early recognition. When embolism occurs, repositioning the patient in the reverse Trendelenburg position, with left lateral tilt, and flooding the surgical field with saline may reduce further air entrainment. If the patient is awake, 100% oxygen should be administered by mask. If the patient is under general anesthesia, nitrous oxide must be discontinued, followed by the administration of 100% oxygen. Intravenous fluids are used to reduce hemoconcentration with increased blood viscosity. If acute cardiovascular collapse occurs, a central venous catheter may be placed to attempt to aspirate air from the right atrium. With evidence of neurologic sequelae or delayed emergence from general anesthesia, paradoxical cerebral air embolism should be suspected, and hyperbaric oxygen therapy should be considered.

PREVENTION Pulmonary Embolism Women with a history of deep venous thrombosis or pulmonary emboli while taking oral contraceptives or during pregnancy are thought to have a 4% to 12% increased risk of recurrent events during subsequent pregnancies. They should receive prophylactic anticoagulation throughout pregnancy. Women with a hypercoagulable state or history of thromboembolism unrelated to pregnancy are also at increased risk and should receive similar prophylaxis.

Amniotic Fluid Embolism There is no evidence that amniotic fluid embolism can be prevented. There are case reports of women who have survived amniotic fluid embolism and gone on to have subsequent uneventful pregnancies.

Venous Air Embolism Venous air embolism is common during cesarean and vaginal deliveries. During cesarean delivery, traction on or externalization of the uterus is associated with an increased incidence of air embolism and should be minimized. Early recognition and the avoidance of further air entrainment can prevent subsequent morbidity or mortality

Further Reading Barbour LA: Thromboembolism in pregnancy. ACOG Pract Bull 19, Aug 2000. Clark SL, Hankins GDV: Amniotic fluid embolism: Analysis of the national registry. Am J Obstet Gynecol 172:1158-1168, 1995. Deblieux PM, Summer WR: Acute respiratory failure in pregnancy. Clin Obstet Gynecol 39:143-152, 1996. Gei AF, Vadhera RB, Hankins GD: Embolism during pregnancy: Thrombus, air, and amniotic fluid. Anesthesiol Clin North Am 21:165-182, 2003. Gilbert W: Amniotic fluid embolism: Decreased mortality in a populationbased study. Obstet Gynecol 93:973-977, 1999. Malinow AM: Embolic disorders. In Chestnut DH (ed): Obstetric Anesthesia: Principles and Practice, 3rd ed. St. Louis, Mosby–Year Book, 2004, pp 683-694. Martin RW: Amniotic fluid embolism. Clin Obstet Gynecol 39:101-106, 1996. McDougal RJ, Duke GJ: Amniotic fluid embolism syndrome: Case report and review. Anaesth Intensive Care 23:735-740, 1995. Toglia MR, Weg JG: Venous thromboembolism during pregnancy. N Engl J Med 335:108-114, 1996. Weissman A, Kol S, Peretz BA: Gas embolism in obstetrics and gynecology: A review. J Reprod Med 41:103-111, 1996.

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Mark A. Zakowski, Manuel C. Vallejo, and Sivam Ramanathan OTHER SURGICAL SUBSPECIALTIES

Case Synopsis A 32-year-old woman, gravida 1, para 0, had uneventful epidural analgesia for labor using 0.125% bupivacaine and fentanyl 2 μg/mL. A 10-mL intravenous bolus was administered, followed by infusion of the same mixture at 10 mL/hour. Subsequently, she required midforceps delivery with manual fetal version for occiput posterior vertex presentation. Before version and extraction of the infant, 20 mL of 2% lidocaine with 1:200,000 epinephrine was administered. The next day, the patient complained of sensory loss in and inability to move both lower extremities, and she had fecal incontinence. Two days later, she regained partial motor function and sensation in both lower extremities but still had fecal incontinence and subsequently developed urinary retention with overflow incontinence. A neurology consultation was obtained. Possible cauda equina syndrome was diagnosed on the fourth postpartum day. At 6 months, the patient still required a wheelchair but had some improvement in bowel and bladder function.

PROBLEM ANALYSIS Definition The reported incidence of neurologic complications with regional anesthesia in obstetric patients is from 1 in 2500 to 1 in 13,000. Persistent complications usually are not due to the anesthetic itself but are more often associated with obstetric trauma during birth. However, more recent data indicate that the incidence of anesthetic complications may be higher than formerly believed. In a closed claim analysis of 1005 regional anesthetics by Lee and colleagues, neuraxial block was performed in all 368 obstetric and 453 of 637 nonobstetric claims. Injuries in 51% of obstetric and 41% of nonobstetric claims were related to neuraxial block. The obstetric group had a significantly greater proportion of neuraxial claims involving transient and low-severity injuries (71%) than did the nonobstetric group (38%), yet the proportion of obstetric claims involving severe adverse outcomes (including death or permanent brain injury) was significantly lower. Among the causes of these adverse outcomes were cardiovascular collapse, respiratory arrest, and neuraxial hematoma in patients with coagulopathies. Wong and coworkers studied 60,057 women who gave birth to live infants and later interviewed 6048 of the women. Fifty-six (0.92%) had new lower extremity peripheral nerve injuries. By logistic regression analysis, multiparity and prolonged second-stage labor were significantly associated with nerve injuries. Patients with nerve injuries spent more time in a semi-Fowler lithotomy position “pushing” than did those without such injury. The median duration of symptoms was 2 months, and injuries involved one of the lower limb peripheral nerves or the lumbosacral plexus. Thus, these findings suggest that neurologic injuries related to childbirth may be related more to childbirth itself rather than the anesthetic.

Recognition When evaluating a patient with suspected neurologic complications, the answers to several questions are pertinent: ● What was the duration of labor? ● How long did the patient “push”? ● Was the patient placed in an exaggerated lithotomy position while pushing? ● Did the obstetrician use forceps to facilitate delivery? ● What was the weight of the neonate? ● What was the position of the presenting part (e.g., occiput posterior)? ● Did the patient have a history of back problems or preexisting neurologic impairment (e.g., multiple sclerosis, human immunodeficiency virus [HIV])? ● What type and amount of local anesthetic were used? ● Did the patient recover sensory or motor function before the onset of new symptoms? If a peripartum neurologic complication develops, epidural analgesia or anesthesia is often implicated. Invariably, the anesthesiologist will be consulted. There are many potential causes of postpartum neurologic injury, and epidurals are only one of them. Such neurologic injuries often result from direct trauma to the major nerve roots or trunks that supply the lower extremities and are caused by the fetal head or forceps. Direct ischemic injury to the lower spinal cord is also possible. This may occur if the fetal head compresses the ascending spinal branch of the internal iliac artery. One should also consider the possibility of epidural hematoma (see Chapter 57). A neurologist must be consulted urgently when extensive neurologic deficits are first noted. Also, magnetic resonance imaging (MRI) or computed tomography scans of the spinal cord should be obtained without delay. 789

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Risk Assessment When calculating the risk for peripartum neurologic injuries, consideration of the anatomy involved is important. Neurologic injuries resulting from childbirth may involve branches of the lumbosacral plexus (i.e., iliohypogastric, ilioinguinal, genitofemoral, lateral femoral cutaneous, anterior tibial, femoral, obturator, and sciatic nerves). Also involved may be the pudendal nerve, derived from the sacral (S3 and S4) nerve roots, and the coccygeal plexus, derived from the S4, S5, and coccygeal nerve roots. Occasionally, extensive injuries may result in the cauda equina syndrome. Involvement of the major plexuses (lumbar and sacral) may cause such extensive injuries, which can take weeks or months to resolve. Branches of the lumbar plexus or sacral plexus (Fig. 197-1) include the sciatic nerve (which contains the common peroneal and tibial nerves), and these may be compressed by the fetal head as it crosses the posterior pelvic brim during birth. Such injuries are unilateral in 75% of cases and bilateral in the rest. Compression injuries are more common in nulliparous parturients with a platypellic pelvis, large fetus, cephalopelvic disproportion, vertex presentation, or forceps delivery. These injuries may involve multiple nerve root levels or present as injuries to the femoral or obturator nerves, with sensory impairment in the L4-L5 dermatomes. Table 197-1 describes some common peripheral nerve injuries in parturients, and Figure 197-2 illustrates the dermatomes subserved by branches of the lumbosacral plexus. With regard to the mechanisms for specific nerve injuries (see Table 197-1), multiple sclerosis relapses often contribute to lateral femoral cutaneous nerve injuries. Numbness of the anterior aspect of the thigh associated with lateral femoral cutaneous nerve injury is termed meralgia paresthetica. This nerve can also be injured by hyperextended lithotomy positioning, pressure from the fetal head, or improper surgical traction during cesarean delivery. When the femoral nerve is injured, hip flexion and knee extension become difficult. Injury is caused by active flexion of the hips during the second stage of labor, leading to compression of the nerve by the inguinal ligament. Therefore, extreme flexion of the hip during “pushing” should be avoided. The legs should be rested between labor contractions and pushing. Also, use of a “squatting bar” to keep the hips hyperflexed during the second stage of labor may cause injury to the femoral nerve. Femoral nerve injury may also be caused by lumbosacral plexus compression by the fetal head. The adductor magnus muscle receives dual innervation from the obturator and sciatic nerves. If the obturator nerve is involved, thigh abduction weakens, with sensory loss along the medial aspect of the thigh. The sciatic nerve is the largest peripheral nerve in the body. An important branch is the common peroneal nerve, which supplies both motor and sensory innervation to the leg. This nerve winds around the neck of the fibula, where it is the only manually palpable nerve in the lower extremity (Fig. 197-3), making it vulnerable to injury, especially by stirrups. Such injury leads to paralysis of the ankle and foot, resulting in footdrop and inversion, with sensory impairment of the anterior aspect of the foot. Occasionally, inflammation or spasm of the piriformis muscle (caused by prolonged sitting or extensive weight

bearing during pregnancy) may cause sciatic nerve irritation. When the thigh is extended and rotated medially, gluteal pain radiating to the knee occurs. Blood supply to the spinal cord is often precarious and subject to important variations (Fig. 197-4). Damage to the spinal cord can occur if the blood supply is interrupted. One anterior and two posterior spinal arteries supply the cord. At certain sites along the spinal cord, there are a number of reinforcing inputs from other arteries, one of which is the artery of Adamkiewicz (or the arteria radicularis magna); this usually arises from the aorta at T9 but can arise anywhere between T9 and T12. Arteries that supply the lower spinal cord usually originate from the left side from one or two of the thoracolumbar segmental arteries (T9 to L2). Thus, injury to these arteries may be implicated in injuries to the lower portion of the spinal cord. In about 15% of cases, the artery of Adamkiewicz originates at the T5 level. If so, the major part of the blood supply to the lower spinal cord is provided by a lumbar branch from the internal iliac artery, which lies in front of the sacral ala and enters the spinal cord via L5-S1 intervertebral foramina. This branch can be compressed by the fetal head, leading to ischemia of the conus medullaris. Acute spinal cord ischemia is often undetectable with conventional MRI. Echoplanar diffusion-weighted MRI is used to diagnose acute spinal cord ischemia, as well as epidural hematoma or abscess.

Implications Neural tissue may be injured by local anesthetic neurotoxicity (chemical injury) or as a result of direct trauma. Chemical injury usually results from accidental injection of an irritant into the epidural or subarachnoid space. CHEMICAL INJURY Preservatives and antioxidants such as sodium bisulfite have been implicated in the development of adhesive arachnoiditis or the cauda equina syndrome. Either disorder can also occur as a result of direct local anesthetic neurotoxicity, and both can obliterate the subarachnoid space. The cauda equina syndrome has also been reported following the use of microcatheters for continuous spinal anesthesia. Such toxicity is believed to result from poor distribution of local anesthetic within the cerebrospinal fluid, with subsequent deposition of toxic drug concentrations at the nerve roots. Although the U.S. Food and Drug Administration has advised against the routine use of spinal microcatheters,1 there is renewed interest in evaluating their utility for obstetric anesthesia. Finally, the cauda equina syndrome may also occur as a result of acute intervertebral disk herniation, which requires immediate surgical intervention. DIRECT NEURAL TRAUMA Direct nerve trauma during regional anesthesia uncommonly causes neurologic deficits. Pain or paresthesias on injection using needles or catheters should be a cause for concern. 1 Faccenda KA, Finucane BT: Complications of regional anaesthesia: Incidence and prevention. Drug Saf 24:413-442, 2001.

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Iliohypogastric n. Quadratus lumborum m.

Ilioinguinal n.

Psoas major m. Genitofemoral n.

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Lateral femoral cutaneous n.

Obturator n. Inguinal ligament

Femoral n.

A

Anterior superior iliac spine Greater trochanter Pubic tubercle

Lesser trochanter Sciatic n. Femur

B Figure 197–1 ■ A, The lumbar plexus is derived from the L1-L5 nerve roots and lies in the psoas compartment between the psoas major and quadratus lumborum muscles. B, The sacral plexus is formed by contributions from L4, L5, and S1-S3. Not shown are the origins of the pudendal nerve and coccygeal plexus, which are formed by branches of the third and fourth sacral roots and the fourth and fifth sacral and coccygeal nerves, respectively.

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Peripheral Nerve Injuries in Obstetric Patients

Nerve

Nerve Roots

Possible Mechanism

Clinical Picture

Lumbosacral trunk Femoral nerve

L4-L5, S1 L2-L4

Forceps injury Fetal head; retractors during cesarean section

Lateral femoral cutaneous nerve

L2-L3

Common peroneal nerve (sciatic)* Tibial nerve (sciatic)

L4-S2

Stirrups; prolonged and exaggerated lithotomy position while pushing Stirrups or bedside rails

Footdrop; quadriceps and adductors affected Quadriceps weakness; weak hip flexion; absent patellar reflex; sensory impairment in thigh and calf Hypalgesia in anterolateral aspect of thigh

L4-S2

Stirrups or bedside rails

Obturator nerve

L2-L4

Fetal head

Footdrop; hypesthesia in lateral calf and anterior aspect of foot Footdrop (muscular branches innervate gastrocnemius and soleus muscles); medial (sural) branches lead to sensory loss in lower leg Weakness on thigh adduction; reduced sensation in medial aspect of thigh

*Owing to its superficial nature, one of the more frequently injured nerves.

Repositioning is of paramount importance. Soft-tip catheters for continuous epidural anesthesia are associated with fewer paresthesias than are more rigid nylon ones. Also, spinal anesthesia is more often associated with neurologic injury than is epidural anesthesia. If paresthesias occur during central neuraxial block, the anesthesiologist should document the severity and location of the paresthesias. It may take anywhere from 48 hours to 3 months for complete recovery from neuropathy due to direct nerve trauma incurred during central neuraxial block.

Direct trauma to nervous tissue may occur at the level of the spinal cord, nerve roots, or peripheral nerves. Epidural needles or catheters are more likely to traumatize the nerve roots. Spinal needles may injure a nerve root or the cord itself

Lateral collateral lig.

Biceps tendon

Common peroneal n.

Deep peroneal n.

Superficial peroneal n. Figure 197–2 ■ Segmental and peripheral nerve distributions can help distinguish central from peripheral nerve injury. (From Redick LF: Maternal perinatal nerve palsies. Postgrad Obstet Gynecol 12:1-6, 1992.)

Figure 197–3 ■ The anatomic location of the common peroneal nerve makes it vulnerable to injury by direct pressure (e.g., stirrups). This is the most frequently damaged nerve in parturients.

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Chapter 197

Basilic trunk Vertebral artery Subclavian artery

Deep cervical artery

Anterior spinal artery

C3-C4 radicular artery

C7-C8 medial radicular artery

T3-T4 medial radicular artery

Posterior spinal artery

Artery of Adamkiewicz

Lumbosacral radicular artery

Figure 197–4 ■ Lateral view of the blood supply of the spinal cord, depicting the anterior and posterior radiculomedullary branches. The primary blood supply to the thoracolumbar spinal cord is the artery of Adamkiewicz. As shown, it arises from the aorta at T9 but can arise anywhere between T9 and T12. With high ARM takeoffs, a lumbar artery usually supplies the major portion of the conus medullaris. (From Djindjian R: Arteriography of the spinal cord. Am J Roentgenol Radium Ther Nucl Med 107:461-478, 1969.)

within the subarachnoid space or nerve roots outside the subarachnoid space. Two thirds of neurologic sequelae are preceded by paresthesias (direct nerve trauma) or pain during injection (intraneuronal injection). Intraneural injection of local anesthetic is more likely to result in prolonged neurologic deficits. In one series of more than 103,000 regional anesthetics, of the 34 patients with neurologic sequelae, 29 had transient deficits, with full neurologic recovery occurring in 48 hours to 3 months. Of interest is that spinal anesthesia was significantly more likely than epidural anesthesia to be associated with neurologic injury (5.9 versus 2 per 10,000) or radiculopathy (4.7 versus 1.7 per 10,000). With mild nerve injury, conduction block occurs only through the damaged nerve segment (i.e., neurapraxia).

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If the condition is corrected, recovery occurs. However, the patient must be told that recovery may take several weeks, depending on the severity of the initial symptoms. Severe injuries cause axonal degeneration (axonotmesis). Regeneration may never be complete, with full or partial loss of function in the affected area. Neurotmesis signifies disruption of epineurium as well. Surgical repair is necessary, but recovery may never be complete.

MANAGEMENT When patients present with postpartum neurologic problems, one must be alert to other causes, including diabetes mellitus, acquired immunodeficiency syndrome (AIDS), and multiple sclerosis. Although diabetic neuropathy is a well-known entity, AIDS-related neuropathy is not, even though it is the most common neurologic complication of type 1 HIV infection and advanced AIDS. It manifests as a distal symmetrical polyneuropathy and occurs mainly with advanced immunosuppression. The number of parturients with advanced HIV disease is increasing, and neurotoxicity may also occur with several antiretroviral agents. Progressive polyradiculopathy occurs with advanced immunosuppression, usually caused by cytomegalovirus infection. In the initial evaluation, the anesthesiologist should document all sensory and motor deficits and consult a neurologist who is familiar with obstetric nerve injuries. Further studies include computed tomography or MRI scans and neuromuscular electrophysiologic studies, which must be performed without delay. Electrophysiologic studies include electromyography (EMG) and nerve conduction studies. EMG is extremely useful for diagnosing the extent of injury to peripheral nerves; however, timing is critical. The presence of abnormal spontaneous activity in quiescent muscle (fibrillation potentials) or increased activity during insertion of the recording needle into muscle (insertion activity) usually indicates preexisting neurologic disease. Insertion activity becomes noticeable on EMG within a few days of injury, whereas fibrillation potentials take 2 to 4 weeks to develop. If fibrillation potentials are recorded soon after the alleged injury, they are more likely due to a previously undiagnosed neurologic condition rather than a new injury. Another EMG sign of nerve injury is the failure to recruit additional motor units when muscle is stimulated. In completely denervated muscle, no recruitment occurs. However, when the nerve is damaged, partial recruitment occurs due to slowed conduction. EMG may also help distinguish whether a plexopathy or radiculopathy exists. Depending on the type and severity of injury, it may take up to 8 weeks for neurologic injuries to resolve completely. Repeat electrophysiologic studies are often necessary to assess progression or regression of injuries. Also, consultation with a physiotherapist is necessary to determine the best rehabilitation program to prevent muscle atrophy. A splint may be required for patients with significant footdrop to prevent permanent deformities. The patient described in the case synopsis had extensive neurologic injury, indicative of damage to the lumbosacral plexus or the spinal cord. Bowel or bladder dysfunction usually indicates spinal cord injury. Although electrophysiologic

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C5-C6 radicular artery

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Differential Diagnosis for Prolonged Neural Block

complete sensory and motor recovery from the anesthetic, the problem is unlikely related to neuraxial block or the agents used for the block.

Drug Effects Prolonged action of local anesthetic Slow regression of block More common after multiple dosing Needle or catheter tip close to nerve root during local anesthetic injection Direct neurotoxicity Rare effect of commonly used drugs (e.g., 5% hyperbaric lidocaine) Incorrect drug administered (e.g., potassium chloride)

Trauma Peripheral nerve Compression from positioning Known peripheral nerve pattern Central neuraxis Direct trauma to neural tissue caused by needle or catheter External compression of nerve root or spinal cord Herniated intervertebral disk Epidural hematoma (early) Epidural abscess (late) Spinal stenosis

Vascular Hemorrhage—spinal cord arteriovenous malformation Decreased blood supply—no evidence of recovery; permanent injury Anterior spinal artery syndrome Compression of arterial blood supply by fetal head Severe hypotension Post cardiac arrest Emboli (e.g., air, thrombotic, amniotic fluid)

Neurologic Disease (Preexisting or New Onset) Multiple sclerosis HIV, immunosuppressive therapy Cytomegalovirus Landry-Guillain-Barré syndrome

Miscellaneous Causes Space-occupying lesions Epidural hematoma Epidural abscess

studies suggested a lesion at the spinal root level or higher, MRI scans of the spinal cord 2 days after delivery appeared normal. However, enhanced MRI performed 1 week later was consistent with spinal cord ischemia. Likely, this was due to compression of the lumbar spinal artery at the level of the sacrum. Other potential causes of prolonged neurologic deficits in parturients are listed in Table 197-2.

PREVENTION For parturients with systemic disease, the anesthesiologist should thoroughly document any preexisting neurologic deficits to prevent potential medicolegal problems. Multiple sclerosis is particularly prone to relapse in the postpartum period. Also, anesthesia care providers in the labor-delivery suite must ensure that the patient has fully recovered from the effects of the local anesthetic before she is returned to the floor. If the patient develops a neurologic deficit after

Further Reading Aminoff MJ: Electrophysiologic testing for the diagnosis of peripheral nerve injuries. Anesthesiology 100:1298-1303, 2004. Auroy Y, Benhamou D, Bargues L, et al: Major complications of regional anesthesia in France: The SOS regional anesthesia hotline service. Anesthesiology 97:1274-1280, 2002. Biglioli P, Roberto M, Cannata A, et al: Upper and lower spinal cord blood supply: The continuity of the anterior spinal artery and the relevance of the lumber arteries. J Thorac Cardiovasc Surg 127:1188-1192, 2004. Bromage PR: Neurologic complications of regional anesthesia in obstetrics. In Hughes SC, Levinson G, Rosen MA (eds): Obstetric Anesthesia, 2nd ed. Philadelphia, JB Lippincott–Williams & Wilkins, 1999, pp 723-748. Confavreux C, Hutchinson M, Hours MM, et al: Rate of pregnancy-related relapse in multiple sclerosis: Pregnancy in Multiple Sclerosis Group. N Eng J Med 339:285-291, 1998. Gray H: Gray’s Anatomy, 27th ed. Philadelphia, Lea & Febiger, 1959, pp 1036-1057. Jaime F, Mandell GL, Vallejo MC, et al: Uniport soft-tip, open-ended catheters versus multiport firm-tipped close-ended catheters for epidural labor analgesia: A quality assurance study. J Clin Anesth 12:89-93, 2000. Kuczkowski KM: Neurologic complications of labor analgesia: Facts and fiction. Obstet Gynecol Surv 59:47-51, 2004. Lee LA, Posner KL, Domino KB, et al: Injuries associated with regional anesthesia in the 1980s and 1990s: A closed claim analysis. Anesthesiology 101:143-152, 2004. Loher TJ, Bassetti CL, Lovblad KO, et al: Diffusion-weighted MRI in acute spinal cord ischemia. Neuroradiology 45:557-561, 2003. Vallejo M, Mariano D, Kaul B, et al: Piriformis syndrome in a patient after cesarean section under spinal anesthesia. Reg Anesth Pain Med 29:364-367, 2004. Wedel DJ, Horlocker TT: Nerve blocks. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 1685-1717. Wlody D: Complications of regional anesthesia in obstetrics. Clin Obstet Gynecol 46:667-678, 2003. Wong CA, Scavone BM, Dugan S, et al: Incidence of postpartum lumbosacral spine and lower extremity nerve injuries. Obstet Gynecol 101:279-288, 2003. Wulff EA, Wang AK, Simpson DM: HIV-associated peripheral neuropathy: Epidemiology, pathophysiology and treatment. Drugs 59:1251-1260, 2000. Zakowski MI: Complications associated with regional anesthesia in the obstetric patient. Semin Perinatol 26:154-168, 2002.

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198 4 OTHER SURGICAL SUBSPECIALTIES

David J. Wlody

Case Synopsis A 24-year-old primigravida underwent cesarean delivery for breech presentation under uncomplicated spinal anesthesia. This was performed with a 27-gauge Whitacre needle. On the second postpartum day she complained of a severe diffuse headache. On the third postpartum day she suffered a grand mal seizure. The obstetrician believes that the headache is a “spinal headache,” and the anesthesiologist is consulted.

PROBLEM ANALYSIS Definition Postpartum headache is defined as any headache occurring during the first 6 weeks after delivery. Such headaches may be due to antepartum conditions, manifestations of an intrapartum event, or unrelated disorders arising coincidentally in the postpartum period. It is often tempting to blame postpartum headache on neuraxial anesthetic, but not all postpartum headaches are post–dural puncture headaches, even if a large-gauge needle was used. This chapter discusses the most common causes of postpartum headache as well as some less common conditions that, if misdiagnosed, could lead to catastrophic outcomes.

These symptoms are typically visual, including light flashes, a blind spot with shimmering edges (scintillating scotomata), or formations of zigzag lines. Numbness of the face or weakness of an arm or leg may also occur. Otherwise, the characteristics of the two subtypes of migraine headache are similar: ● ● ● ●

Unilateral location Pulsating quality Aggravation by routine physical activity Associated with nausea and photophobia and phonophobia

Migraine headaches usually begin in adolescence and occur in 4% to 6% of men and 13% to 18% of women. Although there is no consistent mendelian pattern of inheritance, there is clearly a familial propensity for migraine. In 60% to 80% of cases, there is a family history of migraine headaches.

Recognition Although the incidence of particular types of headache may differ among women who have recently delivered, any headache seen in the general population can occur in postpartum patients. The International Headache Society recently revised the criteria for the diagnosis and classification of headaches. A complete discussion of these criteria is beyond the scope of this chapter, but a division of headaches into primary and secondary categories provides a conceptual framework for discussion (Table 198-1). PRIMARY HEADACHE With primary headache, there is no apparent cause or other conditions that might contribute to or explain the patient’s headache. Primary headaches are confined to migraine- and tension-type headaches. Migraine-Type Headache. Migraine headaches are subdivided into headaches with and without an aura. With the former, reversible neurologic symptoms develop gradually over 5 to 20 minutes and generally last less than 60 minutes.

Table 198–1

■

Classification of Postpartum Headache

Primary Causes of Headache Migraine (with or without aura) Tension-type headache

Secondary Causes of Headache Headache attributed to cranial vascular disorders Intracranial hemorrhage Cerebral venous and sinus thrombosis Headache attributed to nonvascular intracranial disorders Tumor Idiopathic intracranial hypertension Pneumocephalus Headache attributed to disorders of homeostasis Headache with preeclampsia Headache due to a substance or its withdrawal Metabolic disorders Headache due to infectious causes Meningitis Sinusitis Modified from Rapoport AM, Sheftel FD: Headache Disorders: A Management Guide for Practitioners. Philadelphia, WB Saunders, 1996, pp 5-6.

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The higher incidence of migraine headaches in women suggests a hormonal association. These headaches tend to occur during the premenstrual period, and in 15% of women the attacks are exclusively perimenopausal. The effect of pregnancy on migraine is variable. In about 70% of pregnant women, migraine headaches decrease or disappear altogether during pregnancy. However, it is common for migraines to recur early in the postpartum period. New-onset migraine headaches during pregnancy or early in the postpartum period are unusual. Headaches appearing at this time warrant investigation to ensure that they are not caused by some less benign process. Tension-Type Headache. Tension headache is the most common type of headache, with a reported lifetime prevalence as high as 78%. Tension-type headache is not as well studied as migraine and was once thought to be primarily psychogenic. It is now known to have an organic basis. Tension-type headache is divided into infrequent, frequent, and chronic subtypes, defined by the number of episodes suffered per month. Otherwise, they share the following characteristics: ● ● ● ● ●

Bilateral location Pressing, nonpulsating quality Not aggravated by routine physical activity Mild to moderate intensity Absence of nausea, photophobia, and phonophobia

Like migraine, tension headaches are more common in women. Unlike migraine headaches, they seldom begin in adolescence and are more likely to occur in middle age. Commonly, they are associated with chronic anxiety or depression. The relationship between tension headaches and pregnancy has not been well investigated. However, their incidence appears to be increased during gestation, with symptomatic improvement observed in only about 25% of patients. SECONDARY HEADACHE Secondary headache is defined as any new headache occurring in close temporal association with a disorder known to cause headache. These disorders include intracranial vascular and nonvascular disorders, substance use or withdrawal, disorders of homeostasis, and infection. Intracranial Hemorrhage. This category includes subarachnoid hemorrhage, intracerebral hemorrhage, and subdural hematoma. Features of headache due to intracranial hemorrhage are as follows: ● ● ●

Sudden onset Intense severity Possible association with focal signs or alterations in level of consciousness

The incidence of spontaneous subarachnoid hemorrhage does not appear to be greater in pregnant women than in other populations. About 75% of subarachnoid hemorrhages are due to ruptured berry aneurysms.1 The remainder 1 A small, saccular aneurysm of a cerebral artery, typically within the circle of Willis, with the potential to rupture, thereby causing subarachnoid hemorrhage.

are due to bleeding arteriovenous malformations. Hypertension and proteinuria are not uncommon; therefore, subarachnoid hemorrhage can be confused with preeclampsia. Intracerebral hemorrhage is usually seen with severe preeclampsia or eclampsia. Subdural hematoma has been reported in association with post–dural puncture headache; presumably, the reduced intracranial pressure leads to rupture of bridging veins. Cerebral Venous and Sinus Thrombosis. Cerebral venous thrombosis is estimated to occur in 1 in 2500 to 10,000 deliveries. The hypercoagulable state associated with pregnancy is a contributing factor. Patients with cerebral venous or sinus thrombosis should be evaluated for the presence of a hereditary thrombophilia (e.g., protein S or C deficiency, factor V Leiden). Nearly 80% of cases occur during the first 2 weeks post partum, but thrombosis may occur as late as 3 months post partum. Features of headache secondary to intracranial thrombosis vary, depending on whether a large sinus or an isolated cortical vein is thrombosed. With thrombosis of a large sinus, headache, seizures, intracranial hypertension (due to impaired absorption of cerebrospinal fluid), and altered consciousness are common. With a thrombosed cortical vein, focal motor and sensory deficits and seizures are more likely. Interestingly, there are several reported cases of intracranial thrombosis that were initially treated as post–dural puncture headache. If signs and symptoms suggest increased intracranial pressure, this should lead to a more aggressive workup before an epidural blood patch is performed. Magnetic resonance imaging and magnetic resonance angiography are considered gold standards for diagnosing intracranial thrombosis. Venous thrombosis with occlusion leads to increased capillary pressure, often associated with hemorrhagic infarcts. With recanalization of the vessel, capillary pressure decreases, and further hemorrhage is prevented. Although heparin has no thrombolytic properties, it prevents further propagation of the thrombus. Therefore, its use is indicated, even in patients with preexisting hemorrhage. Finally, as a rule, anticonvulsants are reserved for patients with solid evidence of hemorrhage or focal neurologic deficits. Intracranial Neoplasm. Features of headache associated with intracranial neoplasm include the following: ● ● ●

Diffuse, nonpulsating quality Often associated with nausea or vomiting Worsened by physical activity, Valsalva’s maneuver, coughing, or sneezing

The incidence of brain tumor is not increased by pregnancy. However, it is not unusual for symptoms to first manifest during pregnancy, likely due to increased extracellular fluid. There is also a well-established hormonal influence on certain tumors, especially meningiomas and pituitary adenomas. Symptoms of brain tumors are influenced by their location and size and whether they are associated with elevated intracranial pressure.

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Postpartum Headache Other Than Post–Dural Puncture Headache

Idiopathic Intracranial Hypertension. Idiopathic intracranial hypertension, previously known as benign intracranial hypertension or pseudotumor cerebri, is most common in obese young women, suggesting a hormonal component. It is characterized by the following: ●

●

Diffuse, nonpulsating pain Daily occurrence Aggravated by coughing

Patients are alert and may have a normal neurologic examination. The most common neurologic findings are papilledema, sixth cranial nerve palsy, and visual field defects, all of which progress if the patient is not treated. Idiopathic intracranial hypertension is a diagnosis of exclusion, and other intracranial, metabolic, toxic, and hormonal diseases must be ruled out. It is not unusual for idiopathic intracranial hypertension to present for the first time during pregnancy, and symptoms typically worsen in patients with previously recognized disease. Improvement can be expected following delivery. Pneumocephalus. The use of air to identify the epidural space is sometimes complicated by its accidental subarachnoid injection. Headache typically occurs immediately after injection, may be quite intense, and is worsened by upright posturing. Plain skull films easily identify intracranial air. Its absorption is accelerated by breathing 100% oxygen. Substance Use or Withdrawal. Headache is common during therapy with magnesium sulfate, especially after the loading dose. In patients consuming more than 200 mg/day of caffeine, sudden cessation may lead to a headache. This is relieved within 1 hour of the administration of caffeine. Cessation of chronic opioid therapy can lead to headache within 24 hours. It has been suggested that abrupt termination of corticosteroids, tricyclic antidepressants, and nonsteroidal anti-inflammatory drugs can also lead to headache. Preeclampsia and Eclampsia. Headache is a hallmark of severe preeclampsia and may be a precursor to development of eclampsia. Typical features of headache in this setting are as follows: ● ● ● ●

Bilateral, pulsating quality Aggravated by physical activity Accompanied by hypertension and proteinuria Visual disturbances (blurred vision, scotomata)

Headache associated with preeclampsia generally occurs before delivery but may present in the postpartum period. Such patients are at risk for eclampsia and must be carefully monitored. Metabolic Disorders. Fasting may cause headache, even without associated hypoglycemia. Approximately 30% of patients with chronic hypothyroidism have a generalized, nonpulsatile headache that responds well to thyroid hormone replacement therapy. Meningitis. Features of headache secondary to meningitis include the following: ● ●

Diffuse, progressively increasing pain Fever

●

Nuchal rigidity Nausea, vomiting, photophobia

Meningitis is an exceedingly rare complication of regional anesthesia. However, the failure to diagnose and treat it in a timely fashion may be associated with catastrophic sequelae. Post–Dural Puncture Headache. Post–dural puncture headache has many of the same features as headache due to meningitis. Diagnostic lumbar puncture must be considered in any patient with presumed post–dural puncture headache accompanied by fever, leukocytosis, and meningismus. Sinusitis. Headache due to sinusitis is often accompanied by purulent nasal discharge and fever. Tenderness over the affected sinus is common. Chronic sinusitis is not considered a likely cause of headache in the absence of acute exacerbation.

Risk Assessment Headache can occur at any time in the peripartum period and is extraordinarily common after childbirth. Patients with a history of headache or depression are at particularly high risk. Patients with preeclampsia or known intracranial pathology should be evaluated carefully. This is especially so if the headache is more severe than usual, and especially if there are any associated neurologic deficits.

Implications Postpartum headache is not necessarily related to regional anesthesia, even in those patients known to have sustained accidental dural puncture with large-bore needles. Other causes of headache must be entertained before use of an epidural blood patch, especially when atypical features are present, including fever, leukocytosis, or focal neurologic deficits. Vigilance must be especially intense if supposed post–dural puncture headache fails to respond to epidural blood patch.

MANAGEMENT Management of postpartum headache depends on its cause and is summarized in Table 198-2.

PREVENTION Preventive measures depend on headache type: ●

●

●

●

Migraine headache sufferers should avoid known triggering agents such as red wine, cheese, and cured meats. Chronic analgesic therapy should be maintained to avoid rebound headache. Aggressive control of blood pressure is vital in patients with preeclampsia. Strict sterile technique is important when performing neuraxial anesthesia to reduce the risk of infectious complications.

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●

●

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Management of Postpartum Headache

Cause

Treatment

Migraine

β-Blockers, tricyclic antidepressants, serotonin receptor agonists; avoid known triggers or ergot alkaloids in nursing mothers Analgesics, tricyclic antidepressants Decompressive surgery Anticonvulsants, anticoagulants Mannitol, glucocorticoids, surgery Glucocorticoids, carbonic anhydrase inhibitors Supine posture, IV fluid or caffeine, all conservative measures; epidural blood patch (definitive therapy with 90% success rate) Analgesics, denitrogenation Avoidance or adjustment of dosage of causative agents Antihypertensives, magnesium sulfate Correction of metabolic derangement Antibiotics

Tension Intracranial hemorrhage Cerebral venous or sinus thrombosis Intracranial neoplasm Idiopathic intracranial hypertension Post–dural puncture Pneumocephalus Substance use or withdrawal Preeclampsia Metabolic disorders Infectious

Further Reading Aminoff MJ: Neurologic disorders. In Creasy RK, Resnik R (eds): Maternal-Fetal Medicine, 5th ed. Philadelphia, WB Saunders, 2004, pp 1165-1191. Benzon HT, Iqbal M, Tallman MS, et al: Superior sagittal sinus thrombosis in a patient with postdural puncture headache. Reg Anesth Pain Med 28:64-67, 2003. Donaldson JO: Headache. In Neurology of Pregnancy, 2nd ed. Philadelphia, WB Saunders, 1989, pp 217-227. Headache Classification Subcommittee of the International Headache Society: The international classification of headache disorders (2nd ed). Cephalalgia 24(Suppl):1-150, 2004.

Marcus DA: Headache in pregnancy. Curr Pain Headache Rep 4:288-296, 2003. Masuhr F, Mehraein S, Einhaupl K: Cerebral venous and sinus thrombosis. J Neurol 251:11-23, 2004. Silberstein SD: Migraine and pregnancy. Neurol Clin 15:209-231, 1997. Victor M, Ropper AH: Headache and other craniofacial pains. In Adams and Victor’s Principles of Neurology, 7th ed. New York, McGraw-Hill, 2001, pp 175-203. Von Wald T, Walling AD: Headache during pregnancy. Obstet Gynecol Surv 57:179-185, 2002. Weeks SK: Postpartum headache. In Chestnut DH (ed): Obstetric Anesthesia: Principles and Practice, 3rd ed. Philadelphia, Mosby, 2004, pp 562-564.

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Joy L. Hawkins OTHER SURGICAL SUBSPECIALTIES

Case Synopsis A 42-year-old woman, gravida 3, para 0, presents to the operating room for laparoscopic cholecystectomy at 28 weeks’ gestation. Her pregnancy has been uncomplicated, but she has a history of two previous miscarriages in the first trimester. She is extremely anxious about undergoing this procedure while pregnant and asks about the implications of the anesthetic for her fetus and the outcome of the pregnancy.

PROBLEM ANALYSIS

●

Definition and Recognition Most anesthesiologists find it disconcerting when a patient presenting for an otherwise routine surgery is pregnant. About 2% of pregnant women have surgery while they are pregnant, involving about 75,000 anesthetics per year. Most procedures result from conditions that are common in this age group: trauma, ovarian cysts, appendicitis, cholecystectomy, evaluation of a breast mass, and cervical incompetence. However, major procedures such as craniotomy, cardiopulmonary bypass, and liver transplantation have also been performed in pregnant patients with good outcomes for both the mother and the fetus. Despite favorable results, the public has a strong aversion to drugs’ being used or procedures’ being performed during pregnancy, and a pregnant patient requiring surgery is likely to present with extreme anxiety. In the interest of informed consent, the anesthesiologist must address the risks associated with the anesthetic in a pregnant patient undergoing surgery.

Risk Assessment and Implications For a pregnant surgical candidate, the preoperative assessment involves two patients. Several unique concerns must be addressed when creating an anesthetic plan: ● ● ● ● ●

Alterations in maternal physiology Potential teratogenic effects of anesthetic agents Maintenance of uterine perfusion during surgery Fetal effects of surgical and anesthetic manipulations Prevention of preterm labor (the greatest cause of fetal loss)

Alterations in maternal physiology involve every organ system, but those most important to anesthetic management include the following: ●

Respiratory: increased oxygen consumption; reduced functional residual capacity; lower partial pressure of carbon dioxide, due to increased minute ventilation; and higher incidence of difficult intubation

●

●

Cardiovascular: increased blood volume and cardiac output; dilutional anemia; supine aortocaval compression by gravid uterus; reduced vascular but increased baroreceptor responsiveness Gastrointestinal: gastric volume and pH may not be altered; however, lower esophageal sphincter tone is usually reduced Central nervous system: decrease in both minimum alveolar concentration (MAC) for inhalational agents and local anesthetic requirements

Teratogenic effects of anesthetics have not been conclusively shown in humans. The two agents of most concern are nitrous oxide (N2O) and benzodiazepines. N2O may constrict the uterine vasculature and decrease uterine blood flow if it is not combined with another inhalational agent that produces sympatholysis. Benzodiazepines were anecdotally associated with cleft lip anomalies, but subsequent studies failed to show any relationship. Opioids, intravenous agents, and local anesthetics have a long history of safety during pregnancy. Of concern is recent animal work showing that fetal or newborn exposure to NMDA receptor blockers (e.g., ketamine, N2O) and GABA receptor enhancers (e.g., benzodiazepines, intravenous induction agents, volatile anesthetic agents) results in widespread apoptotic neurodegeneration and persistent memory and learning impairment. These effects appear to be most pronounced with isoflurane, but the significance of human exposure is unknown. However, isoflurane has been associated with postoperative cognitive deficits in human adults. Maintenance of uterine perfusion and maternal oxygenation preserves fetal oxygenation and is key to any anesthetic during pregnancy. Above all, maternal hypoxemia and decreased cardiac output must be avoided. Prevention of preterm labor is the most difficult problem to surmount. It is probably not related to anesthetic management but rather to the underlying disease and the surgical procedure.

MANAGEMENT If there is a question about the diagnosis of pregnancy, this should be part of the preoperative assessment. 799

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Mandatory pregnancy testing is a controversial issue. The last menstrual period should be documented on the anesthesia record for any female between the ages of 12 and 50. Testing should be offered if more than 3 weeks has lapsed since the expected time of the menstrual period or by patient request. If possible, delay of surgery to the second trimester should be considered. In the second trimester, concerns about teratogenicity and spontaneous miscarriage are reduced, and preterm labor is not as common as in the third trimester. In addition, the patient should be counseled on anesthetic risks (or the lack thereof) to the fetus and the pregnancy and educated on the need for left uterine displacement and symptoms of preterm labor. Preoperative medications to allay anxiety or pain are often appropriate. Elevated maternal catecholamines may decrease uterine blood flow. Prophylaxis against gastric aspiration should be considered with a combination of an antacid, metoclopramide, or H2-receptor antagonist. Intraoperatively, there is no evidence that one particular anesthetic technique is better than another, so long as maternal oxygenation and perfusion are maintained. Monitoring should include blood pressure, oxygenation, ventilation (end-tidal carbon dioxide), temperature, and blood glucose if the procedure is a long one. If it will not interfere with the surgical field, intermittent or continuous fetal monitoring after about 24 weeks’ gestation may be helpful to ensure that the intrauterine environment is optimal. Loss of beat-tobeat variability in the fetal heart rate is normal during anesthesia, but decelerations may indicate the need to increase maternal oxygenation or blood pressure, increase uterine displacement, change the site of surgical retraction, or begin tocolysis. Fetal monitoring can assess the adequacy of uterine perfusion during induced hypotension, cardiopulmonary bypass, or procedures involving large volume shifts. If the mother is awake during a regional anesthetic, it can be very reassuring to hear the fetal heart tones during the procedure, even if measured intermittently. The conduct of general anesthesia should include full preoxygenation and denitrogenation; rapid-sequence induction with cricoid pressure; high inspired concentrations of oxygen; and judicious reversal of muscle relaxants to avoid any acute increase in acetylcholine, which might induce uterine contractions. Inhalational agents should be kept below 2.0 MAC to prevent decreased maternal cardiac output and uterine blood flow. During the first trimester, ketamine at doses greater than 2 mg/kg may cause uterine hypertonia. N2O and benzodiazepines may be used at the anesthetist’s discretion. Until further research is available, it may be prudent to use other volatile inhalational agents in place of isoflurane. Also, keep in mind that the airway of the pregnant patient is edematous and vascular. Thus, visualization of the epiglottis and laryngeal structures may be more difficult during attempted laryngoscopy and tracheal intubation. The use of regional anesthesia techniques (especially spinal and epidural anesthesia) has the advantage of minimizing drug exposure in early pregnancy, as well as reducing problems in interpreting fetal monitoring changes later during gestation. Hypotension with central neuraxial blocks is minimized with adequate preload and volume replacement,

left lateral uterine displacement, and prompt administration of vasopressors if needed. Both ephedrine and phenylephrine are acceptable drugs for treating hypotension. In the absence of maternal bradycardia, phenylephrine appears to be at least as effective as ephedrine for maintaining maternal blood pressure and umbilical artery pH values during central neuraxial anesthesia for cesarean section.1 The local anesthetic dose is decreased by about one third with spinal or epidural techniques. Continuous epidural analgesia can provide excellent postoperative pain control while reducing the loss of fetal heart rate variability and the need for maternal sedation. Thus, the patient is better able to report symptoms of preterm labor. Postoperative care includes continued monitoring of fetal heart rate and uterine activity. Preterm labor must be treated early and aggressively. This may require recovery in the labor and delivery unit or providing labor and delivery nursing expertise in the surgical recovery area. It should be remembered that any systemic pain medications will cause a loss of fetal heart rate variability. Therefore, regional analgesia techniques should be used whenever possible. Also, pregnant patients are at high risk for thromboembolic complications and should be mobilized as soon as possible (another reason for regional analgesia). Maternal oxygenation and left uterine displacement should be maintained. If the fetus is a viable age, a pediatrician should be notified so that he or she can provide counseling to the parents in the event preterm labor occurs.

PREVENTION Although the need for surgery cannot be prevented, anesthesiologists can provide reassurance to the mother that anesthetic drugs and techniques will not put her fetus or the pregnancy at risk. Prevention of preterm labor is the greatest concern and may require perioperative administration of tocolytics. Good postoperative pain management without sedation aids in the early diagnosis and treatment of preterm labor, as well as early mobilization to prevent thromboembolic events.

Further Reading American College of Obstetricians and Gynecologists: Nonobstetric Surgery in Pregnancy (ACOG Committee Opinion No. 284). Washington, DC, ACOG, August 2003. Boiven JF: Risk of spontaneous abortion in women occupationally exposed to anesthetic gases: A meta-analysis. Occup Environ Med 54:541-548, 1997. Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al: Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 23:876-882, 2003.

1 Vasopressors with primary α-adrenergic activity, including phenylephrine, have been shown in animal models to directly increase intrinsic vascular resistance, thereby directly reducing uterine blood flow. However, agents such as phenylephrine also directly increase central venous vascular tone (i.e., reduce venous capacitance), which augments venous return and cardiac preload. If so, cardiac output and effective uterine blood flow may increase.

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Shiono PH, Mills JL: Oral clefts and diazepam use during pregnancy. N Engl J Med 311:919-920, 1984. Thomas DG, Robson SC, Redfern N, et al: Randomized trial of bolus phenylephrine or ephedrine for maintenance of arterial pressure during spinal anesthesia for caesarean section. Br J Anaesth 76:61-65, 1996. http://www.asahq.org/clinical/obdraft.htm

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Koren G: Drugs in pregnancy. N Engl J Med 338:1128-1137, 1998. Mazze RI, Fujinaga M, Baden JM: Halothane prevents nitrous oxide teratogenicity in Sprague-Dawley rats; folinic acid does not. Teratology 38:121-127, 1988. Reynolds JD, Booth JV, de la Fuente S, et al: A review of laparoscopy for non-obstetric-related surgery during pregnancy. Curr Surg 60:164-173, 2003. Rosen MA: Management of anesthesia for the pregnant surgical patient. Anesthesiology 91:1159-1163, 1999.

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Gurinder M. S. Vasdev Case Synopsis A 28-year-old primigravida with a 24-week gestational age fetus presents with increased shortness of breath. Her past medical history includes mitral valve replacement with a Björk-Shiley valve. Transthoracic echocardiography reveals a poorly functioning valve with organized old thrombus. She is prepared for an urgent mitral valve replacement. Fetal ultrasonography reveals a normal-sized fetus with a heart rate of 125 beats per minute, with good heart rate variability.

PROBLEM ANALYSIS Definition and Recognition With advances in cardiac intervention, women with congenital heart disease are approaching normal life spans. They now account for nearly 4% of all pregnancies. Some of these women require urgent cardiac surgical intervention with cardiopulmonary bypass (CPB) during pregnancy or immediately after delivery. Maternal mortality from CPB ranges from 1.5% to 3%, similar to that for disease-matched, nonpregnant females. Surgery during the first trimester may be associated with a higher risk of teratogenesis and spontaneous miscarriage. Hence, semielective surgery is often deferred to the second or third trimester. However, maximal cardiovascular changes occur during the third trimester. This added stress on the maternal cardiovascular system results in parturients presenting with symptoms of cardiac decompensation, albeit with a viable preterm fetus. If the fetus is viable (>28 weeks’ gestation), combined cardiac surgery and cesarean delivery can benefit the mother by decreasing the cardiovascular burden during the immediate CPB period. In this case, it is important that the abdomen be open during CPB to ensure control of uterine bleeding while the patient is anticoagulated. Initiation of CPB may cause trauma to the blood vessels, activation of the clotting cascade, and alteration in acidbase balance that can affect both the parturient and the fetus. Release of maternal vascular endothelial factors and the formation of microemboli can further affect the placental microcirculation and stimulate uterine contractions. The need for maternal cerebral protection with hypothermia adversely affects fetal oxygen transfer due to a leftward shift of the oxygen-hemoglobin dissociation curve. Hypothermia and nonpulsatile flow may further compromise placental perfusion. Fetal demise remains relatively high (10% to 20%) and is largely attributed to intraoperative hypothermia. Other factors associated with fetal demise are long pump runs and specific types of surgery (e.g., repair of ventricular septal defects, aortic valve replacement). However, there has 802

been a recent decline in mortality from greater than 20% to 12.5%.

Risk Assessment Outcomes for parturients undergoing urgent cardiac surgery with CPB are determined by several different factors. Patient-Related Factors. Parturients with New York Heart Association class III or IV heart failure are considered candidates for surgery. For such parturients, maternal mortality with labor and delivery, but without corrective surgery, varies from 5% to 50% and depends on the nature and severity of the patient’s cardiac disease. With some cardiac lesions, nonCPB intervention (e.g., coronary stenting, balloon valvotomy) may be adequate to get the parturient through labor and delivery. Advances in echocardiography now allow physicians to accurately follow up and determine the optimal timing for cardiac intervention for both the mother and the fetus. Some cardiac surgery can be performed without CPB, which avoids sequelae related to the use of extracorporeal circulation. Surgical Factors. Cardiac valvular repair or revision requires longer bypass times than does replacement of the valve. In addition to the inherent dangers of CPB, parturients are at increased risk due to fetal demands during CPB and reperfusion after CPB. Fetal Factors. The severity of the maternal disease determines the outcome for the fetus. If the surgical procedure can be delayed to the second trimester without adversely impacting the mother’s health, this reduces the risk for fetal teratogenesis. If the fetus is close to term, combined cardiac surgery and cesarean delivery may be a reasonable option. Perfusion. Parturients have a hyperdynamic circulation with high levels of oxygen consumption. Maximal oxygen demand occurs in the third trimester (Fig. 200-1). Thus, when commencing CPB in the third trimester, higher flows and pressures are advised to maintain placental infusion. The shortest possible CPB time is also preferred. Pulsatile flow has been associated with decreased release of endotheliumderived mediators and may be beneficial for optimizing

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hCSm

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Estrogen

Prolactin EPO

803

Aldosterone Plasma volume

Renin

Erythrocytes

Cardiopulmonary Bypass in Pregnancy

Blood volume

Angiotensin II Sympathetic outflow Plasma volume

50

Cardiac output

Stroke volume

% Change

40

Enlarged uterus

30 20

Caval obstruction

10

RBC volume

0 ⫺10 Nonpregnant

Delivery 8

12

16

20 24 28 32 Weeks of gestation

36

40

6 months postpartum

Figure 200–1 ■ Cardiovascular changes associated with pregnancy. EPO, erythropoietin; hCSm, human chorionic somatomammotropin; RBC, red blood cell. (Redrawn from Teerlink JR, Foster E: Valvular heart disease in pregnancy. A contemporary perspective. Cardiol Clin 16:573-598, 1998.)

placental perfusion. These advantages are probably limited, however, so conventional nonpulsatile CPB is still acceptable. Cardioplegia. Particular attention to full recovery from cardioplegia must be paid to minimize adverse effects on the fetus. The surgeon can cannulate the coronary sinus and place a ventricular vent (the blood is discarded) before circulating the cardioplegia solution. High placental potassium levels may result in fetal cardiac arrest. No particular cardioplegia solution has been reported to be more beneficial or protective in pregnant patients. Hypothermia. Maternal core temperatures less than 35°C are associated with increased uterine contractions and reduced oxygen transfer by a leftward shift of the oxygenhemoglobin dissociation curve. The associated loss of fetal heart rate variability and bradycardia may make the diagnosis of fetal distress difficult. Warm bypass is preferable but may compromise maternal cerebral protection. Cerebral protective drugs cross the placenta and may affect the fetus; therefore, their role in CPB for parturients has not been fully established. Anticoagulation. Heparin is highly polarized and does not cross the placenta, but the dose must be adjusted for the increase in antithrombin III levels during pregnancy. The activated clotting time is a valid test for parturients. The use of antifibrinolytic drugs during CPB in parturients does not have Food and Drug Administration approval. Tranexamic acid crosses the placenta, and fetal effects can be dire. There have been case reports of successful aprotinin use after the fetus has been delivered; however, considering the hypercoagulable state of pregnancy, significant postoperative thromboembolic sequelae may complicate its use. After mechanical valve replacement, warfarin is the anticoagulant of choice. It should be initiated as soon as surgical hemostasis is deemed adequate. The use of surgical anticoagulants restricts the perioperative use of central neuraxial analgesia.

Preterm Labor. Intervention for preterm labor includes terbutaline, nitroglycerin, and magnesium sulfate. All these drugs have cardiac effects that must be considered. Fetal Heart Rate Monitoring. Fetal heart rate monitoring can be beneficial even at a nonviable age. The fetus is sensitive to altered placental perfusion and anesthetic agents. Initiation of CPB is associated with decreased fetal heart rate and perfusion pressure; therefore, oxygen delivery must be optimized. The CPB pump may need to be primed with type-specific blood. Umbilical artery and venous Doppler flow monitoring can be helpful in some circumstances.

MANAGEMENT Before any cardiac surgery with CPB is performed on a pregnant patient, a conference regarding her perioperative care is essential. This must involve anesthesia care providers, cardiac surgeons, maternal-fetal medical specialists, neonatologists, and cardiologists. The concerns of each specialty must be addressed. Especially important are the logistics of emergent fetal delivery. Premedication. Diazepam, midazolam, and fentanyl can be used for preoperative sedation. Depending on the severity of cardiac disease, some invasive monitors may be required before induction of anesthesia. Antacid treatment with H2-blockers and a nonparticulate antacid is beneficial for parturients at greater than 18 weeks’ gestation. Fifteendegree left lateral uterine displacement is also required with a greater than 18-week gravid uterus. Induction. A hemodynamically stable induction preserves placental perfusion. The use of volatile agents is beneficial because they relax the uterus. High-dose opiate-based anesthesia is more likely to be associated with fetal bradycardia. This should be taken into account when interpreting fetal

OTHER SURGICAL SUBSPECIALTIES

Heart rate

Total blood volume

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heart rate changes. Fentanyl is the most commonly used opiate during CPB in pregnant patients. Monitoring. In addition to the usual invasive monitors for cardiac surgery, transesophageal echocardiography has increasing intraoperative utility, especially for rapid diagnosis when the patient is removed from CPB. Use of invasive vascular access for monitoring is determined by the nature and severity of the parturient’s disease. Oximetric pulmonary artery catheters can be useful during the reperfusion and postoperative periods; monitoring both oxygen delivery and utilization is helpful for guiding hemodynamic manipulations. Cardiopulmonary Bypass. The shortest possible period of normothermic CPB is preferred. In parturients with severe cardiac disease, blood may be needed to prime the pump. Cardioplegia must be recovered to prevent fetal hyperkalemia, and this necessitates the use of left ventricular and coronary sinus vents. CPB is associated with progressive increases in both peripheral and placental vascular resistance. Optimal mean arterial pressure is provided by noting preinduction values and periodically assessing urine output and fetal well-being. Oxygen consumption trends may help in some circumstances. Increasing cardiac output (or CPB flow) and hematocrit is preferred to the use of vasoactive drugs to preserve mean arterial pressure and oxygen delivery to the mother and fetus. Use of vasopressors may be associated with increased endovascular shear stress and release of vasoactive, endothelium-derived inflammatory mediators. Vasodilatation with volatile agents and nitroglycerin has the additional benefit of relaxing the uterus (tocolysis). If the parturient has had a previous cesarean delivery, vasodilators with less potential to relax the gravid uterine muscle (e.g., hydralazine, possibly dihydropyridine calcium channel blockers)1 might be preferred, because uterine atony could give rise to severe postpartum hemorrhage. Upon rewarming after CPB, an increase in uterine activity may be noted, but tocolytics are administered only if the contractions are regular and strong. Once rewarming is complete, contractions often subside. Internal paddles used for defibrillation should be angled away from the uterus and fetus to reduce the risk of direct electrical stimulation. Weaning from CPB requires meticulous attention to detail, because the stunned myocardium now has to produce a high 1 Based on available evidence, sodium nitroprusside, verapamil, and diltiazem appear to have more potential to cause uterine atony.

cardiac output consistent with the needs of the gravid uterus. The use of pressors, aortic balloons, and ventricular assist devices may result in a considerable decrease in placental flow. In these circumstances, fetal distress or demise may be inevitable and is a direct result of the severity of the mother’s underlying cardiac disease. Postoperative Care. Cardiac surgical intensive care units are usually not equipped for fetal and uterine monitoring. Appropriate nursing coverage should be prearranged. Also, the logistics for performing emergent cardiac surgery if the patient decompensates should be addressed in advance.

PREVENTION In parturients, CPB is more complex because of the needs of the fetus and the altered physiologic state of pregnancy. When possible, delivery of the fetus removes one major component of a challenging situation. The best practice is driven by the underlying cardiac condition of the mother, even though this may necessitate delivery of the fetus before the age of viability. Most parturients who require open-heart surgery with CPB are referred to medical centers with level III neonatal intensive care units. The numbers of such facilities are likely to increase as more and more women with congenital heart disease reach reproductive age.

Further Reading Jahangiri M, Clarke J, Prefumo F, et al: Cardiac surgery during pregnancy: Pulsatile or nonpulsatile perfusion? J Thorac Cardiovasc Surg 126:894-895, 2003. Khandelwal M, Rasanen J, Ludomorski A, et al: Evaluation of fetal and uterine hemodynamics during cardiopulmonary bypass. Obstet Gynecol 88:667-671, 1996. Koren G, Pastuszak A, Ito S: Drugs in pregnancy. N Engl J Med 338:1128-1137, 1998. Murphy BA, Zvara DA, Nelson LH, et al: Clinical conference: Aprotinin use during deep hypothermic circulatory arrest for type A aortic dissection and cesarean section in a woman with preeclampsia. J Cardiothorac Vasc Anesth 17:256-257, 2003. Pardi G, Ferrari M, Iorio F, et al: The effect of maternal hypothermic cardiopulmonary bypass on fetal lamb temperature, hemodynamics, oxygenation, and acid-base balance. J Thorac Cardiovasc Surg 127:1728-1734, 2004. Pomini F, Mercogliano D, Cavalletti C, et al: Cardiopulmonary bypass in pregnancy. Ann Thorac Surg 61:259-268, 1996. Weiss BM, von Segesser LK, Alon E, et al: Outcome of cardiovascular surgery and pregnancy: A systematic review of the period 1984-1996. Am J Obstet Gynecol 176:1643-1653, 1998.

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Kerri M. Robertson Case Synopsis A 38-year-old man with a history of hepatitis C and hepatocellular carcinoma is scheduled for elective liver resection. Preoperative hemoglobin is 10 g/dL. Albumin, creatinine, and prothrombin time are within normal limits. The surgery is uneventful except for an intraoperative blood loss of 2 L, requiring transfusion with 5 units of packed red blood cells. The patient is transferred to the surgical intensive care unit for postoperative care due to oliguria and a potassium level of 6.1 mEq/L. Recovery is unremarkable, except that on postoperative day 4 the patient is noted to be jaundiced.

PROBLEM ANALYSIS Definition Clinically significant acute liver dysfunction is common after anesthesia and surgery. It is chiefly limited to patients with preexisting hepatic disease, massive blood transfusion, hepatic oxygen deprivation, infection, and drug toxicity. Most postoperative jaundice is multifactorial in origin, is difficult to diagnose, and often requires no treatment. The incidence following elective abdominal surgery is less than 1%; however, it is reported to be up to 15% to 17% with major cardiac surgery. The normal serum bilirubin level is 0.3 to 1.1 mg/dL. Jaundice is usually detected clinically when the serum bilirubin exceeds 3 to 5 mg/dL and the patient’s sclerae become icteric. Increased conjugated bilirubin reflects a problem with bilirubin secretion due to hepatocellular dysfunction, intrahepatic cholestasis, or biliary tract obstruction. If the increase in total bilirubin concentration is primarily unconjugated, the most likely cause is either hemolysis of erythrocytes producing a large bilirubin load or defects in the uptake, transport, or conjugation of bilirubin. Jaundice is usually evident within the first week after surgery and is not associated with acute liver failure. Hypoxic hepatocyte insult is the primary mechanism underlying many causes of postoperative hepatic dysfunction and may bear little or no relationship to the actual drugs or anesthetic technique used. There appears to be little correlation between the severity of liver disease and the absolute level of bilirubin. Supportive care is indicated, unless jaundice is caused by biliary obstruction that can be corrected surgically.

Prothrombin time measures activity of the extrinsic coagulation pathway and requires fibrinogen, prothrombin, and factors V, VII, and X. Slight alterations may reflect severe hepatic dysfunction, because only 20% to 30% of normal factor activity is required for coagulation. Plasma half-lives for clotting factors are measured in hours, so even acute liver dysfunction may be associated with a coagulopathy. An international normalized ratio greater than 1.5 not corrected by vitamin K within 24 hours implies severe liver disease. With obstructive biliary disease, however, the failure of bile salt secretion may result in poor absorption of vitamin K, which is a cofactor necessary for the post-transcriptional γ-carboxylation and activation of factors II, VII, IX, and X. Albumin is produced in the liver and represents the best measure of chronic hepatic synthetic dysfunction, so long as increased albumin losses in the urine or gastrointestinal tract are excluded. Owing to albumin’s long half-life (14 to 21 days),

Table 201–1

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Investigational Studies for Evaluation of Liver Function

Parenchymal Damage with Failure of Synthetic Function Prothrombin time Albumin Transaminases: alanine aminotransferase, aspartate aminotransferase Serum ammonia Screen for markers of viral hepatitis and autoimmune disorders Abdominal ultrasonography or computed tomography Liver biopsy

Cholestasis or Biliary Tract Disease

Recognition Owing to the large hepatic functional reserve, routine laboratory values may be normal despite significant underlying hepatic disease. Abnormal results of several common laboratory tests may loosely reflect hepatic dysfunction (Table 201-1).

Bilirubin (total, conjugated, and unconjugated): urine and serum levels Alkaline phosphatase Abdominal ultrasonography or computed tomography Endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography

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severe liver dysfunction lasting 3 to 4 weeks is required before a significant change in serum albumin levels becomes apparent. Alkaline phosphatase is present in the epithelial cells lining the biliary canaliculi; however, it is not specific for liver disease, owing to extrahepatic sources of this enzyme, especially bone. The serum ammonia concentration represents the balance between ammoniagenesis (primarily in the gut and kidney) and hepatic urea synthesis. Because the normal liver’s reserve capacity for urea synthesis is great, elevated serum ammonia concentrations usually indicate significant loss of hepatic function. Of the liver transaminase enzymes, alanine aminotransferase is the gold standard biomarker for hepatocellular injury. Jaundice is the most common and easily recognized sign suggesting hepatic dysfunction. Bilirubin is the primary end product of hemoglobin metabolism. The uptake and transport of unconjugated bilirubin into hepatocytes are followed by hepatic conjugation with glucuronide and subsequent excretion into bile canaliculi. If the total bilirubin concentration is greater than 1.5 mg/dL, it is considered abnormal. Postoperative jaundice can be categorized into three groups: 1. Prehepatic: overproduction of bilirubin 2. Intrahepatic: acute or subacute hepatocellular injury with or without preexisting liver disease 3. Posthepatic: cholestasis from biliary tract obstruction PREHEPATIC CAUSES Prehepatic causes of postoperative jaundice include the following: ● ● ● ●

●

Hemolysis of transfused blood Reabsorption of extravasated blood Intravascular hemolysis after drugs, infection, or fasting Hemolytic anemia: congenital (enzyme deficiencies or hemoglobinopathies) or acquired (immune mediated or traumatic) Idiopathic hyperbilirubinemia (Gilbert, Crigler-Najjar, or Dubin-Johnson syndrome)

Isolated elevated unconjugated bilirubin levels in a postsurgical patient most likely result from a prehepatic mechanism. Often, this is due to a large increase in the load of bilirubin from the hemolysis of erythrocytes, which transiently overwhelms the liver’s capacity to conjugate bilirubin. Up to 10% of red blood cells per unit of transfused blood are hemolyzed within the first 24 postoperative hours to generate 250 mg of bilirubin. The normal liver can conjugate this amount of bilirubin. However, with many liters of extravasated blood, multiple transfusions of red cells, the presence of myoglobin, or impaired liver function, hyperbilirubinemia may result. Pronounced postoperative jaundice commonly occurs in trauma victims. Many of these patients have extensive injuries requiring major surgical intervention and volume resuscitation, often with massive transfusion of red cells and other blood products. Progressive severe jaundice extending beyond the 10th to 12th postoperative day correlates with the development of sepsis, multiorgan failure, and death. The clinical manifestations caused by hemolysis are likely to be accentuated if the patient has underlying chronic liver

disease, has sustained acute ischemic injury to the liver, or has impaired renal function. Sepsis due to streptococci, Escherichia coli, Bacteroides species, and Clostridium species can also cause hemolysis. The mechanism is poorly understood, but it is likely due to bacterial hemolysins and reduced liver uptake of bilirubin associated with hypotension. Diagnosis of hemolytic anemia requires reticulocytosis, unconjugated hyperbilirubinemia, elevated lactate dehydrogenase, and absent or low haptoglobin concentrations. Familial hyperbilirubinemias caused by defects in the uptake, transport, or conjugation mechanisms are exacerbated by stress, infection, and fasting. Usually, bilirubin concentrations peak within the first few postoperative days and resolve over days to weeks. No specific therapy is indicated, other than that directed toward reducing any ongoing red cell breakdown. INTRAHEPATIC CAUSES Intrahepatic causes of postoperative jaundice are listed in Table 201-2. Total hepatic blood flow is 1.5 L/minute (25% to 30% of the normal adult cardiac output). The hepatic artery supplies 25% of total hepatic blood flow, and the portal vein supplies 75%. However, they contribute equally to hepatic oxygenation. In essence, the portal venous system is a passive vascular bed. Flow is dependent on perfusion pressure, cardiac output, and splanchnic vascular resistance. Reductions in portal inflow are usually associated with reciprocal hepatic artery vasodilatation, thereby maintaining total hepatic blood flow and oxygen supply. Normally, hepatic venous oxygen saturation is 35% to 50%. In shock, this may decline to 6% or less as visceral perfusion is reduced. Reduced cardiac output and blood pressure during general anesthesia and surgery decrease hepatic blood flow

Table 201–2

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Intrahepatic Causes of Postoperative Jaundice

Hepatic Parenchymal Disease Oxygen deprivation (ischemia) Chronic hepatitis Cirrhosis; primary biliary cirrhosis Primary sclerosing cholangitis; cholestasis Acute viral hepatitis

Hypoxemia Reduced cardiac output causing hypotension and reduced hepatic blood flow Anemia; hypovolemia

Miscellaneous Causes Primary sclerosing cholangitis Sepsis with or without hepatic or multiple organ system failure Preeclampsia (coagulopathy, liver dysfunction, or HELLP syndrome; see Chapter 189) Drugs or intravenous therapy Haloalkalated anesthetics Alcohol- or drug-induced hepatitis Total parenteral nutrition Major liver injury or surgery HELLP, hemolysis, elevated liver enzymes, and low platelet count in association with preeclampsia.

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and jeopardize liver oxygenation. Contributing factors include the following: ●

●

Surgical manipulation of the right upper quadrant of the abdomen can reduce hepatic blood flow by as much as 60% owing to sympathetic stimulation or direct compression of the vena cava and splanchnic vessels. Compensatory hepatic artery vasodilatation and reduced portal inflow are opposed in a dose-dependent maner by volatile anesthetics. Thus, portal perfusion becomes pressure dependent. Cirrhotic patients are at increased risk for ischemic hepatic injury owing to preexisting impaired perfusion as well as multiorgan system failure from the release of cellular inflammatory mediators. Ischemic hepatitis causes centrilobular hepatic necrosis, not inflammatory necrosis. Usually, the onset of jaundice occurs 1 to 5 days following surgery and peaks after 9 to 18 days. Liver function tests reveal elevated bilirubin, alkaline phosphatase, and transaminase concentrations, often 10 to 100 times the upper limits of normal. Clinical studies indicate that low perfusion pressure alone is insufficient to cause this clinical picture in patients without preexisting liver or cardiac disease. Also, ischemic hepatitis, elevated central venous pressure, and portal venous congestion may contribute to a further reduction in hepatic blood flow. Jaundice occurs in 45% of patients admitted to intensive care units with severe trauma or intra-abdominal sepsis after surgery. Potential causes are infection, the effect of endotoxin-mediated cytokine release on bile acid transport systems, and hemolysis. Sepsis-mediated cholestasis reverses with treatment of the cause. In experimental models (swine), large intravenous bilirubin loads cause extensive hepatic and canalicular membrane injury and intrahepatic cholestasis. This leads to bile stasis and impaired bile salt export pump function. By analogy, small bowel ileus in trauma victims may interrupt the normal endogenous circulation of bile acids between the gut and the liver. If so, this would render hepatocytes more sensitive to the cholestatic effect of bilirubin overload. Halothane hepatitis is well known and is still a common surgical diagnosis for postoperative jaundice, despite the fact that halothane has become obsolete in many institutions with the availability of newer agents that are less likely to be associated with hepatotoxicity (see Chapter 17). Although halothane is the prototypical example of volatile anesthetic hepatitis, other agents have been implicated, including enflurane, desflurane, and isoflurane. Evidence exists for “cross-sensitization” between these agents. Among these, halothane causes the greatest reduction in hepatic blood flow and oxygenation and may promote a mild, self-limited form of hepatitis in 1 in 10,000 exposures. Clinical features include high fever on postexposure days 3 to 14, with the onset of jaundice 1 to 2 days later. There is leukocytosis with eosinophilia in 20% of cases. Fulminant hepatic necrosis is

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rare (1 in 35,000 exposures) but is associated with 40% mortality. Adverse outcomes are associated with patient age older than 60 years, obesity, repeated exposures over a short interval, serum bilirubin greater than 10 mg/dL, and prothrombin time greater than 20 seconds. The most likely mechanism of injury is halothane metabolism and immune-mediated toxicity, but the evidence is inconclusive. Detection of antitrifluoroacetyl antibodies specific for halothane-modified rabbit liver cell membranes may help confirm the diagnosis, but the sensitivity and specificity of this test are unproved, so the diagnosis is usually one of exclusion (see also Chapter 17). There are two types of chronic hepatitis: chronic persistent hepatitis and chronic active hepatitis. The latter is more serious and more commonly progresses to cirrhosis and liver failure. Patients with cirrhosis, regardless of cause, have a reduced life expectancy. Although the probability of hepatic decompensation may be relatively low, after the onset of the first major complication (e.g., ascites, variceal bleeding, jaundice, encephalopathy), mortality is high. Anesthesia and surgery are implicated in hepatic decompensation. Significant factors (by multivariate analysis) associated with perioperative hepatic complications and mortality include the following: ● ● ●

● ● ● ● ● ● ●

Male gender High Child-Pugh score Cirrhosis other than primary biliary cirrhosis (especially cryptogenic cirrhosis) Renal insufficiency Chronic obstructive pulmonary disease Diabetes mellitus Ischemic heart disease or congestive heart failure Preoperative sepsis, gastrointestinal bleeding, or ascites Emergency surgery with a high surgical severity score Documented intraoperative hypotension

Acute hepatitis is usually associated with viral infection or is alcohol or drug induced (e.g., antibiotics, antihypertensives, anticonvulsants, tranquilizers, fentanyl). Rarely, sepsis, congestive heart failure, and pregnancy-induced hepatitis are seen. Viral hepatitis is most commonly due to type A, B, or C viruses. Less commonly, it is due to type D or Epstein-Barr virus or cytomegalovirus. Testing for antigens and antibodies is required for a definitive diagnosis, because many classes of drugs cause hepatitis that is clinically and histologically identical to viral hepatitis. Elevation of aminotransferases in the early phase of hepatitis precedes the appearance of jaundice. A high index of suspicion is required for the early diagnosis of hepatitis. General symptoms include dark urine, fatigue, anorexia, vomiting, dehydration, low-grade fever, myalgias, and right upper quadrant pain. The mortality rate for intraabdominal surgery in patients with severe acute inflammatory hepatitis ranges from 15% (viral) to 55% (alcohol related). Therefore, all elective surgery should be delayed until the infection has resolved, as indicated by normal liver function test results. Recovery may take up to 4 months. In 2004 the incidence of post-transfusion hepatitis from any cause was negligible and would probably warrant a case report. Eighty-five percent of post-transfusion infections were caused by hepatitis C virus. Prior to 1990 there were no screening tests for hepatitis C. The Centers for Disease Control and Prevention currently reports that the rate of post-transfusion hepatitis C infection has decreased from

OTHER SURGICAL SUBSPECIALTIES

●

Anesthetic drugs and adjuncts ● Intravenous and inhalational agents ● Vasodilators, β-blockers, and α -agonists 1 ● H -blockers 2 ● Vasopressin and other vasoconstrictors Hypovolemia and continuous positive airway pressure Hypoxemia, hypercarbia, and acidosis

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8% to 10% to less than 1 in 1 million units of blood or blood products transfused in 2004. Benign postoperative intrahepatic cholestasis usually occurs in patients without previous liver disease following prolonged operative procedures and a stormy intraoperative course associated with hypotension, endotoxemia, and blood loss. Severe jaundice with elevated serum alkaline phosphatase and normal to mildly elevated aminotransferases is typical. It appears to be a self-limited process that resolves completely. Intrahepatic cholestasis may also be associated with surgical stress, infection, and drugs (nonsteroidal antiinflammatory drugs, aspirin, amiodarone, isoniazid, methyldopa, monoamine oxidase inhibitors, phenothiazines, phenytoin, sodium valproate, and estrogens). POSTHEPATIC CAUSES Posthepatic causes of postoperative jaundice include the following: ● ● ● ●

Bile duct injury, tumor, stone, or stricture Acute cholecystitis Pancreatitis Choledocholithiasis

Cholestasis can be intrahepatic or extrahepatic. Biliary obstruction with inadvertent bile duct injury after laparoscopic surgery may cause postoperative cholestasis, especially when jaundice appears within 48 hours of such surgery. Postoperative drugs may also cause biliary obstruction. Pancreatitis, acute cholecystitis, or choledocholithiasis increase both conjugated bilirubin and alkaline phosphatase levels and cause mild to marked elevations in transaminase concentrations. Computed tomography and retrograde endoscopic cholangiography may help confirm the diagnosis of intrahepatic or extrahepatic cholestasis.

Risk Assessment In general, outcome is influenced less by the choice of anesthetic agents than by the urgency or type of surgery and the severity of chronic liver disease. Surgical risk factors for postoperative hepatic dysfunction or isolated hyperbilirubinemia include emergency surgery and surgery with a high severity score, including the following: ● ● ● ●

●

Open-heart surgery Open versus laparoscopic cholecystectomy Trauma surgery, especially involving the liver or biliary tract Major abdominal surgery (e.g., biliary tract surgery, liver resection) Surgery with large blood or blood product transfusion requirements

Differentiation between acute inflammatory liver failure and acute exacerbation of chronic liver disease affects the prognosis. Viral or alcohol- or drug-induced acute hepatitis is a contraindication to elective surgery. Patients with asymptomatic chronic hepatitis likely present little increased anesthetic risk. However, those with symptomatic cirrhosis or chronic hepatitis are at significantly increased risk for postoperative complications, with the degree of risk related to the extent of their disease.

Child’s classification has traditionally been used to predict perioperative mortality in cirrhotic patients undergoing surgical portacaval shunt or esophageal transection. The mortality risk is 10%, 31%, and 76% for Child’s classes A, B, and C cirrhosis, respectively. This classification may also predict perioperative outcomes for nonshunt surgery. However, current perioperative risk assessment for adults with endstage liver disease relies on the MELD scoring system, which is based on bilirubin, creatinine, and international normalized ratio. It accurately predicts 3-month mortality after elective transjugular intrahepatic portosystemic shunt procedures. For patients with known or suspected compensated chronic liver disease, consultation with a hepatologist is necessary to identify those with a Child’s class B or C cirrhosis and with a MELD score greater than 15. Cholelithiasis occurs twice as often in patients with cirrhosis than in those without. Despite recent advances in anesthetic care, the high rates of mortality (7% to 20%) and morbidity (5% to 23%)1 in patients with cirrhosis and portal hypertension having cholecystectomy have not decreased substantially. Thus, cholecystectomy in these patients remains a formidable operation. One contributory factor to the high incidence of multiorgan system failure in these patients may be the surgery-related release of inflammatory mediators and hepatic ischemia. This is more pronounced with open than with laparoscopic cholecystectomy. Yet even with the latter, hepatic perfusion can still be reduced by the head-up tilt and dependent venous pooling. Moreover, carbon dioxide insufflation increases intra-abdominal pressure. Further, direct liver manipulation, hypercarbic acidosis, and the neurohumoral stress response with upper abdominal surgery increase the risk for multiorgan system failure. Predictably, patients with Child’s classes B and C cirrhosis are at very high risk for hepatic dysfunction after cardiac surgery. Mortality is 11.4%, compared with 3% for those without cirrhosis. Patients with severe obstructive jaundice have reduced peripheral vascular resistance. Also, renal salt wasting and reduced left ventricular function, along with splanchnic pooling, put them at risk for hypotension with minimal blood loss. Risk factors for perioperative mortality (8% to 28%) include the following: ● ● ●

● ●

Hematocrit less than 30% Bilirubin greater than 11 mg/dL Malignant biliary obstruction (e.g., pancreatic or bile duct carcinoma) Ascending cholangitis Azotemia or hypoalbuminemia

Postoperative complications in patients with severe obstructive jaundice include infection, renal failure, disseminated intravasacular coagulation, and further deterioration in liver function.

Implications Most postoperative jaundice is self-limited and resolves with supportive therapy. Patients with acute inflammatory hepatitis 1

Due to bleeding, renal failure, or sepsis.

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● ● ● ● ● ● ●

Persistent hypothermia Coagulopathy Acidosis or hyperglycemia (later, hypoglycemia) Renal insufficiency Hemodynamic instability Acute respiratory distress Delayed postoperative awakening

MANAGEMENT For adults with postoperative jaundice, management begins with a systematic review of the patient’s history, physical examination findings, and anesthetic and surgical records. For the last, special attention is paid to associated hypotension, hypoxemia, transfusions, and any drugs used. Attention is also focused on laboratory results, including urinalysis; pre- and postoperative liver function tests; and serum total, direct, and indirect bilirubin concentrations. The most important questions are these: 1. Is there any evidence of hemolysis? 2. Is there evidence of chronic liver disease? 3. Could the jaundice be drug induced, alcohol induced, or infective? 4. Is there evidence of biliary tract obstruction? If the urinalysis is negative for bilirubin and there is increased serum indirect bilirubin (i.e., unconjugated hyperbilirubinemia), this suggests a prehepatic cause due to a large bilirubin load. However, if the urine is positive for bilirubin and there is increased total and direct bilirubin (i.e., conjugated hyperbilirubinemia), this suggests an intrahepatic or posthepatic cause (e.g., cholestasis, acute parenchymal hepatic injury). If both alkaline phosphatase and transaminases are elevated, hepatobiliary ultrasonography is indicated. If this is negative, viral serology, α-fetoprotein, antimitochondrial antibody, and retrograde endoscopic cholangiography are indicated. Evidence of bile duct dilatation is investigated with cholangiography. Focal lesions are further studied with computed tomography or magnetic

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resonance imaging, arteriography, and biopsy. If the diagnosis is still elusive, liver biopsy may be necessary. A strategic management plan includes the following: ●

●

●

● ●

Ensure a homeostatic environment (normalize electrolytes, acid-base status, hematocrit). Attain cardiovascular stability (euvolemia, mean arterial pressure >60 mm Hg). Treat bacterial infections and complications related to liver disease (encephalopathy, ascites, hyponatremia, variceal bleeding, coagulopathy). Avoid hepatotoxic and nephrotoxic drugs. Optimize renal perfusion: ● ● ●

●

Identify intrinsic renal parenchymal disease. Provide intravascular volume expansion. Institute drug therapy with splanchnic vasoconstrictors or renal vasodilators. Treat hemoglobinuria with urine alkalinization and diuresis.

For the majority of fulminant hepatic failure patients, survival ultimately depends on medical stabilization and urgent liver transplantation.

PREVENTION Minimizing the incidence of postoperative hepatic dysfunction begins with a comprehensive preoperative assessment and identification of those patients who might be predisposed. About 1 in 700 patients admitted for elective surgery has abnormal liver function studies. For patients with known hepatic disease, it is important to determine its cause and assess the degree of impairment, as well as any systemic manifestations and comorbidities. Anesthetic management often requires maximally invasive monitoring. The fewest possible anesthetic agents should be used (e.g., fentanyl, isoflurane, cisatracurium, and oxygen). The goal is to preserve hepatic function. This is done by minimizing reductions in hepatic blood flow and preserving oxygen delivery to prevent hepatocellular ischemia. Finally, keep in mind that surgery proximate to the liver or biliary system carries a higher expected rate of postoperative complications.

Further Reading Burroughs A, Dagher L: Acute jaundice. Clin Med 1:285-289, 2001. Chung C, Buchman AL: Postoperative jaundice and total parenteral nutritionassociated hepatic dysfunction. Clin Liver Dis 6:1067-1084, 2002. Friedman LS: The risk of surgery in patients with liver disease. Hepatology 29:1617-1623, 1999. Labori KJ, Bjornbeth BA, Raeder MG: Aetiology and prognostic implication of severe jaundice in surgical trauma patients. Scand J Gastroenterol 38:102-108, 2003.

OTHER SURGICAL SUBSPECIALTIES

or evidence of hepatocellular necrosis are poor surgical risks. In contrast, those with cholestatic disease have lower complication rates. Patients with chronic liver disease and preserved function may not be at increased surgical risk. However, those with cirrhosis do have higher morbidity and mortality rates. A focused preoperative assessment is necessary to identify high-risk patients. Progressive hepatocellular injury may lead to hepatic failure. For high-risk patients, postoperative care and surveillance should take place in a critical care setting. Clinical indicators of suboptimal liver function include the following:

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Surgery in the Morbidly Obese Christina M. Matadial and Jonathan H. Slonin Case Synopsis A 30-year-old woman is scheduled for laparoscopic gastric banding. She is 164 cm (63 inches) tall and weighs 160 kg (339 pounds).

PROBLEM ANALYSIS Definition Obesity affects approximately one third of the adult population in the United States. It is defined as body weight more than 20% greater than ideal weight. Morbid obesity is defined as body weight more than twice the calculated ideal weight. Ideal body weight is generally based on American life insurance statistics regarding height, build, sex, and age. The body mass index (BMI) is the most useful clinical indicator of obesity. The Broca index is a practical way to determine ideal body weight: Height in cm − 100 = ideal weight in kg for males Height in cm − 105 = ideal weight in kg for females The BMI was devised to reduce the effect of height on body weight: BMI = weight in kg/(height in meters)2 Ideal body weight = BMI of 22 to 28 kg/m2 Obesity = BMI of 28 to 35 kg/m2 Morbid obesity = BMI >35 kg/m2

Recognition It is now recognized that obesity is associated with a broad array of medical and surgical diseases leading to increased perioperative morbidity and mortality. Preoperative evaluation should focus on identifying coexisting diseases and conditions and the need for additional testing and invasive monitoring.

Risk Assessment Most of the major obesity-related health risks increase disproportionately with increasing weight. The rate of premature death is increased in patients who are 30% over their ideal weight and is doubled in those weighing 40% to 60% more than their ideal body weight. The incidence of sudden unexplained death is at least 13 times greater in morbidly obese women compared with women at their ideal body weight. 810

In men participating in the Framingham study, obesity was associated with a mortality rate up to 3.9 times greater than that of the normal weight group.

Implications Many organ systems are affected by morbid obesity, including the following: ● ● ● ●

Cardiovascular Respiratory and airway Gastrointestinal Endocrine and metabolic

Morbid obesity causes significant pathophysiologic changes that may increase perioperative morbidity and mortality (Table 202-1). The anesthesiologist is faced with numerous potential anesthetic and surgical challenges (Table 202-2). Cardiovascular disease commonly manifests as hypertension, coronary artery disease, and heart failure (e.g., cor pulmonale, pickwickian syndrome). Obesity appears to be an independent risk factor for ischemic heart disease. These patients may have limited functional capacity. Because they may not experience symptoms at rest, pharmacologic stress testing and imaging may be required to assess patients for myocardial ischemia and ventricular dysfunction. In an obese patient, cardiac output and blood volume must increase to perfuse additional fat stores. Cardiac output is estimated to increase by 0.1 L/minute for each kilogram of additional adipose tissue. Cardiomegaly and hypertension may develop due to this increased need. Long-standing hypertension with associated left ventricular hypertrophy may cause congestive heart failure. Chronic hypoxemia may contribute to the development of pulmonary hypertension and right ventricular dysfunction. When this progresses to right ventricular chamber dilatation and failure (cor pulmonale), the condition is known as the pickwickian syndrome. Other components of this syndrome are somnolence, hypoxemia, and polycythemia. Obesity is associated with reduced functional residual capacity (FRC), expiratory reserve volume, and total lung capacity. Expiratory reserve volume is the primary source of oxygen reserve during apnea. Therefore, in obese patients, preoxygenation is less effective. Lung closing volume may exceed FRC, leading to ventilation-perfusion mismatch and hypoxia. Both induction of anesthesia and supine positioning

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Organs or Organ Systems Affected by Morbid Obesity, with Associated Pathophysiology Associated Pathophysiology

Cardiovascular

Increased stroke volume and blood volume → increased cardiac output Chronic hypoxemia → pulmonary HTN → RV hypertrophy or failure, or any combination of these With cor pulmonale, patients are considered to be “pickwickian” (see below under “Airway and lungs”) Increased cardiac output to perfuse fat → systemic HTN → LV hypertrophy, and possible LV HF Any renovascular disease and insufficiency may aggravate HTN ECG findings: (1) left heart—low QRS voltage, LV strain or hypertrophy, LA abnormality, T-wave flattening in inferior and lateral chest wall leads; (2) right heart—RV strain or hypertrophy, right axis deviation or bundle branch block, P pulmonale with pulmonary HTN and cor pulmonale Cardiac arrhythmias secondary to hypercapnia, hypoxia, or systemic or pulmonary HTN and HF Hypercholesterolemia, hyperlipidemia, and hyperglycemia (i.e., metabolic syndrome) accelerate development of atherosclerotic cardiovascular disease Cerebral, coronary, or renovascular disease → stroke, acute coronary syndromes, or renal insufficiency Hypercoagulability, venous thrombosis, and pulmonary embolism: primary cause of perioperative 30-day mortality RA or LA chamber dilatation and hypercoagulability predispose to atrial tachyarrhythmias or fibrillation with systemic thromboembolism Abundant upper airway soft tissue increases potential for difficult mask airway and tracheal intubation Reduced FRC due to large pannus and increased body mass makes diaphragmatic excursions more difficult and position dependent; augmented by mechanical ventilation (higher airway pressures) Reduced chest wall compliance, lung volumes, and diaphragmatic excursions increase work of breathing Reduced inspiratory and expiratory reserve volumes Closing volume may exceed functional residual volume, leading to ventilation-perfusion mismatch, especially when supine Obstructive sleep apnea consequent to airway narrowing, overly abundant peripharyngeal adipose tissue, and abnormal decrease in upper airway muscle tone during REM sleep Reduced chest wall and diaphragmatic muscle tone with general anesthesia and muscle relaxation further impair oxygenation Predominant diaphragmatic respiration Pickwickian syndrome: morbid obesity, somnolence, alveolar hypoventilation, periodic respiration, hypoxemia, polycythemia, with RV failure and hypertrophy → cor pulmonale Metabolic syndrome → type 2 diabetes (sevenfold increase in incidence) Predisposition to hypothyroidism and Cushing’s disease Increased O2 consumption and CO2 production Increased metabolism of fluorinated volatile anesthetics (e.g., enflurane, methoxyflurane*) Increased pseudocholinesterase activity Increased intra-abdominal pressure with development of hiatal, umbilical, or inguinal herniation Gastroesophageal reflux disease and increased gastric acidity Abnormal liver function tests due to fatty infiltration of liver Increased risk for cholelithiasis and cholecystitis Inactivity secondary to morbid obesity predisposes to thromboembolism Excessive weight bearing accelerates development of osteoarthritis and chronic back pain Increased risk for malignancies involving the breast, colon, cervix, ovary, uterus, pancreas, prostate, and rectum

Airway and lungs

Endocrine/metabolic

Miscellaneous

*Seldom used in the developed world but may still be used in less developed nations. ECG, electrocardiogram; FRC, functional residual capacity; HF, heart failure; HTN, hypertension; LA, left atrial; LV, left ventricle/ventricular; RA, right atrial; REM, rapid eye movement; RV, right ventricle/ventricular. From Adams JP, Murphy JP: Obesity in anaesthesia and intensive care. Br J Anaesth 85:91-108, 2000; Gajraj NM, Whitten CW: Morbid obesity. In Atlee JL (ed): Complications in Anesthesia. Philadelphia, WB Saunders, 1999, pp 848-850; Roizen MF, Fleisher LA: Anesthetic implications of concurrent diseases. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 1017-1149.

further decrease FRC and worsen ventilation-perfusion mismatch. Increased BMI is also associated with reduced respiratory compliance and increased work of breathing. Difficult upper airway management (especially mask ventilation) and endotracheal intubation should be anticipated in obese patients. Increased adipose tissue in the neck and hypopharynx leads to narrowing of the oropharyngeal space. Approximately 5% of obese individuals develop

obstructive sleep apnea. Reduced FRC, atelectasis, and upper airway muscle relaxation predispose to obstructive sleep apnea. Sedative drugs produce a dose-dependent depression of consciousness and lung volumes. Because preoxygenation is less effective, time to desaturation below 90% may be greatly reduced, especially in the morbidly obese. Obese patients are presumed to be at increased risk for pulmonary aspiration of gastric contents due to increased

OTHER SURGICAL SUBSPECIALTIES

Organ or System

Gastrointestinal

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Anesthetic Implications for Surgery in the Morbidly Obese

Preoperative Preparation and Induction of Anesthesia Emotional issues (e.g., passive-aggressive personality, anxiety) Difficult venous access Difficulty with facemask ventilation and securing the airway Difficult direct laryngosopy or fiberoptic intubation Difficulty establishing noninvasive or invasive monitoring Increased risk for pulmonary aspiration

Intraoperative Management Reduced cardiopulmonary reserve Problems with patient positioning and mobilization Technical difficulties with regional anesthesia

Postoperative Complications Airway obstruction Hypoxemia and hypercarbia Deep venous thrombosis → pulmonary embolism (leading cause of perioperative mortality) Wound infection Hyperglycemia

Laparoscopic Surgical Implications Difficult trocar placement Hypercarbia and increased peak airway pressure Reduced venous return and cardiac output → hypotension

residual gastric volume and acidity, the possibility of associated diabetic gastroparesis, and increased intra-abdominal pressure. Also, there is a higher incidence of gastroesophageal reflux and hiatal hernia. Therefore, obese patients should be considered to have potentially full stomachs, even with elective surgery. Difficult airway management increases the risk for pulmonary gastric aspiration, especially when high pressures are required for positive-pressure facemask ventilation and oxygenation. In this situation, at least some inspired gas is diverted to the esophagus and stomach. This is compounded by multiple attempts at tracheal intubation, with positive-pressure facemask ventilation between attempts. Thus, the already increased risk for pulmonary aspiration of gastric contents is compounded by difficult airway management and intubation in obese patients. Glucose intolerance is common in obese patients, and the incidence of diabetes mellitus is higher than in the normal population. This may be due to increased resistance to insulin of peripheral tissues in the presence of excessive adipose tissue. The increased catabolic response to surgery may require the use of exogenous insulin during the perioperative period. In theory, larger fat stores provide an increased volume of distribution for lipid-soluble drugs (e.g., thiopental, benzodiazepines, opioids). Thus, if the loading dose of these drugs is based on actual body weight in obese patients, maintenance doses would be given less frequently owing to reduced clearance. However, with hydrophilic muscle relaxants, increased fat stores have less influence, and dosing should be based on ideal body weight (for adults, 60 to 80 kg for females, and 80 to 100 kg for males). Hepatic clearance of drugs is usually not affected, unless there is hepatic dysfunction due to fatty infiltration of the liver. Renal clearance of

drugs may increase owing to increased renal blood flow and glomerular filtration rate. However, with atherosclerotic renovascular disease, there may be reduced renal clearance due to renal insufficiency. Recovery times from volatile anesthetics are comparable in obese and normal patients with contemporary agents (e.g., desflurane, sevoflurane), provided the procedure is not lengthy (>3 to 4 hours).

MANAGEMENT After a focused history and physical examination, minimum laboratory investigations should include hemoglobin and hematocrit, serum electrolytes, blood glucose, liver function tests, electrocardiogram, and chest radiograph. Invasive cardiac evaluation, such as dobutamine stress echocardiogram or nuclear stress myocardial imaging, may identify patients with inducible ischemia, wall motion abnormalities, and ventricular contractile dysfunction. Any abnormal findings will direct intraoperative management. Baseline arterial blood gases may be indicated for patients with obstructive sleep apnea. No single anesthetic technique is superior. All drug doses must be carefully titrated to clinical effect. Neuraxial anesthesia may be beneficial for open lower abdominal procedures, although the identification of anatomic landmarks may be difficult. Especially in the morbidly obese, dosages of local anesthetics for epidural and spinal anesthesia are adjusted downward by up to 20% to 25%. This is because increased intra-abdominal and airway pressures are believed to cause epidural venous engorgement. Also, increased epidural fat reduces the epidural and subarachnoid spaces. Premedication sedatives and narcotics should be administered cautiously or avoided altogether in patients with hypoxemia, hypercapnia, or a history of obstructive sleep apnea owing to the risk for further respiratory depression and airway compromise. Difficult peripheral venous access may dictate the need for a central line. For indirect blood pressure measurements, a larger-sized cuff is frequently placed on the forearm. However, even when extra-large cuffs are used, systemic pressure measurements may be 20% to 30% above those obtained with an arterial catheter. The latter is often desirable because obese patients are susceptible to large fluctuations in blood pressure. Also, arterial blood gas determinations are often required to assess the adequacy of oxygenation and ventilation. Central venous or pulmonary artery pressure monitoring may be indicated if a patient has evidence of impaired myocardial function. Transesophageal echocardiography may be an alternative to a pulmonary artery catheter, although its use may be limited by the surgical procedure (e.g., the need for an orogastric or nasogastric tube or gastric endoscopy). Recognition of a potentially difficult airway may suggest the need for awake fiberoptic intubation. Obese patients often have a short, thick neck; an anterior larynx and large tongue; and limited movement of the jaw, neck, and head. However, if the preanesthetic assessment suggests that airway management and tracheal intubation will be relatively easy, a rapid-sequence induction and tracheal intubation may be performed. Preoxygenation is especially

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lation. This emphasizes the importance of early ambulation for these patients. Low-dose subcutaneous heparin or enoxaparin (Lovenox) and compression stockings or sequential compression devices should be used perioperatively.

PREVENTION Understanding the pathophysiologic changes of obesity and associated disease processes can help minimize morbidity and mortality. Pertinent history, physical examination, and testing can help identify patients with significant comorbidity and facilitate appropriate risk stratification to minimize the anesthetic risk.

Further Reading Adams JP, Murphy JP: Obesity in anaesthesia and intensive care. Br J Anaesth 85:91-108, 2000. Alpert MA, Alexander JK, et al: The Heart and Lung in Obesity. New York, Futura Publishing, 1998. Alpert MA, Terry BE, Cohen MV, et al: The electrocardiogram in morbid obesity. Am J Cardiol 85:908-910, 2000. Gajraj NM, Whitten CW: Morbid obesity. In Atlee JL (ed): Complications in Anesthesia. Philadelphia, WB Saunders, 1999, pp 848-850. Ogummaike BO, Jones SB, Jones DB, et al: Anesthetic considerations for bariatric surgery. Anesth Analg 95:1793-1805, 2002. Roizen MF, Fleisher LA: Anesthetic implications of concurrent diseases. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 1017-1149.

OTHER SURGICAL SUBSPECIALTIES

important owing to reduced FRC and oxygen reserve and increased oxygen consumption. Desaturation can occur rapidly during apnea. Two-person mask ventilation may be required. Risk for pulmonary gastric aspiration is reduced with the administration of H2-antagonists, nonparticulate antacids, and metoclopramide. When positioning the patient, care must be taken to protect and pad all pressure points. Patients weighing between 400 and 1000 pounds require special operating room tables. In extreme cases, it may be necessary to place two tables together for those with an extremely large abdominal pannus or wide girth. During preparation and induction of anesthesia, the obese patient should lie in a semirecumbent position with the head on a pillow and a bolster placed under the shoulders. In many patients, satisfactory oxygenation and ventilation can be achieved only by changing from the supine to the reverse Trendelenburg position. During mechanical ventilation, positive end-expiratory pressure may be used to improve oxygenation. High inspired oxygen concentrations may be required to prevent hypoxia. Use of a pressure-limited ventilatory mode may be necessary. Postoperative respiratory complications are a significant problem. The risk of postoperative hypoxemia is increased by surgery involving the thorax or upper abdomen (especially vertical incisions). Extubation should be delayed until the effects of muscle relaxants are completely reversed and the patient is fully awake. Postoperative mechanical ventilation may be required until extubation criteria are met. Patients using continuous positive airway pressure devices at home should have these available postoperatively. Aggressive pulmonary care with incentive spirometry, coughing, deep breathing, and early ambulation is beneficial. Adequate postoperative analgesia is essential to prevent diaphragmatic splinting; however, opiates must be carefully titrated to avoid respiratory depression. Use of regional techniques such as epidural analgesia may reduce the incidence of respiratory complications. Finally, the risk of deep venous thrombosis and pulmonary thromboembolism is increased. In fact, it is the leading cause of perioperative mortality in this patient popu-

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Complications of Carcinoid Tumors Kerri M. Robertson

Case Synopsis A 55-year-old man is scheduled for emergency exploratory laparotomy for small bowel obstruction. Anesthesia is induced with intravenous (IV) propofol, remifentanil, and vecuronium and maintained with an infusion of remifentanil and sevoflurane in an air-oxygen mixture. During surgery the patient becomes profoundly hypotensive. His blood pressure does not respond to boluses of IV fluid and phenylephrine. The patient’s face and neck appear flushed.

PROBLEM ANALYSIS Definition

Recognition Features of carcinoid syndrome include the following: ●

Carcinoid tumors are neoplasms of neuroendocrine origin and arise from enterochromaffin cells in various embryonic divisions of the gut. The largest case series (N = 11,842) reported in 2003 by Soga found that carcinoid tumors were most commonly found in the lung (19.8%), followed by the rectum (15%), ileojejunum (12%), stomach (11.4%), appendix (9.6%), and duodenum (8.3%). The overall incidence of the carcinoid syndrome was 7.7%. Carcinoid syndrome results from the direct release of vasoactive amines, polypeptides, proteins, and prostaglandins into the systemic circulation (Table 203-1). Intestinal carcinoids produce large amounts of serotonin (5-hydroxytryptamine [5-HT]), but many other products can be released as well, including histamine, norepinephrine, bradykinins, and prostaglandins. Serotonin is metabolized in the liver, lungs, and brain by monoamine oxidases to 5-hydroxyindoleacetic acid (5-HIAA), which is excreted in the urine. However, substances produced by liver metastases from midgut carcinoids or primary hepatic carcinoid tumors (i.e., 5-HT and other biogenic amines, along with proteins and polypeptides) are released directly into the systemic circulation, thereby bypassing the portal circulation. In addition, primary tumors without portal venous drainage (e.g., bronchial, ovarian, retroperitoneal) can cause carcinoid syndrome by circumventing hepatic metabolism. A life-threatening carcinoid “crisis” is an acute exacerbation of the carcinoid syndrome. It results in profound flushing, hypotension or extreme changes in blood pressure, stupor, diarrhea, confusion, bronchospasm, arrhythmias, and hyperthermia. Such crises can be triggered by tumor palpation, induction of anesthesia and tracheal intubation, inadequate analgesia, surgical stress, druginduced mediator release, chemotherapy, and hepatic arterial embolization. 814

● ● ● ●

Episodic cutaneous vasomotor flushing Diarrhea or abdominal pain Bronchospasm Carcinoid valvular heart disease Pellagra and psychiatric symptoms

There is significant patient variability with regard to the type and severity of symptoms, depending on the anatomic site of the tumor, its venous drainage, and diverse characteristics of the secreted amine and peptide products. Bradykinin and histamine may play a prominent role in hypotension and cutaneous vasomotor flushing, whereas serotonin release contributes to diarrhea, bronchoconstriction, hypertension, and bowel ischemia. Pellagra and psychiatric symptoms are due to depletion of tryptophan, a precursor for serotonin synthesis. Carcinoid tumors are diagnosed by measuring the serotonin metabolite 5-HIAA in a 24-hour urine sample. A small bowel radiographic series, upper and lower gastrointestinal endoscopy, abdominal ultrasonography, and contrast-enhanced computed tomography or magnetic resonance imaging may identify a focal primary lesion. Liver metastases are detected by computed tomography or somatostatin scanning and liver biopsy. Diagnosis of a neuroendocrine tumor is confirmed with immunohistochemical markers. Natriuretic peptides (NT-proBNP) can be used as a simple marker for the diagnosis of carcinoid heart disease, which can then be confirmed by echocardiography. For patients with known carcinoid tumors, carcinoid crisis is suspected if severe intraoperative hypotension occurs that is unusually resistant to IV fluid loading and vasopressors. More rarely, the diagnosis is made by exclusion, but it is a consideration in any case of refractory hypotension.

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Table 203-1

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Amines, Proteins, and Prostaglandins Released in the Carcinoid Syndrome

Amines

Polypeptides and Proteins Adrenocorticotropic hormone Bradykinins Calcitonin Chromogranins Corticotropin-releasing hormone Glucagon Growth hormone Insulin Islet amyloid polypeptide Kallikrein Neurokinin A Neurokinin B Neuropeptide K Neurotensin Pancreatic polypeptide Peptide YY Parathyroid hormone-related peptide Somatostatin Substance P Vasoactive intestinal protein

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Octreotide acetate (Sandostatin) has simplified the perioperative management of patients with carcinoid tumor and is widely considered the standard treatment for carcinoid symptoms and crises. Octreotide is a synthetic octapeptide somatostatin analogue with an elimination half-life of about 1.5 hours following subcutaneous administration. There is evidence that octreotide may prevent mediator release by binding to the sstr-2 subtype of somatostatin G protein-coupled receptors. Symptoms are relieved in more than 70% of patients, although the average response lasts only 18 months. Insulin release in response to hyperglycemia is inhibited as well, which can complicate glucose management in obese patients or non-insulin-dependent diabetics. Unfortunately, octreotide does not prevent the progression of carcinoid cardiac lesions. Veall and coworkers reviewed 21 patients undergoing laparotomy for metastatic carcinoid tumors. The use of intraoperative octreotide allowed the completion of hepatic resections that had previously been aborted due to refractory hypotension with tumor manipulation. Kinney and colleagues reviewed 119 patients having similar surgery. None of the 45 patients who received octreotide intraoperatively experienced complications during surgery. In contrast, 8 of 73 patients who did not receive octreotide had cardiac complications.

Prostaglandins PGE2 PGF2 Modified from Lips CJ, Lentjes EG, Hoppener JW: The spectrum of carcinoid tumours and carcinoid syndromes. Ann Clin Biochem 40:612-627, 2003.

MANAGEMENT Anesthetic management of patients with carcinoid tumors requires the following: ●

●

Risk Assessment Carcinoid tumors occur relatively frequently but are only rarely symptomatic. They occur in 1 to 2 per 100,000 persons per year in the United States. The distribution is age dependent and rises continuously until the eighth decade. Under age 50 years, more women are affected, with the stomach and lungs more commonly involved. Metastatic disease occurs in 20% of all patients with carcinoid tumors. Estimated 5-year survival for localized disease is 75% to 93%. With metastatic disease, it is 15% to 35%. With cardiac involvement, the prognosis is worse. Right heart failure due to tricuspid and pulmonary valve disease may be fatal. The median survival after diagnosis is 1.6 years.

Implications Preoperatively, patients are evaluated for electrolyte imbalance and volume depletion due to secretory diarrhea. Carcinoid heart disease occurs in 20% to 70% of patients with metastatic disease. Classically, this includes right-sided endomyocardial fibrosis, pulmonary hypertension, tricuspid and pulmonary stenosis, and then tricuspid regurgitation with ultimate right heart failure. Inactivation of serotonin by the lung protects the left side of the heart, but occasionally it too is affected.

●

Immediate availability of IV octreotide to treat perioperative carcinoid crises Treatment of hypertension, hypotension, and bronchospasm Monitoring with an arterial line and central access (with or without a pulmonary artery catheter)

Therapeutic options for patients with carcinoid tumors include (1) somatostatin analogues to reduce hormone secretion, (2) resection of the primary tumor, and (3) excision or ablative therapy for liver metastases (e.g., radiofrequency ablation, cryotherapy, arterial chemoembolization). In selected cases, liver transplantation may be a treatment option. Valve replacement is feasible with carcinoid valvular heart disease but is associated with significant morbidity and mortality. Other therapeutic options include MIBG (m-iodobenzylguanidine) preparations, interferon-α, and chemotherapy. In the event of severe hypotension that is unresponsive to IV fluids, patients with known carcinoid tumors should receive IV octreotide (50-μg bolus) as first-line therapy. In one recent case series, the median dose of octreotide administered intraoperatively was 350 μg. Sympathomimetics are often administered but may actually worsen the episode, because α-adrenergic stimulation can cause further peptide release from the tumor. Octreotide has also been used successfully to treat severe carcinoid-induced bronchospasm, after aerosolized albuterol and isoflurane failed. Serotonin accentuates the vascular response to catecholamines by stimulating the release and inhibiting the

OTHER SURGICAL SUBSPECIALTIES

Dopamine Histamine Norepinephrine Serotonin

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reuptake of norepinephrine. It may also directly stimulate postjunctional α1-receptors. The resulting hypertension is amenable to standard treatment, such as increasing anesthetic depth or administering agents such as labetalol, nicardipine, or nitroprusside. Ketanserin (2.5- to 5-mg IV bolus with IV infusion at 5 mg/hour) has also been used. It blocks 5-HT, α1-receptors, and H1-receptors. Continuous blood pressure monitoring is highly desirable, because blood pressure changes may be abrupt. A central venous catheter should be considered for assessing right heart backpressure if there is the potential for extensive surgical blood loss. This is because the effects of circulating mediators may alter the normal physiologic signs of hypovolemia (i.e., negate any potential systemic arterial hypotension). The possible benefit of a pulmonary artery catheter should be weighed against the risk of its placement in a patient with tricuspid or pulmonary valve disease.

Premedication with benzodiazepines to relieve anxiety is important, as is adequate pain relief postoperatively, especially if surgical debulking leaves residual tumor. Ideally, both histamine release and sympathetic stimulation should be avoided. Etomidate or propofol may be better choices for IV induction, although thiopental-triggered histamine release appears to be of little clinical significance. Morphine has the potential to induce histamine release and hypotension. Remifentanil, sufentanil, and fentanyl are alternatives. Succinylcholine-induced fasciculations could theoretically provoke the release of hormones; however, recent reviews reported no adverse effects. Histamine release is more prominent with tumors of foregut origin. Thus, preoperative H1- and H2-receptor blockers and corticosteroids may be useful in patients with gastric or bronchial carcinoids. Ondansetron is the ideal antiemetic agent.

Further Reading PREVENTION To avoid complications in patients with carcinoid tumors, take the following measures: ●

● ● ●

Block histamine (H1- and H2-receptors) and serotonin receptors (octreotide). Avoid drugs that facilitate the release of mediators. Provide adequate anxiolysis and postoperative pain relief. Avoid sympathetic stimulation.

If preoperative control of symptoms with octreotide is successful, patients can be placed on its longer-acting somatostatin analogue lanreotide or Sandostatin LAR. For elective surgery, premedication with subcutaneous octreotide 200 μg daily for 3 days before surgery has been shown to improve the perioperative course of patients with carcinoid tumors. Some advise prophylactic continuous IV somatostatin or octreotide (100 μg/hour) during surgery.

Botero M, Fuchs R, Paulus DA, et al: Carcinoid heart disease: A case report and literature review. J Clin Anesth 14:57-63, 2002. de Vries H, Verschueren RC, Willemse PH, et al: Diagnostic, surgical and medical aspect of the midgut carcinoids. Cancer Treat Rev 1:11-25, 2002. Kinney MA, Warner ME, Nagorney DM, et al: Perianaesthetic risks and outcomes of abdominal surgery for metastatic carcinoid tumours. Br J Anaesth 87:447-452, 2001. Lips CJ, Lentjes EG, Hoppener JW: The spectrum of carcinoid tumours and carcinoid syndromes. Ann Clin Biochem 40:612-627, 2003. Quaedvlieg PF, Lamers CB, Taal BG: Carcinoid heart disease: An update. Scand J Gastroenterol Suppl 236:66-71, 2002. Schnirer II, Yao JC, Ajani JA: Carcinoid—a comprehensive review. Acta Oncol 42:672-692, 2003. Soga J: Carcinoids and their variant endocrinomas: An analysis of 11,842 reported cases. J Exp Clin Cancer Res 4:517-530, 2003. Veall GR, Peacock JE, Bax ND, et al: Review of the anaesthetic management of 21 patients undergoing laparotomy for carcinoid syndrome. Br J Anaesth 72:335-341, 1994. Zimmer C, Kienbaum P, Wiesemes R, et al: Somatostatin does not prevent serotonin release and flushing during chemoembolization of carcinoid liver metastases. Anesthesiology 98:1007-1011, 2003.

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Complications of Thyroid Surgery Samuel A. Irefin

OTHER SURGICAL SUBSPECIALTIES

Case Synopsis A 25-year-old woman with a known history of Graves’ disease presents for subtotal thyroidectomy. A prominent thyroid gland is palpated on physical examination, and she complains of dysphagia. The chest radiograph demonstrates mild displacement of the trachea from the midline.

weight loss, osteoporosis, and myopathy. In the elderly, the only presenting features may be unexplained weight loss, atrial fibrillation, and congestive heart failure.

PROBLEM ANALYSIS Definition Thyroid surgery is performed for removal of an enlarged thyroid gland (goiter) in patients with Graves’ disease. Graves’ disease is the most common cause of hyperthyroidism in the United States, with an estimated annual incidence of 300 cases per 1 million persons. It is an autoimmune disorder characterized by a diffusely enlarged thyroid gland and thyrotoxicosis, caused by thyroid-stimulating immunoglobulins. These immunoglobulins primarily bind to and activate the thyroid-stimulating hormone (TSH) receptors. This results in increased iodine uptake, protein synthesis, growth of the thyroid gland, and synthesis and release of thyroglobulin and thyroid hormones. Complications of thyroid surgery for goiter removal are listed in Table 204-1.

Recognition HYPERTHYROIDISM (GRAVES’ DISEASE)

AND

THYROTOXICOSIS

Signs and symptoms of hyperthyroidism are listed in Table 204-2. Patients with Graves’ disease are at risk for numerous complications related to the disease and its treatment. One such life-threatening complication is thyroid storm. Signs and symptoms of thyrotoxicosis are listed in Table 204-3. Without treatment, severe thyrotoxicosis results in cardiac complications (thyrotoxic crisis or thyroid storm), cognitive disorders, gastrointestinal disturbances, jaundice,

Table 204–1

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Complications of Thyroid Surgery for Goiter Removal

Precipitation of thyrotoxic crisis (“thyroid storm”) Hemorrhage → hematoma → airway compression → acute respiratory distress Recurrent laryngeal nerve injury Superior laryngeal nerve injury Hypoparathyroidism Corneal abrasion

THYROID STORM Thyroid storm is an extreme exacerbation of thyrotoxicosis. It is usually stress related due to infection, trauma, surgery, treatment with radioactive iodine, pregnancy, diabetic ketoacidosis, thyroid replacement therapy, and anticholinergic or adrenergic drugs. Even with early recognition and aggressive therapy, the mortality rate is estimated at 20%. Manifestations of thyroid storm are listed in Table 204-4. The exact pathogenesis of thyroid storm is not fully understood. Thyroid hormones regulate the nuclear transcription of messenger RNA in all cells. Free triiodothyronine (T3) binds to a DNA domain called the “thyroid response element.” Once bound, T3 initiates the transcription of an array of biochemical enzymes that regulate tissue metabolism. One theory suggests that an acute, rapid increase in free thyroid hormone levels, rather than absolute levels, precipitates thyroid storm. Because thyroid storm most often occurs 6 to 24 hours postoperatively, manipulation of the gland during surgery or an acute reduction in binding proteins postoperatively may account for this surge of free thyroid hormones. Other theories include adrenergic

Table 204–2

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Signs and Symptoms of Hyperthyroidism (Graves’ Disease)

Weight loss despite increased appetite Heat intolerance, sweating Diarrhea, abdominal pain Tremors of distal extremities Increased reflexes Proximal muscle weakness Tachyarrhythmias (especially atrial fibrillation) Widened palpebral fissure Decreased blinking Lid lag (ptosis), blurred or double vision Increased systolic pressure with widened pulse pressure Anxiety, restlessness Fatigue Shortened attention span

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Signs and Symptoms of Thyrotoxicosis

Heat intolerance, profuse sweating Diarrhea, vomiting, jaundice Atrial fibrillation, congestive heart failure, unexplained weight loss (elderly) Tachycardia or arrhythmias Hypertension or hypotension with shock state Tremors, seizures, confusion, coma Hyperphagia Osteoporosis and myopathy Increased reflexes (hyperreflexia) Unexplained weight loss despite increased appetite Fever (consistently >101°F)

receptor activation and a direct sympathomimetic effect of thyroid hormone owing to its structural similarity to catecholamines. Diagnosis of thyroid storm is based on its clinical presentation, because laboratory testing is nonspecific. Further, waiting for results only delays treatment. Thyroid storm is an acute, life-threatening progression of thyroid hormoneinduced hypermetabolic (thyrotoxic) states involving multiple organ systems (see Tables 204-3 and 204-4). The differential diagnosis includes malignant hyperthermia, septic shock, hypertensive encephalopathy, central nervous system infection, acute drug intoxication, and pheochromocytoma. RESPIRATORY DISTRESS

FROM

HEMATOMA

The incidence of hemorrhage after thyroid surgery is low (0.3% to 1%). Hematoma formation in the neck resulting in respiratory compromise is a potentially fatal complication, however, because small amounts of blood in the deep tissue spaces near the trachea may cause significant airway obstruction. Patients present with swelling and pain at the incision site, an expanding neck mass, and symptoms of respiratory distress, such as stridor and dyspnea. RECURRENT

OR

SUPERIOR LARYNGEAL NERVE INJURY

Because of the intimate association of the thyroid gland and the nerves supplying the larynx, damage to either the recurrent laryngeal nerve (RLN) or the superior laryngeal nerve (SLN) may be a complication of thyroid surgery. Nerve injury may result from traction, contusion, or crushing during exposure; inclusion of the nerve in a ligature; inadvertent complete or partial nerve transection; or compromised blood supply. The RLN is a branch of the vagus nerve. It innervates all the intrinsic muscles of the larynx, with the exception of the cricothyroid muscle, which is innervated by the SLN.

Table 204–4

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Manifestations of Thyroid Storm after Thyroid Surgery

Hyperthermia (as high as 105°F to 106°F) Hypertension, tachycardia, arrhythmias Mental status changes Cardiovascular collapse (“shock”) Congestive heart failure in patients prone to heart failure

Unilateral RLN injury produces abductor vocal cord paralysis. The affected vocal cord assumes a paramedian position. Patients often present with postoperative hoarseness or a weak, breathy voice, but voice changes may not be apparent for days to weeks. Bilateral vocal cord paralysis is especially a risk after total thyroidectomy. Complete or partial airway obstruction often manifests immediately after extubation. Symptoms include respiratory distress with stridor requiring emergent reintubation or tracheostomy. Occasionally patients complain only of dyspnea or stridor with exertion. The external branch of the SLN innervates the cricothyroid muscle, which tenses and adducts the vocal cords. With injury, laxity of the vocal cord on the side of injury may produce subtle changes in voice quality or fatigue with speech. Techniques for assessing vocal cord mobility include fiberoptic laryngoscopic visualization during spontaneous ventilation or during extubation. For the latter, the anesthesiologist performs direct laryngoscopy under deep general anesthesia and observes the mobility of the vocal cords as the endotracheal tube is removed. Laryngeal electromyography is a diagnostic tool used as a late prognostic indicator for recovery of vocal cord function. HYPOPARATHYROIDISM Hypoparathyroidism may complicate thyroid surgery due to inadvertent trauma to or removal of the parathyroid glands or, more frequently, devascularization of the glands during ligation of the blood supply to the thyroid. The parathyroid glands produce parathyroid hormone (PTH), which increases the serum concentration of calcium through the activation of vitamin D, thereby increasing renal absorption of calcium and bone resorption. Inadequate production of PTH results in hypocalcemia. The diagnosis of hypoparathyroidism is made by the measurement of low PTH or decreased serum ionized calcium concentrations. Hypocalcemia usually occurs 24 to 48 hours after surgery but may occur earlier. Tetany, carpopedal spasm, circumoral paresthesias, mental status changes, seizures, cardiac dysfunction, and stridor are manifestations of decreased ionized calcium concentrations. Confirmatory tests include the Chvostek and Trousseau signs and Q-T prolongation on the electrocardiogram. Postoperative hypoparathyroidism must be differentiated from tetany caused by acute hypocalcemia and from respiratory alkalosis associated with anxiety and hyperventilation. CORNEAL ABRASION Corneal abrasion can occur in patients with exophthalmos and is diagnosed postoperatively with corneal fluorescein staining and examination with a cobalt-blue slit lamp. Patients complain of eye pain, tearing, and a foreign body sensation in the eye.

Risk Assessment THYROID STORM Thyroid storm affects only a small percentage of patients with thyrotoxicosis. Most cases of thyroid storm are associated with Graves’ disease in childhood. However, patients with hyperthyroidism at the time of surgery are at risk for thyroid storm during the perioperative period.

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RESPIRATORY DISTRESS

FROM

HEMATOMA

RECURRENT

OR

SUPERIOR LARYNGEAL NERVE INJURY

RLN injury is uncommon, occurring in 0% to 2.1% of patients during thyroidectomy when the nerve is identified and dissected. When the nerve is not clearly identified, the reported injury rate increases to 4% to 6.6%. Compounding factors include the extent of dissection and resection, especially if performed for malignant disease. HYPOPARATHYROIDISM

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is essential. Controversy exists regarding the use of drains to prevent hematoma formation after thyroid surgery. RECURRENT

OR

SUPERIOR LARYNGEAL NERVE INJURY

Permanent injury of the RLN on one side causes postoperative hoarseness. Patients are usually able to compensate and have minimal or no airway difficulty. The paralyzed vocal cord atrophies over time, leaving the patient with the potential sequelae of dysphagia, risk of aspiration, and permanent changes in voice quality. Bilateral RLN injury results in unopposed adduction of the cords, as the cricothyroid muscle remains innervated by the SLN. Associated partial or complete airway obstruction requires immediate endotracheal intubation and re-exploration of the neck to identify any reversible cause of nerve injury. If the nerves are found to be intact, use of corticosteroids and a trial extubation several days later are warranted. Permanent bilateral RLN injury necessitates tracheostomy.

Hypoparathyroidism with hypocalcemia may be transient or permanent. The incidence of parathyroid injury increases with the magnitude of the operation. It is uncommon with subtotal thyroidectomy for Graves’ disease. The overall incidence of permanent hypoparathyroidism ranges from 0.4% to 13.8%. The rate of transient hypocalcemia is reportedly 2% to 53%. The cause is not clear but may be attributable to temporary hypoparathyroidism from reversible ischemia to the parathyroid glands, hypothermic injury, or acute suppression of PTH production due to the release of endothelin 1.

HYPOPARATHYROIDISM

CORNEAL ABRASION

CORNEAL ABRASION

The likelihood of corneal injury increases with the degree of ophthalmopathy and exophthalmos.

Prognosis is excellent, with most minor abrasions healing within 24 to 48 hours. Deep abrasions in the center of the cornea may leave a scar, with the potential for permanent vision loss. Complications include infection, corneal ulceration, and recurrent epithelial erosion. Ocular medications may cause allergic conjunctivitis or glaucoma in susceptible patients.

Implications Thyroid surgery is associated with a number of potentially serious complications. THYROID STORM Thyroid storm is the most severe form of thyrotoxicosis. It often occurs in patients who have not been rendered euthyroid before thyroid surgery. Consultation with an endocrinologist can assist in optimizing the patient’s preoperative status with antithyroid drugs, iodide therapy, β-blockers, and glucocorticoids. The chest radiograph may reveal cardiac enlargement or pulmonary edema in patients with congestive heart failure. This should be further evaluated by echocardiography. Therapy for congestive heart failure or rate control for atrial fibrillation may be required. In the perioperative setting, differentiating between thyroid storm and malignant hyperthermia may be difficult. RESPIRATORY DISTRESS

FROM

HEMATOMA

Respiratory distress from any cause requires immediate evaluation and treatment. Patients must be followed closely for up to 72 hours postoperatively for evidence of airway compromise. A thin paper tape dressing over the surgical incision allows optimal wound surveillance. Postoperative bleeding can be a devastating and potentially fatal complication of thyroid surgery. Fastidious intraoperative hemostasis

Hypocalcemia may be asymptomatic or it may progress to laryngospasm, tetany, and cardiac dysfunction as early as 6 hours after injury to the parathyroids. Calcium levels may continue to decline over the next 24 to 48 hours, and symptomatic patients require close monitoring of ionized calcium levels with calcium and vitamin D replacement. If the patient remains dependent on oral calcium supplementation for longer than 6 months, it is likely that permanent injury of the hypoparathyroid glands has occurred.

MANAGEMENT Hyperthyroidism (Graves’ Disease) Effective treatment for Graves’ disease includes medical therapy to alleviate symptoms and render the patient euthyroid, in conjunction with surgery. However, as mentioned earlier, thyroid surgery is associated with potentially serious complications, such as thyroid storm.

Thyroid Storm Therapy for thyroid storm is both supportive and therapeutic: ●

Assess airway, breathing, and circulation (ABCs): (1) ensure oxygenation and provide ventilatory support as needed; (2) restore intravascular volume with intravenous fluids; (3) establish invasive monitoring (e.g., direct arterial blood pressure monitoring, central venous access, urinary catheterization) if necessary; (4) treat tachycardia and atrial fibrillation; (5) anticipate heart failure and volume depletion; and (6) administer intravenous dextrose as needed to meet high metabolic demands.

OTHER SURGICAL SUBSPECIALTIES

Respiratory distress may be secondary to laryngeal edema, laryngospasm, bilateral vocal cord paralysis, tracheomalacia, or hypocalcemia. More commonly, however, it occurs with cervical hematomas that are generally venous in origin. If postoperative bleeding is unrecognized, these hematomas may cause airway obstruction and asphyxiation.

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Prevent hyperthermia by covering the patient with ice packs or cooling blankets and administering acetaminophen as needed. Prevent thyroid hormone synthesis by administering propylthiouracil (PTU) or methimazole. Block thyroid hormone secretion by giving intravenous potassium iodide before surgery to reduce gland size in patients with acute thyroid enlargement, especially when goiters are associated with airway compromise. Potassium iodide can also be used to suppress hormone secretion in thyroid storm. Reduce peripheral conversion of thyroxine (T4) to T3 with glucocorticoids, propranolol, and PTU. Relieve hyperadrenergic effects of thyroid hormones with β-blockers as needed. Treat adrenal insufficiency with glucocorticoids as required. Consult an endocrinologist for more definitive management. Monitor patients with thyroid storm in a critical care unit or similar environment.

Antithyroid drugs (e.g., PTU) inhibit iodination and coupling reactions in the thyroid. In addition, they reduce the synthesis of T3 and T4 and inhibit the peripheral conversion of T4 to T3 by blocking type I deiodinase. Therapy with potassium iodide is important because it inhibits the secretion of thyroid hormone; when given preoperatively, it also reduces both the vascularity and the size of the thyroid gland. During thyroid storm, intravenous potassium iodide is often used. After antithyroid drugs have been started, iodide may also be dissolved in water as a retention enema. β-Blockers are used to antagonize the cardiovascular manifestations of the hypermetabolic state, such as tachycardia, increased cardiac output, and tachyarrhythmias (often atrial fibrillation). Sustained hypermetabolic states may lead to congestive heart failure and hypotension. Other benefits of β-blockers include relief of many of the symptoms and signs of hyperthyroidism (see Table 204-2) and thyrotoxicosis (see Table 204-3). Corticosteroids are used to prevent adrenal insufficiency secondary to the hypermetabolic state in thyroid storm. Digoxin may be used to treat congestive heart failure or atrial fibrillation with a rapid ventricular response. Salicylates are not used for hyperthermia; they compete with T3 and T4 for binding to thyroid-binding globulin, which may increase the circulating levels of free thyroid hormone. Instead, acetaminophen is prescribed for hyperthermia.

Respiratory Distress from Hematoma Respiratory distress and impending airway obstruction due to an expanding neck hematoma require immediate (often bedside) neck re-exploration. However, return to the operating room will likely be required for more definitive control of bleeding sites, irrigation, and wound closure. If so, the airway must first be secured. Then the patient is taken to the operating room, with experienced health care providers present for ventilatory support, reintubation, and tracheostomy if needed.

Recurrent or Superior Laryngeal Nerve Injury Management of RLN injury remains controversial. Most patients with unilateral RLN injury need no definitive intervention and recover from reversible causes within 6 months of surgery. For patients with permanent unilateral RLN injury, surgery can improve voice quality and reduce the risk of aspiration. Surgical options are medialization or reinnervation of the vocal cord. However, if the RLN has been transected, it is debatable whether immediate microvascular anastomosis or grafting at the time of surgery is effective therapy. In contrast, with bilateral RLN injury, the patient usually requires immediate airway control with endotracheal reintubation or tracheotomy.

Hypoparathyroidism Hypocalcemia due to parathyroid injury is managed with calcium replacement, depending on the severity of hypocalcemia. Symptomatic hypoparathyroidism is promptly treated with 10 mL of 10% solution of calcium gluconate given over 10 minutes. This is followed by a continuous infusion (1 to 2 mg/kg per hour). Infusions are titrated to the patient’s symptoms and serum ionized calcium concentrations. When the patient is able to tolerate oral fluids, daily oral calcium carbonate and vitamin D supplementation are started.

Corneal Abrasion Corneal abrasions are treated with eye rest, narcotic analgesics, and possibly topical antibiotics (see also Chapter 184). Patching or use of a contact lens impregnated with a nonsteroidal anti-inflammatory drug may help reduce the associated pain.

PREVENTION Thyroid Storm The most common therapy for Graves’ disease is radioactive iodine. This often normalizes thyroid function within 6 to 12 months. However, radioactive iodine itself may precipitate thyroid storm. Iatrogenic hypothyroidism is also a risk. In patients with large or nodular (suggestive of carcinoma) goiters, it is essential that they be clinically and chemically euthyroid before surgery. Preoperative preparation includes antithyroid drug treatment (PTU) for approximately 6 weeks, with or without a β-blocker. Iodine is given by most surgeons for 2 weeks before surgery to reduce thyroid gland vascularity.

Respiratory Distress from Hematoma Thyroid surgery must be performed in a near-bloodless field to facilitate identification of the parathyroid glands and the RLNs and SLNs in the operative area. The key to limiting bleeding is proper positioning and meticulous surgical hemostasis. The patient’s neck is hyperextended, and the head of the operating table is elevated 30 degrees. This provides optimal exposure and reduces cervical venous pressure

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and bleeding. At the end of the procedure, Valsalva’s maneuver is performed with the head lowered to a neutral position. This facilitates the recognition of bleeding vessels. These are then coagulated or ligated. Smooth emergence without coughing or bucking on the endotracheal tube helps prevent early rebleeding.

Prevention of RLN or SLN injury also requires meticulous surgical technique. Identification of the entire course of the RLN is advocated by some, but this is controversial. Some authors recommend routine electrical stimulation of the RLN for identification. An electromyographic device for electrophysiologic monitoring of the RLN during surgery is commercially available. However, it is usually reserved for high-risk cases, such as patients with very large neck masses or prior surgery or irradiation.

Hypoparathyroidism Interruption of the parathyroid blood supply is a common cause of hypoparathyroidism. Therefore, identifying the blood supply and ensuring that it remains intact are important preventive measures. Also, the glands are identified to prevent inadvertent removal. Further, suctioning in the operative field can injure the parathyroid glands. Therefore, it

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is recommended that the field be kept dry by careful blotting with sterile gauze rather than use of a suction device. If the parathyroid glands are damaged or inadvertently removed, autotransplantation may prevent hypoparathyroidism.

Corneal Abrasion Intraoperative eye protection consists of lubrication, padding, taping the eyelids closed, use of protective eyewear, and care during surgical draping and undraping.

Further Reading Kahky MP, Weber RS: Complications of surgery of the thyroid and parathyroid glands. Surg Clin North Am 73:307-321, 1993. Lacoste L, Montaz N, Berrit A, et al: Airway complications in thyroid surgery. Ann Otol Rhinol Laryngol 102:441-446, 1993. Mackin JE, Canary JJ, Pittman CS: Thyroid storm and its management. N Engl J Med 291:1396, 1974. McGowan FX: Anesthesia for major head and neck surgery. In McGoldrick KE (ed): Anesthesia for Ophthalmic and Otolaryngologic Surgery. Philadelphia, WB Saunders, 1992, pp 75-85. Wartofsky L: Diseases of the thyroid. In Isselbacher KH, et al (eds): Harrison’s Principles of Internal Medicine. New York, McGraw-Hill, 1994, pp 1942-1947. Woeber K: Thyrotoxicosis and heart. N Engl J Med 327:94, 1992. Yeung J, Chiu AC: Graves’ disease. Endocrinology Web site. http://www.emedicine.com/med/topic929.htm

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Complications of Adrenal Surgery Michael F. M. James Case Synopsis A 19-year-old man presents in hypertensive crisis with tachycardia, congestive heart failure (CHF), and renal dysfunction. On investigation he is found to have a right adrenal mass. The surgical plan is to investigate the cause of the adrenal mass, stabilize the patient, and proceed to elective excision of the tumor.

PROBLEM ANALYSIS Definition Adrenal disease frequently progresses to secondary hypertension and hypertensive crisis. The adrenal gland has two distinct endocrine entities: the cortex and the medulla. The cortex synthesizes glucocorticoids (e.g., cortisol), and the medulla, mineralocorticoids (e.g., aldosterone) and androgens. The medulla synthesizes catecholamines such as dopamine, norepinephrine, and epinephrine. Catecholamine production is dependent on the enzyme phenylalanine-nmethyltransferase and the high concentrations of glucocorticoids found in the adrenal cortex. The most common functioning adrenal cortical tumors are benign adenomas that produce cortisol or, less frequently, aldosterone. Adrenal carcinoma is less common but produces more severe symptoms. Adrenal hyperplasia secondary to excess adrenocorticotropic hormone (ACTH) release from a pituitary microadenoma results in Cushing’s disease. Excess cortisol production from adrenal tumors or exogenous ACTH results in Cushing’s syndrome. Excess aldosterone production leads to Conn’s syndrome, which accounts for 0.5% to 3% of all cases of hypertension. Conn’s syndrome is usually due to a single adrenal adenoma, possibly in association with bilateral adrenal hyperplasia. Tumors that secrete catecholamines arise from neural crest tissue, including the sympathetic chain and, rarely, the cardiac conduction system. Approximately 90% of pheochromocytomas are unilateral adrenal medullary tumors. Bilateral adrenal medullary tumors are usually associated with congenital conditions or are found in children. Extra-adrenal pheochromocytomas seldom produce epinephrine, and these tumors are frequently both multiple and malignant. Adrenal tumors can secrete both epinephrine and norepinephrine; however, the latter usually predominates. Familial associations include multiple endocrine neoplasia (MEN) type IIA (Sipple’s syndrome), defined as medullary thyroid carcinoma, pheochromocytoma, and (inconsistently) parathyroid adenoma. MEN type IIB is similar to type IIA but also includes marfanoid habitus and mucosal neuromas. It was formerly believed that only 5% of pheochromocytomas were inherited; however, recent data 822

suggest that germline mutations may cause up to 25% of cases previously considered sporadic, especially in children and when the tumor is extra-adrenal. Other associations include von Hippel-Lindau syndrome1 and (rarely) von Recklinghausen’s disease (neurofibromatosis).

Recognition Hypertensive crisis, atypical diabetes, and unexplained cardiomyopathy, especially in young persons, should always raise the suspicion for adrenal disease. Classic features of pheochromocytoma (e.g., headaches, diaphoresis, palpitations) occur in about 80% of patients, but this history is often elicited only by direct questioning. The presentation of pheochromocytoma is variable (Table 205-1), and it may go undiagnosed for several years. The diagnosis of pheochromocytoma is based on the finding of significant levels of catecholamines and their metabolites in the plasma and urine, supported by radiographic evidence. Isolated vanillylmandelic acid measurements have a sensitivity of only 60%; however, if combined with serial metanephrine measurements, sensitivity and specificity increase to about 90%. High-performance liquid chromatography to measure plasma and urinary catecholamine concentrations has similar sensitivity but higher specificity (95%). Contrast imaging with I123-labeled MIBG (m-iodobenzylguanidine) is reserved for extra-adrenal pheochromocytomas or when multiple tumors are suspected. Computed tomography scanning is then used to establish precise tumor localization and definition. Rarely, other tests (e.g., clonidine suppression test) are useful when the diagnosis is still in doubt. Clinical hallmarks of Cushing’s disease are truncal obesity, thin skin, easy bruising, abdominal striae, hypertension, and hyperglycemia (Table 205-2). Cushing’s syndrome is usually clinically obvious and is confirmed by high

1 Von Hippel-Lindau syndrome, or retinocerebral angiomatosis (a type of phakomatosis), consists of retinal hemangiomas (multiple or bilateral) in association with hemangiomas or hemangioblastomas that involve primarily the cerebellum, the walls of the fourth ventricle, and occasionally the spinal cord. The disease has autosomal dominant inheritance and may be associated with renal cysts or hamartomas. These may affect the adrenals or other organs.

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Table 205–1

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Symptoms and Other Findings in Patients with Pheochromocytoma Symptoms and Other Findings

Integumentary Musculoskeletal Cardiovascular

Excessive sweating, cold extremities Muscle tremors Left atrial and ventricular hypertrophy; electrocardiogram abnormalities; cardiomyopathy; episodic (60%) or sustained (35%) hypertension; hypotension (5%); palpitations; peripheral vascular disease with tissue loss Reduced glucose tolerance; diabetes mellitus; diabetic coma; weight loss Nonspecific abdominal pain and nausea; occasionally presents as apparent acute abdomen Headache; anxiety attacks; stroke

Metabolic Gastrointestinal Central nervous

concentrations of serum cortisol. Identification of Cushing’s disease requires the dexamethasone suppression test and the corticotropin-releasing hormone test. The former causes ACTH to fall to very low concentrations in the absence of an ACTH-producing tumor. The latter should cause a marked increase in ACTH release with primary pituitary disease, but not in patients with adrenal tumors or ectopic ACTH production. Primary aldosteronism presents as severe hypertension, muscle weakness, polyuria, and thirst. Renal dysfunction secondary to hypertension and hypokalemia is common. High plasma sodium concentrations, hypokalemia, and metabolic alkalosis suggest Conn’s syndrome. This is confirmed by high serum aldosterone and low plasma renin concentrations.

immunosuppression increases the infectious risk. Furthermore, long-standing disease may result in difficult airway management and tracheal intubation. Pheochromocytoma carries the added risks of catecholamine-induced cardiomyopathy and tachyarrhythmias. Also, there may be associated cardiomyopathy and CHF (Fig. 205-1). Hyperaldosteronism increases the risk for renal dysfunction, muscle weakness, and cardiomyopathy, mainly due to chronic potassium wasting. Patients may present for anesthesia and surgery with severe intracellular potassium deficits, despite apparently adequate plasma concentrations after potassium replacement therapy.

Risk Assessment

Adrenal surgery carries the risk for damage to anatomically proximate structures, including the spleen, pancreas, diaphragm (pneumothorax), and vasculature (e.g., inferior vena cava, renal and portal veins, splenic vessels). Hemorrhagic risk is even greater with pheochromocytomas, because they are often quite vascular. For unilateral tumors, a posterior surgical approach may be preferable, with less blood loss and morbidity. However, when bilateral or extraadrenal tumors are suspected, the anterior approach is preferred, even though this approach increases the risk for inadvertent injury to adjacent organs. Also, access to the venous tumor drainage is more readily obtained early during the procedure. Laparoscopic adrenalectomy has become more popular in recent years and appears to reduce the morbidity associated

Adrenalectomy is a relatively high-risk procedure, mainly due to endocrine pathophysiology and target end-organ damage. Morbidity with simple adrenalectomy can be as high as 40%, with mortality between 2% and 4%. Perioperative mortality is higher (5% to 10%) for bilateral adrenalectomy in patients with Cushing’s disease. Further, such surgery mandates mineralocorticoid and glucocorticoid replacement therapy for the patient’s lifetime. Each individual pathology has associated risk factors. For adrenal tumors, hypertension with end-organ damage (especially involving the heart, brain, or kidneys) must be considered. With Cushing’s syndrome, osteoporosis increases the risk of skeletal injury during surgery, and

Table 205–2

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Implications

Systemic Manifestations of Cortisol Excess Due to Cushing’s Disease

Organ System

Systemic Manifestations

Integumentary Musculoskeletal Cardiovascular Gastrointestinal Respiratory Reproductive

Purple striae on abdomen, buttocks, and thighs; easy bruising; hirsutism; acne Proximal myopathy and weakness; osteoporosis; vertebral collapse Left ventricular hypertrophy; electrocardiogram abnormalities; hypertension (85%) Esophageal reflux Sleep apnea (32%) Women: virilization secondary to hypersecretion of adrenal androgens; loss of libido; oligomenorrhea Men: impotence Reduced glucose tolerance; diabetes mellitus (60%); altered fat metabolism and body distribution (“moon” face, central obesity, “buffalo hump”); increased mineralocorticoid activity—hyponatremia, hypokalemia, metabolic alkalosis Psychiatric symptoms: depression; agitated psychosis (60%-70% of patients)

Metabolic Central nervous

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Organ System

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A

B

Figure 205–1 ■ A, Chest radiograph of a patient presenting with hypertensive crisis, congestive heart failure, and catecholamine-induced cardiomyopathy. Note mitralization of the left heart border, pulmonary edema, elevated left main bronchus, and cardiac enlargement. B, Same patient 6 months after excision of pheochromocytoma. The cardiac silhouette has returned to normal.

with simple adrenalectomy. However, establishment of pneumoperitoneum with carbon dioxide insufflation and increased tumor manipulation may substantially increase catecholamine release from a pheochromocytoma and worsen any hemodynamic instability. The safe performance of adrenalectomy, particularly for pheochromocytoma, depends on skilled surgical and anesthetic management and requires excellent communication between the surgeons and anesthesiologist. The laparoscopic approach for pheochromocytoma resection is not advised unless the surgical-anesthesia team is knowledgeable about and experienced with the technique.

also manifestations of end-organ damage. Hypertensive emergencies require immediate IV therapy with antihypertensive agents. With pheochromocytoma, hypertensive crises are usually emergencies. Thus, IV drugs are the mainstay of treatment. Sodium nitroprusside (SNP) has been the most commonly used agent, but there are now recognized limitations to its use: ●

●

MANAGEMENT Preoperative Management of Hypertensive Crisis Hypertensive crises may be urgencies or emergencies (see Chapter 77). Both require a blood pressure of 160/90 mm Hg or higher. With hypertensive urgencies, there is no evidence of end-organ damage (e.g., renal failure of CHF, myocardial or cerebral ischemia). Also, therapy is less urgent, usually consisting of oral rather than intravenous (IV) drugs. During anesthesia and surgery and in postanesthesia and intensive care units, however, initial therapy is often with IV drugs. With hypertensive emergencies, blood pressure is 160/90 mm Hg or higher, and there is evidence of end-organ damage (see earlier). Also, acute CHF (as in the case synopsis), arrhythmias (e.g., acute atrial fibrillation, ventricular arrhythmias), aneurysm rupture with intracranial hemorrhage (i.e., hemorrhagic stroke), and aortic dissection are

●

Because patients with chronic hypertension are preload restricted, and because SNP is a potent arterial and venous dilator, especially in the venous capacitance beds, there is high potential for untoward hypotension during treatment with SNP. Untoward hypotension caused by SNP may necessitate the use of vasopressors, but those that act indirectly (e.g., ephedrine) may worsen hypertension in patients with pheochromocytoma. The use of SNP for blood pressure management in perioperative settings can be challenging owing to the high potential for increased blood pressure lability. Direct arterial monitoring is advised.

Because of the disadvantages of SNP, clinicians have turned to dihydropyridine (DHP) calcium channel blockers, especially for the management of hypertensive emergencies. DHP calcium channel blockers are arterioselective vasodilators; they have little or no effect on the cardiac calcium channels (sinoatrial node, atrioventricular node, contractility). The only IV calcium channel blocker available at present is nicardipine (Cardene IV), but at least one other is on the horizon. Oral dihydropyridines (e.g., nimodipine, amlodipine) are used for long-term blood pressure control. Nicardipine is compatible with IV β-blockers (e.g., esmolol), and the two can be used together as continuous IV infusions.

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Preoperative Medical Management Patients with Cushing’s or Conn’s syndrome are managed with conventional antihypertensive drugs, although spironolactone may be included to correct fluid overload and hypokalemia in primary aldosteronism. In pheochromocytoma, α-blockade is the cornerstone of therapy. It helps prevent paroxysmal hypertension, lowers intravascular volume, and reduces left ventricular strain. Phenoxybenzamine, a long-acting, noncompetitive, nonspecific α-antagonist, is the most widely used oral α-blocker. The initial dose (10 mg) is increased every 1 to 2 days until the blood pressure is controlled. Most patients require 60 to 250 mg/day. Preparation periods vary from 5 to 14 days, and no benefit has been shown with longer treatment. Adequate α-receptor blockade is indicated by good control of arterial pressure with orthostatic hypotension, nasal congestion, increased sweating, and warm extremities. Electrocardiogram abnormalities seldom revert to normal during preoperative preparation, and unless there is evidence of frank myocardial ischemia, there is no contraindication to surgery. Doxazosin, a long-acting selective α1-blocker, has also been used in doses ranging from 4 to 16 mg daily. Tachycardia normally responds to fluid loading, and β-blockade should not be used until vasodilatation has been achieved. Other drugs (e.g., α-methyl-tyrosine, calcium channel blockers, angiotensin-converting enzyme inhibitors) are used, but not widely so.

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Adrenal surgery increases the risk of hemorrhage, so good IV access is necessary. In addition to standard monitoring, hemodynamic and fluid balance must be monitored with at least an intra-arterial catheter, central venous pressure line, and urinary catheter. A pulmonary artery catheter is seldom helpful. Transesophageal echocardiography is useful, especially in those with cardiomyopathy (with or without CHF), because it allows the assessment of left ventricular contractility and filling. H2-receptor antagonists may be considered in cushingoid patients with reflux esophagitis. Pulmonary artery catheters have been advised but are not mandatory for surgery involving the adrenal cortex. Transesophageal echocardiography is better, because fluid balance problems may prove difficult.

Anesthetic Management Theoretically, drugs that release histamine (e.g., morphine, atracurium) should be avoided in patients with pheochromocytoma, as should those that cause tachycardia or stimulate the sympathetic nervous system (e.g., ketamine, atropine, droperidol, pancuronium). Succinylcholineinduced fasciculations may trigger the release of catecholamines in patients with pheochromocytoma, so this drug is seldom indicated. Among the volatile anesthetics, isoflurane and sevoflurane are theoretically preferable to halothane (which sensitizes myocardium to catecholamines) and desflurane (which increases heart rate). SNP has a rapid onset and short duration of action and has been widely used. Nitroglycerin has also been used successfully, but nicardipine may be better (see earlier). IV bolus phentolamine has too slow an onset-offset to be of use. IV bolus MgSO4 (2-g intermittent boluses) or infusion (2 to 3 g/hour) provides excellent hemodynamic control, inhibits catecholamine release (especially with laryngoscopy), and is an excellent antiarrhythmic. In patients with Cushing’s syndrome, peripheral vascular access may be difficult. Care must be taken when using adhesive tape owing to their very friable skin. Rapid-sequence induction with succinylcholine may be appropriate in those with reflux esophagitis. Care must also be taken with patient positioning, because osteoporosis increases the risk for fractures. Meticulous antisepsis and prophylactic antibiotics are necessary, because these patients have decreased resistance to infection.

Tumor Removal Preanesthetic Considerations and Monitoring If phenoxybenzamine has been used, it is omitted on the morning of surgery owing to its very long half-life. β-Blockade should also be withdrawn, so that the patient is not blocked at the time of tumor excision. Mild sedation with a benzodiazepine is usually adequate.

2 This strongly argues for a selective arterial vasodilator, because CHF is “forward failure” due to increased left ventricular work rather than simple volume overload. The heart still requires adequate preload. A venodilator can always be added if needed.

Pheochromocytomas are very vascular, and it is often difficult to ascertain when complete venous ligation has been attained. Therefore, tumor removal is the only guarantee that further catecholamine surges will not occur. Significant hypotension may occur, and immediate withdrawal of hypotensive agents, together with aggressive intravascular volume expansion (preferably with colloids), should be instituted. If MgSO4 has been used, calcium chloride 1 to 2 g by rapid IV injection may be useful to correct hypotension. Persistent hypotension may require the use of vasopressors (e.g., phenylephrine, norepinephrine) or epinephrine for short periods, but hemodynamic stability should be achieved

OTHER SURGICAL SUBSPECIALTIES

Magnesium sulfate (MgSO4) may be effective if SNP does not adequately reduce and control arterial blood pressure. As noted earlier, intravascular volume may be severely depleted, and fluid therapy may be needed if both CHF and reduced intravascular volume coexist. If so, diuretics are inappropriate and β-blockers are contraindicated, regardless of heart rate, until systemic vascular resistance is reduced and the patient is out of CHF.2 Even then, β-blockers are used mainly for myocardial ischemia. Preoperative assessment requires special attention to the underlying pathophysiology. Hypertension and hyperglycemia must be controlled, and fluid and electrolyte disturbances corrected. The electrocardiogram may reveal left atrial and ventricular hypertrophy, arrhythmias, ischemia, or infarction, and the chest radiography may show CHF. Echocardiography is useful with suspected cardiomyopathy. Potassium deficits may be particularly severe in hyperaldosteronism and should be carefully corrected.

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without vasoactive agents before completion of the surgery. Because these patients have substantial sympathetic paresis, arterial pressure is much more dependent on blood viscosity. A hematocrit of at least 30% should be maintained. In contrast, adrenalectomy for cortisol or aldosterone excess is not associated with such dramatic hemodynamic changes. Fluid balance, however, is critical, and patients having bilateral adrenalectomy require intraoperative mineralocorticoid and glucocorticoid support. Electrolyte disturbances with any of these tumors may increase the patient’s sensitivity to neuromuscular blocking drugs. Care should be taken to ensure complete reversal of neuromuscular blockade at the end of surgery. Postoperative ventilatory support is seldom required, however, unless there are other conditions that necessitate it.

Glucose Management Patients with Cushing’s syndrome (less so those with pheochromocytoma) may have some degree of hyperglycemia and glucosuria both preoperatively and intraoperatively. After tumor excision, hypoglycemia may occur. Blood glucose is monitored hourly for 24 hours postoperatively.

Postoperative Management Postoperative pain and discomfort are managed as usual. The use of epidural analgesia is a matter of personal choice. Catecholamine concentrations return to normal over several days, and about 75% of patients are normotensive within 10 days. Although hypertension may persist for several days after tumor removal, this does not necessarily imply residual tumor. Postoperative hypotension is rare with preoperative α-blockade and adequate volume expansion. If hypotension does occur, occult hemorrhage must be considered. Bilateral adrenalectomy necessitates postoperative steroid replacement with glucocorticoids and mineralocorticoids. However, even with unilateral tumor excision, transient steroid deficiency may occur. Thus, use of additional steroids in the early postoperative period is advised.

Unless the tumor is malignant, the long-term prognosis after adrenalectomy is good. More than 80% of patients return to normal health. Even with catecholamine-induced cardiomyopathy, the prognosis is excellent. This is one of the few forms of cardiomyopathy in which full recovery is the norm (see Fig. 205-1).

PREVENTION Prevention of complications during adrenal surgery is based on a careful preoperative patient assessment, followed by control of hypertension, restoration of intravascular volume, and correction of hyperglycemia and coexisting electrolyte abnormalities. The anesthesiologist should be prepared for significant blood loss and have a high index of suspicion for pneumothorax. Drugs should be readily available for the prompt treatment of both hypotension and hypertension.

Further Reading Atlee JL, Dhamee MS, Olund TL, et al: The use of esmolol, nicardipine or their combination to blunt hemodynamic changes after laryngoscopy and tracheal intubation. Anesth Analg 90:280-285, 2000. Bravo EL: Pheochromocytoma: An approach to anithypertensive management. Ann N Y Acad Sci 970:1-10, 2002. Brunt LM, Moley JF, Doherty GM, et al: Outcomes analysis in patients undergoing laparoscopic adrenalectomy for hormonally active adrenal tumors. Surgery 130:629-634, 2001. Connery LE, Coursin DB: Assessment and therapy of selected endocrine disorders. Anesthesiol Clin North Am 22:93-123, 2004. James MF, Cronje L: Pheochromocytoma crisis: The use of magnesium sulfate. Anesth Analg 99:680-686, 2004. Kinney MA, Warner ME, vanHeerden JA, et al: Perianesthetic risks and outcomes of pheochromocytoma and paraganglioma resection. Anesth Analg 91:1118-1123, 2000. Lenders JW, Pacak K, Eisenhofer G: New advances in the biochemical diagnosis of pheochromocytoma: Moving beyond catecholamines. Ann N Y Acad Sci 970:29-40, 2002. Neumann HP, Bausch B, McWhinney SR, et al: Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 346:1459-1466, 2002. Prys-Roberts C, Farndon JR: Efficacy and safety of doxazosin for perioperative management of patients with pheochromocytoma. World J Surg 26:1037-1042, 2002.

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Complications of Trauma Surgery Maged Argalious

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Case Synopsis A 23-year-old man arrives in the emergency department with a gunshot wound to the right upper quadrant of the abdomen. He is combative and confused. His vital signs include systolic blood pressure, 70 mm Hg; heart rate, 119 beats per minute; and respiratory rate, 22 breaths per minute.

PROBLEM ANALYSIS Definition Trauma-related injury (TRI) is the leading cause of death in the United States for persons between the ages of 1 and 45 years and is the third leading cause of death overall. Because TRI affects primarily the young, it is the leading cause of years of life lost before age 75 years. The World Health Organization (WHO) estimates that TRI is the leading cause of mortality globally for both men and women between 5 and 45 years of age. Also, WHO estimates that by 2020, TRI will be the leading cause of death in all age groups. TRI victims present unique challenges to the health care delivery system. They often have multiple injuries to multiple organ systems that necessitate resource-intensive care. Further, TRI can adversely interact with many chronic underlying medical conditions. Many trauma injuries are preventable. Drugs and alcohol are responsible for nearly 40% of fatal motor vehicle accidents and close to 50% of gunshot wounds. Trauma is classified as either intentional (e.g., homicide) or accidental, as well as according to the mechanism of injury (e.g., penetrating versus blunt). Owing to improvements in trauma care, there has been a decline in trauma-related deaths in recent years.

Recognition Evaluation of acute trauma victims has three key components: rapid overview, primary survey, and secondary survey. Resuscitation can be initiated at any time during this triage. Rapid overview takes only a few seconds and is used to determine whether the patient is stable, unstable, or dead. The primary survey involves the rapid evaluation of functions that are critical to survival. The ABCs of airway patency, breathing, and circulation are assessed, followed by a brief neurologic examination. Priority is given to cervical spine injury or impending cerebral herniation. The secondary survey entails a systematic, comprehensive evaluation of each anatomic region and usually detects injuries that were overlooked initially. Three quarters of such previously undetected injuries are orthopedic. Based on the results of the secondary survey, patients are rushed immediately to the operating room for surgery, transferred to the radiology

suite for further diagnostic studies, or reexamined and observed in an intensive care unit. Knowledge of the patterns of injury associated with different mechanisms of trauma (i.e., clusters of injury) can help anticipate and identify injuries early. The presence of the worst possible injuries should be assumed until the diagnoses are either confirmed or excluded. Many trauma-related complications are diagnosed intraoperatively (Table 206-1). Blunt trauma causes localized or widespread transfer of energy to the body. Depending on the site of impact and the amount of energy, this can cause visceral rupture or tissue disruption, including multiple fractures. Penetrating trauma is commonly limited to the track along which a bullet or sharp object has traveled.

Risk Assessment Triage scoring systems are based on the physical examination and physiologic or mechanism-of-injury parameters. They have traditionally been used to determine patterns of patient referral to trauma centers. Survival is the major outcome variable. The revised trauma score (RTS) is a prospective scoring system that exists in two forms: one is designed for use as a triage tool, and the other is used to evaluate in-hospital patient outcomes. The RTS accurately predicts mortality following traumatic injury, but there is a lack of definitive evidence supporting its use as a primary triage tool in the field or as a predictor of functional outcome and quality of life. To determine the RTS, the Glasgow Coma Scale (GCS) score, systolic blood pressure, and respiratory rate are assigned coded values from 4 (normal) to 0. These are then added and weighted (Table 206-2). When summed, values can range from 0 to 7.84. Higher values indicate a better prognosis. Of the many trauma scoring systems, the RTS is the most popular worldwide. It has been shown that hyperglycemia independently predicts longer intensive care unit and hospital stay and higher mortality in trauma patients. It is also associated with infectious morbidity. These associations hold true for mild and moderate hyperglycemia (glucose concentration >135 mg/dL and >200 mg/dL, respectively). Traumatic injuries and subsequent intraoperative complications depend on patterns of injury. Factors that affect these include age, gender, impact resistance and fixation of 827

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Injuries and Potential Perioperative Complications in Trauma Victims

Central Nervous System Cervical spine instability or injury and possible spinal cord injury Closed head injury with increased intracranial pressure Possible brainstem herniation due to increased intracranial pressure Brain herniation through open skull fracture

Chest and Pulmonary Endobronchial intubation Tension pneumothorax or hemothorax Pneumomediastinum Rib fracture and possible flail chest Pulmonary contusion Bronchopleural fistula Aspiration pneumonitis Bronchospasm Tracheobronchial plugging Fat embolism with long bone (e.g., femur) fracture

Cardiovascular Myocardial contusion or cardiac rupture Pericardial tamponade or pneumopericardium Aortic dissection or disruption Disruption of pulmonary vasculature or vena cava Hypotension: hypovolemic or neurogenic Hypovolemic circulatory shock Air embolism

Abdomen Disruption or laceration of hollow viscera Hepatic laceration Splenic rupture

Coagulation Coagulopathy, especially with massive blood transfusion Disseminated intravascular coagulopathy Primary fibrinolysis Hemolytic transfusion reaction

Electrolyte or Other Imbalance Hypocalcemia secondary to citrate toxicity Hyperkalemia, hypomagnesemia Acid-base imbalance

intoxicated patients, and those with neurologic signs or symptoms. Cervical spine injury is uncommon with penetrating trauma that is remote from the neck. Spine films that visualize all seven cervical and the first thoracic vertebrae in the lateral, anteroposterior, and odontoid views are required before clearing the cervical spine. Even with normal cervical radiographs, the possibility of ligamentous injury can be ruled out only by computed tomography scanning. Recognition of a potentially difficult airway, whether due to anatomic predisposition or the actual trauma, is one of the most important roles of the anesthesiologist. Intubation in a patient with an unstable cervical spine involves the potential for irreversible spinal cord injury. The risk for pulmonary aspiration of the gastric contents is high in trauma victims. Gastric emptying virtually stops at the time of injury, and protective airway reflexes are impaired in obtunded or comatose victims. The greatest risk for aspiration in conscious patients occurs between the induction of anesthesia and endotracheal intubation. The mortality rate with pulmonary aspiration is 5%. Fracture of the first or second ribs, flail chest, a widened mediastinum, massive hemothorax, and scapula fractures often correlate with pulmonary or vascular injury. In blunt trauma, rib fractures are the most common injury; hemothorax or pneumothorax is more common with penetrating injuries. Resuscitation frequently requires massive transfusion of blood and blood components, as well as volume replacement with crystalloids and colloids. For massive uncontrolled traumatic hemorrhage, the priority is for immediate blood, blood component, and volume resuscitation, followed by definitive surgical control of hemorrhage from major vessels. However, transfusion and achieving hemostasis with blood component therapy entail significant risks. Normal saline has been associated with hyperchloremic metabolic acidosis, and the use of large volumes of hetastarch solution has been implicated in coagulopathy and renal insufficiency.

Implications body parts, anatomic protection of organs, and mechanism of injury. Patients at risk for cervical spine injury include conscious patients with neck pain or severe pain with distraction, 20% of unconscious patients with injuries above the clavicle,

Table 206–2

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Revised Trauma Scoring System

Glasgow Coma Scale Score 13-15 9-12 6-8 4-5 3

The risk of cervical spine injury and aspiration determines the method used to secure the airway. If time permits, aspiration prophylaxis includes metoclopramide, an H2-antagonist, and sodium citrate to facilitate gastric emptying and reduce gastric pH. Most patients arrive in the operating room wearing

Systolic Blood Pressure (mm Hg) >89 76-89 50-75 1-49 0

Respiratory Rate (breaths/min) 10-29 >29 6-9 1-5 0

Coded Value 4 3 2 1 0

Revised trauma score = 0.9368(GSCc) + 0.7326(SBPc) + 0.2908(RRc), where GCS is Glasgow Coma Scale score, SBP is systolic blood pressure, RR is respiratory rate, and the subscript c denotes the coded value for the indicted parameter. Adapted from Champion HR, Copes WS, Sacco WJ, et al: Improved predictions from a severity characterization of trauma (ASCOT) over Trauma and Injury Severity Score (TRISS): Results of an independent evaluation. J Trauma 40:42-48, 1996.

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MANAGEMENT Airway Airway management must take into account the presence of cervical spine injury, full stomach, lack of patient cooperation, and anticipated difficult intubation. Use of blind nasal or direct laryngoscopy-assisted oral endotracheal intubation in a conscious patient requires topical anesthesia and possibly light IV sedation. Fiberoptic laryngoscopic or bronchoscopic techniques with topical anesthesia can also be used in awake or sedated patients, or the airway may be secured after IV rapid-sequence induction of general anesthesia. Table 206-3 lists common indications for endotracheal intubation in trauma patients. Indications for a surgical airway include failed intubation, an apneic patient with suspected cervical spine injury, facial trauma with suspected cervical spine injury, and severe facial and laryngeal trauma with altered anatomy.

Table 206–3

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Indications for Endotracheal Intubation in Trauma-Related Injury

Cardiac or respiratory arrest Airway obstruction or respiratory insufficiency Airway protection (e.g., head injury and Glasgow Coma Scale score <9) Need for deep sedation or analgesia up to and including general anesthesia Postresuscitation hypoxia or hypoventilation Delivery of 100% O2 in victims of carbon monoxide poisoning Facilitation of diagnostic workup in uncooperative or intoxicated patient Adapted from Dutton RP, McCunn M: Anesthesia for trauma. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 2157-2172.

Maintaining cricoid pressure during rapid-sequence induction of anesthesia until the cuffed endotracheal tube is properly positioned prevents gastric aspiration or insufflation of the stomach with gas. Also, neck stabilization techniques may impair the laryngeal view, thereby increasing the potential for difficult intubation. The algorithm developed by the American Society of Anesthesiologists Task Force on Difficult Airway Management is applicable in the case of trauma (see Chapters 40 and 42). Devices such as the laryngeal mask airway can be used temporarily as a bridge for establishing airway patency while securing a surgical airway or to facilitate fiberoptic intubation. Surgical options include cricothyrotomy, transtracheal jet ventilation, and tracheostomy. Cricothyrotomy takes less time to perform than tracheostomy and is therefore the preferred surgical approach. Because tracheostomy requires neck extension, it may exacerbate cervical spine injury. Tracheostomy is indicated in laryngeal trauma and with complete tracheal transection.

Breathing Management of ventilation requires attention to oxygen saturation, end-tidal carbon dioxide concentration, and peak inspiratory pressures. If gastric aspiration occurs, treatment includes increasing the inspired oxygen concentration, adding positive end-expiratory pressure, and bronchoscopy with saline lavage for airway plugging. A pressure-limited ventilatory mode can reduce the risk of barotrauma. The treatment for pneumothorax is immediate needle decompression at the second intercostal space in the midclavicular line, followed by thoracostomy tube placement.

Circulation Shock in trauma is due to hypovolemia until proved otherwise. Other causes, such as obstructive shock (due to tension pneumothorax) or neurogenic shock (due to spinal cord transection or spinal vasoparesis), must be excluded. Hemodynamic stabilization requires surgical bleeding control, restoration of circulating blood volume, correction of acidosis, and adequate oxygen transport (hematocrit). Vasopressors may be used to maintain blood pressure during volume restoration.

OTHER SURGICAL SUBSPECIALTIES

a cervical spine collar because cervical spine injury has not been ruled out. Options for securing the airway include fiberoptic-assisted or blind nasal or oral endotracheal intubation after topical oropharyngeal anesthesia in spontaneously breathing patients. Intravenous (IV) sedation may be used, unless contraindicated. Alternatively, the patient is intubated after IV rapid-sequence induction of anesthesia. Before induction, the front portion of the cervical spine collar must be removed, and the cervical spine is stabilized with manual inline traction. Then the patient is preoxygenated, with cricoid pressure applied during rapid-sequence induction and direct laryngoscopy for tracheal intubation with a cuffed endotracheal tube. Once the endotracheal tube cuff is inflated and adequate ventilation and oxygenation are confirmed, the anterior portion of cervical spine collar can be reattached. Placement of sufficient IV access above the diaphragm is crucial. A rapid IV infusion device allows rapid intravascular volume repletion with warmed IV fluids, blood, and blood products. The patient’s volume status, hemodynamic stability, and presence of pulmonary complications (e.g., pneumothorax) determine which agents can be used for the induction and maintenance of general anesthesia. Central venous and direct arterial pressure monitoring are established after the airway is secured. Once the arterial line is secured, an arterial blood sample is withdrawn and sent to determine the patient’s oxygenation (PO2), ventilation (PCO2), pH, and hematocrit. Without prompt correction, hypovolemia and acidosis can lead to irreversible shock and death. Massive transfusion of blood and blood products may complicate trauma surgery. Complications include excessive or inadequate blood product replacement, dilutional coagulopathies, hypocalcemia from citrate toxicity, hypothermia, acid-base and electrolyte disturbances, and sepsis leading to multiorgan system failure. In patients with documented cervical spine or lower spinal cord injury, high-dose IV bolus methylprednisolone (30 mg/kg) within 8 hours of injury, followed by an infusion (5.4 mg/kg per hour) for 24 hours, may improve neurologic recovery.

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Crystalloid replacement may be sufficient with blood loss less than 30% of the total blood volume, but at that point, colloids are usually added. The need for blood products is based on estimated blood loss, vital signs, evidence of active bleeding, and serial hematocrit measurements. The trigger for blood transfusion has been lowered, so that hematocrits in the low to mid-20s are now acceptable. It is rarely necessary to give type O, Rh-positive blood (Rh-negative blood for women of childbearing age), because type-specific blood should be available within 15 minutes. Typed and crossmatched blood (requiring 30 to 45 minutes) is used when available. The concept of delayed blood or blood product resuscitation (“permissible hypovolemia”) until surgical bleeding is controlled is not a widely accepted practice.

coagulation requires identification of the causative agent. Then, clotting factors (fresh frozen plasma), platelet transfusions, and small IV doses of heparin (50 units/kg) are given.

PREVENTION Primary Prevention Public safety campaigns must emphasize the hazards of drinking and driving. Seat-belt and helmet laws must be enforced. Use of gun locks must be encouraged, and gun control laws enforced. Motorcycle and driver safety courses and the use of child restraint seats can also reduce TRI and death.

Secondary Prevention Hypothermia Trauma victims are often hypothermic on arrival in the operating room. Warmed IV fluids and blood products, humidified inspired gases and low fresh gas flows, and forced air warming blankets help keep core temperature at 35.5°C or higher. Hypothermia reduces cardiac output and drug metabolism and attenuates immune responses. Hypothermia can also aggravate vasoconstriction, myocardial ischemia, hypotension, bradycardia, arrhythmias, and coagulopathies. During rewarming, oxygen needs are increased.

Coagulopathy Dilutional coagulopathies due to component deficiencies (fibrinogen, platelets, coagulation factors), fibrinolysis, and disseminated intravascular coagulation are medical causes of bleeding in trauma patients, especially those who have sustained major vascular injuries as well. Routine screens for disseminated intravascular coagulation (prothrombin time, partial thromboplastin time, platelets, fibrinogen, D-dimers) or thromboelastography to assess clot formation and lysis can serve as guides for the correction of coagulopathies. Fresh frozen plasma is used to correct an abnormal prothrombin time. Cryoprecipitate is used if fibrinogen is less than 100 mg/dL. Platelets are used when there is active bleeding and the platelet count is less than 100,000/mm3. ε-Aminocaproic acid, tranexamic acid, or aprotonin is used to treat primary fibrinolysis. Disseminated intravascular

Vigilant and capable anesthesiologists, along with surgeons with expertise in trauma surgery, are key to the secondary prevention of complications related to trauma. However, the anesthesiology-surgery trauma team must work efficiently and in concert with emergency department physicians and staff, as well as operating room and intensive care unit staff. The hospital’s radiology, laboratory medicine, and transfusion services must also be capable of providing the required ancillary support. Taken together, all these capabilities and their efficient deployment can facilitate the timely diagnosis and stabilization of trauma victims, thereby reducing the risk for secondary morbidity or mortality.

Further Reading Capan LM, Miller SM: Trauma and burns. In Barash PB, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 4th ed. Philadelphia, JB Lippincott–Williams & Wilkins, 2001, pp 1255-1296. Duke JC: Anesthesia. In Moore EE, Feliciano DV, Mattox KL (eds): Trauma, 5th ed. New York, McGraw-Hill, 2003, pp 329-353. Dutton RP, McCunn M: Anesthesia for trauma. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 2157-2172. Fingerhut LA, Warner LA: Injury Chartbook: Health: United States, 1996-97. Hyattsville, Md, National Center for Health Statistics, 1998. Gin-Shaw SL, Jordan RC: Multiple trauma. In Marx JA, Hockberger RS, Walls R (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, 6th ed. Philadelphia, Mosby, 2006, pp 300-316. Murray CJL, Lopez AD: The Global Burden of Disease. Cambridge, Mass, Harvard University Press, 1996.

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Complications of Laparoscopic Surgery Shahar Bar-Yosef

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Case Synopsis A 75-year-old man with mild ischemic cardiomyopathy is scheduled for elective laparoscopic cholecystectomy under general anesthesia with endotracheal intubation. As the Veres needle is inserted and carbon dioxide (CO2) insufflation starts, the end-tidal partial pressure of carbon dioxide (ETCO2) increases slowly from 35 to 50 mm Hg and then drops abruptly to 5 mm Hg. The patient becomes severely cyanotic, with bradycardia and no measurable blood pressure.

PROBLEM ANALYSIS Definition The most common causes of cardiovascular depression or collapse with laparoscopy are listed in Table 207-1. Conventional laparoscopic surgery requires general anesthesia, because three or more ports are inserted into the abdomen. One port is used for the insufflation of CO2, which is automatically regulated and maintained at 12 to 15 mm Hg. The other ports are used for the insertion of surgical instruments. Tilting the operating room table head-up (the reverse Trendelenburg position) or head-down (the Trendelenburg position) facilitates visualization of the operative site. Physiologic changes associated with laparoscopic surgery result from the complex interplay of three pathophysiologic mechanisms: positive-pressure CO2 pneumoperitoneum, respiratory acidosis, and the effect of head-up or head-down body positioning (Table 207-2). Positive intra-abdominal pressure compresses abdominal vessels, increasing systemic vascular resistance and reducing venous return. Intraabdominal pressure is transmitted to the thorax, reducing lung compliance and increasing ventilation-perfusion mismatch. Also, pneumoperitoneum causes a significant neurohormonal response. Vasopressin is released, along with activation of the renin-angiotensin-aldosterone axis, both of which contribute to the observed increase in systemic

vascular resistance. CO2 absorption and reduced alveolar ventilation (with positive intra-abdominal pressure) increase systemic acidosis. This increases catecholamine release, mean arterial pressure, and cardiac output. However, severe respiratory acidosis can cause direct myocardial depression. Various positions, especially the steep Trendelenburg (e.g., gynecologic laparoscopy) or reverse Trendelenburg (e.g., laparoscopic

Table 207–2

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Physiologic Changes during Laparoscopy

Physiologic Change

Respiratory ↓ Lung . . compliance ↑ V/Q mismatch ↑ Inspiratory pressures ↑ PaCO2 and ↓ pH

■

Causes of Cardiovascular Depression or Collapse during Laparoscopy

Tension pneumoperitoneum Tension pneumothorax Pericardial tamponade Myocardial ischemia Extreme hypercapnia Venous gas embolism Bleeding and hypovolemia Arrhythmias

↑ IAP; head-down position Basal atelectasis; ↓ functional residual and vital capacities Pneumoperitoneum; head-down position ↑ CO2; ↓ pulmonary perfusion; ↓ alveolar ventilation

Cardiovascular ↑ SVR, PVR, MAP ↑ Cardiac filling Arrhythmias (T or B) ↓ Venous return (VR) ↓ Ejection fraction (EF)

Table 207–1

Mechanism

↓ Cardiac output ↓ Renal blood flow ↓ Splanchnic perfusion

↑ IAP, angiotensin, and catecholamines; hypercapnia ↑ Intrathoracic pressure; head-down position Acidosis, catecholamines (T); ↑ vagal tone due to ↑ IAP (B) Vena cava compression; head-up position ↑ Afterload; hypercapnia-induced myocardial depression ↓ VT and EF; arrhythmias; ↑ LV wall stress ↑ IAP; ↓ renal vasoconstriction ↑ IAP, ADH, and catecholamines; ↓ cardiac output

Other ↓ Urine output ↑ Intracranial pressure

↓ Renal blood flow; ↑ ADH secretion ↓ VR; ↑ CBF; ↓ lumbar CSF absorption; head-down position

ADH, antidiuretic hormone; B, bradyarrhythmias; CBF, cerebral blood flow; CSF, cerebrospinal fluid; IAP, intra-abdominal pressure; LV, left ventricular; MAP, mean arterial pressure; PVR, pulmonary . . vascular resistance; SVR, systemic vascular resistance; T, tachyarrhythmias; V/Q , ventilation-perfusion.

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Differential Diagnosis of Complications during Laparoscopy

Complication

Clinical Sequelae

Extraperitoneal CO2 inflation

Subcutaneous emphysema; pneumomediastinum; simple or tension pneumothorax; pneumopericardium that mimics cardiac tamponade; massive gas embolization that can be vascular, visceral, or both— if vascular, possible cardiovascular collapse Bradyarrhythmias: sinus or ectopic atrial; AV junctional rhythm; idioventricular rhythm; asystole Tachyarrhythmias: atrial, AV junctional, or ventricular origin Blood loss due to inadvertent visceral or vascular injury; vascular compression (especially venous capacitance bed, leading to reduced preload and cardiac output) Modest hypercapnia (CO2 ≤60 mm Hg) is expected; moderate hypercapnia (CO2 ≤80 mm Hg) may occur; severe hypercapnia (CO . .2 >80 mm Hg) may lead to cardiovascular collapse Rare, but possible with V/Q mismatch, endobronchial intubation, gastric aspiration, or severe hypercarbia with low FiO2 Nausea and vomiting: 40%-70% of patients; about half require therapy Pain: due to diaphragmatic irritation

Arrhythmias Hypotension Hypercapnia Hypoxemia Postoperative

. . AV, atrioventricular; FiO2, fraction of inspired oxygen; V/Q , ventilation-perfusion.

cholecystectomy), may either accentuate or alleviate these respiratory and hemodynamic changes. Numerous complications are inherent in laparoscopic surgery, especially during abdominal trocar placement and CO2 insufflation (Table 207-3). Most common is the extraperitoneal insufflation of CO2 (incidence of 0.4% to 2%). Subcutaneous CO2 emphysema results from dissection of gas into tissue planes around the trocar site used for insufflation. This can extend into the mediastinum and to subcutaneous tissues. Gas under pressure may also be introduced into the pleural space via congenital pleural-peritoneal communications or an inadvertent diaphragmatic injury, creating simple or tension pneumothorax. Introduction of gas into the pericardial space creates a pneumopericardium that can mimic the clinical presentation of cardiac tamponade. Massive gas embolization is a catastrophic complication caused by the inadvertent injection of insufflating gas into a vessel or abdominal organ during the induction of the pneumoperitoneum. If the gas is injected into a vein, subsequent obstruction of the right ventricular outflow tract or pulmonary circulation may lead to cardiovascular collapse. The incidence of visceral embolization is 0.002% to 0.08%; however, vascular gas embolism can be detected in up to two thirds of all patients undergoing laparoscopic cholecystectomy if diagnostic transesophageal echocardiography is used. The lethal embolic dose of CO2 is five times greater than that estimated for air. Arrhythmias may occur. Tachyarrhythmias (sinus arrhythmias, atrial and supraventricular ectopic beats and tachycardias, ventricular ectopic beats, ventricular tachycardia or fibrillation) are related mainly to respiratory acidosis and the associated catecholamine surge. Bradyarrhythmias (sinus bradycardia, wandering atrial pacemaker, junctional rhythm, atrioventricular heart block, asystole) are likely vagally mediated or due to extreme hypercarbia and respiratory acidosis. The possibility of hypotension secondary to blood loss from accidental visceral and vascular injury exists and is complicated by the difficulty of achieving rapid control of a bleeding source. Although major vessels can be injured, the more common sites are the epigastric and iliac vessels.

Gastrointestinal perforation or hepatic and splenic tears have also been described. Modest or moderate hypercapnia is a nearly universal occurrence during laparoscopy; if it is severe (PaCO2 > 80 mm Hg), it may be associated with cardiovascular collapse. In contrast, hypoxemia is rare during laparoscopy. Isolated hypoxemia can occur, however, with significant ventilationperfusion mismatch, endobronchial intubation, aspiration, or severe hypercapnia in the setting of a low-normal fraction of inspired oxygen. Postoperative complications are usually benign. Nausea and vomiting occur in 40% to 70% of patients after laparoscopy; about half require antiemetic therapy. Postoperative pain due to diaphragmatic irritation is usually described as vague abdominal, neck, or shoulder discomfort.

Recognition Rapid changes in ventilatory and hemodynamic parameters are most likely to occur early in the laparoscopic procedure. They are caused by changes in body position and introduction of the Veress needle and gas insufflation. Close patient scrutiny and monitoring of vital signs (i.e., electrocardiogram, noninvasive blood pressure, pulse oximetry, capnography) are essential. Capnography is an invaluable diagnostic tool during laparoscopy because it may provide early warning signs of impending catastrophic events. Measurement of ETCO2 concentrations can define changes in pulmonary CO2 elimination, which is dependent on CO2 production, lung perfusion, and alveolar ventilation. The normal range for ETCO2 is 35 to 37 mm Hg. The gradient between CO2 concentration in arterial blood and ETCO2 is usually 5 to 6 mm Hg. However, in some patients, especially those with cardiopulmonary disease, an increased arterial-to-ETCO2 gradient reflects increased ventilation-perfusion mismatch and reduced cardiac output, both of which contribute to an increase in dead-space ventilation. Most patients require a 30% increase in minute ventilation to counter systemic absorption of insufflated CO2.

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Hypercapnia may cause respiratory acidosis (i.e., elevated PaCO2 and low pH). With severe hypercapnia, capnography may reveal spontaneous breathing. ETCO2 also increases with systemic CO2 absorption in the following situations: ● ●

● ● ● ●

A sudden decline in ETCO2 is usually due to obstruction of the airway or sampling tubing, extubation, circuit leak or disconnection, venous air or pulmonary embolism, low cardiac output, or cardiac arrest. Another cause is mainstem endobronchial intubation due to endotracheal tube migration during peritoneal CO2 insufflation, when the lungs are displaced cephalad by the CO2 pneumoperitoneum. To exclude this latter cause, lung auscultation should be performed higher on the chest wall. A sudden increase in peak inspiratory pressures should raise the suspicion for simple or tension pneumothorax. However, a more gradual, modest increase is expected with the reduced lung compliance and functional residual capacity (FRC) associated with pneumoperitoneum. Healthy patients tend to tolerate the reduced lung compliance and FRC with minimal consequences. Finally, increased capnographic plateau pressure is common with position-related, cephalad displacement of the diaphragm during CO2 insufflation. The value of more invasive monitoring has not been studied, but some advocate its use for obese, elderly, or debilitated patients. An arterial catheter allows continuous monitoring of blood pressure and repeated blood gas measurements. If a pulmonary artery catheter is used, filling pressures (central venous pressure and pulmonary capillary wedge pressure) tend to increase with pneumoperitoneum, regardless of actual venous return and cardiac filling pressures. Monitoring of cardiac output and mixed venous oxygen saturation is useful in patients with severe myocardial dysfunction. Transesophageal echocardiography is valuable for detecting hypovolemia, myocardial ischemia, ventricular dysfunction, worsened valvular regurgitation, and venous gas or pulmonary embolism.

Risk Assessment Mortality with laparoscopy is 0% to 0.13%. Most deaths are due to cardiac complications (25%). The rate of major intraoperative events is usually less than 2%. Vascular injury accounts for about one third of the associated morbidity. Relative contraindications to laparoscopic surgery include increased intracranial pressure, ventriculoperitoneal or peritoneal-jugular shunts, hypovolemia, congestive heart failure, severe cardiopulmonary disease, previous abdominal surgery with significant adhesions, morbid obesity, pregnancy, end-stage liver disease, and coagulopathies. Older and sicker patients with limited cardiac reserve or those at increased risk for ischemia or left ventricular failure might not

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tolerate the increase in systemic vascular resistance and left ventricular wall tension that accompanies pneumoperitoneum. Similarly, the deleterious respiratory effects of laparoscopy are predicted to be more severe in patients with preexisting lung disease with increased dead space, reduced compliance and FRC, or severe diffusion defects. Even large increases in minute ventilation in these patients may not be enough to normalize the arterial CO2 tension, and an already reduced FRC may decrease even further. This could lead to significant hypoxemia from atelectasis and intrapulmonary shunting. Bullous emphysema increases the risk for pneumothorax due to barotrauma. Preexisting pulmonary hypertension and right ventricular dysfunction may worsen owing to a CO2-mediated increase in pulmonary vascular resistance. The American College of Cardiology–American Heart Association algorithm for preoperative cardiac evaluation (discussed in Chapter 38) does not distinguish between laparoscopic and open abdominal surgery. However, some advocate echocardiography and spirometry in American Society of Anesthesiologists classes III and IV patients before laparoscopy. Forced expiratory volume less than 70% and diffusion capacity less than 80% are predictive of more severe hypercapnia during laparoscopy. In addition to comorbidities, the type of surgery determines the risk for complications. For example, the incidence of hypercarbia and subcutaneous emphysema are greater with retro- or extraperitoneal gas insufflation for laparoscopic inguinal hernia repair than with intraperitoneal insufflation for laparoscopic cholecystectomy. Patients undergoing laparoscopic Nissen fundoplication are at increased risk for pneumomediastinum, subcutaneous emphysema, and pneumothorax (1% to 5%). Also, they are more likely to have vagally mediated bradyarrhythmias.

Implications Laparoscopic surgery is considered a safe alternative to open procedures. Predictions are that up to 75% of all abdominal surgery will soon be performed endoscopically. Proven benefits of laparoscopic surgeries include smaller incisions, less intraoperative bleeding, shorter surgical times, and attenuation of the stress and inflammatory response accompanying open surgery. These factors lead to reduced postoperative analgesic requirements, improved pulmonary function, more timely ambulation, less ileus, faster recovery and discharge, increased patient satisfaction, and lower costs. Lung function appears to recover more quickly after laparoscopic surgery, FRC and vital capacity are much better preserved, diaphragmatic contractions are stronger, and hypoxemia is lessened. Consequently, laparoscopy is associated with a reduced incidence of postoperative atelectasis and pneumonia. However, physiologic changes due to peritoneal CO2 insufflation and patient positioning can cause significant reductions in blood pressure and cardiac output. If so, intraoperative management requires vigilance and skill on the part of the anesthesiologist. Any of the catastrophic events described earlier can place the patient in an acute lifethreatening situation. Experimental and clinical studies have found that intraoperative declines in the glomerular filtration rate and creatinine clearance during laparoscopy

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●

Pneumoperitoneum Subcutaneous CO2 extravasation Hypermetabolic states (malignant hyperthermia, thyrotoxicosis) Low minute ventilation Metabolism of sodium bicarbonate Use of CO2-enriched gases Rebreathing of exhaled gases.

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quickly reverse. No relationship exists between urine output during surgery and the postoperative serum creatinine concentration. Less is known about the incidence of cardiac complications. However, because perioperative myocardial infarction usually occurs within 24 to 48 hours of surgery and appears to be related to the magnitude of surgical stress, myocardial infarction should be less common after laparoscopic surgery, but this remains unproven. Safety of laparoscopy in the critically ill has not been studied. Theoretical considerations suggest the need for extreme caution. Increased intracranial pressure associated with laparoscopy may be detrimental to patients with closed head injury. Also, patients with sepsis are often hypovolemic, which may exacerbate the decrease in venous return and cardiac output with laparoscopy. Also, critically ill patients commonly have reduced splanchnic perfusion, and laparoscopy may induce mesenteric ischemia. This increases the risk for bacterial translocation and septic complications. Most patients with symptomatic gallstones are candidates for laparoscopic cholecystectomy. Exceptions are those with generalized peritonitis, septic shock from cholangitis, severe acute pancreatitis, end-stage hepatic cirrhosis with portal hypertension, severe coagulopathy unresponsive to treatment, known cancer of the gallbladder, and cholecystoenteric fistulas.

MANAGEMENT Management for hemodynamic perturbations during laparoscopy is complicated because of competing goals. Whereas increased blood pressure may require vasodilators, one must keep in mind that venous return is usually reduced. Therefore, arterial-selective intravenous dilators (e.g., hydralazine, labetalol, nicardipine) are preferred over sodium nitroprusside or nitroglycerin. Tachycardia may prompt treatment with β-blockers, especially in patients at risk for myocardial ischemia. However, this may increase the patient’s susceptibility to bradycardia mediated by increased vagal tone. In patients with myocardial dysfunction, afterload reduction may mitigate the detrimental effect of pneumoperitoneum and increased PaCO2 to increase systemic vascular resistance, left ventricular wall tension, and cardiac output. Rarely, reduction of the insufflation pressure to 10 mm Hg and use of an inotropic agent will be required. If so, some form of cardiac output monitoring is advised at this stage, because it may be difficult to distinguish hypotension due to a reduction in myocardial contractility from that due to other pathophysiologic changes. Generous intravenous fluids must be given to overcome the decrease in venous return caused by positive intraabdominal pressure. Central filling pressures usually are not available to guide fluid therapy. If possible, reducing the degree of reverse Trendelenburg positioning is another way to ameliorate reduced venous return. Rarely, the laparoscopic approach must be abandoned in favor of an open procedure. Therapy for hypercapnia is to increase minute ventilation by increasing the respiratory rate. Rarely, a switch from CO2 to another gas for insufflation is required. This introduces a greater risk of gas emboli due to reduced blood solubility (helium) or explosions (if hydrogen and methane

are present because air, oxygen, and nitrous oxide support combustion). Hypercapnia, which is difficult to correct, should prompt a search for subcutaneous emphysema, which may serve as a large reservoir of CO2. Prolonged postoperative ventilation may be required until the emphysema has sufficiently resolved, which often takes 4 to 6 hours. Giving analgesics or sedatives to patients with respiratory compromise secondary to airway obstruction, chronic obstructive pulmonary disease, or diminished respiratory drive subjects them to an increased risk of respiratory arrest. Tension pneumothorax requires immediate needle aspiration at the second intercostal space in the midaxillary line. Further gas insufflation should be stopped, and the pneumoperitoneum temporarily released. With positive-pressure ventilation, the needle catheter should be left in place until the surgery is completed. Rarely is a chest tube needed, because any CO2 will be absorbed quickly. Serial postoperative chest radiographs are mandatory. Once venous gas embolism is diagnosed or suspected, gas insufflation should be stopped immediately, the pneumoperitoneum released, and the patient placed in a steep head-down position and right side up. This places the right ventricular outflow tract in a dependent position relative to the right atrium and may help release a gas lock to forward blood flow. Ventilation with 100% oxygen should be started, and pressors should be given for hemodynamic support as needed. Right heart catheterization with a multiorifice catheter and aspiration of gas bubbles can be attempted but is rarely effective. In extreme cases, cardiopulmonary bypass may be required for evacuation of gas emboli. The possibility of paradoxical emboli through a patent foramen ovale must always be kept in mind. Thus, the patient should be evaluated for neurologic changes when he or she is awake and able to follow commands.

PREVENTION Insufflation of CO2 to create pneumoperitoneum increases intra-abdominal pressure. This enhances venous stasis, reduces portal venous and renal arterial blood flow, and increases airway pressures. Collectively, these changes impair ventilatory and circulatory function. Intraoperative steps that can be taken to reduce these changes include the following: ● ●

● ●

●

Reducing insufflation pressures to 10 to 15 mm Hg Moderating the degree of Trendelenburg or reverse Trendelenburg positioning Adjusting ventilation to reduce hypercapnia and acidosis Using sequential, intermittent lower extremity compression devices to reduce venous stasis Volume loading to minimize impaired renal and myocardial perfusion

Pressure-controlled ventilation is used to reduce the risk of barotrauma in patients with greatly increased airway pressures. An oro- or nasogastric tube is inserted for gastric decompression. A urinary catheter decompresses the bladder and reduces the risk for injury. Precautions should be used during extreme postural positioning to reduce the risk of nerve injury (e.g., shoulder braces for the Trendelenburg position, foot boards for the reverse Trendelenburg position).

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“Gasless laparoscopy” (i.e., abdominal wall lifting devices rather than gas insufflation) might be considered for patients with significant cardiopulmonary derangements or at high risk for them. If this is not an option, a more practical approach is to limit the degree of Trendelenburg or reverse Trendelenburg positioning to attenuate any adverse physiologic effects.

Eagle KA, Berger PB, Calkins H, et al: ACC/AHA update for perioperative cardiovascular evaluation for noncardiac surgery. Circulation 105:1257-1267, 2002.

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Harris SN, Ballantyne GH, Luther MA, et al: Alterations of cardiovascular performance during laparoscopic colectomy: A combined hemodynamic and echocardiographic analysis. Anesth Analg 83:482-487, 1996. Leonard IE, Cunningham AJ: Anesthetic considerations for laparoscopic cholecystectomy. Best Pract Res Clin Anaesthesiol 16:1-20, 2002. Nguyen NT, Goldman CD, Ho HS, et al: Systemic stress response after laparoscopic and open gastric bypass. J Am Coll Surg 194:557-566, 2002. Struthers AD, Cuschieri A: Cardiovascular consequences of laparoscopic surgery. Lancet 352:568-570, 1998. Wahba RWM, Tessler MJ, Kleiman SJ: Acute ventilatory complications during laparoscopic upper abdominal surgery. Can J Anaesth 43: 77-83, 1996.

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Further Reading

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Postoperative Urinary Retention D. Janet Pavlin Case Synopses Case 1 A 24-year-old man undergoes a 1-hour outpatient knee arthroscopy under spinal anesthesia with 10 mg bupivacaine. After 3.5 hours in the recovery room, he has voided 100 mL and is otherwise ready for discharge. Although the patient has experienced no pain or sense of fullness, a bladder scan reveals a postvoid residual volume of 700 mL. A diagnosis of urinary retention is made; the patient undergoes in-out catheterization for 700 mL of urine and is then discharged. The patient is able to void spontaneously 7 hours later at home, and no subsequent episodes of urinary retention occur. Case 2 A 45-year-old man undergoes drainage of a perirectal abscess under general anesthesia. The patient last voided 4 hours before surgery. He receives 1500 mL of fluid during surgery. In the recovery unit, he experiences considerable pain at the surgical site, for which he receives intravenous and oral opioid medication. He also reports a painfully distended bladder but is unable to void after 2 hours in the recovery unit. Inout bladder catheterization is performed, and 650 mL of urine is obtained. He is allowed to go home, but 14 hours later he returns to the emergency room with a painful distended bladder and inability to void. A bladder catheter is inserted, and 750 mL of urine is obtained. The patient is discharged with an indwelling catheter and returns 2 days later to have the catheter removed. He has no subsequent problems with voiding.

PROBLEM ANALYSIS Definition Urinary retention is defined as the inability to void in the presence of a full bladder. The normal adult bladder capacity is from 500 to 600 mL. Postoperative urinary retention is relatively common. Its frequency depends on the nature and location of surgery, type of anesthesia used, drugs given, and the patients’ underlying physiology and medical conditions. Knowledge of normal bladder function is a prerequisite to understanding how and why urinary retention occurs postoperatively. Voiding is neurally regulated and is normally a reflex response to a full bladder—known as the micturition reflex (Table 208-1). It requires bladder distention, followed by transmission of sensory input from the bladder to the midsacral region of the spinal cord, involuntary simultaneous contraction of the bladder, and reflex inhibition of the internal urethral sphincter. These must be coupled with voluntary relaxation of the external urethral sphincter. Visceral sensory afferents from the bladder travel primarily in the pelvic splanchnic nerves to synapse in the midsacral spinal cord (S2-S4), with projections to the 836

micturition center in the brain. The efferent limb of this reflex consists of the following: ●

Preganglionic parasympathetic fibers originating at S2-S4 travel in pelvic splanchnic nerves to peripheral cholinergic receptors within the bladder wall and stimulate bladder contraction during the active phase of voiding.

Table 208–1

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Neural Control of Voiding

Bladder distention Visceral afferent fibers via pelvic splanchnic nerves Synapse at the micturition center in the midsacral cord (S2-S4) Parasympathetic efferent cholinergic fibers (they arise at S2-S4, travel with the pelvic splanchnic nerves, synapse at cholinergic sites in the bladder wall, and then stimulate contraction) Sympathetic efferent fibers (they arise at T10-L2, travel via hypogastric plexuses to the internal urethral sphincter, and are involuntarily inhibited during voiding) Somatic efferent fibers (they travel via the pudendal nerve to striated muscle of the external urethral sphincter and are voluntarily relaxed during voiding) The entire reflex arc is subject to control by the pontine micturition center and higher centers in the brain via the spinobulbar tracts

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●

●

The micturition reflex is subject to modulation or control by higher brain centers, including the pontine micturition center (dorsolateral pons), areas of the diencephalon, and the cerebral cortex. Receptors in the spinal portion of the pathway are susceptible to modulation by opioids, acetylcholine, dopamine, serotonin, norepinephrine, GABA, excitatory and inhibitory amino acids, and other neuropeptides. Urinary retention can occur due to interruption of the micturition reflex at any point in the circuit. Spinal or epidural anesthesia interferes with the afferent and efferent limbs of the reflex. Opioids and anticholinergics may block transmission at cholinergic sites in the bladder wall or in the spinal cord. Increased sympathetic activity, due to pain in a lumbosacral nerve distribution or overdistention of the bladder itself, may interfere with reflex inhibition of sympathetic tone to the internal urethral sphincter. Inability to void may also result from failure to coordinate bladder contraction with sphincter relaxation (dyssynergia) as a result of disease or dysfunction of the spinal cord. Additionally, retention may be the result of obstruction to outflow at the level of the urethra due to prostatic disease or other acute or chronic conditions affecting urethral patency. Various other factors may act through cortical or subcortical mechanisms to inhibit the ability to void, including fear, embarrassment, and possibly recumbency.

Recognition Urinary retention may be painful or painless. Neuraxial blocks, analgesics, or sedation may prevent pain related to bladder overdistention. Although a high index of suspicion, palpation, and percussion can sometimes detect an overdistended bladder, this is often not possible or is unreliable. Both the duration of surgery and the amount of intraoperative fluids given significantly correlate with bladder volume at the end of surgery. Yet these relationships are variable and of limited value for diagnosing or predicting bladder volume in individual patients. In unconscious patients, a portable ultrasound scan may be the only practical, reliable, noninvasive means of diagnosing urinary retention and bladder overdistention. In one study, the correlation between surgery duration and urinary bladder volume after surgery was 0.32 (P =.0002). The correlation between intraoperative intravenous fluid volumes and urinary bladder volume was 0.26 (P =.0021). Also, ultrasound-determined bladder volumes correlated with measured volumes (r = 0.9; P <.0001). In-out urinary bladder catheterization is used to confirm an overdistended bladder. If bladder volume is categorized by patients or nurses as empty, moderately full, or overly distended based on usual clinical criteria, studies have confirmed that patients incorrectly estimate bladder volume in 56% of cases, and nurses err in 46% of cases.

Postoperative Urinary Retention

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Risk Assessment Risk factors for postoperative urinary retention are listed in Table 208-2. Urinary retention is often related to the use of neuraxial blockade. The incidence may be greater than 60% with long-acting local anesthetics. With low-dose, short-acting local anesthetics without vasoconstrictors (e.g., lidocaine, chloroprocaine), the incidence is relatively low. Mulroy and colleagues reported that the incidence was 3 in 201 patients after short-acting spinal or epidural anesthesia. Vasocontrictors prolong the duration of sacral anesthesia with epidural, caudal, or spinal anesthesia and thus increase the incidence of urinary retention. Surgery in the lumbosacral nerve distribution can also cause urinary retention. Hernia repair and rectal surgery are commonly associated with urinary retention (14% to 35% for hernia repair; 1% to 52% for rectal surgery). Partly, these differences depend on the method used for assessment. Furthermore, urinary retention can be caused by pain and by increased sympathetic activity in the distribution of the lumbosacral nerves, which counters reflex-inhibition of tone to the internal urethral sphincter. Mechanical trauma to the urethra or preexisting outlet obstruction accounts for most cases of urinary retention after urologic surgery. Spinal cord disease in the lumbosacral distribution can locally interfere with micturition or impair central coordination of voiding, as in patients with spinal cord injury. A history of urinary retention increases the incidence of postoperative urinary retention. Mechanisms include any of the causes described earlier. Also, mandatory recumbency is associated with the inability to void in many patients. The author found an 18% incidence of urinary retention in patients confined to bed after foot surgery, with or without a sciatic nerve block (unreported observations). Other factors, including systemic opioids, anticholinergics, and excessive intravenous fluids (see Table 208-2), contribute to difficulty with micturition and postoperative urinary retention.

Implications Acutely, overdistention of the bladder can cause pain, or incontinence may ensue. Reflex-increased sympathetic activity may cause systemic hypertension; this is more likely in patients with spinal cord transection (autonomic dysreflexia). Studies in animal models have shown that bladder overdistention leads to bladder wall ischemia. If sustained (>3 to 10 hours),

Table 208–2

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Risk Factors for Urinary Retention

Neuraxial local anesthetics Neuraxial or systemic opioid therapy Anticholinergics Urethral outlet obstruction Surgery of the lower urinary tract or surrounding area Surgery in a lumbosacral nerve distribution area (groin, perirectal, penile) Previous history of retention Spinal cord disease or dysfunction Recumbency Excessive fluid administration

OTHER SURGICAL SUBSPECIALTIES

Sympathetic efferent fibers originating from T10 to L2 travel via the superior and inferior hypogastric plexuses to the internal urethral sphincter. Their output maintains sphincter tone during continence and is reflex-inhibited during voiding. Somatic efferent fibers course in the pudendal nerves to the striated muscle of the external urthethral sphincter, which must be voluntarily relaxed during voiding.

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urothelial cell damage, hemorrhage, and edema may occur. This is followed by parasympathetic nerve ending loss, reduced parasympathetic activity, and failure of the detrusor muscle to contract normally. Functional effects of impaired parasympathetic activity include inability to empty the bladder fully, leading to frequent small voidings (frequency, nocturia), weak stream, hesitancy, dribbling, and bladder instability. If sustained, urinary stasis can lead to urosepsis. Most often, cellular regeneration occurs over several weeks, with gradual recovery of normal bladder function. However, intercellular junction rupture and interstitial collagen deposition can occur. This leads to permanent impairment of impulse transmission throughout the bladder wall and may require operative intervention (e.g., MarshallMarchetti-Krantz bladder suspension or creation of an ileal conduit).

MANAGEMENT Postoperative urinary retention typically results from overfilling of the bladder when the micturition reflex is impaired by anesthesia or surgery. Because this is usually temporary, some episodes of retention can be prevented simply by ensuring that the patient has an empty bladder immediately before surgery and by avoiding excessive fluid administration during surgery. This is particularly relevant when either the surgery or the anesthetic is known to predispose to urinary retention or when there is a history of urinary retention. Given that the normal rate of urine formation is about 75 mL/hour (adults), the time required to attain a full bladder (600 mL) is roughly 8 hours. Based on animal investigations, the critical duration for bladder overdistention to avoid potential nerve injury is 4 hours. Thus, clinicians can assume that it is undesirable to have an overdistended bladder for longer than 4 hours. Table 208-3 shows the estimated time required to attain a bladder volume that exceeds 600 mL for 4 hours (i.e., theoretical critical duration), assuming a rate of urine formation of either 50 or 100 mL/hour. Assuming an empty bladder at the outset, the critical time would be 10 hours at a rate of 100 mL/hour and 16 hours at a rate of 50 mL/hour. However, if the initial volume was 400 mL, the critical times

Table 208–3

■

Starting Residual Bladder Volume (mL) 0 100 200 400 600

Predicted Time to Achieve Critical Bladder Volume Time (hr) to Achieve > 600 mL for > 4 Hours Urine Formation at 50 mL/hr 16 14 12 8 4

Urine Formation at 100 mL/hr 10 9 8 6 4

would be 6 and 8 hours, respectively. Thus, to avoid complications related to postoperative retention, the following steps are prudent: ● ●

●

Ensure that all patients void before surgery. Ensure that postoperative patients void or are catheterized within approximately 8 to 10 hours of their last voiding. Use an indwelling urinary catheter for procedures expected to last longer than 5 to 6 hours, assuming that the patient will be unable to void until 1 to 2 hours after surgery.

PREVENTION If a patient has not voided within 6 to 8 hours of his or her last voiding, the bladder volume should be assessed before the patient leaves the recovery room. Bladder volume can be determined noninvasively by ultrasonography. The bladder should be drained if the volume is more than 600 mL. Alternatively, if a scanner is not available, bladder volume can be assessed by palpation and the bladder emptied by inout catheter drainage. This is especially important in patients with known risk factors for postoperative urinary retention (see Table 208-2). One recent study noted a 24% incidence of urinary retention in patients arriving in the recovery room after various surgeries performed without an indwelling bladder catheter. For outpatient surgery, a decision must be made whether patients should be required to void before discharge. At least two studies suggest that patients with no underlying risk factors for urinary retention should be allowed to go home without voiding before discharge. In such patients, the incidence of urinary retention was less than 1%. In patients with risk factors for urinary retention, it is prudent to require them to void before discharge. This avoids a persistently overdistended bladder if a patient fails to seek medical attention for this problem in a timely manner. Thus, patients having rectal, groin, or urologic surgery and those with spinal cord disease or a history of urinary retention should be required to void or be catheterized before discharge. After spinal or epidural anesthesia, patients should be required to void or be catheterized, with some possible exceptions. Patients who have had neuraxial blocks with short-acting local anesthetics (≤50 mg lidocaine without vasopressors, or 2-chloroprocaine) can safely be discharged without voiding if a bladder scan reveals a bladder volume of less than 400 mL at the time of discharge. Owing to the short duration of action of these two agents, it is almost certain that any residual effects of the local anesthetic will resolve before a “critical volume” is exceeded for longer than 4 hours. However, bupivacaine blocks have been associated with impaired voiding for longer than 10 hours. Patients who have received this anesthetic or other similarly long-acting local anesthetics should not be discharged without voiding or having catheter drainage of the bladder. Ideally, high-risk patients who do void should have the postvoid residual volume checked to ensure that the bladder is empty. In many cases, voiding by straining results in the expulsion of a small quantity of urine, but the residual volume may still exceed 400 to 600 mL, and the micturition reflex may not have recovered. This is best evaluated with an

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Further Reading Azadzoi KM, Pontari M, Vlachiotis JU, Siroky MB: Canine bladder blood flow and oxygenation: Changes induced by filling, contraction and outlet obstruction. J Urol 155:1459-1465, 1996. DeGroat WC, Yoshimura N: Pharmacology of the lower urinary tract. Ann Rev Pharmacol Toxicol 41:691-721, 2001.

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839

Kamphuis ET, Ionescu TI, Kuipers PWG, et al: Recovery of storage and emptying functions of the urinary bladder after spinal anesthesia with lidocaine and with bupivacaine in men. Anesthesiology 88:310-316, 1998. Lamonerie L, Marret E, Deleuze A, et al: Prevalence of postoperative bladder distension and urinary retention detected by ultrasound measurement. Br J Anaesth 92:544-546, 2004. Lasanen LT, Tammela TL, Kallioinen M, et al: Effect of acute distension on cholinergic innervation of the rat urinary bladder. Urol Res 20:59-62, 1992. Lloyd-Davies RW, Clark AE, Prout WG, et al: The effects of stretching the rabbit bladder. Invest Urol 8:145-152, 1980. Mulroy MF, Salinas FV, Larkin KL, et al: Ambulatory surgery patients may be discharged before voiding after short-acting spinal and epidural anesthesia. Anesthesiology 97:315-319, 2002. Pavlin DJ, Pavlin EG, Fitzgibbon DR, et al: Management of bladder function after outpatient surgery. Anesthesiology 91:42-50, 1999. Pavlin DJ, Pavlin EG, Gunn HC, et al: Voiding in patients managed with or without ultrasound monitoring of bladder volume after outpatient surgery. Anesth Analg 89:90-97, 1999.

OTHER SURGICAL SUBSPECIALTIES

ultrasound scan. If this is unavailable, one can reasonably suspect that there is a high postvoid residual volume (>400 mL) if the patient has voided less than 300 mL. If so, patients should be requested to stay until they have voided again and fully emptied the bladder. Alternatively, the bladder can be drained by in-out catheterization to ensure that it is empty before discharge. Finally, all patients, whether at high or low risk, should be instructed to return to a medical facility if they are unable to void within 8 to 10 hours of discharge from the hospital.

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Intraoperative Penile Erection

209

Terri G. Monk Case Synopsis A 50-year-old man is scheduled for a transurethral resection of the prostate. After premedication with 2 mg midazolam given intravenously, a hyperbaric spinal anesthetic is placed, and a T6 sensory level is achieved. During placement of the resectoscope sheath, a full erection occurs, preventing free movement and control of the scope. The bladder is emptied and the resectoscope is removed, but the erection persists. The surgeon states that the erection prevents him from continuing with the procedure and asks the anesthesiologist to treat it.

PROBLEM ANALYSIS Definition Priapism is the persistence of a penile erection for longer than 4 to 6 hours, unaccompanied by sexual excitement or desire. Priapism can be classified as primary (idiopathic) or secondary (Table 209-1). Primary priapism is the result of physical or psychological stimuli unaccompanied by a disease state that could cause or sustain an erection. Secondary priapism is the result of factors that directly or indirectly affect penile erectile reactivity.

Recognition Intraoperative penile erections under anesthesia can be classified as primary priapism and generally occur during scrub preparation of the genitalia, Foley catheter insertion, or transurethral procedures. Erections under anesthesia are

Table 209–1

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Causes of Priapism

Primary (Idiopathic) Causes Physical or psychological stimuli Intraoperative tactile stimulation

Secondary Causes Neurogenic Thromboembolic Sickle cell disease Leukemia Malignant penile infiltration Medications Antihypertensive agents Phenothiazines Antidepressants Alcohol Marijuana Miscellaneous causes Genital trauma Self-injection therapy for impotence Coagulopathy

840

generally of shorter duration than other forms of priapism and may not persist long enough to be considered true priapism. The exact mechanism for penile erection is poorly understood, but it may result from a complex combination of psychological, neuroendocrine, and vascular factors acting on penile erectile tissues. Parasympathetic penile innervation is from the sacral (S2-S4) spinal cord segments via the nervi erigentes. When the penis is flaccid, high sympathetic tone increases intrinsic muscle tone in the arterioles, thereby reducing blood flow to the corpora cavernosa. At the same time, venules draining the corpora cavernosa remain open. For an erection to occur, parasympathetic impulses dilate the arterioles, allowing more blood flow into the corpora cavernosa; simultaneously, there is partial occlusion of venous outflow. Detumescence occurs when this cycle is reversed. Vasoactive mediators, including nitric oxide, vasopressin, and bradykinin, also affect the state of penile tumescence. Persistent tumescence, or priapism, results from failure of the mechanisms of detumescence, including blockage of venous drainage, excessive release of neurotransmitters, paralysis of the intrinsic detumescence mechanism, or prolonged relaxation of the intracavernosal smooth muscles. Blood continues to accumulate in the cavernosal sinusoids, and if the erection persists for more than 6 hours, it may become painful.

Risk Assessment Intraoperative penile erection is reported to occur in approximately 2.4% of male patients undergoing surgery. The incidence of erection varies according to age, with a frequency of 8% in male patients younger than 50 years and 0.9% in older patients. Penile stimulation during preparation and instrumentation may result in penile erection even in the presence of general or regional anesthesia. The incidence appears to be similar for general (3.5%) and epidural (3.8%) anesthesia, but it is lower with spinal anesthesia (0.3%). Foley catheterization has been reported to produce penile erection in approximately 1% of male patients undergoing cardiac surgery with general anesthesia.

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Implications

MANAGEMENT Numerous modes of therapy have been suggested for the treatment of intraoperative penile erection (Table 209-2). At the first sign of penile tumescence, all genital stimulation, including surgical preparation, urethral manipulation, and Foley catheter insertion, should be terminated immediately. If a cystoscope is in place, it must be removed, if possible. Because intraoperative erections often occur early in the procedure during “light” anesthesia, the anesthetic level should be deepened. If a spinal or epidural anesthetic is used, adequate blockade of the sacral segments should be ensured. In the lithotomy position, the scrotum hangs below the anus in a male patient when the sacral segments are blocked. If conservative treatment fails to produce detumescence, prompt intervention is necessary. Ethyl chloride spray to the penis or a dorsal penile nerve block can be used to suppress sensory input to the penis, thereby interrupting the sacral reflex arc that is maintaining the erection. A multitude of pharmacologic agents have been used to treat prolonged erections, but it is unlikely that any single agent will be effective in all cases. The use of intracorporal sympathomimetic agents is most commonly reported in the urologic literature. Owing to the high vascularity of this area, the uptake of these medications occurs rapidly, and systemic cardiovascular effects are common. Some of the more commonly used agents are discussed here. Phenylephrine, a pure α1-adrenergic agonist, has been given intracavernosally in doses of 100 to 200 μg. The success rate with this technique is reportedly 100% by 2 to

Table 209–2

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Treatment for Intraoperative Penile Erection

Termination of tactile stimulation of genital area Assurance of adequate anesthetic depth Ethyl chloride spray to penis Dorsal penile nerve block Intracavernosal drug injection Intravenous pharmacologic agents Ketamine Vasodilators Vasoconstrictors Terbutaline Anticholinergic agents

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3 minutes. Although this treatment may be associated with an intermittent rise in mean blood pressure, no untoward cardiovascular events are associated with its use. Some reports suggest that metaraminol is a preferred medication for intracavernosal injection, with doses as low as 10 to 25 μg producing detumescence without untoward cardiovascular effects. However, others caution against the use of metaraminol, norepinephrine, and epinephrine because all these drugs have at least some β1 activity, with the potential for β1-mediated adverse cardiovascular events. Ketamine, a dissociative anesthetic agent, is given intravenously in doses of 0.5 to 1.8 mg/kg, based on the assumption that the erection has occurred in response to external stimuli, and the drug’s dissociative effect on the limbic system might block this response. Ketamine may also exert its penilerelaxing effect by decreasing central vagal outflow, blocking reuptake of norepinephrine at the neuroeffector junction in cavernosal erectile tissues, or blocking transmission through parasympathetic ganglia. When using ketamine, it is important to remember that this drug has sympathomimetic actions and must be used with caution in elderly patients and those with significant cardiovascular disease. Vasodilators, such as inhaled amyl nitrite (one inhalant capsule of 0.3 mL emptied into the reservoir breathing bag) or intravenous nitroprusside, relax the corpora cavernosa venous drainage sites and produce a rapid fall in blood pressure. This leads to compensatory reflex sympathetic discharge, which may mimic the sympathetic discharge that occurs during orgasm, precipitating arteriolar constriction to terminate the erection. Vasodilating agents should be avoided in patients with a regional block because of the danger of inducing severe hypotension. They are also contraindicated in patients with increased intraocular or intracranial pressure. Terbutaline (0.2 to 0.5 mg intravenously), a β2adrenoreceptor agonist, has been used successfully to manage intraoperative penile erection. The action of this agent is unclear, but it is thought that terbutaline relaxes the stretched corporal smooth muscles, thereby releasing the impediment to venous blood flow from the penis. Terbutaline must be used with caution in patients with significant coronary artery disease because it can cause tachycardia, pulmonary edema, or hypokalemia. Anticholinergics may cause detumescence by blocking the effect of acetylcholine on the nitric oxide system. Of these medications, glycopyrrolate is preferred over atropine or scopolamine because it causes less tachycardia and lacks central nervous system effects.

PREVENTION Intraoperative penile erections can occur with any type of anesthesia, but the incidence is lowest with spinal blockade, probably because this technique provides the most profound sensory block of the sacral area. Thus, the administration of a spinal block for transurethral procedures should prevent most episodes of intraoperative tumescence. Whatever type of anesthesia is used, genital skin preparation and urethral manipulation should be delayed until an adequate level of anesthesia is present, because intraoperative erections are generally caused by tactile stimulation of the genital area.

OTHER SURGICAL SUBSPECIALTIES

An intraoperative penile erection may delay or even necessitate the cancellation of planned surgery. It can make passing or manipulating a cystoscope nearly impossible. Difficulty with transurethral cystoscope passage can also traumatize the urethra, predisposing to postoperative stricture formation. Aggressive therapy for intraoperative penile erection is necessary to prevent other long-term sequelae, including fibrosis and thrombosis. During penile surgery requiring an incision, penile tumescence can increase intraoperative bleeding. If an intraoperative erection is unresponsive to treatment, the procedure should be postponed.

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During regional anesthesia, it is especially important to ensure that sensory blockade of the sacral area is present before proceeding. Anesthetic agents associated with an increased incidence of erections during general anesthesia include fentanyl, propofol, and droperidol, but there is no conclusive evidence that avoidance of a particular anesthetic agent will prevent this problem.

Further Reading Kouriefs C, Watkin NA: What to do if it gets “bigger.” Ann R Coll Surg Engl 85:126-128, 2003. Lue TF: Physiology of erection and pathophysiology of impotence. In Walsh PC, Retik AB, Stamey TA, et al (eds): Campbell’s Urology, 6th ed. Philadelphia, WB Saunders, 1992, pp 709-728.

Roy R: Cardiovascular effects of ketamine given to relieve penile turgescence after high doses of fentanyl. Anesthesiology 61:610-613, 1984. Seftel AD, Resnick MI, Boswell MV: Dorsal nerve block for management of intraoperative penile erection. J Urol 151:394-395, 1994. Shantha TR, Finnerty DP, Rodriquez AP: Treatment of persistent penile erection and priapism using terbutaline. J Urol 141:1427-1429, 1989. Staerman F, Nouri M, Coeurdacier P, et al: Treatment of the intraoperative penile erection with intracavernous phenylephrine. J Urol 153: 1478-1481, 1995. Tsai SK, Hong CY: Intracavernosal metaraminol for treatment of intraoperative penile erection. Postgrad Med J 66:831, 1990. Valley MA, Sang CN: Use of glycopyrrolate to treat intraoperative penile erection. Reg Anesth 19:423-428, 1994. van Arsdalen KN, Chen JW, Smith MJV: Penile erections complicating transurethral surgery. J Urol 129:374-376, 1983.

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210

Vinod Malhotra and Vijayendra Sudheendra OTHER SURGICAL SUBSPECIALTIES

Case Synopsis An otherwise healthy 70-year-old man undergoes combined transurethral resection of the prostate (TURP) and transurethral resection of a bladder tumor (TURB) under spinal anesthesia with sedation. His blood pressure is 130/90 mm Hg, heart rate is 68 beats per minute, respirations are 16 breaths per minute, and hematocrit is 38%. Ninety minutes into surgery, the patient becomes restless. His blood pressure is 180/100 mm Hg, and his heart rate is 40 beats per minute. The electrocardiogram (ECG) shows depressed T waves. Laboratory values are as follows: hematocrit 27%, sodium 23 mEq/L, potassium 3.0 mEq/L, and chloride 95 mEq/L.

Recognition

PROBLEM ANALYSIS Definition TURP syndrome is a general term used to describe a wide range of neurologic and cardiopulmonary symptoms and signs caused by intravascular absorption of hypotonic bladder-irrigating fluids during transurethral procedures, especially TURP. In conscious or sedated patients, the sudden onset of restlessness should raise the suspicion for TURP syndrome. Hypertension is indicative of hypervolemia. Reflex bradycardia occurs in response to the increased blood pressure. T-wave depression on the ECG is caused by glycine in the irrigating fluid. Hyponatremia is yet another sign of hypotonic irrigant absorption (Table 210-1). A reduced hematocrit is most likely due to a combination of blood loss and hemodilution. Bradycardia may also occur after bladder perforation. In this case, bradycardia is an efferent vagal response to peritoneal stimulation secondary to any extravasated fluid. Abdominal or shoulder pain and hypotension usually accompany the bradycardia.

The case synopsis illustrates three significant complications of transurethral surgery: (1) TURP syndrome, (2) severe hemorrhage, and (3) bladder perforation. TURP SYNDROME TURP syndrome is a constellation of signs and symptoms that result from the following circumstances or conditions: ● ● ● ● ● ● ●

Circulatory overload Water intoxication or hypo-osmolality Hyponatremia Glycine toxicity Ammonia toxicity Hemolysis Coagulopathy

These signs and symptoms may occur simultaneously (Table 210-2). The clinical presentation may be further complicated by bacteremia or septicemia, which causes chills, hypotension, and tachycardia or bradycardia. SEVERE HEMORRHAGE

Table 210–1

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Hypotonic Irrigants Used for Transurethral Resection of the Prostate or a Bladder Tumor

Solution Water Glucose, 2.5% Sorbitol, 3.5% Urea, 1% Glycine, 1.2% Cytal (sorbitol 2.7% and mannitol 0.54%) Glycine, 1.5% Mannitol, 5%

Osmolality (mOsm/kg) 0 139 165 167 175 178 220 275

Severe hemorrhage is usually evident as surgical bleeding, although it is difficult to measure because blood is mixed with copious amounts of irrigating fluid. Occult internal bleeding may occur if bladder perforation has occurred. Clinical signs of excessive bleeding include hypotension and reflex tachycardia. However, tachycardia may not occur in the presence of age-related sinus node dysfunction or with the use of β-blockers or high spinal anesthesia. BLADDER PERFORATION Bladder perforation is difficult to recognize during general anesthesia. Hypotension and bradycardia or tachycardia may occur, but these are nonspecific findings. An experienced surgeon, however, usually recognizes a bladder perforation immediately. With spinal anesthesia, the complaint of abdominal or shoulder pain is helpful in making the diagnosis. 843

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Table 210–2

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Pathophysiology and Clinical Features of TURP Syndrome

Pathophysiology

Clinical Features

Fluid overload

Hypertension; bradycardia; arrhythmia; angina; pulmonary edema and hypoxemia; ventricular failure and hypotension Confusion and restlessness; twitching or seizures; lethargy or coma; dilated, sluggish pupils; papilledema; low-voltage EEG; hemolysis CNS changes as above; reduced inotropy; widened QRS complex; low-voltage ECG; T-wave inversion on ECG Nausea and vomiting; headache; transient blindness; loss of light and accommodation reflexes (blink reflex preserved); myocardial depression; ECG changes Nausea and vomiting; CNS depression Anemia; acute renal failure; chills, clammy skin; chest tightness and bronchospasm; hyperkalemia resulting in malignant arrhythmias or bradyasystole Severe bleeding; primary fibrinolysis; disseminated intravascular coagulation

Water intoxication or hypo-osmolality Hyponatremia Glycine toxicity Ammonia toxicity Hemolysis Coagulopathy

CNS, central nervous system; ECG, electrocardiogram; EEG, electroencephalogram; TURP, transurethral resection of the prostate gland.

Risk Assessment Approximately 400,000 TURP procedures are performed annually in the United States. About 10% of men older than 65 years require TURP. The incidence increases to 20% to 30% for men older than 80 years. Seventy-seven percent of patients undergoing TURP have one or more of the following conditions or factors: ● ● ● ● ●

Heart disease Hypertension Diabetes Chronic obstructive pulmonary disease History of smoking

Perioperative morbidity is related to associated disease, age, and sepsis. Morbidity is increased in blacks and in patients to whom the following factors apply: ● ● ● ●

Resection time longer than 90 minutes Prostate weighing more than 45 g Acute urinary retention Age greater than 80 years

The amount of absorbed irrigating fluid is influenced by the following factors: ● ● ● ● ●

Resection time Prostate gland size Hydrostatic pressure of the irrigating fluid Number and size of venous sinuses opened Whether the prostatic capsule is intact

Chronic inflammation, repeated instrumentation, and indwelling Foley catheters increase prostatic vascular congestion and predispose to increased bleeding and bacteremia during TURP. Prolonged resection of a large prostate allows for significant release of plasminogen activators from prostatic tissue into the bloodstream. This can cause primary fibrinolysis. Prostatic tissue and multiple microthrombi may also enter the circulation, leading to disseminated intravascular coagulation (DIC). Bladder perforation occurs in up to 1% of cases. A higher likelihood of bladder perforation is expected if the bladder

tumor is sessile versus pedunculated, is large and fragile, or infiltrates the bladder wall. A bladder wall that is chronically inflamed, previously irradiated, or thin and stretched is more prone to perforation. The likelihood of perforation is further increased if the tumor is difficult to access, bleeding obscures the surgeon’s vision, the patient unexpectedly moves or coughs, or instrumentation is difficult or traumatic.

Implications Overall mortality of TURP is 0.2% to 0.8%. Perioperative morbidity ranges from 7% to 20%. Most mortality and morbidity occur in patients who develop complications of TURP, including TURP syndrome, bladder perforation, or sepsis. In 15% of patients, bacteremia occurs. Of these, 6% to 7% develop septicemia, which is associated with 25% to 75% mortality. Because the consequences of these complications are severe, aggressive management is required.

MANAGEMENT TURP Syndrome Immediate aggressive therapy is essential if the patient is to survive. The following measures are suggested: ● ● ●

●

●

Terminate the surgery as soon as possible. Administer 20 mg of intravenous (IV) furosemide. Immediately obtain the following laboratory tests: hematocrit; serum electrolyte, creatinine, and glucose concentrations; serum osmolality (if available); arterial blood gas analyses; and 12-lead ECG. Continue or start the administration of normal saline. Hypertonic saline (3% or 5%) may be administered (at a rate <100 mL/hour) if the serum sodium concentration is less than 100 mEq/L, severe central nervous system side effects of hyponatremia and hypo-osmolality are evident, or reduced inotropy results in cardiovascular collapse. Administer IV midazolam in 1-mg incremental doses to treat twitching or seizures; a barbiturate may be added if seizures persist.

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Chapter 210

●

● ●

Bladder Perforation As soon as bladder perforation is detected, undertake the following measures: ● ●

●

●

Stop surgery and achieve hemostasis. Treat hypotension with IV crystalloids, vasopressors, and inotropes. Obtain a hematocrit. Start blood transfusion if brisk bleeding continues. Occult blood loss into the intraperitoneal or retroperitoneal space may occur. Perform a cystourethrogram to locate the perforation.

For most perforations, suprapubic cystotomy, an indwelling Foley catheter, and (occasionally) ureteral stents are sufficient. In some instances, immediate exploratory laparotomy may be necessary to control bleeding and repair the perforation.

Septicemia Chills and fever should be treated aggressively and immediately with IV antibiotics. Cardiovascular support may be necessary.

PREVENTION TURP Syndrome Take the following preventive measures: ● ● ●

●

●

Limit resection time to less than 1 hour. Keep the prostate capsule intact until the end of resection. Maintain irrigating fluid height less than 60 cm above the prostate gland. Measure serum electrolyte levels during and after the procedure. Use regional anesthesia and very light or no sedation to allow early detection of changes in the patient’s mental status.

Bladder Perforation; Bacteremia and Septicemia Avoid overdistention of the bladder, rough instrumentation, patient movement, and extensive prostate or bladder tumor

Complications of Transurethral Surgery

845

resections at one sitting. Use broad-spectrum antibiotic prophylaxis for bacteremia and septicemia.

Laser Prostatectomy and Other Techniques Laser prostatectomy has generated renewed interest among urologists and is being performed in several centers. Based on the initial experience, it promises to replace conventional TURP in the near future. The neodymium:yttrium-aluminum-garnet laser has been replaced by the holmium laser, which coagulates and vaporizes prostate tissue. The main advantages over conventional TURP include minimal blood loss (as little as 50 to 70 mL) and minimal fluid absorption, which should nearly eliminate these two major complications of TURP. However, other complications are possible, including coagulation through the prostatic fossa and sloughing of prostatic debris in the postoperative period. The latter can lead to urinary obstruction and retention. Protective eyewear should be worn, and a means of evacuating the smoke plume is required. Caudal anesthesia has been used successfully for laser prostatectomy in patients with severe cardiopulmonary disease, because the use of smaller volumes of continuous irrigation, along with minimal bleeding, minimizes bladder distention. Cryosurgery is technically complex and is not a popular technique. Microwave ablation of the prostate is another promising technique that can be performed on an outpatient basis under local or sacral block. Classic TURP is still the gold standard, however.

Further Reading Azar I: Transurethral resection of prostate. In Malhotra V (ed): Anesthesia for Renal and Genitourinary Surgery. New York, McGraw-Hill, 1996, pp 93-109. Catalona WJ: Urothelial tumors of the urinary tract. In Walsh PC, Retik AB, Stamey TA, et al (eds): Campbell’s Urology, 6th ed. Philadelphia, WB Saunders, 1992, pp 1094-1158. Gravenstein D: Transurethral resection of prostate (TURP) syndrome: A review of pathophysiology and management. Anesth Analg 84: 438-446, 1997. Jensen V: The TURP syndrome. Can J Anaesth 38:90-95, 1991. Malhotra V: Transurethral resection of prostate. Anesthesiol Clin North Am 18:883-897, 2000. Malhotra V: Anesthesia and renal and genitourinary systems. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 2175-2207. Malhotra V, Perlmutter A: Caudal anesthesia provides effective anesthesia for laser prostatectomy. Reg Anesth 22:93, 1997. Mebust WK, Holtgrieve HL, Lockett ATK: Transurethral prostatectomy: Immediate and postoperative complications: A cooperative study of 13 participating institutions evaluating 3885 patients. J Urol 141:243, 1989. Pientka L, Van Loghen J, Hahn E: Comorbidities and perioperative complications among patients with surgically treated prostatic hyperplasia. Urology 38:43-48, 1991.

OTHER SURGICAL SUBSPECIALTIES

●

Auscultate chest and obtain chest radiographs to detect pulmonary edema. Intubate and mechanically ventilate the patient at the earliest evidence of pulmonary edema. Transfuse packed red blood cells as necessary. If bleeding continues, investigate for DIC or primary fibrinolysis. DIC is treated with crystalloids and blood products to achieve hemodynamic stability and normal coagulation. Primary fibrinolysis responds well to aminocaproic acid (Amicar) administered as an IV infusion of 3 to 5 g in the first hour, followed by continuous IV infusion at 1 g/hour until the bleeding is controlled. Institute invasive monitoring and provide supportive therapy to maintain circulation and pulmonary function and to prevent renal failure.

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211

Terri G. Monk Case Synopsis A 68-year-old man with borderline hypertension undergoes radical retropubic prostatectomy. Following induction of general anesthesia, his blood pressure is 128/80 mm Hg. The procedure is uneventful until the surgeon mobilizes the prostate gland and separates the dorsal venous complex from the urethra. Bright red blood instantly fills the operative field, and the patient’s blood pressure falls to 78/50 mm Hg. During the next 30 minutes, the patient loses 4500 mL of blood and requires transfusion of 3 units of packed red blood cells. The remainder of the case is uneventful.

PROBLEM ANALYSIS Definition The term radical refers to extensive operations directed at the extirpation of a morbid process. In urology it is used to differentiate a cancer operation from a simple operation for benign disease. Commonly performed radical urologic procedures are radical prostatectomy, radical cystectomy, radical nephrectomy, and radical surgery for testicular cancer. ●

●

●

●

Radical prostatectomy involves the en bloc surgical removal of the entire prostate gland, the seminal vesicles, the ejaculatory ducts, and a portion of the bladder neck. Radical cystectomy in males (cystoprostatectomy) involves en bloc removal of the bladder, prostate gland, lower ureters, vas deferens, seminal vesicles, and pelvic lymph nodes. Radical cystectomy in females involves removal of the bladder, urethra, uterus, fallopian tubes, ovaries, anterior vaginal wall, and pelvic lymph nodes. After cystectomy, either an ileal conduit or a bladder substitution procedure is performed for urinary diversion. Radical nephrectomy involves preliminary ligation of the renal artery and vein, followed by removal of the kidney, adrenal gland, and perinephric fat outside of the surrounding (Gerota’s) fascia. Retroperitoneal lymph node dissection is performed for the staging of testicular cancers.

The most common operative complication during radical urologic procedures is hemorrhage. Other intraoperative complications include respiratory abnormalities, air embolism, nerve injury, and thromboembolic events.

Recognition HEMORRHAGE Extensive bleeding can occur if one of the branches of the hypogastric veins is inadvertently lacerated during pelvic lymphadenectomy with radical prostatectomy or cystectomy. The venous drainage of the prostate is into Santorini’s 846

plexus (Fig. 211-1). Hemorrhage is common during transection of this dorsal venous complex during radical prostatectomy or cystectomy. During radical nephrectomy or retroperitoneal lymph node dissection, hemorrhage can occur if extensive retroperitoneal dissection is necessary or if the inferior vena cava or its tributaries are damaged. Because the bleeding during radical urologic surgery is mainly venous in nature, positive end-expiratory pressure should be avoided during mechanical ventilation; this has been shown to increase venous pressure and probably increases intraoperative bleeding. This complication is recognized by direct observation of blood loss and signs of hypovolemia, including tachycardia, hypotension, and a decrease in central venous or pulmonary artery wedge pressure. RESPIRATORY ABNORMALITIES General anesthesia causes major alterations in ventilation, and the positions required for radical urologic surgery can aggravate these changes. During radical retropubic prostatectomy and cystectomy, the patient is supine but in the Trendelenburg (head-down) position to facilitate surgical exposure. This position increases the work of breathing and promotes the development of atelectasis because the abdominal contents rest on the diaphragm. Other ventilatory changes with the Trendelenburg position include reduced pulmonary compliance and lung volumes, as well as an increased incidence of endobronchial intubation. During radical nephrectomy, patients are positioned in a lateral decubitus (“kidney”) position, with the spine flexed and the kidney rest elevated. This position produces a decrease in thoracic compliance, tidal volume, vital capacity, and functional residual capacity. Altered ventilatory function is recognized by hypoxemia, hypercarbia, or reduced lung compliance. Most patients require general anesthesia and controlled ventilation because this position imposes severe restrictions on ventilation that predispose to the development of atelectasis in the dependent lung. During radical nephrectomy, pneumothorax can occur. To identify pleural tears, the surgeon fills the wound with saline while the anesthetist hyperinflates the lungs. Auscultation reveals diminished or

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Urogenital diaphragm Deep dorsal vein of penis

Pubic symphysis OTHER SURGICAL SUBSPECIALTIES

Superficial branch (deep dorsal vein) Puboprostatic ligament Prostate Lateral venous plexus Bladder

Middle hemorrhoidal vein Hypogastric vein

A

B

Inferior vesical vein

Urethra

Figure 211–1 ■ The prostatic vein drains into Santorini’s plexus, which receives blood from the penis, prostate, bladder, and seminal vesicles. This plexus also communicates with the pubic, pudendal, deep epigastric, obturator, and hemorrhoidal veins. (From Reiner WG, Walsh PC: An anatomical approach to the surgical management of the dorsal vein and Santorini’s plexus during radical retropubic surgery. J Urol 121:198-200, 1979.)

absent breath sounds with pneumothorax or atelectasis. A chest radiograph confirms these findings. Bleomycin is a chemotherapeutic agent that is often used to treat testicular carcinoma before retroperitoneal lymph node dissection (see Table 30-1). Its use is associated with pulmonary toxicity, and there are numerous reports of postoperative respiratory failure after retroperitoneal lymph node dissection in these patients. Respiratory problems usually begin 3 to 10 days after surgery. Although intraoperative exposure to hyperoxia (inspired oxygen concentrations >30%) has been linked to postoperative pulmonary toxicity, the relationship is controversial. A retrospective study found that intravenous (IV) fluid management, especially red blood cell transfusion, was the most significant factor associated with postoperative respiratory failure. It is now recommended that IV fluid administration consist primarily of colloids and be limited to the minimum volume necessary to maintain hemodynamic stability and renal perfusion. CIRCULATORY ABNORMALITIES Hypotension and tachycardia can occur with acute hemorrhage during any of the radical urologic procedures. During radical nephrectomy, it is also common to see an acute decrease in blood pressure when the kidney rest is elevated during positioning. In 5% to 10% of patients undergoing radical nephrectomy, the tumor extends into the inferior vena cava and right atrium. With or without such extension, tumor may embolize into the proximal vena cava, right atrium, and pulmonary artery during the procedure to impede right heart outflow, reduce venous return to the left

heart, and compromise systemic circulatory dynamics. If the tumor occludes the vena cava or right atrium, it can block right heart output and cause acute cardiovascular collapse. Cardiopulmonary bypass may be required to prevent tumor embolization during surgery in patients at high risk for such adverse cardiovascular events. AIR EMBOLISM With either the Trendelenburg or the kidney position, the surgical field is above the level of the heart, creating a negative pressure gradient between the wound and the heart. Air embolism can occur if Santorini’s venous plexus (see Fig. 211-1) is opened while the patient is in a headdown position during radical prostatectomy or cystoprostatectomy or if the vena cava is entered during radical nephrectomy. The most sensitive monitors for the detection of air embolism are transesophageal echocardiography and precordial Doppler. However, these are rarely used during urologic surgery. There may be a decrease in end-tidal carbon dioxide or an increase in end-tidal nitrogen with significant air embolism. Physical findings consistent with air embolism include sudden hypotension, hypoxemia, arrhythmia, and the presence of a mill-wheel murmur. If a large embolism creates an airlock that blocks outflow from the right side of the heart, cardiovascular collapse will occur. NERVE INJURY Damage to the obturator nerve can occur due to retractor placement or transection during pelvic lymph node dissection in radical retropubic prostatectomy or cystectomy.

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During perineal prostatectomy, the exaggerated lithotomy position is used, and damage to the brachial plexus can occur if shoulder braces are improperly placed. Injury to the brachial plexus is also possible during surgery performed in the kidney position if the lower shoulder and upper arm remain directly under the rib cage. Peripheral nerve injury is discussed in Chapter 221.

usually occurs within 6 weeks. However, if the nerve is severed or the injury is severe, permanent sensory and motor deficits could occur, or recovery might take months. Deep venous thrombosis and pulmonary embolism are frequent postoperative complications following radical pelvic surgery, and they may be fatal if diagnosis and treatment are delayed.

THROMBOEMBOLISM

MANAGEMENT

Patients undergoing radical pelvic surgery, particularly radical prostatectomy and radical cystectomy, are at high risk for developing pelvic and deep venous thrombosis. Pulmonary emboli are reported in up to 5% of patients; however, the incidence varies with the sensitivity of the diagnostic test chosen to detect thromboembolism. During resection of renal tumors, there is a high risk for tumor embolism to the lungs, especially when the tumor extends into the vena cava. Thromboembolism is discussed further in Chapters 89 and 216.

Hemorrhage

Risk Assessment HEMORRHAGE During radical prostatectomy and cystoprostatectomy, severe hemorrhage is more likely in patients who have had previous transurethral prostate resection or multiple prostatic biopsies. This is because the dorsal venous complex can become adherent to the anterior surface of the prostate. A large prostate gland and prior pelvic irradiation or surgery are also associated with increased operative blood loss. In patients undergoing radical nephrectomy, the risk of hemorrhage or tumor embolism is greatly increased if the tumor invades the inferior vena cava or extends into the right atrium. RESPIRATORY ABNORMALITIES The risk of surgically induced pneumothorax during radical nephrectomy is increased with a large kidney, thoracic approach, or resection of the 12th rib for better exposure. NERVE INJURY Peripheral nerve injuries are common if improper positioning results in compression or stretching of a nerve. Overzealous surgical manipulation or retraction may traumatize nerves. Patients with preexisting diseases such as diabetes mellitus, hypertension, and arteriosclerosis are more prone to peripheral nerve injury. THROMBOEMBOLISM Thromboembolic events are common in all patients undergoing radical pelvic surgery for carcinoma.

Implications Hemorrhage and air embolism can result in cardiovascular collapse and death if they are not detected and treated promptly. Position-related nerve injuries are often neurapraxic; that is, localized myelin degeneration may occur at the injury site, but without axonal degeneration. Therefore, recovery

Extensive blood loss is anticipated in all radical urologic procedures. In high-risk or elderly patients, direct arterial blood pressure and central venous monitoring may facilitate early recognition and treatment of acute blood loss, and several large-bore catheters should be placed for venous access. Persistent bleeding can be managed by temporary packing if surgical efforts must be directed elsewhere. Hemorrhage must be treated promptly with blood products, volume expansion, and vasopressors as needed to maintain cardiac filling and systemic perfusion.

Respiratory Abnormalities Respiratory alterations and work of breathing are best managed with endotracheal intubation and controlled positivepressure ventilation during the perioperative period. Small pleural injuries during radical nephrectomy can be repaired surgically. A chest tube is required to treat a tension pneumothorax of 10% or greater.

Air Embolism If air embolism occurs, the patient is ventilated with 100% oxygen. If cardiovascular collapse ensues, cardiopulmonary resuscitation is instituted immediately, and the patient is placed in the head-down, left lateral decubitus position to allow air trapped in the pulmonary outflow tract to float back into the right side of the heart. Aspiration of air from the right side of the heart may be attempted if a central line is in place.

Nerve Injury An initial neurologic examination is performed to document the extent of all peripheral nerve injuries. Nerve injuries that persist for longer than 2 weeks after surgery should be evaluated with electromyography and nerve conduction studies.

Thromboembolism Pulmonary embolism is treated with systemic anticoagulation using a continuous heparin infusion as soon as surgical bleeding is controlled. Heparin is continued for 7 to 10 days while oral anticoagulation therapy is initiated. Anticoagulation therapy should be continued for 3 months postoperatively.

PREVENTION Measures to prevent complications of radical urologic surgery are summarized in Table 211-1.

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Prevention of Complications of Radical Urologic Surgery

Hemorrhage Meticulous surgical technique

Respiratory Abnormalities

Nerve Injury Padding of pressure points Pillows under feet, ankles, and knees Padding between operating table and rib cage* Avoidance of shoulder braces

Thromboembolism Compression stockings Early ambulation *In the lateral decubitus position, padding prevents compression of nerves and blood vessels in the axilla.

Complications of Radical Urologic Surgery

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be routinely placed under the feet, ankles, and knees. If the lateral kidney position is used, a small pad should be placed between the operating table and the dependent thorax to prevent brachial plexus injury. Shoulder braces are usually not necessary, except with the extreme lithotomy position. If this position is required, care must be taken to place the shoulder braces over the acromial processes to prevent brachial plexus injury.

Thromboembolism For operations on a right-sided renal tumor in the lateral kidney position, placing the patient in a steep Trendelenburg position should help prevent fatal air embolism, because air entering the vena cava cannot easily pass to the heart. Compression stockings should be used intraoperatively, and patients should ambulate on the first postoperative day to prevent thromboembolic events.

Further Reading Hemorrhage Intraoperative bleeding is minimized during radical urologic surgery by meticulous attention to surgical technique.

Respiratory Abnormalities Endotracheal intubation and positive-pressure ventilation help reduce the risk of ventilatory abnormalities. Periodic auscultation of the lungs after positioning the patient and during the surgical procedure can verify optimal pulmonary ventilation.

Nerve Injury All pressure points should be padded, and the patient should be moved with care during positioning and transport. Foam should be used under bony prominences, and pillows should

Malhotra V, Sudheendra V, Diwan S: Anesthesia and the renal and genitourinary systems. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 2175-2207. Monk TG: Cancer of the prostate and radical prostatectomy. In Malhotra V (ed): Anesthesia for Renal and Genitourologic Surgery. New York, McGraw-Hill, 1996, pp 177-195. O’Hara JF, Cywinski JB, Monk TG: The renal system and anesthesia for urologic surgery. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 5th ed. Philadelphia, JB Lippincott–Williams & Wilkins, 2005. Prentice JA, Martin JT: The Trendelenburg position: Anesthesiologic considerations. In Martin JT (ed): Positioning in Anesthesia and Surgery. Philadelphia, WB Saunders, 1987, pp 127-145. Shah N: Radical cystectomy, radical nephrectomy, and retroperitoneal lymph node dissection. In Malhotra V (ed): Anesthesia for Renal and Genitourologic Surgery. New York, McGraw-Hill, 1996, pp 197-226. Smith RB: Complications of renal surgery. In Smith RB, Ehrlich RM (eds): Complications of Urologic Surgery, 2nd ed. Philadelphia, WB Saunders, 1990, pp 128-159. Welborn SG: Unusual positions—urology: Anesthesiologic considerations. In Martin JT (ed): Positioning in Anesthesia and Surgery. Philadelphia. WB Saunders, 1987, pp 249-254.

OTHER SURGICAL SUBSPECIALTIES

Endotracheal intubation Positive-pressure ventilation Frequent auscultation of lungs

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212

Complications of Lithotripsy Jerome F. O’Hara, Jr. Case Synopsis A 78-year-old woman with a history of severe coronary artery disease underwent extracorporeal shock wave lithotripsy with general anesthesia. Ten minutes after placement in the water bath, the patient’s heart rate increased from 78 to 138 beats per minute, and pink frothy fluid was noted in the endotracheal tube. The patient was removed from the water bath, and an immediate chest radiograph revealed congestive heart failure.

PROBLEM ANALYSIS Definition Extracorporeal shock wave lithotripsy (ESWL) is accomplished by the transmission of shock waves through the patient’s body to pulverize urinary calculi. Unlike secondgeneration lithotriptors, first-generation units require that the patient be immersed in a water bath (Fig. 212-1). In addition to anesthetic risks, this unique environment exposes patients to potential complications from water immersion and the release of energy by the shock waves. During ESWL, a mechanically generated shock wave passes through water as a single pressure impulse. On reaching the patient, the wave passes through the patient’s tissues en route to the “target zone,” which is defined as the area that contains the calculus (Fig. 212-2). Fluoroscopy is used to confirm that the urinary calculi remain in the target zone. When the shock wave encounters a different density, such

Figure 212–1

850

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as the urinary calculus, it releases energy to fragment the calculus into sandlike particles, which is the desired therapeutic effect. However, damage to other tissues or implanted mechanical devices can occur. To prevent cardiac arrhythmias, the lithotriptor can be synchronized to trigger the shock wave during the refractory period of the patient’s cardiac cycle. In certain patients, hydrostatic pressure created by immersion can significantly compromise cardiovascular and pulmonary function.

Recognition Undesirable effects of the shock wave energy include the following: ●

●

●

Cardiovascular instability from atrial or ventricular arrhythmias Potential damage to and malfunction of a pacemaker or implantable cardioverter-defibrillator Hypotension from perirenal or intra-abdominal bleeding

First-generation lithotriptor with the patient in a chair hoist, immersed in the water bath (left). Newer, second-generation lithotriptor (right).

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Figure 212–2 ■ Illustration of how the shock wave is generated and then delivered to the renal calculi.

OTHER SURGICAL SUBSPECIALTIES

●

●

Skin petechiae and painful ecchymoses, especially in thin patients Patient discomfort and movement from inadequate analgesia

Undesirable effects during immersion lithotripsy include the following: ●

●

● ●

Nerve and musculoskeletal injury from pressure points associated with use of the hoist chair Hyperthermia or hypothermia caused by the temperature of the water bath Relative inaccessibility of the patient’s airway Cardiovascular and pulmonary changes (Table 212-1)

●

●

Neurologic damage if air is introduced into the epidural space during administration of epidural anesthesia Possible damage to and rupture of a calcified aortic or renal artery aneurysm

Cardiovascular and pulmonary changes associated with water immersion can lead to serious complications in some patients. For example, acute congestive heart failure can occur in patients with severe ventricular dysfunction. Patients with significant chronic obstructive pulmonary disease may not be able to maintain adequate ventilation under regional anesthesia. Absolute and relative contraindications to ESWL are listed in Table 212-2.

Implications Risk Assessment If the shock wave is misdirected or encounters tissue other than the urinary calculi, energy may be released and injure the patient. Such injuries include the following: ●

Pulmonary contusion and hemoptysis, especially in children, because the lung base and kidney are in close proximity Table 212–1

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Cardiopulmonary Changes on Immersion during Lithotripsy

System

Variable

Direction of Change

Cardiovascular

Central blood volume Central venous pressure Pulmonary artery pressure Pulmonary blood flow Vital capacity Functional residual capacity Tidal volume Respiratory rate

Increased Increased Increased Increased Decreased Decreased Decreased Increased

Respiratory

Modified from Malhotra V: Anesthesia and the renal and genitourinary systems. In Miller RD (ed): Anesthesia. New York, Churchill Livingstone, 1994, p 1961.

To avoid complications that can arise during ESWL, the anesthesiologist must understand the physics of shock wave generation and delivery to the patient. Certain risks need to be considered during the preoperative evaluation of a patient who requires an anesthetic for this elective procedure.

Table 212–2

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Contraindications to Extracorporeal Shock Wave Lithotripsy

Absolute Contraindications Obstruction distal to renal calculi Bleeding disorder or anticoagulation Pregnancy

Relative Contraindications Large calcified aortic or renal artery aneurysm Untreated urinary tract infection Pacemaker or implantable cardioverter-defibrillator Morbid obesity

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MANAGEMENT The choice of anesthesia depends on the type of lithotriptor and the anesthesiologist’s preference. High-energy shock waves (>18 kV) usually require general or regional anesthesia, whereas low-energy shock waves (<18 kV) often require only intravenous sedation. The advantage of general anesthesia is the ability to secure the airway with endotracheal intubation and to deliver smaller, more consistent tidal volumes. Small, consistent volumes minimize the displacement of renal or ureteral calculi, ensuring that they remain within the target zone. Regional anesthesia allows the patient to participate in positioning within the chair hoist and permits easier patient transport if an additional urologic procedure is needed at a different location. A T4-T6 sensory block is required with spinal or epidural anesthesia. Potential disadvantages of regional anesthesia include the following: ● ● ● ●

Time required to establish anesthesia Altered respiratory dynamics Potential for inadequate sensory block Inability to redose after a single-dose injection

Regardless of the anesthetic used, recovery from ESWL involves mainly recovery from the effects of anesthesia. Thus, ESWL should be approached as an outpatient procedure. Patients with cardiopulmonary disease need to be identified and their increased risk of immersion-related complications understood. Although invasive monitoring may be required for a patient who has substantial cardiopulmonary compromise, controlling the speed and depth of immersion is equally important. To prevent crush, pressure, brachial plexus, or neck injuries during anesthesia, proper positioning and padding are required, especially if a water bath is used. Certain patients scheduled for ESWL require the following specific considerations: ●

●

●

●

Pediatric patients usually receive general anesthesia so that their movements can be controlled during the procedure. Styrofoam padding is used to protect the lower lung fields from the shock waves. Paraplegic patients require anesthesia because of the risk of autonomic hyperreflexia. Morbidly obese patients can exceed the mechanical capacity of the lithotriptor to support or properly position them. This must be evaluated before the induction of anesthesia. Patients with cardiac rhythm management devices (CRMDs)—that is, pacemakers or internal cardioverterdefibrillators (see Chapter 97)—can safely undergo ESWL, but changes in programmed parameters may occur. The following steps should be taken: ● It is advisable to turn off the programmed adaptive-rate response in patients with CRMDs.

●

●

●

An internal cardioverter-defibrillator must be deactivated and shielded with Styrofoam to protect it from the shock waves, and the device should be interrogated after the procedure. This applies to pacemakers as well. The indication for the CRMD must be known so that the team is prepared to treat arrhythmias, especially if some CRMD therapies (e.g., tachyarrhythmias) have been turned off. If so, temporary pacing capability and an external cardioverter-defibrillator must be available. Preprocedure and postprocedure pulse generator functions must be confirmed when treating a patient who has an implantable CRMD.

PREVENTION The anesthesiologist must identify patients at risk for ESWLrelated complications and vigilantly monitor the patient’s position and hemodynamic changes during ESWL, especially during water bath immersion and on the initiation of shock wave therapy. It is advisable to establish and rehearse a plan of action for gaining airway access or treating cardiac arrest in patients who are immersed. An emergency protocol to facilitate the transfer of a patient with cardiac instability from a freestanding or mobile ESWL unit to a critical care setting should also be in place.

Further Reading American Society of Anesthesiologists Task Force on Perioperative Management of Patients with Cardiac Rhythm Management Devices: Practice advisory for the perioperative management of patients with cardiac rhythm management devices: Pacemakers and implantable cardioverter-defibrillators. Anesthesiology 103:186-198, 2005. Chung MK, Streem SB, Ching E, et al: Effects of extracorporeal shock wave lithotripsy on tiered therapy implantable cardioverter defibrillators. Pacing Clin Electrophysiol 22:738-742, 1999. Drach GW, Weber C, Donovan JM: Treatment of pacemaker patients with extracorporeal shock wave lithotripsy: Experience from 2 continents. J Urol 143:895-896, 1990. Liguori G, Trombetta C, Bucci S, et al: Reversible acute renal failure after unilateral extracorporeal shock-wave lithotripsy. Urol Res 32:25-27, 2004. Monk TG, Weldon BC: The renal system and anesthesia for urologic surgery. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 4th ed. Philadelphia, JB Lippincott–Williams & Wilkins, 2001, pp 1022-1025. Morgan GE, Mikhail MS: Anesthesia for genitourinary surgery. In Morgan GE, Mikhail MS (eds): Clinical Anesthesiology. Stamford, Conn, Appleton & Lange, 1996, pp 601-610. Saberski LR, Kondamuri S, Osinubi OY: Identification of the epidural space: Is loss of resistance to air a safe technique? Reg Anesth 22:3-15, 1997. Stowe DF, Bernstein JS, Madsen KE, et al: Autonomic hyperreflexia in spinal cord injured patients during extracorporeal shock wave lithotripsy. Anesth Analg 68:788-791, 1989. Vasavada SP, Streem SB, Kottke-Marchant K, et al: Pathological effects of extracorporeally generated shock waves on calcified aortic aneurysm tissue. J Urol 152:45-48, 1994.

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Autonomic Dysreflexia David L. McDonagh Case Synopsis

PROBLEM ANALYSIS Definition Autonomic dysreflexia or hyperreflexia (see also Chapter 114) is a syndrome of episodic autonomic hyperactivity in the setting of spinal cord injury. The syndrome is more common in complete spinal cord injuries, with no sensation or motor function below the level of the lesion. Lesions at or above T6 (above the splanchnic sympathetic outflow) put a patient at risk for this problem; lesions below T6 rarely cause the syndrome. A variety of noxious stimuli below the level of the spinal cord lesion can result in an afferent volley of neural input to the spinal cord and unchecked reflex efferent sympathetic outflow. This sympathetic outflow would normally be suppressed by supraspinal, descending inhibition, but connection to the brain no longer exists. The result is an unchecked vasopressor response that results in hypertension (sometimes severe), along with other symptoms described below.

Recognition In 1860 Hilton first described a quadriplegic patient with episodes of autonomic dysreflexia. Symptoms include anxiety, throbbing headache, facial flushing, blurred vision, nausea, and nasal congestion. Muscle spasms can also occur. On physical examination, signs include hypertension and usually, but not always, reflex bradycardia (Table 213-1). Below the level of the spinal cord injury, where sympathetic outflow predominates, the skin is typically cool, and there is piloerection. Above the level of the injury, where a parasympathetic counterregulatory response predominates, the skin is warm, flushed, and diaphoretic. Hypertension is invariably present

but is not necessarily extreme. These patients may have low normal blood pressure (≤120/80 mm Hg) at rest,1 but with stimulation, they may become symptomatic. Blood pressure may increase into what is typically considered the high normal range (>120/80 mm Hg) or stage 1 hypertension (>140/90 but <160/110 mm Hg), although severe (stage 2) hypertension (≥160/110 mm Hg) can be present.

Risk Assessment All patients with spinal cord injury at or above T6 should be considered at risk for autonomic dysreflexia. The overall incidence is greater than 50%, and men are more commonly affected than women. Those with complete spinal cord injuries are at the highest risk. The syndrome can be seen following the initial injury, after spinal shock resolves. Patients with a history of previously diagnosed autonomic dysreflexia or a history of compatible symptoms should be managed with vigilance. Recent symptoms should prompt a search for any inciting causes (Table 213-2). The most common causes are bladder distention, urinary retention, and fecal impaction. A variety of noxious stimuli below the level of the spinal cord lesion (i.e., in the area of sensory loss) can provoke autonomic dysreflexia. Keep in mind that any surgical procedures or other stimulation below the spinal cord lesion may provoke autonomic dysreflexia, even though the patient may not have sensation in that body part.

1

As defined in the JNC 7 report; see Further Reading.

Table 213–2

Table 213–1

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Signs and Symptoms of Autonomic Dysreflexia

Hypertension Bradycardia Arrhythmias Visceral and muscular spasms Piloerection Pallor or flushing Nasal obstruction Severe headache

Anxiety Convulsions Loss of consciousness Profuse sweating Facial tingling Blurred vision Shortness of breath Nausea and vomiting

OTHER SURGICAL SUBSPECIALTIES

A 35-year-old woman with spinal cord transection at T1 sustained in a motorcycle accident is scheduled for elective breast surgery. In the preoperative holding area she feels anxious and has a pounding headache, facial flushing, and hypertension (163/100 mm Hg). Her admission blood pressure was 92/58 mm Hg.

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Potential Inciting Causes of Autonomic Dysreflexia

Bladder distention or urinary retention Fecal impaction, rectal examination Surgery below level of spinal cord lesion Uterine contraction, labor Urologic procedures Ingrown toenail Intramuscular injection Decubitus ulcers Hemorrhoids Acute abdominal processes Skin irritation Restrictive clothing

853

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Implications Severe hypertension is the primary insult in autonomic dysreflexia. If it is uncontrolled, sustained hypertension can result in end-organ injury—a hypertensive emergency.2 The main concerns are seizure, hemorrhagic stroke, subarachnoid hemorrhage from aneurysmal rupture, intraocular hemorrhage, arrhythmia, and myocardial strain leading to myocardial ischemia or infarction. The syndrome of autonomic hyperreflexia can be fatal on rare occasions.

MANAGEMENT Management considerations include the following: ● ● ● ● ● ● ● ● ●

Search for the inciting cause Upright or reverse Trendelenburg positioning Treatment of the underlying cause Choice of anesthetic Appropriate intra- and postoperative monitoring Vasodilator drugs Vasopressors and intravenous fluids Deepening of general anesthesia Postponement of an elective case

Most commonly, bladder distention, urinary retention, or fecal impaction promotes this problem. Intraoperatively, surgical stimulation below the level of the spinal cord lesion may also be responsible. Be sure to consider and rule out similar syndromes, such as preeclampsia. Sitting the patient upright causes some orthostatic hypotension and should be the initial maneuver to correct hypertension. Initial treatment for the underlying cause includes bladder catheterization (or flushing of an indwelling catheter), followed by a rectal examination with fecal disimpaction if necessary. The choice of anesthetic (regional or general) should be tailored to the surgical procedure and the needs of the patient. Spinal or epidural anesthesia is very effective for ablating the afferent neural activity that results in autonomic dysreflexia and should be used when appropriate. The possibility of provoking autonomic dysreflexia with injection of a local anesthetic for peripheral nerve block or skin infiltration should be kept in mind. Succinylcholine should be avoided in these patients owing to the risk for hyperkalemia. For intra- and postoperative monitoring, consider arterial line placement in addition to the standard monitors. Have vasodilator drugs immediately available. Acute blood pressure reduction can be accomplished with a variety of

2 Hypertensive crises include urgencies and emergencies. Both require an acute blood pressure elevation to 160/110 mm Hg or higher. However, with the former, there is no evidence of end-organ damage; with the latter, there is.

agents. Intravenous labetalol, nicardipine, nitroglycerin, and nitroprusside are acceptable and can be given as a bolus or by continuous infusion. Have additional intravenous fluids and vasopressors (e.g., phenylephrine, ephedrine) ready to correct iatrogenic hypotension. Be prepared to quickly deepen the level of anesthesia if using a general anesthetic. Vasoactive drugs can then be administered if necessary. Finally, postpone an elective case if preoperative autonomic dysreflexia cannot be promptly evaluated and treated.

PREVENTION General preventive measures are tailored to the inciting factor in a given patient. Regular urinary catheterization and laxative use to ensure regular bowel activity are commonly needed. Patients should be taught to recognize the symptoms, correct the problem if possible, and seek emergency medical care if needed. In the perioperative setting, adequate anesthesia and the appropriate medication to control blood pressure should be present before the delivery of any noxious stimuli, which include anesthetic or surgical procedures, intramuscular injections, opioid-induced urinary retention or constipation, or any other factor that may stimulate pain receptors below the level of the spinal cord lesion.

Further Reading Blackmer J: Rehabilitation medicine. 1. Autonomic dysreflexia. CMAJ 169:931-935, 2003. Campagnolo DI: Autonomic dysreflexia in spinal cord injury. eMedicine J 2004. Available at www.emedicine.com Chobanian AV, Bakris GL, Black HR, et al: National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 report. JAMA 289:2560-2572, 2003. Consortium for Spinal Cord Medicine: Acute Management of Autonomic Dysreflexia: Individuals with Spinal Cord Injury Presenting to Health Care Facilities, 2nd ed. Washington, DC, Consortium, Paralyzed Veterans of America, 2001. Available at www.pva.org Karlsson AK: Autonomic dysreflexia. Spinal Cord 37:383-391, 1999. Kuczkowski KM: Peripartum anaesthetic management of a parturient with spinal cord injury and autonomic hyperreflexia. Anaesthesia 58: 823-824, 2003. Moss J, Glick D: The autonomic nervous system. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 617-677.

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Complications of Deliberate Hypotension: Visual Loss Aarti Sharma and Kerri M. Robertson Case Synopsis A 49-year-old man weighing 125 kg is scheduled for decompression laminectomy and instrumented fusion of the lumbar spine at multiple levels for lumbar stenosis. General anesthesia proceeds uneventfully with prone positioning, and the patient’s face and eyes are protected from direct pressure with a foam headrest. Despite the use of deliberate hypotension, titrating the mean arterial pressure to 55 to 65 mm Hg with continuous intravenous sodium nitroprusside, the estimated blood loss is 2.3 L, and the lowest hematocrit reading is 25%. Somatosensory evoked potentials are monitored intraoperatively. The surgery lasts 8 hours. On postoperative day 2, the patient complains of bilateral visual loss.

PROBLEM ANALYSIS Definition Deliberate hypotension is a controlled lowering of blood pressure. In normotensives, it reduces systolic blood pressure (SBP) to 80 to 90 mm Hg and mean arterial pressure (MAP) to 50 to 70 mm Hg. Significant hypotension is SBP or MAP 40% or more below baseline. The goals of using deliberate hypotension during surgery are to reduce blood loss, improve operating conditions, decrease surgical time, and reduce the need for allergenic red blood cell transfusions when surgical blood loss is expected to be great. The efficacy of deliberate hypotension has been both confirmed and refuted in various studies. Deliberate hypotension is used in neurovascular surgery, major orthopedic cases (e.g., total hip arthroplasty, complicated spinal surgery), surgery on large vascular tumors, head and neck surgery, and a variety of plastic surgeries, as well as in patients who refuse blood products. In most cases, deliberate hypotension is attained with continuous infusions of vasodilators (with or without β-blockers) or by increasing the inspired concentration of volatile anesthetic. Continuous positive airway pressure is sometimes used to reduce venous return. Techniques and agents used to achieve deliberate hypotension include the following: ●

Direct-acting vasodilating drugs (sodium nitroprusside, nitroglycerin, hydralazine)1

1 Arterial-selective vasodilators (e.g., hydralazine, nicardipine) may be a better choice for deliberate hypotension than a primary venous dilator (nitroglycerin) or a combined venous and arterial dilator (sodium nitroprusside). Sodium nitroprusside is also more likely to cause excess hypotension.

● ● ●

● ● ●

● ● ●

β-Adrenergic receptor blockers (metoprolol, esmolol) Spinal and epidural anesthesia Deepening of anesthesia with volatile anesthetic agents (isoflurane, sevoflurane) Autonomic ganglion-blocking drugs (trimethaphan) α-Adrenergic receptor blockers (phentolamine) Combined α- and β-adrenergic receptor blockers (labetalol) Calcium channel blockers (nicardipine) Prostaglandin E1 Continuous positive airway pressure

Recognition Deliberate hypotension reduces SBP primarily by vasodilatation. This can be selective arterial dilatation (to reduce systemic vascular resistance and afterload) or venous dilatation (to reduce venous return, preload, and cardiac output). However, when using deliberate hypotension, it must be remembered that oxygen (O2) delivery is determined by cardiac output, hemoglobin (Hb) concentration, and O2 saturation: O2 delivery (mL O2/min) = Cardiac output (L/min) × Hb concentration (g/L) × 1.31 (mL O2/g Hb) × % O2 saturation Although deliberate hypotension may be safe when used at relatively high hemoglobin levels, little is known about its clinical safety when combined with acute normovolemic hemodilution or when a reduction in cardiac output limits O2 delivery to tissues. Postoperative visual loss associated with spinal surgery or hip arthroplasty is a risk for patients and a medicolegal issue for both surgeons and anesthesiologists. The American 855

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Society of Anesthesiologists (ASA) Closed Claims Project (www.asaclosedclaims.org) established the Postoperative Visual Loss Registry in 1999 in an attempt to identify risk factors in patients who develop visual deficits within 7 days after nonophthalmic surgery. Anemia (median estimated blood loss 2.3 L; hematocrit 25.5%) and venous congestion of the head and neck were factors that contributed to morbidity associated with prolonged hypotension, presumably due to a reduction in O2 delivery to the optic nerve or visual cortex. Identified patient-related factors included middle age or elderly, morbid obesity, hypertension, a history of smoking, diabetes mellitus, and atherosclerosis. Since the Food and Drug Administration approved the use of spinal interbody cages in 1996, spinal instrumentation has resulted in longer operative times and increased blood loss. Additional risk factors include fluid management, facial swelling, external globe compression, emboli, adverse drug effects, anatomic variations in optic nerve blood supply, vasculitis, and use of vasoconstrictors such as epinephrine. None of these factors has been causally linked to visual loss in randomized controlled trials or animal studies. Ischemic optic neuropathy (ION) is the most frequently cited cause of postoperative visual loss associated with spinal surgery in prone patients. The estimated incidence is 1 in 500 cases. The differential diagnosis includes central retinal artery occlusion and cortical blindness. Preliminary results from the ASA database indicate that 81% of 53 spinal surgery patients were diagnosed with ION, but only 13% were diagnosed with central retinal artery occlusion. Posterior ION is caused by ischemia of the posterior part of the optic nerve and is more common than anterior ION after spinal surgery. Patients present with visual acuity ranging from normal to no light perception or with optic nerve–related visual field defects. The latter may be central scotomata, peripheral narrowing, or defects affecting various quadrants of the eye. Further, these visual defects may be altitude related. Early funduscopic examination in posterior ION is normal, but after about 5 to 6 weeks, the optic disks become pale from atrophy. The pupillary light reflex becomes delayed or absent. Both eyes were affected in more than 50% of the cases reported to the ASA registry. Some recovery occurred in 40% to 45% of patients, but vision rarely returned to baseline. Diagnostic studies include ophthalmic examination (visual acuity, intraocular pressure, color testing, visual fields, pupillary reflexes, funduscopy with pupillary dilatation), fluorescein fundus angiography, and optic nerve enhancement on magnetic resonance imaging. Computed tomography is not useful for the diagnosis of ION. Visual evoked potentials are useful before optic disk pallor is detectable but cannot be used as an intraoperative monitor of optic nerve function owing to the effects of general anesthesia (intravenous or volatile).

Risk Assessment The precise incidence of complications associated with deliberate hypotension is difficult to determine. Mortality appears to be no different from that for all anesthetics (0.007% to 0.01%). Identifiable risk factors for postoperative visual

disturbances include preoperative hypertension, smoking, diabetes, vascular disease, prone positioning, increased intraocular pressure, eyeball pressure points, intraoperative hypotension, prolonged surgical time, excessive surgical blood loss, anemia, disorders that result in increased blood viscosity, and structural factors related to optic nerve anatomy. Spinal surgery patients with ION from the ASA database had large operative blood losses (median 2.3 L), long duration in the prone position (median 8 hours), hypotension (median lowest MAP was a 37% decrease below baseline), and moderate anemia (median hematocrit 25.5%). Venous congestion is also thought to play a significant role in the development of this devastating complication. Perfusion pressure of the optic nerve is dependent on the difference between the MAP and venous (or intracranial) pressures. Both intraocular pressure and intracranial pressure increase in the prone and Trendelenburg positions owing to venous engorgement of the head and neck and increased central venous pressure. Thus, MAP changes from baseline with deliberate hypotension during general anesthesia can significantly reduce optic nerve perfusion pressure. Vascularization of the retrobulbar portion of the optic nerve depends on pial vessels originating from distal branches of the ophthalmic artery. These pial vessels lack autoregulatory mechanisms and appear to be prone to ischemia with systemic hypotension. Of the first 23 cases analyzed in the ASA registry, there was significant hypotension in 52% of cases, with deliberate hypotension used in 42% of these. Thus, the effects of deliberate hypotension on various vascular beds can be quite complex. The rationale for recommending a target MAP of 50 to 55 mm Hg with deliberate hypotension is that cerebral autoregulation in normal patients is still operative at this range. Otherwise (e.g., patients with chronic hypertension), MAP should be maintained within 20% of baseline for spinal surgery in prone patients, because a reduction in inflow with deliberate hypotension or an increase in venous congestion with the Trendelenburg position may cause a critical reduction in optic nerve perfusion pressure. Patients with conditions that affect cerebral autoregulation (e.g., hypertension, cerebrovascular disease, mass lesions) are at increased risk for ischemic injury with the use of deliberate hypotension. Coronary blood flow depends on coronary perfusion pressure as well as the resistance to and duration of flow. The latter is determined by heart rate (i.e., time spent in diastole) and primarily affects the left ventricle. During deliberate hypotension, maintenance of an O2 supply sufficient for the metabolic needs of the myocardium is of primary importance. The intact coronary circulation undergoes a high degree of pressure-flow autoregulation that is little disrupted by volatile anesthetic agents. However, progressive systemic hypotension gradually depletes the coronary vasodilatory reserve and reduces the heart’s ability to cope with stress, which increases myocardial O2 demand. Also, arterial hypotension obtained with vasodilators often leads to reflex tachycardia, and tachycardia increases myocardial metabolism and shortens diastole. Thus, myocardial perfusion (especially of the left ventricle) is jeopardized. The situation is even worse in patients with coronary artery disease, in whom the

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Complications of Deliberate Hypotension: Visual Loss

Implications There are no adequate randomized, controlled trials showing measurable benefits of deliberate hypotension in prone patients undergoing spinal surgery. It is unclear whether reducing the MAP decreases bleeding to the same degree it does during hip surgery, given the significant effect of increased intra-abdominal pressure causing high venous backpressure. This reduces spinal cord blood flow and potentially increases venous bleeding. Small case series suggest reduced blood loss but no benefit in terms of shortening the operating time. High-risk orthopedic procedures with the potential for significant blood loss include multiple levels of instrumentation, redo spine operations, and surgery for specific conditions (e.g., Charcot joints, infection, vascular tumors). It is difficult to understand the pathophysiology of postoperative blindness after spinal surgery because of its rarity and the lack of a homogeneous clinical presentation. Regardless of the surgical procedure, primary causes of postoperative visual loss include the following: ●

● ●

Anterior or posterior ION (ischemia or edema resulting in compartment syndrome involving the optic nerve) Cortical blindness due to hypotension and emboli Central retinal artery occlusion from external globe compression

The incidence of significant visual complications after noncardiac surgery in patients receiving general or central neuraxial regional anesthesia is 1 in 118,783 (0.0008%). Visual changes may be reported between postoperative days 1 and 12, with 81% of cases noted by postoperative day 2. Patients often assume that their visual problems are part of the normal recovery process or that subtle changes in vision are due to their eyes being lubricated and taped shut during surgery. This is the reason for most delays in the diagnosis of ION. Considering the many facets of deliberate hypotension, anesthesiologists must determine patient suitability. Patients with a history of cerebrovascular disease, renal insufficiency, liver dysfunction, severe peripheral claudication, hypovolemia, and severe anemia are not candidates for deliberate hypotension because their reserves for adequate organ perfusion are markedly diminished. The use of invasive monitoring is based on the type and length of surgery; anticipated transfusion requirements; the need to measure central venous and arterial pressures; required blood sampling for hematocrit, serum electrolytes, glucose, and blood gases; and the extent to which the blood pressure needs to be lowered from baseline. Any specialized monitoring is selected on a case-by-case basis. This might

include somatosensory evoked potentials, electroencephalogram, near-infrared spectroscopy, cerebral artery Doppler flow measurement, and tissue pH measurement.

MANAGEMENT Postoperative visual loss is a devastating complication. Early consultation with an ophthalmologist is strongly advised for both diagnosis and treatment. Treatment is mainly supportive. The prognosis for visual recovery is generally poor in patients with ION. High-dose steroids, hyperbaric O2 therapy, diuretics, mannitol, and ocular hypotensive agents have all been advocated, but with only variable success. Some clinicians advocate optic nerve fenestration for decompression with anterior ION. However, results of the Ischemic Optic Neuropathy Decompression Trial showed that surgical treatment had no efficacy. Subsequent complications of ION may include visual loss in the other eye and adverse side effects from long-term steroid use.

PREVENTION Despite a better understanding of ION, the best means of preventing it remain unclear. The following considerations should be adopted in high-risk individuals: ●

●

● ●

●

●

●

●

●

●

Balance the possible benefits of deliberate hypotensive anesthesia with the risk that it may contribute to complications in some patients. Establish a minimum SBP or MAP for each patient preoperatively, and do not allow the pressure to “drift” below that value. Aggressively replace intraoperative blood losses by using the cell saver or predonated autologous blood to maintain an adequate hematocrit. Consider antifibrinolytic agents to minimize blood loss. Stage the procedure and minimize the time the patient is in the prone position, especially for long procedures that require multiple surgical approaches. Avoid venous congestion of the head and neck by elevating the head, placing the head in a neutral position, and avoiding constrictive ties around the patient’s neck. Use colloid rather than crystalloid. This has the potential to reduce the edema believed to be associated with optic nerve compression. Pay strict attention to eye protection during patient positioning (this applies to both surgeons and anesthesiologists). Perform and document eye checks often during the case. Unless absolutely required to suppress recurrences of lifethreatening arrhythmias (see Chapters 12 and 79), avoid amiodarone because it has been implicated as a cause of ION. Monitor closely for visual deficits in the postanesthesia recovery room. Obtain early ophthalmology consultation when visual changes are identified.

Understanding the advantages and limitations of inducing deliberate hypotension permits its rational use. Integral to improving surgical success while minimizing complications

OTHER SURGICAL SUBSPECIALTIES

vasodilatory ability is diminished even at normal coronary perfusion pressures; thus, hypotension directly decreases myocardial perfusion in direct proportion to the amount of blood pressure reduction and is more likely to cause ischemia. Therefore, in patients with coronary artery disease, deliberate hypotension is undertaken only with pressing indications, and then only with stringent monitoring (e.g., pulmonary artery catheter or transesophageal echocardiography).

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are patient selection and use of the most appropriate technique, based on the type of surgery, the length of the procedure, and the need to reduce surgical blood loss. Lack of informed patient consent regarding the risk for visual loss with deliberate hypotension may place the anesthesiologist at medicolegal risk.

Further Reading Alexandrakis G, Lam BL: Bilateral posterior ischemic optic neuropathy after spinal surgery. Am J Ophthalmol 127:354-355, 1999. Dilger JA, Tetzlaff JE, Bell GR, et al: Ischaemic optic neuropathy after spinal fusion. Can J Anaesth 45:63-66, 1998. Gardner JW: The control of bleeding during operation by induced hypotension. JAMA 132:572, 1946.

Katz DM, Trobe JD, Cornblath WT, Kline LB: Ischemic optic neuropathy after lumbar spine surgery. Arch Ophthalmol 112:925-931, 1994. Lagerkranser M: Controlled hypotension in neurosurgery: Pro. J Neurosurg Anesth 3:150, 1991. Myers MA, Hamilton SR, Bogosian AJ, et al: Visual loss as a complication of spine surgery: A review of 37 cases. Spine 22:1325-1329, 1997. Roth S, Nunez R, Schreider BD: Unexplained visual loss after lumbar spinal fusion. J Neurosurg Anesthesiol 9:346-348, 1997. Rucker JC, Biousse V, Newman NJ: Ischemic optic neuropathies. Curr Opin Neurol 17:27-35, 2004. Toivonen J, Virtanen H, Kaukinen S: Labetalol attenuates the negative effects of deliberate hypotension induced by isoflurane. Acta Anaesthesiol Scand 36:84, 1992. Warner ME, Warner MA, Garrity JA, et al: The frequency of perioperative vision loss. Anesth Analg 93:1417-1421, 2001.

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Fat Embolism Syndrome Jennifer T. Fortney

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Case Synopsis

PROBLEM ANALYSIS Definition Showering of fat emboli to the pulmonary and systemic circulations is common in trauma and orthopedic surgical patients. Many episodes result in subclinical symptoms, but an estimated 1% to 5% are associated with clinical symptoms severe enough to be termed fat embolism syndrome (FES) (Table 215-1). Two theories exist concerning the cause of FES. The mechanical theory proposes that injuries of the long bones or the pelvis, and surgical maneuvers that increase intramedullary pressure, force large fat droplets into the systemic venous circulation. After embolizing to the right heart and

Table 215–1

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Clinical Findings in Fat Embolism Syndrome

Cardiovascular Persistent tachycardia (early finding) Possible hypotension

Respiratory Tachypnea Dyspnea Hypoxia Hemoptysis

Cerebral Delirium Stupor Seizures Coma

Ophthalmic Retinal hemorrhages with intra-arterial fat globules (may be seen on funduscopic examination)

Cutaneous Petechial rash—nonpalpable; head, neck, anterior thorax, axillae (20%-50% of cases) Hemorrhages and petechiae—both subconjunctival and oral possible

Other Fever Jaundice Oliguria or anuria

OTHER SURGICAL SUBSPECIALTIES

A 29-year-old man who has suffered fractures of the femur and tibia in a motorcycle accident is brought to the operating room for intramedullary nailing of both injuries. Surgery is unremarkable, but the patient is noted to have persistent tachycardia in the recovery room, despite adequate fluid resuscitation and pain control. The following morning, he is tachypneic and complains of significant shortness of breath. On examination, his pulse oximeter reading is 88% on room air, and he has a petechial rash on his chest and neck. A chest radiograph shows diffuse bilateral infiltrates.

lungs, they cause acute pulmonary hypertension. The contributing factors are mechanical obstruction of the pulmonary microcirculation and an increase in pulmonary vascular resistance. Lodged droplets induce localized ischemia and inflammation, with the release of proinflammatory mediators. Fat emboli may also gain access to the systemic arterial circulation through intracardiac shunts or by traversing the pulmonary capillary bed. Subsequent systemic manifestations include cerebral and cutaneous embolization and fatinduced acute lung injury. The biochemical theory states that biochemical (specifically, hormonal) changes that occur with trauma and sepsis induce the systemic release of free fatty acids as chylomicrons. C-reactive protein and other phase reactants cause these chylomicrons to coalesce. Free fatty acids are directly toxic to pneumocytes and pulmonary capillary endothelium and produce interstitial hemorrhage and chemical pneumonitis. This theory is especially attractive when FES occurs in the absence of trauma.

Recognition Fat embolism is primarily a clinical diagnosis. The diagnosis may be missed because of subclinical symptoms, a delay in onset of 24 to 72 hours, or the presence of additional traumatic injuries. Although a number of predisposing conditions are associated with FES (Table 215-2), a high index of suspicion is necessary to make the diagnosis based on the classic triad of a petechial rash associated with pulmonary and cerebral dysfunction. Early persistent tachycardia may be the first sign of impending problems. Within 24 to 72 hours of the insult, patients may become tachypneic, dyspneic, and hypoxemic owing to ventilation-perfusion abnormalities. This lung injury pattern may progress to full-blown acute respiratory distress syndrome (ARDS). A reddish brown, nonpalpable petechial rash involving the head, neck, anterior thorax, and axillae appears in 20% to 50% of patients. This rash is easily missed because it resolves quickly. Emboli to the cerebral circulation may result in neurologic changes, including confusion, sedation, and coma. Retinal hemorrhages, with intra-arterial fat droplets, may be visible on funduscopic examination. A fulminant form of FES is occasionally encountered in the operating room during joint replacement procedures. 859

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Predisposing Conditions Associated with Fat Embolism Syndrome

Table 215–3

Trauma Blunt trauma, especially to liver Fractures—long bone or pelvic, multiple or closed fractures (incidence may be as high as 15%-20%)

Orthopedic Surgery Joint replacement, especially revisions or bilateral procedures Nonvented, intramedullary nailing Femoral metastases

Tissue Manipulation Bone marrow harvest or transplantation Liposuction

Exogenous Plastic surgery—fat injections Total parenteral nutrition Lymphography

Other Hepatic failure Alcoholism Acute pancreatitis Sickle cell crisis Altitude sickness Cardiopulmonary bypass Burns

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Laboratory and Other Findings that Support but Do Not Establish the Diagnosis of Fat Embolism Syndrome

Hematologic Thrombocytopenia: >50% decrease Anemia: >20% decrease Other: elevated erythrocyte sedimentation rate, hypofibrinogenemia, fat macroglobulinemia

Radiologic Chest radiograph: diffuse bilateral infiltrates with “snowstorm” appearance, usually within 48 hr of clinical onset Chest CT: may be normal, but parenchymal changes are consistent with acute lung injury; ARDS may be present Head CT: usually negative, but may show diffuse white matter hemorrhages consistent with microvascular injury MRI: scant data, but possible nonconfluent, hyperintense lesions on proton-density and T2-weighted images

Other Lipase and phospholipase A2 may be elevated Increased pulmonary shunt fraction (without another identifiable cause) Increased alveolar-to-arterial gradient (without another identifiable cause) Urinalysis: stained fat globules (poor specificity) Elevated pulmonary artery pressure (poor sensitivity) ARDS, acute respiratory distress syndrome; CT, computed tomography; MRI, magnetic resonance imaging.

Large amounts of fat from the medullary cavity of long bones may be forced into the venous circulation over a short period. In patients with limited cardiac reserve, acute pulmonary hypertension may precipitate right ventricular failure with hypotension, bradycardia, hypoxemia, and cardiovascular collapse. In contrast to fulminant FES, the symptoms occurring with subacute FES are postulated to be secondary to the toxic effects of the free fatty acids that result from hydrolysis of the embolized fat droplets. Laboratory and other diagnostic tests are nonspecific and not sufficiently sensitive to establish the diagnosis of FES, but they may add weight to the clinical findings (Table 215-3). The chest radiograph may reveal diffuse bilateral infiltrates with a “snowstorm” appearance. Computed tomography (CT) scans of the head may be normal or may show edema or nonspecific infarctions. Chest CT may also be normal, although changes consistent with lung contusion, acute lung injury, or ARDS may be present. In the absence of other lung pathology, an increase in the alveolar-to-arterial gradient is strongly suggestive of FES. Hematologic findings may include thrombocytopenia, anemia (thought to be secondary to intra-alveolar hemorrhage), fat macroglobulinemia from a pulmonary capillary blood sample, or a markedly elevated sedimentation rate. Lipase and phospholipase A2 may be elevated within a few hours of the insult but can return to normal within 24 hours.

Risk Assessment Orthopedic and trauma patients, especially those with lower extremity long bone and pelvic fractures, have a 20% incidence of fat embolism. Displaced fractures are considered a lower risk than nondisplaced ones, because displacement is thought to provide a “vent” for bone marrow fat, thus

lessening the potential for intravasation. Patients with fractures of the middle and proximal parts of the femoral shaft are at increased risk, as are those with multiple fractures. Delayed stabilization (>24 hours) increases the risk for fat embolization. Young men constitute the largest at-risk group for FES owing to the high incidence of skeletal and multiple trauma in this group. The elderly make up the second largest patient group because of the prevalence of hip fractures, total joint replacement procedures, and underlying cardiopulmonary disease. Intramedullary rod placement for closed or impending fractures has also been shown to increase the incidence of fat emboli. Joint replacement surgery, especially revisions or bilateral procedures, is associated with FES, as are femoral metastases and procedures that disrupt the adipose layer (liposuction) or bone marrow (harvest or transplantation). Case reports have also linked fat injections performed during cosmetic surgery with significant fat embolism. The alcohol-induced fatty liver is capable of spontaneously releasing large numbers of embolus-sized fat globules when fatty cysts rupture into adjacent sinusoids and veins. Blunt trauma to the liver has also been associated with fat embolism. Some controversy exists over whether highdose corticosteroids, which can increase the fat content of the liver, increase the risk for FES.

Implications The mortality rate for FES may be as high as 5% to 15%, especially in elderly and debilitated patients. Mortality from fulminant FES is typically due to acute right ventricular

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MANAGEMENT Treatment of FES is aimed at prevention of further fat dissemination, correction of hypoxemia, and hemodynamic stabilization. FES-induced acute lung injury requires supportive respiratory care to maximize oxygenation and ventilation, ensure airway protection, and prevent aspiration. This may require intubation, insertion of an arterial line for blood gas sampling, and mechanical ventilation of those patients with severe pulmonary compromise or altered mental status. Blood products, clotting factors, and platelets are administered to correct any coagulopathy in patients scheduled for surgery who are actively bleeding. Volume status may be critical, especially if right ventricular dysfunction is present; a central venous or pulmonary artery catheter may be useful in guiding fluid management. Inotropic support should be used, as needed, to maintain blood pressure, improve right ventricular output, and prevent ventricular ischemia. Prophylactic care aimed at preventing deep venous thrombosis and stress-related gastrointestinal bleeding is indicated. Surgical care for patients with long bone fractures should be aimed at stabilizing the fracture as early as possible. Heparin use has been suggested because, in theory, it acts to clear lipids from the serum by stimulating lipase. However, the data are contradictory, and heparin has no clear role at this time. The role of corticosteroids in FES is less clear. They are thought to stabilize the capillary and alveolar membranes to prevent further damage to the lung. However, studies have obtained varying results. Also, the dose, optimal timing, and duration of therapy remain undetermined. Management of fulminant FES, an acute life-threatening condition, requires advanced cardiac life support techniques.

PREVENTION Because the majority of FES cases are associated with trauma, the rapid stabilization of fractures and correction of hypovolemia should be among the highest priorities for reducing the incidence of FES. If the patient is sufficiently stable to proceed to surgery, surgical fixation of fractures should occur within 24 hours of injury. Surgical techniques that may help reduce the volume of fat intravasation during intramedullary

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reaming, nailing, and prosthesis replacement include the following: ●

● ●

●

●

Drilling a small hole in the distal bone to vent fat and marrow during surgery Use of an uncemented prosthesis for total hip arthroplasty Lavage of the canal after each reaming to remove debris and clots Use of fluted rods during total knee arthroplasty to allow marrow contents to exit into the knee Modification of reaming techniques (avoidance, or use of low driving speed or small-cored reamers)

Again, it is important to recognize which patients are at increased risk for FES (see Table 215-2). Optimizing the physical status of high-risk patients, rapidly stabilizing atrisk fractures, using techniques to reduce intraoperative fat embolization, and rapidly identifying and treating FES can help reduce the morbidity and mortality associated with this condition.

Further Reading Alho A: Fat embolism syndrome: Etiology, pathogenesis and treatment. Acta Chir Scand (Suppl) 499:75-85, 1980. Bouaggad A, Harti A, Elmouknia M, et al: Neurologic manifestations of fat embolism. Cah Anesthesiol 43:441-443, 1995. Dalgorf D, Borkhoff CM, Stephen DJ, et al: Venting during prophylactic nailing for femoral metastases: Current orthopedic practice. Can J Surg 46:427-431, 2003. Georgopoulos D, Bouros D: Fat embolism syndrome: Clinical examination is still the preferable diagnostic method. Chest 123:982-983, 2003. Gitin TA, Seidel T, Cera PJ, et al: Pulmonary microvascular fat: The significance? Crit Care Med 21:673-677, 1993. Jones JP Jr: Alcoholism, hypercortisolism, fat embolism and osseous avascular necrosis. Clin Orthop 393:4-12, 2001. Kirkland L: Fat embolism. eMedicine J 2004. Available at www.emedicine .com/med/topic652.htm Marshall PD, Douglas DL, Henry L: Fatal pulmonary fat embolism during total hip replacement due to high-pressure cementing techniques in an osteoporotic femur. Br J Clin Pract 45:148-149, 1991. Mellor A, Soni N: Fat embolism. Anaesthesia. 56:145-154, 2001. Papagelopoulos PJ, Apostolou CD, Karachalios TS, et al: Pulmonary fat embolism after total hip and total knee arthroplasty. Orthopedics 26:523-527, 2003. Peltier LF: Fat embolism: An appraisal of the problem. Clin Orthop 187: 3-17, 1984. Pitto RP, Blunk J, Kossler M: Transesophageal echocardiography and clinical features of fat embolism during cemented total hip arthroplasty: A randomized study in patients with a femoral neck fracture. Arch Orthop Trauma Surg 120:53-58, 2000. Slye DA: Orthopedic complications: Compartment syndrome, fat embolism syndrome, and venous thromboembolism. Nurs Clin North Am 26:113-132, 1991. Sutton GE: Pulmonary fat embolism and its relation to traumatic shock. BMJ 2:368, 1918. Tedeschi CG, Castelli W, Kropp G, et al: Fat macroglobulinemia and fat embolism. Surg Gynecol Obstet 126:83-90, 1968. Thaunat O, Thaler F, Loirat P, et al: Cerebral fat embolism induced by facial fat injection. Plast Reconstr Surg 113:2235-2236, 2004. Wilson JV, Salisbury CV: Fat embolism in war surgery. Br J Surg 31:384, 1954. Yoon SS, Chang DI, Chung KC: Acute fatal stroke immediately following autologous fat injection into the face. Neurology 61:1151-1152, 2004.

OTHER SURGICAL SUBSPECIALTIES

failure with cardiovascular collapse. Respiratory failure is the most common cause of death in the subacute presentation of FES. Almost 90% of FES cases are associated with blunt trauma. Therefore, a high index of suspicion must be maintained when treating these patients. The majority of patients can be expected to recover from the pulmonary sequelae of FES with appropriate supportive care. Acute mental status changes often do not resolve immediately, even with improvement in oxygenation. This may take several days. However, long-term or permanent neurologic sequelae are occasionally seen in patients with visual disturbances or focal neurologic deficits.

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Thromboembolic Complications Robert F. Helfand Case Synopsis A 72-year-old man has total hip arthroplasty under general anesthesia. A postoperative visit the next day finds him mildly tachypneic, apprehensive, and complaining of pain in his calf on the operative side.

PROBLEM ANALYSIS Definition Embolic events are a major cause of morbidity and mortality following lower extremity orthopedic surgery. This chapter focuses on thrombotic sources of emboli. Chapters 175, 215, and 217 discuss embolization secondary to air, fat, and methylmethacrylate, respectively. In contrast to the arterial thromboembolic and vasoocclusive events associated with vascular surgery, orthopedic thromboembolic events affect primarily the venous system. As such, their cause is associated with endothelial damage, venous stasis, and hypercoagulability (Virchow’s triad). These conditions facilitate the formation of deep venous thromboses (DVTs), which usually begin in the lower leg veins and then extend proximally to the deep thigh veins before ultimately embolizing to the right heart and pulmonary circulation.

embolization may reveal hypoxemia or hypercapnia, but findings are often normal. An ECG may show evidence of right ventricular strain (new right bundle branch block, right axis deviation), sinus tachycardia, or anterior T-wave inversion, but it is usually normal. Monitored patients may have reduced cardiac output or increased pulmonary arterial pressure and vascular resistance. Transesophageal echocardiography (TEE) visualizes the central pulmonary arteries and evaluates right ventricular function. During surgery, TEE is recommended as the initial diagnostic test for suspected massive PE or in cases of unexplained hypotension, hypoxemia, or cardiac arrest. TEE has a reported sensitivity of 76% to 96.7% and a specificity of 86% to 100% for identifying central PE.

Risk Assessment Patient and surgical factors contribute to the risk of thromboembolic complications after orthopedic surgery (Table 216-1).

Recognition DVTs and pulmonary emboli (PE) are notoriously difficult to diagnose. Most patients with DVT have no obvious disease. The most commonly used diagnostic tool is duplex ultrasonography. Ultrasound tests are noninvasive and can be easily repeated, but they lack sensitivity for calf vein thrombosis. PE are difficult to recognize both during and after anesthesia, but they should be suspected in any patient with sudden, unexplained dyspnea after a surgery. Symptoms may include chest pain, dyspnea, hemoptysis, apprehension, or cough, but they are generally nonspecific. Physical findings include tachypnea, tachycardia, rales, or an accentuated pulmonic component of the second heart sound (P2). Most patients with PE do not exhibit signs of thrombophlebitis. High-resolution spiral computed tomography scanning is often chosen instead of ventilation-perfusion lung scanning as the initial diagnostic test for PE. Pulmonary angiography was once the standard test for the diagnosis of PE, but it is now used less frequently. D-dimer measured by the ELISA test is an additional screening tool, but it is neither specific nor sufficiently sensitive to make or exclude the diagnosis of PE. A normal chest radiograph, arterial blood gas analysis, or electrocardiogram (ECG) does not exclude the diagnosis of PE. Arterial blood gas analysis at the time of 862

Table 216–1

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Risk Factors for Thromboembolic Complications with Lower Extremity Orthopedic Surgery

Patient Risk Factors Low cardiac output states (CHF, MI) Prolonged immobilization or paralysis Obesity Prior DVT, PE, or varicose veins Age older than 40 yr Cancer Hypercoagulable states Pregnancy Inflammatory bowel disease Nephrotic syndrome

Surgical Risk Factors Major surgery >70 min No DVT prophylaxis Hypothermia Positioning Surgical technique Hypotension Trauma (pelvis, hip, or leg fracture) Indwelling central venous catheter CHF, congestive heart failure; DVT, deep venous thrombosis; MI, myocardial infarction; PE, pulmonary emboli.

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Implications

●

MANAGEMENT Intraoperative management of PE is supportive and focuses on optimizing cardiopulmonary function. Specific measures include volume support of right ventricular preload, administration of inotropic drugs, afterload reduction for the right ventricle, and increasing the fraction of inspired oxygen; positive end-expiratory pressure may be added. Patients can have delayed findings of atelectasis and pulmonary infiltrates 24 to 72 hours following PE. Patients with serious cardiorespiratory compromise may benefit from placement of a pulmonary artery catheter and measurement of cardiac output. Therapeutic intervention for PE consists of full heparinization or fibrinolytic therapy. In most cases, however, neither is appropriate intraoperative treatment. For patients with cardiac arrest or persistent hypotension and hypoxemia, options include the following: ●

●

Emergency operative embolectomy, which requires cardiopulmonary bypass Bilateral thoracotomy, with massage of the pulmonary vessels

Table 216–2

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Incidence of Thromboembolic Complications after Orthopedic Procedures without Prophylaxis

Procedure

Total DVT (%)

Proximal DVT (%)

Total PE (%)

Fatal PE (%)

Total hip arthroplasty Total knee arthroplasty Repair of hip fracture

42-57 41-85 46-60

18-36 5-22 23-30

0.9-28 1.5-10 3-11

0.1-2 0.1-1.7 2.5-7.5

DVT, deep venous thrombosis; PE, pulmonary emboli.

Thromboembolic Complications

863

Interventional radiology for attempted thrombus extraction or catheter-directed fibrinolytic therapy

Mortality with surgical removal of PE is greater than 50%.

PREVENTION Thromboembolic complications after orthopedic surgery are unique. The process frequently begins intraoperatively, extends quietly postoperatively, and often results in sudden death. Thus, prevention is imperative, especially because therapeutic interventions are often associated with serious hemorrhagic complications. Prophylaxis includes both mechanical and pharmacologic modalities. The anesthetic technique may also play a significant role in prevention.

Mechanical and Pharmacologic Modalities Compression stockings that provide a 30 to 40 mm Hg compression gradient are an effective adjunctive treatment for limiting or preventing the extension of thrombus. Mechanical modalities, such as intermittent pneumatic compression devices, can reduce the incidence of thrombus formation by decreasing venous stasis, improving blood flow velocity, and increasing circulating fibrinolysins. Their effectiveness is not diminished when applied to only one leg during surgery. Pneumatic devices significantly decrease the incidence of distal thrombi but have no effect on more proximal thrombi in the iliac and femoral veins. The American College of Chest Physicians recommends the use of oral warfarin or parenteral low-molecular-weight heparin products for DVT prophylaxis. The latter include enoxaparin (Lovenox) or the novel parenteral anti–factor Xa agent fondaparinux sodium (a synthetic pentastarch). Aspirin is never used alone. Also, standard unfractionated heparin should not be used for high-risk patients. DVT prophylaxis regimens are specific. Patients are stratified by risk to four categories, as well as to those having total knee replacement or total hip replacement. Warfarin is usually started the night before surgery or immediately postoperatively; the therapeutic international normalized ratio target of 2.5 (range, 2 to 3) is usually not achieved until the third postoperative day. Low-molecular-weight heparin is usually started 12 to 24 hours postoperatively. For total hip replacement, low-molecular-weight heparin may also be given 4 to 6 hours after surgery at half the full dose, followed by a full dose the next day. Preoperatively, it can be given 12 hours before surgery, followed by a full dose 12 to 24 hours postoperatively. Following hip surgery, treatment needs to continue for at least 10 days for lower-risk patients and for 28 to 35 days for higher-risk patients. Although these modalities are more efficacious than placebo, their relative efficacy and value are controversial and probably vary according to the type of surgery.

Anesthetic Management A convincing number of studies support the choice of regional anesthesia over general anesthesia for reducing thromboembolic complications, especially DVT. When compared

OTHER SURGICAL SUBSPECIALTIES

DVT is common following hip and knee arthroplasty, and especially after hip fracture. DVT is a clot that develops in the large distal veins of the legs, usually deep within the muscle. Less frequently, DVT develops in the proximal pelvic veins. The clot is usually attached at one end. However, if it breaks loose and enters the bloodstream, it may embolize to the right heart and main pulmonary artery branches. The patient is especially at risk when the DVT extends proximally into deep thigh veins. Fatal PE occurs in up to 7% of lower extremity orthopedic procedures and constitutes the greatest source of perioperative mortality in these patients (Table 216-2). Emboli may also traverse an intracardiac communication to enter the arterial circulation. This can cause stroke or acute arterial occlusion in the extremities or other major organs. At least half of venous thrombi start intraoperatively; the remainder occur during the first 24 to 48 postoperative hours. Nevertheless, some PE do not become clinically apparent until 1 week after surgery. The high risk of morbidity and mortality mandates prophylactic measures to reduce the occurrence of thromboembolic complications.

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with general anesthesia, epidural anesthesia reduces the incidence of deep thigh DVT 2.5- to 5-fold and PE 3-fold after hip arthroplasty. Regional anesthesia also results in a 31% reduction of DVT following repair of hip fracture. It is unclear why regional anesthesia appears to reduce thromboembolic complications, but it may counter sympathoadrenal stimulation of the coagulation cascade (see Chapter 89). Regional techniques clearly improve rheology by reducing viscosity and increasing lower extremity blood flow. Less clear is the membrane-stabilizing role of local anesthetics themselves. These effects appear to decrease platelet aggregation while increasing fibrinolysis and normalization of antithrombin III levels. In addition, local anesthetics may inhibit the activation of leukocyte factors linked to hypercoagulability. Unfortunately, the choice of regional anesthesia is not so clear-cut. Two issues regarding the risk of spinal (epidural) hematoma deserve consideration by the anesthesiologist. One is practical and the other theoretical. The practical issue concerns placement of central neuraxial blocks in patients who are either receiving or are about to receive anticoagulants. Warfarin therapy begins the night before surgery in many patients having joint replacement or in the immediate postoperative period. Available literature supports the safety of perioperative regional techniques in this setting (see also Chapter 57). More ominous is the issue of the concurrent use of unfractionated or low-molecular-weight heparin and central neuraxial anesthesia (see also Chapter 57). Low-molecularweight heparin is a relative contraindication to central neuraxial regional techniques because of its long half-life, the difficulty of monitoring its anticoagulant effects, and several reports of associated spinal (epidural) hematoma. These limitations have restricted the use of indwelling neuraxial catheters for postoperative epidural analgesia in many centers, as well as increasing interest in the use of singleinjection and continuous peripheral nerve blocks for postoperative pain relief. Anesthesiologists face a theoretical dilemma when choosing the anesthetic technique for lower extremity orthopedic surgery: Does regional anesthesia’s benefit in terms of thromboembolism prophylaxis outweigh the risk of spinal (epidural) hematoma? In most of the aforementioned stud-

ies that support the use of regional versus general anesthesia for reducing thromboembolic complications, especially DVT, patients did not receive thromboembolism prophylaxis. It remains unclear whether regional anesthesia is superior to or synergistic with standard thromboembolism prophylactic techniques. Because most patients do receive pharmacologic prophylaxis, the general recommendations of the American Society for Regional Anesthesia include a single needle pass, atraumatic needle placement, and no indwelling neuraxial catheters. For recommendations regarding specific agents used for thromboembolism prophylaxis, refer to Chapter 57 under Management. For patients receiving selective factor Xa inhibitors, there is insufficient evidence to make a specific recommendation regarding the use of continuous or singleinjection central neuraxial anesthetic techniques. One review of the prospective, randomized experience with fondaparinux sodium found that this agent did not increase the risk of epidural hematoma when used with neuraxial anesthesia.

Further Reading Cannavo D: Use of neuraxial anesthesia with selective factor Xa inhibitors. Am J Orthop 31:S21-S23, 2002. Geerts WH, Pinco GF, Heit JA, et al: Prevention of venous thromboembolism: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126:338s-400s, 2004. Horlocker T: Regional anesthesia in the anticoagulated patient: Defining the risk (the Second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Reg Anesth Pain Med 28:172-197, 2003. Liu SS, Carpenter RL, Neal JM: Epidural anesthesia and analgesia: Their role in postoperative outcome. Anesthesiology 82:1474-1506, 1995. Rosenfeld BA: Benefits of regional anesthesia on thromboembolic complications following surgery. Reg Anesth 21:9-12, 1996. Sharrock NE, Ranawat CS, Urquhart B, et al: Factors influencing deep vein thrombosis following total hip arthroplasty under epidural anesthesia. Anesth Analg 76:765-771, 1993. Sorenson RM, Pace NL: Anesthetic techniques during surgical repair of femoral neck fractures: A meta-analysis. Anesthesiology 77:1095-1104, 1992. Wedel DJ (ed): Orthopedic Anesthesia. New York, Churchill Livingstone, 1993. Wedel DJ, Horlocker TT: Anesthesia for orthopedic surgery. In Barash PR, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 3rd ed. Philadelphia, Lippincott-Raven, 1997, pp 1036-1037.

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Methylmethacrylate Kathryn P. King

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Case Synopsis

PROBLEM ANALYSIS Definition Polymethylmethacrylate bone cement is a polymer formed by mixing highly volatile liquid methylmethacrylate (MMA) monomer with an accelerator, polymethylmethacrylate powder. This bone cement is used during orthopedic surgery to implant prostheses for joint replacement. MMA has been implicated as a cause of adverse cardiopulmonary events observed most frequently during hip replacement surgery. Symptoms include hypoxemia, bronchoconstriction, pulmonary hypertension, and right ventricular failure with hypotension. Fatal cardiac arrest, though rare, has been reported in 0.6% to 1% of patients in some case series. The clinical presentation just described is termed bone implantation syndrome (BIS) or bone cement implantation syndrome (BCIS). Proposed mechanisms for MMA-induced injury include a neurogenic reflex, release of vasoactive and myocardial depressant substances by the cement, intravascular thrombin generation in the lungs, direct vasoactive effects of absorbed MMA, and acute pulmonary microembolization. After application of polymethylmethacrylate, unbound MMA monomer is quickly absorbed into the systemic circulation and eliminated by the lungs. Its peak level is reached in expired air within 2 to 5 minutes. The extent of systemic absorption depends on the area of contact between the bone cement and vascularized tissue and on the degree of curing. MMA is a peripheral vasodilator. However, the amount released during reaming in joint replacement is 10- to 20-fold less than that required to produce hypotension in experimental models. Further, studies have demonstrated that hypotension also occurs in the absence of the polymer. Thus, the most likely explanation of the pathogenesis of this syndrome is acute pulmonary microembolization. During implantation of the cement and prosthesis, the high intramedullary pressure generated in the long bone marrow cavity forces medullary contents into the venous circulation, with embolization to the lungs. The pathologic nature of the emboli is not certain; it may be fat, marrow, thrombus, air, or bone cement. Emboli appear as echogenic masses during reaming, cementing, prosthesis placement, and manipulation of the bone. Pulmonary embolization activates the clotting cascade and triggers the production of proinflammatory substances. Further, cemented prostheses are associated with a longer duration of embolization, larger emboli, and a higher

OTHER SURGICAL SUBSPECIALTIES

A 62-year-old man presents for a total hip arthroplasty for degenerative joint disease. His medical problems include hypertension and mild exercise-induced asthma that is treated with an albuterol inhaler. He declines regional anesthesia. General anesthesia is induced and proceeds uneventfully. During cementing and insertion of the femoral prosthesis, the patient develops hypotension, tachycardia, and hypoxemia.

percentage of right atria filled by emboli compared with noncemented prostheses. Intramedullary pressure peaks are 680 mm Hg in humans with cemented arthroplasty, compared with peaks of less than 100 mm Hg with noncemented arthroplasty. There are also chronic issues related to MMA and other polymers used in orthopedic surgery. Controlled occupational exposure to MMA has not been shown to affect workers’ mortality from colon and rectal cancer. The recommended maximum exposure of MMA vapor is 100 parts per million over the course of an 8-hour workday. Acute exposure to extremely high levels of MMA vapor can cause liver necrosis, pulmonary edema, and pulmonary emphysema. Occupational exposure of medical personnel is well below the levels necessary to elicit these toxic effects. However, other less dramatic effects might occur. MMA is known to be a potent allergenic sensitizer and can cause local reactions with dermal exposure. It is also known to be a potential pulmonary toxin, with chronic exposure causing occupational asthma. The direct pulmonary effect of MMA in the absence of pulmonary embolization is not well defined. However, indirect evidence suggests that it may trigger bronchoconstriction.

Recognition Clinical signs of BIS are similar to those found in pulmonary embolism or fat embolism. These include fever, tachycardia, hypotension, hypoxemia, and, in spontaneously breathing patients, dyspnea and tachypnea. End-tidal carbon dioxide may decrease with a large embolus. Also, fat emboli may cause petechiae, fat globules in the urine, and anuria or oliguria. In awake patients, they can cause mental status changes. The electrocardiogram may show right axis deviation or right bundle branch block. Collectively, these signs reflect increased pulmonary artery pressure and intrapulmonary shunt, potentially leading to right ventricular failure and cardiac arrest.

Risk Assessment This patient population includes elderly or chronically ill patients undergoing either elective or emergent surgery. Careful preoperative evaluation may identify coexisting conditions, such as pulmonary or cardiovascular disease, that can be stabilized or improved preoperatively in anticipation of hemodynamic instability during surgery. A frail 865

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individual with additional risk factors, such as pulmonary hypertension, coronary artery disease, or severe osteoporosis, may benefit from invasive monitoring.

Invasive monitoring may be indicated for patients with marginal cardiac or pulmonary reserves. Finally, adequate volume replacement and supplemental oxygen are essential.

Implications

Further Reading

Although hypotension and hypoxia frequently occur during implantation of the prosthesis, these findings are usually transient and self-limited. Larger emboli causing right ventricular outflow tract obstruction may require resuscitation with intubation, mechanical ventilation with 100% oxygen, intravenous fluids, inotropic agents, afterload reduction of the right ventricle, and, occasionally, heroic measures such as cardiopulmonary bypass and surgical thrombectomy.

Berman AT, Price HL, Hahn JF: The cardiovascular effects of methylmethacrylate in dogs. Clin Orthop 100:265-269, 1974. Christie J, Robinson CM, Pell AC, et al: Transcardiac echocardiography during invasive intramedullary procedures. J Bone Joint Surg Br 77:450-455, 1995. Dahl OE, Molnar I, Vinje A, et al: Studies on coagulation, fibrinolysis, kallikrein-kinin and complement activation in systemic and pulmonary circulation during hip arthroplasty with acrylic cement. Thromb Res 5:875-884, 1988. Elmaraghy AW, Humeniuk B, Anderson GI, et al: The role of methylmethacrylate monomer in the formation and haemodynamic outcome of pulmonary fat emboli. J Bone Joint Surg Br 80:156-161, 1998. Ereth MH, Weber JG, Abel MD, et al: Cemented versus non-cemented total hip arthroplasty—embolism, hemodynamics, and intrapulmonary shunting. Mayo Clin Proc 67:1066-1074, 1992. Fallon KM, Fuller JG, Morley-Forster P: Fat embolization and fatal cardiac arrest during hip arthroplasty with methylmethacrylate. Can J Anaesth 48:626-629, 2001. Lamade WR, Friedl W, Schmid B, et al: Bone cement implantation syndrome: A prospective randomised trial for use of antihistamine blockade. Arch Orthop Trauma Surg 114:335-339, 1995. Lopez-Duran L, Garcia-Lopez A, Duran L, et al: Cardiopulmonary and haemodynamic changes during total hip arthroplasty. Int Orthop 21:253-258, 1997. Mellor A, Soni N: Fat embolism. Anaesthesia 56:145-154, 2001. Orsini EC, Byrick RJ, Mullen JB, et al: Cardiopulmonary function and pulmonary microemboli during arthroplasty using cemented or non-cemented components: The role of intramedullary pressure. J Bone Joint Surg Am 69:822-832, 1987. Rinecker H: New clinico-pathophysiological studies on the bone cement implantation syndrome. Arch Orthop Trauma Surg 97:263-274, 1980. Tomenson JA, Bonner SM, Edwards JC, et al: Study of two cohorts of workers exposed to methyl methacrylate in acrylic sheet production. Occup Environ Med 57:810-817, 2000.

MANAGEMENT Treatment of BIS is limited to supportive care. This includes monitoring vital signs and the use of supplemental oxygen and intravenous fluids, with vasopressor support as needed. In some patients, positive inotropic agents may also be needed.

PREVENTION Emboli occur frequently during surgical manipulation and placement of both cemented and noncemented orthopedic prostheses. Avoidance of MMA may not significantly reduce the occurrence of these events. However, lavaging the marrow cavity, placing a vent hole in the bone during reaming to reduce intramedullary pressure, and thorough removal of bone marrow and bone debris can minimize the dislodgment of particulates. Allowing the freshly mixed MMA to vaporize for as long as possible may help minimize MMA absorption.

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Extremity Tourniquets H. David Hardman

218

Case Synopsis

PROBLEM ANALYSIS Definition Postoperative neurologic dysfunction with the use of arterial tourniquets is a well-documented but rare phenomenon. Estimates of incidence range from 0.15% to 0.6% for all patients. Owing to greater soft tissue mass insulation, thigh tourniquets are less likely to cause neurologic injury than are arm tourniquets; the risk is increased with calf and forearm tourniquets. Permanent tourniquet-induced neurologic deficits are uncommon. The majority of nerve injuries resolve spontaneously within 6 weeks, with complete recovery by 6 months. Arterial tourniquets are widely used in upper and lower extremity surgery and in intravenous regional anesthesia. This practice continues because it is widely accepted that the benefit from minimizing surgical blood loss and creating a bloodless operative field exceeds the risk for tourniquetrelated complications. It is important for anesthesiologists to be aware of the potential for tourniquet-related tissue injury, systemic effects of tourniquet inflation and deflation, and the possibly catastrophic events that could occur at these times. Also, it should be recognized that surgeons and anesthesiologists share any medicolegal liability for tourniquetrelated complications. Documentation should include the location of the tourniquet, the use of padding and draping, and inflation pressure and duration. Also, tourniquet pressure relative to systemic blood pressure values, prolonged inflation, and total vascular occlusion times must be communicated to the surgical team and documented on the anesthesia record. LOCAL INJURY Pressure-related injuries to skin, muscles, nerves, and blood vessels depend on the pressure of tourniquet inflation and its duration. Also, absent arterial blood flow distal to the tourniquet causes ischemia, which leads to progressive acidosis, hypoxemia, and hypercarbia. The associated release of inflammatory mediators increases capillary permeability and tissue edema. This worsens ischemia, especially after reperfusion.

OTHER SURGICAL SUBSPECIALTIES

A 75-year-old woman is undergoing a revision of a left total knee arthroplasty under regional anesthesia. She is morbidly obese, on chronic opioids for pain relief, and an insulin-dependent diabetic. Continuous catheter lumbar plexus and sciatic nerve blocks are chosen, along with supplemental intravenous narcotics and sedatives as needed. A conventional rectangular thigh tourniquet is placed for surgical hemostasis. After limb exsanguination, the cuff pressure is set at 300 mm Hg. Surgery proceeds uneventfully, with a total tourniquet time of 2 hours. The catheters are removed the next day, and the patient is started on enoxaparin for deep venous thrombosis (DVT) prophylaxis. Subsequently, she complains of numbness and weakness in her left leg.

The ultrastructural cellular changes are detectable after 30 minutes of ischemia but are reversible with ischemia lasting 2 hours or less. High-energy intracellular phosphate depletion occurs more gradually. However, injury to the Na+, K+-ATPase–dependent ion exchange pump causes extracellular potassium leak and intracellular edema. The sarcoplasmic reticulum loses glycogen, the mitochondria swell, and myelin degeneration occurs. Skin. Trauma to the skin can be caused by pressure necrosis due to inadequate padding between the skin and tourniquet or friction burns due to movement of a poorly applied tourniquet. Obese patients with redundant upper extremity skin folds are at increased risk for skin injury. Chemical burns from skin preparation solutions have been reported. These solutions soak into the padding under the tourniquet, and under pressure, this continuous contact with the skin can cause full-thickness burns. Muscle. Myocytes are very sensitive to compression and ischemia. Injury is more severe with lengthy tourniquet inflation or high pressure. Usually, injury is greatest beneath the tourniquet. Associated ischemia, edema, and microvascular congestion cause the post-tourniquet syndrome. This includes stiffness, pallor, and weakness (not paralysis), with subjective extremity numbness. Nerve. Mechanical pressure compresses nerves directly beneath the tourniquet cuff. Shear forces at the proximal and distal edges of the cuff also cause nerve injury ranging from paresthesia to complete paralysis. Distal ischemia plays a lesser role. The contribution of tourniquet time to the development of nerve injury is unclear. Paralysis has been reported with as little as 30 minutes of tourniquet inflation. Lower extremity nerve injury usually involves the sciatic nerve. The upper extremity is more vulnerable to injury. Radial injury is more frequent than ulnar or median nerve injury. Localized nerve injuries tend to be neurapraxic (i.e., without evidence of structural damage to the axon or perineurium). If so, the prognosis for full recovery is good. In contrast, axonotmesis (i.e., damage to the axon but not to the perineurium) causes nerve degeneration distal to the injury and takes longer to recover. Rarely, a permanent nerve deficit occurs. 867

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Vasculature. Arteries and veins, especially prosthetic grafts (e.g., arteriovenous fistulas, arterial bypass grafts), are susceptible to traumatic injury from mechanical compression. Although direct arterial injury is rare (0.03% to 0.14% incidence), fractured atherosclerotic plaque may cause localized thrombosis or embolize distally to cause ischemia. Although DVT is a known and common complication of lower limb surgery, tourniquets bear no relation to deep venous stasis and thrombus formation. Rather, systemic hypercoagulability is due to catecholamine release and platelet aggregation caused by tourniquet-related or surgical pain. In contrast, active bleeding after tourniquet release may be aggravated by ischemia-caused tissue plasminogen activator release and fibrinolysis.

a transient increase in minute ventilation by 50% for about 5 minutes to maintain normocapnia. Hyperventilation can prevent the associated increase in cerebral blood volume and intracranial pressure that might otherwise be detrimental to a patient with a severe head injury.

SYSTEMIC EFFECTS

Core Body Temperature. Most patients remain normothermic. Tourniquet inflation above arterial pressure transiently increases core body temperature, and tourniquet deflation transiently decreases it. The decline in core body temperature due to the return of hypothermic venous blood from the previously occluded limb into the systemic circulation is usually 0.7°C or less.

Systemic effects occur with tourniquet inflation and deflation. The intensity and duration of these derangements are directly proportional to the length of tourniquet inflation time and the size and number of tourniquet-isolated limbs. Autotransfusion. Limb exsanguination and rapid tourniquet inflation shunt blood into the central circulation (autotransfusion) and increase systemic vascular resistance. As much as 800 mL of blood is autotransfused with the simultaneous inflation of bilateral thigh tourniquets. This causes a transient increase in central venous pressure and systolic blood pressure, which gradually returns to baseline. In patients with compromised left ventricular function, congestive heart failure due to circulatory overload and cardiac arrest has been reported. Hypertension. Tourniquet-induced hypertension is common. Patients develop an increase in heart rate and systolic and diastolic blood pressures within 30 to 60 minutes of inflation, which persists until tourniquet deflation. This increase in mean arterial pressure has been attributed to (1) an acute increase in systemic vascular resistance with removal of a vascular bed; (2) limb exsanguination before tourniquet cuff inflation, which causes acute central blood volume expansion; and (3) pain associated with tourniquet compression and limb ischemia. The pain mechanism is not well understood, but it may involve the activation of type C nerve fibers. In turn, these activate NMDA receptors, leading to a hypertensive response. This response is less common and less intense under regional anesthesia compared with general anesthesia. Hypotension. Tourniquet deflation results in reduced blood pressure and central venous pressure secondary to a shift of blood volume back into the extremity and postischemic reactive vasodilatation. Also, with reperfusion, metabolites released from ischemic areas into the systemic circulation have the potential to cause myocardial depression and further reduce blood pressure. Hypotension is usually self-limited (≤15 minutes). Hypercapnia. End-tidal carbon dioxide (ETCO2) increases after tourniquet release owing to the efflux of hypercapnic venous blood from the ischemic limb into the systemic circulation. The peak ETCO2 increase occurs by 1 minute, and it returns to baseline by 10 to 13 minutes. Spontaneously breathing patients compensate by increasing their respiratory rate. However, those with controlled ventilation require

Metabolic Acidosis. Elevated serum lactate and reduced pH are observed for approximately 30 minutes after reperfusion of the isolated extremity. Blood Oxygen Saturation. Arterial oxygen saturation usually remains normal. However, as large volumes of deoxygenated blood are returned to the central circulation after tourniquet release, mixed venous oxygen saturation is transiently decreased.

Deep Venous Thrombosis, Pulmonary or Systemic Thromboembolism. These potentially devastating complications may occur with lower limb trauma and surgery, but rarely intraoperatively. Although studies with transesophageal echocardiography have shown up to a 70% incidence of right atrial embolization following tourniquet release, most emboli are small and are unlikely to cause major morbidity. However, this risk is increased in patients with hypercoagulable states and thrombus due to trauma or prolonged immobilization. In this case, it is believed that thrombus becomes dislodged during limb exsanguination or with tourniquet inflation. Catastrophic events such as DVT or pulmonary or systemic thromboembolism are more likely to occur postoperatively during rehabilitation. Use of enoxaparin for DVT prophylaxis has dramatically reduced the incidence of fatal pulmonary embolism. However, given that pulmonary and cerebral emboli have been reported during both inflation and deflation of tourniquets, anesthesiologists should be especially vigilant during these times. Attention should be focused on the patient’s neurologic status and any sudden, unexpected changes in arterial oxygen saturation and ETCO2. Significant pulmonary emboli result in an acute reduction in ETCO2, with tachycardia and hypotension, followed by hypoxemia and myocardial ischemia. Right ventricular dysfunction may also be observed (also see Chapters 215 to 217).

Recognition Given the increased use of regional blocks for lower extremity surgery, which significantly reduces postoperative pain scores and permits earlier ambulation, how does one differentiate a nerve injury related to use of a tourniquet from one related to regional anesthesia? Post-tourniquet syndrome is the most common problem associated with tourniquet use. Mild weakness, diffuse subjective numbness, swelling, stiffness, and slight pallor of the affected limb usually develop several hours after tourniquet deflation. Also, ischemic injury to muscle is distinguished from nerve injury by normal nerve conduction studies and

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Risk Assessment Both tourniquet-related and anesthesia-related nerve injuries resolve in approximately the same time frame, so cause is usually not important. However, for anesthesiologists working in high-risk malpractice environments, the possibility of nerve injury may be a consideration when choosing the type of anesthesia for patients at high risk for tourniquet-induced neurologic injury. Factors that may increase the risk of complications with tourniquet use are listed in Table 218-1. The safe upper limits for inflation time and pressure for arterial tourniquets are controversial. Nerves appear most susceptible to mechanical pressure and muscles to prolonged ischemia. Most clinicians recommend the shortest tourniquet inflation time possible, with a limit of 2 hours in healthy patients. For surgical procedures exceeding 2 hours, the tourniquet should be deflated every 2 hours to allow 10 minutes of limb reperfusion. Muscle injury, especially beneath the cuff, can occur even with short tourniquet times. Elderly trauma patients and those with peripheral vascular disease are most susceptible to muscle injury. Therefore, the lowest pressure needed to produce arterial occlusion should be used. Van Roekel and Thurston recommend that in a normotensive, average-size adult patient, an inflation pressure of 200 mm Hg should be adequate for the upper limb and 250 mm Hg for the lower limb. The tourniquet pressure

Table 218–1

■

Extremity Tourniquets

869

Factors That May Increase the Risk of Tourniquet-Related Complications

Tourniquet Related Equipment not regularly serviced and inspected for pressure accuracy Bilateral tourniquet use Revisions, malignancies, or other surgeries requiring longer tourniquet times

Vascular and Metabolic Diabetes Peripheral vascular disease Obesity Raynaud’s disease Prosthetic vascular grafts

Coagulopathies Sickle cell disease and trait Preexisting coagulopathies Patients at increased risk for deep venous thrombosis

Other Peripheral neuropathy Prolonged immobilization before surgery Traumatized limb with extensive soft tissue injury Localized infection Latex allergy (must use latex-free tourniquets and tubing)

should be maintained 50 to 150 mm Hg above the systolic pressure. The application of wider, curved cuffs permits the use of lower inflation pressures to produce arterial occlusion.

Implications Most tourniquet-related compressive nerve injuries are neurapraxic and resolve completely over a few hours to days without specific therapy. With nerve disruption, recovery can take weeks or months, but incomplete recovery is rare. Also, there is the potential for a causalgia syndrome to develop, with significant disability. Weakness and swelling due to post-tourniquet syndrome can interfere with rehabilitation and wound healing. Pressure-related skin injuries increase the risk of infection. Compartment syndromes pose a significant risk for ischemic necrosis and permanent contracture of the involved muscle groups. Unrecognized arterial insufficiency can lead to necrosis of soft tissue and bone. In patients given regional anesthesia, tourniquet pain and associated hypertension may require deep sedation with propofol or ketamine or even general anesthesia. Opiates alone are usually ineffective. Hypotension with tourniquet deflation is expected and usually self-limited. If not, a fluid challenge and small doses of vasopressors are used until the hypotension resolves. Massive pulmonary embolism causes hemodynamic instability, right ventricular strain, and cardiovascular collapse. Nonfatal embolism may result in hypoxemia due to ventilation-perfusion mismatching, myocardial infarction, or stroke due to paradoxical cerebral embolism with intracardiac shunts.

OTHER SURGICAL SUBSPECIALTIES

the presence of elevated creatine kinase (MM) enzymes and myoglobinuria. If the tourniquet has produced a compressive nerve injury, it may be difficult to distinguish this injury from one related to regional block. However, as noted earlier, tourniquetrelated nerve injury can range from paresthesia to complete paralysis. The sciatic nerve is often involved in lower extremity surgery, and radial nerve injury is more common than ulnar or median nerve injury with upper extremity surgery. Further, localized tourniquet-related nerve injury is often neurapraxic, in which case the prognosis for full recovery is good. In contrast, injuries to nerves caused by needles or indwelling catheters may involve damage to the axon or perineurium. Brief neurologic assessment of the affected extremity should follow surgery. Evidence of motor and sensory deficits requires neurologic consultation and nerve conduction studies to determine the site of the defect. With regional anesthesia, there may be a delay in the diagnosis of nerve injury, especially if indwelling catheters are used for postoperative analgesia. Acute compartment syndrome has been observed immediately after surgery or after a delay of several hours. The limb is typically swollen, muscles are stiff, and pain is more severe than the physical findings would suggest. Neurologic dysfunction is a common sequela. Confirmation is by measurement of intracompartmental pressures. Postoperative causalgia presents weeks or months after surgery. Burning pain and autonomic dysfunction develop, followed by dystrophic changes in the extremity. Skin injuries are usually evident upon tourniquet cuff removal. Ecchymoses, persistent erythema, bullae formation, or skin burns may be present. Vascular insufficiency due to arterial injury should be suspected when cuff deflation does not result in reperfusion of all or part of the extremity.

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MANAGEMENT

●

●

Nerve injuries that do not resolve within 48 hours should be referred to a neurologist for assessment and follow-up nerve conduction studies. Post-tourniquet syndrome is managed with elevation of the extremity, monitoring of wound healing, and physical therapy. Pressure-related skin injuries are treated as needed. Bullae or chemical burns require burn care. However, they may be avoided by applying a nonpermeable plastic barrier drape over the distal end of the tourniquet cuff before preparing the skin. Causalgia requires management by a comprehensive chronic pain management team, and early referral is essential. Compartment syndromes are a surgical emergency and require fasciotomy to decompress the affected muscle compartments. Arterial insufficiency of an extremity requires surgical revascularization or thrombolytic therapy. Diagnosis of intraoperative pulmonary emboli is facilitated with transesophageal echocardiography. Therapy for pulmonary emboli is supportive and includes controlled ventilation, oxygen, pressor support, and cardiopulmonary resuscitation if needed. Systemic anticoagulation, thrombolytic therapy, surgical thrombectomy, or thrombus removal by interventional radiology may be necessary in some patients. Cerebral emobilization is diagnosed with computed tomography scans, and therapy is directed by a neurosurgeon and neurologist.

PREVENTION Catastrophic complications are minimized by judicious patient selection. During screening of patients at high risk for DVT (prolonged immobilization, hypercoagulable state), if thrombus is detected, surgery should be postponed. However, screening all patients for right-to-left intracardiac shunts with contrast-enhanced transthoracic echocardiography is not cost-effective, and it is questionable whether the presence of a right-to-left intracardiac shunt would affect anesthetic or surgical management. Safety factors in the use of pneumatic tourniquets for hemostasis during hand surgery were first described in 1951, and Bruner’s 10 rules were subsequently revised by Braithwaite and Klenerman in 1996. Fortunately, most pneumatic tourniquet complications in extremity surgery are avoided by limiting maximum tourniquet pressure and tourniquet inflation time. Although there are no randomized, controlled, prospective clinical studies to provide us with evidence-based guidelines, there are sufficient animal studies and clinical data to make the following recommendations: ● ● ●

● ●

●

Carefully select patients preoperatively. Use a wide, low-pressure tourniquet cuff. Inflate tourniquets to the lowest pressure needed to prevent bleeding. Limit tourniquet ischemia time to 2 hours or less. Set maximum tourniquet pressure settings as follows: arm tourniquets, 50 to 75 mm Hg above the baseline systolic pressure; leg tourniquets, 75 to 100 mm Hg above the baseline systolic pressure. Ensure adequate padding beneath the tourniquet.

●

Use barrier techniques to prevent any skin preparation solutions from running underneath the tourniquet cuff. Alternate the use of two tourniquets. Ensure tourniquet reliability with regular maintenance checks.

There are other simple things that we can do to reduce tourniquet-related injuries, without waiting for advances in research and technology. Using the following general guidelines may result in tourniquet cuff pressures 30% to 50% lower than those currently used in routine clinical practice: ●

●

●

Use conical, tapered tourniquet cuffs instead of conventional rectangular cuffs. These can reduce limb occlusion pressure by as much as 23% compared with conventional cuffs. Also, they are more efficient at transmitting surface pressure to deep tissues because they more nearly conform to the shape of the extremity. Set tourniquet pressures by determining limb occlusion pressure with Doppler or portable ultrasonography. Then set tourniquet pressures 40 to 80 mm Hg above limb occlusion pressure. Subsystolic occlusion pressures can be generated with wider conical cuffs or with a cuff width–to–extremity circumference ratio greater than 0.5.

In the future, tourniquet-related injuries may be minimized and allowable tourniquet times extended with ischemic preconditioning of skeletal muscle, more frequent reperfusion intervals, or combined regional hypothermia and ischemic preconditioning. Finally, the recent availability of sustained-release epidural morphine compounds, along with general anesthesia, may offer the best of both worlds for anesthesiologists who wish to provide good postoperative analgesia without concern about possible postoperative neuropathies with peripheral nerve or plexus blocks, especially when extremity tourniquets will be used during surgery.

Further Reading Al-Ghamdi AA: Bilateral total knee replacement under tourniquet in a homozygous sickle cell patient. Anesth Analg 98:543-544, 2003. Braithwaite I, Klenerman L: Burns under tourniquets—Bruner’s ten rules revisited. J Med Def Unions 12:14-15, 1996. Bruner JM: Safety factors in the use of the pneumatic tourniquet for haemostasis in surgery of the hand. J Bone Joint Surg Am 33:221-224, 1951. Duffy PJ: The arterial tourniquet. Available at http://www.uam.es/ departamentos/medicina/anesnet/gtoa/hm1.html Iwama H, Kaneko T, Ohmizo H, et al: Circulatory, respiratory and metabolic changes after thigh tourniquet release in combined epidural-propofol anaesthesia with preservation of spontaneous respiration. Anaesthesia 57:588-592, 2002. Kam P, Kavanaugh R, Yoong F: The arterial tourniquet: Pathophysiological consequences and anaesthetic implications. Anaesthesia 56:53-54, 2001. Tredwell S, Wilmink M, Inkpen K, et al: Pediatric tourniquets: Analysis of cuff and limb interface, current practice, and guidelines for use. J Pediatr Orthop 21:671-676, 2001. Van Roekel HE, Thurston AJ: Tourniquet pressure: The effect of limb circumference and systolic blood pressure. J Hand Surg 10:142-144, 1985. Weiss SJ, Cheung AT, Stecker MM, et al: Fatal paradoxical cerebral embolization during bilateral knee arthroplasty. Anesthesiology 84:721-723, 1996.

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Complications of Spinal Surgery Michelle L. Lotto

OTHER SURGICAL SUBSPECIALTIES

Case Synopsis A 28-year-old woman with severe kyphotic deformity from a prior crush injury is undergoing T6 corpectomy with posterior spinal fusion and instrumentation. Before surgery, the patient is neurologically intact. During spinal instrumentation, the motor evoked potential (MEP) from the left gastrocnemius muscle and the cervical and cortical somatosensory evoked potentials (SEPs) from the left posterior tibial nerve are suddenly lost (Figs. 219-1 and 219- 2). Reversal of induced hypotension (85/55 mm Hg) to baseline pressure (120/60 mm Hg) does not improve the SEP or MEP responses. Some return of SEP amplitude is seen after removal of the spinal retractors, but the MEP remains depressed. The procedure is aborted because of the evolving neurologic deficit.

PROBLEM ANALYSIS Definition NEURAL INJURY Damage to neural structures is a dreaded consequence of spinal surgery. In addition to direct surgical injury to neuronal tissue, nerve injury can occur because of stretch, compression, or both. The mechanism underlying tension-related or ischemic nerve injury is increased intraneural pressure that reduces the cross-sectional area of the nerve and compromises its blood flow. Compression generates relative venous hypertension within the nerve sheath, necessitating an increase in the arterial pressure for adequate perfusion. Patients undergoing spinal surgery are at risk not only for surgical injury to the spinal cord but also for positionrelated injuries to the peripheral and, rarely, the optic nerves. Diabetes mellitus, alcohol abuse, vitamin deficiencies, malnutrition, renal disease, hypothyroidism, and emaciation can increase the risk for perioperative peripheral nerve injury.

Recognition Patients undergoing spinal procedures with general anesthesia do not manifest signs or symptoms of spinal cord injury unless the insult is extreme, such as cord transection with spinal shock. Neurophysiologic monitoring modalities, including SEPs, transcranial MEPs, and electromyography, are used to detect neurologic insult during spinal surgery. Intraoperative spinal cord monitoring is intended to reduce permanent neurologic deficits by allowing the early detection of impending neurologic injury and the implementation of corrective interventions. SEP monitoring provides a continuous evaluation of the somatosensory system through repetitive stimulation of a peripheral nerve and the recording of multiple responses obtained from the spinal cord and somatosensory cortex. Although SEP monitoring is useful for determining the integrity of the spinal cord during procedures that may cause overdistraction of the cord, it does not specifically reflect injury to the motor tracts. The ability of SEP monitoring to detect ischemic motor injury is significantly limited by the differential blood supply to the anterior and posterior spinal cord tracts.

HYPOTENSION Hypotension is a potentially serious complication of spinal surgery. Although hypovolemia is the most common cause of intraoperative hypotension, other causes are excessive depth of anesthesia, allergic reactions, pulmonary embolism, and cardiovascular dysfunction. HEMORRHAGE

Left med. gastroc.

Right med. gastroc.

13:01 13:25 13:26 13:30

Significant blood loss can be a major complication of certain spinal procedures. Bone decortication and epidural venous bleeding are the chief causes of blood loss during spinal surgery. The surgical team should be prepared for the possibility of massive blood transfusion in patients undergoing corpectomy, multilevel spinal instrumentation, and fusion surgery, especially when it involves the thoracolumbar spine.

13:33 13:34 13:34

50 uV 20 msec

13:35

Figure 219–1 ■ Sudden loss of motor evoked potential recorded from the left gastrocnemius muscle.

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Figure 219–2 ■ Loss of the left subcortical and cortical somatosensory evoked potentials (far right panel) with stimulation of the left posterior tibialis nerve.

MEP monitoring is a newer modality that offers direct monitoring of the motor system through transcranial electrical stimulation of the motor cortical structures and recording of myogenic responses in the target muscle groups. Although MEP monitoring is more specific to motor injury than is SEP, MEP shows greater sensitivity to anesthetic agents and a much larger variability in amplitude over time than does SEP. Newer transcranial stimulation techniques involving multiple trains of higher-intensity electrical stimuli have improved the reliability of MEP monitoring in patients under general anesthesia. However, MEP amplitudes are somewhat variable over time. Therefore, the criteria used to determine a significant change in MEP can vary among centers. However, generally accepted criteria for significant changes in SEP and MEP are as follows: ●

●

SEP ● 50% decrease in amplitude ● 10% increase in latency MEP ● Loss in amplitude greater than 80% ● Complete loss of the potential

Risk Assessment SEP monitoring is most commonly used during surgical correction of spinal deformities. Although it has been used in a variety of spinal procedures, the benefit of SEP monitoring in conditions other than kyphoscoliosis repair is less well established. There is mounting evidence that MEP monitoring may provide more specific and sensitive detection of neurologic injury in many types of spinal surgeries, including scoliosis repair, spinal cord tumor resection, and spine stabilization. However, the sensitivity of MEPs to anesthetic agents, as well as the difficulty in obtaining MEPs in patients with preexisting motor deficits, makes it a more technically challenging monitoring modality than SEPs. However, changes can occur in both modalities in response to alterations in physiology and pharmacology, as well as to interference from electrical devices in the operating room. Factors that interfere with SEP monitoring include the following: ● ●

Anesthetic agents (Table 219-1) Hypotension

● ● ● ●

Hypoxemia Hypothermia Alkalosis or acidosis Cold surgical irrigation

Implications Failure to heed significant changes in SEPs or MEPs may lead to permanent neurologic injury. In the case synopsis, changes in both SEPs and MEPs resulted in halting the surgical procedure, thereby preventing possible irreversible neural injury and paralysis.

Table 219–1

■

Effect of Anesthetics on Cortical Somatosensory and Motor Evoked Potentials

Anesthetic

SEP Amplitude

SEP Latency

MEP Amplitude

↓ ↓↓

→ ↑

↓ ↓↓↓

↑ ↑↑

↓↓↓ ↓↓↓

↓↓ ↓↓ ↓↓

↑ ↑ →

↓↓↓ ↓↓↓ ↓↓

↑↑ →↑ ↓ ↓↓↓

↑ ↑ ↓ ↑↑

→ →↓ ↓↓ ↓↓↓

↓↓ ↑

↑ →

↓ ↓

Inhalational Agents Desflurane 0.5 MAC 1 MAC Isoflurane 0.5 MAC 1 MAC Sevoflurane 0.5 MAC 1 MAC N2O (60%)

Intravenous Induction Agents Etomidate Ketamine Propofol Thiopental

Adjuncts Benzodiazepines Opioids

→, no change; ↓ or ↑, 10%-20% change; ↑↑ or ↓↓, 30%-50% change; ↑↑↑ or ↓↓↓, >50% change. MAC, minimal alveolar concentration; MEP, motor evoked potential; N2O, nitrous oxide; SEP, somatosensory evoked potential.

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MANAGEMENT

PREVENTION Careful attention to patient positioning and SEP and MEP monitoring for neural injury can help prevent spinal cord injury. Several methods are used to reduce blood loss and the need for blood transfusions or component therapy.

Monitoring To optimize the detection of spinal cord injury, the anesthesia team should try to maintain a constant pharmacologic and physiologic state. Both SEP and MEP monitoring modalities may show false-positive changes in response to sudden changes in anesthetic depth, as well as acute physiologic changes, including hypotension, hypoxia, and hypothermia. MEPs show greater dose-dependent sensitivity to both volatile and intravenous anesthetic agents than do SEPs, and complete muscle relaxation must be avoided. Continuous intravenous infusions of propofol and opioids provide fairly stable monitoring conditions for both SEPs and MEPs. Abrupt changes in anesthetic depth or intravenous bolus

873

doses of analgesics should be avoided at points during spinal surgery when spinal cord injury is most likely to occur.

Patient Positioning Positioning for spinal surgery can present many challenges for the anesthesiologist. Prone positioning is associated with twice as many claims for peripheral nerve injuries as are other surgical positions. Vulnerable sites (e.g., bony prominences, axilla [brachial plexus], elbow [ulnar nerve], face, breasts) should be padded to disperse pressure. Unfortunately, meticulous attention to padding does not guarantee avoidance of injury. In addition to debilitating peripheral nerve injury, postoperative visual loss has emerged as a rare but devastating complication of spinal surgery. Multiple mechanisms may contribute to postoperative blindness; however, ischemic optic neuropathy is the most common cause in patients having spinal surgery. Risk factors for postoperative visual loss are listed in Table 219-2. Postoperative blindness may occur despite the use of positioning techniques that avoid eye compression, such as the use of Mayfield tongs or special prone face pillows. Early blood transfusion, maintaining mean arterial pressure greater than 80% of baseline, and head-up positioning have been recommended to avoid perioperative blindness. However, there are no controlled trials to support the efficacy of these preventive measures.

Blood Loss and Transfusion Requirements Anesthesiologists have several techniques available for reducing blood loss and transfusion requirements, including induced hypotension, autologous blood salvage, and normovolemic hemodilution. INDUCED (ELECTIVE) HYPOTENSION Induced hypotension has been shown to reduce blood loss and transfusion requirements during elective spinal surgery. Sodium nitroprusside, nitroglycerin, or β-blockers are given intravenously, possibly with continuous positive airway pressure and deep inhalation anesthesia, to initiate and maintain induced hypotension. Recently, nicardipine, an arterioselective vasodilator, has gained favor over sodium nitroprusside and nitroglycerin. The former is an arterial and venous vasodilator, and the latter is a venodilator, so both can reduce venous return and cardiac preload; thus, both have an increased potential to cause untoward hypotension compared with nicardipine. Nicardipine is compatible with β-blockers, and continuous positive airway pressure

Table 219–2

■

Risk Factors for Postoperative Blindness

Patient Factors

Intraoperative Events

Hypertension Diabetes mellitus Smoking history Peripheral vascular disease

Anemia (hematocrit ≤25) Hypotension Prolonged surgical time Prone positioning

OTHER SURGICAL SUBSPECIALTIES

Detection of neurologic injury and timely initiation of corrective measures require good communication between the neurophysiologic monitoring personnel and the anesthesia and surgical teams. Changes in anesthetic depth or bolus dosing of medications should be avoided during periods of high spinal cord risk, such as spinal distraction. When significant changes in spinal potentials occur, technical error should be ruled out, and the surgeon should be alerted. Reduced mean arterial pressure and anemia or hypoxia increase the risk for spinal cord injury. Thus, measures to correct these conditions can improve spinal cord perfusion and oxygenation. If the response to therapy is inadequate, and significant changes in SEPs or MEPs persist, the surgical team must evaluate the patient for procedure-related complications and then make the necessary alterations to reverse an evolving insult. When using SEPs as the sole monitoring modality, evaluation should include a wake-up test, during which the patient is allowed to emerge from anesthesia so that the motor system can be evaluated. Although the wake-up test is the gold standard for evaluation of the spinal cord, the use of both MEPs and SEPs may reduce the need for this assessment. Treatment of hypotension first requires assessment of the cause. Blood loss and hypovolemia are the most common causes of hypotension during spinal cord surgery, and replacement of fluids is adequate treatment in most situations. Positioning may contribute to hypovolemia when patients are placed on the Jackson table or in the kneeling position for spinal surgery. In these positions, venous return may be reduced by the sequestration of blood volume in the capacitance vessels of the abdomen and legs. Pharmacologic treatment (e.g., phenylephrine) may be necessary to augment arterial blood pressure until fluid resuscitation is adequate. The requirement for blood or blood product transfusions must be assessed on an individual basis.

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can be added if further blood pressure reduction is needed. Although animal experimentation suggests that nitroglycerin is best for preserving spinal cord blood flow during hypotension, this has not been confirmed in humans. The use of induced hypotension is based on clinical judgment, taking into account the overall physical status of the patient and the type of spinal surgery to be performed. Extreme caution should be used in the induction of hypotension in patients with significant spinal cord compression. Spinal injury impairs the normal autoregulatory process of the spinal cord vessels. External compression related to vertebral displacement or surgical retraction further decreases spinal blood flow. Hypotension has been associated with worse neurologic outcomes after traumatic spinal cord injury.

of blood is removed from the patient in the operating room before or at the beginning of surgery and stored. It is then transfused back into the patient after most of the expected surgical blood loss has occurred. As blood is removed, it is replaced with colloid (1:1), crystalloid (3:1), or both. Platelet function and coagulation factors are preserved. Excessive hemodilution can reduce oxygen transport and cause a decrease in systemic vascular resistance and hypotension. In addition, it has been suggested that the combination of hypotension and low hemoglobin may contribute to the risk of optic ischemia and postoperative blindness in prone spinal surgery patients. Contraindications to acute normovolemic hemodilution include severe cardiovascular, pulmonary, renal, or hepatic dysfunction and coagulopathy.

INTRAOPERATIVE AUTOLOGOUS BLOOD SALVAGE

Further Reading

Autologous blood salvage is a useful tool for preserving the blood lost during spinal surgery, but it can be associated with coagulopathy. Salvaged blood is autotransfused as needed after it has been washed or filtered, based on the type of equipment used. A micropore filter should be used to remove microaggregates, bone, and fat particles. However, fibrinolysis, inhibition of the clotting system, and possibly disseminated intravascular coagulation may occur with filtration-type autotransfusion. The removal of soluble products by cell washing systems can also induce coagulopathy, as well as the loss of coagulation factors and platelets. Purulent infection and malignancy were relative contraindications to autologous blood salvage in the past, but use of these systems is possible in these conditions with appropriate filtration. ACUTE NORMOVOLEMIC HEMODILUTION Acute normovolemic hemodilution is another method of reducing intraoperative blood loss. A predetermined amount

Banoub M, Tetzlaff J, Schubert A: Pharmacologic and physiologic influences affecting sensory evoked potentials: Implications for perioperative monitoring. Anesthesiology 99:716-737, 2003. Goto T, Crosby G: Anesthesia and the spinal cord. Anesthesiol Clin North Am 10:493-519, 1992. Grundy BL, Nash CL, Brown RH, et al: Deliberate hypotension for spinal fusion: Prospective randomized study with evoked potential monitoring. Can Anaesth Soc J 29:452-462, 1982. Kroll DA, Caplan RA, Posner K, et al: Nerve injury associated with anesthesia. Anesthesiology 73:202-207, 1990. Lauer KK: Visual loss after spine surgery. J Neurosurg Anesthesiol 16:77-79, 2004. Lotto ML, Banoub M, Schubert A: Effects of anesthetic agents and physiologic changes on intraoperative motor evoked potentials. J Neurosurg Anesthesiol 16:32-42, 2004.

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Jeffrey L. Lane Case Synopsis

PROBLEM ANALYSIS Definition Respiratory insufficiency is defined as the inability of the patient’s lungs to provide sufficient oxygen (O2) or expel sufficient carbon dioxide (CO2) to satisfy whole body metabolic demands. In the postoperative setting, this can be related to (1) airway obstruction, (2) arterial hypoxemia, or (3) hypercarbia (Table 220-1). Airway obstruction is often mechanical, caused by occusion of the posterior oropharynx by the tongue. Hypoxemia is defined as a reduction in arterial oxygen tension (PaO2) below 60 mm Hg. It can be the result of atelectasis, pulmonary edema, pulmonary aspiration, pneumothorax, or pulmonary embolism. The differential diagnosis of hypoxemia includes decreased minute ventilation, low fraction of inspired oxygen (FiO2), ventilation-perfusion mismatch, and block of O2 diffusion across the alveolar membrane. Arterial oxygenation (PaO2 in mm Hg) declines with age. When the subject is breathing room air, it can be estimated using this formula: 100 – (0.3 × age). Hypercarbia is defined as an increase in arterial CO2 tension (PaCO2) above 45 mm Hg. It results from decreased CO2 elimination (hypoventilation, respiratory depression, lung pathology that increases dead space), increased CO2 production (fever, sepsis, shivering, thyrotoxicosis, malignant hyperthermia), or CO2 rebreathing. In the PACU, hypercarbia most often indicates respiratory depression from opiates or residual anesthetics. In contrast to PaO2, PaCO2 does not change with age.

Recognition AIRWAY OBSTRUCTION Airway obstruction presents with a combination of labored breathing pattern, chest wall retraction, nasal flaring,“snoring” or “grunting” noises (partial obstruction), absence of breath sounds (complete obstruction), paradoxical movement of

SPECIAL TOPICS

A 53-year-old morbidly obese man is recovering in the postanesthesia care unit (PACU) after undergoing an open Nissen fundoplication. He has a history of smoking. A left subclavian central line was placed without complication shortly after the induction of anesthesia. The intraoperative course was unremarkable, and the patient was extubated in the operating room. Shortly after arriving in the PACU, the patient becomes dyspneic. The oxygen saturation is 90%, heart rate is 110 beats per minute, blood pressure is 168/98 mm Hg, and respiratory rate is 32 breaths per minute.

the chest wall (e.g., “rocking boat” or “seesaw” respirations), stridor, wheezing, and patient anxiety. Cardiovascular manifestations include hypertension and tachycardia. As mentioned earlier, postoperative airway obstruction is usually due to tongue occlusion (partial or total) of the posterior oropharynx caused by opioids or residual anesthetics. Such occlusion may or may not be relieved by a head tilt or jaw thrust or by the placement of a nasopharyngeal airway. If these maneuvers do not relieve the occlusion, other causes must be considered (see Table 220-1). Laryngospasm is usually seen immediately after extubation in the operating room or PACU. It results from stimulation of the glottal structures by secretions or airway equipment in a lightly anesthetized patient. It is usually characterized by a high-pitched inspiratory stridor (“cooing” or “crowing”) or by the absence of sounds in cases of complete closure. Airway edema from surgical trauma, patient positioning, or airway instrumentation may cause airway obstruction. Procedures that increase this risk include oral or extensive head and neck surgery and direct manipulation or instrumentation of the airway (e.g., vocal cord biopsy, bronchoscopy). Prolonged Trendelenburg or prone (or combined) positioning can lead to extensive airway edema. Further, patients with anticipated or unanticipated difficult airway management and prolonged airway instrumentation are at increased risk for airway edema. Residual neuromuscular blockade is recognized by signs of inadequate neuromuscular relaxant reversal, including the presence of fade with tetanus and less than four out of four twitches on train-of-four stimulation. Clinically, the patient exhibits inadequate head lift (<5 seconds) and rapid, shallow breathing. Wound hematoma following neck surgery (e.g., carotid endarterectomy, anterior cervical diskectomy, thyroidectomy) must be recognized quickly because it can lead to rapid airway obstruction and death. PACU nursing staff must be trained to recognize an expanding neck hematoma and immediately notify the anesthesiologist and surgeon for possible reintubation and wound drainage. In addition, patients 877

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Causes of Postoperative Respiratory Insufficiency

Airway Obstruction Mechanical (relaxed tongue) Airway edema Laryngospasm Residual neuromuscular block Foreign body aspiration Neck hematoma Vocal cord paralysis

Hypoxemia Atelectasis Pulmonary edema Pulmonary embolism Pneumothorax Pulmonary aspiration Bronchospasm

Hypercarbia Decreased CO2 elimination Hypoventilation Respiratory depression High dead space Increased CO2 production Fever or sepsis Shivering Malignant hyperthermia Thyrotoxicosis Overfeeding with total parenteral nutrition CO2 insufflation Bicarbonate administration CO2 rebreathing

having neck surgery may have airway obstruction due to vocal cord paralysis, which presents similarly to laryngospasm. HYPOXEMIA Hypoxemia in patients recovering from general anesthesia is common and is usually relieved by supplemental O2. In today’s PACU, hypoxemia is usually recognized by low oxygen saturation (SpO2) measured by peripheral pulse oximetry. This can be confirmed by direct arterial blood gas measurements, with low PaO2 values. Manifestations of hypoxemia are (1) pulmonary (increased respiratory rate and pulmonary artery pressure due to hypoxic pulmonary vasoconstriction), (2) cardiovascular (increased blood pressure, tachycardia, and possibly arrhythmias), and (3) central nervous system signs (confusion, restlessness, combativeness, obtundation). When SpO2 does not improve with supplemental O2, other causes of hypoxemia must be ruled out. Atelectasis is the most common cause of low postoperative SpO2 values. General anesthesia causes a decrease in lung volumes (i.e., tidal volume, vital capacity, functional residual capacity). This can persist for up to 1 week postoperatively. General anesthesia also reduces chest wall and pulmonary compliance and inspiratory muscle tone. Further, it displaces the diaphragm in a cephalad direction. This leads to airway closure in highly perfused, dependent areas of the lung, increasing intrapulmonary shunt. Postoperative pulmonary edema usually manifests as hypoxemia, tachypnea, and dyspnea. It is confirmed by chest auscultation (bibasilar rales) and chest radiograph (cephalization of the pulmonary vasculature). Pulmonary edema

can be classified as cardiogenic or noncardiogenic. Cardiogenic (or hydrostatic) pulmonary edema is commonly due to overhydration (positive intraoperative fluid balance >1500 mL) or cardiac dysfunction (myocardial ischemia or infarction, cardiomyopathy, severe hypertension, valvular stenosis). Cardiogenic pulmonary edema leads to high central venous and pulmonary capillary wedge pressures, with or without decreased urine output. Noncardiogenic (permeability) pulmonary edema occurs with acute respiratory distress syndrome and aspiration pneumonitis. Damage to alveolar cells allows fluid to transmigrate (“leak”) into the alveolar space, causing pulmonary edema. With this type of pulmonary edema, central venous and pulmonary artery pressures are usually normal. Pulmonary embolism must always be considered in the setting of postoperative hypoxemia. Air, fat, or thrombotic emboli may lodge in the pulmonary arterial circulation to cause dyspnea, tachypnea, tachycardia, hypotension, and increased venous pressure and alveolar dead-space ventilation. The last manifests as an increased PaCO2 to end-tidal CO2 gradient. In the PACU, pneumothorax may be a cause of hypoxemia in patients with recent central line placement, rib fractures, intercostal blocks, or surgery near or involving the diaphragm (e.g., liver resection, nephrectomy, splenectomy, hiatal hernia repair, esophageal resection, upper stomach surgery). Signs and symptoms include dyspnea, tachypnea, unequal breath sounds, high peak inspiratory pressures, and possibly hypotension due to tension pneumothorax. Chest radiographs showing partial to complete lung collapse confirm the diagnosis. HYPERCARBIA Hypercarbia (hypoventilation) is common after general anesthesia. In most instances, it is mild and of no major consequence. Respiratory acidosis due to moderate hypercarbia (PaCO2 >50 mm Hg) manifests with sympathomimetic signs and symptoms: hypertension, tachycardia, headache, nausea, sweating, and agitation. Severe hypercarbia (PaCO2 >80 mm Hg) can result in somnolence (CO2 narcosis), arrhythmias, and direct myocardial depression. If hypercarbia is suspected, arterial blood gas determinations can confirm the diagnosis. The next step is to determine the cause of hypoventilation. Drugs are the most common cause of postoperative respiratory depression with hypoventilation. Residual inhaled anesthetics and intravenous or neuraxial opioids are the most common offenders in PACU settings. Inhaled anesthetics usually cause a rapid, shallow breathing pattern, whereas opioid-induced respiratory depression results in a slow respiratory rate in association with large tidal volumes and pinpoint pupils. “Splinting” occurs when inspiratory effort is retarded by significant incisional pain, abdominal distention, or tight abdominal dressings. It occurs most often after upper abdominal or thoracic surgery and may lead to hypoventilation and hypercarbia. Residual neuromuscular blockade is another cause of hypoventilation in the PACU. It results from inadequate reversal, overdose, pharmacologic interactions (e.g., antibiotics, magnesium), altered pharmacokinetics (e.g., hypothermia,

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renal or hepatic dysfunction), or metabolic factors (e.g., hyperkalemia and acidosis). The clinical diagnosis is made by the inability of a conscious patient to maintain a 5-second head lift or by the use of a nerve stimulator in an unconscious patient.

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Table 220–2

● ●

Hypoxemia

Hypercarbia

Pulmonary

Tachypnea Pulmonary vasoconstriction

Cardiac

Early Tachycardia Hypertension Arrhythmias Late Bradycardia Hypotension Cardiac arrest Restlessness Combativeness Confusion Obtundation Increased ICP Metabolic lactic acidosis

Tachypnea Pulmonary vasoconstriction Bronchodilatation Hypertension Tachycardia Arrhythmias

● ● ● ● ●

Preoperative pulmonary function tests are useful for predicting postoperative pulmonary dysfunction only after pulmonary resection; in other situations, they do not predict postoperative pulmonary complications. For patients with one or more of the preceding risk factors, anesthetists must strongly consider delaying tracheal extubation until there has been satisfactory progress with temporary mechanical ventilation and weaning (i.e., satisfactory unassisted ventilation and oxygenation).

Implications Postoperative respiratory insufficiency can lead to serious patient morbidity and even death. Pulmonary complications are the most common serious postoperative complications, and they must be recognized and dealt with expeditiously to prevent adverse patient outcomes. Both hypoxemia and hypercarbia have detrimental systemic effects (Table 220-2). Hypertension, tachycardia, tachypnea, and arrhythmias place cardiac patients at increased risk for myocardial ischemia and infarction; this risk is increased even further with anemia (due to intraoperative blood loss) or shivering (due to altered temperature regulation). Patients with underlying neurologic disease are at even greater risk, because hypoxemia and hypercarbia alter mental status and increase intracranial pressure.

MANAGEMENT As in most anesthetic emergencies, management of postoperative respiratory insufficiency begins with evaluation and establishment of a patent airway. In patients with mechanical airway obstruction, supplemental O2 should be given while head-tilt and jaw-thrust maneuvers are performed to help displace the tongue anteriorly. Also, an oral or nasal airway can help alleviate any tongue-related obstruction. Use of a nasal airway is preferred in semiconscious or awake patients, owing to less discomfort (gagging) and better tolerance

Neurologic

Metabolic

Increased ICP Obtundation

Respiratory acidosis Hyperkalemia

ICP, intracranial pressure.

(unlikely to provoke partial or complete laryngospasm). If these measures do not alleviate the obstruction, laryngospasm must be suspected. If this is the case, gentle positivepressure mask ventilation may be effective. In many cases, however, a muscle relaxant must be administered, followed by reintubation. Minor upper airway edema is usually relieved by maintaining the patient in a semisitting (semi-Fowler) position, followed by the use of humidified gases, intravenous steroids (e.g., hydrocortisone, dexamethasone), and racemic epinephrine. If these conservative measures fail, immediate intubation and mechanical ventilation are necessary. In patients recovering from neck surgery who develop respiratory insufficiency, neck hematoma must be considered, with planning and setup for immediate drainage and possible intubation. In fact, early reintubation may prevent a lethal complication. A rapidly expanding neck hematoma can distort airway anatomy and make airway management extraordinarily difficult. Hypoxemia management starts with O2 via a nasal cannula or facemask. Hypoxemia in the PACU is usually relieved with O2 concentrations greater than 50%. Short-term therapy with 100% O2 by facemask may be necessary. If higher inspired O2 concentrations are needed to maintain PaO2 greater than 60 mm Hg, more aggressive treatment (e.g., continuous positive airway pressure by mask or intubation and mechanical ventilation) is required. After ensuring adequate oxygenation, treatment is directed toward the cause. A chest radiograph may reveal pulmonary edema, infiltrates, or pneumothorax. Diuretics are given for pulmonary edema. Significant pneumothorax requires early chest tube placement. For bronchospasm, aerosolized bronchodilators are indicated. Bronchoscopy may be necessary to remove pulmonary secretions and mucous plugs. Hypercarbia management is also directed toward the underlying cause. Often, simply encouraging the patient to breathe more vigorously is sufficient to relieve hypercarbia

SPECIAL TOPICS

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Surgical site (upper abdominal, thoracic) Smoking Underlying chronic obstructive pulmonary disease or asthma Emergency surgery Anesthesia time longer than 180 minutes Advanced age Obstructive sleep apnea Morbid obesity

Effects of Hypoxemia and Hypercarbia

System

Risk Assessment Postoperative pulmonary complications (including respiratory failure) following general anesthesia are common (up to 20% to 30% in some series), so the need to assess patient risk is critical. Risk factors for the development of postoperative respiratory failure include the following:

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until residual drug effects have subsided. If opioids are the cause, intravenous naloxone should be carefully titrated (≤40-μg increments) until ventilation is adequate. Larger doses may cause an acute hyperadrenergic crisis (hypertension, tachycardia, fulminant pulmonary edema)1 brought on by the sudden awareness of acute pain. If splinting due to pain leads to hypoventilation, additional analgesics must be given. Alternative pain control (epidural or spinal narcotics, intercostal block, local anesthetic wound infiltration by the surgeon) may also reduce pain-related splinting. Residual neuromuscular block may require intubation and controlled ventilation until its effects dissipate. Whatever the cause, severe hypoventilation may call for tracheal intubation and controlled ventilation until the primary cause has been determined and treated.

obstructive pulmonary disease undergoing high-risk (upper abdominal, thoracic) surgery, continuous epidural anesthesia is known to reduce the incidence of postoperative pulmonary complications. Although adequate analgesia helps limit postoperative respiratory insufficiency, judicious use of intravenous opioids is warranted to prevent overdose and hypoventilation. To prevent hypoventilation, hypercarbia, and hypoxemia due to residual neuromuscular block, short-acting neuromuscular blockers, along with a nerve stimulator to monitor their effects, can ensure an adequate return of neuromuscular function (e.g., sustained tetanus, return to control response to train-of-four or double-burst stimulation, 5-second head lift) before extubation.

Further Reading PREVENTION All patients recovering from general anesthesia or regional anesthesia with sedation should receive supplemental O2 during transport to the PACU. As in the operating room, pulse oximetry should be used in the PACU to monitor SpO2, with confirmation by arterial blood gas sampling if necessary. Routine PACU pulse oximetry monitoring allows practitioners to detect hypoxemia early and intervene appropriately. To limit reduced lung volumes and functional residual capacity, patients (especially those who are obese) should be maintained in the semisitting (semi-Fowler) position to minimize upward displacement of the diaphragm. This, along with the routine use of nasal airways in obese patients before extubation, will help reduce mechanical airway obstruction. Incentive spirometry may be used to limit atelectasis and improve functional residual capacity. Also, continuous positive airway pressure reduces the incidence of postoperative pulmonary complications. Pain alleviation may also help prevent postoperative respiratory insufficiency. In high-risk patients with chronic

1 The editor saw three such cases shortly after intravenous naloxone was first used in PACUs to reverse relative opioid overdose. In each case, the initial doses were 200 or 400 mg—amounts then used to treat heroin overdoses in emergency rooms. Within minutes, the patients spewed “cotton candy” oral secretions, likely due to forward heart failure. Fortunately, all three patients survived.

Adhere C, Brunson C, Roizen M: Sleep apnea, obstructive. In Roizen M, Fleisher L (eds): Essence of Anesthesia Practice, 2nd ed. Philadelphia, WB Saunders, 2002, p 307. Barash P, Cullen B, Stoelting R: Clinical Anesthesia, 4th ed. Philadelphia, JB Lippincott, 2000, pp 1385-1392. Benumof J: Obesity, sleep apnea, the airway and anesthesia. ASA Refresher Courses in Anesthesiology 30:27-40, 2002. Gruber A, Hsu J: Hypoxemia. In Pardo M, Sonner J (eds): The Manual of Anesthesia Practice, version 1.2. PocketMedicine.com, 2004. Gwirtz K: Management of recovery room complications. Anesthesiol Clin North Am 14:307-399, 1996. Hsu J: Hypercarbia. In Pardo M, Sonner J (eds): The Manual of Anesthesia Practice, version 1.2. PocketMedicine.com, 2004. Morgan G, Mikhail M, Murray M: Clinical Anesthesiology, 3rd ed. Chicago, McGraw-Hill/Lange, 2002, pp 942-946. Price J, Rizk N: Postoperative ventilatory management. Chest 115: 130s-137s, 1999. Rock P: Evaluation and perioperative management of the patient with respiratory disease. ASA Refresher Courses in Anesthesiology, 2002. Stoelting R, Dierdorf S: Anesthesia and Co-existing Disease, 4th ed. Philadelphia, Churchill Livingstone, 2002, pp 217-219, 444-446. Warner D: Preventing postoperative pulmonary complications: The role of the anesthesiologist. Anesthesiology 92:1467-1472, 2000.

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David A. Nakata and Robert K. Stoelting Case Synopsis

PROBLEM ANALYSIS Definition Neuropathies are classified into three histologic groups, with increasing levels of severity: neurapraxia, axonotmesis, and neurotmesis. Clinically, any or all of these injury patterns can be present in the affected nerve. With neurapraxia, there is no disruption of actual anatomic neural elements. However, there may be temporary conduction block during ischemia or some degree of demyelination, with greater effects on the function of large fibers (i.e., motor, joint position sense, soft touch). Changes accompanying neurapraxia usually resolve within a few weeks, with complete recovery expected. With axonotmesis, axons are disrupted, but the nerve sheaths remain intact. Wallerian degeneration follows, but axon regeneration results in recovery of function over weeks to months. Even so, some degree of sensory or motor deficit may persist. Neurotmesis is the most serious injury, with disruption of the entire nerve, including transection of the axons and myelin sheaths. This typically prevents regeneration and recovery, resulting in poor functional recovery. Often, the nerve is replaced with fibrous scar tissue. The majority of postoperative neuropathies are due to nerve ischemia. Most commonly, this is caused by either stretch or compression. Direct mechanical compression can obviously lead to reduced blood flow, and stretch produces a reduction in the cross-sectional area of the neural structures, leading to compression of the vasculature (Fig. 221-1).

occurring in the postoperative period. This is in sharp contrast to the historical belief, still held by many, that the development of neuropathy represents an intraoperative deviation from the standard of care.

Risk Assessment Many factors are known to be associated with the development of postoperative neuropathies (Table 221-1). In the patient described in the case synopsis, male gender, preoperative chemotherapy, and diabetes mellitus are known risk factors associated with the development of neuropathies. In males, the ulnar nerve appears to be at greater risk of injury owing to anatomic differences between the sexes. The tubercle of the coronoid process is approximately 1.5 times larger in men than in women, perhaps predisposing to increased bony compression of the nerve. In addition, women generally have a larger fat pad within the medial aspect of the elbow, which may help protect the ulnar nerve (Fig. 221-2). Also, it has been suggested that the cubital tunnel retinaculum

Recognition Postoperative neuropathies are commonly ascribed to events that occur intraoperatively. In numerous cases, however, despite close follow-up, symptoms are not reported until days after the operative procedure. It stands to reason that if intraoperative events were responsible for the development of these neuropathies, symptoms would be reported more proximate to the patient’s emergence from anesthesia. Given the reporting delay, consideration must be given to the possibility that many of these neuropathies stem from events

Figure 221–1 ■ Nerve stretch is associated with a decrease in crosssectional area and an increase in intraneural pressures. (From Butler DS: Mobilization of the Nervous System. New York, Churchill Livingstone, 1991.)

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A 28-year-old man with insulin-dependent diabetes mellitus for 15 years was diagnosed with testicular cancer. His chemotherapy regimen consisted of bleomycin and cisplatin. He underwent postchemotherapy retroperitoneal lymph node dissection under general anesthesia. The surgery, which took 2 hours, was unremarkable, as was his stay in the postanesthesia care unit. On postoperative day 3, the patient noted a decreased level of sensation in the fourth and fifth digits of his left hand. He had no prior history of peripheral neuropathy. He was subsequently diagnosed with a left ulnar neuropathy.

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Factors That May Increase the Risk of Perioperative Neuropathy

Alcoholism Amyloidosis Arthritis Atherosclerotic disease Autoimmune disorders Bell’s palsy Cancer Chemotherapy Connective tissue diseases Diabetes mellitus Direct nerve trauma Gender (male) Hepatic failure Hypothyroidism Infectious diseases Malnutrition Nerve entrapment syndromes Renal failure Trauma to adjacent structures Vitamin deficiencies

Ulnar nerve

Cubital tunnel retinaculum FCU

Figure 221–3 ■ The cubital tunnel retinaculum is a tough, fibrous band that is in close proximity to the ulnar nerve. Compression of the ulnar nerve can occur between this retinaculum and the medial epicondyle. FCU, flexor carpi ulnaris (ulnar head). (From Warner M: Perioperative neuropathies, blindness, and positioning problems. American Society of Anesthesiologists 53rd Annual Refresher Course Lectures, 2002, Orlando, Fla.)

in men is more robust and may place greater compressive force on the ulnar nerve when stretched (Fig. 221-3). Peripheral nerves are much more tolerant to ischemia than are nerves within the central nervous system. Peripheral nerves are commonly subjected to ischemia during the placement of vascular tourniquets for hemostasis. When inflated, the applied force is often greater than 100 mm Hg above the systolic pressure. This degree of pressure has been shown to produce slowing of nerve conduction directly under the area of compression, followed by more distal slowing as tourniquet times increase. In clinical practice, an “ischemic” tourniquet time of less than 2 hours is generally accepted. Animal studies have shown that ischemia is tolerated for up to 4 hours without causing permanent nerve damage. Compressive forces produced by tourniquets are generally greater than those produced by placing the arms or legs on a padded operating room table. Thus, individuals who undergo operative procedures lasting

Inferior ulnar collateral artery Ulnar nerve

Coronoid process Tubercle on proximal coronoid process

Medial epicondyle

Posterior ulnar recurrent artery

Olecranon Figure 221–2 ■ The ulnar nerve and ulnar collateral artery at the elbow are relatively superficial and easy to compress. The coronoid process in males is larger than in females, and the adipose layer is less prominent. These factors increase the risk of compression to the ulnar nerve in males. (From Warner M: Perioperative neuropathies, blindness, and positioning problems. American Society of Anesthesiologists 53rd Annual Refresher Course Lectures, 2002, Orlando, Fla.)

less than 2 hours should be almost immune to the development of postoperative neuropathies from tourniquet application or accepted positioning maneuvers. The patient described in the case synopsis had multiple risk factors for the development of neuropathies, including a long history of diabetes mellitus and recent chemotherapy. Preexisting conditions likely play an important role in the development of neuropathies in many individuals. This patient had no preexisting symptoms of peripheral nerve involvement, but neuropathies associated with metabolic conditions (e.g., diabetes mellitus, chemotherapy) generally have an insidious onset. This gradual onset provides an opportunity for subclinical neuropathies to become well established before the onset of symptoms, and it also leads to increased susceptibility for the development of a symptomatic neuropathy. A well-described potential cause for such increased risk is the double crush syndrome. Double crush syndrome is a peripheral nervous system disorder in which dual lesions in the same nerve act synergistically to enhance each one’s severity. Nemoto and coworkers showed that placing a low-compression clamp on a dog’s peripheral nerve could produce an incomplete conduction block. This caused only mild axonal degeneration, with no obvious clinical sequelae. If a second, equally low-compression clamp was placed more distally on the same peripheral nerve, complete conduction blockade with marked axonal degeneration was shown. This double crush injury model provides insight into how comorbidities may increase the risk of perioperative neuropathies. Also, the model may explain why some individuals develop neuropathies while others do not, despite the use of similar positioning precautions. Double crush syndrome likely plays an important role in the development of neuropathies in patients with preexisting nerve entrapment syndromes. For example, cubital tunnel syndrome is a common nerve entrapment syndrome, second in frequency only to carpal tunnel syndrome. The cubital tunnel is an enclosed space surrounded by tough

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fibrous materials and bone. Because of these anatomic boundaries, the cubital tunnel has a limited ability to expand during fluid accumulation. Postoperatively, patients retain third-space (i.e., interstitial) fluid, some of which accumulates in the cubital tunnel. This accumulation may increase pressure within the cubital tunnel, leading to double crush ulnar nerve compression. Pregnancy-induced carpal tunnel syndrome is a well-known example in which fluid retention can lead to a clinically significant peripheral neuropathy.

ME

Implications

OI

A

ME

OI

CTR

B Figure 221–4 ■ A, Anatomy during elbow extension. B, During elbow flexion, the cubital tunnel retinaculum (CTR) is stretched between the medial epicondyle (ME) and the olecranon process (Ol), leading to compression of the ulnar nerve (arrow). Also, the ulnar nerve is physically stretched during elbow flexion, causing reduction in its cross-sectional area and blood flow. (From Warner M: Perioperative neuropathies, blindness, and positioning problems. American Society of Anesthesiologists 53rd Annual Refresher Course Lectures, 2002, Orlando, Fla.)

PREVENTION In 2000 the American Society of Anesthesiologists published a practice advisory for the prevention of perioperative peripheral neuropathies. This advisory made several recommendations that may decrease the incidence of ulnar neuropathy: ●

MANAGEMENT No specific guidelines exist regarding when a neurologist should be consulted for the complaint of peripheral neuropathy. Consideration of the duration and severity of the findings is required. If the supposed peripheral neuropathy resolves within a short period, neurapraxia is the most likely diagnosis, and a full recovery can be expected. However, if the findings persist with no improvement, a neurology consultation should be considered to assist in both diagnosis and management. In some instances, nerve conduction studies may be warranted.

CTR

SPECIAL TOPICS

The American Society of Anesthesiologists’ closed claims analyses recognize postoperative ulnar neuropathies as among the most common, if not the most common, postoperative peripheral neuropathy. In 1999, 28% of all claims for such nerve injuries involved the ulnar nerve. More recent analyses of claims in which anesthesia care was implicated suggest that some injuries did not occur until after anesthesia care had ended. In a prospective study, Warner and colleagues found that the median time for reporting symptoms of ulnar neuropathy was 4 days after surgery (range, 2 to 7 days). Another prospective study by Warner’s group showed that ulnar neuropathies also occurred in medical patients who did not undergo surgery. Considering these reports, it is implausible to assume that all perioperative neuropathies occur during the intraoperative and perianesthetic care periods. Thus, other mechanisms for such neuropathies need to be sought. Postsurgical patients routinely receive opiates for pain control. These drugs blunt not only pain sensation but also the sensation of any paresthesias the patient might experience. Pain medications also produce sedation, so that patients are less mobile. Such immobility might extend the time patients spend in positions that could result in nerve stretch or compression injury. Finally, during postoperative rounds, it is common to find patients resting with their arms folded across the chest or abdomen. Elbow flexion is known to raise the pressure within the cubital tunnel and also to stretch the ulnar nerve, either of which can increase the likelihood of nerve ischemia (Fig. 221-4). Often, this crossed arm position places the cubital tunnel directly in contact with the bed, further compressing the ulnar nerve. Finally, the ulnar nerve may be injured when patients sit in armchairs with their arms flexed, which can place the cubital tunnel in direct contact with the armrests.

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Arm abduction should be limited to 90 degrees in supine patients; patients who are positioned prone may comfortably tolerate arm abduction greater than 90 degrees. Arms should be positioned to decrease pressure on the postcondylar groove of the humerus (ulnar groove). When arms are tucked at the sides, a neutral forearm position is recommended. When arms are abducted on armboards, either supination or a neutral forearm position is acceptable. Padded armboards may decrease the risk of upper extremity neuropathies. Padding at the elbow and at the fibular head may decrease the risk of upper and lower extremity neuropathies, respectively.

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Given the multitude of factors that may contribute to perioperative ulnar neuropathy, it cannot be assumed that all perioperative nerve injuries are due to a violation of the standard of care. This idea is reinforced, in most cases, by the relatively long interval between the operative procedure and the initial report of symptoms.

Further Reading Bentley FH, Schlapp W: Experiments on the blood supply of nerves. J Physiol 102:62, 1943. Cheney FW, Domino KB, Caplan RA, et al: Nerve injury associated with anesthesia: A closed claims analysis. Anesthesiology 90:1062-1069, 1999.

Gelberman RH, Yamaguchi K, Hollstien SB, et al: Changes in interstitial pressure and cross-sectional area of the cubital tunnel and of the ulnar nerve with flexion of the elbow: An experimental study in human cadavera. J Bone Joint Surg Am 80:492-501, 1998. Nemoto K, Matsumoto N, Tazaki K, et al: An experimental study on the “double crush” hypothesis. J Hand Surg [Am] 12:552-559, 1987. Practice advisory for the prevention of perioperative peripheral neuropathies: A report by the American Society of Anesthesiologists Task Force on Prevention of Perioperative Peripheral Neuropathies. Anesthesiology 92:1168-1182, 2000. Warner MA, Warner DO, Harper C, et al: Ulnar neuropathy in medical patients. Anesthesiology 92:613-617, 2000. Warner MA, Warner DO, Matsumoto JY, et al: Ulnar neuropathy in surgical patients. Anesthesiology 90:54-59, 1999.

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Delayed Emergence Deborah A. McClain

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Case Synopsis A 50-year-old man undergoes general anesthesia for umbilical hernia. He weighs 120 kg and has a history of hypertension, gastroesophageal reflux disease (GERD), polysubstance abuse, hepatitis C, and post-traumatic stress disorder (PTSD). He is taking hydrochlorothiazide, an ACE inhibitor, cimetidine, omeprazole, citalopram, and trazodone. The anesthetic and surgery progress uneventfully. The patient is extubated and taken to the postanesthesia care unit (PACU). After 15 minutes, the patient fails to respond to verbal stimuli.

Definition Delayed emergence is failure of the patient to regain the expected level of consciousness within 20 to 30 minutes of the end of anesthetic administration. Intervention is necessary to rule out potentially harmful, reversible conditions. Possible causes can be classified as follows: ● ● ● ● ●

Anesthetic drugs Medications Electrolyte disorders Metabolic disorders Systemic effects

Recognition As with all assessments, the ABCs (airway, breathing, circulation) take priority and should be reevaluated throughout the course of delayed emergence. Other assessment tools include the following: ● ● ● ● ●

Pharmacologic agents Physical examination Laboratory examination Computed tomography (CT) of the head Neurology consultation

The diagnosis of delayed emergence is made in the PACU, and the cause may be multifactorial. An anesthesiologist must evaluate these patients promptly to differentiate delayed emergence from the life-threatening problems that may falsely manifest as delayed emergence: airway obstruction, hypoxia, and hypercarbia. The patient should be evaluated immediately with assessment of vital signs (especially the rate and character of spontaneous breathing and oxygen saturation) and a physical examination. Further evaluation must consider the patient’s preexisting medical problems, any pharmacologic agents taken preoperatively or administered in the perianesthetic period, and the nature of the operative procedure performed. A thorough physical examination must be performed, with particular emphasis on vital signs (including temperature), smelling of the patient’s breath for residual volatile anesthetics, and neurologic examination. A firm tactile stimulus may

arouse the obtunded patient more effectively than verbal stimulation. Prompt laboratory evaluation includes arterial blood gas analysis to assess pH, oxygen and carbon dioxide partial pressures, and blood glucose concentration. Serum electrolytes, including calcium and magnesium, should also be evaluated. Obtaining a urine sample for toxicologic evaluation may be prudent. Finally, a CT scan of the patient’s head and consultation with a neurologist may be necessary.

Risk Assessment Although delayed emergence has many causes, its predictability and the rate at which it will occur have not been specifically assessed. Most cases are purely anecdotal, and thus no occurrence rate has been determined. Nevertheless, some level of responsiveness to stimulation should occur within 90 minutes of the cessation of anesthetic administration. Certain patients are at greater risk for delayed emergence from anesthesia. These include patients with preexisting cognitive or psychiatric disorders and patients who chronically take sedative medications. Patients who were anesthetized while intoxicated by alcohol or recreational drugs may be more difficult to arouse. Finally, those who were physically exhausted prior to surgery may have prolonged emergence.

Implications Depending on the cause of the delayed emergence, the consequences may be catastrophic or minor. However, prompt, efficient assessment and treatment are key to minimizing potential catastrophes.

MANAGEMENT Anesthetic Drugs Many factors influence the effect of inhalational or intravenous drugs on the patient’s level of consciousness: ● ● ●

Central nervous system (CNS) sensitivity Metabolism/excretion Redistribution 885

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PROBLEM ANALYSIS

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Amount of drug administered Plasma concentration

Biologic variation in CNS sensitivity follows the bellshaped Gaussian curve. Some patients require very small amounts of drugs for induction and maintenance, whereas others require larger and larger quantities. The majority, of course, fall in the middle. The concentration of drug that reaches the brain receptor and the sensitivity of the receptor to that specific drug determine the response. Decreased hepatic metabolism occurs in patients at the extremes of age, in malnourished patients, in hypothermic patients, and in patients who simultaneously receive several drugs that are detoxified by the hepatic microsomal enzyme system (e.g., ethanol, barbiturates). While redistribution is responsible for the short action of some drugs (such as thiopental), it can contribute to delayed emergence as well, especially when given in repeated doses. Fat-soluble drugs, such as inhalation anesthetics, are distributed to fat stores. The result is a storage depot that releases anesthetic back into the circulation after the conclusion of the case. This is especially true for long-acting anesthetics and in obese patients. Plasma concentration and the portion of drug available to interact with receptors are affected by other factors, such as albumin and other proteins that influence protein binding. The less drug that is bound to plasma proteins, the more that is available to interact with receptors. Protein binding is also affected by pH. For example, protein binding of fentanyl decreases as the plasma becomes more acidotic, resulting in more free fentanyl. Other drugs in the patient’s system may compete for binding sites and thus result in more free drug. Volatile anesthetics, narcotics, sedatives, and muscle relaxants all can lead to delayed emergence. Phase II blockade or a pseudocholinesterase deficiency can result in prolonged neuromuscular blocking effects when succinylcholine is administered. In this case it is usually better to avoid attempts at reversal. Furthermore, some antibiotics enhance and prolong the action of nondepolarizing relaxants.

Medications Prescribed medications, such as sleeping aids, pain medications, and lipid-lowering drugs, affect minimum alveolar concentration (MAC) or occupy some of the receptors. Over-the-counter medications should also be considered as a source of delayed emergence (see also Chapter 39). H2-receptor antagonists cimetidine and ranitidine impair hepatic microsomal oxidation of some drugs. Greenblatt and colleagues found that although healthy volunteers showed no increase in sensitivity to midazolam or benzodiazepines, other drugs that depend on hepatic metabolism may be affected, as may less healthy patients. Herbal supplements also have the potential to cause excessive sedation and delayed emergence. Kava, St. John’s wort, and valerian are the primary culprits. Herbal products should be discontinued 1 day to 1 week prior to anesthesia (see also Chapter 39). Chemotherapeutic agents, such as L-asparaginase and vincristine, often produce CNS depression and even electrocardiographic changes. Although these agents are a rare cause of

delayed emergence, they are included in the differential diagnosis (see also Chapter 30).

Electrolyte Disorders Hyponatremia, especially if acute, can cause lethargy, delayed awakening, and seizures. The most common cause encountered in connection with anesthesia is the TURP (transurethral resection of the prostate) syndrome. The circumstances and serum sodium below 130 mEq/L make the diagnosis relatively simple to make. Correction should proceed at no more than 2 mEq/L per hour until a serum sodium of 130 mEq/L ± 2 mEq/L is reached. Hypercalcemia and hypermagnesemia can produce CNS depression even to the point of coma.

Metabolic Disorders Extremes of serum glucose, hypoglycemia from fasting or insulin, or hyperglycemia (hyperosmotic, hyperglycemia, nonketotic coma) can result in prolonged unconsciousness. Other endocrine abnormalities, primarily hypothyroidism and adrenal suppression or deficit, should also be considered as a cause for delayed emergence.

Systemic Effects Respiratory depression can lead to CO2 narcosis. This may be more difficult to diagnosis in the PACU, where end-tidal CO2 is not routinely monitored. Hypoxia resulting from depression or ventilation-perfusion mismatching should also be ruled out. Hypothermia can also contribute to the lowered level of consciousness. Although body temperature between 30 and 32°C does not cause unconsciousness alone, its effects on biotransformation and inhalational anesthetic solubility may contribute to prolonged emergence. Temperatures lower than 30°C can cause cold narcosis through a direct effect on the brain. Hyperthermia >40°C, such as is seen in heatstroke or malignant hyperthermia, does result in loss of consciousness. Neurologic events including stroke and seizures should also be considered in the differential diagnosis. Increased intracranial pressure caused by a cranial bleed or resulting from an intracranial mass, especially with an elevation in end-tidal CO2, can augment the effects of the latter to worsen CO2 narcosis.

TREATMENT Reversal agents (naloxone, flumazenil, physostigmine, neostigmine) may be used for treatment for as well as diagnosis of prolonged effects of narcotics, benzodiazepines, inhalation anesthetics, and muscle relaxants. Electrolyte and metabolic abnormalities should be corrected in symptomatic patients, but this must be done carefully to avoid serious undesired effects. Causes for hypoxia or hypercarbia should be assessed even as ventilatory support is initiated. A thorough neurologic evaluation should be performed to seek localizing signs versus global effects.

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A neurology consultation or CT scan may be appropriate if other causes have been eliminated. Appropriate reversal dosages are listed below: ●

● ●

Naloxone, 40-μg doses every 2 minutes IV to a total of 200 μg Flumazenil, 0.2 mg/min IV to a total of 1.0 mg Physostigmine, 1.25 mg IV

PREVENTION

Further Reading Cohen ML, Chan S, Way WL, et al: Distribution in the brain and metabolism of ketamine in the rat after intravenous administration. Anesthesiology 39:370, 1973. Curtis D, Stevens WC: Recovery from general anesthesia. Int Anesthesiol Clin 29:1, 1991.

Delayed Emergence

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Gerich JE, Martin MN, Recant L: Clinical and metabolic characteristics of hyperosmolar non-ketotic coma. Diabetes 20:228, 1971. Ghoneim MM, Dembo JH, Block RI: Time course of antagonism of sedative and amnestic effects of diazepam by flumazenil. Anesthesiology 70:899, 1989. Greenblatt DJ, Locniskar A, Scavone JM, et al: Absence of interaction of cimetidine and ranitidine with intravenous and oral midazolam. Anesth Analg 65:176, 1986. Lyew MA, Mondy C, Eagle S, et al: Hemodynamic instability and delayed emergence from general anesthesia associated with inadvertent intrathecal baclofen overdose. Anesthesiology 98:265, 2003. McClain DA, Hug CC: Intravenous fentanyl kinetics. Clin Pharmacol Ther 28:111, 1980. Narins RG: Therapy of hyponatremia: Does haste make waste? N Engl J Med 314:1573, 1986. Prough DS, Roy R, Bumgarner J, et al: Acute pulmonary edema in healthy teenagers following conservative doses of intravenous naloxone. Anesthesiology 60:485, 1984. Reves JG, Glass PSA, Lubarsky DA, et al: Intravenous nonopioid anesthetics. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, p 317. Stoelting RK, Eger EI II: The effects of ventilation and anesthetic solubility on recovery from anesthesia. Anesthesiology 30:290, 1969. Tinker JH, Gandolfi AJ, Van Dyke RA: Elevation of plasma bromide levels in patients following halothane anesthesia. Anesthesiology 44:194, 1976. Ward CF: Pulmonary edema and naloxone. J Clin Anesth 8:690, 1996. Weiss HD, Walker MD, Wiernik PH: Neurotoxicity of commonly used antineoplastic agents. N Engl J Med 291:75, 127, 1974 Wood M: Plasma drug binding: Implications for anesthesiologists. Anesth Analg 65:786, 1986.

SPECIAL TOPICS

Delayed emergence may be minimized by careful perioperative care of the patient, including a precise history and physical examination, vigilant intraoperative care and monitoring, and early evaluation of potential postoperative problems. Judicious and appropriate titration of reversal agents may alleviate the prolonged anesthetic medication effects. Careful evaluation of serum chemistries, neurologic evaluation, consultation with a neurologist, and CT scan may be necessary if neurologic injury has occurred.

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Postoperative Delirium Philip Levin

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Case Synopsis An 86-year-old woman with history of stable angina, chronic obstructive pulmonary disease, hypertension, and hypothyroidism undergoes general anesthesia for pinning of a femur fracture. The surgery and anesthetic are uneventful. In the postanesthesia care unit (PACU), the patient becomes disoriented and combative.

PROBLEM ANALYSIS Definition Postoperative delirium is a state in which patients have altered consciousness, orientation, memory, perception, and behavior. It is usually noted in the PACU.

Recognition Postoperative delirium can have multiple causes and should be promptly evaluated by an anesthesiologist in the PACU. Assessment of the patient’s breathing and circulatory status is extremely important to rule out life-threatening problems such as hypoxia, hypercarbia, and airway obstruction. A thorough medical history, a complete listing of medications administered during the perioperative period, and review of the anesthesia and surgical course (including the type of surgery) should be obtained. Then a detailed physical examination and any indicated laboratory testing are performed. Severe pain (surgical, urinary, or gastric distention) can cause altered mental status and should be treated promptly. Certain metabolic, endocrine, and infectious disorders can also cause altered mental status and must be ruled out. Intracerebral pathology should be ruled out in patients with focal neurologic findings and gait disturbances. In addition, effects of residual anesthetic agents may mimic postoperative delirium. It may be difficult to distinguish residual sedation resulting from the effects of sedatives, antiemetics, or anesthetics that lead to disinhibition from causes that require treatment with sedatives. Patients with postoperative delirium are at risk of physically harming themselves or PACU personnel. Patients may tear open their bandages or wounds or pull out their intravenous lines. Patients with postoperative delirium are also at risk for falls and fractures.

Risk Assessment Risk factors for developing postoperative delirium are divided into three categories: preoperative, intraoperative, and postoperative. Preoperative risk factors include advanced age, pathologic brain states (e.g., cerebrovascular disease), administration of multiple drugs and drug interactions, abrupt withdrawal of alcohol or sedative-hypnotics, endocrine and metabolic disorders (e.g., hyper- or hypothyroidism, hyponatremia, hypoglycemia), depression, and dementia or anxiety disorders. 888

Intraoperative risk factors include the type of surgery. Patients having cardiac surgery appear to be at greater risk of developing postoperative delirium, possibly due to hypoperfusion or microembolism (air or thrombus). Further, certain orthopedic procedures may predispose to postoperative delirium, possibly due to fat emboli. Some ophthalmic procedures may be associated with bilateral loss of vision (possibly due to the use of anticholinergic drugs and eyedrops), which can contribute to postoperative delirium. Certain anesthetic drugs, including anticholinergics, barbiturates for premedication, and benzodiazepines, have been linked to an increase in postoperative delirium. Interestingly, several studies have found no difference in the effects of general, epidural, or spinal anesthesia on the development of postoperative delirium. Postoperative risk factors for delirium include hypoxia, hypocarbia, and sepsis.

Implications Postoperative delirium can result in complications such as prolonged hospital stay, delayed functional recovery, and increased morbidity.

MANAGEMENT Identifying and Correcting the Underlying Cause Initially, it is important to identify and correct underlying causes. A thorough medical history is important, including any additional information that family members or caregivers may provide (e.g., baseline behavior and mental status). A careful physical examination, including a detailed neurologic and psychiatric examination, should be performed. The patient’s vital signs and overall medical condition must be monitored carefully until underlying causes (e.g., change in respiratory status, infection, fluid or electrolyte imbalance) have been identified and corrected or stabilized. It is also important to review any pertinent laboratory and radiographic studies.

Pharmacologic Measures Identification and correction of the underlying condition may be sufficient to reverse delirium. Specific pharmacologic intervention may be necessary to reduce the intensity

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Environmental Interventions Supportive measures are useful for treating the symptoms of delirium. These include reorienting the patient to time, place, and person and minimizing excessive noise. Having a family member near the bedside may help calm the patient. Because delirium can be aggravated by sensory impairment, restoring the patient’s vision (eyeglasses or contact lenses) or hearing (replacing a hearing aid) may be helpful. The use of physical restraints should be minimized; they may aggravate the patient’s confusion, because they create the impression of being tied down.

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Psychiatric and Neurologic Care Obtaining a psychiatric consultation may be necessary if other treatment measures fail and more aggressive management is necessary. If postoperative delirium appears to have a neurologic cause, the appropriate neurologic or neurosurgical consultation should be obtained.

PREVENTION Little is known about the prevention of postoperative delirium. There is some evidence that aggressive management of established risk factors may help. Some intraoperative measures that may be effective include maintaining good oxygenation and normal blood pressure, using correct drug dosages, and maintaining normal electrolyte levels. Drugs associated with an increased risk of delirium should be used cautiously. These include H2-antagonists, digitalis, phenytoin, and anticholinergic medications. If an anticholinergic is necessary, a quaternary amine such as glycopyrrolate should be used. In general, drugs with short elimination half-lives are preferable to long-acting drugs. Adequate postoperative analgesia is also important for the prevention of postoperative delirium.

Further Reading American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC, American Psychiatric Association, 1994. Breitbart W, Tremblay A, Gibson C: An open trial of olanzepine for the treatment of delirium in hospitalized cancer patients. Psychosomatics 43:175-182, 2002. Chung F: Postoperative mental dysfunction. In McLeskey CH (ed): Geriatric Anesthesiology. Philadelphia, Williams & Wilkins, 1997, pp 487-495. Kaneko T, Cai J, Ishikura T, et al: Prophylactic consecutive administration of halperidol can reduce the occurrence of postoperative delirium in gastrointestinal surgery. Yonago Acta Med 42:179-184, 1999. Litaker D, Locala J, Franco K, et al: Preoperative risk factors for postoperative delirium. Gen Hosp Psychiatry 23:84-89, 2001. Lynch EP, Lazor MA, Gellis JE, et al: The impact of postoperative pain on the development of postoperative delirium. Anesth Analg 86:781-785, 1998. McGowan NC, Locala JA: Delirium. Cleveland Clinic Disease Management Project, Oct 24, 2002. Available at www.clevelandclinicmeded.com/ diseasemanagement/psychiatry/delirium/delirum1.htm. Parikh S, Chung F: Postoperative delirium in the elderly. Anesth Analg 80:1223-1232, 1995. Weber JB, Coverdale JH, Kunik ME: Delirium: Current trends in prevention and treatment. Int Med J 34:115-121, 2004.

SPECIAL TOPICS

and duration of delirium. Many studies have demonstrated the safety and efficacy of antipsychotics. In this category, haloperidol is the drug of choice because of its favorable cardiovascular and respiratory side effect profile compared with other antipsychotics. Also, it has negligible anticholinergic effects. Haloperidol can be administered orally, intramuscularly, or intravenously in doses ranging from 0.25 to 2 mg. This dose is repeated or doubled every 30 to 60 minutes until the patient is sedated and calm. Droperidol has been used for more rapid tranquilization. Chlorpromazine is also effective, but it can lead to severe hypotension. Neuroleptic antipsychotic medications may lengthen the Q-T interval, thus increasing the risk of torsades de pointes. Patients who receive this treatment should have a baseline electrocardiogram. If the patient’s Q-T interval becomes prolonged to greater than 25 percent of baseline or longer than 450 msec, dose reduction or discontinuation of therapy may be needed. Recent studies show that the novel antipsychotic drug olanzapine might also be effective for treating postoperative delirium and has fewer side effects than more typical neuroleptic drugs. Further studies are warranted. Benzodiazepines are not effective therapy for postoperative delirium, except for that caused by withdrawal from alcohol or sedative-hypnotics. Lorazepam is the benzodiazepine most commonly used; it is administered orally, intramuscularly, or intravenously in doses ranging from 0.5 to 2 mg. The dose of lorazepam is repeated or doubled every 30 to 60 minutes, depending on the patient’s level of sedation. The use of physostigmine is controversial, but it may still be available in some locations. This drug was often used in the past to treat postoperative delirium, especially that due to central cholinergic crisis. Compared with quaternary anticholinergics (e.g., atropine, glycopyrrolate), physostigmine (a tertiary amine) crosses the blood-brain barrier more readily.

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Intractable Nausea and Vomiting

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David A. Nakata and Robert K. Stoelting Case Synopsis A 28-year-old, 110-kg woman presents with intractable nausea and vomiting in the postanesthesia care unit after undergoing laparoscopic cholecystectomy under general anesthesia. The anesthesia was unremarkable except for preoperative anxiety and moderate postoperative upper airway obstruction, which was easily corrected by insertion of an oral airway. Past medical history was significant for unanticipated hospital admission for postoperative nausea and vomiting following previous inguinal hernia repair.

PROBLEM ANALYSIS Definition Postoperative nausea and vomiting (PONV) is an important cause of morbidity following all types of anesthesia. It typically occurs in the immediate postanesthesia period, with most cases lasting less than 24 hours. Nausea is a subjective sensation best evaluated by the patient and is mediated via unknown neural pathways. It often, but not always, arises as the antecedent event to retching or vomiting. Vomiting (emesis) is defined as the forceful retrograde oral expulsion of gastric contents. Retching differs from vomiting by the lack of expulsion of gastric contents. PONV has multiple causes that can be subdivided into patient-, surgical-, and anesthetic-related factors.

Recognition The sensation of nausea is familiar to everyone, but because of its subjective nature, it is often difficult to appreciate, especially in a disoriented postoperative patient. Nausea is typically accompanied by decreased or inappropriate gastrointestinal activity and may include hypotonicity of muscular sphincters, hypoperistalsis or reverse peristalsis, and hyposecretion. The autonomic nervous system, especially the parasympathetic system, can also be affected, leading to manifestations such as skin pallor, diaphoresis, increased salivation, vasovagal reactions, and anorexia. If these symptoms persist, they invariably deteriorate to retching and vomiting. Vomiting, unlike nausea, is virtually unmistakable in its presentation. The neuroanatomic pathways and mediators that produce vomiting are better understood than those associated with nausea. Two distinct areas in the brain are responsible for the initiation and coordination of vomiting: the chemoreceptor trigger zone in the fourth ventricle, and the vomiting center in the lateral reticular formation. The chemoreceptor trigger zone contains a high density of dopaminergic receptors and is connected by neural pathways to the vomiting center. Figure 224-1 is a schematic representation of the factors that are known to interact with the areas 890

responsible for vomiting. In addition, numerous physiologic changes occur, including relaxation of the gastric fundus and lower esophageal sphincter and the forceful contraction of the abdominal musculature, leading to the ejection of gastric contents.

Risk Assessment The incidence of postoperative vomiting is typically reported to be between 20% and 40%. Table 224-1 presents factors that have been implicated in the development of PONV. A number of these factors are widespread throughout the general surgical population, making it common for individual patients to have multiple risk factors. These factors, in addition to specific patient characteristics, are useful in predicting which patients are at greatest risk of developing PONV. Unfortunately, there is no formal scheme that allows clinicians to predict which prophylactic maneuvers will yield the greatest success. Some of the less obvious factors that influence the incidence of nausea and vomiting include anxiety, gender, obesity, experience of the anesthesiologist, and anesthetic agent. Anxiety may exacerbate PONV via the release of catecholamines. Experimental models exist in which vomiting can be induced by instilling catecholamines into the cerebral ventricles. This may also account for the increased incidence of nausea and vomiting associated with the use of anesthetic agents that increase circulating catecholamines. The increased incidence of PONV in women has traditionally been ascribed to a hormonal cause. This is supported by a decreased incidence of PONV in females at the extremes of age when compared with age-matched males. However, a recent study postulates that the increased incidence of PONV in women may actually be due to a greater sensitivity to dopamine. Obesity may interfere with positive-pressure ventilation, leading to gastric distention. The case synopsis provides examples of some of the common predisposing conditions that can increase a patient’s risk for PONV, including female gender, obesity, previous history of PONV, anxiety, laparoscopic abdominal surgery, placement of an oral airway, and general anesthesia. Other factors may include increased gastric inflation or hypoxemia

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Figure 224–1 ■ Factors known to interact with the chemoreceptor trigger zone and the vomiting center to initiate vomiting.

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Motion

Intractable Nausea and Vomiting

Hypoxia Pain

Increased intracranial pressure Smell, sight, taste Psychotropic factors

Vestibular labyrinth

Cerebellum

Cortical afferents

Drugs Radiation

Chemoreceptor trigger zone

891

Vomiting center

Act of vomiting

Visceral afferents

Disease of: Heart Digestive tract Biliary tract Genitourinary tract

from difficult positive-pressure ventilation and increased arterial carbon dioxide tension from inadequate mask ventilation or abdominal insufflation of carbon dioxide during laparoscopy. Although contemporary volatile anesthetics are not known to promote nausea and vomiting, nitrous oxide has been incriminated. Possible mechanisms might be increased middle ear pressure with stimulation of the chemoreceptor trigger zone or distention of the gastrointestinal tract.

Table 224–1

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Implications Table 224-2 lists a number of complications associated with nausea and vomiting. A number of coexisting diseases and certain surgical procedures may predispose a patient to the development of more serious sequelae of PONV, including increased intracranial pressure (leading to tentorial herniation) and esophageal disruption (Mallory-Weiss tear or Boerhaave’s syndrome). PONV can also cause wound dehiscence and

Factors That May Influence the Risk of Postoperative Nausea and Vomiting

Age: children at greater risk than adults Anesthetic technique Anxiety Concurrent illness Ethanol intoxication Increased intracranial pressure Metabolic disturbance Experience of the anesthetist Fasting Female gender Day of the menstrual cycle Gastric inflation Hypercarbia Hypotension Inhalational anesthetics Intravenous anesthetics Etomidate Methohexital Thiopental

Medications Nasogastric tube Nitrous oxide Obesity Opioids Pain Placement of airways Previous history of postoperative nausea and vomiting Prolonged operative procedure Standing Sympathetic stimulation Transportation or movement of patient Type of surgery Head and neck surgery Intra-abdominal surgery Laparoscopic abdominal surgery Strabismus surgery

SPECIAL TOPICS

Metabolic disturbances

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Complications Associated with Nausea and Vomiting

Aspiration pneumonia Dehydration Delayed discharge from postanesthesia care unit Delayed discharge from hospital Increased cost Inconvenience Electrolyte imbalance Hypokalemia Hypochloremia Hyonatremia Alkalosis Esophageal rupture (Boerhaave’s syndrome) Increased postsurgical bleeding Increased intracranial pressure Mallory-Weiss tear

disruption of complex surgical repairs. Retching or vomiting following procedures involving the head and neck is of special concern because of the fragile nature of these tissues. In addition, an especially risky situation may be created by procedures involving the oral cavity in which the mandible is fixed in the closed position. Under these circumstances, if a patient were to vomit, significant quantities of gastric contents could be aspirated.

MANAGEMENT Table 224-3 lists antiemetic agents available for the prevention and treatment of nausea and vomiting. These drugs can be subdivided into gastrointestinal prokinetic drugs, phenothiazines, butyrophenones, anticholinergics, antihistamines, serotonin (5-HT3) receptor antagonists, and steroids. No single agent is universally effective for the prevention or treatment of PONV. Many of these drugs are associated with side effects,

Table 224–3

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Antiemetics

Anticholinergics Scopolamine (IV or transdermal patch) Atropine Antihistamines Cyclizine (Marezine) Dimenhydrinate (Dramamine) Diphenhydramine (Benadryl) Butyrophenones Droperidol (Inapsine) Phenothiazines Promethazine (Phenergan) Prochlorperazine (Compazine) Perphenazine (Trilafon) Prokinetics Metoclopramide (Reglan) Domperidone (Motilium) Serotonin (5-HT3) antagonist Ondansetron (Zofran) Dolasetron (Anzemet) Granisetron (Kytril) Steroids Dexamethasone (Decadron)

such as sedation and extrapyramidal reactions. This may cause some clinicians to restrict the use of these drugs, especially when one considers the typically negligible impact of PONV on overall outcome. In addition, when consideration is given to the large number of factors that can affect the development of PONV, choosing the most efficacious antiemetic can be difficult.

PREVENTION Routine antiemetic prophylaxis is not warranted because less than 30% of patients experience postoperative emesis. When it occurs, it is often brief in duration. In addition, the sedation and delayed awakening caused by some of the commonly used antiemetic agents may hinder their usefulness. Even though antiemetic prophylaxis is not routinely advised, consideration must be given to the reality that the treatment of PONV is often less efficacious than its prevention. Therefore, there may be specific instances when the prophylactic use of these agents is warranted for patients known to be at risk. Given the multiple factors involved in the development of PONV, it is difficult to provide specific recommendations regarding prophylaxis. This is in contrast to the nausea and vomiting associated with radiation and chemotherapy, in which the inciting agents are more readily identifiable. Additionally, in refractory cases of PONV, a combination of drugs may be needed to increase efficacy. Unfortunately, combination therapy is markedly more expensive than single drug therapy, and even with multidrug therapy, success is not assured. Other factors aiding in the prevention of PONV include nonpharmacologic therapies such as decompressing the stomach with an oro- or nasogastric tube. However, the presence of a gastric tube in the postoperative period may stimulate the gag reflex, thus mitigating the benefit of gastric decompression. Additionally, fluid hydration has been advocated to decrease the incidence of PONV. Given the relative low cost and safety associated with this therapy, it seems reasonable to consider it. Other, more exotic nonpharmacologic therapies include acupuncture, acupressure, and specific herbs. Finally, new drugs include tropisetron, a 5-HT3 antagonist now marketed in Europe that is currently in clinical trials in the United States.

Further Reading Apfel CC, Korttila K, Abdulla M, et al: A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 350:2441-2451, 2004. Camu F, Lauwers MH, Verbessem D: Incidence and aetiology of postoperative nausea and vomiting. Eur J Anaesthesiol 9(Suppl 6):25-31, 1992. Divatia JV, Vaidya JS, Badwe RA, et al: Omission of nitrous oxide during anesthesia reduces the incidence of postoperative nausea and vomiting: A meta-analysis. Anesthesiology 85:1055-1062, 1996. Korttila K: The study of postoperative nausea and vomiting. Br J Anaesth 69(Suppl 1):20S-23S, 1992. Palazzo MGA, Strunin L: Anesthesia and emesis. Can Anaesth Soc J 31: 178-187, 1984. Rowbotham DJ: Current management of postoperative nausea and vomiting. Br J Anaesth 69(Suppl 1):46S-59S, 1992. Watcha MF, White PF: Postoperative nausea and vomiting. Anesthesiology 77:162-184, 1992.

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Unanticipated Hospital Admission and Readmission

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Zhuang T. Fang Case Synopsis

PROBLEM ANALYSIS Definition Unanticipated hospital admission is any admission not anticipated preoperatively. Unanticipated hospital readmission includes patients who are readmitted to the hospital within 30 days of discharge. The incidence of unanticipated hospital admission ranges from 1% to 6%, and that of unanticipated readmission ranges from 1% to 3%. UNANTICIPATED HOSPITAL ADMISSION An unanticipated hospital admission requires that there be no preoperative expectation that a patient will require an increased level of care following surgery. This unscheduled hospitalization can be at a freestanding outpatient center or at a community hospital. Unanticipated admission for all outpatient procedures is about 1.5% on average. However, it is higher for some surgeries: 4% for otologic surgery, 5% for laparoscopic cholecystectomy or gynecologic laparoscopy, and up to 6% for microdiscectomy. Rates are similar for adults and children, males and females, and patients at the extremes of age. Surgical causes account for 40% to 50% of unanticipated admissions, and anesthesia-related causes account for 25%. The remainder occur for social or medical reasons. UNANTICIPATED HOSPITAL READMISSION The rate of unanticipated hospital readmission is about 2.5%, but this too varies among surgical procedures. Higher rates correlate with greater surgical invasiveness and the indications for the surgery.

Recognition Careful preoperative assessment and patient selection are essential for identifying anesthetic or surgical risk factors for

SPECIAL TOPICS

A 70-year-old woman is in the recovery room of an ambulatory surgery facility after a 3-hour repair of a cystocele under general anesthesia. She has nausea and vomiting and is complaining of pain. Interventions have been ineffective, and the surgery facility is scheduled to close in 30 minutes. The chart review indicates an American Society of Anesthesiologists (ASA) class II patient with a history of controlled hypertension and hypothyroidism. Significant past surgery was a left mastectomy 5 years ago for breast cancer. This surgery was associated with postoperative nausea and vomiting (PONV).

unanticipated hospital admission. It is prudent to plan to admit high-risk patients for an overnight stay rather than be faced with a last-minute, unplanned admission. In the case synopsis, the patient’s possible need for hospitalization was not appreciated and anticipated. The identification of intraoperative risk factors (e.g., technical difficulty, invasiveness, and duration of the procedure), early recognition of anesthesia and surgical complications and aggressive remedial intervention, and attention to postoperative issues (e.g., pain, PONV) are crucial to preventing unanticipated admission or readmission. Vigilance in the recovery room can also facilitate early remedial or preventive intervention, more timely decisions, and a smooth transition to hospital admission if necessary.

Risk Assessment Risk factors for unanticipated admission or readmission include the following: ● ● ● ● ● ●

Surgical bleeding and related complications PONV Uncontrolled pain Respiratory complications High ASA status Lack of postoperative social support

Surgical oozing and other complications (e.g., a more extensive procedure than planned, requiring longer postoperative observation) account for the majority of unanticipated hospital admissions. Among adults undergoing ambulatory surgery, most anesthesia-related unanticipated admissions are due to PONV, uncontrolled pain, and urinary retention. In addition, higher ASA status is directly related to the incidence of unanticipated hospital admission. Pediatric patients are often admitted for respiratory complications or PONV; they are usually not admitted for uncontrolled pain. Owing to a significant increase in the rate of unanticipated admissions because of complications such 893

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as bronchospasm, laryngospasm, and postoperative oxygen desaturation, surgery should be postponed in pediatric patients with symptomatic upper respiratory tract infections. Suggested protocols for canceling surgery in a pediatric patient with a mild upper respiratory infection or who is recovering from one include the following: ● ● ●

Age younger than 1 year Surgery lasting longer than 45 minutes Possibility of the need for tracheal intubation

In the case synopsis, several factors placed the patient at high risk for unanticipated hospital admission: female gender, past history of PONV, and invasiveness and long duration of the planned surgery. A more extensive list of risk factors for PONV is provided in Table 225-1. Although it was appropriate to perform the surgery in this patient, recognition of her increased risk for PONV and postoperative pain should have prompted preemptive interventions, including the use of anesthetic techniques to reduce the likelihood of PONV and pain. PONV is effectively treated and prevented with multimodal antiemetic management. The use of regional anesthesia techniques and local anesthetic surgical wound infiltration can reduce the need for opioids or sedative-hypnotics (e.g., midazolam) to control postoperative pain. Table 225-2 lists factors responsible for high rates of unanticipated hospital admission. As reliance on ambulatory surgery has grown, more elderly patients are being cared for in the outpatient setting. It is generally agreed that age alone does not increase the risk for unanticipated hospital admission unless the patient is older than 85 years, is male, and has significant comorbidities (ASA class II or III). A history of inpatient hospitalization within the previous two quarters of the year is especially relevant. Further, the incidence of intraoperative cardiovascular events is higher in this age group compared with younger patients. Still, age alone is significant only as it correlates with increased medical comorbidities

Table 225–1

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Risk Factors for Postoperative Nausea and Vomiting (PONV) in Adults

Patient-Specific Factors Female sex Nonsmoking status History of PONV or motion sickness

Anesthetic Factors Use of volatile anesthetics within 2 hr Use of nitrous oxide Use of intraoperative or postoperative opioids

Surgery-Related Factors Surgery duration: each 30-min increase in surgery duration corresponds to a 60% increase in PONV incidence (e.g., a baseline risk of 10% is increased by 16% after 30 min) Surgery type: high-risk surgery includes ear, nose, and throat; laparoscopy; neurosurgery; breast surgery; strabismus surgery; laparotomy; plastic surgery Modified from Gan TJ, Meyer T, Apfel CC, et al: Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 97:62-71, 2003.

Table 225–2

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Factors Responsible for Unanticipated Hospital Admission

History of PONV Respiratory illness (even mild URI) and higher ASA status in pediatric patients Significant coexisting disease or age older than 85 yr Major procedures beginning in late afternoon or finishing after 3:00 PM Prolonged surgical procedures (>60 min) Poor social support for patient ASA, American Society of Anesthesiologists; PONV, postoperative nausea and vomiting; URI, upper respiratory infection.

and reduced social support postoperatively. For logistical reasons (e.g., time for recovery from anesthesia or to obtain adequate pain control), in both adult and pediatric patients, surgery performed or completed after 3:00 PM is more likely to result in unanticipated hospital admissions.

Implications Both the patient and his or her family are affected by an unscheduled hospital admission. This is especially true with pediatric patients, whose unanticipated hospital admission can affect the parents’ work schedules. Therefore, good communication with and support for the family are essential. Unanticipated admission or readmission rates not only reflect the quality of the outpatient surgery service but also have a significant financial impact on hospitals. The mean charges for all hospital readmissions were $8088 ± $29,425. Charges for unanticipated admission for pain control were $1869 ± $4553, compared with $12,000 ± $36,886 for non-paincontrol reasons.

MANAGEMENT Once a decision is made to admit a patient for anestheticrelated reasons, the anesthesiologist should immediately communicate with both the surgical team and the family to coordinate the process. In freestanding surgical centers with the capability to care for patients overnight, this is often the least expensive alternative. Most patients’ problems, such as PONV or severe pain, can be dealt with overnight, and the patient can be discharged the next morning. Most facilities equipped for overnight admissions, however, do not accept pediatric patients. In this case, plans must be made for admission to a hospital. For children with respiratory complications, admission to an observation or an intensive care unit should be strongly considered to ensure that the patient has supplemental oxygen and monitoring of oxygen saturation throughout the night. In all cases, documentation of the complication that has occurred, the treatment provided, and the necessity for admission is essential for both insurance and medicolegal reasons. Patients who are readmitted are usually under the care of a surgical team. Because inadequately controlled pain is one of the major reasons for readmission, every effort should be made to initiate pain control intraoperatively and postoperatively with a multimodal approach, including regional blocks,

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nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, and opioids.

PREVENTION Preoperative considerations include the following: ●

●

●

Assess risk factors from an anesthetic, medical, surgical, and social standpoint. Refer cases that are inappropriate for outpatient surgery to inpatient surgery. Plan for an overnight stay for high-risk patients undergoing high-risk procedures. Intraoperative considerations include the following:

●

●

●

●

Use regional anesthesia or monitored anesthesia care whenever possible. In patients with a history of or at high risk for PONV: ● Administer propofol for general anesthesia. ● Use multimodal antiemetic therapy. ● Provide generous hydration. ● Use narcotics sparingly. ● Consider the use of analgesic adjuncts, such as ketorolac or COX-2 inhibitors. ● Consider eliminating nitrous oxide and volatile anesthetics. ● Minimize the use of neostigmine. For patients at high risk of postoperative pain, use a multimodal approach, including: ● Nerve blocks ● Wound infiltration with local anesthetics ● NSAIDs and COX-2 inhibitors ● Opioids Avoid drugs that can cause sedation and altered mental status. In children with mild upper respiratory infections, avoid intubation. Postoperatively, take the following precautions:

● ● ●

Provide supplemental oxygen. Treat hypotension aggressively. If patient has PONV: ● Evaluate and treat pain. ● Hydrate vigorously. ● Use antiemetics early. ● Keep the patient recumbent until treated and fluid repleted.

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Avoiding unanticipated admission begins with an assessment of the risk for such admission and continues in the operating room and throughout the postoperative period, including cancellation of any inappropriately scheduled ambulatory cases. Recognition of risk factors preoperatively, aggressive pain control, use of multimodal therapy to prevent PONV (e.g., hydration, dexamethasone, metoclopramide, H2-blockers, serotonin inhibitors), and use of maneuvers to avoid bronchospasm and laryngospam intraoperatively (e.g., deep extubation) are advised. Postoperative management is vital. All patients at increased risk for unanticipated hospital admission should be well oxygenated and hydrated. Because pain alone may cause PONV, it should be treated promptly and aggressively. If the patient has refractory PONV, rescue therapy with other types of drugs (e.g., butyrophenones, phenothiazines, dopaminergic agents) should be considered. Finally, aggressive and early treatment in the recovery room can often avert an unanticipated hospital admission.

Further Reading Aldwinckle RJ, Montgomery JE: Unplanned admission rates and postdischarge complications in patients over the age of 70 following day case surgery. Anesthesia 59:57-59, 2004. Awad IT, Moore M, Rushe C, et al: Unplanned hospital admission in children undergoing day-case surgery. Eur J Anaesthesiol 21:379-383, 2004. Coley KC, Williams BA, da Pos SV, et al: Retrospective evaluation of unanticipated admissions and readmissions after same day surgery and associated costs. J Clin Anesth 14:349-353, 2002. Dornhoffer J, Manning L: Unplanned admissions following outpatient otologic surgery: The University of Arkansas experience. Ear Nose Throat J 79:713-717, 2000. Fleisher LA, Pasternak LR, Herbert R, et al: Inpatient hospital admission and death after outpatient surgery in elderly patients: Importance of patient system characteristics and location of care. Arch Surg 139: 67-72, 2004. Fortier J, Chung F, Su J: Unanticipated admission after ambulatory surgery: A prospective study. Can J Anaesth 45:612-619, 1998. Gan TJ, Meyer T, Apfel CC, et al: Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 97:62-71, 2003. Gupta A, Wu CL, Elkassabany N: Does the routine prophylactic use of antiemetics affect the incidence of postdischarge nausea and vomiting following ambulatory surgery? Anesthesiology 99:488-495, 2003. Hedayati B, Fear S: Hospital admission after day-case gynecological laparoscopy. Br J Anaesth 83:776-779, 1999. Lau H, Brooks DC: Predictive factors for unanticipated admissions after ambulatory laparoscopic cholecystectomy. Arch Surg 136:1150-1153, 2001. Shaikh S, Chung F, Imarengiaye C: Pain, nausea, vomiting and ocular complications delay discharge following ambulatory microdiscectomy. Can J Anaesth 50:514-518, 2003.

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Uncontrolled Pain Rodolfo Gebhardt and Nader D. Nader Case Synopsis A 75-year-old man with chronic obstructive pulmonary disease is recovering in the postanesthesia care unit following open cholecystectomy. He has shallow, rapid respiration and appears slightly cyanotic. He is moaning and says that his stomach hurts. You note that he received 100 μg fentanyl 2 hours earlier (at the beginning of surgery) and that no local anesthetics were used.

PROBLEM ANALYSIS Definition The International Association for the Study of Pain defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Pain is always subjective; each individual learns the application of the word through experience related to injury in early life.” In the postoperative setting, pain results mainly from the peripheral activation of nociceptors in injured tissues; however, a psychological component of lesser magnitude is always present. Factors such as a sense of hopelessness, a lack of control, and the underlying meaning of pain feed into the psychological aspect of pain. For instance, patients with postoperative pain following cancer surgery can be expected to have a different interpretation of their pain than patients recovering from noncancer surgery. The interpretation may include relief that the cancer is removed or fear that the pain reflects an ongoing cancerous process.

Recognition Some patients may not complain of pain or may be unable to communicate their degree of pain (Table 226-1). This usually reflects the age of the patient and is most common in younger patients or elderly patients with mental impairment. An advantage of pain scores or scales is that response to medication can be measured objectively and used to predict the further need for medication.

Table 226–1

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Assessment of Pain

Anticipate according to surgery Note analgesia given intraoperatively Measure according to age: <4 yr: physiologic parameters—heart rate, blood pressure, respiratory rate; verbal—”boo-boo,” “owie”; parental opinion (other causes for distress, e.g., hunger, strange environment) 4-7 yr: non-numeric (facial expressions) pain score >7-adult: visual or numeric analog pain score Treat based on assessment of pain Reassess patient frequently, repeating this cycle

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Risk Assessment It appears from many studies that all postoperative patients are at risk for poorly controlled pain. Particularly painful operations include thoracic, abdominal, and orthopedic (major joint) surgery. In contrast, body surface operations are associated with less pain. Delayed healing and wound infection may contribute to the prolongation of pain that might otherwise have been expected to resolve spontaneously. In the event of prolonged pain or pain out of proportion to the injury, a new (usually surgical) cause such as wound dehiscence, infection, or ischemia should be suspected.

Implications Poorly controlled postoperative pain may be associated with an increased incidence of myocardial ischemia and decreased bowel motility due to increased sympathetic activity. Respiratory splinting may cause a reduction in functional residual capacity of the lungs and increased sputum retention. Optimal analgesia can reverse some of these adverse events, but just making a patient “comfortable” with opioids actually does little to improve outcome. In contrast, in patients at high risk, optimal analgesia with thoracic epidural anesthesia may reduce the incidence of adverse outcomes if continued for at least 48 hours postoperatively. Importantly, patients express more satisfaction with their overall care if they are maintained in a pain-free or low-pain state postoperatively.

MANAGEMENT Methods of postoperative pain control are summarized in Table 226-2. The most important aspect of management is anticipation and frequent assessment of a patient’s pain, with appropriate treatment. An acute pain service can facilitate timely and appropriate intervention in pain management and can be used to educate nursing staff. Pain should be charted along with other physiologic measurements such as blood pressure and temperature. Patients should be encouraged to report pain and be reassured that doing so will not result in a painful injection (a common problem with children); patients should also be discouraged from thinking that nothing can be done to relieve pain (a common assumption in elderly patients). It is important to consider both physical (e.g., heat and massage) and psychological (e.g., distraction, relaxation, imagery) techniques for pain

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Table 226–2

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Summary of Methods for Postoperative Pain Control

Analgesics Opioids NSAIDs Acetaminophen Ketamine Others

Anesthetics Regional blocks and catheters Wound infiltration Nerve block

Physical

Behavioral Biofeedback Relaxation

Cognitive Imagery Distraction Hypnosis Choice and control NSAID, nonsteroidal anti-inflammatory drug; TENS, transcutaneous electrical nerve stimulation.

control, as well as the more commonly used pharmacologic methods (Table 226-3). Greater use of local anesthetics is encouraged to reduce pain. These can be injected into the wound edges, used for peripheral nerve blocks, or given via an epidural catheter. These methods are associated with few adverse side effects if special consideration is given to avoiding local anesthetic toxicity and one is mindful of associated sympathetic blockade with central neuraxial techniques. Opioids are highly effective in reducing pain. They work in both the spinal cord and the brain, with probable synergy between the two sites. Within the brain, opioids are less selective; euphoria is likely an important factor in

Table 226–3

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Pharmacologic Methods for Postoperative Pain Control

Local Anesthetics Tissue infiltration Peripheral nerve block Nerve plexus block: single injection or infusion Central neuraxial anesthesia: single injection or infusion Patient-controlled epidural pump

Opiods Oral Patient-controlled analgesia pump Intravenous infusion Central neuraxial analgesia: single injection or infusion Patient-controlled epidural pump

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producing analgesia. Intravenous opiates should be given by continuous infusion to children younger than 7 years and by patient-controlled analgesia pump to older children and adults. In patients with frequent demands for dosing, especially at night, when sleep is repeatedly interrupted, a background infusion of opioid can be added. This effectively prolongs the half-life of each bolus. There are reports of many beneficial aspects of epidural anesthesia and analgesia, including better suppression of surgical stress, positive effect on postoperative nitrogen balance, reduced blood loss, better peripheral vascular circulation, more stable cardiovascular hemodynamics, and better postoperative pain control. It seems likely that high-risk patients undergoing major intra-abdominal surgery would benefit from combined general and epidural anesthesia intraoperatively, with continuing postoperative epidural analgesia. Combining epidural opioids with subanesthetic concentrations of local anesthetics is important for three reasons: (1) it reduces the required doses of both drugs, (2) it enhances or at least maintains the desired degree of pain relief, and (3) it produces fewer adverse drug effects. Epidural catheters should be clearly labeled and skin sites inspected at least daily for signs of infection. Also, careful consideration should be given to the fact that any benefits may decrease over time, while associated risks may increase. In a review of randomized trials, Rodgers and colleagues found improved survival in patients receiving a neuraxial blockade. The mortality rate in this group was about one third less than that in patients receiving general anesthesia alone. The observed improvement in survival was due to a reduction in deaths from pulmonary embolism, cardiac events, and stroke. There was no difference in total mortality based on whether patients received a combined general-neuraxial anesthetic or a neuraxial anesthetic alone. In this same analysis, the odds ratios for respiratory depression were reduced by 59% in patients allocated to neuraxial blockade. The authors found a reduced risk of venous thromboembolism, myocardial infarction, bleeding complications, pneumonia, respiratory depression, and renal failure. The benefits attributed to neuraxial blockade may be due to a number of mechanisms, including altered coagulation, increased blood flow, improved ability to breathe when pain free, and reduction in the surgical stress response. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce opioid needs postoperatively. They represent a useful adjunct to opioids and, in some cases, provide adequate analgesia when used alone. It is important to remember that postoperative patients are under metabolic stress and thus predisposed to gastric ulcers. NSAIDs should therefore be used for only limited periods. Consideration should be given to providing gastric protection with drugs that reduce acid, coat the gastric mucosa, and restore the mucous barrier. As with balanced anesthesia, it is often better to use a balanced approach to analgesia. Attacking pain at different pain receptors with NSAIDs, opioids, oral or rectal acetaminophen, and low concentrations of local anesthetics is often more efficacious and results in fewer side effects than treating pain with a single treatment modality or higher drug doses.

SPECIAL TOPICS

Thermal Massage Physical therapy TENS

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Special Topics

PREVENTION Animal studies have provided convincing data to support the idea of preemptive analgesia, whereby the pain of surgery is blocked at the spinal cord dorsal horn level with either local anesthetics or opioids. Unfortunately, to date, human studies of preemptive analgesia do not confirm a reduction in postoperative pain, either at rest or with movement. Wound hyperalgesia may be reduced, but this does not translate into greater comfort for the patient. Prophylaxis therefore involves ensuring adequate analgesia so that the patient awakes without severe pain. This may be a challenge, especially if rapid awakening and early discharge are expected.

Further Reading Beyer JE, Denyes MJ, Villarruel AM: The creation, validation, and continuing development of the Oucher: A measure of pain intensity in children. J Pediatr Nurs 7:335-346, 1992.

Cousins M: Acute and postoperative pain. In Wall PD, Melzack R (eds): Textbook of Pain. Edinburgh, Churchill Livingstone, 1994, pp 357-385. Curley J, Castillo J, Hotz J, et al: Prolonged regional nerve blockade: Injectable biodegradable bupivacaine/polyester microspheres. Anesthesiology 84:1401-1410, 1996. Liu S, Carpenter R, Neal R: Epidural anesthesia and analgesia: Their role in postoperative outcome. Anesthesiology 82:1474-1506, 1995. Pounder DR, Steward DJ: Postoperative analgesia: Opioid infusions in infants and children. Can J Anaesth 39:969-974, 1992. Rigg JRA: Does regional block improve outcome after surgery? Anaesth Intensive Care 19:404-411, 1991. Rodgers A, Walker N, Schug S, et al: Reduction of postoperative mortality and morbidity with epidural or spinal anesthesia: Results from overview of randomized trials. BMJ 321:1493-1497, 2000. US Department of Health and Human Services: Acute Pain Management: Operative or Medical Procedures and Trauma: Clinical Practice Guidelines. AHCPR Publication No. 92-0032. Yeager MP, Glass DD, Neff RK, et al: Epidural anesthesia and analgesia in high risk surgical patients. Anesthesiology 66:729-736, 1987.

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Hemodynamic Instability Padmavathi Perala, Eileen Watson, and Nader D. Nader

227

Case Synopsis An 84-year-old man who just underwent colon resection for colon cancer has a blood pressure (BP) of 82/48 mm Hg and a heart rate of 120 beats per minute after 15 minutes in the postanesthesia care unit (PACU). New ST-T changes are noted in lead V5 of the electrocardiogram (ECG).

PROBLEM ANALYSIS

Hemodynamic instability in the PACU setting is a change from baseline cardiovascular dynamics sufficient to cause potential harm to end organs. Harm may be due to inadequate tissue perfusion (e.g., hypotension, arrhythmias), reduction in oxygen delivery relative to demand (e.g., tachycardia, hypertension), or direct damage to organs such as the brain or kidney (e.g., hypertension). Clinical signs of hemodynamic instability include severe hypertension, hypotension, tachycardia, bradycardia, and arrhythmias (Table 227-1).

Recognition Hemodynamic instability can occur any time after the induction of anesthesia to well into the postoperative period. There are many causes. Anticipation of potential problems results in earlier recognition, more timely intervention, and improved outcomes. Potential problems are identified by the routine monitoring of BP and ECG in the PACU. When vital signs are outside the norm for a given patient, it is prudent, especially if the patient is otherwise without complaints, to quickly determine whether the BP measurement is spurious. BP cuffs that are too large can result in falsely low measurements, and the converse is true for cuffs that are too small. The ECG monitor must be adjusted so that it counts only QRS complexes, not T waves as well. Supraventricular tachycardia may be difficult to diagnose without the use of a faster monitor speed, strip-chart recordings, 12-lead ECG, and calipers. In some instances, particularly to distinguish QRS

Table 227–1

■

Risk Assessment Events meeting the definitions given in Table 227-1 occur frequently in the PACU (about 6% to 8% of PACU admissions).

Definitions of Clinical Signs of Hemodynamic Instability

Sign

Definition

Hypertension

Increase of 20% over baseline preoperative value for 15 min (50% for single measurement), or SBP >180 mm Hg, or DBP >110 mm Hg* Decrease of 20% from baseline preoperative value for 15 min (50% for single measurement), or SBP <80 mm Hg, or DBP <50 mm Hg Increase of 20% over baseline preoperative value for 15 min, or >120 beats/min for patients older than 2 yr Decrease of 20% from baseline preoperative value, or <50 beats/min Any rhythm other than sinus at a rate appropriate for the circumstances

Hypotension Tachycardia Bradycardia Arrhythmia

*The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) defines severe (stage 2) hypertension as SBP >160 mm Hg and DBP >160/100 mm Hg (see also Chapter 77). DBP, diastolic arterial blood pressure; SBP, systolic arterial blood pressure.

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SPECIAL TOPICS

Definition

aberrancy from ectopy, a full 12-lead ECG is required. Finally, bradycardia may reflect youthful age or a high level of physical fitness. The causes of hemodynamic deterioration in the PACU, in order of prevalence, are (1) alterations in volume status (e.g., preoperative dehydration, recent hemodialysis, intraoperative blood or third-space loss, volume overload), (2) compromise of the cardiovascular system (e.g., myocardial ischemia, valvular pathology, thromboembolic events, arrhythmias), (3) drug-related events (e.g., allergic reactions, systemic absorption of local anesthetics, withdrawal or overdose of antihypertensives and β-blockers), and (4) residual effects of anesthetic agents after neuraxial blockade. Hypercarbia or hypoxia with inadequate ventilation or shunting can cause hypertension, tachycardia, or arrhythmias. When severe hypoxemia is present, bradycardia, hypotension, and malignant arrhythmias are seen more often. Following placement of a central line, tension pneumothorax may cause hypotension due to reduced preload. Postoperative pain and emergence delirium can result in tachycardia and hypertension. Vasovagal response due to postoperative pain can also contribute to hemodynamic changes. Though uncommon, malignant hyperthermia, pheochromocytoma, or thyroid storm may manifest for the first time in the PACU, and these disorders should be included in the differential diagnosis of tachycardia and hypertension in PACU patients.

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Table 227–2

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Special Topics

Causes of Hemodynamic Instability in the Postanesthesia Care Unit

Event

Patient Factors

Surgical Factors

Other Factors

Hypertension

Increasing age Tobacco use Renal disease Increasing age Female gender Structural heart disease Chronic pulmonary disease Sepsis Increased age ASA status I or II β-blocker or calcium channel blocker use

Intracranial procedure

Intraoperative hypertension Postoperative pain, hypoventilation, nausea, or vomiting Intraoperative hypotension Postoperative shivering, nausea, or vomiting Pain Hypovolemia

Hypotension Tachycardia, including tachyarrhythmias Bradycardia, including bradyarrhythmias

Intra-abdominal procedure Emergency procedure Cardiothoracic surgery Duration >4 hr Congenital or valvular heart surgery

Intraoperative bradycardia Postoperative nausea or vomiting

ASA, American Society of Anesthesiologists.

The most important causes of each of these are shown in Table 227-2. It should be noted that patients with severe cardiovascular disease undergoing major procedures are largely absent from studies of PACU events because they are often admitted directly to an intensive care unit (ICU) for continued invasive monitoring or ventilatory support or for other surgical or anesthetic reasons. Morbidity and mortality from the hemodynamic instability varies. Patients’ ability to tolerate hemodynamic changes depends on preexisting conditions, such as hypovolemia, medications, and coronary artery disease (CAD). Patients with CAD tolerate any changes in heart rate or BP poorly. More than 11 million Americans suffer from CAD, and the prevalence is expected to rise as the number of elderly persons continues to increase. Patients with CAD are a significant proportion of surgical patients, and they have a significantly increased risk for perioperative myocardial ischemia and infarction. Surgery-associated reductions in coronary blood flow can cause transient or permanent myocardial injury in any patient. However, both the risk and the severity of perioperative cardiac ischemia are increased in patients with CAD. Perioperative myocardial ischemia in such patients is particularly serious, and the development of strategies to reduce the resultant tissue injury is an important goal. Although no specific anesthetic technique has proved to be superior in protecting against perioperative myocardial ischemia and infarction, there is mounting evidence that the administration of volatile anesthetics during myocardial ischemia with reperfusion can protect against myocardial injury. Volatile anesthetics have been shown to enhance indices of myocardial performance, as well as metabolic and ultrastructural myocardial recovery after global and regional myocardial ischemia. After a brief period of ischemia (myocardial stunning), both systolic and diastolic dysfunction of the heart continues for a significant time after reperfusion. Systolic dysfunction manifests as decreased contractile function of the heart and low cardiac output and stroke work indices. In contrast, primarily left ventricle relaxation is impaired with diastolic dysfunction. Although the frequency of diastolic dysfunction is higher than that of systolic dysfunction, the clinical importance of isolated diastolic heart failure is still debated by many clinicians. Improved calcium

homeostasis of the myocardium through the activation of both cytoplasm and mitochondrial KATP channels is the most likely explanation for the myocardial protection afforded by volatile anesthetics.

Implications There is a recognized potential for severe morbidity if hemodynamic instability is not recognized and treated expeditiously. Myocardial infarction, cerebral infarction or hemorrhage, renal failure, and death are possible outcomes. Not all abnormal parameters are equal in predicting serious adverse outcomes. Table 227-3 shows that patients with hypertension or tachycardia in the PACU are many times more likely than those without such findings to be admitted to an ICU or to die. However, those with bradycardia or hypotension are no more likely to suffer such extreme outcomes than are those without such cardiovascular events. Once again, patients with severe cardiovascular disease and

Table 227–3

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Rate and Outcome of Unplanned Intensive Care Unit Admissions in Patients with (or without) Cardiovascular Events in the Postanesthesia Care Unit

Event Hypertension (no hypertension) Tachycardia (no tachycardia) Bradycardia (no bradycardia) Hypotension (no hypotension)

Unplanned ICU Admission (%)*

Mortality (%)*

2.6† (0.2)

1.9† (0.3)

4.0† (0.2)

2.3† (0.4)

0.2 (0.2)

0.7 (0.4)

0.7 (0.2)

0.7 (0.4)

*Numbers in parentheses are the admission rates for patients without the specific cardiovascular event. † P < .01 vs those without the cardiovascular event. Adapted from Rose DK, Cohn MM, DeBoer MM, et al: Cardiovascular events in the PACU. Anesthesiology 84:772-781, 1996.

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those undergoing major surgery are largely absent from such studies. Whether intervention is warranted for specific hemodynamic instability findings depends on the underlying cause and physiologic consequences, as well as patient-specific comorbidity and other factors.

MANAGEMENT

Figure 227–1 ■ A systematic approach to the diagnosis and management of postoperative hypotension. HCT, hematocrit; I&O, intake and output.

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hemorrhages) is a hypertensive emergency that requires rapid intervention with intravenous vasodilators (e.g., nicardipine, nitroprusside, nitroglycerin, hydralazine), β-blockers or mixed β- and α-adrenergic blockers (esmolol, labetalol), or both. Although sublingual nifedipine has been used, a distinct disadvantage of this drug is its unpredictable absorption, with a recognized potential for precipitous, dangerous hypotension. Hypotension in the PACU is usually a sign of hypovolemia or blood loss. Hypotension due to heart failure is rarely reported in PACU patients, likely because those at highest risk for heart failure go directly to the ICU. Hypovolemia may be absolute (inadequate fluid replacement), ongoing (hemorrhage), relative (high neuraxial blockade), or mechanical (impaired venous return with vena cava compression, pneumothorax, pericardial tamponade). Therapy is dictated by the cause, comorbid conditions, and presence or absence of signs or symptoms indicating adverse effects on end-organ perfusion. Figure 227-1 outlines a systematic approach to the diagnosis and management of hypotension. Tachycardia in the PACU is commonly associated with increased sympathetic tone. Therapy is first directed toward the cause, especially if the patient is otherwise stable. Causes are similar to those for hypertension. Tachycardia is also the most common presenting feature of malignant hyperthermia, and this diagnosis must be entertained and excluded. If the patient is experiencing chest pain or mental status changes, if the tachycardia does not resolve with correction of presumed causes, or if no underlying problem can be identified, other means are necessary to determine management.

SPECIAL TOPICS

Hypertension in the PACU should first be considered a sign of excessive adrenergic stimulation. Emergence excitement, excessive pain, urinary retention, hypoxemia, hypercarbia, hypothermia (35°C), and nausea should be excluded as causes. If one or more of these factors are present, eliminating them will likely reduce the BP. If not, more serious processes (e.g., intracranial hypertension) must be excluded, and a decision to treat or simply observe must be made. Postoperative hypertension in patients without a history of prior hypertension is not uncommon and usually follows a benign course, with resolution in 3 to 5 hours. For those with hypertension, heart disease, or cerebrovascular disease, hypertension should be treated to bring BP to within 20% to 25% of the patient’s optimal preoperative BP. The choice of agents to accomplish this depends on comorbidities and whether there are signs or symptoms of end-organ damage (headache, disorientation, chest pain, hematuria). BP 160/100 mm Hg or higher with evidence of end-organ damage (e.g., renal dysfunction, myocardial ischemia or infarction, stroke, retinal

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An ECG rhythm strip or increased strip-chart monitoring speed (25 to 50 mm/second) may help determine whether a wide complex tachycardia is supraventricular with ventricular aberration or ventricular in origin, or whether a narrow QRS complex rhythm is atrial or atrioventricular (AV) junctional. Laboratory testing may be needed to identify contributing factors such as electrolyte imbalance or excessive drug concentrations (e.g., digoxin, theophylline). Therapy for ventricular tachyarrhythmias is directed at abolishing the cause or mechanism (automaticity, triggering, reentry) with drugs such as lidocaine, procainamide, and amiodarone. With severe hemodynamic compromise, immediate cardioversion or defibrillation is the preferred initial treatment, with drugs used to prevent recurrences (see Chapters 79 to 81 and 229). Therapy for supraventricular tachyarrhythmias is intended to reduce automaticity or triggering (β-blockers, calcium channel blockers, magnesium) or to slow AV node conduction and increase refractoriness (adenosine, calcium channel blockers, β-blockers, digoxin, edrophonium). For all other perioperative tachyarrhythmias, including those with ventricular preexcitation or Q-T interval prolongation, refer to Chapters 79 to 81 and 229. Cardioversion should always be considered first for any nonsinus-origin supraventricular tachycardia with evidence of acute circulatory compromise (e.g., shortness of breath, chest pain, ST segment changes, mental status changes). Overdrive atrial or ventricular pacing may also be effective against atrial flutter or paroxysmal supraventricular tachycardia. Cardioversion or defibrillation is first-choice therapy, along with airway support and chest compressions if needed, for any patient who has lost consciousness or is pulseless. For any patient with tachyarrhythmias that are not readily or easily identified or explained, a cardiologist should be consulted. Most bradyarrhythmias in the PACU are caused by an excess of parasympathetic tone (see Chapter 82). The rhythm may be sinus or atrial in origin (bradycardia or sinus arrhythmia, wandering atrial pacemaker) or AV junctional. Alternatively, there may be intermittent or no transmission of supraventricular impulses with AV junctional or ventricular escape beats or rhythms. If the patient is symptomatic, urgent therapy consists of positive chronotropes (e.g., atropine, β-agonists); if these fail or only aggravate the arrhythmia, temporary transcutaneous, transesophageal, or transvenous pacing is used. If there is reasonable hemodynamic stability (e.g., new first degree or type 1 second degree AV block, AV junctional rhythm with AV dissociation), urgent intervention may not be necessary; however, such intervention should be readily available in case it becomes necessary. Any patient with potentially unstable bradyarrhythmias or who needs pacing should receive the benefit of a cardiology consultation. If the patient is asymptomatic and hemodynamically stable, he or she may be observed. Normal sinus rhythm is often restored after dissipation of anesthetic effects with redistribution or metabolism and restoration of normal body temperature. Ectopic beats of atrial or ventricular origin are common postoperatively. They are often a sign of increased sympathetic

tone, as is sinus tachycardia. Up to five ectopic ventricular beats per minute can be considered normal. If they are more frequent or have a multiform appearance, more careful evaluation and correction of the cause are necessary. If ectopic ventricular beats predispose to sustained ventricular tachycardia, treatment is mandatory, along with a search for and correction of the cause. Ventricular bigeminy is also relatively common in the PACU; it is the result of stress and is usually self-limited. In patients with heart disease or severe physiologic imbalance, however, any ventricular arrhythmia is a more ominous sign.

PREVENTION Many factors that predispose patients to postoperative hemodynamic instability are beyond the control of the anesthesiologist. Included are patient factors (e.g., age, comorbid conditions) and surgical factors (e.g., duration and location of surgery). However, some factors are within the control of the anesthesiologist: ● ● ●

● ● ● ● ●

Assurance of adequate volume and blood replacement Maintenance of appropriate intraoperative hemodynamics Avoidance of excessive sympathetic stimulation: ● Adequate analgesia ● Adequate ventilation ● Avoidance of hypothermia ● Plan for the treatment of nausea and vomiting Avoidance of excessive parasympathetic tone Adequate ventilation to remove volatile agents Judicious use of cholinesterase inhibitors Proper use of anticholinergics Plan for the prevention and treatment of postoperative nausea and vomiting

Further Reading Chobanian AV, Bakris GL, Black HR, et al: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 report. JAMA 289:2560-2572, 2003. Essentials of ACLS. In Cummins RO (ed): Textbook of Advanced Cardiac Life Support. Dallas, American Heart Association, 1994, pp 1-32-1-40. Gwirtz K: Management of recovery room complications. Anesthesiol Clin North Am 14:307-339, 1996. Hines RI, Barash PG, Watrous G, et al: Complications occurring in the PACU. Anesth Analg 74:503-509, 1992. Moyes J, Oyos T: Cardiovascular system. In Brown M, Brown E (eds): Comprehensive Postanesthesia Care. Baltimore, Williams & Wilkins, 1997, pp 117-134. Nader ND: Anesthetic preconditioning: A new horizon on myocardial protection. In Salerno TA, Ricci M (eds): Myocardial Protection. Armonk, N.Y., Blackwell Publishing (Futura), 2003, pp 33-42. Rose DK: Recovery room problems or problems in the PACU. Can J Anaesth 43:116-122, 1996. Rose DK, Cohen MM, DeBoer MM, et al: Cardiovascular events in the PACU. Anesthesiology 84:772-781, 1996. Tanaka K, Ludwig LM, Kersten JR, et al: Mechanisms of cardioprotection by volatile anesthetics. Anesthesiology 100:707-721, 2004.

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Mijin Lee Case Synopsis

PROBLEM ANALYSIS Definition ECT is used primarily to treat severe depression or catatonia that is refractory to medical therapy. A generalized seizure is induced by an electrical stimulus applied to one or both cerebral hemispheres. The seizure must last 30 to 60 seconds to have a therapeutic effect.

Recognition Although ECT is relatively safe, it generates profound cardiac and cerebrovascular responses. The cardiovascular effect results from autonomic nervous system activation, initially with predominant parasympathetic discharge (the tonic phase) lasting approximately 5 to 10 seconds. This is followed immediately by pronounced sympathetic discharge (the clonic phase). Clinical consequences of these two phases are as follows: 1. Tonic phase: transient bradycardia, hypotension, and, rarely, asystole lasting several seconds 2. Clonic phase: tachycardia, hypertension, and arrhythmias peaking 1 minute after ECT shocks and generally resolving within 5 to 10 minutes thereafter ECT-induced cerebrovascular changes also include a 100% to 400% increase in cerebral blood flow above baseline, which is primarily due to a seizure-associated increase in cerebral metabolic rate and, to a lesser extent, elevated blood pressure. In susceptible patients, the consequent increase in intracranial volume may cause a dangerous increase in intracranial pressure. All patients should be monitored by at least electrocardiogram lead II, with a V4 or V5 lead in patients at risk for coronary artery disease. Also, continuous arterial oxygen saturation monitoring by pulse oximetry and noninvasive blood pressure measurement every 3 to 5 minutes are necessary.

SPECIAL TOPICS

A 55-year-old man who has major depression but is otherwise healthy presents for electroconvulsive therapy (ECT). Immediately following the electrical stimulus, he develops a 5-second episode of asystole, followed by a rapid increase in heart rate to 140 beats per minute and in blood pressure to 185/120 mm Hg. On emergence, the patient has copious oral secretions and is disoriented, but his vital signs have stabilized.

Risk Assessment Several contraindications to ECT have been described (Table 228-1). These largely reflect the significant cardiovascular and cerebrovascular changes associated with ECT. It should be noted, however, that ECT has been performed safely on a variety of high-risk patients, including those with recent myocardial infarction, cerebral aneurysm, and recent

Table 228–1

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Contraindications to Electroconvulsive Therapy

Absolute Pheochromocytoma Recent myocardial infarction (<4-6 wk)* Recent cerebrovascular accident† Recent intracranial surgery† Intracranial mass lesion Unstable cervical spine

Relative Angina‡ Congestive heart failure§ Cardiac rhythm management device¶ Severe pulmonary disease Major bone fracture Glaucoma Retinal detachment Thrombophlebitis Pregnancy *Current American College of Cardiology–American Heart Association guidelines advise waiting 4-6 wk after an uncomplicated myocardial infarction (residual New York Heart Association [NYHA] class III or IV heart failure or persistent hemodynamically disadvantageous arrhythmias) to perform elective surgery. No specific recommendations are made for electroconvulsive therapy, although it would seem reasonable to classify it as a minor or (at worst) an intermediate-risk procedure. † Recent here means within 3 mo. ‡ Chronic, stable angina for which no catheter or surgical intervention is indicated. § Likely not NYHA class III and certainly not class IV heart failure. ¶ Seizures may generate sufficient myopotentials to be interpreted by an internal cardioverter-defibrillator as a tachyarrhythmia, initiating antitachycardia pacing or shock therapies. Alternatively, they may cause pacemaker inhibition (in a pacemaker with unipolar sensing) or high-rate ventricular pacing (in an adaptive-rate pacemaker).

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cerebrovascular accident. Indeed, one study noted that major cardiovascular complications occurred equally among patients considered at high risk for coronary events and those at low risk for such events.

Implications The physiologic effects of ECT are listed in Table 228-2. The overall morbidity associated with ECT is quite low. In one large study, the complication rate was 0.75%. Complications included vertebral body compression, circulatory insufficiency, laryngospasm, status epilepticus, tooth damage, and allergic reactions. Another study noted that the incidence of aspiration among elderly patients was 2.5%. The mortality rate is 0.029% during a course of ECT therapy, whereas that for a single ECT treatment is 0.000045%. Malignant tachyarrhythmias, myocardial infarction, congestive heart failure, and cardiac arrest are rare but constitute the major sources of morbidity and mortality. They generally occur during the recovery period. Patients with increased intracranial pressure, intracranial mass lesions, or vascular anomalies may not tolerate the large increase in cerebral blood flow associated with ECT. One study found that the overall morbidity for patients with brain tumors undergoing ECT was 74%, with a 1-month mortality rate of 28%. Also, disorientation is common, occurring in 12% of the elderly and 9% of younger patients. Transient muscle aches, memory disturbances, and headaches are among the more common patient complaints following ECT.

MANAGEMENT The most common complications are related to hemodynamic changes. Bradycardia and transient asystole generally do not require treatment, as both are short-lived. Occasionally, anticholinergic agents are administered, but their routine use may exacerbate the predictable, longer-lasting tachycardia that follows. Tachycardia and hypertension are better managed with a short-acting β-blocker such as esmolol

Table 228–2

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Physiologic Effects of Electroconvulsive Therapy

Cardiovascular Parasympathetic nervous system (tonic phase) Decreased heart rate Hypotension Bradyarrhythmias (transient asystole; escape beats or transient escape rhythms) Sympathetic nervous system (clonic phase) Increased heart rate Hypertension Tachyarrhythmias; atrial or ventricular extrasystoles

Cerebral Increased cerebral blood flow Increased intracranial pressure

Other Increased intraocular pressure Increased intragastric pressure

given in 10- to 20-mg increments. However, combined intravenous bolus esmolol and nicardipine control both increased heart rate and blood pressure better than either drug alone.1 Labetalol may lower the seizure duration, has a longer onset of action, and prolongs any decrease in blood pressure after ECT. Nitroglycerin can be used if hypertension is a greater problem than tachycardia.2 Midazolam (0.5 to 2 mg intravenously) effectively treats post-ECT agitation.

PREVENTION Before ECT, all patients should take nothing by mouth for at least 8 hours to reduce the risk of aspiration. Anticholinergics such as glycopyrrolate and atropine may be used to prevent bradycardia, asystole, and excessive salivation in patients with a previous history of such events. Glycopyrrolate is preferred; atropine is associated with a more pronounced increase in heart rate. Routine use of anticholinergics, however, has been criticized as unnecessary. Induction of anesthesia for ECT has been performed successfully with a number of agents, including methohexital, propofol, and etomidate. Methohexital remains the gold standard for induction of anesthesia, but other agents have their place as well. Methohexital has a rapid onset, a short duration of action, minimal anticonvulsant effects, and a rapid recovery. Remifentanil added to a reduced dose of methohexital has been shown to help prolong seizures in patients with suboptimal seizure duration. Propofol has the advantage of superior hemodynamic stability and more rapid return of cognitive function. It may also help shorten seizure duration in patients with prolonged seizures and minimize postictal nausea and vomiting. Etomidate may be preferred in patients with compromised cardiac status, because it has the least potential for untoward effects on cardiovascular function and minimal anticonvulsant effects. Muscle relaxation is required to avoid violent muscle contractions, which can cause bone fracture during ECT. Succinylcholine is the agent of choice owing to its rapid onset and short duration of action. In patients in whom succinylcholine is contraindicated, a short-acting nondepolarizing agent such as mivacurium can be used. If so, more prolonged sedation (e.g., bolus propofol plus an intravenous infusion of propofol) should be considered for these patients, because the duration of muscle relaxation may outlast that of the induction agent. Increased hemodynamic stability has been attempted by pretreatment with esmolol, labetalol, or nitroglycerin.3 Esmolol (2 mg/kg) given 2 minutes before ECT significantly reduced tachycardia and hypertension compared with

1 This is based on studies of both drugs’ effectiveness for blunting hyperadrenergic responses to laryngoscopy and tracheal intubation (Anesth Analg 90:280-288, 2000) or ECT (Anesthesiology 89:A218, 1998). When the drugs are combined for ECT, ideal intravenous bolus doses are esmolol 1 mg/kg and nicardipine 30 mg/kg. 2 Use of nitroglycerin, which is a primary venodilator, is ill advised in patients with chronic hypertension or who are preload restricted, owing to the potential for untoward hypotension. 3 See notes 1 and 2.

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nitroglycerin (3 μg/kg) or placebo. Also, up to 4.4 mg/kg of esmolol given before ECT was not associated with increased asystole, even without anticholinergic premedication. In contrast, labetalol has been associated with prolonged depression of systolic blood pressure after ECT. Finally, in patients known to be agitated after ECT, prophylactic use of midazolam is effective after completion of the ECT-generated seizure activity.

Further Reading Abrams R: The mortality rate with ECT. Convulsive Ther 13:125-127, 1997. Avramov MN, Husain MM, White PF: The comparative effects of methohexital, propofol, and etomidate for electroconvulsive therapy. Anesth Analg 81:596-602, 1995. Bailine SH, Petrides G, Doft M, et al: Indications for the use of propofol in electroconvulsive therapy. J ECT 19:129-132, 2003.

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Castelli I, Steiner LA, Kaufmann MA, et al: Comparative effects of esmolol and labetatol to attenuate hyperdynamic states after electroconvulsive therapy. Anesth Analg 80:557-561, 1995. Eagle KA, Berger PB, Calkins H, et al: ACC/AHA update for perioperative cardiovascular evaluation for noncardiac surgery. Circulation 105:1257-1267, 2002. Folk JW, Kellner CH, Beale MD, et al: Anesthesia for electroconvulsive therapy: A review. J ECT 16:157-170, 2000. Labbate LA, Miller JP: Midazolam for treatment of agitation after ECT. Am J Psychiatry 152:472-473, 1995. Morgan GF, Mikhail MS, Murray MJ: Clinical Anesthesiology, 3rd ed. New York, McGraw-Hill, 2002. Rice EH, Sombrotto LB, Markowitz JC, et al: Cardiovascular morbidity in high-risk patients during ECT. Am J Psychiatry 151:1637-1641, 1994. Smith DL, Angst MS, Brock-Utne JG, et al: Seizure duration with remifentanil/methohexital vs methohexital alone in middle-aged patients undergoing electroconvulsive therapy. Acta Anaesthesiol Scand 47:1064-1066, 2003. SPECIAL TOPICS

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Cardioversion Melissa Franckowiak and Nader D. Nader Case Synopsis A 79-year-old man with a history of two myocardial infarctions and coronary artery disease was referred for coronary artery bypass grafting for angina with anterolateral ischemia. Quadruple bypass grafting was performed, and intraoperatively he received cardiac ablation for definitive treatment of a persistent arrhythmia. The intraoperative course was uneventful. However, on the second postoperative day, the patient developed atrial fibrillation (AFB) and was scheduled for elective cardioversion. After three attempts at synchronized cardioversion (75 J, 100 J, and 150 J), he had asystole lasting 45 seconds but then spontaneously converted to sinus rhythm at 60 beats per minute. On a follow-up visit 10 days later, his functional status had improved, and he was angina free.

PROBLEM ANALYSIS Definition Direct-current cardioversion (CV) or defibrillation (DF) is commonly used to treat cardiac tachyarrhythmias to promptly restore hemodynamic stability and prevent myocardial ischemia. Synchronized shocks (CV) are used to restore sinus rhythm in patients with reentrant ventricular and supraventricular tachyarrhythmias with distinct R or S waves. CV does this by depolarizing all or at least a critical mass of excitable myocardium to terminate reentry pathways. With CV, shocks are synchronized with the QRS complex to avoid the risk of triggering ventricular fibrillation if energy is delivered during the vulnerable period of myocardial repolarization (ST segment). Usually, external CV requires that paddles be applied firmly (about 25 pounds of pressure) to the chest wall, with one paddle applied to the right side of the sternum at the level of the second rib and the other paddle applied at the fifth intercostal space in the midclavicular line. Alternatively, CV pads are used to improve energy transmission and the ability to pace the patient transcutaneously.

Recognition CV or DF is the preferred initial treatment for all unstable tachyarrhythmias amenable to termination by such means under the current advanced cardiovascular life support (ACLS) guidelines. Only ectopic cardiac rhythm disturbances (i.e., escape rhythms or tachycardia, uniform or multiform atrial ectopic tachycardia) cannot be so terminated. Further, CV is increasingly being advised as the initial management for stable tachycardias, with drugs used to prevent recurrences. This is due in part to the recognition that antiarrhythmic drugs may cause proarrhythmic events far more often than previously believed (see Chapters 12 and 79). Patients with a diseased myocardium, especially with impaired myocardial function (ejection fraction ≤0.35), rarely should receive multiple pharmacologic treatments in an attempt to convert either unstable or stable tachyarrhythmias. 906

Risk Assessment It is critical for anesthesiologists and all ACLS providers to recognize the difference between stable and unstable tachyarrhythmias, because the time course for treatment can be dramatically different. Patients with stable hemodynamics (i.e., the arrhythmia does not compromise hemodynamics sufficiently to pose an immediate threat to life or vital organ perfusion) can undergo elective CV in most hospital locations, as long as the equipment required for safe airway management and an appropriate anesthetic plan are in place. However, in those with unstable tachyarrhythmias (i.e., the arrhythmia compromises hemodynamics or poses an immediate threat to life or vital organ perfusion), CV or DF may be required in less than ideal circumstances to save the patient’s life or avoid the risk of permanent end-organ injury (e.g., the brain). Unstable tachyarrhythmias are those associated with signs or symptoms of an acute coronary syndrome (e.g., angina, electrocardiogram changes indicating ischemia), heart failure (e.g., pulmonary edema, rales, jugular venous distention, peripheral edema), brain hypoperfusion (e.g., mental status changes, altered consciousness), diaphoresis, or impaired perfusion of other vital organs. Of course, some of these signs will be absent if the patient is heavily sedated or under general anesthesia. In this case, it is necessary to rely more heavily on the electrocardiogram, blood pressure, pulse oximeter, end-tidal carbon dioxide, skin color, peripheral pulses, and evidence of vital organ perfusion (e.g., reduced urine output, bispectral index or patient state analyzer changes). Unstable tachyarrhythmias require prompt treatment with CV or DF.

Implications The recent widespread availability of external cardioverterdefibrillators that provide CV or DF with biphasic shock waves has substantially reduced the amount of energy needed for CV or DF. However, elective CV is still painful and requires anesthesia care to provide sedation and to ensure circulatory stability and adequate respiratory function. General anesthesia is performed safely and effectively with the newer intravenous

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MANAGEMENT Anesthesiologists are often asked to treat patients having CV outside of the operating room or postanesthesia care environment, where providing adequate care can be challenging. A complete medical history and focused physical examination are always necessary to diagnose and prevent untoward complications associated with anesthesia for elective CV. Patients presenting for elective CV are strongly advised to avoid the intake of solid food for 6 hours and liquids for at least 2 hours. When CV is performed outside of the operating room or postanesthesia care unit, a complete setup must be present, including equipment for suctioning and emergency intubation, laryngeal masks, an Ambu bag with attached facemask, and an oxygen source. The selection of the anesthetic agent is based on the anticipated required duration of action, as well as the patient’s hemodynamic stability and associated comorbidities. Short-acting intravenous induction agents and midazolam have been used to provide general anesthesia for CV. Although midazolam has a more prolonged duration of action, it is associated with greater interpatient variability. Both thiopental and propofol are suitable for elective CV in hemodynamically stable patients with preserved myocardial function. In patients with reduced ejection fractions, etomidate is often used to reduce hypotension. An initial decrease in blood pressure occurs with both etomidate and propofol after CV, but blood pressure returns to baseline faster with propofol. Propofol also causes more bradycardia and apnea than etomidate, but emergence from anesthesia is faster. Propofol may be administered via bolus or infusion (the latter attenuates its hypotensive effects). There is no difference in psychomotor skills after either etomidate or propofol. Etomidate is sometimes avoided because of its potential to cause involuntary

Cardioversion

907

muscle movements. These may be sensed and interfere with synchronized CV and electrocardiogram interpretation. Intravenous lidocaine (50 to 100 mg) is commonly used before propofol to reduce pain at the injection site. Lidocaine in doses greater than 100 mg does not affect CV thresholds with single or sequential shocks. Hemodynamic stability is maintained with judicious intravenous fluid administration and, if needed, vasoactive drugs. Pulmonary complications require supportive therapy to ensure adequate oxygenation and ventilation. Bone fractures (often of the vertebral bodies) are usually treated conservatively. Bed rest and analgesics for pain often provide satisfactory results. Neurologic sequelae are rare but may be associated with cord compression due to severe compression fractures or vertebral dislocation. Surgical intervention may be necessary.

Emergent Cardioversion for Unstable Tachyarrhythmias Current ACLS guidelines recommend a sequence of energy levels for synchronized, monophasic shocks for CV in adults. It begins with 100-J shocks and sequentially increases to 200, 300, and 360 J. Energy levels for biphasic shock (BPS) CV vary among the different cardioverter-defibrillators and are provided in the operator’s manual for each device. Exceptions to these guidelines include atrial flutter, which converts with as little as 50 J (BPS), and polymorphic ventricular tachycardia (VT), which requires higher energy levels, beginning with 200 J (BPS). Recent evidence indicates that as the cumulative energy and the number of shocks for external DF increase, the potential for myocardial dysfunction increases. Thus, the lowest possible energy levels should be used. Premedication is recommended whenever possible, even in emergent cases, owing to the painful nature of the procedure. Emergent CV is advised for AFB or atrial flutter if the ventricular rate is greater than 150 beats per minute in adults. Children, especially neonates, tolerate much higher heart rates than adults do. In fact, they rely on increased heart rate more than on stroke volume to maintain cardiac output with hypovolemia and sepsis. With tachycardia and ventricular rates greater than 220 beats per minute in neonates or 180 beats per minute in children, tachycardia is often supraventricular in origin. Even so, hemodynamic stability must be assessed. Even in children with supraventricular tachycardia, hemodynamic stability is often maintained in conditions such as Wolff-Parkinson-White syndrome and other disorders. If so, CV can be performed under more controlled conditions while hemodynamics are monitored. With supraventricular tachycardia, in contrast to sinus tachycardia, there is usually no obvious cause (e.g., sepsis, pain, hypovolemia) for the degree of tachycardia. Drug treatment for specific supraventricular tachycardias is discussed elsewhere in this book (see Chapters 10 to 13, 79, and 80). DF is used for pulseless VT or ventricular fibrillation in children and adults, or whenever R and S waves cannot be distinguished. R-wave or S-wave synchronized shocks (CV) are used for VT with palpable pulses. With VT, the rate is at least 120 beats per minute, and QRS complexes are widened (>120 msec). Such QRS widening can also occur with QRS

SPECIAL TOPICS

agents that have a rapid onset of action and fast recovery. Spontaneous breathing is usually maintained, so muscle relaxants are often unnecessary. Hemodynamic dysfunction with tachyarrhythmias (e.g., myocardial ischemia, heart failure, loss of atrial transport function, reduced perfusion to vital organs) compounds any hemodynamic effects of hypnotic agents such as propofol or barbiturates. Underlying valve pathology and enlarged atria may predispose to atrial flutter or fibrillation that is refractory to CV. Common complications of CV include failure to convert the tachyarrhythmia, asystole, hypotension, respiratory depression, gastric aspiration, and difficult airway management. Complications related to airway management can be reduced by careful preoperative examination. Full stomach, obesity, and hiatal hernia are among the risk factors for pulmonary aspiration and pneumonitis. Bone fractures have been reported in elderly patients. These are related to seizure-like muscle contractions similar to those with electroconvulsive therapy and are more likely in patients with osteoporosis and other mineral-deficient bone disorders. A meta-analysis by Swedish researchers showed that the relative risk for all fractures increased 1.5-fold for each one standard deviation decrease in bone mineral density at any skeletal site. However, vertebral mineral density is superior for estimating the risk of vertebral fracture (relative risk 2.3).

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aberration (see Chapters 80 and 81). In the absence of structural heart disease, poisoning, or severe physiologic imbalance, primary VT is rare in children. With VT and palpable pulses in children, CV begins at 0.5 to 2 J/kg (BPS) and is followed by drugs to prevent recurrences (e.g., amiodarone 5 mg/kg intravenously over 30 to 60 minutes). With destabilizing hemodynamics, CV should not be delayed, and sedation should be used whenever possible.

Cardioversion for Atrial Fibrillation Management for AFB is also discussed in Chapters 79 and 80. Emergency CV should not be used for AFB lasting longer than 48 hours, unless there is severe hemodynamic compromise. For AFB of such long duration, anticoagulation therapy is advised before CV to reduce the likelihood of thromboembolism. Many physicians now use echocardiography to rule out the possibility of atrial thrombus. The success rate of CV varies from 65% to 90%. A major determinant of success with external CV is the duration of AFB. It is far more difficult to convert and maintain normal sinus rhythm with chronic AFB than with AFB of recent onset, such as after cardiovascular or thoracic surgery. With external CV and antiarrhythmic therapy, less than 10% of patients with AFB after coronary artery bypass grafting who are discharged in sinus rhythm will have recurrent AFB within 6 weeks of discharge. Complications include brief post-CV hypotension and bradycardia. Bradycardia is more common in patients with sick sinus syndrome and after acute myocardial infarction. Arryhythmias with CV may be due to improper synchronization or digitalis toxicity. Ventricular fibrillation caused by improper synchronization can be terminated by repeat shocks, but deaths have been reported from this complication. The lead with the largest R or S waves should be used for synchronization, and one must be certain that tall, peaked T waves will not interfere with proper synchronization to cause inadvertent DF. Pronounced ST segment elevation after CV occurs infrequently; coronary artery spasm has been proposed as the mechanism for this, but definitive evidence is lacking.

PREVENTION Assurance of nothing-by-mouth status, a semirecumbent position, and the administration of metoclopramide 30 minutes before CV can help decrease residual gastric volume and reduce the risk of vomiting with aspiration. Bite protectors are used to prevent laceration of the lips and tongue from involuntary biting. It is advised that patients with hiatal hernias receive rapid-sequence induction and intubation before CV. Intravenous agents should be given in small boluses and carefully titrated to effect to avoid apnea or hypoventilation in spontaneously breathing patients. Assisted facemask ventilation can help prevent respiratory acidosis, which can aggravate arrhythmias. In elderly patients, post-CV lateral spine radiography is advised. In the presence of osteoporosis or bone demineralization, muscle paralysis is advised using a short-acting agent, along with manually assisted ventilation.

Further Reading Atkins DL, Dorian P, Gonzalez ER, et al: Treatment of tachyarrhythmias. Ann Emerg Med 37:S91-S109, 2001. Canessa R, Lema G, Urzua J, et al: Anesthesia for elective cardioversion: A comparison of four anesthetic agents. J Cardiothorac Vasc Anesth 5:566-568, 1991. Coll-Vinent B, Sala X, Fernandez C, et al: Sedation for cardioversion in the emergency department: Analysis of effectiveness in four protocols. Ann Emerg Med 42:767-772, 2003. Cummins R: ACLS Provider Manual. Dallas, American Heart Association, 2002, pp 157-185. Gazmuri RJ: Effects of repetitive electrical shocks on postresuscitation myocardial function. Crit Care Med 28:N228-N232, 2000. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6. Advanced cardiovascular life support. Section 2. Defibrillation. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation 102(8 Suppl):I90-I94, 2000. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6. Advanced cardiovascular life support. Section 5. Pharmacology I: Agents for arrhythmias. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation 102(8 Suppl):I112-I128, 2000. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6. Advanced cardiovascular life support. Section 6. Pharmacology II: Agents to optimize cardiac output and blood pressure. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation 102 (8 Suppl):I129-I135, 2000. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6. Advanced cardiovascular life support. Section 7D. The tachycardia algorithms. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation 102(8 Suppl):I158-I165, 2000. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 7. The era of reperfusion. Section 1. Acute coronary syndromes (acute myocardial infarction). The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation 102(8 Suppl):I172-I203, 2000. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 10. Pediatric advanced life support. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation 102(8 Suppl):I291-I342, 2000. Haghi D, Schumacher B: Current management of symptomatic atrial fibrillation. Am J Cardiovasc Drugs 1:127-139, 2001. Hullander RM, Leivers D, Wingler K: A comparison of propofol and etomidate for cardioversion. Anesth Analg 77:690-694, 1993. Kugler JD, Danford DA: Management of infants, children, and adolescents with paroxysmal supraventricular tachycardia. J Pediatr 129:324-338, 1996. Kugler JD, Danford DA, Gumbiner CH: Ventricular fibrillation during transesophageal atrial pacing in an infant with Wolff-ParkinsonWhite syndrome. Pediatr Cardiol 12:36-38, 1991. Lip GY, Watson RD, Singh SP: ABC of atrial fibrillation: Cardioversion of atrial fibrillation. BMJ 312:112-115, 1996. Maisel WH, Rawn JD, Stevenson WG: Atrial fibrillation after cardiac surgery. Ann Intern Med 135:1061-1073, 2001. Marshall D, Johnell O, Wedel H: Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312:1254-1259, 1996. Mehta PM, Reddy BR, Lesser J, et al: Severe bradycardia following electrical cardioversion for atrial tachyarrhythmias in patients with acute myocardial infarction. Chest 97:241-242, 1990. Siwach SB, Katyal VK: DC cardioversion and coronary artery spasm. J Assoc Physicians India 37:545, 1989. Zheng F, Qi X, Liu H, et al: Transesophageal cardioversion of atrial flutter and atrial fibrillation using an electric balloon electrode system. Chin Med J (Engl) 116:1325-1328, 2003.

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Radiation Oncology Kate Huncke

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Case Synopsis A 4-year-old boy with medulloblastoma undergoes a fourth course of cranial radiation therapy. Anesthesia is induced with propofol infused through a Hickman catheter and titrated to maintain spontaneous ventilation. When the child is sufficiently sedated, he is placed in a prone position. While the patient is monitored from an adjacent room with an audiovisual camera, laryngospasm develops.

Definition Anesthesia is frequently used for radiation therapy in children. The treatment is painless, but absolute immobility is required to precisely focus the radiation beam on tumor cells, thereby sparing adjacent healthy tissue. The total dose of radiation to treat a tumor is divided into daily doses given over several weeks. Each session lasts only a few minutes, but the total dose of radiation per session is high (180 to 250 rad), which means that radiation oncology and anesthesia personnel cannot remain in the immediate treatment area. Several problems can arise when patients are subject to the daily administration of anesthetics. Tachyphylaxis may develop to anesthetics such as ketamine, propofol, and barbiturates. Daily endotracheal intubation traumatizes the trachea and can lead to stenosis. If a permanent central catheter is not in place, securing and maintaining intravenous (IV) access may be difficult. Prolonged, repetitive fasting and delayed recovery from anesthesia can further compromise nutritional intake in a child who is already anorexic from chemotherapy and malignancy. Administration of anesthesia outside of the operating room poses challenges. The radiation suite is typically located a distance from trained anesthesia backup personnel and supplies. Access to the patient is limited during the procedure.

Table 230–1

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Anesthetic delivery and patient monitoring occur from an adjacent room using audiovisual equipment and monitors. A radiostethoscope allows continuous auscultation of heart tones and breath sounds from outside the room. Owing to poor lighting, however, early signs of an impending complication, such as airway obstruction, may be missed with remote monitoring. Also, it may be difficult to ensure the proper operation of IV infusions or anesthetic delivery systems while the anesthesiologist is stationed in the adjacent room.

Recognition As with any procedure requiring anesthesia, the initial patient evaluation should be thorough. The specific tumor diagnosis has a significant impact on anesthetic management because of associated tumor-related complications (Table 230-1). A complete history and physical examination need not be repeated at each visit, but the anesthesia provider should be aware that the patient’s physical status may deteriorate during the course of therapy owing to disease progression or adjuvant chemotherapy. Previous anesthetic records should be reviewed for complications and signs of tachyphylaxis to anesthetic drugs. In addition to the usual evaluation of the anesthesia machine, the radiation suite should be carefully inspected before treatment. Even modern facilities may not have wall suction and oxygen. A portable suction machine can be used

Systemic Complications of Common Pediatric Radiation-Sensitive Tumors

Tumor

Complications

Neuroblastoma

Gastrointestinal compression due to large abdominal mass Respiratory compromise from pulmonary metastases Tumor-related secretion of vasoactive amines, leading to diarrhea and metabolic disturbances Motor or sensory deficit with epidural metastases Gastrointestinal compression due to large abdominal mass Anemia from hematuria Renal insufficiency Hypertension Hyperaldosteronism Increased intracranial pressure with advanced disease Increased intracranial pressure Motor and sensory deficits Airway obstruction with pharyngeal location Renal insufficiency with genitourinary location

Wilms’ tumor

Retinoblastoma Medulloblastoma Rhabdomyosarcoma

909

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PROBLEM ANALYSIS

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if wall suction is unavailable, but anesthetic gases cannot be scavenged under these conditions. A full oxygen tank and functional Ambu bag should be available in the event the central oxygen supply fails. Electrical outlets should be examined for their ability to accommodate anesthesia equipment and monitors. The anesthesiologist should verify proper positioning of monitors in front of the audiovisual equipment. Any special supplies that may be needed, such as a fiberoptic bronchoscope, should be transported to the area. The anesthesia cart should be fully stocked with all necessary supplies. An emergency cart should be readily available, and the personnel present during the procedure must be familiar with its use.

Risk Assessment Anesthetic risk increases with the severity of disease. A large abdominal mass can cause gastrointestinal compression, increasing the risk for pulmonary aspiration (see Table 230-1). Patients with intracranial masses may develop intracranial hypertension if anesthetic agents are administered that increase cerebral blood flow. Spontaneous ventilation during deep sedation or general anesthesia can lead to increased arterial carbon dioxide, which may further increase previously elevated intracranial pressure. Metabolic disturbances and dehydration due to inappropriate hormonal secretion or gastrointestinal upset can result in hemodynamic instability during anesthesia. Limited airway access also increases anesthetic risk. Securing the airway daily with an endotracheal tube is generally avoided because of the short duration of the procedure and the risk of repetitive airway trauma. In patients with tumor-related airway abnormalities, airway obstruction during deep sedation or general anesthesia is a potential problem. Extreme head and neck positions, which are sometimes needed to focus the beam on the affected area, can cause even a normal airway to become obstructed.

Implications Myriad complications can occur during the delivery of any anesthetic. Compared with management in the operating room, treatment of a problem that occurs during radiation therapy may be delayed because of limited access to the patient and a lack of backup personnel and supplies. Obviously, if the anesthesiologist can anticipate a potential complication, the necessary supplies and personnel should be readily available.

MANAGEMENT The referring physician, anesthesiologist, and radiation oncology staff should establish a workable plan for collecting the necessary preprocedural information about each patient. Ideally, the anesthesiologist should personally interview the patient or his or her parents or guardians before beginning a course of therapy. If this is not possible, the anesthesiologist should have access to the patient’s chart and should contact the patient or the parents or guardians by telephone before the procedure. Compliance with fasting

guidelines and continuance of essential medications should be emphasized on a daily basis. General anesthesia or deep sedation is required to ensure absolute immobility in the pediatric population. Numerous agents and techniques are available to reliably produce unconsciousness and immobility for a brief period. Selection of the appropriate agent is influenced by the patient’s age, medical disease, previous reaction to anesthesia, positioning requirements, and availability of an anesthesia machine. Children younger than 6 years having repetitive procedures often require premedication to facilitate separation from parents. A variety of agents (benzodiazepines, barbiturates, opioids, ketamine) can be given by the oral, nasal, rectal, or intramuscular route. Premedication can also be given via a permanent central line. Alternatively, a heparinlocked peripheral IV line is minimally traumatic for the child and avoids the need for a separate procedure and recovery to establish central IV access. If an anesthesia machine is available, general anesthesia using an inhalational technique offers several advantages. Induction, emergence, and titration to effect are rapid. Tachyphylaxis in response to volatile agents has not been reported. IV access does not necessarily need to be established before induction. Unfortunately, many radiation suites are not equipped with wall suction for scavenging anesthetic gases. General anesthesia can also be achieved using only IV agents. Propofol given by bolus or infusion is safe and efficacious. For short procedures, there is faster recovery and less nausea and vomiting with propofol than with isoflurane. Propofol has the disadvantage of causing burning pain when it is given through a peripheral line. Although this can be reduced by prior injection of lidocaine or alfentanil through the IV line, the efficacy of this measure varies among patients and is not universally accepted. Ketamine can also be used for general anesthesia in the radiation suite. An IV catheter need not be placed before induction, because intramuscular injection rapidly produces unconsciousness. A single intramuscular injection may be sufficient for the entire procedure. Atropine or glycopyrrolate must be given to prevent increased airway secretions with ketamine. Spontaneous ventilation is better preserved with ketamine than with propofol or volatile agents. Recovery from ketamine can be prolonged, however, and is frequently associated with an unpleasant emergence delirium. Tachyphylaxis with either ketamine or propofol has been reported. A laryngeal mask airway (LMA) can be used to secure the airway. It eliminates airway obstruction due to relaxation of the tongue and supraglottic soft tissue. Repeated trauma to the trachea is avoided, but uvular and pharyngeal trauma can occur during placement of the LMA. As is the case with mask ventilation, laryngospasm and coughing can occur if the patient is stimulated under light anesthesia. Pediatric LMAs are susceptible to kinking because of their small radius. Maintaining the proper position of the LMA may require manipulation of the mandible and neck, which can be difficult if the patient is not in the supine position. The LMA is contraindicated in patients at risk for aspiration or with low pulmonary compliance who will need positivepressure ventilation.

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The recovery area should be equipped with oxygen, suction, and basic monitoring. Staff trained in anesthesia recovery should be available; otherwise, the patient should be transported to the operating room recovery area.

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would adversely affect the anesthetic outcome, the case should be delayed pending further evaluation. Tachyphylaxis in response to anesthetic agents cannot be prevented. Alternative agents to produce general anesthesia should be readily available. All patients receiving an anesthetic, whether general, regional, or monitored anesthesia care, should receive appropriate postanesthesia management. Recovery can take place in the postanesthesia care unit or in the procedure room. Monitoring standards for temperature, ventilation, circulation, and oxygenation must be observed, regardless of location. Finally, when discharge criteria are met, this must be documented on the patient’s medical chart by the anesthesiologist.

Further Reading Bell C: Outpatient anesthesia in non operating room setting. In McGoldrick K (ed): Ambulatory Anesthesia: A Problem-Oriented Approach. Baltimore, Williams & Wilkins, 1995, pp 550-571. Brann C, Janik D: Anesthesia in the radiology suite. Prob Anesth 6:413-429, 1992. Greenberg D, Romanoff M: Anesthesia outside the operating room: An overview. Prob Anesth 6:299-310, 1992. Kotob F, Tewersky R: Anesthesia outside the operating room: General overview and monitoring standards. In Osborn I (ed): Anesthesia Outside the Operating Room: International Anesthesia Clinics. Philadelphia, JB Lippincott–Williams & Wilkins, 2003, pp 1-15. McDowall R, Scher C, Barst S: Total intravenous anesthesia for children undergoing brief diagnostic or therapeutic procedures. J Clin Anesth 7:273-280, 1995.

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Risks and complications can be minimized by thorough evaluation of the patient, careful consideration of the planned procedure, and familiarity with the radiation suite and the location of necessary supplies and equipment. The anesthesiologist should never proceed without verifying the working order of all required equipment. If a problem is anticipated, backup personnel should be alerted, and special supplies should be transported to the area. Basic monitoring standards of general anesthesia should be observed. The American Society of Anesthesiologists has published guidelines for non– operating room locations that list the minimal standards for monitoring. If more invasive monitoring is required because of the patient’s illness, it should be used during therapy. Failure to comply with these standards can result in loss of accreditation. The patient and his or her parents or guardians should be questioned daily about any new symptoms and the last oral intake. Fasting guidelines should be strictly enforced. In patients who are at risk for aspiration, the airway should be protected with an endotracheal tube, even on a daily basis if necessary. Antacids and metoclopramide should be given if indicated. If the patient develops any new symptoms that

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Embolization Procedures George A. Higgins

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Case Synopsis Six days after revision surgery for a hip replacement, a 78-year-old patient presents from the rehabilitation department with frank hemorrhage from the operated extremity. Angiography and possible embolization are proposed for a 9:00 PM start time. The on-call anesthesia team is requested to provide analgesia and sedation for the procedure. The patient has previously been anticoagulated for deep venous thrombosis prophylaxis and has a history of hypertension, chronic renal insufficiency, stable angina, and esophageal reflux disease. A complete blood count and type and crossmatch are pending, and the patient had a full meal 3 hours before admission.

PROBLEM ANALYSIS Definition Members of the anesthesia care team are occasionally asked to provide unpredictable and varying levels of sedation, including possible progression to general anesthesia, for endovascular embolization procedures. The indications for such procedures are diverse (Table 231-1), ranging from elective ablation of a cerebral arteriovenous malformation to embolization of a life-threatening uterine hemorrhage in a Jehovah’s Witness parturient. The interventional radiology suite is often located in a remote part of the hospital, far from the surgery and intensive care departments. The work environment is usually not designed or adaptable for a full repertoire of anesthesia and monitoring equipment. Portable communications devices, such as pagers, two-way radios, and cell phones, are often nonfunctional in the shielded surroundings. The space is often cramped, and access to oxygen, suctioning, monitors, and the resuscitation cart may be blocked or made awkward by radiology equipment (Fig. 231-1). The required use of ungainly lead aprons and the diminished lighting increase

Table 231–1

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Indications for Endovascular Embolization

Arteriovenous malformation Arteriovenous fistula Intracranial aneurysm Recurrent epistaxis Hemoptysis Traumatic solid organ hemorrhage Preoperative major organ tumor embolization for blood loss reduction Gastrointestinal hemorrhage Uterine leiomyoma (fibroid) Uterine hemorrhage Pelvic fracture hemorrhage Postoperative hemorrhage after prosthetic hip or knee replacement Varicocele

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the risk of injury to the anesthesia provider and the patient from overhanging equipment, needle sticks, drug swaps, and inability to assess the patient’s condition. The embolization procedure itself has inherent risks, including unrecognized hemorrhage, vascular damage, allergic reactions to contrast or embolic media, nontarget embolization injury, ischemic pain in the target organ, and nausea or vomiting. Unlike the anesthesia team, the radiology team is generally not focused on the patient’s comorbidities and the implications for sedation or analgesia. The duration of embolization procedures is indeterminate. Commonly, the patient reaches maximal endurance before completion of the procedure. Specialized embolization agents (e.g., coils, microspheres, acrylic glue, detachable balloons) may not be routinely stocked in the needed size, causing unanticipated delays. The anesthesia team is expected to provide a motionless and cooperative patient with stable vital signs throughout the procedure, usually under conditions of monitored anesthesia care. Rapid neurologic assessment is periodically required, especially for procedures involving the blood supply to the brain.

Figure 231–1 ■ Interventional radiology suite. Note the location of the anesthesia monitors, the oxygen and suction regulators, and the code cart and the layout of the work space.

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Recognition

Risk Assessment Patients undergoing embolization procedures can be assumed to be at high risk, especially in emergency circumstances. Each patient deserves a brief but thorough history; review of systems, medications, and allergies; and physical examination focusing on the airway, cardiorespiratory status, and neurologic stability and function. Documentation of baseline neurologic function and inspection of recent laboratory values, especially hemoglobin and clotting parameters, are important. Patients with diabetes or a history of seizures require special attention. Their medications and blood levels should be checked before the start of the procedure and intraoperatively, if indicated. Time of last oral intake should be established, and evaluation for gastroesophageal reflux disease and recent emetic episodes should be performed. Blood availability should be personally confirmed with the blood bank. Verification of informed consent for the procedure, anesthesia, and associated risks is mandatory. The radiology suite should be assessed for ergonomic hazards, including the following: ● ●

●

Adequacy of dedicated electrical circuits Patency and functioning of oxygen and suction lines and regulators Location of telephones, crash cart (with confirmation of its functional status), and emergency exits

An attempt should be made to group oxygen, suction, and monitoring functions in a segregated area that does not interfere with the procedure but allows direct visualization of the patient’s airway.

Implications The embolization procedure has potential risks and expected side effects. Complications that may require the intervention of the anesthesia team include the following: ●

Nausea, vomiting, or aspiration

● ● ● ● ● ●

● ●

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Uncontrollable pain or agitation under sedation Hypoventilation, hypoxemia, and airway obstruction Vagal-mediated reflexes Hypotension, septic shock, or myocardial infarction Stroke or seizure Cardiac or respiratory arrest Organ insult due to hypoperfusion or nontarget embolism Internal hemorrhage due to vascular perforation or rupture Anaphylactic reactions from either radiologic or anesthetic agents

All these complications should be anticipated, with a well-rehearsed plan of action in place to deal with such occurrences. The ability to immediately convert from monitored anesthesia care to general endotracheal anesthesia should always be maintained.

MANAGEMENT A departmental protocol, including a checklist of required equipment, medications, and personnel for every satellite hospital location (including telephone numbers), should be developed. Also, there must be firsthand knowledge of the location of oxygen and suctioning equipment, electrical circuits, lighting controls, and the crash cart. There must be sufficient time to fully check the listed items. For example, code carts are frequently kept outside the suite in a locked medicine supply room. If so, verification that the door is unlocked and that the monitors and defibrillator are functional is a time-consuming but important task. Complications must be anticipated, a general treatment plan formulated, and the appropriate resources for management identified. Some events, such as hypoventilation or a mild drug reaction, can be adequately managed without aborting the procedure. Others, however, may require that the procedure be terminated and the patient transferred to a better location for treatment and more invasive monitoring. In the case of uncontrolled vascular hemorrhage, resuscitation is best carried out in a surgical intensive care unit or adjacent to the operating room while awaiting arrival of the surgical team. Successful management of possible complications involves bringing appropriate resources to the patient or bringing the patient to those resources. The remote location of the radiology suite usually hinders quick access to such resources. For example, the blood bank may not be familiar with the location of the radiology suite or how to rapidly deliver blood products to it. During evening or nighttime hours, there may not be enough personnel available to deliver supplies or to transport the patient. If so, the patient is in jeopardy until he or she can be moved to a more central site.

PREVENTION Prevention of complications requires assessment and preparation in the following areas. Patient Evaluation. Each patient should be evaluated with a concise history, systems review, medication and allergy review, and physical examination. Procedure-specific systems

SPECIAL TOPICS

In addition to routine monitoring (electrocardiogram, noninvasive blood pressure, and arterial oxygen saturation), some assessment of respiratory effort is crucial. Nasal cannulas with carbon dioxide sampling lines are routinely used. A radiopaque precordial stethoscope can also be effective. If available, the side port of the radiologist’s femoral artery introducer can be used for arterial pressure monitoring or blood gas sampling. A large-bore peripheral intravenous line with a distal side port should be established. The patient’s needs (maintaining body temperature and position preferences), as well as a consideration of his or her past experiences and current expectations, guide the provider’s choice of technique. Previous experience with similar procedures can be used as a guide to how the patient will react to the embolization procedure. Some brief familiarization with the planned procedure can spotlight important monitoring points along the way. It is helpful to be able to recognize sentinel events of the embolization procedure. Knowledge of expected and unexpected outcomes of the embolization procedure itself is useful for monitoring the patient’s status.

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need to be assessed and documented. All questions should be answered, and a description of the events during the procedure, including any expected discomfort, unusual sensations, and possible complications, should be provided. Anesthesia Equipment. Using a checklist, each location should be evaluated for the existence and functioning of the following equipment and supplies: oxygen (both piped in and reserve tanks), suctioning, emergency electrical outlets dedicated to anesthesia, emergency lighting, telephones, anesthesia machine and equipment, anesthetic and emergency drugs, crash cart, and radiology table for immediate airway access equipment in case the airway must be accessed emergently. Communication. Specific goals of both the anesthesia team and the radiology team should be discussed. Criteria for aborting the procedure and exit strategies are best defined before beginning the procedure. Resource Availability. Regardless of assurances from the radiology team, the ability to secure additional resources if necessary is mandatory. The telephone and pager systems must be functional, and key personnel (e.g., blood bank, surgery, transport, intensive care, anesthesia technical support services) should be notified that their services might be required.

Anesthetic Technique. Use of short-acting or reversible agents (e.g., midazolam, alfentanil, propofol) for a monitored anesthesia technique permits the patient to quickly return to baseline. This allows for efficient neurologic or cardiovascular evaluation, if needed. Similarly, short-acting and easily reversed muscle relaxants and inhalational anesthetics are available if general anesthesia is required. In summary, many untoward events associated with providing anesthesia care for embolization procedures can be reduced or eliminated by careful preprocedural preparation and planning.

Further Reading Andrews RT, Spies JB, Sacks D, et al: Patient care and uterine artery embolization for leiomyomata. J Vasc Interv Radiol 15:115-120, 2004. Barriga A, Valenti Nin JR, Delgado C, Bilbao JJ: Therapeutic embolisation for postoperative haemorrhage after total arthroplasty of the hip and knee. J Bone Joint Surg Br 83:90-92, 2001. Forbes RB: Anesthesia for nonsurgical procedures. In Longnecker (ed): Principles and Practice of Anesthesiology, 2nd ed. St. Louis, Mosby, 1998. Schonholz DH: Blood transfusion and the pregnant Jehovah’s Witness patient: Avoiding a dilemma. Mt Sinai J Med 66:277-279, 1999. Ward JF, Velling TE: Transcatheter therapeutic embolization of genitourinary pathology. Rev Urol 2:236-262, 2000.

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Catheter Ablation for Arrhythmias

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Glyn D. Williams Case Synopsis A 15-year-old boy with Wolff-Parkinson-White syndrome and a history of recurrent paroxysmal tachycardia undergoes percutaneous catheter radiofrequency ablation of an accessory pathway while under general anesthesia. The procedure is successful, as demonstrated by the loss of δ waves and restoration of a normal P-R interval (Fig. 232-1). Postoperatively, the patient complains of weakness in his right arm. Examination reveals that he has sustained a brachial plexus injury.

Definition Brachial plexus injury is a recognized complication of catheter ablation procedures. General anesthesia, lengthy procedures, and positioning the patient’s hands above the head (for lateral fluoroscopic views of the chest) are important contributory factors.

Recognition Supraventricular tachycardia is relatively common in children (see also Chapters 79 and 80). Mechanisms for supraventricular tachycardia include both reentry and automatic tachycardias. Atrioventricular (AV) reciprocating tachycardia (of which Wolff-Parkinson-White syndrome is a subset) and AV node reentry tachycardia are the most common forms of reentrant tachycardia in children. For patients in whom medical therapy is inadequate or undesirable, invasive electrophysiology techniques are a viable option. Percutaneous catheter ablation is used to selectively interrupt cardiac conduction pathways. Indications for catheter ablation are listed in Table 232-1. Three regions can be ablated: the AV bypass tracts, the AV node margins, and ventricular reentry pathways. Radiofrequency (RF) energy is low-power, high-frequency alternating current that causes injury by generating heat at the electrode-tissue interface. RF allows good control of energy delivery, creates a small area of injury, can be used safely in thin-walled structures such as the coronary sinus, and seldom triggers malignant arrhythmias. The energy is delivered via an intracardiac catheter to endocardium adjacent to the area of abnormal conduction.

Figure 232–1 ■ Electrocardiogram from a patient with Wolff-Parkinson-White syndrome showing loss of δ waves and restoration of a normal P-R interval after radiofrequency ablation of the accessory pathway.

Injured tissue becomes electrophysiologically inactive and scars, thereby preventing recurrent arrhythmias. Recently, cryoablation has been used for creating endocardial lesions. Liquid nitrous oxide is circulated through the ablation catheter, cooling the tip to subfreezing temperatures and resulting in destruction of tissue directly beneath the catheter tip. Cryoablation has several advantages over RF systems, because the area of interest can be temperaturemapped at a temperature of –22°C to –30°C. This results in alteration of the tissue’s electrical conductivity. Usually, this area can be rewarmed if the freeze time is limited (i.e., “ice mapping”). Further cooling to a lower setpoint (–75°C) creates a permanent lesion. Thus, an area is ice-mapped to predetermine whether subsequent lower setpoint cryoablation at this site will be successful and whether there will be any undesirable effects (especially AV block) due to creation of a permanent lesion. Another advantage of cryoablation over RF ablation is that the catheter tip freezes tightly onto the endocardium during mapping and ablation, thereby reducing the risk of injury to surrounding tissue from motion of the beating heart. Compared with RF techniques, cryoablation causes less discomfort in awake patients, but the possibility of supraventricular tachycardia reoccurrence may be greater. Cryoablation is a particularly appealing option for ablation in the region around the AV node, where the risk of causing iatrogenic complete AV heart block is highest. RF ablation can cause mild to moderate retrosternal angina-like pain, but it is applied for only short periods (<1 to 2 minutes). To facilitate the ablation procedure, the patient must remain motionless. Adults can often be managed with sedation, but most children require general anesthesia. During the initial application of cryoablation, a brief period of patient apnea may be desirable to limit intrathoracic

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PROBLEM ANALYSIS

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Table 232–1

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Indications for Catheter Ablation of Tachyarrhythmias

Symptomatic supraventricular or ventricular tachyarrhythmias refractory to drugs Intolerable side effects or other adverse drug effects (e.g., ventricular proarrhythmia) “Tachycardiomyopathy (i.e., tachycardia-induced myocardial dysfunction) Presurgical control of tachyarrhythmias with congenital heart disease Desire of patient or family

movement, thereby enhancing contact between the catheter tip and the endocardium. Ideally, the anesthetics or sedatives used should not alter intrinsic pacemaker function, impulse propagation, refractoriness, or autonomic tone or prevent intentional triggering of reentrant arrhythmias. In addition, anesthesia should be rapidly reversible, with minimal delay in emergence. A few studies have examined the effects of anesthetic agents on the conduction system, but many are flawed by the confounding effects of drugs used to induce anesthesia. Analgesia for catheter insertion can be achieved with local anesthetic agents, but care should be taken, because a dose of 3.2 mg/kg of 1% lidocaine can reportedly have an adverse influence on the inducibility of arrhythmias in children. The following anesthetic techniques have minimal effect on either the normal conduction system or the accessory pathways in patients with Wolff-Parkinson-White syndrome: ● ● ● ● ● ●

Alfentanil and midazolam infusions Sufentanil and lorazepam infusions Alfentanil, nitrous oxide, pancuronium Isoflurane, nitrous oxide, pancuronium Propofol, nitrous oxide, pancuronium Remifentanil and ketamine

One study concluded that propofol anesthesia was acceptable during RF ablation for most tachyarrhythmias except for atrial ectopic tachycardia, which could not be induced after propofol administration. Another investigation noted that isoflurane prolonged the effective refractory period of the antegrade accessory pathway in children with WolffParkinson-White syndrome and advised care when interpreting measurements. One review concluded that either balanced general anesthesia (with isoflurane being the preferred volatile agent) or monitored anesthesia care with opioids, benzodiazepines, and propofol was acceptable. Effective ablation can be tested by attempting to retrigger the offending arrhythmia with the administration of isoproterenol infusions (0.02 to 0.1 μg/kg per minute) or atropine (10 to 20 μg/kg).

Risk Assessment Risks associated with catheter ablation are summarized in Tables 232-2 and 232-3.

Implications A recent prospective, multicenter study reported a 96% success rate with catheter ablation for supraventricular tachycardia

Table 232–2

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Risks Factors Associated with Catheter Ablation

Risk Factor

Focus

Patient’s clinical status

Associated heart disease, other system pathology Antiarrhythmic drugs, anticoagulants Airway obstruction, respiratory depression Hemodynamic stability, airway management, positioning See Table 232-3 Hypothermia, limited access to patient, remoteness from help Patient exposure, caregiver exposure

Patient’s medications Sedation techniques General anesthesia techniques Catheter ablation Environment Radiation

in children. Factors that reduce the likelihood of success include aberrant conduction via a right free wall pathway, other heart disease, and greater body weight. Unintentional catheter-induced mechanical trauma to accessory pathways can result in discontinuation of the ablation procedure and lower success rates. Right anteroseptal and right atriofascicular pathways appear to be especially vulnerable. The complication rate for catheter ablation (4%) is similar for adults and children and is slightly greater than the complication rate for diagnostic cardiac catheterization. The occurrence of complete AV block has great significance, especially for children, because the child will be burdened by the need for lifelong artificial cardiac pacing. Complication rates in children have been correlated with very low body weight and limited institutional experience. Deaths have occurred after catheter ablation.

MANAGEMENT Preoperative preparation includes a thorough history, physical examination, laboratory testing, and optimization of medical therapy. The cardiologist who will conduct the ablation and the anesthesiologist should confer and formulate a management plan. Antiarrhythmic agents are discontinued several days before the procedure to promote initiation of the arrhythmia. Patients who decompensate during arrhythmias should be identified, and the presenting symptoms should be elicited. All patients should fast before surgery. Reassurance, premedication, or both may help minimize excessive sympathetic tone. Because the electrophysiology suite is likely remote from the operating room, it is important to have all the necessary anesthetic equipment and drugs available (similar to preparation for embolization procedures; see Chapter 231). Typical monitoring includes continuous electrocardiography, pulse oximetry, noninvasive blood pressure (possibly direct arterial pressure), body temperature monitoring, and expired carbon dioxide analysis. For the last, the nasal cannulas used for oxygen delivery must have an aspiration port for end-tidal CO2 analysis. Depth of anesthesia can be assessed by processed electroencephalography. For this, either a bispectral index or processed spectral array monitor can

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Table 232–3

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Complications of Catheter Ablation

Complication

Comments

Related to Cardiac Catheterization Arrhythmias Hematoma at catheter site Arterial trauma Perforation Catheter entrapment Infection Air embolism Thromboembolism Hypotension

Specific to Ablation Procedure Atrioventricular block Arrhythmia Valvular regurgitation Coronary spasm Skin burn Perforation

Relatively common; may require transvenous pacemaker Uncommon Reported Reported Reported Pericardial tamponade after ablation near coronary sinus

be used. The defibrillator is checked, and the leads are attached to the patient. Patients at risk for ventricular arrhythmias have hard-wired defibrillator gel pads placed over the sternum and back. Attention to positioning and padding is required. Hypothermia and hypoglycemia are risks, especially in children. Use of antiemetic agents should be considered, because nausea and vomiting are relatively common after the procedure. Patients with good preoperative clinical status and normal cardiac anatomy who undergo uncomplicated catheter ablation may be allowed to return home after discharge from the postanesthesia care unit. In contrast, high-risk patients may warrant admission to an intensive care unit after the ablation procedure.

PREVENTION In the author’s experience, brachial plexus injury is most likely to occur in thin teenagers who receive general anesthesia for catheter ablation procedures of long duration. Patients must be informed of this risk before the procedure. After induction, the patient is positioned carefully; pressure points are padded, and these are checked periodically during the procedure.

Whenever possible, the arms are kept at the patient’s sides. These precautions can reduce the occurrence of brachial plexus nerve injury.

Further Reading Chun TUH, Van Hare GF: Advances in the approach to treatment of supraventricular tachycardia in the pediatric population. Curr Cardiol Rep 6:322-326, 2004. Jackman WM, Wang XZ, Friday KJ, et al: Catheter ablation of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome) by radiofrequency current. N Engl J Med 324:1605-1611, 1991. Javorski JJ, Hansen DD, Laussen PC, et al: Pediatric cardiac catheterization: Innovations. Can J Anaesth 42:310-329, 1995. Kugler JD, Danford DA, Deal BJ, et al: Radiofrequency catheter ablation for tachyarrhythmias in children and adolescents. N Engl J Med 330:1481-1487, 1994. Lavoie J, Walsh EP, Burrows RA, et al: Effects of propofol or isoflurane anesthesia on cardiac conduction in children undergoing radiofrequency catheter ablation for tachydysrhythmias. Anesthesiology 82:884-887, 1995. Stobie P, Green MS: Cryoablation for septal accessory pathways: Has the next ice age arrived? J Cardiovasc Electrophysiol 14:830-831, 2003. Van Hare GF, Javitz H, Carmelli D, et al: Prospective assessment after pediatric cardiac ablation: Demographics, medical profiles and initial outcomes. J Cardiovasc Electrophysiol 15:759-770, 2004.

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Contrast media Nerve injury Pneumothorax

Atrioventricular block, sinus bradycardia, supraventricular tachycardia, and ventricular tachycardia can be clinically important Most common complication; heparin therapy may contribute Especially in children, owing to relatively large catheter size Perforation of heart or great vessels is rare Uncommon; may require surgical intervention Antibiotic prophylaxis is indicated in some cases Systematic emboli possible if an intracardiac shunt is present Consider heparin prophylaxis in high-risk cases Causes include hypovolemia, hypoxia, acidosis, arrhythmia, myocardial infarction, cardiac tamponade, and catheter obstruction of flow Allergic reactions, hyperosmolar effects, renal toxicity, pain on injection, histamine release Brachial plexus especially at risk Central venous line placement

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233

Magnetic Resonance Imaging Hind M. Gautam and Christopher M. B. Heard Case Synopsis A 5-year-old boy requires magnetic resonance imaging (MRI) of the brain for delayed mental development. An attempt at the procedure has already failed after the boy received an oral sedation regimen. Anesthesia has been requested to facilitate the investigation.

PROBLEM ANALYSIS Definition MRI is a noninvasive diagnostic imaging modality that produces precise images of the body. It is free of ionizing radiation and does not, by itself, produce any known biologically deleterious effects. It is based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy, which are then emitted as radio waves and reconstructed into computerized images. Magnetic field strengths generally range from 0.15 to 2.0 tesla (T), although magnetic field strengths of 3 T are increasingly being used. The patient is required to lie still within a small space while multiple images are obtained. MRI requires a longer time to develop than computed tomography scanning; therefore, any movement by the patient degrades the image quality. In fact, any change in the patient’s position may affect the homogeneity of the magnetic field, which is optimized at the beginning of the scan. Studies can take from 45 minutes to more than 2 hours, with individual sequences taking from 3 to 10 minutes. The scanner is noisy, and the restricted space and lack of movement can induce claustrophobia in some patients. Patients also may experience a slight increase in temperature.

Recognition Most adults and children older than 6 years are capable of lying still for the scan. With the use of headphones and music, MRI is a well-tolerated procedure. However, there are several groups of patients who may require anesthesia for the scan to be performed (Table 233-1). Table 233–1

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Indications for Deep Sedation or Anesthesia for Magnetic Resonance Imaging

Very young or agitated patient Patient unsuitable for oral sedation regimen (history of apnea, gastroesophageal reflux, severe respiratory disease) Patient who has failed an oral sedation regimen Prolonged study (multiple scans) Anxious patient Claustrophobic patient Intensive care patient

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Risk Assessment Table 233-2 lists some common contraindications to MRI. If there is any uncertainty, the radiologist should be consulted. These contraindications are related either to the possibility of the magnet causing a ferromagnetic object to move or heat up or to the induction of an electrical current from the radiofrequency pulses and magnetic gradients used to generate the images. The effect on the unborn fetus is unknown, and MRI should probably be avoided in the first trimester unless absolutely indicated based on the patient’s medical condition. Permanent cosmetic makeup and tattoos can cause skin irritation during MRI scanning. Anesthesia risk is increased because the patient is in a remote location, with limited airway access and visibility. The presence of gastroesophageal reflux, seizures, or raised intracranial pressure affects the choice of anesthetic. Other potential problems that may arise are listed in Table 233-3.

Implications Monitors must be suitable for use in the MRI suite. They should be nonferromagnetic, and cables should be screened from electromagnetic interference (fiberoptic is ideal). The signal should be filtered to avoid radiofrequency interference, which affects image quality. Despite specialized technology, some problems remain (Table 233-4).

Table 233–2

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Absolute or Relative Contraindications to Magnetic Resonance Imaging

Cardiac pacemaker* Aneurysm clips Implanted cardiac defibrillator* Neurostimulator* Pacing wires* Cochlear implant* Implanted insulin pump* Penile prosthesis History of ocular injury involving metal object History of vascular surgery within 3 mo (metallic clips or sutures) History of soft tissue metal foreign body within 3 mo History of orthopedic hardware within 3 mo *Consult the device manufacturer or patient follow-up clinic about the specific procedure.

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Table 233–3

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Potential Problems Related to Magnetic Resonance Imaging

\

Malfunction of anesthesia equipment Malfunction of monitoring equipment Anesthesia equipment interfering with image quality High-velocity ferromagnetic projectile from loose object Disruption of electronic devices, credit cards

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Anesthesia Options

Intravenous Sedation with Supplemental Oxygen for Pediatric Patients Propofol bolus of 2 to 3 mg/kg and infusion of 100 μg/kg/min Oral chloral hydrate (<3 yr) 75 to 100 mg/kg for procedures up to 1 hr Rectal methohexital 20 to 30 mg/kg for procedures up to 30 min (good for children up to 6 yr; may be contraindicated in patients with temporal lobe epilepsy) Ketamine ≤1.0 mg/kg IV (1–3 mg/kg IM if no IV is available; avoid use with elevated intracranial pressure)

Benzodiazepines for Sedation and Anxiolysis in Adults May be induced orally or intravenously Good method for patients with few medical problems and an easily maintained airway; minimally invasive Rapid recovery; little nausea or vomiting; glycopyrrolate is a useful antisialagogue

General Anesthesia with Endotracheal Tube Ventilation Inhalation anesthesia or propofol infusion Good for very young patients or those with gastroesophageal reflux, full stomach, or raised intracranial pressure

General Anesthesia and Spontaneous Respiration with Laryngeal Mask Airway Inhalation anesthesia or propofol infusion

MANAGEMENT As with any anesthesia induction, the monitoring standards of the American Society of Anesthesiologists should be adhered to. To avoid problems due to monitoring cables, it is advisable to place them as near as possible to the center of the long axis of the MRI magnetic field. They also should be placed on the part of the patient that is most distant from the radiofrequency field. Avoid coiled or crossed wires. The anesthetic technique is dictated by the age of the patient and concurrent diseases (Table 233-5). Vaporizers are accurate in the MRI suite. Intravenous infusion pumps must be outside the 5-gauss limit for magnetic fields. The electric motor in such pumps emits electromagnetic radiation, which may cause the pump to run at an abnormal speed in the presence of a strong magnetic field. The pump is also a projectile risk. Intravenous infusions via long tubing from outside the scanner are useful so that the depth of anesthesia can be altered without having to enter the MRI scanner.

Table 233–4

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The use of a cuffed endotracheal tube or armored laryngeal mask may affect the quality of the image owing to the presence of metal in the valve of the pilot balloon or used to reinforce the mask airway. The use of a contrast agent is often required. Fortunately, MRI contrast agents (based on gadolinium) are associated with fewer allergic reactions than their x-ray counterparts. Severe reactions occur in less than 1 in 100,000 patients. MRI contrast agents are also nontoxic to the kidneys. If a patient comes from the intensive care unit, special care must be taken to ensure that all cables and transducers are carefully screened and ferromagnetic objects are removed. Cables should be straightened to prevent burns. For invasive blood pressure monitoring, the transducer should be as far from the patient as possible and separated with a saline-filled pressure line. If cardiac arrest occurs, the patient should be removed from the magnetic field. The defibrillator should be kept outside the magnetic field and checked regularly. Use of a nonferromagnetic code cart is also advised. It is essential

Monitoring Problems in Magnetic Resonance Imaging

Monitor

Problem

Electrocardiogram (ECG)

T waves and ST segments are often altered, and qualitative information is lacking during MRI scanning cycle; ECG cables may cause burn injury; special ECG electrodes are required to avoid burn injury Malfunction, heating of probe may cause burn injury; fiberoptic connection to patient is best Requires long tubing, resulting in prolonged upsweep and delay in display of real-time measurements; respiratory rate and trends can still be useful, however Requires a filtered cable Long tubing; sounds are obscured by noisy scan Nonmagnetic lithium battery is required; expect reduced battery life Noninvasive: connections for cuff and hoses should be plastic Invasive: use fiberoptic system and transducers with nonferrous components

Pulse oximeter Capnograph Temperature Precordial stethoscope Oxygen analyzer Blood pressure

SPECIAL TOPICS

All anesthesia equipment, as well as the pulse oximeter, intravenous line pole, and anesthesia cart, should also be nonferromagnetic. MRI-safe anesthesia machines, laryngoscopes (lithium batteries), and stethoscopes are available. Any equipment with a transformer must be kept out of the magnetic field. Gas cylinders must be aluminum. If inhalation anesthesia is used, a suitable scavenging system should be available.“MRI-safe” vaporizers may have minimal amounts of ferromagnetic materials and should not be taken into the MRI suite unless mounted on the anesthesia machine or ventilator. The area surrounding a magnetic field stronger than 5 gauss should not contain any ferromagnetic items.

Table 233–5

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that the code team follow the rules about removing any loose magnetic items before entering the MRI suite to avoid the release of a potentially lethal projectile.

PREVENTION To prevent complications with MRI, one must be aware of the contraindications (see Table 233-2). Good communication between the radiology and anesthesiology departments is essential to ensure that the correct anesthesia and monitoring equipment is available from the outset and that atrisk patients undergo prescan anesthesia evaluations. The anesthesia staff involved with providing care in the MRI suite should be aware of all the potential technical problems that may arise in this unique environment.

Further Reading Dempsey MF, Condon B: Thermal injuries associated with MRI. Clin Radiol 56:457-465, 2001. De Wilde JP, Rivers AW, Price DL: A review of the current use of magnetic resonance imaging in pregnancy and safety implications for the fetus. Prog Biophys Mol Biol 87:335-353, 2005.

Frankville DD, Spear RM, Dyck JB: The dose of propofol required to prevent children from moving during magnetic resonance imaging. Anesthesiology 79:953-958, 1993. Gooden CK, Dilos B: Anesthesia for magnetic resonance imaging. Int Anesthesiol Clin 41:29-37, 2003. Holshouser BA, Hinshaw DB Jr, Shellock FG: Sedation, anesthesia, and physiologic monitoring during MR imaging. J Magn Reson Imaging 3:553-558, 1993. Jorgenson NH, Messick JM Jr, Gray J, et al: ASA monitoring standards and magnetic resonance imaging. Anesth Analg 79:1141-1147, 1994. Kaplan RF: Pediatric sedation for diagnostic and therapeutic procedures outside the operating room. In Cote CJ, Todres DI (eds): A Practice of Anesthesia for Infants and Children, 3rd ed. Philadelphia, WB Saunders, 2001, pp 584-609. Menon DK, Peden CJ, Hall AS, et al: Magnetic resonance for the anaesthetist. Part I. Physical principles, applications, safety aspects. Anaesthesia 47:240-255, 1992. Peden CJ, Menon DK, Hall AS, et al: Magnetic resonance for the anaesthetist. Part II. Anaesthesia and monitoring in MR units. Anaesthesia 47:508-516, 1992. Zimmer C, Janssen MN, Treschan TA, et al: Near miss accident during magnetic resonance imaging by a “flying sevoflurane vaporizer” due to ferromagnetism undetected by hand held magnet. Anesthesiology 100:1329-1330, 2004. Zorab JSM: A general anaesthesia service for magnetic resonance imaging. Eur J Anaesth 12:387-395, 1995.

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Misidentification of a Patient Kenneth Kuchta Case Synopsis

PROBLEM ANALYSIS Definition Throughout a patient’s interaction with the health care system, his or her identity must be verified to match any test result and any intended order or intervention for that patient. Patient misidentification is exemplified by the following: ●

● ●

●

●

A patient receives a nonintended medical or surgical intervention. A patient receives mismatched or the wrong blood products. A patient receives the wrong drug or does not receive an ordered drug. A patient is identified with the wrong laboratory or test results (e.g., radiograph, computed tomography scan, magnetic resonance imaging scan). Planned surgery is performed on the wrong limb, or a procedure is performed without a patient’s informed consent.

The accurate identification of patients is also required for dietary personnel to comply with any special dietary orders. For example, a surgical patient who is supposed to receive nothing by mouth is given breakfast on the morning of surgery. This is undiscovered, and during the induction of anesthesia, the patient aspirates gastric contents and subsequently develops aspiration pneumonitis.

Recognition Patients, family members, or medical personnel may recognize patient identification errors at any point during the provision of health care. Attempts to discover, define, and quantify all types of patient misidentifications might provide useful statistical or actuarial data that could be used toward quality-improvement efforts; however, this would be a daunting task. Instead, the emphasis is more correctly placed on measures to prevent patient identification errors, including minimizing their occurrence and discovering them when they do happen.

SPECIAL TOPICS

A 51-year-old man with diabetes and peripheral vascular disease develops gangrene of the right foot, and he agrees to a below-the-knee amputation of the affected leg. Upon admission, he is mistakenly booked for a below-the-knee amputation of the left leg. The error was noted twice before surgery, but attempts to correct it failed, and the wrong leg was amputated.

Risk Assessment Voluntary and mandatory databases fail to provide sufficient data about the frequency with which invasive procedures are performed on the wrong patient or wrong procedures are performed on a given patient. Such errors are likely underreported. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) collected 17 reports of patient identification errors over 7 years. New York State, where a mandatory reporting system exists, experienced 27 blood transfusion errors over a 45-month period. Wrongsite surgery was reported to JCAHO 114 times in slightly more than 6 years, while New York State had 46 such reports over 2 years. Mismatched blood transfusions have been studied extensively, and it is believed that patient misidentification during blood transfusion is grossly underreported. It is estimated that about half of ABO-incompatible transfusions occur due to patient misidentification. The chance of suffering a fatality due to an ABO-incompatible transfusion is estimated to be nearly the same as that of being infected with human immunodeficiency virus (HIV) from that transfusion. There is only a 36% chance of a random donor and recipient having incompatible blood, and a less than 10% chance of such a transfusion being fatal.

Implications Many cases of patient misidentification, even when discovered, may cause no more than minor annoyance or embarrassment (e.g., a patient finding the wrong name on the slip he takes to the blood bank for a preoperative type and crossmatch). If an adverse outcome occurs, however, the consequences can be significant. The potential impact on the patient and family is obvious. Despite recent attempts to view patient misidentification as an inevitable part of the complex system of health care provision, both practitioners and their institutions are vulnerable to litigation. One need only look at the popular press to see the implications in terms of large malpractice settlements, loss of licenses or accreditation, and tarnished reputations for both the individuals and their institutions. No matter how complicated health care 921

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provision has become, clearly the public expects all procedures, medicines, and blood products to be delivered correctly.

MANAGEMENT If an error in patient identification occurs, do the following: ● ●

● ● ●

Be forthright regarding the incident. Promptly notify all parties and the appropriate risk management or quality assurance committees. Clearly document what has occurred in the patient’s chart. Continue to follow the patient, and document these visits. Undertake an immediate investigation to prevent recurrences.

We are morally and ethically obligated to be forthright with patients when identification errors occur, especially when they may be associated with significant adverse outcomes. Increasingly, this is codified in both the law and health care policy,1 and such admissions are often surprisingly well received by patients. In fact, candidness may actually reduce the likelihood of litigation. A show of empathy and continued interest in the patient’s well-being is certainly better than avoiding the situation altogether. Documentation of these post hoc visits not only is good medicine but also confirms the practitioner’s ongoing concern if the case goes to litigation. Undoubtedly, practitioners who make identification errors remember them for some time. All parties involved in the case should be notified of the error immediately. This includes hospital risk management or quality assurance committees and any insurance companies that might be involved. Clearly document what has occurred in the patient’s chart. An immediate investigation should ensue to determine how the mistake occurred and what preventive measures must be instituted immediately to avoid recurrences. Increasingly, such investigations focus less on the person who made the mistake and more on discovering the circumstances that led to the commission of the error. With the foregoing in mind, clearly the individual and the institution are obligated to pursue these investigations to determine what can be done to minimize the risk of future occurrences, which are often committed by a different practitioner.

PREVENTION Given the complexity of modern health care, the chance of patient misidentification is ever present. Traditionally, when such errors occurred, the usual solution was to counsel the practitioner to be more careful in the future and to educate others to exercise vigilance. Thus, the assumption appeared to be that the offender did not exercise due care and that other health care professionals might make the same mistake. Hospitals then instituted procedures to prevent further patient identification errors. For example, the operating room (OR) nurse must check the patient’s identification bracelet against the patient’s hospital record and then check the consent form to confirm that it is indeed the same 1

Since 2001, JCAHO has required that patients be informed of unanticipated outcomes.

patient who has consented to the planned procedure. However, this approach makes no use of other resources available in the OR. In fact, both the anesthesiologist and the surgeon should check and confirm the same information. Other industries—notably, commercial aviation—instituted such backup systems long ago. In the case of airlines, all available resources, information, equipment, and personnel are used to ensure safe and efficient flight operations. Such risk reduction practices are also used in manufacturing industries to prevent on-the-job injuries. Now, JCAHO has indicated its intention to follow a similar direction. Its recently implemented Universal Protocol for Preventing Wrong Site, Wrong Procedure, Wrong Person Surgery expands on previous efforts found in the JCAHO National Patient Safety Goals. The new protocol recommends that all relevant documents (e.g., consent form, history and physical examination, relevant laboratory and other test results) be available for review in the OR to ensure consistency. There should also be a note in the chart by the surgical team stating the planned procedure.2 This must match the patient’s expectation and understanding of what is or is not going to be done, including details about which limb or body side (and if the latter, at what level) is to be operated on. Also, it is necessary to confirm whether an implant will be needed. The protocol then requires a “timeout” for final verification before starting the procedure. Active involvement of all members of the various OR teams is emphasized, and the procedure must not start until all concerns have been resolved. JCAHO’s new protocol clearly intends to fully involve the most valuable OR resource—personnel—to cross-check one another and catch errors before they can result in an adverse outcome. JCAHO also established ground rules for ensuring proper identification as patients move through the health care system. These rules require at least two independent patient identifiers (the patient’s room number alone is insufficient) when administering blood or medications, taking specimens, or performing procedures or treatments. These same two identifiers must match all relevant documents (e.g., consent forms, laboratory slips and labels, blood product documents and labels). Further, JCAHO mandates that the operative site be marked and prohibits any marking of the nonoperative site. Finally, it discourages the use of an X to mark the operative site, which could be misinterpreted. JCAHO has mandated these changes as a means of avoiding patient misidentification before it causes an adverse event. Many institutions also encourage patients’ active participation in the process. Patient interviews should use the already accepted standard of asking nondirected questions. For example, patients should be asked to state their names and the planned surgical procedure (e.g., “What is going to be done to you?” or “What do you expect to happen while you are here?”), rather than merely confirming these from a chart review. Patient brochures and public service announcements now emphasize both these safety measures. Patients should also be encouraged to ask questions when things appear to be other than expected. 2 These precautions apply to other invasive procedures as well, including those performed by oncologists (e.g., radiation therapy or implants) and interventional cardiologists and radiologists.

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● ● ● ● ● ●

Absent wristbands (71.6%) Wristband from another patient (1.1%) Erroneous information on wristband (6.8%) Missing information on wristband (9.1%) Illegible information (7.7%) Conflicting information, such as a patient with two wristbands (3.7%)

Any of these errors could also apply to bar code wristbands used for patient identification. Thus, bar codes are merely an adjunct to existing patient identification practices. More emphasis should be directed toward detecting errors related to the wristbands themselves, with or without bar codes. An emerging technology, radiofrequency identification (RFID), may eventually replace bar codes in many medical settings. These devices consist of small integrated circuits

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containing patient-identifying information and other data. With an antenna, they can interact with RFID readers. Power is supplied by a field generated by the reader, and the RFID tags themselves have been miniaturized to the size of a piece of glitter. They offer several advantages over current practices, including the ability to store more information, update this information, and use the device without line-of-sight access to the tag (as required for bar codes). However, privacy concerns have been a significant barrier to their introduction to the marketplace, and these must also be addressed for medical use. Moreover, similar to the problem with implanted cardiac rhythm management devices (see Chapter 97), the potential adverse interactions with other medical equipment (both inside and outside the patient) have not been fully explored. Even so, cost is likely a bigger limitation. At present, placing an RFID tag on a patient’s wristband costs only 25¢, but the cost for using them for every dose of any drug prescribed would be prohibitive. In the final analysis, bar coding (and possibly RFID in the future) offers a backup tool for medical personnel to confirm a patient’s identification. Bar codes provide assistance, but they should never replace health care professionals working as a team to ensure that all patients receive the expected and appropriate care during surgery or other invasive interventions.

Further Reading Helmreich RL: On error management: Lessons from aviation. BMJ 320: 781-785, 2000. Linden JV, Wagner K, Voytovich AE, Sheehan J: Transfusion errors in New York State: An analysis of 10 years’ experience. Transfusion 40: 1207-1213, 2000. Wachter RM, Shojania K: Internal Bleeding: The Truth behind America’s Terrifying Epidemic of Medical Mistakes. New York, RuggedLand, 2004. Wald H, Shojania KG.: Prevention of misidentifications. In Shojania KG, Duncan BW, McDonald KM, Wachter RM (eds): Making Health Care Safer: A Critical Analysis of Patient Safety Practices. Evidence Report/Technology Assessment No. 43. AHRQ Publication No. 01-E058. Rockville, Md., Agency for Healthcare Research and Quality, July 2001. Available at http://www.ahrq.gov/clinic/ptsafety/

SPECIAL TOPICS

Because human fallibility is a fact of life, technologic aids are being advocated. Bar codes are now being implemented in health care. Compared with keystrokes, bar codes greatly improve accuracy. Keystroke errors are about 1 in 300, whereas bar code errors range anywhere from 1 in 394,000 to 1 in 612,900,000, depending on the bar code and the circumstances. The Food and Drug Administration recently mandated bar coding for all medications as a first step. The hope is that full implementation of bar coding will control medication errors in both hospital and outpatient settings (prescription drugs). Universal drug coding would be expected to replicate the accuracy of bar codes. In this case, all medications would be matched to a wristband bar code for the individual patient. Because the latter cannot be massproduced, however, there is some risk for keystroke errors during wristband production. In fact, the instigating error in the case synopsis turned out to be a keystroke error in the admissions office that was difficult to correct. Further, the accuracy of bar codes mentioned earlier reflects a laboratory setting; this may not be duplicated in clinical medicine. A study of problems related to the use of wristbands for patient identification found an error rate of 7.4%, which was reduced to only 3.04% with quality improvement efforts. The errors identified included the following:

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Syringe Swaps Carsten Nadjat-Haiem Case Synopsis A healthy 32-year-old woman is scheduled for elective myomectomy. General endotracheal anesthesia is induced successfully, and the surgeon requests a dose of prophylactic cefazolin. The anesthesiologist picks up a 10-mL syringe and administers 2 mL of its contents. When disconnecting the syringe from the three-way stopcock, he realizes that the syringe is labeled phenylephrine (Fig. 235-1). He administers incremental nitroglycerin to reduce anticipated hypertension from the drug error. The patient suffers no ill consequences.

PROBLEM ANALYSIS Definition A syringe swap is the accidental administration of an incorrect drug or dosage to a patient. This occurs when a syringe is mislabeled or when it is correctly labeled but mistaken for a different medication. Syringe swaps account for more than 6% of all drug administration errors.

affected by this error, although American Society of Anesthesiologists class I and II patients are more likely to be involved in a syringe swap. Usual causes include the following: ● ● ● ● ● ●

Recognition

● ●

A syringe swap is usually recognized when unexpected results are obtained after the administration of a drug or an event occurs without a readily apparent explanation; the swap may also be recognized before any effect is observed. The most common error is administering another dose of muscle relaxant when reversal is desired, resulting in the continued paralysis of the patient.

Lack of vigilance when drawing up medications Lack of vigilance in administering drugs Failure to label syringes correctly Failure to use labels Similar appearance of drug vials Poor drug tray organization Haphazard organization of syringes Fatigue

Syringe swap is a common event. Eighty-five percent of respondents in one study reported at least one drug administration error in their careers, and a significant number had actually harmed patients due to the administration of an incorrect drug.

Implications Risk Assessment Any patient under anesthesia care is at risk for syringe swap. Less healthy patients are more likely to be adversely

Consequences of a syringe swap can be benign or life threatening. There may be no apparent complications, or there may be serious morbidity and even death.

Figure 235–1 ■ Syringe labeling. If labels are placed longitudinally, they might be partially or fully hidden (A) or not visible with other syringe orientations (B). Circumferentially placed labels (C, D) eliminate the risk of hidden labels. The fact that the labels were hidden and the syringes containing phenylephrine and cefazolin were the same size and located next to each other on the anesthesia work station may explain the error illustrated by the case synopsis.

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MANAGEMENT Management of a syringe swap includes the following measures: ● ● ● ●

Recognize the mistake. Treat the consequences. Investigate the incident. Institute measures to prevent recurrences.

1 Of course, this presumes that any medications used in earlier cases have been returned to the pharmacy or disposed of during room turnover between cases.

Figure 235–2 ■ Drug tray organization. Consistent clustering of drugs into pressors (A), reversal agents (B), induction agents (C), antihypertensives (D), and neuromuscular blockers (E) reduces the risk of syringe swap. Especially important is spatial separation of neuromuscular blockers and reversal agents. Additional labels on vials that appear similar, such as neostigmine (B) and pancuronium (E), can further reduce the risk of drug misidentification. Note also that there is only one prepackaged syringe (epinephrine, between the two trays [arrow]), reducing the risk of syringe swap.

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925

instigate precautionary measures to differentiate drug vials (Fig. 235-2). From a medicolegal perspective, a syringe swap is a violation of the standard of care and a clear example of negligence. Advice from risk management should be sought at an early stage.

PREVENTION The best way to prevent a syringe swap is vigilance by the anesthesiologist when drawing up and administering medications. Adhere to a strict routine for drawing up medications, and check and recheck the labels on all syringes before administering their contents. The following specific measures will help prevent medication errors: 1. Check all drug vial labeling closely before drawing the contents into a syringe. This includes checking the name, expiration date, and concentration of the drug. One recent report described the nearly identical appearance of 0.2% and 0.75% ropivacaine. Also inspect the solution for any abnormal appearance or odor. 2. All syringes should be labeled before medications are drawn. The best system is to have well-organized, preprinted, color-coded labels on the anesthesia cart, with blank labels for seldom-used medications (Fig. 235-3). Syringes should also be labeled circumferentially, so that the contents can be identified regardless of the syringe orientation (see Fig. 235-1). 3. Use of syringes of different sizes is helpful. For example, induction agents are commonly placed in larger (20 or 30 mL) syringes, muscle relaxants in 10-mL syringes, and narcotics and other sedatives in smaller (3 or 5 mL) syringes. Most syringe swaps are between syringes of the same size.

SPECIAL TOPICS

If an incorrect drug has been administered, management initially consists of recognizing the mistake and treating any acute consequences. If the mistake is discovered quickly, as in the case synopsis, the practitioner should treat the consequences expectantly. If the mistake is not immediately apparent and an adverse event occurs, an immediate investigation should begin in the operating room. The room should be sealed off and any subsequent cases delayed or moved to a different room to prevent a recurrence. The investigation should be systematic and thorough, including all drugs used during the case. All drug containers and syringes used during the case should be inspected.1 Analyses of syringe contents may also be necessary. Preventive measures should be instituted immediately by the anesthesia department to ensure that the mistake is not repeated. If a complication results from the mistake, the patient and all parties immediately involved in the patient’s care should be notified. Any adverse consequences of the syringe swap should be clearly documented in the chart. The hospital risk management or quality assurance committee should be notified, as well as any other parties that may become involved (e.g., pharmacy, insurance carriers). If a syringe swap is the result of the similar labeling of medications, any drug companies involved and the Food and Drug Administration should be notified of the problem. The anesthesia department or responsible pharmacy should also

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Figure 235–3 ■ Color-coded syringe labels. A wellorganized and well-stocked tray of color-coded syringe labels facilitates the quick labeling of syringes.

4. Avoid drugs packaged in premixed syringes that have similar appearances. For example, both lidocaine and epinephrine come packaged in prelabeled glass syringes that look very similar. Their labels can be particularly hard to read. If drugs with this type of packaging are used, place an additional label on the plastic part of the syringe that can be easily recognized, or restrict the use of prepackaged medications to one per anesthesia cart (see Fig. 235-2). 5. Avoid drug containers that have similar appearances. If drugs with similar packaging are placed on the cart, bright warning labels should be put on the vials (see Fig. 235-2). Also, high-strength medications should be identified as such by additional labels or not routinely placed on the drug tray at all. Medications should be clustered by group on the medication tray (see Fig. 235-2). 6. Never administer any drug (contents) from an unlabeled syringe. 7. Consistency in the way the anesthesia cart is stocked is of utmost importance. Drugs should always be placed in the same location on the cart and be clustered by group actions (e.g., reversal agents, antihypertensives, muscle relaxants; see Fig. 235-2).

8. Resident and non-physician anesthetist education should include techniques to ensure that meticulous attention is paid to the handling of drugs. All personnel should be encouraged to develop strict routines for labeling and organizing syringes on the anesthesia cart.

Further Reading Bastien JL: Ropivacaine packaging: A potential for drug error. Anesthesiology 101:551, 2004. Fastings S, Gisvold SE: Adverse drug errors in anesthesia, and the impact of coloured syringe labels. Can J Anaesth 47:1006-1007, 2000. Irita K, Tsuzaki K, Sawa T, et al: Critical incidents due to drug administration error in the operating room: An analysis of 4,291,925 anesthetics over a four year period. Masui 53:577-584, 2004. Liang BA, Bramhall J, Cullen B: Which syringe did I use? Anesthesiologist confusion and potential liability for a medical error. J Clin Anesth 14:371-374, 2002. Orser BA, Chen RJ, Yee DA: Medication errors in anesthetic practice: A survey of 687 practitioners. Can J Anaesth 48:139-146, 2001. Warltier DC, Howard SK, Rosekind MR, et al: Fatigue in anesthesia: Implications and strategies for patient and provider safety. Anesthesiology 97:1281-1294, 2002.

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Quality Assurance Donald A. Kroll and Victoria Coon Case Synopsis

PROBLEM ANALYSIS Definition Quality management in medical practice has been notoriously difficult to define. It should not be surprising, therefore, that quality assurance is equally difficult, especially with continually evolving concepts and changing targets. The implementation of a QA program varies considerably from one institution to another, but most have the following features in common: ● ● ● ●

Incident reporting Occurrence screening Peer review Risk management

Incident Reporting. This provides a means of identifying critical or sentinel events. In the past, reporting typically involved only cases in which an injury had occurred. The injury may have resulted in major morbidity, mortality, or

SPECIAL TOPICS

A hospital quality management (QM) specialist is investigating an incident report filed by a postanesthesia care unit (PACU) nurse. A patient had respiratory difficulty in the PACU and required reintubation after a second dose of drugs to reverse neuromuscular blockade. The nurse states that this seems to be a frequent problem with the anesthesiologist, Dr. X. The QM specialist notes that Dr. X’s documentation is poor, making it difficult to reconstruct the facts. Twenty-five of Dr. X’s charts undergo a focused review. The review shows that 17 of the charts have substandard documentation. The medication practices in three cases are determined to be similar to those in the present case, which led to reintubation for postanesthetic respiratory depression. In two of these cases, plus an additional five cases, Dr. X’s response to the PACU’s request to assess a patient’s status was delayed. In response to this focused review, the medical staff conducts a formal hearing to determine whether to reduce Dr. X’s privileges or terminate him from the medical staff. At the hearing, Dr. X states that he is being targeted for dismissal because he did not cooperate in signing a new managed care contract. He alleges that his practice is no different from that of his associates and that all of the anesthesiologists have a problem responding to the PACU after they have started another case. He further alleges that the cases reviewed were not randomly selected but rather were selected based on foreknowledge of the complications involved. He acknowledges that his charting has been scanty and promises to improve. Additionally, he states that he has retained an attorney and will sue if his privileges are reduced or terminated. The QM Department stands by its analysis. It is convinced that Dr. X has shown a consistent pattern over time of both poor documentation and risky practices. The latter have already caused complications in several patients, and QM recommends that Dr. X be terminated for cause. The threat of litigation involves the legal department, which reports directly to the hospital chief executive officer (CEO). He expresses extreme displeasure that the situation has gotten so far out of hand and blames the Anesthesiology Department for failing to have an effective quality assurance (QA) program. The CEO wants to disband the department and hire a professional management firm whose brochure he received in the mail last week.

some other less adverse outcome, such as the need for additional hospitalization or delayed recovery. Because the reporting mechanism was voluntary and subject to bias, it was potentially problematic. Compliance with the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) guidelines now requires an in-depth, root-cause analysis of those sentinel events that can be reviewed. Some events do not require actual injury but only the potential for injury. The mechanism by which a hospital handles incident reporting has become a key factor in the accreditation process. Failure to comply results in the initiation of an accreditation watch for the institution. Occurrence Screening. This is a means of tracking how frequently certain events happen. The JCAHO provided some standardization for occurrence screening by suggesting the following key indicators: ● ● ●

Stroke Acute myocardial infarction Peripheral neuropathy 927

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Cardiac arrest Mortality within 2 days of surgery

The selection of these indicators was flawed, however, by their relative infrequency and lack of specific correlation to anesthetic management. One or two cases may make a major difference in the rate of adverse occurrences, and there is not necessarily a cause-and-effect relationship between an event and the quality of anesthesia care. Indeed, it is possible to adhere to or even exceed practice standards and still have an occasional adverse outcome. Although it is no longer a JCAHO focus, occurrence screening is a good method for assessing perceived problem areas. Peer Review. This is the practice of having one health care provider assess the care rendered by another. The peer reviewer is expected to render an expert medical opinion regarding the cause of injury and its possible attribution to the provider, the health care system, or the patient’s primary condition or comorbidities. Given the complexity of anesthesiology practice, peer review is essential to the analysis of sentinel events and occurrence screening. The peer review process, however, suffers from providers’ general lack of willingness to participate and their reluctance to call another’s care substandard. It is also subject to potential negative bias based on personalities, secondary agendas, and the severity of injury. Risk Management. This implies that it is possible to both identify and manage risks inherent in health care delivery. There is wide latitude in defining the nature of the risks and who should manage them. In most hospitals, however, the practice consists of a method of minimizing the consequences of adverse events that have already occurred. Eichorn described the four components of classic risk management: 1. 2. 3. 4.

Identification of a problem Assessment and evaluation Resolution of the problem by change Follow-up to ensure elimination of the problem

These components define the process of continual quality improvement. Thus, the general components of a QA or risk management program include a similar, continuing process with the goal of improving patient care and outcomes.

Recognition As in the case synopsis, the recognition that an institution has a problem with its QA program typically occurs only when the consequences become significant. The fundamental problem with recognizing such problems is the lack of broadly accepted and applicable guidelines. It is extremely difficult to evaluate a process unless incidence and outcomes are known: ● ● ●

●

How many provider problems are expected each year? How many indicators, and which ones, should be tracked? How is it determined that acceptable limits have been transgressed? How can the reliability and fairness of peer review be verified?

The complex nature of data collection and validation, process management, peer review, and the establishment of standards has led to the creation of professional QM

consulting firms. Such firms offer independent data tracking and benchmarking for both QA and utilization review purposes. However, the ultimate role for such QM consultants has yet to be established.

Risk Assessment Avoidance of complicated situations is best done proactively. A careful review of the components of the institution’s QA process is helpful. Each should be examined to determine its effectiveness and fairness. PROBLEM IDENTIFICATION There must be a published policy on when to file an incident report. The reporting mechanism must be applied equally to all events and be independent of the provider’s identity. Occurrence screening may either sample some patient records or review them all; sampling underreports occurrences, but 100% review is generally too labor-intensive. Regardless, because the anesthesia record is filled out by the provider, it amounts to voluntary reporting unless there is unbiased data capture (e.g., electronic charting). Screened occurrences should be reviewed periodically. Rare occurrences are not useful for tracking. A reliable method is one proved to identify previously solved problems. PROBLEM ASSESSMENT Parameters for interpreting occurrence data and outliers must be formulated prospectively. They should also be compatible with the scope-of-practice definitions by which a provider is evaluated. For example, anesthesia care providers who manage primarily patients having ambulatory gynecologic procedures might reasonably be expected to show a higher incidence of postoperative nausea and vomiting than those who do only cardiovascular anesthesia. The latter, however, are expected to show a higher incidence of perioperative myocardial infarction. The method of case selection for focused reviews should be known in advance and designed to obtain a representative sample of the provider’s care, especially if his or her behavior or clinical competence is at issue. Also, peer review must be impartial and aimed toward definable practice standards. If deficiencies are noted, the exact deviation from these standards should be specified. In all cases, the standard applied should be that of reasonable and prudent care, not necessarily state-of-the-art practice. PROBLEM RESOLUTION Ideally, there should be a remedy short of dismissal for all but the most egregious errors and those involving conduct that clearly violates the medical staff bylaws. Depending on the problem, the provider should be given an opportunity to change his or her practices or procedures or to improve behavior and communication skills. In any case, the result should be a clearly defined and measurable expectation of performance. FOLLOW-UP The effects of any advised change in practices or procedures should be measured for an appropriate, finite period.

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During this time, there should be feedback on the provider’s compliance with expectations. Failure to meet the criteria for change should have known consequences, and it should be known that compliance will avoid those consequences.

Implications

MANAGEMENT Compliance with the methods outlined for QA is costly, but the stakes are very high. The institution must follow up on any charges, because it has independent and corporate responsibility to ensure the competency of its providers. Certainly the institution would be liable for any future similar adverse outcomes. Further, the provider is forced to pursue legal action because of the impact on his or her ability to practice. The entire department is at risk of being forced out and replaced. This is a no-win situation for all parties, and resolution can only attempt to minimize losses. Typically, QA violations are resolved by negotiation, mediated by an internal or external review board to arbitrate such disputes. Often, due process leads to voluntary resignation from the medical staff in exchange for dismissal of charges. The final disposition depends entirely on the strength of the evidence, with allowance for give-and-take. Given that statutory immunity is provided to the peer review process (stemming from society’s overriding interest in public protection), the physician has the distinct disadvantage of having to prove that the process was unfair or capricious.

PREVENTION QM has become a big business, and hospitals are not exempt. Within the hospital community, anesthesiology departments

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have been disbanded for failure to institute and maintain acceptable QA practices. The steps listed under Risk Assessment offer suggestions for initiating problem prevention within an existing program. In addition, the use of smarter technology may provide some remedies. One of the central tenets of QM is that the process is driven by data rather than belief. Data management is the first area of emphasis for problem prevention. Credibility of any charted data is an essential component. Automated (electronic) anesthesia charting systems have emerged as a solution to the problem of data capture and validation. However, selecting indicators of quality is commonly hampered by the lack of both a clear focus on what is important to measure and easily measured parameters to describe quality. Consequently, health care professionals tend to repetitively measure the same parameters rather than seeking feedback from patients and staff about other methods of improving and implementing metrics to assess results. Data gathering is followed by aggregation and reporting. Often, this involves computing each provider’s incidence versus the average incidence for all other members of the department. Such analysis requires significant judgment, owing to variable case types and mixes; therefore, it is subject to personal bias. Also, provider-centered analysis shifts the emphasis away from any opportunity to improve the process and tends to alienate the staff. Therefore, shifting to system- or process-oriented analysis has become a second area of emphasis for problem prevention. Finally, recent JCAHO guidelines emphasize that root-cause analysis should focus primarily on systems and processes rather than on individuals.

Further Reading Dornette WHL: Legal Issues in Anesthesia Practice. Philadelphia, FA Davis, 1991. Eichorn JA: Risk management in anesthesia. In 47th Annual Refresher Course Lectures and Clinical Update Program. Park Ridge, Ill., American Society of Anesthesiologists, 1996. Posner KL, Cheney FW, Kroll DA: Professional liability, risk management, and quality improvement. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 4th ed. Philadelphia, JB Lippincott, 2001, pp 89-96.

SPECIAL TOPICS

The success of a QA program has implications for hospitals, providers, and patients. Failure to have an effective QA program may result in loss of accreditation or repeat site visits. This can have a significant financial impact on the institution. Providers who have been identified as having QA problems face possible loss of medical staff privileges and mandatory reporting to medical licensing agencies. Their ability to continue to practice medicine may be jeopardized. Patients are theoretically the prime beneficiaries of an effective QA program. They should be able to have confidence in the quality of the health care institution and the provider’s services.

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Cost Containment Victoria Coon and Donald A. Kroll

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Case Synopsis A 59-year-old, otherwise healthy man with degenerative osteoarthritis is scheduled for a right total hip replacement. He is evaluated in a preoperative clinic, where the only medically indicated laboratory test is a complete blood count. On the day of surgery, he presents with a urinary tract infection, necessitating cancellation of the surgery. The surgeon is upset that the patient did not get a “routine” preoperative urinalysis, which, he believes, would have prevented the cancellation.

PROBLEM ANALYSIS Definition Cost containment has become a driving force in health care management. To control ever-rising costs, managers and providers need to know the principal determinants. Expenditures controlled by anesthesia providers constitute 3% to 5% of the total health care costs in the United States. They can be broken down as follows: ● ● ●

Preoperative testing ($11.7 billion) Provider services ($9 billion) Equipment, facilities, and supplies (not quantified to date)

PREOPERATIVE TESTING Gone are the days when a “shotgun” approach to preoperative laboratory testing was economically feasible. Cost versus benefit is a prime consideration, and the performance of such tests should be data driven and based on a defined medical indicator. In a 1990 study at the Mayo Clinic, Narr and colleagues estimated that the elimination of routine laboratory testing in healthy patients younger than 40 years would decrease annual health care spending by $2.9 billion to $4.2 billion. For older patients, only medically indicated tests should be performed. In the case synopsis, in the absence of symptoms of urinary tract infection, no medical indicator was present for urinalysis at the time of the patient’s preoperative visit. Further, the subsequent development of the urinary tract infection would not have been “prevented” by a urinalysis. Diagnosis by clinical history was the determining factor in the decision to cancel the operation on the day of surgery, and if the same clinical history had been elicited during the preoperative evaluation, a similar decision might have been reached. In an attempt to create a standardized list of medical conditions that warrant further testing, a Delphi study was done at an urban Veterans Affairs (VA) hospital to obtain a consensus among anesthesia providers. Implementation of the results caused a significant decrease in the amount of tests ordered, with no increase in the surgery cancellation rate. However, savings on laboratory testing could not be realized until there was a reduction in laboratory personnel, capital equipment renewal, or reagent use. The documented cost savings from the VA study, an estimated $5 million per year, 930

occurred when the streamlined preoperative evaluation process allowed a reduction in the length of preoperative admission time and the closure of surgical beds. Published reports purporting to save money by ordering fewer laboratory tests fail to recognize that reagent cost is the smallest expense. Until personnel are reduced or capital equipment costs are avoided, no significant saving can be realized. PROVIDER COSTS The provision of health care is essentially a service industry. As such, the majority of cost is incurred in providing personnel. The personnel who provide anesthesiology services may include physicians, nurse anesthetists, residents and other trainees, or anesthesia assistants. There is a growing competition among some specialty surgeons, as well as dentists and oral surgeons, to deliver anesthesia care. Currently, in the majority of cases in the United States, anesthetics are delivered by an anesthesia care team (ACT) consisting of anesthesiologists and certified registered nurse anesthetists (CRNAs). The ACT concept affords the lowest incidence of anesthesia-related deaths and, when evaluating the indirect costs of adverse outcomes, is quite efficient. Attempts to determine optimal staffing ratios to minimize costs while preserving quality are hampered by lack of data, practice variations, and political posturing. Nonetheless, non-ACT personnel (e.g., health care economists) who are not necessarily fully informed may attempt to determine optimal staffing ratios to minimize costs. Several studies attempting to quantify costs have concluded that there are few direct cost savings when anesthesia is provided by one anesthesiologist supervising two CRNAs rather than by two anesthesiologists. In the Los Angeles area, as CRNA costs have risen and anesthesiologist costs have declined, it is actually less expensive to use two anesthesiologists rather than one anesthesiologist and two CRNAs. Because of vigilance issues and the need to provide breaks for the anesthesia provider, the safety of having a second provider involved might still make a 1:2 anesthesiologist-toCRNA ratio a viable option. A 1:3 or 1:4 ratio is obviously more cost-effective but may compromise quality and safety, depending on the patient population. Although Klein reported in a Kaiser Permanente study that a 1:4 anesthesiologist-toCRNA ratio was associated with no unexpected adverse outcomes, the results may not be widely applicable. Fassett and Calmes studied the perceptions of nurse anesthetists working

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on an ACT and concluded that excessive medical direction may contribute to overall costs of the ACT. These perceptions generated much rebuttal from the anesthesiologist community, however. It can only be concluded that adjustments in staffing ratios should be individualized on the basis of a sound rationale that includes both cost and quality, not merely perceptions. COST

OF

EQUIPMENT, SUPPLIES,

AND

FACILITIES

Recognition As noted earlier, there is a tendency to assume that reducing the number of laboratory tests performed or shortening recovery time automatically reduces costs. This is not true. Cost savings can be realized only when there is an actual reduction in personnel or expenses. Until then, there are only potential cost savings. Another pitfall is using charges to determine costs.

Risk Assessment There are three important concepts to consider when attempting to analyze costs: fixed costs, variable costs (direct and indirect), and marginal costs or marginal capacity. All businesses, companies, and physicians have a finite capacity to deliver a product or service. The difference between the maximal capacity and the current capacity is the marginal capacity. The decision to increase capacity above the current margin should be based on an analysis of incremental benefits and costs. A common business example might be the decision to add a second or third shift to a production line rather than paying overtime. This type of decision would take into account the current and future market for the product (will the company be able to sell all the additional units?) and the increased direct and indirect costs of raw materials and labor (variable costs). These would be weighed against the fixed costs of the existing facility. A variable cost is a cost that varies with production; a fixed cost is independent of production.

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It should be noted that fixed costs may be hidden within categories that consist primarily of variable costs. A worker’s hourly wage is a variable cost, but benefits may be a fixed cost. As a general rule, the higher the ratio of fixed costs to variable costs, the greater the desirability of increasing marginal capacity. The airline industry provides another prime example: it costs about the same to fly a half-full plane as a full plane, which is why supersaver discount airfares are offered. Hospitals have been managed much like the airline industry, in that the majority of their costs are fixed. They must remain open all day, every day, regardless of the inpatient population. The wards must be staffed by nurses, the laundry and food services must operate, and the emergency room and operating rooms must be available. It does not cost the hospital much more to admit one additional patient (low incremental cost) if the capacity to do so is in place. In other words, the biggest cost is for the facility, which is already a “sunk” cost. In hospitals where anesthesia providers are salaried, personnel costs are actually a fixed cost at any given point in time, and they become variable only when the number of staff changes. The only practical way to contain the cost per case in this environment is to either increase the number of cases or reduce the number of staff. The situation differs for fee-for-service anesthesiologists and depends on the specific features of their practice situations (their “overhead”). Anesthesiologists who purchase their own equipment or pay high malpractice premiums have relatively higher fixed costs than those who do not. Billing costs are usually variable costs. In most situations, it does not cost the anesthesiologist much to take on another case (low marginal cost). The issue is whether he or she has the ability to add capacity.

Implications The basic assumption of managed care medicine is that the physicians will be willing to work harder (increase capacity, take on more cases) to make the same income. This assumption necessarily follows the observation that the fee is discounted. If an anesthesiologist makes 20% less for a case, he or she has to take on 20% more cases to make the same amount as before, if all else stays the same. The marginal cost for the physician is measured not in terms of actual fixed and variable business costs but rather in the intangible threat that failure to contract will result in loss of business (an adverse or undesired increase in marginal capacity). Stated more simply, the only way to maintain a market share in a price war is to cut prices.

MANAGEMENT AND PREVENTION In both the health maintenance organization and fee-forservice models, the driving force for cost containment is avoiding loss of income (which has been stated as an adverse increase in marginal capacity). When viewed in this way, it becomes clear that the most effective means of containing costs is to create more marginal capacity by improving time efficiency to the point where another case can be completed in the original amount of time (an actual increase in productivity for the same fixed cost).

SPECIAL TOPICS

To date, only 1% to 2% of anesthesia studies include a cost analysis. Although it is not the greatest area of expense controlled by anesthesia providers, the judicious, rational use of drugs and disposable and capital equipment is important. Careful analysis of the cost-to-benefit ratio should be performed. Pharmaceuticals are an easy target for cost control analysis, although they make up a relatively small percentage of overall anesthesia costs. Direct and indirect costs, however, should be included in the cost-benefit analysis. An example might be the direct cost of an expensive antinausea drug being offset by a decrease in the indirect costs of postanesthesia care unit services and the avoidance of an unplanned hospital admissions following ambulatory surgery. The most significant problem with such studies is that no savings can be realized until the number of personnel is reduced. There are also intangible costs to consider, such as patient satisfaction and quality-of-life issues. These are critical when the value to the patient decreases to the point were he or she goes elsewhere for care.

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Special Topics

Further Reading Abenstein JP, Warner MA: Anesthesia providers, patient outcomes, and costs. Anesth Analg 82:1273-1283, 1996. Becker KE: Personnel cost analysis. ASA Newsletter 59:3, 1995. Becker KE, Carrithers J: Practical methods of cost containment in anesthesia and surgery. J Clin Anesth 6:5, 1994. Cromwell J, Rosenbach M: The impact of nurse anesthetists on anesthesiologist productivity. Med Care 28:2, 1990. Fassett S, Calmes SH: Perceptions by an anesthesia care team on the need for medical direction. AANA J 63:2, 1995. Jenkins CE: The effect of standardized preoperative evaluations on operating room surgical schedules [master’s thesis]. Los Angeles, University of California, 1994. Johnstone RE, Martinec CL: Costs of anesthesia. Anesth Analg 76:840-848, 1993.

Klein JD: When will managed care come to anesthesia? J Health Care Finance 23:3, 1997. Narr BJ, Hanser TR, Warner MD: Preoperative laboratory screening in healthy Mayo patients: Cost effective elimination of tests and unchanged outcomes. Mayo Clin Proc 66:155-159, 1991. Stein CS: A patient based approach to medical direction within the anesthesia care team [master’s thesis]. Los Angeles, University of California, 1994. Suver J, Arikian SR, Doyle JJ, et al: Use of anesthesia selection in controlling surgery costs in an HMO hospital. Clin Ther 17:3, 1995. Warner MA: Cost containment in anesthesia, is it worth the effort? In Annual AMA Refresher Course Lectures, 1996. White PF, White LD: Cost containment in the operating room: Who is responsible? J Clin Anesth 6:351-356, 1994. Wiklind RA, Barash PG: Anesthesiology. JAMA 271:21, 1994.

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238

Alleged Malpractice Robert D. Kaye and Christopher M. B. Heard Case Synopsis A 23-year-old woman undergoes emergency cesarean section under general anesthesia for fetal bradycardia and placental abruption. She is hypotensive (blood pressure 70/30 mm Hg) and tachycardic (heart rate 150 beats per minute) as the procedure begins. After delivery, the baby has poor Apgar scores, with evidence of fetal acidosis (cord pH, 7.01). Postoperatively, the patient complains of awareness during surgery. The baby develops cerebral palsy, seizures, and developmental delay. Two years later, a malpractice action is brought that accuses the anesthesiologist of negligence.

Definition A lawsuit is a civil case seeking monetary damages based on a claim of professional negligence. The plaintiff must show that there was failure to apply an accepted standard of care for the defendant’s specialty area in the particular case. A poor outcome in itself is not evidence of negligence. The manner in which an anesthesiologist acts is often just as important as the evidence in deciding the case.

Recognition There are several ways that the practitioner may become aware of a malpractice complaint. A complaint to a nurse by a relative of the patient may be the first clue. This information may pass to the anesthesiologist involved while the patient is still hospitalized. Another possibility is that a patient lodges a formal complaint with the hospital administration concerning the practice of a particular anesthesiologist at that hospital. Formally, a lawsuit begins when an anesthesiologist is served a complaint and summons. The complaint declares how the plaintiff was injured by substandard care and the particulars on which the claim is based. The malpractice carrier should be notified immediately and sent a copy of all documents received.

factor in less than half of newborn brain damage suits. Half of all obstetric anesthesia claims are filed for minor injuries (e.g., headache, backache, pain during surgery, emotional distress). In approximately 40% of all lawsuits in the ASA Closed Claims Project, payment was made to the plaintiff despite the reviewers’ findings of appropriate anesthesia care.

Implications There is a sequence of events that ensues following alleged malpractice (Table 238-2). Once a formal complaint has been lodged, it must be answered. The professional liability carrier assigns an attorney to defend the anesthesiologist and prepare the answer. The anesthesiologist has the option to request a specific attorney, as long as he or she is on a list of attorneys approved by the malpractice carrier. The anesthesiologist may also retain a personal attorney at his or her own expense. Usually this is not necessary unless the case will lead to licensure problems or grave economic hardships. Each allegation of the complaint may be admitted, denied, or denied in part. During the early planning stages, it is imperative that the anesthesiologist be completely candid with the attorney and share all information, both positive and negative. Malpractice attorneys have a surprising amount of medical knowledge. The anesthesiologist must educate the attorney

Causes of Alleged Malpractice

Risk Assessment

Table 238–1

The incidence of anesthesia malpractice has decreased over the past 20 years. Increased use of pulse oximetry and capnography may be partially responsible for the lower incidence of poor outcomes. Table 238-1 lists several causes of alleged malpractice. Certain areas of anesthesia practice are associated with a higher risk, such as obstetrics, trauma, and pediatrics. Outcomes such as death or severe neurologic damage are often associated with failure to maintain adequate oxygenation or circulation. The majority of obstetric claims involve cesarean delivery, with maternal death (21%) and newborn brain damage (17%) being the most common complaints. Reviewers in the American Society of Anesthesiologists (ASA) Closed Claims Project found improper anesthetic care to be a contributing

Failure to supply adequate oxygenation Intubation error Oxygen supply failure Obstructed airway Failure to maintain adequate circulation Hypotension Arrhythmias Cardiac arrest Aspiration Awareness Neurologic injury Peripheral nerve injury Spinal cord damage Extradural foreign body Dental injury Corneal injury

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PROBLEM ANALYSIS

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Table 238–2

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Special Topics

Stages in a Malpractice Lawsuit

Complaint and summons Answer Discovery Motions Pretrial conference Jury trial

MANAGEMENT The discovery process is the exchange of information among all the participants in a lawsuit. Table 238-3 lists the main methods of discovery. The deposition is the most familiar method of discovery. Under oath, the defendant is asked questions that he or she must answer, similar to the format used in court. A professional attitude, appearance, and demeanor are important during a deposition. What the anesthesiologist says at a deposition carries as much weight as what he or she says in court. The plaintiff ’s attorney will be appraising the anesthesiologist to judge what kind of witness he or she would be before a jury. The anesthesiologist’s attorney will meet with him or her before the deposition to go over what to expect, including what questions to anticipate, how to answer specific queries, and how to behave. Questions should be answered directly and factually. Do not volunteer any information. Do not show anger or use slang or humor. Motions are requests to the court for an order requiring a participant in a lawsuit to carry out a certain action.

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The Course of a Trial

Jury selection Opening statements Plaintiff’s proofs Defendant’s proofs Closing arguments Jury instruction by presiding judge Jury deliberation Verdict

on the salient medical features of the case and help the attorney prepare the defense by being candid about other therapeutic options. Confidentiality is an important consideration. Any information provided by the client to the attorney or by the attorney to the client is privileged and need not be divulged. Likewise, information shared between the insurance company’s investigator and the anesthesiologist is privileged. Discussions the anesthesiologist has with a colleague concerning the substance of a case are not privileged and are fully discoverable (the discovery process is discussed under Management). Any document concerning the litigation that an anesthesiologist includes in the patient’s medical report is discoverable. Documents involved in a malpractice case need to be kept in a separate file in a secure location.

Table 238–3

Table 238–4

Motions do not usually require the physician’s presence in court. The attorney will advise the client of any motions that require him or her to act. Before the trial, all attorneys involved in the case meet at a hearing held by the court. The anesthesiologist does not attend this conference. At the pretrial conference, matters such as deadlines for pretrial discovery, disclosure times for expert witnesses, and a trial date may be discussed. Some states have a mandatory pretrial mediation to attempt to settle the case before jury trial. The testimony during a trial is similar to that of a deposition, with certain differences. There is a presiding judge to settle questions of law. There is a lay jury that is not as medically knowledgeable as the attorneys who conducted the depositions. The course of a trial is briefly outlined in Table 238-4. Insurance policy considerations are important. Many physicians worry that a malpractice award will be higher than the limits of their policy. The typical anesthesia malpractice policy has a per occurrence limit of $1 million. Only 4% of the payments in the ASA Closed Claims Project exceeded this amount. The percentage of malpractice awards greater than $1 million has not increased since the beginning of data collection by the ASA. Malpractice policies do not reimburse physicians for time away from practice or the loss of income associated with a lawsuit. All policies have a clause that specifically excludes defense for intentional acts of wrongdoing. Many policies have a clause requiring reasonable cooperation by the physician with the assigned attorney and the insurer’s claims investigator. A practitioner who refuses to comply with discovery requests, attend preliminaries conferences, or give a deposition will not be defended.

PREVENTION The prevention of malpractice is based on maintaining a specialist standard of care at all times. Table 238-5 lists

The Discovery Process

Method

Description

Interrogatories Requests to produce medical information Requests to produce documents Deposition of witnesses

Written requests consisting of a long list of questions that the defendant is expected to reply to Requests for copies of pertinent medical records; most hospitals secure medical charts involved in malpractice actions in a separate area These can involve any document the plaintiff or defendant believes is important to the case (e.g., a plaintiff might request a copy of a board certification certificate) Testimony taken under oath in a format similar to that used in court

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Table 238–5

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Important Considerations to Maintain Standard of Care

Preoperative patient interview Explanation of risks and alternatives Adherence to ASA monitoring recommendations Correct labeling of medications Accurate, legible anesthesia record keeping Familiarity with anesthesia equipment Appropriate request for assistance Familiarity with procedure being performed Care with positioning of anesthetized patients Postoperative follow-up visit

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Further Reading Caplan RA: Anesthetic liability: What it is and what it isn’t. Anesth Analg 74(Suppl):19-24, 1992. Chadwick HS, Posner K, Caplan RA, et al: A comparison of obstetric and nonobstetric anesthesia malpractice claims. Anesthesiology 74: 242-249, 1991. Cheney FW, Posner K, Caplan RA, et al: Standard of care and anesthesia liability. JAMA 261:1599-1603, 1989. Kroll DA: What to do if you are sued: Medicolegal update. ASA Refresher Course Lect 165:1-6, 1995. Lear E (ed): Examining the scope of professional liability. ASA Newsletter 60:6-28, 1996. Strunin L (ed): Post graduate education issue: Symposium on mishap or negligence. Br J Anaesth 73:1-117, 1994.

ASA, American Society of Anesthesiologists.

SPECIAL TOPICS

several standards that should be applied in all cases. Visiting the patient preoperatively and postoperatively is important to ensure adequate communication and to address patient concerns. A continual quality improvement program is also a usual adjunct.

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239

The Hostile-Combative Patient Doron Feldman, James M. T. Foster, and Christopher M. B. Heard Case Synopsis A 17-year-old boy with mental retardation is scheduled for elective surgery for tendon release. He has had multiple previous surgeries and suffers from a seizure disorder. He is in the preoperative holding area in an agitated state, refusing to go to the operating room. His parents are present and are very distressed.

PROBLEM ANALYSIS Definition A hostile-combative patient is one who is uncooperative with the medical and nursing staff. This may be intentional or result from impaired neurologic function. It may occur at any time during the perioperative period. Preoperatively, the patient may refuse to be interviewed or examined or to allow required preoperative investigations. It may be difficult to persuade the patient to enter the operating room, to be positioned in an appropriate manner for induction of anesthesia, and to cooperate in a safe manner during the induction process. If the patient is awake or semiconscious during the procedure (e.g., regional or intravenous sedation techniques), he or she may become agitated during the procedure. Postoperatively, the patient may be uncooperative in the postanesthesia care unit (PACU).

security staff if the patient’s behavior is extremely dangerous or disruptive. In the case of prior criminal behavior, a police officer may be escorting the patient. It is wise, whenever possible, to review a patient’s chart for information about his or her previous perioperative behavior. If the patient was uncooperative in the past, how was the issue dealt with? Table 239-1 lists several potential problems that may be encountered when dealing with uncooperative patients.

Risk Assessment There are many reasons for a patient’s uncooperative behavior (Table 239-2). In some cases, behavior problems can be anticipated based on the patient’s medical history, medications the patient has received, or the procedure he or she is undergoing. In emergency situations, these problems are more difficult to anticipate.

Recognition

Implications

Often these problems can be anticipated by the patient’s history (previous similar encounters) or the planned procedure (e.g., a magnetic resonance imaging scan during which patient’s entire body or upper torso will be inside the scanner). If there is suspicion that belligerent behavior might be an issue, possibly during the patient’s transfer to the preoperative holding area, the anesthetist should be informed as soon as possible. This often allows for proper planning and a smooth encounter, making it more pleasant for the patient, the family, and staff and other patients in the holding area. In some cases, it may be necessary to call for the hospital

A patient’s lack of cooperation has implications for perioperative anesthetic management. The transfer of an uncooperative patient may be fraught with problems. It may be

Table 239–1

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Potential Problems with HostileCombative Patients

Refusal to submit to preoperative investigations Refusal to go to the operating room Refusal of monitoring Refusal of intravenous line placement Verbal attack Physical attack

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Table 239–2

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Causes of Uncooperative Behavior

Mental retardation Anxiety Fear of needles or anesthesia Drugs: sedatives, recreational Drug withdrawal Alcohol Alcohol withdrawal Recurrent procedures Young age Hypoxia Psychotic disorders Pain Electrolyte abnormalities (e.g., hyponatremia after transurethral prostate resection) Postoperative emergence phenomena (e.g., ketamine) Increased intracranial pressure Sociopathic behavior disorder

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Table 239–3

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Implications for Perioperative Anesthetic Management

Safety of patient Safety of staff and other patients Inability to proceed with anesthesia and operation Increased risk of laryngospasm (in children) Urgency of procedure Legal considerations Age of consent Patient’s ability to give informed consent Parents’ wishes (for children)

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need of an emergency cesarean section but refuses a regional anesthetic must still have the procedure performed. If, after reasonable efforts to persuade the patient otherwise, she still insists on general anesthesia, it must be provided. The same holds true for an adult patient who refuses a blood transfusion. Legally, minors can receive blood and blood products if the physician deems such treatment to be lifesaving. In elective circumstances, when a patient makes a request that the anesthesiologist in good conscience cannot grant, the case should be postponed until the procedure can be carried out according to the patient’s wishes or the patient agrees to an acceptable alternative. The initial approach to uncooperative or combative patients is to try to change their behavior through conversation, education, and persuasion. Success is variable and depends on the anesthesiologist’s interpersonal skills, the patient’s support system, and the degree of his or her pathology. With children, it is sometimes possible to alter their behavior with toys, play-acting, and the like. Often, it is helpful to seek the aid of the parent or guardian and the surgeon in this endeavor. The next step is to decide whether there is a need for premedication. Pharmacologic intervention is often used for both cooperative and uncooperative patients, and preoperative sedation can be administered orally, intramuscularly, intranasally, intravenously, or rectally (Table 239-4). If the patient is agreeable to receiving premedication, the oral route is usually preferred. Otherwise, an intravenous or, more commonly, an intramuscular approach is used. Gentle restraint, often after premedication, may control patients who are physically small. Although physical restraint is usually an option of last resort, it is sometimes necessary for patient and staff safety.

MANAGEMENT PREVENTION A patient who is uncooperative, hostile, or otherwise indicates that he or she does not agree to receive the planned medical care presents physicians with a medicolegal dilemma. Some patients present the anesthetist with a list of self-mandated conditions, the granting of which may compromise the patient’s well-being and could lead to a conflict that causes the patient to become uncooperative. Examples include a patient who refuses blood administration on religious grounds (e.g., a Jehovah’s Witness), a patient who tries to dictate the type of anesthetic induction (intravenous or mask), or a patient who insists on general anesthesia when the anesthesiologist believes that a regional technique would be safer (e.g., cesarean section). It is extremely important to be sure that it is legal to treat a patient. Small children are often uncooperative, and unless the situation is life threatening, consent must be obtained from the child’s legal guardian (parent, foster parent, or institutional or governmental agency). A patient who is not a minor and is not a custodian of the state must give consent for any procedure to be performed. Otherwise, treating such a patient may constitute a battery. If the patient has been declared incompetent by the state, legal permission to proceed with care should be granted by a court. Such permission is often obtained by the hospital administration. In the case of an emergency procedure, the patient’s wishes should be followed. For example, a patient who is in

A preoperative interview is probably the most effective method of preempting the problem of an uncooperative patient.

Table 239–4

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Options for Dealing with an Uncooperative Patient

Cancel case, but only after good-faith efforts to resolve the situation Reschedule the procedure after appropriate action Provide explanation and reassurance Use a regional technique if the patient is afraid of general anesthesia Use EMLA (eutectic mixture of lidocaine and prilocaine), nitrous oxide, or high-flow volatile inhalation anesthetic induction (e.g., sevoflurane) in cases of “needle phobia” Give preoperative sedation Midazolam syrup (0.25 to 0.35 mg/kg, up to 20 mg maximum) Midazolam IM (0.1 to 0.15 mg/kg, up to 7.5 mg maximum) Midazolam IV (titration in increments of 1.0 to 1.5 mg, to effect) Midazolam intranasally (0.2 mg/kg up to 20 mg maximum; but not routinely advised because it produces stinging or burning sensation) Fentanyl (oral or transmucosal administration of 5 to 15 μg/kg, up to 400 μg maximum) Ketamine IM (1 mg/kg) or PO (3 mg/kg) Rectal methohexitone-methohexital (20 to 30 mg/kg)

SPECIAL TOPICS

difficult to maintain an adequate degree of monitoring if the patient repeatedly removes the pulse oximetry probe, or to supply supplemental oxygen via facemask or nasal prongs if these are removed. An uncooperative patient is also at risk of injury if he or she falls. Table 239-3 lists other implications for perioperative anesthetic management. It may be impossible to use the most appropriate form of anesthesia because of the patient’s behavior. Intubation of a presumed difficult airway in an uncooperative patient can be challenging. Also, although regional anesthesia may be an attractive option (e.g., in a patient at high risk for aspiration), it may not be practical in an uncooperative patient. Finally, the safety of anesthesia care providers, surgeons, operating room personnel, and PACU and patient transport staff is of the utmost importance. Patients who were cooperative preoperatively may become disoriented and violent during transport or in the PACU.

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It allows the patient’s fears to be addressed and a plan of action to be proposed, enabling the case to continue. If the patient cannot reason, owing to age or mental impairment, the parents or guardians must be involved. Although this is often helpful, there are times when family members only add to the problem—for example, if they too suffer from phobias or are uneducated about the proposed anesthetic plan. The use of premedication before the patient is brought to the operating area, while he or she is still in a quiet room, may be useful. Always make sure that premedicated patients are appropriately monitored to prevent dangerous side effects (e.g., respiratory depression, falls). Also avoid the temptation to premedicate the patient before transport to the operating room or at home, unless accompanied by appropriate personnel. Another possibly helpful but controversial technique (studies have been inconclusive) is to have one of the child’s parents present at induction of anesthesia. Most problems related to interactions with hostile or combative patients can be solved with common sense, reason, and kindness. In our experience, cancellation of a case due to inappropriate patient behavior is extremely rare. Full disclosure and communication can ameliorate a stressful experience, as well as reduce the risk of litigation.

Further Reading Bragg CL, Miller BR: Oral ketamine facilitates induction in a combative mentally retarded patient. J Clin Anesth 2:121-122, 1990. Coté CJ: Pediatric anesthesia. In Miller RD (ed): Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 2367-2407. Fukuta O, Braham RL, Yanase H, et al: The sedative effects of intranasal midazolam administration in the dental treatment of patients with mental disabilities. Part 1. The effect of a 0.2 mg/kg dose. J Clin Pediatr Dent 17:231-237, 1993. Fukuta O, Braham RL, Yanase H, Kurosu K: The sedative effects of intranasal midazolam administration in the dental treatment of patients with mental disabilities. Part 2. Optimal concentration of intranasal midazolam. J Clin Pediatr Dent 18:259-265, 1994. Moyers JR, Vincent CM: Preoperative medication. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 4th ed. Philadelphia, JB Lippincott–Williams & Wilkins, 2001, pp 551-565. Rosenberg M: Oral ketamine for deep sedation of difficult to manage children who are mentally handicapped: Case report. Pediatr Dent 13:221-223, 1991. Wu CL: Acute postoperative pain. In Miller RD (ed): Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005, pp 2729-2762.

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Awareness under Anesthesia Marcia M. Lee Case Synopsis

PROBLEM ANALYSIS

Some factors, however, have been implicated as causative events, including the following:

Definition

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Patient awareness under anesthesia (AUA) can take many forms. A working definition is the spontaneous recall of events occurring under general anesthesia. AUA includes both explicit and implicit memory. Explicit memory is information consciously recollected by the patient, and implicit memory is information that is not associated with any conscious recollection. Recall of implicit memories may occur during dreaming or while under hypnosis or with the use of other psychological methods.

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Recognition Traditional methods for monitoring levels of AUA were based on indirect hemodynamic measurements, such as heart rate and blood pressure. These are now widely accepted as merely crude and nonspecific measures of the brain’s hypnotic state; however, in many cases (especially in the less developed world), they are still the only methods available to monitor AUA. Of note, with the increasing number of procedures being performed under conscious or procedural sedation, it is critical that the diagnosis of AUA be carefully and distinctly made. Patients commonly perceive that they were “asleep” when general anesthesia was not actually administered. This can lead to confusion and, perhaps, a misdiagnosis of AUA, especially if a clear explanation of the type of anesthesia is not provided. The majority of studies of AUA specifically restrict that term to patient populations undergoing general anesthesia.

Risk Assessment The incidence of AUA is usually cited as slightly less than 1%. Reviews of patient experiences show that auditory perception and the sensation of paralysis are among the most frequently listed complaints, followed by pain perception. Unfortunately, the cause of AUA is not clearly understood.

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Machine malfunction, whereby the desired amount of anesthetic is not delivered. Deliberate limitation of the amount of anesthetic delivered because of clinical conditions. These conditions include hypovolemia (e.g., in trauma cases) or cesarean section, when attempts are made to minimize depression of the infant. The use of cardiopulmonary bypass. Such patients may have an increased risk of AUA or recall. Failure to administer anesthetic agents in a timely fashion. For example, during protracted or difficult intubations, plasma concentrations of anesthetic induction drugs may wane, so that supplemental dosing is required. Even in smooth inductions, the effect of shorter-acting agents may decline before that of maintenance agents is attained. Increased use of neuromuscular blockers during maintenance of anesthesia, as well as their use to facilitate tracheal intubation. Their anticipated use may contribute directly to patients’ anxiety. Among the patients experiencing AUA in the study by Moerman and colleagues, 85% reported the sensation of weakness and paralysis as the overriding reason for their anxiety and panic. Their inability to alert anyone of their awareness was as disturbing as the actual AUA. Inadvertent administration of muscle relaxants due to syringe swaps (see Chapter 235). One Australian review noted that 6 of 16 cases of AUA were due to the unintentional use of suxamethonium instead of fentanyl. Expanded use of shorter-acting anesthetic induction and maintenance agents, especially as the number of same-day surgeries increases. For these surgeries, the goals of home readiness and early discharge encourage the use of shortacting anesthetics.

Implications Awareness under anesthesia is commonly feared by both anesthesiologists and patients. For the latter, possible adverse psychological sequelae include anxiety, sleep disorders, 939

SPECIAL TOPICS

“I was put under the anesthetic but suddenly woke. I was wide awake but couldn’t move. All I could feel was terrible, terrible pain. I was crying and screaming. But nobody knew” (from Cobcroft and Forsdick). “I had the strange (but at the time it seemed logical and right) sensation of coming out of myself; of being up by the ceiling looking down on the proceedings. And after the initial realisation that I couldn’t communicate at all, came the feeling of acceptance” (from Cobcroft and Forsdick).

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depression, nightmares, panic attacks, and long-term psychiatric disorders. Much of the psychological trauma following AUA appears to be related to the patient’s feeling of a lack of control or that something has gone terribly wrong, along with the inability to communicate such feelings.

MANAGEMENT What should the anesthesiologist do if he or she believes that AUA or recall has occurred? First, there must be honest, sincere, and full disclosure of what happened. The possible reasons for AUA should be explained to the patient at the earliest possible time postoperatively. Second, sympathy and empathy must be conveyed. Third, the patient should be reassured that repetition of AUA during a future anesthetic is not an inevitable or even a likely occurrence. Fourth, it is essential to maintain contact with the patient though follow-up. Fifth, if necessary, referral for psychological counseling or psychiatric care should be given. Last, the institution’s risk management or quality assurance department must be notified.

PREVENTION Because there is no single coherent explanation for the development of AUA, it is impossible to provide a comprehensive plan to prevent such occurrences. However, there are some measures (see also Ghoneim and Block) that may help reduce the risk of a patient’s developing AUA: ●

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Ensure that all devices used to deliver anesthetics are checked thoroughly and frequently (at least daily), including the anesthesia machine and vaporizers, as well as any infusion pumps. Monitor end-tidal inhalational anesthetic concentrations. Administer inhalational anesthetics at an end-tidal concentration of 0.6 minimal alveolar concentration (MAC). Work by Dwyer and colleagues showed that conscious recall can be prevented with 0.6 MAC end-tidal isoflurane. However, this MAC value may not apply to other inhalational anesthetics and might be lower (diethyl ether) or higher (desflurane, sevoflurane). Among the inhalational anesthetics used today, isoflurane appears to be more effective for preventing awareness or recall than equivalent MAC levels of nitrous oxide, desflurane, and sevoflurane. Use agents with amnestic properties, especially when AUA is likely (e.g., trauma surgery, hypovolemia, emergent cesarean section, open-heart surgery). Benzodiazepines or scopolamine can be used as either premedications or supplements to the anesthetic. However, one must not rely solely on these agents, because their effectiveness for preventing AUA is dose dependent and often patient specific. Minimize muscle relaxant use, and avoid complete paralysis whenever possible. Patient movements, although an extremely crude measure, may indicate AUA. Encourage all operating room personnel to refrain from making disparaging remarks about a patient’s condition or body habitus. There is evidence that cognitive processing

of derogatory or distressing auditory information occurs, even during presumably “adequate” anesthesia. Direct monitoring of brain wave activity has been proposed as a method of preventing AUA. Use of electroencephalograms (EEGs) has been proposed to prevent AUA, especially during spinal surgery. However, an EEG does not reliably predict the depth of inhalation anesthesia. In fact, there are reports showing that EEG signals do not correlate with or predict anesthetic depth (e.g., adrenergic cardiorespiratory responses to surgical stimulation, appropriate responses to verbal commands). Also, the EEG is a technically complex study and requires a knowledgeable EEG interpreter. Today, EEG indices derived from raw EEG signals recorded by disposable electrodes on the patient’s forehead are used to monitor the effects of anesthetic drugs on the brain. Commercial systems include the bispectral index monitor (BIS, Aspect Medical Systems, Natick, Mass) and the patient state analyzer (PSA, Physiometrix, Inc., North Billerica, Mass). Disposable electrode arrays are marketed for use with these systems, including the XP sensor for BIS monitors and the PSArray2 for PSA monitors. The former was designed to reduce electrocautery interference, which was problematic with earlier BIS electrodes. The latter was designed to save time and reduce the patient discomfort associated with the application of earlier PSA electrodes. Both BIS and PSA have a high probability of correctly predicting both loss and recovery of consciousness with general anesthesia. Both indices allow anesthesia providers to manipulate anesthetic levels and thus reduce emergence times. A recent cost analysis by White and associates showed that per patient costs for BIS and PSA are the same. They also reported less surgical electrocautery interference with the PSA system with PSArray2 sensors compared with BIS and PSArray2 sensors. The Food and Drug Administration has approved both systems as clinical monitors for anesthetic effects on the brain. The question is, can they be used to prevent AUA? The use of BIS or PSA to prevent AUA has been suggested. Both use proprietary algorithms to arrive at a “dimensionless”1 score, ranging from 100 (fully awake) to 0 (absence of any brain activity). Although both BIS and PSA appear to be equally reliable for evaluating the level of consciousness during induction of and emergence from general anesthesia, no adequately powered or controlled prospective trial has shown that either one is a useful monitor for AUA. Indeed, Schneider and Wagner’s small observational study found that a BIS value of 50 to 60 (the range suggested for general anesthesia is 40 to 60) before intubation was inadequate to prevent an awareness reaction (squeezing the investigator’s hand in response to a command) immediately after endotracheal intubation in patients induced with propofol and alfentanil. Because BIS could not differentiate between patients with and without an awareness reaction, the authors concluded that its value as a monitor for awareness is questionable. No comparable trials for PSA were available in mid-2005. Further, there is the issue of cost. O’Connor and Daves estimated the cost of using BIS to prevent AUA. It was 1

This term was used by White and colleagues; see Further Reading.

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Further Reading Cobcroft M, Forsdick C: Awareness under anaesthesia: The patients’ point of view. Anaesth Intensive Care 21:837-843, 1993. Dwyer R, Bennett HL, Eger EI, et al: Isoflurane anesthesia prevents unconscious learning. Anesth Analg 75:107-112, 1992.

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Ghoneim M, Block R: Learning and consciousness during general anesthesia. Anesthesiology 78:279-305, 1992. Glass P, Gan TJ, Sebel PS: Comparison of the bispectral index (BIS) and measured drug concentrations for the monitoring effects of propofol, midazolam, alfentanil and isoflurane. Anesthesiology 83:3A, 1995. Halliburton JR.: Awareness under general anesthesia: New technology for an old problem. CRNA 9:39-43, 1998. Heneghan C: Clinical and medicolegal aspects of conscious awareness during anesthesia. Int Anesthesiol Clin 31:1-11, 1993. Liu W, Thorp S, Aitkenhead AR, et al: Incidence of awareness with recall during general anesthesia. Anaesthesia 46:435-437, 1991. McLeskey C: Awareness under anesthesia. 45th Annual Refresher Course Program. Park Ridge, Ill., American Society of Anesthesiologists, 1994. Moerman N, Bonke B, Dosting J: Awareness and recall during general anesthesia. Anesthesiology 79:454-464, 1993. Myles PS: Bispectral index monitoring to prevent awareness during anesthesia: The B-Aware randomized controlled trial. Lancet 363:1747-1748, 2004. O’Connor MF, Daves SM: BIS monitoring to prevent awareness during general anesthesia. Anesthesiology 96:255-256, 2002. Osborne G, Webb RK, Runciman WB, et al: Patient awareness during anaesthesia: An analysis of 2000 incident reports. Anaesth Intensive Care 21:653-654, 1993. Schneider G, Wagner K: Bispectral index (BIS) may not predict awareness reaction to intubation in surgical patients. J Neurosurg Anesthesiol 14:7-11, 2002. White PF, Tang J, Ma H, et al: Is the patient state analyzer with the PSArray2 a cost-effective alternative to the bispectral index monitor during the perioperative period? Anesth Analg 99:1429-1435, 2004.

SPECIAL TOPICS

determined that if cases of AUA are rare (e.g., 1 in 20,000), the estimated cost of using BIS solely to reduce AUA is $400,000 per case. If AUA is more common (e.g., 1 in 100), the cost decreases to $2000 per case. Both estimates, however, presume that the monitor is 100% effective in preventing AUA, which is uncertain. Unfortunately, recent sensational media attention concerning the problem of AUA and the mandate of the Joint Commission on Accreditation of Healthcare Organizations to formulate policies to prevent AUA make a rational assessment of this problem difficult. Because no monitor is universally accepted as having the ability to detect, monitor, and eliminate AUA, measures to prevent it become even more important. In high-risk situations, when the preservation of life precludes deep anesthesia, prudent use of amnestic agents (e.g., ketamine or even scopolamine) might help protect against AUA. However, even these agents cannot guarantee that AUA will not occur. Finally, because there is no good explanation for the mechanism of its development, it is not possible to identify patients at greater risk for AUA or to prevent all occurrences. Isolated incidents of AUA will likely continue, despite good practice and adherence to accepted monitoring standards.

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Adverse Outcomes: Withheld Information or Misinformation

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Donald A. Kroll Case Synopsis A 55-year-old man is in the intensive care unit with unstable angina. Catheterization data show a 95% obstruction of the left main coronary artery and high-grade lesions in the right coronary artery. He is not considered a candidate for angioplasty because of diffuse disease in the left anterior descending and circumflex arteries. He is scheduled for surgery the following morning. At midnight, the patient complains of unrelenting chest pain, and it is determined that he is having an acute myocardial infarction. The decision is made to take him immediately to the operating room for emergency revascularization. At the end of an uneventful bypass period, the surgeon requests the anesthesiologist to start a dopamine infusion as the patient is simultaneously weaned from bypass. The initial attempt at weaning is complicated by profound hypotension, arrhythmias, and circulatory collapse, despite the addition of an epinephrine infusion. The decision is made to put the patient back on bypass. At that time, the anesthesiologist discovers that because he was distracted by starting the dopamine infusion, he neglected to turn the ventilator back on, which was probably the sole cause of the problem. He says nothing and charts nothing, hoping for a good outcome. Unfortunately, the patient suffers a severe stroke, eventually resulting in a chronic vegetative state and the need for long-term skilled nursing care. The surgeon tells the family that the cause of the stroke is not known for certain, but strokes are a well-known complication of this type of surgery.

PROBLEM ANALYSIS Definition The doctor-patient relationship is fiduciary in nature, meaning that it is based on the patient’s trust or confidence in the doctor. Once established, this relationship creates certain obligations or duties that the doctor owes the patient. One of the basic duties of physicians is to tell patients the truth about their diseases or conditions. Exceptions are allowed in certain circumstances if knowing the truth might be medically harmful to the patient. There are no exceptions, however, to the obligation to reveal the nature of adverse outcomes. Patients are absolutely entitled to a frank disclosure of the facts concerning their cases, especially when the results are adverse. Failure to provide a forthright account of the events, either by withholding information or by providing misleading information, is known as fraudulent concealment. This creates new and serious complications for the physician that are separate and distinct from the initial complication.

Recognition Anyone who has worked in a hospital knows that it is virtually impossible to prevent the spread of information or disinformation (e.g., rumors). Given the presence of numerous 942

providers from several disciplines in most situations in which anesthesia care is provided, it is extremely unlikely that an error will be entirely unnoticed. In the case synopsis, however, it is conceivable that the error might go undetected. Medicolegal experts have estimated that 10 potentially compensable negligent acts resulting in injuries occur for every malpractice case filed. Because of the solo (“concealed by the drapes”) nature of anesthesia practice, it may be more feasible for an anesthesiologist to cover up a negligent act than for other specialists. Real case examples are hard to find, however, and the serious consequences if such an attempt is discovered make intentional (fraudulent) concealment both an unethical and an unwise choice. In cases involving other specialties, recognition that material facts have been concealed may come from other percipient witnesses, inconsistencies in the medical record, internal hospital reviews or interviews, or suspicions of subsequent health care providers.

Risk Assessment There is a natural tendency to present bad news in the most favorable light possible. The law allows for some latitude in communication, even when the relationship between parties is based on trust. As long as the information given to a patient or a family member is as factual and complete as feasible under the circumstances, there is unlikely to be

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a problem. It is understood that the practice of medicine is not an exact science, and a miscommunication based on incomplete or inaccurate information available to the doctor is unlikely to be considered fraudulent concealment. Problems occur when a doctor intentionally lies or fails to convey all the material facts. Concealing unfavorable information is viewed, at best, as a negligent breach of the general duty to disclose information to the patient; at worst, it becomes what is known as an intentional tort. In simplest terms, the risk incurred is that of changing a straightforward negligence case into an intentional tort. If it is reasonable to conclude that the information not disclosed was withheld to avoid the discovery of negligence, the withholding is considered to constitute an attempt to defraud.

Most states have a statute of limitations for medical malpractice (for negligence) of 2 years from the date the injury was discovered. The date of discovery is interpreted as the time at which a reasonable person with fair access to the facts either knew or should have known that an injury might be due to a negligent act. If it can be shown that material facts or relevant information was intentionally withheld, the statute of limitations does not begin until the date that the fraudulent concealment of information is discovered (intentional tort). The statute of limitations can then be extended to 4 years or more. Deceitful behavior by a doctor is not likely to be viewed favorably by a jury, which may wish to either punish the doctor (punitive damages) or set an example to other doctors that such behavior will not be tolerated by the public (exemplary damages). These damages may be three times the actual damages awarded for the negligent act itself. Intentional torts are not covered by malpractice policies. Most likely, the physician will be held personally responsible for paying the damages.

MANAGEMENT Responding appropriately when an adverse incident occurs may decrease the chance of a lawsuit. In addition to documenting the facts in the medical record, other options may help avoid a malpractice suit. Obviously, it is most important to ensure that optimal medical care is provided. Consultation should be obtained, when appropriate, to ensure that all diagnostic and therapeutic steps have been taken and that the continued care of the patient is provided by the most suitable specialists. Obtaining the opinion of another anesthesiologist when an adverse situation occurs is one of the most frequently overlooked opportunities for consultation. If another anesthesiologist is asked to help during an emergency and the patient still suffers harm, the anesthesiologist should make a note on the record verifying all events, including documentation of the requested consultation. Many hospitals have begun to use a system of risk management whereby specially trained people are available to

intervene whenever a question of liability arises. Such persons and departments have several names: patient-staff relations, patient advocate, ombudsman, risk management coordinator, and so forth. They may fall under the administrative supervision of the hospital attorney’s office or be located elsewhere in the hospital administration. If such people are available, they should be notified immediately of any adverse incident. They can help gather information about the incident, offer support for the patient and the patient’s family, and act as liaison between the family and any physicians involved. They may be invaluable in reducing the likelihood of a lawsuit or the amount of the damages eventually awarded. The anesthesiologist should notify his or her malpractice insurance carrier of any events that may lead to a lawsuit. Many companies require such notification as part of the agreement to insure. It is extraordinarily unlikely that the anesthesiologist will be adversely affected by giving the insurance company prompt notice of an incident. Although the anesthesiologist’s role is that of a consultant to the primary care physicians, he or she should continue to follow the patient’s in-hospital progress after any adverse incident or outcome that might be related to anesthesia. Failure to do so might be construed as abandoning the patient and indicates disinterest in and disregard for the patient’s welfare. If the anesthesiologist believes that the incident is clearly unrelated to anesthesia care, he or she should clearly state in the medical record why this is so and that his or her services as a consultant are no longer required. Additionally, the anesthesiologist should indicate his or her further availability if future services are required.

PREVENTION The prevention of adverse outcomes is the subject of risk management and quality assurance programs, discussed elsewhere in this book (see Chapter 236). The steps outlined earlier are critical to preventing an adverse outcome from becoming a malpractice suit. Prevention of misinformation and withheld information is a fundamental integrity issue that can be furthered by accurate and complete charting in the medical record and frank discussions with the patient and family members.

Further Reading Dornette WH (ed): Legal Issues in Anesthesia Practice. Philadelphia, FA Davis, 1991. Kroll DA: Professional Liability and the Anesthesiologist. Park Ridge, Ill., American Society of Anesthesiologists, 1987. Kroll DA: Medicolegal aspects: An American perspective. In Healy TEJ, Cohen PJ (eds): Churchill-Davidson’s Practice of Anaesthesia. London, Edward Arnold, 1995, ch 73. Kroll DA, Cheney FW: Medicolegal aspects of anesthetic practice. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 2nd ed. Philadelphia, JB Lippincott, 1992. LeBlang TR, Basanta WE, Peters JD, et al: The Law of Medical Practice in Illinois. Rochester, N.Y., Lawyers Cooperative Publishing, 1986. Peters JD, Fineberg K, Kroll DA, et al: Anesthesiology and the Law. Ann Arbor, Mich., Health Administration Press, 1983.

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Implications

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Patient Confidentiality Gail A. Van Norman

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Case Synopsis A 17-year-old girl presents for dilation and curettage (D&C) for irregular menses; she is accompanied by her mother. A review of her chart reveals that the patient is pregnant and that the D&C is for termination of pregnancy. The chart notes indicate that the patient does not want her mother to know about her pregnancy.

PROBLEM ANALYSIS Definition ETHICAL CONSIDERATIONS Physicians’ ethical obligation to protect patient confidentiality arises out of the individual right to privacy. Just as the ethical and legal principles requiring respect for patient autonomy give patients the right to determine what will be done to them, respect for autonomy also confers rights to control information about themselves. These rights are especially strict when they involve sensitive information about medical, emotional, and mental status. Additionally, in the United States, federal laws now guard patient privacy and specify serious penalties when that privacy is violated. Physicians also have an ethical and legal obligation of fidelity to patients, meaning that physicians are obliged to keep both explicit and implicit promises made during patient care. The promise to keep patient information confidential is at least as old as the Hippocratic oath, which states: “What I may see or hear in the course of treatment in regard to the life of men, which on no account one must spread abroad, I will keep to myself.” The ethical obligation to keep patients’ confidences is justified by the consequences that a breach might cause. If patients cannot trust their physicians with personal information, they would be reluctant to provide full and accurate disclosure, impairing the physicians’ ability to treat them. Ultimately, violation of confidentiality harms the doctorpatient relationship. The Patient Bill of Rights, adopted by the American Hospital Association in 1973, states: The patient has the right to every consideration of privacy concerning his own medical care program. Case discussion, consultation, examination, and treatment are confidential and should be conducted discreetly. Those not directly involved in his care must have the permission of the patient to be present. The patient has the right to expect that all communications and records pertaining to his care should be treated as confidential. Although maintaining patient confidentiality is a strict ethical obligation, some circumstances allow the infringement of confidentiality. The 1980 American Medical Association Code of Ethics states that physicians should not violate rules of confidentiality unless they are required to do so by law or 944

unless it becomes necessary to protect the welfare of the individual or society. LEGAL CONSIDERATIONS Before 2003, case law established a federal right to privacy with regard to medical records. In Whalen v. Roe, the U.S. Supreme Court held that there is a constitutional basis for patients’ right to privacy regarding their medical records. In addition to federal rights, state laws address the right to privacy concerning medical information. Legal precedents also recognize certain areas of heightened confidentiality, including the following: ● ● ●

Mental health treatment Treatment for sexually transmitted disease Treatment for substance abuse

In 2003, full compliance with the 1996 Health Insurance Portability and Accountability Act (HIPAA) became mandated, with widespread implications for patient privacy and provider duties. HIPAA requires that patients be informed of their privacy rights and regulates who can have access to personally identifiable medical information. HIPAA imposes both financial and criminal penalties on entities that violate patient privacy. Providers must take care to avoid any and all discussions of private patient information in settings where they might be overheard. Patients must give permission before even family members can be present for or take part in discussions that include medical information. Violations of patient privacy can result in fines of up to $250,000 and imprisonment of up to 10 years if the health care information is disclosed “for commercial advantage, personal gain, or malicious harm.” Many states have specific laws pertaining to the confidentiality of the medical records of minors. Generally, to the extent that minors provide their own consent for care, they may have a privacy expectation about what information can be provided to their parents. Under HIPAA, for example, parents may not be given information about their minor child’s health care without first obtaining the child’s permission if state law allows the child to give consent for his or her own care. Laws vary by state, but some areas in which minors’ medical information is strictly protected and for which minors can consent to their own care, even to the exclusion of parental knowledge, include the following: ● ● ●

Abortion Birth control Reproductive functions

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Treatment for sexually transmitted disease Treatment for mental illness Treatment for drug addiction

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Suspected child abuse Epilepsy (to the department of motor vehicles) Sexually transmitted disease (to the public health department) Gunshot wounds (to local police)

Recognition In the case synopsis, it is clear that informing the patient’s mother of her pregnancy would violate patient confidentiality. However, many less obvious violations of patient confidentiality occur in everyday practice. Common examples are indiscreet discussion of patient information in public places, discussions with individuals not directly involved in the patient’s care, and review of charts by individuals not involved in either the care of the patient or quality assurance. In the operating room, violation of patient confidentiality may occur when informed consent discussions occur where they might be overheard, or when persons who are not members of the surgical team are allowed in the operating room without the express permission of the patient. Such individuals might include drug and equipment sales representatives, student observers, or health care personnel not directly involved in the patient’s care.

Risk Assessment All patients are at risk of having their privacy violated during the course of medical care.

Implications Violation of patient confidentiality can result in harm to the doctor-patient relationship. Physicians can also face legal action owing to unjustified violations of patient confidence. In addition, they may face significant monetary penalties or even imprisonment under current HIPAA regulations.

MANAGEMENT When circumstances might require an intentional violation of a patient’s confidentiality, the patient’s permission to

Patient Confidentiality

945

disclose the information should be sought first. If the patient refuses, the physician’s ethical and legal obligations are to protect the patient’s confidence, but these obligations may be interpreted less stringently when harm might result to other persons if confidentiality is kept. The hospital attorney and hospital ethics committee can be helpful in resolving such legal and ethical issues. Management of unintentional violations of patient privacy starts with a heightened awareness of the ways confidentiality may be compromised, and avoiding them.

PREVENTION Anesthesiologists have an especially important responsibility in guaranteeing patient confidentiality and taking measures to protect the privacy of patients who are undergoing anesthesia. This is especially so because any drugs ordered or administered can impair the patient’s ability to protect him- or herself. Guidelines include the following: ●

●

●

●

●

●

●

Do not disclose patient information to individuals not directly involved in the patient’s care, unless the patient has granted permission for such disclosure. Maintain possession of the patient’s chart, and limit chart accessibility by individuals not involved in the patient’s care. Review a patient’s chart only if you are directly involved in the patient’s care or as part of a quality assurance function. Discuss medical issues with patients and family only in locations that ensure privacy, and then only after obtaining permission from the patient for family members to be present. Know or identify each person in the operating room and why he or she is there. Do not allow anyone into the operating room who does not have express or implicit permission from the patient to be there. Do not discuss other patients and their care in the operating or during the course of surgery, particularly if the patient having surgery is awake and might overhear the information.

Further Reading Annas GJ: HIPAA regulations—a new era of medical-record privacy? N Engl J Med 348:1486-1490, 2003. Beauchamp TL, Childress JF: Principles of Biomedical Ethics, 4th ed. New York, Oxford University Press, 1994, pp 418-429. Burnum JF: Secrets about patients. N Engl J Med 324:1130-1133, 1991. Emson HE: Minimal breaches of confidentiality in health care research: A Canadian perspective. J Med Ethics 20:165-168, 1994. Gostin L: National health information privacy: Regulations under the Health Care Portability and Accountability Act. JAMA 285:3015-3021, 2001. Guidelines for the ethical practice of anesthesiology. In ASA Standards, Guidelines and Statements. Park Ridge, Ill., American Society of Anesthesiologists, 1995, pp 9-12. Jonsen AR, Siegler M, Winslade WJ: Clinical Ethics, 3rd ed. New York, McGraw-Hill, 1992, pp 126-131. Kleinman I: Confidentiality and the duty to warn. Can Med Assoc J 149:1783-1785, 1993.

SPECIAL TOPICS

Just as ethical principles recognize that patients’ right to confidentiality may be limited, especially if harm would result to another individual, legal precedent has recognized that in some circumstances, patient confidentiality can be or even must be violated. In the case of Tarasoff v. Regents of the University of California, a patient confided to his therapist his intention to kill Tatiana Tarasoff. When the patient carried out his threat, the therapist was held liable for the woman’s death for failing to reveal his patient’s intentions. The court ruled that the patient’s right to confidentiality was limited when he became a threat to another individual. Legal precedent recognizes other circumstances in which protecting patient confidentiality may cause harm to the patient or others and thus requires the physician to report confidential information, such as the following:

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Gail A. Van Norman Case Synopsis A 76-year-old man presents for foot amputation for peripheral vascular disease. He has right hemiparesis and mild expressive aphasia from a previous stroke. His chart carries a do-not-resuscitate (DNR) order. After discussion with the patient, including the risks of anesthesia, he states that he does not want cardiopulmonary resuscitation if cardiac arrest occurs while he is anesthetized. Anesthetic induction is uneventful, but during infusion of intravenous antibiotics, the patient develops hypotension and bradycardia. Despite the administration of epinephrine, he becomes asystolic.

Definition

The prognosis for patients who experience cardiac arrest and are resuscitated in the OR is better than that for patients resuscitated in other hospital locations, with 50% to 85% of patients surviving to discharge.

CARDIOPULMONARY RESUSCITATION

ETHICAL CONSIDERATIONS

Kouwenhoven and colleagues first described closed-chest cardiac massage in the 1960s as therapy for in-hospital cardiac arrest. Despite the subsequent enthusiastic use of cardiopulmonary resuscitation (CPR), survival was dismal, with studies in the 1960s and 1980s showing that only 9% to 15% of patients survived to hospital discharge. Increasing costs of resuscitation and intensive care and a heightened awareness that not all patients desire life-sustaining treatment under all circumstances led practitioners in the 1970s and 1980s to question whether all patients should automatically be given CPR. Efforts by the Massachusetts General Hospital in Boston led to the development of DNR orders, now widely used in the United States. Conflicts can occur when patients with DNR orders undergo surgery. The definition of arrest and procedures of resuscitation have different implications in the operating room (OR) than in other hospital settings. For example, respiratory arrest on a hospital ward is a defining event, requiring immediate recognition and intervention to save life, including mouth-to-mouth resuscitation, possible intubation and ventilatory support, and concurrent cardiovascular support, which may include pharmacologic support and CPR. Many patients and physicians intend DNR orders to include refusal of respiratory support, pharmacologic intervention, and closed-chest massage. During surgery, however, anesthetic agents may depress respiration, even to the point of cessation. Far from extraordinary care, assisted or mechanical ventilation is a feature of many routine anesthetic procedures. Further, common and predictable changes in circulatory parameters may require the administration of fluid and vasoactive drugs. Indeed, pharmacologic intervention (i.e., chemical resuscitation) is the essence of anesthetic practice. Consequently, it follows that DNR orders do not exclude closed-chest cardiac massage in the OR, unless otherwise specified by the patient or legal guardian.

Physicians have an ethical obligation to respect patient autonomy. Once they are properly informed, patients who are mentally capable of understanding and consenting to treatment have the right to refuse medical interventions, even when they might be lifesaving, including CPR. Despite patients’ rights to determine the course of their own medical treatment, multiple studies have shown that a disturbing percentage of patients who are capable of participating in resuscitation decisions (up to 46% in at least one study) are not consulted before DNR orders are entered in their charts. In 1995 the SUPPORT study found that less than half of physicians were even aware when their patients did not want resuscitation. Other than for reasons of medical futility, DNR orders are usually entered in patient charts because the physician perceives that the quality of life before or after CPR will be poor. However, ethically, only the patient or someone the patient has designated to speak for him or her can make such quality-of-life decisions. Physician perceptions regarding CPR can be affected by personal values and conflicts, unrealistic expectations, unconscious motivations, fear of professional failure, and fear of legal retribution. Several studies indicate that physicians’ perceptions of quality of life often differ significantly from those of their patients.

PROBLEM ANALYSIS

946

LEGAL CONSIDERATIONS Patients’ legal right to determine the course of their medical care is firmly established. In 1914, in Schloendorff v. Society of New York Hospital, Justice Cordozo declared that “every human being of adult years and sound mind has the right to determine what shall be done with his own body.” Such autonomous rights have been supported by innumerable legal decisions since then, many of which cite the 11th and 14th Amendments to the U.S. Constitution.

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and a reevaluation of the patient’s DNR status in light of the perioperative circumstances. Because many primary care physicians and surgeons are not knowledgeable about the risks of anesthesia and the better risk-benefit ratio of CPR in the OR, the most appropriate physician to have this discussion with the patient is the anesthesiologist. Many patients or their surrogate decision makers rescind DNR orders for the perioperative period once they are informed of the favorable outcomes for patients who have CPR in the OR. Therefore, for a patient who is about to undergo anesthesia and surgery, the following guidelines apply: ● ●

●

●

●

●

Recognition When patients with DNR orders come to the OR, anesthesiologists fail to recognize that such an order is in place in as many as 69% of cases. Furthermore, in up to 46% of cases, competent patients with DNR orders do not know that there is a DNR order in the chart.

947

●

●

Determine whether the patient has a DNR order. Be aware that when a DNR order exists, even a competent patient may not know that it has been entered in the chart. Discuss the order with the patient or the surrogate decision maker, including the risks and benefits of resuscitation in the OR. Document changes to the DNR order, if any, in the medical record. Inform other members of the health care team of the patient’s DNR status and of any exceptions that will be applied in the OR or during subsequent care (e.g., postanesthesia care unit). When questions arise about the appropriateness of a patient’s DNR status, helpful resources include the hospital attorney and ethics committee. If you cannot respect a patient’s wish to continue a DNR order in the perioperative period, refer the patient to a colleague who will. When emergencies arise, endeavor to provide the best medical care possible, in keeping with the patient’s goals.

Risk Assessment DNR orders are often associated with patients who are in failing health or at the end of life, but any patient can come to the OR with a DNR order or another advance directive that refuses CPR.

Implications Once competent patients are fully informed of the excellent prognosis for resuscitation in the OR, they often rescind their DNR orders for the perioperative period. However, automatically rescinding all DNR orders for surgery without a discussion with the patient is no more ethical than entering a DNR order in a competent patient’s chart without his or her knowledge. Both ignore patients’ ethical and legal rights to determine their own medical care. Physicians who ignore a patient’s refusal of CPR do so at some legal peril.

MANAGEMENT Appropriate management of a patient undergoing surgery with a DNR order mandates a discussion of the risks and benefits of resuscitation with the patient or the surrogates

Further Reading Beauchamp TL, Childress JF: Principles of Biomedical Ethics, 4th ed. New York, Oxford University Press, 1994, pp 120-142, 196-202, 290. Ethical guidelines for the anesthesia care of patients with do-not-resuscitate orders or other directives that limit treatment. In ASA Standards, Guidelines, and Statements. Park Ridge, Ill., American Society of Anesthesiologists, 1995, pp 8-9. Hackleman T: Violation of an individual’s right to die: The need for a wrongful living cause of action. U Cin L Rev 62:1355-1371, 1966. Jonsen AR, Siegler M, Winslade WJ: Clinical Ethics, 3rd ed. New York, McGraw-Hill, 1992, pp 27-31. Keffer MJ, Keffer HL: Do-not-resuscitate in the operating room: Moral obligations of anesthesiologists. Anesth Analg 74:901-905, 1992. Martin R: Liability for failing to follow advanced directives. Physician’s News Digest, 1999. SUPPORT principal investigators: A controlled trial to improve care for seriously ill hospitalized patients: The Study to Understand Prognosis and Preferences for Outcomes and Risks of Treatments (SUPPORT). JAMA 274:1591-1598, 1995. Troug R: Do-not-resuscitate orders during anesthesia and surgery. Anesthesiology 74:606-608, 1991. Van Norman G: Ethical decision/end-of-life care in patients with vascular disease. In Kaplan JA, Lake CL, Murray MJ (eds): Vascular Anesthesia, 2nd ed. Philadelphia, Churchill Livingstone, 2004, pp 397-400. Walker RM: DNR in the OR: Resuscitation as an operative risk. JAMA 266:2407-2412, 1991.

SPECIAL TOPICS

Legislation in New York State in the 1970s required that competent patients or the surrogates of incompetent patients give permission before any DNR order was entered into a patient chart. Since that time, legal rulings in many other states now require documentation that patients or their surrogates have been consulted and have given permission for DNR status. Because education has failed to produce widespread changes in physician behaviors with regard to resuscitation, legal scholars have proposed creating a tort of “wrongful living” (in distinction from “wrongful life” cases arising over conception, birth, and neonatal health issues) to provide damages to patients and their families when their wish to refuse therapy is violated by an unconsented resuscitation. In Anderson v. St. Francis–St. George Hospital, Inc., Edward Winter sued for damages when he suffered a stroke after a resuscitation effort was carried out in disregard for his stated preferences. In Klavan v. Chester Crozier Medical Center, the family of a physician who was left in a permanent vegetative state after unwanted resuscitation also sued for wrongful living. Although neither case has yet resulted in damage awards, more cases can be expected to arise as a result of unwanted resuscitation.

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The Jehovah’s Witness Patient Gail A. Van Norman Case Synopsis A 23-year-old woman who is a Jehovah’s Witness suffers postpartum hemorrhage, necessitating emergency hysterectomy. She previously refused blood transfusion. After induction of anesthesia, her hematocrit is 11%. With continued hemorrhage, the patient becomes hypotensive and bradycardic. Despite transfusion with 2 units of O-negative packed red cells, she dies. Her family sues. First, they allege that the anesthesiologist ignored the patient’s wishes. Second, they accuse him of committing medical malpractice for transfusing too little blood too late to save the patient’s life.

PROBLEM ANALYSIS

therapy poses serious ethical conflicts for anesthesiologists, whose goals are to ensure the patient’s survival in this life, not the next.

Definition RELIGIOUS CONSIDERATIONS

LEGAL CONSIDERATIONS

The beliefs of Jehovah’s Witnesses regarding transfusion are based on numerous biblical passages forbidding the “eating” of blood, even in emergencies; those who do face the loss of eternal life. For example: “Moreover, ye shall eat no manner of blood, whether it be of fowl or of beast in any of your dwellings. Whatsoever soul it be that eatest any manner of blood, even that shall be cut off from his people” (Leviticus 7:26, 27). The policy regarding blood transfusions was first introduced in 1945 and has been enforced by the Watchtower Society since 1961 through the practice of “disfellowshipping,” the shunning of individuals who willfully accept blood transfusion. Community, church, and family members may not associate with a “disfellowshipped” member. In some cases, willful acceptance of blood transfusion has been cited as justification for marriage dissolution. Beliefs regarding blood transfusion among members of the Society are not universal, however, nor are the requisite consequences. Depending on individual beliefs, fractionated blood components may be acceptable, and transplantation of solid organs (which contain some donor blood components) has been accepted by the Society. Bulgarian Jehovah’s Witnesses are given “free choice” when it comes to blood transfusion. In 2000, the Society issued a directive to the effect that members not complying with its policy on blood refusal would no longer be “disfellowshipped.” Rather, an individual’s decision to accept a blood transfusion would indicate that he or she no longer wished to be a member of the Society. A significant number of Jehovah’s Witnesses have publicly voiced opposition to the Society’s policy on blood transfusion. The seeming arbitrariness within the Society regarding blood transfusions is confusing for health care providers and may mistakenly lead to the assumption that individual decisions regarding blood transfusion are not heartfelt or spiritually based. Further, withholding routine, low-risk, lifesaving

In a landmark 1914 legal decision, Schloendorff v. Society of New York Hospital, Justice Cordozo stated, “every person of adult years and sound mind has a right to determine what shall be done to his own body.” This ruling, made in the case of unwanted medical intervention in an anesthetized patient, is the legal foundation for both informed consent and informed refusal of medical care in the United States. Further, the case of Nancy Cruzan sealed the right of competent individuals or their legal surrogates to refuse any medical therapy, even if it might be lifesaving. Many cases have affirmed that physicians may not arbitrarily override the wishes of competent patients with regard to refusing blood therapy. In 2002 the Supreme Court of South Carolina reviewed Harvey v. Strickland. In that case, doctors obtained permission from the mother of an unconscious adult Jehovah’s Witness to transfuse blood, even though they knew that before losing consciousness, the patient had specifically refused transfusion. The patient recovered fully and then sued for malpractice, medical battery, and lack of informed consent. Although a lower court found in favor of the physicians, the South Carolina Supreme Court reversed the decision and remanded the case for retrial, affirming that the patient’s original health care directives were legally binding. Court rulings usually support the provision of transfusions to pregnant patients, minors, and adults who cannot communicate and have not provided clear advance directives. Some courts have ruled that the state has an interest in preserving the life of a person who is the sole provider for others—for example, to prevent that person’s dependents from becoming the state’s responsibility. Others have pointed out that courts do not curtail the rights of sole providers to engage in a range of other risky activities, such as skydiving, on the chance that their death will leave orphans.

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has not been previously appointed by the patient, such as the spouse, parents, children, or siblings. Anesthesia and critical care providers should know their state’s hierarchy regarding surrogate decision makers. PREGNANT PATIENTS Ethical principles and legal precedent in the United States soundly support the right of privacy of pregnant women. Although a pregnant woman can make medical decisions that may sacrifice the life of her fetus early in pregnancy (Roe v. Wade), it is less clear how the legal rights of a potentially viable fetus in late pregnancy affect a woman’s right to refuse medical therapy. Nor is it clear how ethical principles should be weighed. MINOR PATIENTS

The importance of blood component therapy is undeniable, but the actual line where blood transfusion becomes necessary to maintain life varies with the patient and the circumstances. Often, physicians overestimate its importance. Although a recent study demonstrated that Jehovah’s Witness patients experiencing obstetric hemorrhage had a 44-fold increase in the risk of death, the absolute risk was quite low (0.5%). A study of blood loss in trauma patients found no significant increase in the risk of death in Jehovah’s Witness patients compared with other religious groups.

Most pediatric patients are not considered autonomous because of cognitive and emotional immaturity. Further, a pediatric patient has never previously been autonomous and cannot ethically or legally express autonomous choices through an intermediary. Ethical and legal experts rely on a “best interest” standard to guide medical decision making for children or other patients who have never achieved autonomy. This standard is not based on respect for patient autonomy; it presumes a single “best” decision for the child, which would be the same regardless of who the decision maker was. In practice, such decisions usually fall to the parents, because someone has to determine what is in the child’s best interests and because, in most cases, there is no reason to think that anyone is better qualified than the parents. If the parents refuse lifesaving care for their child, ethical principles demand a reexamination of the parental decision in the context of the “best interest” standard. Courts are more likely to intervene in such cases to require treatment of the child.

Recognition

INCOMPETENT PATIENTS SITUATIONS

MEDICAL CONSIDERATIONS

Clinical situations can evolve rapidly and may require quick decisions. It is useful to consider some common circumstances and responses before the actual case arises. ADULT COMPETENT PATIENTS When the patient has been informed of relevant risks, ethical principles weigh heavily in favor of respecting the patient’s decision, even if death results. Legal principles almost uniformly support the right of competent adults to make such decisions. ADULT INCOMPETENT PATIENTS The ethical principle of respect for patient autonomy includes decisions that patients make in anticipation of future incapacity. Such decisions have legal support through various documents, such as living wills and advance directives, and the designation of legal surrogate decision makers via durable powers of attorney or guardianships. Surrogate decisions made for incompetent adult patients are supported legally, unless it is not clear that the surrogate decision maker is expressing the patient’s wishes. Many states have a legal hierarchy that designates a surrogate decision maker if one

IN

EMERGENCY

AND

ELECTIVE

For these patients, the same ethical and legal principles apply as outlined for competent adult patients if the patient has previously been competent and has expressed his or her wishes. When an adult patient has never been declared competent, the considerations are similar to those for a minor patient.

Implications Overriding a patient’s wishes violates the ethical principle of respect for patient autonomy and may also place the physician in legal jeopardy. Unwanted medical intervention may precipitate criminal charges of assault and battery, as well as civil action, against the physician.

MANAGEMENT When dealing with a patient who is a Jehovah’s Witness, take the following actions: ●

Provide appropriate information to the patient about the risks of refusing blood transfusion, including the

SPECIAL TOPICS

Respect for patient autonomy means that competent patients have the right to self-determination in medical care. Physicians may argue that withholding lifesaving therapy harms them professionally and spiritually. However, ethically, physicians are generally required to subordinate their own interests to serve those of the patient, even when the result is the patient’s death. Respecting the wishes of a Jehovah’s Witness is also in accordance with ethical principles of beneficence (doing good) and nonmalfeasance (avoiding harm). By respecting the wishes of Jehovah’s Witnesses, we support their spiritual beliefs in a good spiritual life after death. We also avoid the harm of everlasting damage to the patient’s spiritual well-being. In the case of pregnant patients, minors, and incompetent adults without advance directives, one adult makes a decision that may end the life of another. Physicians have an ethical obligation to promote good, and in these cases, an autonomous decision by the individual whose life is at stake may be unclear or nonexistent. In these cases, the best action might be to give a transfusion and err on the side of preserving life.

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Section 10

Table 244–1

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Special Topics

Perioperative Techniques and Therapies That May Be Acceptable to Jehovah’s Witnesses

Anesthesia technique Hypotensive anesthesia Induced hypothermia Extracorporeal circulation* (non–blood primed) Hemodilution* Fluid management Crystalloid solution Synthetic colloid solution Dextran Human albumin* Some fractionated blood components* Blood salvaging techniques In-line blood reservoirs Cell-saver systems Blood replacements Perfluorocarbons Therapy to enhance hematocrit Iron supplements Erythropoietin* Miscellaneous Desmopressin *These measures may be unacceptable to some Jehovah’s Witnesses and should be discussed with the individual patient.

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potential for stroke, myocardial infarction, and other organ damage. Discuss alternatives to blood transfusion, such as those outlined in Table 244-1, because individual beliefs may vary. Remember that Jehovah’s Witnesses are not universal in their beliefs about blood transfusions, and individual decisions may vary. Therefore, be sure to determine the individual patient’s preferences with regard to transfusion. If possible, postpone elective surgery in patients with low hematocrit, and institute therapy (e.g., erythropoietin, supplemental iron). Make transfusion decisions in advance of the procedure, and with the patient’s knowledge. Resolve questions about the patient’s ability and right to decide before surgery, whenever possible. In general, ethical and legal principles dictate that a competent patient’s refusal of transfusion must be respected. When surgery proceeds, institute acceptable measures to minimize red blood cell loss and to salvage blood components. If the decision to transfuse is reached, always adhere to medically accepted practice with regard to transfusion triggers.

PREVENTION Many conflicts regarding the management of Jehovah’s Witness patients can be avoided by prospective knowledge and planning: ● ●

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Know the local legal standards. Recognize situations in which a decision to withhold transfusion may violate ethical or legal standards. Be especially cautious with pregnant patients, minors, and potentially incompetent patients. Have a prospective plan to handle ethically or legally “gray” situations. Available resources include the hospital attorney and hospital ethics committee. Know the blood salvaging techniques available at your hospital. Know which blood salvaging techniques are available at other institutions, and refer patients if better resources are available elsewhere. When you cannot respect an autonomous patient’s wishes because of extreme personal conflict, refer the patient to a colleague who will. When emergencies arise, endeavor to provide the best medical care possible, in keeping with the patient’s directives.

Further Reading Beauchamp TL, Childress JF: Principles of Biomedical Ethics, 4th ed. New York, Oxford University Press, 1994, pp 120-181. Benson KT: The Jehovah’s Witness patient: Considerations for the anesthesiologist. Anesth Analg 69:647-656, 1989. Elder L: Why some Jehovah’s Witnesses accept blood and conscientiously reject official Watchtower Society blood policy. J Med Ethics 26: 375-380, 2000. Healy JM: The Jehovah’s Witness parent’s right to refuse treatment. Conn Med 54:357, 1990. Jonsen AR: Blood transfusions and Jehovah’s Witnesses: The impact of the patient’s unusual beliefs in critical care. Crit Care Clin 2:91-100, 1986. Jonsen AR, Siegler M, Winslade WJ: Clinical Ethics, 3rd ed. New York, McGraw-Hill, 1992, pp 51, 59-64, 170-172. Layon AJ, D’Amico R, Caton D, et al: And the patient chose: Medical ethics and the case of the Jehovah’s Witness patient. Anesthesiology 73: 1258-1262, 1990. Muramoto O: Bioethical aspects of the recent changes in the policy of refusal of blood by Jehovah’s Witnesses. BMJ 322:37-39, 2001. Rothenberg DM: The approach to the Jehovah’s Witness patient. Anesthesiol Clin North Am 8:589-607, 1990. Singla AK, Lapinski RH, Berkowitz RL, Saphier CJ: Are women who are Jehovah’s Witnesses at risk of maternal death? Am J Obstet Gynecol 185:893-895, 2001. Varela JE, Gomez-Marin O, Fleming LE, Cohn SM: The risk of death for Jehovah’s Witnesses after major trauma. J Trauma 54:967-972, 2003.

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Index Note: Page numbers followed by f refer to figures; those followed by t refer to tables.

A Abciximab, in cardiac surgery patients, 359 ABCs, in burn injuries, 505 in poisoning cases, 508 in thyroid storm, 819 in trauma surgery, 827 Abdominal aortic aneurysm, complications with, 390 management and prevention of, 392-393 recognition of, 390-391, 391f risks of, 391-392, 392t repair of, 390-393 open vs. endovascular, 392, 392t Abdominal pain, in pancreatitis, 473 ABO blood group, acute hemolytic transfusion reaction and, 202, 204 Abortifacient effects, of herbs and nutraceuticals, 152t Abortion, spontaneous, bleeding with, 774, 776t, 777t Abrasion, corneal, 741, 741f, 742, 742f after thyroid surgery, 818, 819, 820, 821 in children, 692-693, 692f Abruptio placentae. See Placental abruption. Abscess, epidural, radiographic diagnosis of, 240, 240f signs of, 239, 240 vs. spinal hematoma, 235t with central neuraxial blockade, 239-241 Absence seizures, 200 Abstinence, for drug addiction, 121, 126 Accelerated idioventricular rhythm, causes, prevention, and treatment of, 321t electrocardiographic features of, 320t Accessory atrioventricular pathways, anticholinergic toxicity and, 30 conduction in, non-DHP calcium channel antagonists and, 51 refractory period in, 324 ventricular preexcitation and, 324 Accreditation, quality assurance program and, 929 ACE inhibitors, 17-19, 17f actions and side effects of, 4t for hypertension, 52, 314 refractory hypotension and, 21 Acetylcholine, anticholinergic actions and, 28 in Alzheimer’s disease, 494 in myasthenic disorders, 484, 485f in Parkinson’s disease, 490

Acetylcholine (Continued) succinylcholine and, 86 Acetylcholinesterase, in myasthenic disorders, 484, 485f Acid(s), in acid-base balance, 436, 437t Acid-base balance, basic principles of, 436 disorders of, anion gap theory and, 438-439, 439f classification of, 436, 437t diagnosis of, 437, 438-439, 438f, 439f management of, 439-440, 439f, 440f prevention of, 440-441, 440t recognition of, 436-437, 437t local anesthetic–induced toxicity and, 231 of stored blood, 680, 680t Acidosis, metabolic, 437 acute respiratory distress syndrome and, 348 in children, delayed emergence and, 439-627 in diabetic ketoacidosis, 418 tourniquet release and, 868 treatment of, 439, 439f Acinar cell dysfunction, pancreatitis and, 473 Acquired immunodeficiency syndrome (AIDS), 446-450 blood-borne HIV infection and, 208 neuropathic complications in, 449, 793 ACTH. See Adrenocorticotropic hormone (ACTH). Actin, in uterine contractions, 763 Actinomycin D, mechanisms, uses, and toxicities of, 111t Activated charcoal, for poisoning, 509, 511t Activated clotting time, commercial measuring devices for, 291 in cardiac surgery, 291, 306 in cardiopulmonary bypass, 291, 292 Activated partial thromboplastin time, after cardiac surgery, postoperative bleeding and, 306 heparin and, 291 Activated protein C, in sepsis, 499 resistance to, 362 Acute coronary syndrome, ventricular tachycardia and, 320 Acute myelogenous leukemia, daunorubicin for, 110 Acute renal failure, antepartum bleeding and, 777 in thoracic aortic aneurysm repair, 386-387 management and prevention of, 345-346

Acute renal failure (Continued) metabolic acidosis and, 437 postoperative, 342-346 cause of, 342 definition of, 342 risk factors for, 344 vs. prerenal syndrome, 344 Acute respiratory distress syndrome (ARDS), 62 amiodarone and, 45 diagnosis of, 347-348, 348t fat embolism syndrome and, 859 in burn injuries, 505 in sepsis, 498 management of, 350-351 massive blood transfusion and, 680 mortality from, 349-350 pathogenesis and incidence of, 348 pathophysiology of, 347, 347t prevention of, 351 pulmonary aspiration and, 783 risk factors for, 348-350 steroid therapy in, 132 Acute tubular necrosis, acute renal failure and, 342, 345 ischemic, 342, 343f nephrotoxic, 342, 343f, 345 Adalimuab, risks with, 502t Adamkiewicz, artery of, celiac plexus block and, 255f in thoracic aortic aneurysm repair, 387, 387f obstetric neurologic injuries and, 790, 793f Addiction, 119, 120. See also Drug dependence. cocaine, 125 definition of, 278t in health professionals, 121, 126 prevention of, 121, 126 in opioid-tolerant patients, 280-281 Addison’s disease, 131, 442 Adenoma, pituitary, 712 Adenosine, 32-35 actions and side effects of, 4t advantages of, 33-34, 34f adverse effects of, 32-33 management and prevention of, 34, 34f, 35 dosing of, 35 drug interactions with, 34-35

951

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Index

Adenosine (Continued) for anticholinergic-induced tachycardia, 31 for identification of arrhythmogenic mechanisms in tachycardias, 33-34, 34f for reentrant supraventricular tachycardia, 43 proarrhythmic effects of, 33 management of, 33, 34, 34f risk assessment for, 33-34 Adenosine triphosphate, in uterine contractions, 763 Adenotonsillectomy, hospital admission after, 691t in children, 688-691 Adenylyl cyclase, in uterine contractions, 763 muscarinic receptor stimulation and, 28 Adhesive arachnoiditis, in obstetric patients, 790 Adhesive tape, for eye protection during anesthesia, 744 Adjunct therapy, 53-65 Adrenal crisis, 131, 444 Adrenal function, corticosteroids and, 501 Adrenal insufficiency, 131, 442-445 causes of, 442, 443t chronic, 443t management and prevention of, 444-445 recognition of, 132, 442-443 risk assessment of, 131, 444 signs and symptoms of, 443t, 822 types of, 131, 442 Adrenal tumors, 822 adrenalectomy and, 823, 824f, 825-826 Adrenalectomy, anesthetic management with, 825 approach to, 823-824 postoperative management with, 826 preoperative management with, 825 Adrenergic agonists, α, actions and side effects of, 4t for bradycardia, 14-15, 95 for myocardial ischemia, 311 increased pulmonary artery pressure and, 7 α1, for hypotension, 95 for myocardial ischemia, 311 α2, actions and side effects of, 4t adverse effects of, 94-95 prevention of, 96 as anesthetic adjuncts, 94-96 for myocardial ischemia, 311 for prevention of shivering, 422 β, for anaphylactic or anaphylactoid reactions, 99 for bronchospasm in asthmatics, 190, 191, 191t for hyperkalemia, 57 β2, for tocolytic therapy, 763, 764 Adrenergic antagonists, α, actions and side effects of, 4t for adrenalectomy with pheochromocytoma, 826 β, calcium channel antagonists used with, heart block and, 41-42, 42t cardiovascular risk and, 149 conditions managed with, 42t for cardiac surgery, 359-360 for carotid endarterectomy, 382 for congenital long QT syndrome, 329 for hypertension, 314 for hyperthyroidism or thyroid storm, 456, 820 for induced hypertension, 873 for myocardial ischemia, 311 for postpneumonectomy problems, 378

Adrenergic antagonists, β (Continued) for revascularization for peripheral vascular disease, 397 for tachycardia and rebound hypertension, 95 synergistic effects with, 40-43 Adrenocorticotropic hormone (ACTH), excess, 822 for post–dural puncture headache, 225 release of, 442, 443f short test with, 131, 132, 133 Adriamycin flare, 117 Advance directives, 949 Afterdepolarizations, early, magnesium infusion and, 59, 60 polymorphic ventricular tachycardias and, 36, 37 torsades de pointes and, 36, 37, 327 triggered activity and, 37, 37t Afterload, in cardiomyopathy, 668 venous air embolism and, 706 Age. See also Children; Elderly. digitalis toxicity and, 25-26 gestational, postoperative apnea and, 611, 612f hypothermia and, 419 pain assessment and, 896, 896t Parkinson’s disease and, 490 postconceptual, 611, 612f, 613, 613f thermal injury from warming devices and, 551 tonsillectomy and, 688, 689, 690, 691 unanticipated hospital admission and, 894 Agitation, emergence, in children, 685-686 in Alzheimer’s disease, 494 AIDS (acquired immunodeficiency syndrome), 446-450 blood-borne HIV infection and, 208 neurologic complications in, 449, 793 Air, entrainment of, 704, 705f Air embolism, cerebral, in children, delayed emergence and, 629 intra-aortic balloon pump and, 409 in cardiopulmonary bypass, massive, 302-303, 302f in children, 629, 673-676 in radical urologic surgery, 847, 848, 849 massive, 302-303, 302f paradoxical, 673, 834 pulmonary, 675 venous, 704-707 central venous catheter–related, 582t in cardiopulmonary bypass, 302303, 302f in children, 629, 673-676 in posterior fossa surgery, 708, 709, 710 in pregnancy, 786, 787, 787t, 788 management and prevention of, 675-676, 706-707 monitoring for, 673-675, 673f, 674f, 706, 706f patient position and, 673, 676, 704, 705t, 706, 708, 709, 788 rapid fluid and blood delivery system use and, 553, 554 recognition of, 553, 704-705 risk factors for, 705-706, 705t terminology of, 673 Air lock, in cardiopulmonary bypass, 301 Airway, airflow resistance in, in bronchospasm, 189 in infants, 603, 604f bronchial smooth muscle tone and, 189

Airway (Continued) compression of, by anterior mediastinal mass, 671 control of, in gastric aspiration, 783-784, 784t in spinal cord injury, 739 in thoracic aortic aneurysm repair, 386 in trauma victims, 828, 829, 829t in traumatic brain injury, 730, 734 nonbarbiturate anesthetics and, 83 difficult, cannot ventilate, cannot intubate, 159-173 algorithm for, 159, 160f injuries with, 164 management of, 164-166, 165t, 167f, 167t, 168-172, 168t, 170f, 171t, 172f, 172t prevention of complications with, 172-173 recognition of, 161, 162, 163f, 163t, 164 risk assessment for, 164, 164t definition of, 159, 161t fiberoptic bronchoscopy and endotracheal intubation of, 165-166, 167f, 167t, 168, 168t in cesarean delivery, 761, 772 in children, 603-606, 604f, 730 adjuncts for, 605, 605f examination of, 604, 604t management of, 604-605, 605f in laryngoscopy, 750, 751 in morbidly obese, 811, 811t, 812 in posterior fossa surgery, 709 in trauma victims, 828 lighted stylet oral intubation of, 168-169, 168t management of, awake, 165, 165t emergency, 169, 772 invasive methods of, 169-172 prevention of complications with, 172-173 opiate-induced muscle rigidity and, 174-175 preoperative information on, 165, 165f pulmonary aspiration prevention and, 188, 784 risk assessment of, 164, 164t edema of, 877 in preeclamptic patients, 760 management of, 879 humidification of, for hypothermia prevention, 665 laryngeal mask, 168-169. See also Laryngeal mask airway. laser surgery of, fire risk with, 562, 563, 564, 565, 568, 569, 750, 751 lower, bronchoscopic suctioning of, 187 sarcoidosis in, 457 obstruction of, 877-878 ACE inhibitor–induced angioedema and, 19 complete, 600-601, 600f from foreign body aspiration, 753-755 from tracheal intubation, 184, 185f in infants and children, 615, 637, 649-650, 650t in radiation oncology, 910 laryngeal nerve injury and, 819 partial, 600-601, 601f postobstruction pulmonary edema and, 213, 214t, 215, 634-636, 689, 690f upper respiratory tract infection and, 649-650, 650t

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Airway (Continued) surgical, 170-172, 171t, 172f, 172t in trauma victims, 829 upper, airflow in, in infants, 603, 604f postobstruction pulmonary edema and, 213, 214t sarcoidosis in, 457, 458f Albumin, acid-base balance and, 436, 437t, 440 for metabolic alkalosis, 437 for subarachnoid hemorrhage, 721 postoperative hepatic dysfunction and, 805-806 Alcohol, H1- and H2-blocker effects and, 93 in drug overdose, 508, 509 porphyrias and, 471t, 472 Alcohol abuse, consequences of, 122, 125 liver disease and, 123, 466 symptoms of, 123-124 treatment of, 126, 126t Aldosterone, excess, 822, 823 Alfentanil, manual infusion dosing regimens for, 549t muscle rigidity with, airway difficulties with, 174-175 plasma concentration of, infusion duration and, 546-547, 546f, 547f Alkalosis, metabolic, 437, 439-440, 440f respiratory, 347, 437, 439 Alka-Seltzer, for prevention of pulmonary aspiration, 643t Alkylating agents, 110 Allergens, anaphylactic or anaphylactoid reactions and, 100 Allergic reactions, antihistamines for, 92 to aspirin, 275 to blood transfusions, 203, 203t, 204, 205, 205t to drugs, 97-98 to fruit, in children, latex allergy and, 651 to latex, 217, 651-653. See also Latex allergy. to local anesthetics, 233 to NSAIDs, 275, 276 Aloe, common uses and problems with, 155t Alpha-blockers. See Adrenergic antagonists, α. Alprostadil, actions and side effects of, 4t Alveolar capillaries, in acute respiratory distress syndrome, 349 pulmonary vascular resistance and, 316 Alveolar epithelium, in acute respiratory distress syndrome, 349 in postobstruction pulmonary edema, 213 Alzheimer’s disease, 493-494 in AIDS patients, 449 Amantadine, in Parkinson’s disease, 491, 491t Ambu bag, in pipeline supply failure, 516 Ambulatory surgery, anesthesia and analgesia in, 265 goals for, 265 orthopedic peripheral nerve block for, 265-268 unanticipated hospital admission and, 894-895 American Academy of Pediatrics, guidelines for sedation of children and, 621 American Society of Regional Anesthesia and Pain Medicine (ASRAPM), guidelines of, 258, 259, 271, 271t Amines, in carcinoid syndrome, 815t Aminocaproic acid, for hereditary angioneurotic edema, 427 for prevention of intracranial aneurysm rerupture, 716 for reduction of blood loss after cardiac surgery, 307t for TURP syndrome, 845

Aminoglutethimide, 110 Aminoglycosides, complications of, 102t δ-Aminolevulinic acid, acute porphyria attacks and, 470, 470f, 471 Aminophylline, for anaphylactic or anaphylactoid reactions, 99 Amiodarone, for atrioventricular reciprocating tachycardia in Wolff-Parkinson-White syndrome, 326 for cardiac arrest in tricyclic antidepressant toxicity, 107 for digitalis toxicity, 26-27 for perioperative tachyarrhythmias, 323, 326, 360, 378 perioperative complications with, 45, 46 pulmonary toxicity of, 45, 46 risks of with anesthesia, 46 torsades de pointes risk and, 45 Ammonia, serum, postoperative hepatic dysfunction and, 806 Amniotic fluid embolism, in pregnancy, 786, 787, 787t, 788 Amphetamine abuse, 509-510 Ampicillin, complications of, 102t Amputation, below-knee, hemorrhagic complications with peripheral nerve block and, 270 Amrinone, action and uses of, 22 Amsorb, carbon dioxide absorption by, 534, 536 Amyl nitrite, for detumescence of penile erection, 841 Amylase, serum, in pancreatitis, 474 β-Amyloid, in Alzheimer’s disease, 493 Anabolic steroids, for hereditary angioneurotic edema, 427 Anakinra, risks with, 502t Analgesia, caudal epidural, postoperative apnea in infants and, 614 epidural. See also Epidural anesthesia. in nonobstetric surgery in pregnancy, 800 in opioid-tolerant patients, 280 in preeclamptic patients, for labor and vaginal delivery, 761 in opioid-tolerant patients, 279-280, 279t in outpatient orthopedic surgery, multimodal methods of, 265 in Parkinson’s disease, 491, 491t in posterior fossa surgery, 709 in revascularization for peripheral vascular disease, 394 neuraxial opioids for, 261-264 postoperative, for early extubation anesthesia, 358 preemptive, 898 psoas compartment block for, after hip or knee replacement, 258 Analgesic effects, of herbs and nutraceuticals, 152t Anaphylactic shock, 97 Anaphylactoid reaction(s), 97-100 management of, 98-99 perioperative drugs associated with, 98, 99t prevention of, 99-100 to blood transfusions, 203, 203t to nondepolarizing muscle relaxants, 90 to NSAIDs, 275 vancomycin-induced histamine release as, 101 Anaphylactoid syndrome of pregnancy, 786 Anaphylaxis, 97-100 clinical manifestations of, 97-98, 97t, 98t differential and laboratory diagnosis of, 98 drug, 98, 99t, 624-625 angioedema and urticaria and, 427

953

Anaphylaxis (Continued) in general anesthesia, 90 management of, 98-99 mediators released during, 97t nondepolarizing muscle relaxants and, 624-625 perioperative, blood transfusions and, 203, 203t latex allergy in children and, 651, 652, 652f management of, 652 NSAID administration and, 275 prevention of, 99-100 Anastrozole, mechanisms, uses, and toxicities of, 111t Ancrod, for heparin-induced thrombocytopenia in cardiopulmonary bypass, 292 Anemia, after psoas compartment block, 257, 259 anthracycline antibiotic action and, 116 differential diagnosis of, 257 hemolytic, postoperative jaundice and, 806 in neonates, hypoxemia and, 639 pernicious, nitrous oxide anesthesia and, 69 postoperative apnea and, 611, 612f, 613, 613f postoperative visual loss and, 856 prevention of, 198t Anemic hypoxia, 195-196, 195f, 196f Anesthesia, awareness under, 939-941 cardiac, early extubation management of, 356-360 fast-track, 356-360 daily administration of, problems with, 909 emergence from. See Emergence. epidural. See Epidural anesthesia. general. See General anesthesia. in HIV patients, 449 induction of. See Induction. inhalation. See also Anesthetic drug(s), inhalational. agents used in, for early extubation anesthesia, 358 for prevention of bronchospasm in asthmatics, 190, 191 for emergent cesarean delivery, 772 postoperative apnea in infants and, 613 outside operating room, problems with, 909 regional. See Regional anesthesia. spinal. See Spinal anesthesia. total intravenous. See Total intravenous anesthesia. Anesthesia care team, 930 for intraoperative cardiac arrest, 616 Anesthesia cart, 926 Anesthesia machine, breathing circuit of, 422, 527-530 components of, 527t flowmeter malfunction and, 518-520, 519f humidifiers and, 422, 543, 543f, 544, 545 liquid agent in, 532, 532t, 533 possible problems in, 527-528, 527t vs. vaporizer problems, 531, 532 scavenging systems and, 541-542 in radiation oncology suite, 910 maintenance of, 520 oxygen flush valve of, 524, 524f, 525f oxygen proportioning device of, 518, 520, 521-523, 521f, 522f pipeline source failure and, 515-517 scavenging systems of, 540-542, 541f Anesthesiologist(s), nonopioid dependency in, 122-127 on anesthesia care team, 930 opioid dependency in, 119-121

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Anesthetic adjunct(s), 85-96 α2-adrenoceptor agonists as, 94-96 antihistamines as, 92-93 nondepolarizing neuromuscular relaxants as, 89-91 succinylcholine as, 85-87 Anesthetic drug(s). See also names of specific drugs, e.g., Halothane. analyzers of, high concentration limits alarm of, 533 automated delivery of, complications with, 546, 546f, 547, 547f, 548f, 548t pharmacokinetic models and, 548, 548f barbiturates as, 74-77 delayed emergence and, 885-886 emergence agitation in children and, 686 halogenated, precautions with, 566t hepatitis and, postoperative jaundice and, 807 hypnotic effects of, in children, 627 immune function and, 501, 502 in cirrhosis, 468 inflammatory response after cardiopulmonary bypass and, 353 inhalational, awareness under anesthesia and, 940 for early extubation anesthesia, 358 for emergent cesarean delivery, 772 for prevention of bronchospasm in asthmatics, 190, 191 hazards of, 66 postoperative apnea in infants and, 613 intrathecal opiates as, 72-73 ketamine as, 78-79 manual infusion dosing regimens for, 549t neurophysiologic effects of, 729t nitrous oxide as, 69-71 nonbarbiturate, 80-83 porphyrias triggered by, 74-77, 470, 471, 471t, 472 postoperative delirium and, 888 residual effects of, in postanesthesia care unit, 899 skin testing of, 100 somatosensory and motor evoked potential effects of, 872t teratogenic effects of, 799, 800 traumatic brain injury and, 736 volatile, delayed emergence and, in children, 630 fetal sensitivity to, 767 in carotid endarterectomy, 382 in patients with porphyrias, 76 inhalational, hazards of, 66 maternal, for EXIT procedure, 609, 610 myocardial protection and, 900 organ toxicity and, 66-68 vancomycin with, hypotension and, 101-102, 103t Anesthetic equipment, 515-545 Anesthetic gases and vapors, monitoring of, 574, 575 Anesthetists, registered nurse, on anesthesia care team, 930 Aneurysm(s). See also Aortic aneurysm. intracranial, endovascular treatment of, 716 rebleeding with, 714-718 intraoperative, 714, 715 management of, 716, 716t prevention of, 716-718, 717t risks with, 715, 715t signs of, 714-715, 715t surgical clip-ligation of, 716, 717, 717t vasospasm and, 719-723 Angina, non-DHP calcium channel antagonists and, 51

Angina-like pain, adenosine and, 32 Angioedema, ACE inhibitor–induced, 17-19 and urticaria, 426-428 classification of, 426t management and prevention of, 427-428 of head and neck, ACE inhibitors and, 17-18 recognition of, 426-427 risks of, 427 Angiogenesis, systemic inflammatory response syndrome and, 497 Angiography, cerebral, for vasospasm diagnosis, 719 Angioneurotic edema, hereditary, treatment of, 427-428 Angioplasty, carotid, 381 transluminal balloon, for treatment of vasospasm, 721 Angiotensin II receptor antagonists, 17-19, 17f refractory hypotension and, 21 Angiotensin-converting enzyme (ACE), in sarcoidosis, 457-458 inhibitors of, 17-19, 17f, 314 actions and side effects of, 4t refractory hypotension and, 21 Animal glandular products, raw, 151 Anion(s), in acid-base balance, 436, 437t partially dissociated, 436, 437t Anion gap, 438, 439f Antacids, for prevention of pulmonary aspiration, 643t, 784 Anterior mediastinal masses, in children, 670-672 Anterior spinal artery syndrome, 235t, 387 Anthracycline antibiotics, anesthesia and, 116 cardiotoxicity with, 116-117, 118 mechanism of action of, 116 metabolism of, 116 risks with, 117 toxicity of, 116-117 uses of, 110, 116 Antiarrhythmic drugs, class I, 36-39. See also specific drugs, e.g., Procainamide. adverse effects of, 38-39 doses for, 38, 39t mechanisms of action of, 38 proarrhythmia with, 38 subdivisions of, 37 toxicity induced by, 37 class II, 40-43. See also Adrenergic antagonists, β. class III, 44-46 risks of, 45, 46 class IV, 48-52 toxic effects of, 48, 49f, 50-51 management and prevention of, 51-52 drug-induced torsades de pointes and, 46, 328t, 329 for acquired long QT syndrome, 329 Antibiotics, 110. See also names of specific drugs, e.g., Vancomycin. anaphylactic reactions associated with, 99t anthracycline, 110, 116-118 for central venous catheter–related infection, 584, 585 for epidural abscess, 241 for nosocomial bacterial pneumonia, 211 for pulmonary aspiration in children, 642 inflammatory response after cardiopulmonary bypass and, 354 prophylactic, complications of, 101-104, 102t in acute pancreatitis, 475 in continuous perineural local anesthetic infusion, 283 Q-T interval prolongation by, 328t systemic inflammatory response syndrome and, 498

Antibodies, antiphospholipid, lupus anticoagulants as, 363 digoxin-specific, for digitalis toxicity, 26, 27 enzyme-linked, for substance abuse testing, 123 heparin-dependent, 306 absent, 292 HIV, 446 immunoglobulin A, 203, 204 immunoglobulin E, 97, 275, 651 immunoglobulin G, 292 in myasthenia gravis, 484 in transfusion reaction, 202, 203, 204 monoclonal, in heparin-induced thrombocytopenia in cardiopulmonary bypass, 293 Anticholinergic agents, 28-31 complications with, 30, 31, 135t effects of, 28-30, 29t emergence agitation and, 685-686 for bradycardia, 14, 95 α2-agonist–induced, 95 for detumescence of penile erection, 841 for Parkinson’s disease, 491, 491t for postoperative nausea and vomiting, 646t for premedication, 28 for pulmonary aspiration prevention, 643t, 784 receptor site affinity of, 134t toxicity of, 28, 29, 30t differential diagnosis of, 29, 29t vs. anticholinesterase poisoning, 29-30 Anticholinesterase drugs, anticholinergic agents and, 30 for myasthenia gravis, 485 postoperative nausea and vomiting and, 647 toxidrome with, vs. anticholinergic toxicity, 29-30 Anticoagulants, after psoas compartment block, 258, 259 cardiovascular risk assessment with, 149 in cardiac surgery, 149, 291-293 in cardiopulmonary bypass, 293 in pregnant patients, 803 in central neuraxial techniques, ASRAPM guidelines for, 271, 271t intra-aortic balloon pump and, 409, 410 peripheral nerve block and, 266, 269-272 postoperative bleeding and, 305 pulmonary embolism in pregnancy and, 788 retroperitoneal hemorrhage and, 257, 259 spinal hematoma and, 236-237, 237t ventricular assist device placement and, 411 Anticonvulsants, for epilepsy, 201 Antidepressant(s), 105-109 monoamine oxidase inhibitors as, 105-106 Q-T interval prolongation by, torsades de pointes and, 328t selective serotonin reuptake inhibitors as, 107-108 St. John’s wort as, 108-109 tricyclic, 106-107, 128, 129, 130 Antidiuretic hormone, diabetes insipidus and, 712-713 exogenous replacement of, 713 hyponatremia and, 431, 432 in adrenal insufficiency, 443 Antidotes, poisoning, 509, 510t Antiemetic drugs, 134-136. See also names of specific drugs, e.g., Chlorpromazine. anesthetic technique with, 136 for Parkinson’s disease, 491, 491t for postoperative nausea and vomiting, 645, 646t, 647, 892t preoperative management of, 136

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Antiemetic drugs (Continued) Q-T interval prolongation by, torsades de pointes and, 328t receptor site affinity of, 134t side effects of, 135t Antiepileptic drugs, congenital anomalies and, 200-201 Antifibrinolytic drugs, for reduced blood loss after cardiac surgery, 307t in cardiopulmonary bypass, central neurologic injury and, 341 prophylactic, for early extubation anesthesia, 358 Antihistamines. See also H1-receptor antagonists; H2-receptor antagonists. adverse reactions to, 92-93, 92t for anaphylactic or anaphylactoid reactions, 99 for carcinoid syndrome, 816 for intraoperative angioedema and urticaria, 427 for neuraxial opioid complications, 263 for postoperative nausea and vomiting, 646t for pulmonary aspiration prevention, 784 receptor site affinity of, 134t side effects of, 135t Antimalarial drugs, for sarcoidosis, 460 Antimetabolites, 110 Antimitotics, 110 Antiphospholipid antibodies, lupus anticoagulants as, 363 Antiplatelet drugs, after carotid endarterectomy, 381 in cardiac surgery patients, 359 neuraxial blockade with, ASRAPM guidelines for, 271t spinal hematoma and, 236-237, 237t Antipsychotic drugs, for postoperative delirium, 889 Q-T interval prolongation by, torsades de pointes and, 328t Antiretroviral drugs, for HIV infection, 447-448, 448t Antiseptic drugs, central venous catheter–related infection and, 584 corneal injury from, 741, 742 Antiserotonin, 134t, 135t Antithrombin, deficiency of, 362, 363, 364 heparin therapy and, 364 in coagulation process, 361 Antithrombin III, for coagulation factor deficiencies, 308 heparin activity and, 291 in cardiopulmonary bypass, 291, 292, 293 Antithyroid drugs, after thyroid storm, 820 Anxiety, in Alzheimer’s disease, 494 in children, 682-684 emergence agitation and, 685 postoperative nausea and vomiting and, 890 Anxiolysis, 619 Aorta, cannulation of, air embolism in, 302-303, 302f for cardiopulmonary bypass, air embolism in, 302-303, 302f aortic dissection after, 299-300, 299f central neurologic injury and, 340, 341 cross-clamping of, acute renal failure and, 344 in abdominal aortic aneurysm repair, 390-391, 391f, 393 in thoracic aortic aneurysm repair, 386, 387, 388 inflammatory response with, 352, 354

Aorta (Continued) manipulation of, central neurologic injury and, 340, 341 occlusion of. See also Aorta, cross-clamping of. hemodynamic changes with, 390, 391t, 393 rupture of, with psoas compartment block, 257 stenosis of, vasodilator drugs for, 3 thoracic, cross-clamping of, 386, 387, 388 diseases of, 384 surgical approach to, 386 Aortic aneurysm, abdominal, complications with, 390 management and prevention of, 392-393 recognition of, 390-391, 390f, 391f risks of, 391-392, 392t repair of, 390-393 open vs. endovascular, 392, 392t thoracic, classification of, 384, 384f, 385f recognition of, 384-385, 385t risks of, 385-386 signs and symptoms of, 385t surgical repair of, 386-388, 389 Aortic dissection, after aortic cannulation in cardiopulmonary bypass, 299-300, 299f classification of, 384, 384f signs and symptoms of, 385t Aortic insufficiency, ventricular assist device placement and, 411 Aortic root, cannulation of, 300f, 301 aortic dissection after, 299-300, 299f APACHE II score, in acute pancreatitis, 474, 475t Apnea, after succinylcholine administration, 86 in early vs. late extubation after cardiac surgery, 357t in infants, 611-614, 639 in total spinal anesthesia, 248 obstructive sleep, in morbidly obese patients, 811 in muscular dystrophy, 481 in tonsillectomy, 688, 688t, 689, 690, 691 sedation in children and, 620 of prematurity, 611, 612 postoperative, in infants, 611-614 apoE e-4 allele, 340 Apomorphine, in Parkinson’s disease, 490, 491t, 492 Apoptosis, alveolar epithelial, in acute respiratory distress syndrome, 349 Aprotonin, anaphylactic or anaphylactoid reactions and, 100 for blood conservation, 297t, 298, 307t in cardiac surgery, 307t, 341, 354, 359 in cardiopulmonary bypass, central neurologic injury and, 341 inflammatory response after, 354 in celite activated clotting time testing, 291 in massive blood transfusion in children, 678 in pregnant patients, 803 Ara-C, mechanisms, uses, and toxicities of, 113t Arachidonic acid, in NSAID action, 273, 273f Arachnoid membrane, 242 Arachnoiditis, adhesive, in obstetric patients, 790 Argatroban, for heparin-induced thrombocytopenia in cardiopulmonary bypass, 292 Arginine vasopressin, adverse effects of, 9 applications of, 6 as supplementary vasopressor, 9

955

Argon gas, in surgical diathermy, 557-558 Arndt endobronchial blockers, in left-sided thoracotomy, 386 Aromatase inhibitors, 110 Arrhythmias, adenosine and, 32-33, 34 anthracycline antibiotics and, 116 atrial. See also Atrial fibrillation; Atrial flutter. in cardiac surgery patients, 359-360 automaticity and, 36-37 β-blockers or calcium channel blockers for, 42t cardiac risk and, 147 catheter ablation for, 915-917 central venous catheter–related, 582t digitalis toxicity and, 24, 25, 25t, 26t hemodynamic instability and, 899t, 900, 900t, 902 hyperkalemia and, 53-54, 56, 57 hypokalemia and, 54, 55, 56t, 57 hypomagnesemia and, 59, 60 hypothyroidism and, 453 in children, cardiac arrest and, 615 oculocardiac reflex and, 695, 696f succinylcholine use and, 623, 624, 625 in laparoscopic surgery, 832, 834 in muscular dystrophy, 480, 482 local anesthetic–induced, 231, 233 oculocardiac reflex and, in children, 695, 696f in retrobulbar block, 748 postpneumonectomy, 378 pulmonary artery catheter–related, 588, 589, 590 subarachnoid hemorrhage and, 723 succinylcholine use and, 87 in children, 623, 624, 625 tricyclic antidepressant toxicity and, 106, 107 ventricular. See Ventricular arrhythmias; Ventricular tachycardia. Arrhythmogenic right ventricular cardiomyopathy, 668, 669 Arteria radicularis magna, obstetric neurologic injuries and, 790, 793f Arterial blood gas analysis, oxygen status and, 197 Arterial carbon dioxide tension, 350, 382 Arterial hypotension. See Hypotension, arterial. Arterial oxygen tension, in children and infants, 637t pulse oximetry and, 570, 570f Arterial thromboembolism, 363. See also Thromboembolism. Arteriovenous malformation, resection of, 724, 725f normal perfusion pressure breakthrough after, 724-727 Arteritis, secondary pulmonary hypertension and, 660 Artery(ies), cannulation of, complications with, 579-580, 580f, 580t catheterization of, for detection of venous air embolism, 675 iliolumbar, in retroperitoneal space, 258, 259f injuries of, from arterial tourniquet, 868 lactate concentrations in, vasopressor therapy and, 9 of Adamkiewicz, celiac plexus block and, 255f in thoracic aortic aneurysm repair, 387, 387f obstetric neurologic injuries and, 790, 793f

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Page 956

Index

Artery(ies) (Continued) puncture of, central venous catheter– related, 582 segmental lumbar, 258, 259f spinal, in thoracic aortic aneurysm repair, 387, 387f spinal cord, celiac plexus block and, 254, 255f tourniquets on, nerve injuries from, 867-870 vertebral, local anesthetic injection into, 248 Arthritis, rheumatoid, cervical spine instability and, 176-177 Ascites, in cirrhosis, 468 Aseptic meningitis, NSAID allergy and, 276 Aseptic technique, 502 Asian products, contamination of, 151 L-Asparaginase, 110 mechanisms, uses, and toxicities of, 111t Aspiration [procedure], central line, for prevention of venous air embolism, 707 for pneumothorax, 253 Aspiration [event], foreign body, 753-755 pulmonary, 186-188 definition of, 186, 641 in children, 641-642, 641t, 642t in morbidly obese, 811-812, 811t in parturients, 782-785 in trauma victims, assessment for, 828 management of, 187, 783-784, 784t prevention of, 187-188, 187t, 784-785 risk factors for, 186-187, 187t, 641-642, 641t, 642t, 783 signs and symptoms of, 186, 186t, 641, 782-783, 783t Aspiration pneumonia, postobstruction pulmonary edema and, 635 Aspiration pneumonitis, in children, 641-643 in pregnancy, 767 Aspirin, action of, 274 allergy to, 275 for prevention of thrombogenic events, 276 postpneumonectomy cardiac complications and, 378 spinal hematoma and, 236, 237, 237t Assessment, preanesthetic, 141-157 Asthma, 190, 191t intraoperative bronchospasm in, 189, 190, 191 Atelectasis, in hypoxemia, 878 Atheromatous plaque, carotid endarterectomy and, 380 Atlantoaxial instability, conditions associated with, 176t congenital, 176 inflammatory, 176-177 traumatic, 176 Atlantoaxial subluxation, 176-180 Atonic seizures, 200 Atracurium, 89t in children, 626 complications with, 623 dose, clearance, and side effects of, 624t Atraucan needle, 224f Atrial fibrillation, 319, 319f adenosine and, 33 catecholamine-induced tachyarrhythmias and, 9 causes, prevention and treatment of, 321t electrocardiographic features of, 320t emergent cardioversion for, 908 in cardiac surgery patients, 359-360 in Wolff-Parkinson-White syndrome, 324f, 325, 326

Atrial fibrillation (Continued) magnesium infusion and, 59, 60 postpneumonectomy, 378 Atrial flutter, 319 adenosine and, 33 causes, prevention, and treatment of, 321t electrocardiographic features of, 320t in Wolff-Parkinson-White syndrome, 324f, 325, 326 postpneumonectomy, 378 Atrial septostomy, for pulmonary hypertension in children, 661 Atrial tachycardia, paroxysmal, with atrioventricular heart block, digitalis toxicity and, 25 Atrioventricular bypass tracts, radiofrequency ablation in, 915 Atrioventricular heart block, α2-agonist–induced hypotension and, 95 adenosine and, 33 bradycardia and, 42, 332-333, 333f calcium channel antagonists and, 50, 51 complete, in myotonic dystrophy, 480 first degree, 334 management of, 42-43, 334-335 Mobitz, 333, 333f pacing for, indications for, 401t, 402 prevention of, 43 pulmonary artery catheter–related, 589, 590 recognition of, 41, 41f risk assessment of, 41-42, 42t second degree, 334-335 third degree, 40, 335 transient, 33 Atrioventricular junctional rhythm, bradycardia as, 332 digitalis toxicity and, 25 management of, 334 tachycardia as, 320t, 321t Atrioventricular node(s), adenosine effects on, 32-33, 34 conduction in, anticholinergic toxicity and, 30 calcium channel antagonist effects on, 40, 48, 49f, 50, 51 radiofrequency ablation in, 915 Atrioventricular pathways, accessory, anticholinergic toxicity and, 30 conduction in, non-DHP calcium channel antagonists and, 51 refractory period in, 324 ventricular preexcitation and, 324 Atrioventricular reciprocating tachycardia, 324, 324f, 325, 326 antidromic, 325, 326 in Wolff-Parkinson-White syndrome, 324-326 orthodromic, 325, 326 paroxysmal, 325, 326 Atropine. See also Anticholinergic agents. action of, 28 edrophonium and, 30 effects of, 28-29, 29t for bradycardia, side effects of, 15 for calcium channel antagonist toxicity, 51 for digitalis toxicity, 26 for drug-induced torsades de pointes, 46 for laryngospasm in children, with succinylcholine, 601-602 for oculocardiac reflex in children, 696 in electroconvulsive therapy, 904 in open fetal surgery, 768 overdose of, in infants, 30

Atrovent (ipratropium), 29 Ausculation, chest, for diagnosis of doublelumen tube malposition, 365, 366f, 367f Autoantibodies, in Lambert-Eaton myasthenic syndrome, 485 in myasthenia gravis, 484 Autoimmune disorders, airway assessment in, 501 Automaticity, antiarrhythmic drug actions and, 38 clinical arrhythmias and, 36-37 Autonomic dysreflexia/hyperreflexia, 477-478, 477t, 853-854 manifestations of, 853t potential causes of, 853, 853t Autonomy, patient, 944, 946, 947, 949 Autoregulation, cerebral, after subarachnoid hemorrhage, 722 in intracranial aneurysm rerupture, 714 in traumatic brain injury, 733 normal perfusion pressure breakthrough and, 727 vascular, mean arterial pressure and, 7 Autotransfusion, devices for, in children, 679 techniques of, 295-298, 295t tourniquet inflation and, 868 Awake neurologic assessment, for detection of cerebral ischemia, 380-381, 380t Awareness under anesthesia, 939-941 prevention of, 940 Axillary nerve block, neurologic complications with, 282, 285-286 Axonotmesis, 881 Ayurveda, 150 Azotemia, 342 hypovolemia and, 63 B Back pain, epidural abscess and, 239, 240 “Backleak,” in acute renal failure, 342 Bacteremia, central neuraxial block and, 241 Bacterial colonization, intracranial pressure monitoring and, 593, 594 Bacterial pneumonia, 210-212. See also Pneumonia. in HIV patients, 448-449 Bar codes, patient misidentification and, 923 Baralyme, carbon dioxide absorption by, 534-536, 535f Barbiturates, for carotid endarterectomy, 382 for traumatic brain injury, 735 porphyrias and, 74-77, 471t, 472 Barium hydroxide lime, carbon dioxide absorption by, 534-536, 535f Barotrauma, anesthesia breathing circuit and, 528, 542 minimization of, 171, 172t oxygen flush valves and, 524, 525, 525t Barrier precautions, central venous catheter–related infection and, 584 for nosocomial pneumonia prevention, 211 Base deficit-excess (BDE), 437, 438-439, 438f, 439f calculation of, 438-439 Basiliximab, 501 Bayes’ theorem, 141 Becker’s muscular dystrophy, protein dysfunction in, 479-480 Behavior, hostile-combative or uncooperative, 936-938 causes of, 936t management of, 937, 937t maladaptive postoperative, in children, 682, 683t substance abuse and, 125

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Behavioral therapy, in Alzheimer’s disease, 494 Belladonna alkaloids, anticholinergic toxicity with, 28 Benzamide, receptor site affinity of, 134t side effects of, 135t Benzocaine, methemoglobinemia and, 233 Benzodiazepines, adenosine and, 35 awareness under anesthesia and, 940 effects of, reversal of, 128, 129t, 886 in Alzheimer’s disease, 494 in carcinoid syndrome, 816 neurophysiologic effects of, 83, 729t teratogenic effects of, 799, 800 Benztropine, in Parkinson’s disease, 491, 491t Benzylisoquinoline, in children, complications with, 623-624 Beta-blockers. See Adrenergic antagonists, β. Bias, in quality assurance programs, 928, 929 Bicarbonate, in diabetic ketoacidosis, 418 Bile, reflux of, pancreatitis and, 473 Bilirubin, in postoperative jaundice, 805, 806, 809 Biopsy, lung, in sarcoidosis, 458, 459 muscle, in malignant hyperthermia, 655 of anterior mediastinal mass, 671, 672 Bispectral index monitor, awareness under anesthesia and, 940 Bite blocks, postobstruction pulmonary edema and, 216 Bivalirudin, for heparin-induced thrombocytopenia in cardiopulmonary bypass, 292 Biventricular assist device, 407 Bladder, distention of, autonomic dysreflexia and, 853, 854 urinary retention and, 837-838, 838t loss of control of, celiac plexus block and, 254 normal function of, 836-837, 836t perforation of, in transurethral surgery, 843, 844, 845 volume of, after surgery, 838-839 Bladder tumor, transurethral resection of (TURB), 843-845 Blanket(s), warming, for hypothermia prevention, 421, 422, 665 Bleeding. See also Blood loss; Hemorrhage; Rebleeding. after cardiac surgery, 305-308 hypotension with, 305 management of, 306, 307t, 308 prevention of, 308 recognition of, 305 risk of, 305-306 antepartum, 774-778 characteristics of, 776, 776t management and prevention of, 777-778 recognition of, 775-776, 776t risks with, 776-777, 777t types of, 774-775, 775f fetal risk of, in fetal intrauterine surgery, 767 gastrointestinal, in transesophageal echocardiography, 577, 578 in end-stage renal disease, 462-463, 464 in hypothermia, 420 in retrobulbar block, 748 in thoracic aortic aneurysm repair, 386 postoperative, in cardiac surgery patients, 359 in tonsillectomy, 688, 689, 690-691 postpartum, 779-781 surgical vs. nonsurgical, 305, 306

Bleomycin, 110 in retroperitoneal lymph node dissection, 847 mechanisms, uses, and toxicities of, 111t Blindness, open globe injury and, 745 postoperative, in children, 693-694 in spinal surgery, 873 with deliberate hypotension, 855-858 with delirium, 888 Blood, conservation of. See Blood salvage. contamination of, 295 infections of, central venous catheter–related, 582, 583-585, 583t, 585f, 586f prevention of, 584-585, 587 rapid delivery devices for, 553-554 stored, metabolic derangement in, 680, 680t transfusion of. See Blood transfusion(s). Blood components. See Blood products. Blood flow, cerebral, in carotid endarterectomy, 382 in diagnosis of vasospasm, 719, 720 in intracranial aneurysm rerupture, 714 in traumatic brain injury, 733 measurement of, 381 normal perfusion pressure breakthrough and, 725, 726, 727 coronary, deliberate hypotension and, 856-857 hepatic, calcium channel antagonists and, 51 intraoperative, postoperative jaundice and, 806-807 renal, acute renal failure and, 345 calcium channel antagonists and, 51 spinal cord, in thoracic aortic aneurysm repair, 387 transcranial Doppler measurement of, 381 uteroplacental, in fetal intrauterine surgery, 767 in preeclampsia, 760 Blood loss. See also Blood transfusion(s); Hemodilution. after cardiac surgery, antifibrinolytic drugs for, 307t after intracranial aneurysm rerupture, 716, 716t in antepartum bleeding, 777 in burn-injured patients, 506 in obstetric hemorrhage, 774, 776t, 777 in spinal surgery, 873-874 in spontaneous abortion, 774 in thoracic aortic aneurysm repair, 386 intraoperative, 63, 64 ischemic optic neuropathy and, 693 maternal, in EXIT procedure, 608, 609 minimum hemoglobin levels and, 295, 296, 297 postpartum, 779 safe tolerable limits of, 297 Blood pressure. See also Hypertension; Hypotension. α2-agonist–induced changes in, 94-95 arterial, for detection of venous air embolism, 675 monitoring of, 579-580 control of, intracranial aneurysm rerupture and, 716, 716t, 717, 717t normal perfusion pressure breakthrough and, 726 herb and nutraceutical effects on, 152t hypovolemia and, 63. See also Hypovolemia. in carotid endarterectomy, 382 in laparoscopic surgery, 833, 834 in morbidly obese, 812 in postanesthesia care unit, 899, 900-901

957

Blood pressure (Continued) in revascularization for peripheral vascular disease, 397 monitoring of, 388, 579-580 NSAID action and, 274 Blood products. See also specific products, e.g., Crystalloid(s). anaphylactic or anaphylactoid reactions associated with, 99t for sepsis, 498 homologous, 295 in trauma victims, 830 replacement, in antepartum bleeding, 777 indications for, in children, 678, 679t transfusion of. See Blood transfusion(s). warmed, 422 Blood salvage, autologous intraoperative, blood transfusion and, 295t, 296, 297, 339, 341 in spinal surgery, 874 other potential techniques of, 297-298, 297t Blood transfusion(s), acute normovolemic hemodilution and, 295t, 296, 297 autologous predonation for, 295-296, 295t, 297 autotransfusion techniques for, 295-298, 295t, 339, 341, 679 blood salvage and. See Blood salvage. complications with, 295, 341, 677, 678, 678t prevention of, 295-298 fresh frozen plasma for, 308, 679t hemolysis of, 806 hepatitis and, 207-208 HIV infection transmission and, 207-208, 446 in antepartum bleeding, 777 in children, 677-681, 937 in EXIT procedure, 608 in Jehovah’s Witnesses, 948-950, 950t in spinal surgery, 873-874 in trauma victims, 828, 829, 830 infection and, 207, 295, 446, 502 prevention of, 207, 208, 208t inflammatory response after cardiopulmonary bypass and, 354 legal, ethical, and religious considerations with, 948-949 massive, dilutional coagulopathy and, 678 hyperkalemia and, 55 hypothermia in, 422 in children, 677-681 algorithm for, 681f complications with, 677, 678, 678t management of, 678-681, 679t, 680t, 681t problems with, 678-681, 679t, 680t, 681t in trauma victims, 828, 829 indications for, 677 patient misidentification and, 922 patient refusal of, 937 reaction to, 202-205. See also Transfusion reaction(s). subarachnoid hemorrhage and, 720 Blood urea nitrogen, 63, 342-343 Blood vessels, access to, in burn-injured patients, 507 erosion of, central venous catheter–related, 583t intraneural, ischemia of, nerve injury and, 336-337 of retroperitoneal space, 258, 259f, 260 trauma to, from arterial tourniquet, 868 intravascular coagulation and, 361 nerve injury with, 336-337

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Page 958

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Blood vessels, trauma to (Continued) peripheral nerve block and, 270 postpartum hemorrhage with, 779t, 780 Blood viscosity, in carotid endarterectomy, 382 in hyperviscosity syndrome, 363 in revascularization for peripheral vascular disease, 397 Blood volume. See also Hypovolemia. cerebral, intracranial pressure and, 594, 702, 702t fetal, 767 in pregnancy, 776-777 Body mass index, body weight measurement and, 810 Body temperature, core, 419, 422, 423 delayed emergence and, 886 hypothalamic regulation of, 663, 664f in anesthesia, 664, 664f in poisoning cases, 508 measurement sites for, 421-422, 423 tourniquet use and, 868 critical, 665 in revascularization for peripheral vascular disease, 397 in spinal cord injury, 738, 739 interthreshold range of, 420f, 421-419 monitoring of, 421-422, 423 normal, 419, 423 in intracranial aneurysm rerupture, 716, 716t Bone cement implantation syndrome, 865-866 Bone implantation syndrome, 865-866 Bone marrow surgery, fat embolism syndrome and, 860 Bony prominences, thermal injury from warming devices and, 550-551, 551t Bovie electrocautery, electromagnetic interference and, 404 in surgical diathermy, 557 Bowel, in celiac plexus block, 254 in colon surgery, 63, 64 Bowel gas, flammable, in operating room, 563, 565t Brachial neuritis, idiopathic, 336 Brachial plexus, anatomy of, 337 injury to, in cardiac surgery, 336, 337 in catheter ablation procedures, 915, 917 Brachial plexus block, supraclavicular and infraclavicular approaches to, 251, 251f, 252f Bradyarrhythmias, 331-335. See also Arrhythmias; Bradycardia. adenosine-induced, 34, 34f anatomy of, 331, 332t causes of, 331, 331t, 333-334 escape pacemaker rhythms in, atrioventricular heart block and, 332-333 in laparoscopic surgery, 832, 834 in postanesthesia care unit, 902 management and prevention of, 333-335 succinylcholine use and, in children, 624, 625 Bradycardia, α2-agonist–induced, 94, 95, 96 after cardioversion for atrial fibrillation, 908 atrioventricular heart block and, 42, 332-333, 333f atrioventricular junctional, 332 β-blockers for, 40-43 calcium channel antagonists in anesthesia and, 51 hemodynamic instability and, 899t, 900, 900t, 902 hyperkalemia and, 53 in autonomic hyperreflexia, 477, 853

Bradycardia (Continued) in infants and children, in induction of anesthesia, 28, 615 oculocardiac reflex and, 695, 696f intraoperative, algorithm for, 15 causes of, 14, 15f in heart transplant patients, 14, 15, 16 local anesthetic–induced, 231 oculocardiac reflex and, 695, 696f pacing for, 402 recognition of, 41 sinus, 40, 41, 231, 331, 332f, 334 management of, 334 oculocardiac reflex in children and, 695, 696f subsidiary atrial, 331 widened QRS complex with, tricyclic antidepressant toxicity and, 106 with absent P waves, 14, 14f Bradycardia-tachycardia, 334 Bradykinin, angioedema and, ACE inhibitors and, 18 Brain, air embolism in, in children, delayed emergence and, 629 intra-aortic balloon pump and, 409 herniation of, intracranial pressure and, 702 in carotid endarterectomy, protection of, 382 in post–dural puncture headache, 223 infarction of, 714, 720 injury of, primary and secondary, 732-733, 732t, 733t traumatic, in children, 728-731 magnesium function in, 59 parenchyma of, intracranial pressure and, 702t. See also Intracranial pressure. water content of, 594 in hypernatremia, 433 in hyponatremia, 429, 430f Brain natriuretic peptide, 4t Brain tumor, in children, 728-731 postpartum headache with, 796 Brainstem, in unintended intrathecal injection, 243 posterior fossa surgery and, 708, 709, 710 tumors in, 709 Breathing. See also Respiratory entries; Ventilation. in trauma victims, 829 periodic, in infants, 639 work of, in radical urologic surgery, 846-847, 848 in sarcoidosis, 458, 460f respiratory failure and, 347, 348 Breathing circuit of anesthesia machine, 527-530. See also Anesthesia machine. components of, 527t flowmeter malfunction and, 520 humidifiers and, 422, 543, 543f, 544, 545 liquid agent in, 532, 532t, 533 possible problems in, 527-528, 527t scavenging system and, 541-542 vs. vaporizer problems, 531, 532 Breathing pressure limiting protection module, 529 Broca index, for ideal body weight, 810 Bromocriptine, in Parkinson’s disease, 490, 491t Bronchial blocker, 368, 370 placement of, 365 Bronchial cuff, volume of, 370 Bronchitis, chronic, bronchospasm and, 190 Bronchoalveolar lavage, in sarcoidosis, 458 Bronchodilators, for prevention of bronchospasm in asthmatics, 190, 191t Bronchopleural fistula, postpneumonectomy, 378 Bronchopulmonary lavage, for pulmonary aspiration, 642

Bronchoscope, fiberoptic, flexible, 605 Bronchoscopy, fiberoptic, for compressed tracheobronchial tree, 373f for difficult airway management, 165-166, 167f, 167t for one-lung ventilation, 369-370 for repositioning double-lumen endobronchial tube, 368 for sarcoidosis, 459 in children, 605 for pulmonary aspiration in children, 642 suctioning in, pulmonary aspiration and, 187 Bronchospasm, 189-191 causes of, 189-190, 189t, 190t factors contributing to, 189, 189t, 190 in children, after rapacuronium bromide, 624, 625 upper respiratory tract infection and, 649-650, 650t ipratropium for, 29 management and prevention of, 190-191, 191t symptoms and signs of, 189 treatment of under anesthesia, 191, 191t Brown fat, in hypothermia, 664 Budd-Chiari syndrome, 363 Bullard laryngoscope, for children, 605 Bundle branch block, pulmonary artery catheter–related, 588, 589, 590 Bupivacaine, cardiotoxicity of, 232 in cesarean delivery in preeclamptic patients, 761 maximal plasmal concentrations of, 232t vs. lidocaine, neurotoxicity of, 229 toxicity of, 231, 232 Burn injuries, 504-507 airway and facial, in airway laser surgery, 750, 751 body surface area in, 506, 506t characteristics of, 504 complications of, 504-505, 505t esophageal, 577 hyperkalemia and, 55 in surgical diathermy, 558, 559 pulse oximetry and, 571 tissue, recognition of, 550 warming systems causing, 550, 551f, 552 Burst suppression, electroencephalographic, for prevention of intracranial aneurysm rerupture, 718 for traumatic brain injury treatment, 735 Busulfan, mechanisms, uses, and toxicities of, 111t 1,4-Butanediol, common uses of/problems with, 155t γ-Butyrolactone, common uses of/ problems with, 155t Butyrophenone, receptor site affinity of, 134t side effects of, 135t Butyrylcholinesterase, in myasthenia gravis, 489 C C3 activation products, in anaphylaxis, 98 C3-C5 nerve roots, in unintended intrathecal injection, 243 C5 activation products, in anaphylaxis, 98 Cabergoline, in Parkinson’s disease, 490, 491t Caffeine, anesthesia with, postoperative apnea in infants and, 613 for post–dural puncture headache, 225 postpartum headache with, 797 Caffeine halothane contracture test, for malignant hyperthermia, 655

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Calcium, defective release of, in malignant hyperthermia, 654, 656 in sudden unexplained death, 654 extracellular, L-type calcium channel function and, 50 in uterine contractions, 763 magnesium antagonism of, 59, 59t Calcium channel(s), types and properties of, 50 Calcium channel blockers, 48-52 actions and side effects of, 4t anthracycline antibiotic–induced cardiotoxicity and, 117 β-blockers used with, cardiovascular effects of, 48 heart block and, 41-42, 42t cardiac electrophysiology and pharmacology of, 50-52 conditions managed with, 42t, 51, 52 dihydropyridine, cardiac conduction and, 50, 51 for hypertension, 314, 824-825 in pregnancy, 761 drug interactions with, 48, 49t, 117 for cardiovascular disease, 51, 52 for hypertension, 52, 314, 824-825 for myocardial ischemia, 311 for tocolytic therapy, 765 for uterine contractions, 763 L-type, 48, 50 N-type, 50 P-type, 50 Q-type, 50 R-type, 50 T-type, 48, 51 toxic effects of, 48, 50-52 Calcium chloride, for calcium channel antagonist toxicity, 51 for hyperkalemia, 57 for hypotension, in adrenalectomy for pheochromocytoma, 825 Calcium gluconate, for hyperkalemia, 57 for hypoparathyroidism, 820 Calf, enlargement of, in Duchenne’s and Becker’s muscular dystrophy, 479, 480 Camptothecin analogues, 110 Cancer. See also Mass(es); Tumor(s). marijuana smoke and, 124 pancreatic, celiac plexus block and, 254 thromboembolic disease and, 362, 363 Cannabis, 122, 124 Cannon a waves, 319 Cannot ventilate, cannot intubate situation. See under Airway, difficult. Cannula(s), access for, in burn-injured patients, 507 aortic, in cardiopulmonary bypass, 302-303, 302f central neurologic injury and, 340, 341 aortic root, aortic dissection and, 299-300, 299f problems with, 300f, 301 arterial, complications with, 579-580, 580f, 580t in management of cirrhosis, 468 femoral artery, 257 inferior vena cava, in cardiopulmonary bypass, 301 neurovascular sheath, 269-270 radial artery, 579, 580, 580f, 580t superior vena cava, in cardiopulmonary bypass, 301 venous, placement of ventricular assist device and, 409, 410-411 Capillary(ies), alveolar, in acute respiratory distress syndrome, 349 pulmonary vascular resistance and, 316

Capillary(ies) (Continued) defective, normal perfusion pressure breakthrough and, 725 permeability of, in burn-injured patients, 504, 505, 507 NSAID action and, 275 Capnography, 574, 574f, 575, 576. See also End-tidal carbon dioxide. for venous air embolism detection, 674, 675, 705, 787 improved outcomes and, 933 in children, delayed emergence and, 627 in laparoscopic surgery, 832-833 Capnometry, 574, 574f Carbamate insecticides, poisoning with, 30 Carbidopa, in Parkinson’s disease, 490, 491t Carbon dioxide, arterial partial pressure of, hypoxemia and, 194t in acid-base balance, 436 end-tidal. See End-tidal carbon dioxide. expiratory, monitoring of, 574, 574f, 575, 576 insufflation of, in laparoscopic surgery, 831, 832, 834 Carbon dioxide absorbents, fire hazards with, 563, 566t problems with, 534-536, 535f Carbon monoxide, in histiocytic hypoxia, 197 poisoning with, in burn injuries, 505 low-flow anesthesia and, 534-535, 535f, 536 Carboxyhemoglobin, 196, 196f pulse oximetry and, 197, 571, 572t Carcinogen(s), herbs and nutraceuticals as, 152t Carcinoid syndrome, 814, 815t crisis in, 814 management and prevention of, 815-816 Carcinoid tumors, complications of, 814-816 Cardiac action potential, 50, 106 Cardiac arrest, do-not-resuscitate orders and, 946 foreign body aspiration and, 754 hypoxemia and, 639 in congenital long QT syndrome, 328, 329 in tricyclic antidepressant toxicity, 107 intraoperative, in children, 615-618 management of, 616, 617f, 618, 618f prevention of, 618 local anesthetic–induced, 231, 231t opiate-induced respiratory depression and, 73 posterior fossa surgery and, 710 succinylcholine use and, 85, 85t, 86, 87 in children, 624, 625, 626f venous air embolism and, 704 Cardiac Arrhythmia Suppression Trial (CAST), 36 Cardiac catheterization. See also under Catheter(s). pulmonary hypertension diagnosis and, 316 retroperitoneal hemorrhage and, 257 Cardiac conduction. See Conduction, cardiac. calcium channel antagonist effects on, 48, 49f, 51 Cardiac disease. See also Heart disease; Heart failure. in dialysis-dependent patients, 463 in pregnancy, cardiopulmonary bypass and, 802 pulmonary hypertension and, 659-660, 659t ventricular tachycardia associated with, 320 Cardiac drug(s), 20-53 adenosine as, 32-35 antiarrhythmic drugs as, β-blockers, 40-43 calcium channel blockers, 48-52 class I, 36-39

959

Cardiac drug(s), antiarrhythmic drugs as (Continued) class II, 40-43 class III, 44-46 class IV, 48-52 potassium channel blockers, 44-46 anticholinergics as, 28-31 digitalis as, 24-27 phosphodiesterase inhibitors as, 20-23 Cardiac dysfunction, digitalis use and, 24, 25, 25t in hyperkalemia, 53-54 in muscular dystrophy, 481, 482 in sarcoidosis, 458, 459 in subarachnoid hemorrhage, 722-723 postpneumonectomy, 378-379 Cardiac effects, of herbs and nutraceuticals, 152t Cardiac function, fetal, in EXIT procedure, 608 Cardiac glycoside–like effects, of herbs and nutraceuticals, 152t Cardiac output, in abdominal aortic aneurysm repair, 390, 390f in anterior mediastinal masses, 671 in cardiomyopathy, 668 in cirrhosis, 466 in pregnancy, 777 in subarachnoid hemorrhage, 721 inotropic drug use and, 11, 12 after cardiopulmonary bypass, 11, 12 Cardiac resynchronization therapy, 399, 400f Cardiac rhythm management devices. See also Pacemakers; Pacing. electromagnetic interference with, 404, 404f for congenital long QT syndrome, 329 in surgery and anesthesia, management of, 404-405 interrogation and reprogramming of, 405 lithotripsy and, 852 problems with, 399-405 surgical diathermy interference with, 556, 557, 558, 559 Cardiac risk assessment, 147-149 in peripheral vascular disease, 394, 396 Cardiac stress test, carotid endarterectomy and, 381, 382 in revascularization for peripheral vascular disease, 397 perioperative cardiac risk and, 148-149 Cardiac surgery, 291-364. See also Cardiopulmonary bypass. anticoagulation in, 291-293 bleeding after, 305-308 brachial plexus injury in, 336, 337 early extubation in, 357-360 fast-track, 356-360 perioperative tachyarrhythmias with, 319 positioning in, 337 postoperative care for, 359-360 postoperative delirium and, 888 vs. noncardiac surgery, nerve injury in, 336 Cardiac transplantation, chronotropic drug use and, 14 ventricular assist device placement and, 408 Cardiomyocytes, defective calcium release in, 656 Cardiomyopathy(ies), adrenal disease and, 822 anthracycline antibiotics and, 110, 117, 118 arrhythmogenic right ventricular, 668, 669 catecholamine-induced, 823, 824f classification of, 667 definition of, 667 dilated, characteristics of, 667 in children, 668-669 in muscular dystrophy, 480, 482 management of, 669

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Page 960

Index

Cardiomyopathy(ies) (Continued) hypertrophic, 667-668 in children, 667-669 management of, 668-669 prevention of complications with, 669 in cirrhosis, 466 in muscular dystrophy, 480-482 non-DHP calcium channel antagonists and, 51 restrictive, 668, 669 Cardioplegia solutions, in pregnant patients, 803 inflammatory response after cardiopulmonary bypass and, 354 postoperative bleeding and, 306 Cardiopulmonary bypass, acute renal failure and, 344 anticoagulation in, 291-293 aortic cannulation site for, 340, 341 aortic dissection in, 299-300, 299f arterial hypotension in, 341 carotid artery hyperperfusion in, 300-301, 300f central neurologic injury in, 340, 341 circuit of, central neurologic injury and, 339, 340 mechanical complications with, 352, 353t postoperative bleeding and, 306 common problems in, 299-304 early extubation anesthesia and, 356, 357-358 management of, 358-359, 359t prevention of complications with, 359-360 hypokalemia and, 53, 53f hypothermia in, 341 in pregnancy, 802-804 inflammatory response to, 352-355 innominate artery hyperperfusion in, 300-301, 300f low cardiac output after, inotropic drugs for, 11, 12 massive gas embolism in, 302-303, 302f obstructed venous return during, 301 off-pump, central neurologic injury and, 339, 340 organ dysfunction after, 352-355 postoperative bleeding and, 304-306 pump or oxygenator failure in, 303-304 stress response to, hypertension and, 313 vancomycin and, 102 ventricular assist device placement and, 408 Cardiopulmonary compromise, anterior mediastinal masses and, 670, 671, 672 Cardiopulmonary resuscitation, cardiac arrest and, 615, 616 do-not-resuscitate orders and, 946-947 maternal, with amniotic fluid embolism, 788 Cardiorespiratory effects, of naloxone, 128, 129, 130 of opioids, 174 Cardiorespiratory monitoring, postoperative apnea in infants and, 614 Cardiotoxicity, of anthracycline antibiotics, 116-117 of local anesthetics, 231-232 vs. total spinal anesthesia, 248 Cardiovascular compromise, anterior mediastinal masses and, 670, 671, 672 in autonomic hyperreflexia, 477 in cirrhosis, 466 in laparoscopic surgery, 831, 831t in laryngeal microsurgery, 750, 751 in spinal cord injury, 738 local anesthetic–induced, 231, 233

Cardiovascular compromise (Continued) posterior fossa surgery and, 708 propofol effects and, 81 surgical risk and, 147, 147t, 148-149, 148t Cardiovascular disease, β-blockers or calcium channel blockers for, 42t in end-stage renal disease patients, 463 in HIV patients, 449 in morbidly obese patients, 810, 811t in peripheral vascular disease, 395t, 396 in postanesthesia care unit, 899, 900, 901, 902 nonbarbiturate anesthetics and, 81, 83 sildenafil and, 22 Cardiovascular effects, of class IV antiarrhythmic drugs, 48, 49f of electroconvulsive therapy, 903, 904, 904t of hyperglycemia, 417 of pregnancy, 802, 803f of water-immersion lithotripsy, 851, 851t Cardiovascular risks, in fetal intrauterine surgery, 767 Cardioversion, 905-908. See also Internal cardioverter-defibrillators. anesthesia needs for, 905-906, 907 complications with, 906, 908 emergent, for atrial fibrillation, 908 for unstable tachyarrhythmias, 907-908 for adenosine-induced tachycardia, 34, 34f for anticholinergic-induced tachycardia, 31 for atrial fibrillation or flutter, 43 for atrioventricular reciprocating tachycardia in WPW syndrome, 326 for cardiac arrest in tricyclic antidepressant toxicity, 107 for drug-induced torsades de pointes, 46 for perioperative tachyarrhythmias, 323 for postpneumonectomy atrial tachyarrhythmias, 378 for stable and unstable tachyarrhythmias, 905 for tachycardia, 32, 34 in postanesthesia care unit, 902 preparation for, 907 Carotid angioplasty, vs. carotid endarterectomy, 381 Carotid artery, hyperperfusion of, in cardiopulmonary bypass, 300-301, 300f occlusion of, in carotid endarterectomy, 380 Carotid disease, coronary artery disease and, 381, 382 Carotid endarterectomy, 380-382 complications with, management and prevention of, 382 postoperative, 381, 381t risk factors for, 381-382 Carotid sinus, hypersensitive, pacing for, 401t, 402 Carotid stump pressure, for detection of cerebral ischemia, 381 Catechol-O-methyltransferase inhibitors, in Parkinson’s disease, 490, 491t Catecholamine(s). See also Vasopressors. as vasopressors, therapy with, 9 endogenous, ketamine use and, 78 reuptake of, by tricyclic antidepressants, 106, 107 vasodilator use and, 5 hypercoagulability induced by, 8 immune-modulating effects of, 8 inotropic drugs as, 11, 11t monoamine oxidase inhibitors and, 105 side effects of, 7-8

Catheter(s), central venous, complications with, 582t, 583-587, 583t, 585f, 586f for detection of venous air embolism, 675 epidural, 241, 243 for detection of venous air embolism, 674, 675 in continuous perineural local anesthetic infusion, 283 in traumatic brain injury, 733 indwelling, nerve injury from, 286 thrombosis and, 364 infections related to, 239-241, 583, 584, 585, 585f, 586f antibiotic-coated or -impregnated, 585 cultures of, 583, 584, 585f nontunneled, 586f intra-aortic balloon pump, 410 intubating, 162 microdialysis, 733 peripheral nerve block, 266, 267f pulmonary artery, complications with, 588-590 for detection of venous air embolism, 674-675 in abdominal aortic aneurysm repair, 390, 390f in management of cirrhosis, 468 placement of, 588, 589, 590 postpneumonectomy confusion about, 379 pulmonary hypertension diagnosis and, 316 sciatic nerve block, 266, 267f Catheter ablation techniques, for arrhythmias, 915-917, 916t, 917t Cation exchange resins, 57 Cauda equina syndrome, 227-229 causes of, 227-228 in obstetric patients, 790 management and prevention of, 228-229 risk factors for, 228 vs. spinal hematoma, 235t Causalgia, postoperative, tourniquet use and, 869, 870 Cautery, bipolar, 404, 405 in surgical diathermy, 557, 557f Caveolin deficiency, in muscular dystrophy, 480 Cavitary lung disease, in HIV-infected patients, 448 CD4 T cells, in HIV infection and AIDS, 446, 447f Celecoxib, toxicity of, 275, 276 Celiac plexus block, side effects and complications of, 254-256 Celite-activated clotting time, 291 Cell(s), disruption of, hyperkalemia and, 55 dysfunction of, in systemic inflammatory response syndrome, 497 hyperglycemic effects on, 416-417 transmembrane potential of, in hypokalemia, 55 Cell membranes, anthracycline antibiotic interaction with, 116 Cell salvage systems, in cardiac surgery, 306 in massive blood transfusion in children, 679 Central nervous system, anticholinergic effects on, 30 disorders of, delayed emergence in children and, 629 in poisoning cases, 508 effects on, of herbs and nutraceuticals, 152t, 153t in acute porphyria, 75, 76

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Central nervous system (Continued) in autonomic hyperreflexia, 478, 853 in cirrhosis, 467 in coronary artery bypass grafting, 339-341 in hypernatremia, 433 in hyperthermia, 424 in hyponatremia, 429, 431, 432 in total spinal anesthesia, 248 local anesthetic–induced toxicity of, 230, 231, 232, 233 lymphoma of, in AIDS patients, 449 sensitivity of, delayed emergence and, 885, 886 tricyclic antidepressant action in, 106 Central pontine myelinolysis, 432 Central venous catheter, complications with, 582t, 583-587, 583t, 585f, 586f for detection of venous air embolism, 675 Central venous pressure, in abdominal aortic aneurysm repair, 390, 390f monitoring of, complications with, 582-587, 582t Cephalosporins, 102t Cerebral angiography, for diagnosis of vasospasm, 719 Cerebral artery, middle, detection of cerebral ischemia and, 381 Cerebral autoregulation, in intracranial aneurysm rerupture, 714 in subarachnoid hemorrhage, 722 in traumatic brain injury, 734, 734f normal perfusion pressure breakthrough and, 727 Cerebral blood flow. See Blood flow, cerebral. Cerebral blood volume, intracranial pressure and, 702, 702t reduction of, methods of, 594 Cerebral edema, hyponatremia and, 431, 432 in children, 728 normal perfusion pressure breakthrough and, 724, 726, 727 Cerebral ischemia, clonidine withdrawal and, 95 delayed emergence in children with, 629 in carotid endarterectomy, 380-381, 380t, 382 intracranial pressure and, 702 Cerebral metabolic rate, 340 Cerebral monitoring, for placement of surgical shunt, 380-381, 380t Cerebral perfusion pressure, definition of, 591 in brain injury assessment, 733 in intracranial pressure monitoring, 591 in traumatic brain injury, 733, 734, 734f, 735 Cerebral toxoplasmosis, in AIDS patients, 449 Cerebral vasospasm. See Vasospasm. Cerebrospinal fluid, in post–dural puncture headache, 223, 223f in thoracic aortic aneurysm repair, 387 in unintended intrathecal injection, 242, 243 intracranial pressure and, 594, 702, 702t opioid spread in, 261 vs. other fluids, tests for, 243 Cerebrovascular accident. See Stroke. Certified registered nurse anesthetists, on anesthesia care team, 930 Cervical spine, injury to, 177, 737 assessment of, 179 collar for, 177, 829 computed tomography of, 178 diagnostic algorithm for, 178f immobilization of, 177, 829 magnetic resonance imaging of, 178

Cervical spine (Continued) management of, 179-180 radiography of, 177-179, 178f signs of, 177 traumatic, 828 in children, 729 unstable, 176-180 Cesarean delivery, anesthesia for, in preeclamptic patients, 761 emergent, 771 EXIT procedure and, 608 in HIV-infected patients, 449 malpractice claims and, 933 pulmonary aspiration and, 783 venous air embolism and, 788 Chamomile, common uses and problems with, 155t Charting systems, automated, 929 Chemical dependency. See also Drug dependence. non-opioid dependent, 122-127 opioid, 119-121 Chemical injury, burns from, 504 corneal, 741-742, 742f of neural tissue, in obstetric patients, 790 Chemical(s), flammable, in operating room, 563, 565t Chemical pneumonitis, in parturients, 782-785 Chemokines, acute respiratory distress syndrome and, 349 Chemoprophylaxis, for HIV postexposure, 208 for pulmonary aspiration, 187-188, 187t Chemoreceptor trigger zone, 644, 645f, 890, 891f Chemotherapeutic agents, 110-118, 882 delayed emergence and, 886 Chest, auscultation of, for double-lumen tube malposition, 365, 366f, 367f compression of, intraoperative cardiac arrest and, 616 percussion of, in pneumothorax, 252 Chest radiograph, in acute respiratory distress syndrome, 348f in child with anterior mediastinal mass, 670f, 671 in pancreatitis, 474 in pneumothorax, 252 in sarcoidosis, 457-458, 458t one-lung ventilation and, 370 Chest tube, 253, 305, 306 Chest wall, in ventilation in infants, 603-604, 638 opiate-induced rigidity of, 174 Child-Pugh score, in cirrhosis, 467, 468t Children. See also Infants; Neonates. adenotonsillectomy in, 688-691 air emboli in, 673-676 anesthesia in, emergence from, agitation with, 685-686 delayed, 627-630 induction of, 28, 604-605 anterior mediastinal masses in, 670-672 anticholinergic toxicity in, 28, 29 aspiration pneumonitis in, 641-643 bradycardia in, 28 bronchospasm in, 189 cardiac arrest in, intraoperative, 615-618 cardiomyopathy in, 667-669 catheter ablation procedures in, 915-917 choking in, 753, 754 coexisting disease and altered states in, 649-665 congenital heart disease in, 402 difficult airway in, 603-606, 604f emergent cardioversion in, 908 epiglottitis in, 216

961

Children (Continued) fluid requirements in, calculation of, 658t foreign body aspiration in, 753-755, 753f halothane-induced hepatic necrosis in, 67 hospital admission in, unanticipated, 893-894 hyperglycemia in, 657-658 hypoglycemia in, 657-658 hypothermia in, 663-665 hypoxemia in, 637-639 laryngospasm in, 599-602 latex allergy in, 651-653 lithotripsy and, 852 magnetic resonance imaging in, 918 malignant hyperthermia in, 654-656 massive blood transfusion in, 677-681 mediastinal masses in, 374 medical decision making for, 949 muscle relaxants in, 623-626 myopathy in, succinylcholine administration and, 86, 481 neurosurgery in, 728-731 nitrous oxide neurotoxicity in, 70 ophthalmic complications in, 692-697 pacing in, temporary or permanent, 400t, 402 postintubation croup in, 631-632 postobstruction pulmonary edema in, 216, 634-636 postoperative nausea and vomiting in, 644-648 propofol exclusion in, 82 psychological trauma in, 682-684, 683f pulmonary hypertension in, 659-662 radiation oncology in, 909-911 sedation of, 619-622 guidelines for, 621, 622 succinylcholine in, 86, 481 tonsillectomy in, 688-691 uncooperative, 937 upper respiratory tract infection in, 649-650 vaccination of, against H. influenzae type B, 216 vancomycin in, 102 with undiagnosed muscular dystrophy, succinylcholine in, 481 Chinese medicine, 150 Chin-lift maneuver, in airway obstruction, 601 in cervical spine injuries, 179 Chloral hydrate, sedation in children and, 620, 621 Chlorhexidine, in central neuraxial block, 241 in continuous perineural local anesthetic infusion, 283 in nosocomial pneumonia, 211 Chloride, in metabolic alkalosis, 437, 439 Chlorpromazine, for postoperative delirium, 889 receptor site affinity of, 134t side effects of, 135t Choking, 754-755 mortality from, 753 Cholecystectomy, laparoscopic, 63, 64, 834 Cholelithiasis, cirrhosis and, 808 Cholestasis, postoperative jaundice and, 807, 808 Cholinesterase inhibition, in Alzheimer’s disease, 494 Chronic obstructive pulmonary disease, 29 Chronotropic drugs, 14-16 in heart disease, 14 in heart transplant patients, 15-16 Cilomast, 22 Cimetidine, 93 for anaphylactic or anaphylactoid reactions, 99, 100 for pulmonary aspiration, 188, 643t

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Ciprofloxacin, for nosocomial bacterial pneumonia, 211 Circle of Willis, 380 Circulation. See also Blood flow; Blood pressure. abnormalities of, in acute renal failure, 344 in radical urologic surgery, 847 failure of, prevention of, 198t in acute respiratory distress syndrome, 350 in intraoperative cardiac arrest, 616 in trauma victims, 829-830 Circulatory hypoxia, 197 Cirrhosis, 466-469 causes of, 466t characteristics of, 466 classification and scoring system for, 808 complications of, 467t management and prevention of, 468 postoperative jaundice and, 807, 808 recognition of, 466-467 risk assessment in, 467-468, 467t Cisatracurium, 89t in children, 623 dose, clearance, and side effects of, 624t Cisplatin, mechanisms, uses, and toxicities of, 112t Citrate, for pulmonary aspiration, 188 hyperkalemia and, 55 Claudication, intermittent, in peripheral vascular disease, 394 Clerical errors, acute hemolytic transfusion reaction and, 202, 204 Clindamycin, complications of, 102t Clonidine, actions and side effects of, 4t in opioid-tolerant patients, 121, 281 properties of, 94 withdrawal of, adverse effects of, 94-96 Clopidogrel, hemorrhagic complications with, 270 spinal hematoma and, 236-237, 237t Clot formation, intra-aortic balloon pump and, 409 Coagulation factors, deficiencies in, 308 in coagulation cascade, 361 in infants and children, 677-678 in postoperative bleeding, after cardiac surgery, 306 Coagulation process, herbal and nutraceutical effects on, 153t in surgical diathermy, 557, 557f kaolin-activated clotting time in, 291 regulation of, 361 Coagulopathy, dilutional, with massive blood transfusion, in children, 678 in antepartum bleeding, 776-777 in children, laboratory testing for, 679, 679t with massive blood transfusion, 678 in cirrhosis, 467, 468 in end-stage renal disease, 462-463 in trauma victims, 830 in traumatic brain injury, 734, 735 inflammatory response after cardiopulmonary bypass and, 354 peripheral nerve blocks and, 272 postoperative hepatic dysfunction and, 805 Cobalamin, deficiency of, 69, 70 Cocaine Anonymous, 126 Cocaine dependence, 122, 124, 124t consequences of, 125 treatment of, 126, 126t Cockroft-Gault formula, for calculation of creatinine clearance, 344 Codeine, anaphylactic and anaphylactoid reactions and, 98, 99t equianalgesic conversion doses of, 279t

Coenzyme Q10, common uses and problems with, 155t Coexisting disease, in children, 649-665 Cognitive disorders, preexisting, delayed emergence and, 885, 886 Collar, cervical, 177, 829 Colloid(s), acid-base balance and, 440 in acute normovolemic hemodilution, 296, 297 in antepartum bleeding, 777 in revascularization for peripheral vascular disease, 397 in septic conditions, 498 in subarachnoid hemorrhage, 721 in trauma victims, 830 ischemic optic nerve compression and, 857 warmed, 422 Colon surgery, fluid management in, 63, 64 Coma, intracranial pressure monitoring and, 591, 593 Combitube, esophageal-tracheal, 169 Common peroneal nerve, in childbirth, 790, 791f, 792f, 792t Communication, between anesthesiologist and surgeon, 616, 709 Compartment syndrome, 505, 869, 870 Complement 1 esterase inhibitor deficiency, 426 Complementary and alternative medicine (CAM), 150, 151. See also specific term, e.g., Herbs. Compound A, 22, 534, 535, 535f Compression, protection of eyes from in anesthesia, 693 Compression stockings, 863 Compressive injuries, cauda equina syndrome and, 227, 228 Computed tomography, abdominal, after psoas compartment block, 257, 258f contrast-enhanced, 474, 719-720 for anterior mediastinal mass, 671f, 672 for brain injury, 733 for central neurologic injury, 339 for cervical spine injuries, 178 for compressed tracheobronchial tree, 374f for pancreatitis, 474 for pneumothorax, 252 for sarcoidosis, 458, 459f for vasospasm, 719-720 one-lung ventilation and, 370 Computed tomography–angiography, for vasospasm diagnosis, 719-720 Conduction, cardiac, abnormalities of, hyperkalemia and, 53-54, 57 calcium channel antagonist effects on, 48, 49f, 50-51 catheter ablation of, 915, 915f in atrioventricular node, 48, 49f in muscular dystrophy, 480, 481, 482 in sinoatrial node, 48, 49f local anesthetic–induced depression of, 230-231 Conduction block. See also Heart block. atrioventricular, 40. See also Atrioventricular heart block. management of, 42-43 risk assessment of, 41-42, 42t calcium channel antagonists with β-receptor antagonists and, 48 types of, 40 Confidentiality, of patients, 944-945 in malpractice cases, 934 Congenital heart disease, hypoxemia and, 639 pacing for, 402 pulmonary hypertension and, 316 Congenital myasthenic syndromes, 485, 486t, 487t differential diagnosis of, 488t

Congestive heart failure, anthracycline antibiotic–induced, 116, 117, 118 detection of, 117 digitalis for, 24 hypoxemia and, 639 intraoperative, in muscular dystrophy, 481, 482 pheochromocytoma and, 823, 824, 824f proarrhythmia risk with antiarrhythmic drugs and, 38 sildenafil use in, 21 vasopressor therapy and, 8 Conjunctival sac, irrigation of, 742, 743, 743f Conn’s syndrome, adrenal disease and, 822, 823, 825 Conscious sedation, 619 Consciousness, in hypernatremia, 433 in trauma patients, 177 Consent, in Alzheimer’s disease, 493, 494 medicolegal aspects of, 937 of minors, 944-945 Context-sensitive decrement-time, of plasma drug concentration, 546, 547, 547f Context-sensitive half-time, of plasma drug concentration, 546, 546f, 547 Continuous positive airway pressure, in acute respiratory distress syndrome, 350 in one-lung ventilation, 369, 370 in postobstruction pulmonary edema, 215, 216 Contractures, in muscular dystrophy, 482 Cooling, for treatment of hyperthermia, 424 Coombs’ test, acute hemolytic transfusion reaction and, 202, 204 Cor pulmonale. See also Pulmonary edema. acute or chronic, 667 in sarcoidosis, 460 tonsillectomy and, 689, 690 Cornea, abrasion of, 741, 741f, 742, 742f after thyroid surgery, 818, 819, 820, 821 in children, 692-693, 692f chemical injury of, 741-742, 742f, 743t staining patterns of, 741, 742f Coronary artery, perforation of, in laser surgery, 568 Coronary artery bypass grafting, central neurologic injury after, 339 management of, 340-341 recognition of, 339-340 risk factors for, 340 early extubation anesthesia and, 356, 357-358 management of, 358-359 off-pump, acute renal failure and, 344 results of, 357 surgery for, hypertension and, 313 vancomycin and, 102 Coronary artery disease, abdominal aortic aneurysm repair and, 390, 391, 392 anticholinergic toxicity and, 30 β-blockers or calcium channel blockers for, 42t, 50 carotid disease and, 381, 382 deliberate hypotension and, 856-857 hemodynamic instability and, 900 hypothyroidism and, 453 myocardial ischemia in, 25 peripheral vascular disease and, 395t, 396 risk factors for, 21, 147-149, 147t sildenafil use in, 21 vasopressor therapy and, 8 ventricular tachycardia and, 320 Coronary steal, nitroprusside and, 314

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Corticosteroids, 110, 131-133 adrenal function and, 131-133, 444, 501 after thyroid storm, 820 chronic administration of, 444 for acute spinal cord injury, 739, 740 for anaphylactic or anaphylactoid reactions, 99 for bronchospasm in asthmatics, 190, 191, 191t for fat embolism syndrome, 861 for intracranial pressure lowering, 702, 702t for intraoperative angioedema and urticaria, 427 for Pneumocystis jirovecii pneumonia, 448 for postintubation croup, 632 for postoperative nausea and vomiting, 646t for pulmonary aspiration, 187 for sarcoidosis, 460 for sepsis, 498 for stressed patients with adrenal insufficiency, 131-133, 444-445 glucocorticoid and mineralocorticoid potencies of, 132t inflammatory response after cardiopulmonary bypass and, 355 intracranial pressure and, 594 perioperative supplementation of, 132, 132t Corticotropin-releasing factor, release and function of, 442, 443f Cortisol. See also Hydrocortisone. adrenal release of, 442, 443f, 445 evaluation of, 444 excess, 822, 823, 823t glucocorticoid and mineralocorticoid potencies of, 132t in surgery or stress, 131 Cost(s), containment of, 930-931 false-positive test results and, 142 missing or inadequate test results and, 145 of cardiac surgery, 356, 357-358, 358t of early vs. late extubation anesthesia, 357-358, 358t of systems monitoring consciousness under anesthesia, 940, 941 Cosyntropin, 131 stimulation test with, 444, 445 Coughing, intraocular pressure increase and, 695 COX-1 pathway, allergic reactions and, 275 in NSAID action, 273, 273f, 274 COX-2 pathway, in NSAID action, 273, 273f, 274, 274f inhibitors of, 274, 274f Cranial nerve(s), in posterior fossa surgery, 709, 710 Craniotomy, posterior fossa, patient position used in, 710, 710t venous air emboli and, 673, 675, 708, 709 Crawford classification, of aortic aneurysm, 384, 385f C-reactive protein, in pancreatitis, 474 Creatine kinase, in early vs. late extubation after cardiac surgery, 357t in myocardial infarction and ischemia, 309 Creatinine, acute renal failure and, 342, 343, 344 clearance of, 344 hypovolemia and, 63 preoperative, 344 Cricoid pressure, for prevention of pulmonary aspiration, 188, 643, 784, 829 Cricothyrotomy, contraindications to, 171t in cervical spine injuries, 179 in trauma victims, 829 rapid, technique of, 172t surgical, 171-172 transtracheal jet ventilation with, 170-171, 172f, 172t

Croup, postintubation, in children, 631-632 Cryoablation, of cardiac conduction pathways, 915 Cryoprecipitate, for bleeding in uremic patients, 464 for coagulation factor deficiencies, 308 for disseminated intravascular coagulopathy in pregnancy, 777 transfusion with, 679t Crystalloid(s), for acute normovolemic hemodilution, 296, 297 for perioperative management, 62, 64 for postoperative bleeding after cardiac surgery, 306 for revascularization in peripheral vascular disease, 397 for sepsis, 498 for subarachnoid hemorrhage, 721 for trauma victims, 730, 830 warmed, 422 Cubital tunnel retinaculum, 881-883, 882f, 883f Cubital tunnel syndrome, 882-883 Cullen’s sign, in pancreatitis, 474 Cultures, catheter, in catheter-related infections, 583, 584, 585f Cushing’s disease, adrenal tumors and, 822 adrenalectomy and, 823, 825 manifestations of, 822, 823t Cushing’s reflex, in traumatic brain injury, 733, 735 Cushing’s syndrome, adrenal tumors and, 822 adrenalectomy and, 823, 825, 826 manifestations of, 822-823 Cyanide poisoning, in burn-injured patients, 507 Cyanosis, oxygen status and, 197 Cyclic adenosine monophosphate (cAMP), H2 receptor antagonists and, 93 in uterine contractions, 763 phosphodiesterase-3 inhibitors and, 22 Cyclic guanosine monophosphate, 20, 21 Cyclooxygenase, in NSAID action, 273, 273f, 274 Cyclophosphamide, mechanisms, uses, and toxicities of, 112t Cyclosporine, for sarcoidosis, 460 interaction of, with anesthetic drugs, 501 toxicity of, 501 Cystectomy, radical, 846-849 Cytarabine, 110 mechanisms, uses, and toxicities of, 113t Cytochrome enzymes, hepatic, calcium channel antagonists and, 51 Cytochrome P-450, 2C9 pathway of, sildenafil and, 22-23 St. John’s wort interactions with, 109 3A4 pathway of, mibefradil and, 51 sildenafil and, 22-23 St. John’s wort interactions with, 109 anthracycline antibiotics and, 116 H1- and H2-blockers and, 93 halothane metabolism and, 67 heme synthesis and, 74 Cytokines, cardiopulmonary bypass and, 353 hypotension and, 7 in acute respiratory distress syndrome, 349 Cytomegalovirus, blood transfusion and, 295 Cytotoxic agents, for sarcoidosis, 460 D Da Nang lung syndrome, 62 Daclizumab, 501 Dactinomycin, mechanisms, uses, and toxicities of, 111t

963

Danaproid sodium, for heparin-induced thrombocytopenia in cardiopulmonary bypass, 292 Dantrolene, for hyperthyroidism, 456 for malignant hyperthermia, 655, 656 Data management, in quality assurance programs, 929 Datex-Ohmeda, proportioning systems of, 518, 521, 521f, 523 Daunorubicin, 110, 116 DDAVP (desmopressin acetate), for antidiuretic hormone replacement, 713 for bleeding in uremic patients, 464 for platelet dysfunction after cardiac surgery, 306, 308 Dead space, 193 Death. See Mortality. DeBakey classification, of aortic dissection, 384f Debridement, in burn-injured patients, 506 Deep venous thrombosis, acquired causes of, 362, 363, 364 after orthopedic surgery, 862-864, 868 in morbidly obese, 813 inherited causes of, 362, 363 prevention of, 364, 863-864 tourniquet use and, 868 Defibrillation, 905-908. See also Cardioversion. for cardiac arrest, in tricyclic antidepressant toxicity, 107 for drug-induced torsades de pointes, 46 for unstable tachyarrhythmias, 323, 907-908 in postanesthesia care unit, 902 Defibrillators, precautions with, 564t Dehydration, in diabetes insipidus, 712, 713 Delirium, emergence agitation in children and, 686 postoperative, 888-889 Delivery. See Labor and delivery; Pregnancy. Delta waves, in Wolff-Parkinson-White syndrome, 324, 325 Dementia, 493-494 in AIDS patients, 449 Demerol, for sedation in children, 620, 621 Demyelination, methionine deficiency and nitrous oxide anesthesia and, 69 Denial, of substance abuse, 123 Dental injuries, 181-183 Dentist, referral to, 183 Deposition, in malpractice cases, 934 Dermatitis, irritant, latex and, 217, 218t Desflurane, hepatic toxicity and, 66 neurophysiologic effects of, 729t Desmopressin acetate (DDAVP), for antidiuretic hormone replacement, 713 for bleeding in uremic patients, 464 for platelet dysfunction after cardiac surgery, 306, 308 Destination therapy, ventricular assist device placement and, 408 Detoxification, for substance abuse addicts, 121, 125 Dexamethasone, complications of, 136 for acute laryngeal edema, 185 for adrenal insufficiency, 444 for hyperthyroidism or thyroid storm, 456 for postintubation croup, 632 for postoperative nausea and vomiting, 646t for prevention of intracranial aneurysm rerupture, 718 for prevention of neuraxial opioid complications, 263 glucocorticoid and mineralocorticoid potencies of, 132t perioperative supplementation with, 133

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Index

Dexemedetomidine, adverse effects of, 94-96 for shivering prevention, 422 Dexrazoxane, anthracycline antibiotic–induced cardiotoxicity and, 117 Dextran, anaphylactic or anaphylactoid reactions and, 100 for post–dural puncture headache, 225-226 Diabetes insipidus, central vs. nephrogenic, 66, 67 nephrogenic, 712 neurogenic, 712 pituitary tumors and, 712-713 postoperative, in traumatic brain injury in children, 730-731 Diabetes mellitus, acid-base balance and, 440 atypical, adrenal disease and, 822 features of, 415 in morbidly obese, 811t, 812 inflammatory response after cardiopulmonary bypass and, 353 perioperative management of, 417, 418 peripheral neuropathy and, 793, 882 risks with, 416-417, 882 Diabetic ketoacidosis, hyperkalemia and, 55 management of, 417-418, 417t pathogenesis of, 415, 416f Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), drug dependence criteria in, 119, 123, 125 Diagnostic interventions, anesthesia for, 903-920 Dialysis, acute renal failure and, 344, 345 allergic reactions to blood transfusion and, 204 for end-stage renal disease, 462-465 for septic conditions, 499 perioperative management with, 462-465 Diaphragm, in ventilation in infants, 603-604 Diarrhea, in carcinoid syndrome, 814, 815 Diathermy, surgical, 556-559 Diazoxide, actions and side effects of, 5t Dibucaine, abnormal pseudocholinesterase variants and, 86t, 87 Diclofenac, in cardiac surgery patients, 359 toxicity of, vs. celecoxib, 275, 276 Dietary Supplement Health and Education Act, 150 Dietary supplements, common uses of, 155t, 156t components of, 150 labeling requirements for, 150 perioperative management of, 151, 154 resources for further information on, 157t risk assessment for, 151 side effects of, 150, 151, 152t-154t Diffusion limitation, hypoxemia and, 195, 198t prevention of, 198t Digibind, for digitalis toxicity, 26, 27 Digital plethysmography, 580 Digitalis, 24-27. See also Digoxin. action of, 24 cardiac complications of, 24, 25 for congestive heart failure, 24 hyperkalemia and, 55 therapeutic effects of, 24, 25, 25t, 26t toxicity of, extracardiac manifestations of, 25 factors predisposing to, 25-26, 26t management and prevention of, 26-27, 26t Digoxin. See also Digitalis. after thyroid storm, 820 heart block and, 40 serum assays for, after Digibind treatment, 27 Dihydropyridine calcium channel blockers. See Calcium channel blockers, dihydropyridine.

Diltiazem, 48-52 actions and side effects of, 4t β-blockers used with, heart block and, 41-42, 42t cardiac conduction and, 51 for hypertension, 314 propranolol and, 48, 49t Dilutional coagulopathy, with massive blood transfusion in children, 678 Dimenhydrinate, for postoperative nausea and vomiting, 646t Diphenhydramine, 92, 93 for anaphylactic or anaphylactoid reactions, 99, 100 for postoperative nausea and vomiting, 646t receptor site affinity of, 134t side effects of, 135t Diprifusor, 548 Dipyridamole, 22t adenosine and, 32, 33, 34, 35 Disease, coexisting, 442-512 Disopyramide, dose of, 39t Disseminated intravascular coagulopathy, in antepartum bleeding, 776-777 in TURP syndrome, 844, 845 Diuretics, for reduction of brain tissue water, 594 for sarcoidosis, 460 loop, for acute renal failure, 345 for hyperkalemia, 57 for intracranial pressure, 702, 702t thiazide, for acute renal failure, 345 DNA, anthracycline antibiotic action and, 116 methionine deficiency and nitrous oxide anesthesia and, 69 Dobutamine, as inotropic drug, 11-12, 12t for sepsis, 498 Doctor-patient relationship, 942 Documentation, in malpractice cases, 934 of adverse incidents, 943 of blood-contaminated injuries, 208 of dental injuries and preexisting conditions, 183 of intraoperative cardiac arrest, 616, 617f of patient consent for DNR status, 947 quality assurance reviews and, 927 Dolasetron, for postoperative nausea and vomiting, 646t receptor site affinity of, 134t side effects of, 135t Domperidone, in Parkinson’s disease, 490, 491t Donepezil, in Alzheimer’s disease, 494 Dong quai, common uses of/problems with, 155t Do-not-resuscitate orders, in operating room, 946-947 Dopamine, antagonists of, for postoperative nausea and vomiting, 646t as inotropic drug, 11, 12t receptor agonists of, for hypertension, 314 for Parkinson’s disease, 490, 491t renal dose of, for prevention of acute renal failure, 345 side effects of, 7, 8t Doppler ultrasonography, esophageal, for intraoperative fluid management, 64-65 for venous air embolism, 674, 675, 705, 787 transcranial, for cerebral ischemia, 381 for vasospasm, 720 Double crush syndrome, peripheral neuropathy risk and, 882, 883 Down’s syndrome, postintubation croup and, 632

Doxacurium, 89t in children, dose, clearance, and side effects of, 624t Doxazosin, for adrenalectomy with pheochromocytoma, 826 Doxorubicin, 110 cardiomyopathy and, 117 local toxic effects of, 117 metabolism of, 116 synthetic analogues of, 110 DPT (Demerol, Phenergan, Thorazine), sedation in children with, 620, 621 Dräger anesthesia machine, proportioning systems of, 518 scavenging system of, 540, 541f Drainage, surgical, for epidural abscess, 241 Draping, fire hazards with, 565, 568 Dressings, central venous catheter–related infection and, 585 Dronabinol (Marinol), for marijuana abuse, 126 Droperidol, for neuraxial opioid complications, 263 for postoperative delirium, 889 for postoperative nausea and vomiting, 136, 646t, 647 neurophysiologic effects of, 729t potential complications of, 136 Q-T interval prolongation and, 37 receptor site affinity of, 134t side effects of, 135t Drug(s). See also names of drug classes, e.g., Opioids; names of specific drugs, e.g., Morphine. adjunctive, in analgesia for opioid-tolerant patients, 280 antiepileptic, congenital anomalies and, 200-201 cost issues with, 931 fat-soluble, delayed emergence and, 886 hypersensitivity reactions of, to HIV drug treatment, 447 in postanesthesia care unit, 899 internal cardioverter-defibrillator interaction with, 403 intravenous delivery systems for, 546-549 labeling of, syringe swaps and, 925, 926 plasma concentration of, delayed emergence and, 886 infusion duration and, 546-547, 546f, 547f porphyrinogenic, 75, 76, 76t reactions of, allergic and nonallergic, 97-98 anaphylactic and anaphylactoid reactions associated with, 98, 99t angioedema and urticaria and, 427 redistribution of, delayed emergence and, 886 tray organization of, 925, 925f withdrawal from, 119 prevention of, in opioid-tolerant patients, 281 risk of, 279 Drug dependence, complications of, 120-121 detection of, 119 definitions of, 119 on nonopioids, 122-127 among physicians, 122-127 behavior problems with, 125 case histories of, 122 diagnosis of, 123-125, 123t, 124t management of, 125-126, 126t prevention of, 126-127 screening tests for, 123, 123t on opioids, 119-121 overdose deaths in, 120, 121 pain management in, in opioid-tolerant patients, 279-280, 279t

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Drug interactions, delayed emergence and, 886 in children, 627 digitalis toxicity and, 26, 26t in immunocompromised patients, 501 with calcium channel antagonists, 49t with herbs and nutraceuticals, 153t Drug testing, for drug dependence, 119 random, 121, 123, 127 Dual block, succinylcholine and, 85 Duchenne’s muscular dystrophy, 479 protein dysfunction in, 479-480 Duodenal ulcer disease, 93 Duodopa, in Parkinson’s disease, 490, 491t Dural puncture, headache following, in spinal anesthesia, 223-226 Dyes, anaphylactic or anaphylactoid reactions associated with, 99t circulating, pulse oximetry and, 571, 572t Dysequilibrium syndrome, in end-stage renal disease, 463 Dyspnea. See also Breathing. adenosine and, 32 in transfusion reaction, 204 Dysreflexia, autonomic, 477-478, 477t, 853-854 causes of, 853, 853t manifestations of, 853t Dystrophin, in cardiomyopathy in muscular dystrophy, 480 Dystrophinopathies, 479-480 E Ear, nose, and throat procedures, 750-755 Early afterdepolarizations, causes of, and triggered activity, 37, 37t magnesium infusion and, 59, 60 polymorphic ventricular tachycardias and, 36, 37 torsades de pointes and, 36, 37, 327 Ebselen, for vasospasm, 722 Ecarin clotting time, 293 Echinacea, common uses and problems with, 155t Echocardiography, for muscular dystrophy, 481 for pulmonary hypertension, 316 for venous air embolism, 674, 674f transesophageal, complications with, 577-578 contraindications to, 577t for abdominal aortic aneurysm repair, 390 for acute respiratory distress syndrome, 348-349 for aortic dissection, 299f for early extubation anesthesia, 359 Eclampsia, definition of, 759 postpartum headache with, 797 ECT. See Electroconvulsive therapy. Ectopic atrial tachycardia, 320t, 321t Ectopic beats, in postanesthesia care unit, 902 Ectopic pregnancy, bleeding in, 774, 776t, 777t Edema, airway, 760, 877, 879 cerebral, hyponatremia and, 431, 432 in children, 728 normal perfusion pressure breakthrough and, 724, 726, 727 facial, histamine release and, 101 in burn injuries, glottal or laryngeal, 504, 505 peripheral, 505, 506 in preeclampsia, 760 laryngeal, angioedema and, 426, 427 in burn injuries, 504, 505 postintubation croup and, 632 treatment of, 185 NSAID use and, 275, 276 pulmonary. See Pulmonary edema.

Edema (Continued) spinal cord, in thoracic aortic aneurysm repair, 387 subglottic, postintubation croup and, 631, 632 Edinger-Westphal nucleus, in total spinal anesthesia, 248 Edrophonium, atropine and, 30 in myasthenia gravis, 485 Effervescence, air emboli and, 673 EHNA, 22t Elastance, intracranial, 701f Elastase, in pancreatitis, 473 Elbow flexion, cubital tunnel pressure and, 883 Elderly. See also Age. clonidine withdrawal in, 95 fat embolism syndrome and, 860 H1-blocker effects and, 93 hypernatremia in, 433 thermal injury from warming devices in, 551 unanticipated hospital admission for, 894 vitamin B12 deficiency in, 70 Electric current, AC outlet frequency vs. radiofrequency, 558 in operating room equipment, 560 grounding for, 561 in surgical diathermy, 556-557, 557f, 558, 559 in tissue, 560 safety issues with, 560-561 Electric shock, 560-561 rapid fluid and blood delivery system use and, 553, 554 Electrical burns, 504 Electrocardiography, α2-agonist–induced changes in, 94-95 after subarachnoid hemorrhage, 722-723 after succinylcholine use in patients with hyperkalemia, 86 digitalis-induced changes in, 24-25, 25t in atrioventricular heart block, 41, 41f in bradycardia, 331, 332, 332f, 333, 333f in carotid endarterectomy, 382 in class IV antiarrhythmic drug toxicity, 48 in cor pulmonale, 667 in hyperkalemia, 54, 54f, 462, 463t in hypertrophic cardiomyopathy, 667 in hypokalemia, 54, 54f, 54t in long QT syndrome, 44 in muscular dystrophy, 481 in myocardial ischemia and infarction, 309 in perioperative tachyarrhythmias, 319, 320t in postanesthesia care unit, 899, 902 in venous air embolism, 704 in Wolff-Parkinson-White syndrome, 324f, 325 perioperative proarrhythmias and, 45 tricyclic antidepressant–induced changes in, 107 Electrocautery, alternatives to and precautions with, 404, 405 complications with, 556-559 electromagnetic interference with, 404 in surgical diathermy, 557, 557f intra-aortic balloon pump placement and, 410 Electroconvulsive therapy, anesthesia for, 903-905 contraindications to, 903t physiologic effects of, 904, 904t Electrocution, in surgical diathermy, 558 Electroencephalographic burst suppression, 718, 735 Electroencephalography, awareness under anesthesia and, 940 for detection of cerebral ischemia, 381

965

Electrolyte abnormalities, delayed emergence and, 886 herb- and nutraceutical-induced, 153t, 154t in acid-base disorders, 439 in burn injuries, 505 in diabetic ketoacidosis, 418 in traumatic brain injury, NSAID action and, 274-275 postoperative hyponatremia and, 431 Electromagnetic interference, in surgical diathermy, 558, 559 pacemaker and cardioverter-defibrillator malfunction and, 403-404, 404f, 558 precautions with, 405 sources of in hospitals, 404 Electromyography, Lambert-Eaton myasthenic syndrome and, 485 Electrophysiologic studies, of nerve injuries, 337 in obstetric procedures, 793 Electrosurgical unit, precautions with, 564t Embolism, 361-364 after carotid endarterectomy, 381 air. See Air embolism. amniotic fluid, in pregnancy, 786, 787, 787t, 788 fat. See Fat embolism syndrome. gas, massive, in cardiopulmonary bypass, 302-303, 302f in laparoscopic surgery, 832, 834 in pregnancy, 786-788 methylmethacrylate, 865-866 pulmonary. See Pulmonary embolism. thrombotic sources of, after orthopedic surgery, 862-864. See also Thromboembolism. venous air. See Air embolism, venous. Embolization procedures, endovascular, 912-914 normal perfusion pressure breakthrough and, 726 tumor, in radical nephrectomy, 847 Emergence, blood pressure control in, for prevention of intracranial aneurysm rerupture, 718 delayed, 885-887 causes of, 885-886 hypothermia and, 420 in children, 627-630 algorithm for, 628f causes of, 627, 629, 629t differential diagnosis of, 629t management and prevention of, 629-630 management of, 885-886 prevention of, 887 risks of, 885 St. John’s wort and, 109 in children, agitation with, 685-686 in traumatic brain injury, 730 Emergencies, in incompetent patients, medical decision making by, 949 in patients with spinal cord injury, 739 in uncooperative or combative patients, 937 Emery-Dreifuss muscular dystrophy, 480 cardiac involvement in, 480-481 Emesis. See Nausea and vomiting. EMLA cream, methemoglobinemia and, 233 Enalaprilat, actions and side effects of, 4t for hypertension, 314 Encephalopathy, hepatic, 467 Endobronchial blockers, Arndt, in left-sided thoracotomy, 386

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Endobronchial tube, double-lumen, complications with, 368, 368t malposition of, 365-366, 365f, 366f, 367f, 368, 369f management of, 368-369, 369f placement of, 365, 365f suggested sizes of, 370 single-lumen, in one-lung ventilation, 368 Endocrine abnormalities, adrenal insufficiency and, 444 in systemic inflammatory response syndrome, 497, 498 new syndrome involving, 499 Endoscopic retrograde cholangiopancreatography, in acute pancreatitis, 475 Endothelial cell injury, in preeclampsia, 760 Endothelium-derived relaxing factor, secondary pulmonary hypertension and, 660 Endotracheal intubation. See Trachea, intubation of. Endotracheal tube, care of, for prevention of nosocomial pneumonia, 211, 212 damage from, 184 fiberoptic, 165-166, 168 fire risk with, 562, 564, 568, 569 in blind nasal intubation, 168, 168t in lighted stylet oral intubation, 168-169 in retrograde tracheal intubation, 170, 171t introducer for, 162 medications delivered by, in intraoperative cardiac arrest, 616 placement of, monitoring of, 576 removal of, 162, 164 securing of, in burn-injured patients, 507 “softened,” in fiberoptic nasal intubation, 166 Endovascular embolization, 912-914 End-stage renal disease, clinical abnormalities in, 463t dialysis for, 462 surgery and anesthesia in, 463t, 464t, 465 risks of, 463-464 End-tidal carbon dioxide, in bronchospasm, 189 in double-lumen tube malposition, 367 in laparoscopic surgery, 832-833 in venous air embolism, 674, 675, 705, 787 inspiratory and expiratory gas monitoring and, 576 intraoperative cardiac arrest and, 615 tourniquet release and, 868 Enflurane, hepatic toxicity and, 66 in Parkinson’s disease, 491t, 492 neurophysiologic effects of, 729t renal toxicity with, 67 Enoxaparin, for prevention of deep venous thrombosis, 863, 868 for prevention of vasospasm, 722 peripheral nerve block and, 270 Enoximone, action and uses of, 22, 22t Entacapone, in Parkinson’s disease, 490, 491, 491t Enzyme(s), 110 dietary substances and, 151 hepatic cytochrome, calcium channel antagonists and, 51 in porphyrin synthesis, 74, 74f proteins with, in muscular dystrophy, 480 Enzyme-inducing drug(s), porphyrias triggered by, 470, 471, 471t, 472 Enzyme-linked antibodies, for substance abuse testing, 123 Enzyme-linked immunosorbent assay (ELISA), for detection of heparin-platelet 4 antigens, 292 for drug dependence detection, 119

Ephedra, common uses of/problems with, 155t Ephedrine, for α2-agonist–induced hypotension, 95 for anaphylactic or anaphylactoid reactions, 100 for bradycardia, 15 for emesis, 136 maternal, in open fetal surgery, 768 monoamine oxidase inhibitors and, 105 side effects of, 8t Epidural abscess, radiographic diagnosis of, 240, 240f signs of, 239, 240 vs. spinal hematoma, 235t with central neuraxial blockade, 239-241 Epidural analgesia, in nonobstetric surgery in pregnancy, 800 in opioid-tolerant patients, 280 in preeclamptic patients, for labor and vaginal delivery, 761 Epidural anesthesia, deep venous thrombosis prophylaxis regimens with, 864 for bronchospasm prevention in asthmatics, 191 for emergent cesarean delivery, 771, 772 local anesthetic neurotoxicity with, 229 lumbar, in autonomic hyperreflexia, 478 neurologic complications with, in obstetric patients, 789, 793 postoperative pain control and, 897 test doses for, 243 thoracic, for early extubation anesthesia, 358-359 Epidural blood patch, for post–dural puncture headache, 225, 225f in HIV-infected patients, 449 prophylactic use of, 226 Epidural space, anatomy of, 242 injection into, for opioid administration, 261 for post–dural puncture headache, 225 unintended intrathecal, 242-243 unintended subdural, 244-247 local anesthetic spread in, after psoas compartment block, 258 Epiglottis, in infants, 603, 604f, 637 Epiglottitis, in children, postobstruction pulmonary edema and, 216 Epilepsy, 200-201. See also Seizure(s). Epinephrine, for acute laryngeal edema, 185 for anaphylactic or anaphylactoid reactions, 99, 652 for intraoperative angioedema and urticaria, 427 for intraoperative bradycardia in heart transplant patients, 15-16 for postintubation croup, 632 for tricyclic antidepressant toxicity, 107 for venous air embolism, 707 in heart disease, deleterious effects of, 14 in open fetal surgery, 768 inotropic effects of, 11, 12t side effects of, 8, 8t test dose of, 233, 233t with lidocaine spinal anesthesia, neurotoxicity and, 229 with milrinone, for low cardiac output after cardiopulmonary bypass, 12 Epipodophyllotoxins, 110 Epirubicin, 110, 116 Epithelium, alveolar, in acute respiratory distress syndrome, 349 in postobstruction pulmonary edema, 213

Epoprostenol, actions and side effects of, 4t applications of, 6 for pulmonary vasodilatation without systemic vasodilatation, 6 Eptifibatide, in cardiac surgery patients, 359 Equipment and supplies, anesthetic, 515-545 cost issues with, 931 electrical, 561 for difficult airway in children, 605, 605f for oxygen administration, hypoxemia and, 639 in electrophysiology suite, 916 in interventional radiology suite, 912, 912f, 913, 914 in magnetic resonance imaging suite, 918-919, 919t in radiation oncology suite, 909-910 Erectile dysfunction, 21 Ergonovine, for uterine atony, 781 Ergot alkaloids, for uterine atony, 781 Erythromycin, complications of, 102t Erythropoietin, for bleeding in uremic patients, 464 supplemental, in autologous blood predonation, 296, 297 Esmolol, for hyperthyroidism or thyroid storm, 456 for tachyarrhythmias, heart block and, 40 in electroconvulsive therapy, 904 Esophageal sphincter, lower, pulmonary aspiration and, 186 Estrogen, conjugated, for bleeding in uremic patients, 464 Etanercept, 502t Ethanol. See Alcohol. Ethical considerations, blood transfusions and, 949 do-not-resuscitate orders and, 946, 947 patient confidentiality and, 944, 945 Ethopropazine, in Parkinson’s disease, 491, 491t Ethyl chloride spray, for detumescence of penile erection, 841 Etodolac, action of, 274, 274f, 275 Etomidate, adrenal insufficiency and, 442 dose of, 80t for external cardioversion, 907 heart block and, 40 hemodynamic, respiratory and other effects of, 81, 81t in electroconvulsive therapy, 904 intraocular pressure and, 746 mechanism of action of, 80 neurophysiologic effects of, 729t pharmacokinetic properties of, 80, 80t selection of, 81t, 82 Euthyroid sick syndrome, thyroid function studies in, 452t Euvolemia, for prevention of intracranial aneurysm rerupture, 716, 717t Evaporation, of heat energy, 663 Ex utero intrapartum therapy (EXIT), 766-769 indications for, 607, 608t, 609 management of, 768-769 procedures used in, 607-610 risks and benefits of, 609 timing and reason for, 766, 766t Excitation-contraction coupling, L-type calcium channel function and, 50 EXIT (ex utero intrapartum therapy), 607-610, 766-769 Explosions, in operating room, 562-566 causes of, 562, 562t

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Extracellular matrix proteins, in muscular dystrophy, 480 Extracorporeal circulation, in management of pulmonary hypertension in children, 661 in thoracic aortic aneurysm repair, 386, 388 Extracorporeal membrane oxygenation, 407, 408 Extracorporeal shock-wave lithotripsy. See Lithotripsy. Extraocular muscles, oculocardiac reflex and, 695, 696t Extrapyramidal effects, antiemetic drug action and, 136 Extremities. See also Leg(s). lower, after celiac plexus block, 254 tourniquets of, 867-870 Extubation, difficult, 162, 164, 164t early tracheal, after cardiac surgery, 356-360 in cervical spine injuries, 180 in laryngeal edema, 185 in morbidly obese, 813 in traumatic brain injury in children, 730 pulmonary aspiration prevention and, 643, 784 tracheal, postobstruction pulmonary edema and, 216 Eye(s), anticholinergic effects on, 30 injuries of, anesthesia-related, 692 corneal, 741-744 open globe, 745-746 penetrating, in children, 694-695 in retrobulbar block, 748 postoperative, 692-697 in spinal surgery, 693-694, 856, 857, 873 visual loss with, 693-694, 856, 857, 873. See also Blindness. protection of, during anesthesia, 693, 743-744, 744t in laser surgery, 568 retrobulbar block in, 747-749, 748f Eye pads, 744 Eyeball, cross-section of, 743f F Face, edema of, histamine release and, 101 flushing of, adenosine and, 32 Facemask, for laser plume protection, 568 Facemask ventilation, difficult, 159 difficult extubation with, 162, 164 patient factors with, 159, 161t signs of, 161t Facial nerve, block of, with retrobulbar block, 747 lesions of, in posterior fossa surgery, 709 monitoring of, 709 Facilities, cost issues with, 931 Factor V Leiden mutation, 362, 363 Fagan nomogram, 142, 142f Famotidine, 93 for pulmonary aspiration, 188, 643t Fasting, guidelines for, for pulmonary aspiration in children, 642, 643t for sedation of children, 621t in children, 621t, 642, 643t, 657 in patients in labor, 784 pulmonary aspiration prevention and, 642, 643t, 784 Fastrack, 605 Fasudil, in prevention of vasospasm, 722 Fat, brown, in hypothermia, 664 Fat embolism, postoperative delirium and, 888 Fat embolism syndrome, 859-861, 859t, 860t Fat-soluble drugs, delayed emergence and, 886 Fatiguability, in myasthenic disorders, 484

Fatty liver, alcohol-induced, fat embolism syndrome and, 860 Fecal impaction, autonomic dysreflexia and, 853, 854 Femoral artery, cannulation of, retroperitoneal hemorrhage and, 257 Femoral cutaneous nerve, lateral, 790, 792t Femoral nerve, block of, for outpatient knee surgery, 267t injuries of in childbirth, 790, 792t Fenoldopam, actions and side effects of, 5t for hypertension, 314 for prevention of acute renal failure, 345 Fentanyl, anesthesiologists’ dependence on, 120 equianalgesic conversion doses of, 279t fetal, in ex utero intrapartum therapy, 769 in open fetal surgery, 768 for early extubation anesthesia, 358 heart block and, 40 infusion duration with, 546-547, 546f, 547f intrathecal, 72, 261, 262 manual infusion dosing regimens for, 549t monoamine oxidase inhibitors with, 105 muscle rigidity induced by, airway difficulties with, 174-175 neuraxial use of, 261, 262 transmucosal, in children, 684 Fetal distress, 770-773, 773t Fetal heart rate monitoring, 770, 771f cardiopulmonary bypass in pregnant patients and, 803 electronic, 770, 772f in emergent cesarean delivery, 771 in nonobstetric surgery in pregnancy, 800 Fetal surgery, anesthetic complications in, 607-610 intrauterine, management and prevention of complications in, 768-769 risks with, 766-768 in EXIT procedure, 607-608 open, indications for, 607, 607t management of, 768 monitoring for, 768 types of, 766, 766t Fetal teratogenesis, anesthetic drugs and, 799 maternal cardiac disease and, 802 Fetoscopic surgery, indications for, 607, 607t management of, 769 timing and reason for, 766, 766t Fetus, circulation in, hypoxemia and, 639 heart rate of. See also Fetal heart rate monitoring. neuraxial opioid use and, 263 hemoglobin level in, 196, 196f hypoxemia and, 639 indomethacin effects on, for tocolytic therapy, 765 Fever, central venous catheter–related, 583, 584, 585f in transfusion reaction, 204 Feverfew, common uses and problems with, 155t Fiberoptic bronchoscopy, for compressed tracheobronchial tree, 373f for difficult airway, 165-166, 167f, 167t for one-lung ventilation, 369-370 for repositioning double-lumen endobronchial tube, 368 for sarcoidosis, 459 in children, 605 Fiberoptic cables, precautions with, 564t Fiberoptic-compatible oral airway, 166, 167f Fibers, Purkinje, in bradycardia, 332

967

Fibrin clot, for post–dural puncture headache, 225, 225f Fibrin S, in coagulation cascade, 361 Fibrinogen, for disseminated intravascular coagulopathy in pregnancy, 777 Fibrin-stabilizing factor, in coagulation cascade, 361 Fibronectin, in preeclampsia, 760 Fingers, ischemia of, arterial cannulation and, 579 Fire(s), carbon dioxide absorbents and, 535 in operating room, 562-566 causes of, 562, 562t laser-induced, 568, 569, 750, 751 surgical, definition of, 562 operating room staff training and, 563 surgical diathermy and, 558, 559 Fistula, bronchopleural, postpneumonectomy, 378 Flail chest, in trauma victims, 828 Flecainide, dose of, 39t for atrioventricular reciprocating tachycardia in WPW syndrome, 326 Flowmeter(s), calibration of, 518, 520 design of, 518, 519f electronic, 518 malfunction of, 518-520, 519f FDA checklist for, 518, 520 Flow-volume loop, with intrathoracic mass, 374f Fludrocortisone, glucocorticoid and mineralocorticoid potencies of, 132t in adrenal insufficiency, 444 Fluid(s), acid-base balance and, 440 electrolyte abnormalities and, in traumatic brain injury, 734 NSAID action and, 274-275 extracellular, angiotensin II effects on, 17 hydrogen ion concentration of, 436 in postobstruction pulmonary edema, 635 intravenous, anaphylactic or anaphylactoid reactions and, 99t in radical urologic surgery, 847 in traumatic brain injury, 734, 735t intracranial hypertension and, 702 management of, esophageal Doppler monitoring for, 64-65 in cervical spine injuries, 179 in diabetic ketoacidosis, 417-418 in revascularization for peripheral vascular disease, 397 in traumatic brain injury in children, 730 perioperative, 62-65, 64t oral, in labor, pulmonary aspiration prevention and, 784 rapid delivery devices for, 553-554 replacement. See also Fluid resuscitation. for perioperative anaphylaxis to latex, 652 in children, calculation of, 658t in cirrhosis, 468 in hypernatremia, calculation of, 434 in spinal cord injury, 873 warming of, for hypothermia prevention, 665 Fluid equilibrium, of lung, in pulmonary edema, 213, 214f Fluid resuscitation. See also Fluid(s), replacement. acid-base balance and, 440 excess, complications of, 62 recognition of, 63 in burn-injured patients, 505, 506, 506t, 507 in diabetic ketoacidosis, 417-418 in hypernatremia, 434 in intraoperative angioedema and urticaria, 427

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Index

Fluid resuscitation. (Continued) in systemic inflammatory response syndrome, 498 in traumatic brain injury, 734, 735t insufficient, complications of, 62 recognition of, 62-63 Flumazenil, 128-130 clinical parameters of, 128, 128t delayed emergence from anesthesia and, 887 in children, 629, 630t dose of, 128, 129t side effects of, 128, 130 Fluoride, abnormal pseudocholinesterase variants and, 86t, 87 Fluoxetine (Prozac), 108 FMS2000 rapid fluid and blood delivery system, 553, 554f Folate, deficiency of, nitrous oxide and, 69, 71 Fondaparinux, 364 for prevention of deep venous thrombosis, 863 Food, aspirated, 753 Food and Drug Administration, black box warning on droperidol and, 37 checklist of, for anesthesia breathing circuit operation, 529, 530t for anesthesia machine operation, 518, 520, 523 dietary supplements and, 150 Manufacturer and User-Friendly Device Experience, 550, 551 Forced-air blanket, for hypothermia prevention, 421, 422 Forearm, skin ischemia of, 579, 580 Foreign body(ies), aspiration of, 753-755 diagnosis of, 753 management and prevention of, 754-755 Fractures, in trauma victims, 828 long bone and pelvic, fat embolism syndrome and, 860 Framingham Heart Study, 147 Fraudulent concealment, by anesthesiologist, 942, 943 Free fatty acids, fat embolism syndrome and, 859 Free oxygen radicals, anthracycline antibiotic action and, 116 Fresh frozen plasma, for coagulation factor deficiencies, 308 transfusion with, 679t Fruit allergy, in children, latex allergy and, 651 Fukutin-related protein, in muscular dystrophies, 480 Fulminant hepatic necrosis, halothane and, 66 management and prevention of, 68 recognition of, 67 risk factors for, 67 Furosemide, for acute renal failure, 345 for brain tissue water, 594 for intracranial pressure lowering, 702, 702t for TURP syndrome, 844 G G proteins, muscarinic receptor interaction with, 28 Gag reflex, in poisoning cases, 508 Gallamine, dose, clearance, and side effects of, 624t Gallstones, laparoscopic surgery for, 834 Gamma knife radiosurgery, normal perfusion pressure breakthrough and, 726 Garlic, common uses and problems with, 155t

Gas(es), inspiratory and expiratory, monitoring of, 574-576, 575t waste anesthetic, scavenging systems for, 540-542 Gas chromatography, for drug dependence detection, 119 for substance abuse testing, with mass spectroscopy, 123 Gas delivery, equipment failure with, anesthesiarelated complications with, 529 Gas embolism. See also Air embolism. massive, in cardiopulmonary bypass, 302-303, 302f in laparoscopic surgery, 832, 834 Gas exchange, alveolar-capillary, diffusion limitation of, 195, 198t in hypoxemia, 193, 194f, 194t, 195, 195f pulmonary, pulmonary aspiration and, 187 Gastric acid, 186, 641, 642, 783, 784 Gastric contents, aspiration of, 186-188 in morbidly obese, 811t, 812 in parturients, 782-785 risk factors for, 186-187, 187t Gastric emptying, in poisoning cases, 509, 510t in pregnancy, 782 Gastric lavage, 509, 511t Gastric tube, for prevention of pulmonary aspiration, 188 Gastric ulcer disease, antihistamines for, 93 Gastroesophageal reflux, in morbidly obese, 811t, 812 pulmonary aspiration and, 186, 187 in infants, 641 Gastrointestinal complications, of cirrhosis, 467 postpneumonectomy, 379 Gastrointestinal effects, of anticholinergics, 30 of NSAIDs, 273, 275, 276 Gastrointestinal obstruction, pulmonary aspiration and, 186, 188 Gastroprokinetics, for pulmonary aspiration, 188 GE Healthcare proportioning systems, 521, 522, 523 Gene(s), dystrophin, 479, 480 encoding glycosyltransferases, in muscular dystrophies, 480 lamin A/C, 480 mutations of, in malignant hyperthermia, 655, 656 in torsades de pointes, 327 prothrombin, 362 phosphodiesterase, 22 sarcoglycan, 480 titan, 480 General anesthesia, anaphylactic or anaphylactoid reactions to, 99 antepartum bleeding and, 778 autonomic hyperreflexia and, 478 bradyarrhythmias and, 333 for anterior mediastinal masses, cardiopulmonary compromise and, 670, 671, 672 for cesarean delivery, emergent, 771, 772 in preeclamptic patients, 761 for EXIT procedure, 609 for nonobstetric surgery in pregnant patients, 800 for orthopedic outpatient surgery, 265-266 for radiation oncologic procedures, in children, 910 for status epilepticus, 201 for surgery in Alzheimer’s disease patients, 494 heat redistribution in, 664, 664f total intravenous, in muscular dystrophy, 482

Genetic factors, in renal injury, 344 in torsades de pointes, 327 Genetic testing, for malignant hyperthermia, 655 Gertie Marx needle, 224f Gestational age, postoperative apnea and, 611, 612f Gestational hypertension, 759 Ginger, common uses of/problems with, 155t Ginkgo, common uses of/problems with, 155t Ginseng, common uses of/problems with, 155t Glascow Coma Scale, 720 in assessing brain injury, 732, 732t in revised trauma score, 827, 828t in traumatic brain injury in children, 728, 729 Glaucoma, anticholinergics and, 30 Gleevec (imatinib mesylate), mechanisms, uses, and toxicities of, 113t Globe, optic, injury of, 745-746, 748 Glomerular filtration rate, in acute renal failure, 342, 343-344 Glucocorticoid deficiency, in adrenal insufficiency, 443 Gluconeogenesis, systemic inflammatory response syndrome and, 497 Glucose, and insulin, for treatment of hyperkalemia, 57 for acute porphyria, 76 in lidocaine spinal anesthesia, neurotoxicity and, 229 Glucose blood levels, brain, in carotid endarterectomy, 382 control of, for infection control, 499, 502 in acute respiratory distress syndrome, 349 in adrenalectomy for Cushing’s syndrome, 826 definitions of, 415, 657 of herbs and nutraceuticals, 154t plasma, in perioperative hyperglycemia, 417, 418 normal, 415, 415t Glucose tolerance, 415 impaired, in morbidly obese, 811t, 812 in systemic inflammatory response syndrome, 497 Glycolysis, aerobic, in systemic inflammatory response syndrome, 497 Glycoprotein IIb/IIIa receptor antagonists, in cardiac surgery patients, 359 in heparin-induced thrombocytopenia, 293 spinal hematoma and, 236-237, 237t Glycopyrrolate. See also Anticholinergic agents. action of, 28 effects of, 28-29, 29t for pulmonary aspiration prevention, 643t in electroconvulsive therapy, 904 neostigmine and, 30 Glycosyltransferases, in muscular dystrophies, 480 Goggles, for eye protection in laser surgery, 568 Goiter, 454, 455f surgical removal of, 817, 817t Goldenseal, common uses of/problems with, 156t Gott shunt(s), in left-sided thoracotomy, 386 Grafting, devices for, in cardiopulmonary bypass, 341 in burn-injured patients, 506 Granisetron, for postoperative nausea and vomiting, 646t, 647 receptor site affinity of, 134t side effects of, 135t Granulomas, sarcoid, 457, 457f, 458, 458f

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Graves’ disease, prevention of, 820 signs and symptoms of, 817t surgery for, 817-819, 817t treatment of, 819 Grey Turner’s sign, in pancreatitis, 474 in retroperitoneal hemorrhage, 257, 258f Ground fault circuit interrupters, 561 Guanfacine, rebound hypertension and, 95 Guanylate cyclase, in erectile dysfunction, 21 phosphodiesterase-5 inhibitors and, 20 Gum-elastic bougie, blind placement of, 162 H H1-receptor antagonists, adverse reactions to, 92-93, 92t H2-receptor antagonists, adverse reactions to, 92t, 93 delayed emergence and, 886 for nosocomial pneumonia prevention, 211 for pulmonary aspiration prevention, 188, 643t, 784 HAART (highly active antiretroviral therapy), for HIV infection, 447, 448t, 450 Hair, patient, fire hazard with, 563, 565t Haloperidol, for emergence agitation in children, 686 for postoperative delirium, 889 Halothane, hazards of, 68 hepatic toxicity and, 66 in Parkinson’s disease, 491t, 492 neurophysiologic effects of, 729t renal failure and, 66-67 Halothane hepatitis, 66 postoperative jaundice and, 807 Hand, ischemia of, arterial cannulation and, 579 Handwashing, central venous catheter–related infection and, 584 immunocompromised patients and, 502 nosocomial pneumonia and, 211 Harmonic scalpel, 404, 405, 559 Hashimoto’s thyroiditis, 452 Head and neck, angioedema of, ACE inhibitors and, 17-18 surgery of, fire risk with, 562, 563 Head injury, 732-736. See also Traumatic brain injury. hyperventilation in, 702 intracranial pressure monitoring and, 591, 593 management of, 734-736, 735f open globe injury and, 745 prevention of, 736 pulmonary edema and, 215 Headache, in autonomic hyperreflexia, 477 in intracranial hypertension, 701 migraine, postpartum, 795-796, 798t post–dural puncture, clinical features of, 223 epidural blood patch for, in HIV-infected patients, 449 management and prevention of, 224-226, 225f postpartum, 797 with spinal anesthesia, 223-226 postpartum, 795-798 classification of, 795t management of, 796, 798t migraine-type, 795-796, 798t secondary, 796-797, 798t tension-type, 796, 798t tension-type, postpartum, 796, 798t Health care workers, addiction in, 119, 120 blood-contaminated injuries of, 207, 208 cost containment issues and, 930 drug dependence in, nonopioid, 122-127 opioid, 119-121

Health care workers (Continued) latex reactions in, 217-219 postexposure prophylaxis for HIV in, 447 viral hepatitis transmission and, 468 Health Insurance Portability and Accountability Act, 146, 944 Heart. See also under Cardiac; Cardiovascular; Myocardial. compression of, by mediastinal mass, 374, 375 fetal. See also Fetal heart rate monitoring. in EXIT procedure, 608 in carotid endarterectomy, 382 tricyclic antidepressant effects on, 106 Heart block, atrioventricular. See Atrioventricular heart block. β-blockers for, 40-43 infranodal third degree, 40, 41, 41f intraoperative, risk factors for, 42t types of, 40 P waves in, 14 Heart disease. See also Cardiac disease. anticholinergic toxicity and, 30 in carcinoid syndrome, 814, 815 left ventricular, in abdominal aortic aneurysm repair, 390 in muscular dystrophy, 481 in postobstruction pulmonary edema, 635, 635f intra-aortic balloon pump and, 409 vasodilator drugs for, 3 valvular, ventricular assist device placement and, 411 Heart failure. See also Congestive heart failure. cardiac risk and, 147, 148t renin-angiotensin system antagonists for, 17 right-sided, compensatory, 3 in sarcoidosis, 460 pulmonary hypertension management with, 316, 317-318, 317t venous air embolism and, 704, 705 Heart massage, intraoperative cardiac arrest and, 616 Heart rate, α2-agonist–induced changes in, 94-95 fetal, fetal distress and, 770 monitoring of, 770, 771f cardiopulmonary bypass in pregnancy and, 803 electronic, 770, 772f in emergent cesarean delivery, 771 in nonobstetric surgery in pregnancy, 800 neuraxial opioid use and, 263 slow, chronotropic drugs for, 14-15 tricyclic antidepressant toxicity and, 106 Heart transplantation, chronotropic drugs for, 15-16 for pulmonary hypertension in children, 661 intraoperative bradycardia in, 16 Heart-lung transplantation, for pulmonary hypertension in children, 661 Heartmate left ventricular assist device, 411 Heat, from surgical diathermy, complications from, 558 Heat and moisture exchanger, 545 Heat loss, in anesthetized infants and children, mechanisms of, 663-664, 664f, 665 Heatsroke, malignant hyperthermia and, 655 Heimlich maneuver, 754 HELLP syndrome, 759, 760, 761 Hematin, for acute porphyria, 76 Hematocrit, in traumatic brain injury, 735 in treatment of subarachnoid hemorrhage, 721 postoperative visual loss and, 856

969

Hematologic complications, of cirrhosis, 467 Hematoma. See also Bleeding; Hemorrhage. after thyroid surgery, 818, 819, 820-821 endoneural, 286 in retrobulbar block, 748 intracranial pressure monitoring and, 594 neck, 879 peripheral nerve block and, 269, 270-272, 271t psoas compartment, hemorrhage after, 270 retroperitoneal, chronic anticoagulant therapy and, 257, 259 spinal, 235-238 differential diagnosis of, 235-236, 235t management of, 237 neuraxial blockade and, thromboembolism prophylaxis and, 864 prevention of, 237-238 risk of, with anticoagulants, 236-237 wound, after carotid endarterectomy, 381 in airway obstruction, 877-878, 879 Heme synthesis, 74, 74f disorders of, 470t metabolic pathways of, 470f porphyrias and, 470-472 Hemidiaphragmatic paresis, vs. pneumothorax, 251 Hemocytometer, postoperative bleeding and, 306 Hemodialysis, continuous venovenous, for acute renal failure, 345 for bleeding in uremic patients, 464 Hemodilution, 295-298. See also Bleeding; Hemorrhage. acute normovolemic, 295t, 296, 297 in spinal cord surgery, 874 minimum hemoglobin levels and, in anesthetized patients, 295t, 296, 297 postoperative bleeding and, 306 Hemodynamic stability/instability, in acute renal failure, 345 in acute respiratory distress syndrome, 350 in aortic occlusion, 390, 391t in electroconvulsive therapy, 904-905 in external cardioversion, 907 in postanesthesia care unit, 899-902 in posterior fossa surgery, 709, 710 in postobstruction pulmonary edema, 213, 214t in revascularization for peripheral vascular disease, 397 in thoracic aortic aneurysm repair, 386, 388 in trauma victims, 829 in traumatic brain injury in children, 730 Hemofiltration, inflammatory response after cardiopulmonary bypass and, 354 Hemoglobin, fetal, 196, 196f hypoxemia and, 639 in sepsis, 498 minimum levels of, 196 blood loss and, 295, 296, 297 structure-function relationship of, 195 Hemoglobinuria, in transfusion reaction, 204 Hemolysis, massive blood transfusion and, 680-681 nonimmune-mediated causes of, 203t of transfused blood, postoperative jaundice and, 806 Haemophilus influenzae type B, vaccination of children against, 216 Hemoptysis, pulmonary artery catheter–related, 589 Hemorrhage. See also Bleeding; Blood loss. antepartum, 774-778 assessment of, 776t characteristics of, 776t

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Page 970

Index

Hemorrhage, antepartum (Continued) management and prevention of, 777-778 recognition of, 775-776, 776t risks with, 776-777, 777t types of, 774-775, 775f in children, intraoperative cardiac arrest and, 615 in cirrhosis, 468 in radical urologic surgery, 846, 847f, 848, 849 in retrobulbar block, 748 in spinal surgery, 871, 873-874 in thoracic aortic aneurysm repair, 386 in transurethral surgery, 843 in trauma victims, 828, 829 intracerebral, headache with, 796 in children, delayed emergence and, 629 intracranial, normal perfusion pressure breakthrough and, 724, 726 massive, 828, 829 peripheral nerve block and, 269, 270-272, 271t postoperative, in tonsillectomy, 688, 689 postpartum, 779-781 pulmonary artery catheter–related, 589 retroperitoneal, lumbar sympathetic block and, 270 management and prevention of, 259-260, 259t recognition of, 257, 257t risk of, 258-259, 258t, 259f with psoas compartment block, 257-260 risk of, after psoas compartment block, 258 subarachnoid, complications with, 714t headache with, 796 intracranial aneurysm rupture and, 714-718 recurrence of, 715 vasospasm and, 717, 719-723 Hemorrhagic shock, in retroperitoneal hemorrhage, 257 Hemostatic function, in children, laboratory testing for, 679, 679t in surgery, 362, 363t Hemothorax, in trauma victims, massive, 828 Heparin, in cardiac surgery, 291-293, 306 in cardiopulmonary bypass, 292, 293 clotted oxygenator and, 304 in pregnant patients, 803 resistance to, 291, 292 reversal of, 293 in central neuraxial techniques, ASRAPM guidelines for, 271t in joint replacement surgery, 864 in fat embolism syndrome, 861 in hypercoagulable disorders, 364 in spinal hematoma, 236, 237, 237t low-dose subcutaneous with neuraxial block, 236, 237, 237t low-molecular-weight, for prevention of deep venous thrombosis, 863 for prevention of vasospasm, 722 in cardiopulmonary bypass, 293 in central neuraxial techniques, ASRAPM guidelines for, 271t in joint replacement surgery, 864 off-label applications of, 236, 237, 237t peripheral nerve block and, postoperative use of, 266 with Coumadin, 270 postoperative bleeding and, after cardiac surgery, 306 unfractionated, 271t, 291 Heparin rebound, after cardiac surgery, 306 Heparin-coated bypass circuits, inflammatory response after cardiopulmonary bypass and, 354 Heparin-induced platelet aggregation assay, 292

Heparin-induced thrombocytopenia, 306 in cardiopulmonary bypass, 292-293 types of, 291-292 Heparin-protamine titration, in cardiopulmonary bypass, 291 Hepatic dysfunction, in systemic inflammatory response syndrome, 497 postoperative, 805-809 causes of, 806-808, 806t diagnosis of, 805-806, 805t management and prevention of, 809 risk assessment in, 808-809 Hepatic insufficiency, 466-469 management and prevention of, 468 recognition of, 466-467 risk assessment in, 467-468, 467t Hepatic metabolism, delayed emergence and, 886 Hepatic toxicity, halothane-induced, 66, 807 in children, 67 in fulminant hepatic necrosis, 66-68 management and prevention of, 68 of herbs and nutraceuticals, 154t Hepatitis, diagnosis of, 807 halothane, 66 postoperative jaundice and, 807 recognition of, 67 ischemic, intraoperative, 807 postoperative jaundice and, 807, 808 post-transfusion, 207-208, 807-808 viral, in cirrhosis, 468 Hepatitis B, post-transfusion, 207, 208 vaccination against, 208, 468 Hepatitis C, chronic, interferons for, 501 postexposure management for, 208 post-transfusion, 207, 208, 807-808 Hepatocytes, in cirrhosis, 466 Hepatopulmonary syndrome, 467 Herbal therapy and alternative medicine, 150-157 Herbs, adverse effects of, 150, 151 central neuraxial techniques with, ASRAPM guidelines for, 271t common uses of, 155t, 156t delayed emergence and, 886 most frequently used, 151 perioperative management of, 151, 154, 157t resources for further information on, 157t risk assessment for, 151 side effects of, 151, 152t-154t Hereditary angioneurotic edema, 426 treatment of, 427-428 Hernia, repair of, urinary retention and, 837 Herniation, brain, intracranial pressure and, 702 cardiac, postpneumonectomy, 379 Highly active antiretroviral therapy (HAART), for HIV infection, 447, 448t, 450 Hilar lymphadenopathy, in sarcoidosis, 459f Hip fracture, deep venous thrombosis after, 863 Hip replacement, analgesia after, psoas compartment block for, 258 deep venous thrombosis prophylaxis regimens in, 863 methylmethacrylate emboli in, 865-866 postoperative visual loss and, 855 thromboembolism and, 364 Hirudin, for heparin-induced thrombocytopenia in cardiopulmonary bypass, 292 Histamine(s), for anaphylactic or anaphylactoid reactions, 99, 100 release of, in anaphylaxis, 98 signs of, 101 vancomycin-induced, 101, 102, 103 with nondepolarizing muscle relaxants, 90, 623-624, 625 Histiocytic hypoxia, 197

HIV infection, and AIDS, 446-450 characteristics of, 446 management of, 447-450 neuropathy with, postpartum, 793 postexposure prophylaxis for, 208, 447 post-transfusion, 207-208 prevention of, 208, 447, 450 risks with, 446, 447, 501 Hodgkin’s lymphoma, doxorubicin for, 110 Homeopathy, 150 Homocysteine, nitrous oxide and, 69, 70 Hormones, 110 abnormalities of, in systemic inflammatory response syndrome, 497 anaphylactic or anaphylactoid reactions associated with, 99t Hospital(s), admission and readmission to, unanticipated, 893-895, 894t risk management systems in, 943 Host defense mechanisms, 500t Hot wire cautery, precautions with, 564t Human immunodeficiency virus (HIV). See HIV infection. Human recombinant B-type natriuretic peptide, for prevention of acute renal failure, 345 Humidifiers, 543-545 hot-water, problems with, 544t Hydralazine, actions and side effects of, 5t for hypertension, 314 in pregnancy, 760-761 Hydration, preoperative, risks of volatile anesthetics and, 67 venous air embolism prevention and, 707 Hydrocephalus, after subarachnoid hemorrhage, 722 intracranial aneurysm rerupture and, 714 obstructive, posterior fossa surgery and, 708, 709, 710 Hydrocodone, equianalgesic conversion doses of, 279t Hydrocortisone. See also Cortisol. for myxedema, 453 glucocorticoid and mineralocorticoid potencies of, 132t in adrenal insufficiency, 444, 445 in septic shock, supraphysiologic doses of, 9 in subarachnoid hemorrhage, 721 supplemental dose of, 132, 133 Hydrogen ion concentration, in arterial blood, 436 Hydrogen-potassium pump, 93 Hydromorphone, epidural placement of, 262 equianalgesic conversion doses of, 279t neuraxial use of, 261, 262 Hydrophilic drugs, neuraxial opioid use and, 262 Hydrostatic pulmonary edema, 348 γ-Hydroxybutyrate, common uses of/problems with, 155t 5-Hydroxyindoleacetic acid, 814 5-Hydroxytryptamine reuptake transport, 107 5-Hydroxytryptamine3 receptor antagonists, for nausea and vomiting, 646t Hydroxyurea, 110 Hyperaldosteronism, 823 Hypercapnia, in acid-base disorders, 439 in laparoscopic surgery, 832, 833, 834 in traumatic brain injury, 733 tourniquet release and, 868 Hypercarbia. See also Hypoventilation. carbon dioxide absorber problems and, 534-536, 535f definition of, 877 delayed emergence and, 885, 886 in children, 627 effects of, 879t

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Page 971

Index

Hypercarbia (Continued) in respiratory insufficiency, 878-879 management of, 879-880 Hypercoagulable disorders. See also Thromboembolism; Thrombosis. acquired, 362-363, 362t risk of, 363-364 catecholamine-induced, 8, 9 classification of, 361, 362t inherited, 362, 362t risk of, 363 intravascular coagulation and, 361 management of, 364 postoperative, in revascularization for peripheral vascular disease, 394 prevention of complications with, 364 Hyperdynamic therapy, for cerebral vasospasm, 721, 723 Hyperemia, cerebral, normal perfusion pressure breakthrough and, 727 Hyperforin, actions of, 109 Hyperglycemia, definition of, 415, 657 delayed emergence and, 886 diabetic ketoacidosis and, 415-418 in carotid endarterectomy, 382 in children, 657-658 in trauma, 827 in traumatic brain injury, 734, 735 perioperative, 416-417, 416t recognition of, 415-416 systemic inflammatory response syndrome and, 497 treatment of, 735 unrecognized, in children, 658 Hyperglycemia stress syndrome, 415 Hyperhomocysteinemia, 363 Hypericin, in St. John’s wort, 109 Hypericum perforatum, 108 Hyperkalemia, 53-58 bradyarrhythmias due to, 334 causes of, 55t definition of, 53-54 in cervical spine injuries, 179 in children, intraoperative cardiac arrest and, 615 succinylcholine use and, 624, 625, 626f with massive blood transfusion, 680 in end-stage renal disease, 462, 463t, 464, 464t NSAID action and, 275 prevention of, 57-58 recognition of, 54, 54f risks associated with, 55, 56 succinylcholine use and, 85, 85t, 86, 87 in children, 624, 625, 626f treatment of, 57 Hypermagnesemia, adverse effects of, 60, 60t bradyarrhythmias due to, 334 incidence of, 60 management and prevention of, 61 recognition of, 60, 60t Hypernatremia, 432-435 causes of, 433, 434t management and prevention of, 434-435, 434t recognition of, 433 risks of, 433, 434t Hyperpigmentation, in adrenal insufficiency, 442 Hyperpyrexia, anticholinergics and, 30, 31 Hyperreflexia, autonomic, 477-478, 477t, 853-854 causes of, 853, 853t manifestations of, 853t

Hypersensitive carotid sinus syncope, pacing for, 402 Hypersensitivity reactions, antihistamines for, 92 delayed, to latex, 218, 218t, 651 Hypertension, α2-adrenoreceptor agonists for, 94-96 calcium channel blockers and, 52, 314, 824-826 for treatment of subarachnoid hemorrhage, 721 gestational, 759 hemodynamic instability and, 899t, 900, 900t, 901 hypothermia and, 420 in abdominal aortic aneurysm repair, 390, 391t in autonomic hyperreflexia/dysreflexia, 477, 478, 853, 854 in brain injury assessment, 733 in carcinoid syndrome, 815, 816 in postanesthesia care unit, 901 in preeclampsia, 760 in pregnancy, 759-762, 759t treatment for, 760-761 in thoracic aortic aneurysm repair, 388 intracranial, 701-703 in children, after traumatic injury, 729 delayed emergence and, 629 intracranial pressure monitoring and, 591, 593, 594 management and prevention of, 702-703 postpartum headache with, 797 risk factors for, 701-702 signs and symptoms of, 701 perioperative, 313-314 definition of, 313 management and prevention of, 20, 313-314 recognition of, 313 risk factors for, 313 portopulmonary, in hepatopulmonary syndrome, 467 pulmonary. See Pulmonary hypertension. rebound, after clonidine withdrawal, 94, 95 treatment of, 95, 96 renin-angiotensin system antagonists for, 17, 18 secondary, adrenal disease and, 822 tourniquet-induced, 868 vasodilators for, 313-314 Hypertensive crisis, adrenal disease and, 822 in autonomic hyperreflexia/dysreflexia, 477, 854 pheochromocytoma and, 823, 824, 824f preoperative management of, 824-825 Hyperthermia, 423-424 adverse effects of, 423-424 causes of, 423, 424t definition of, 423 delayed emergence and, 886 humidifier complications and, 544 malignant. See Malignant hyperthermia. management and prevention of, 424 patient warming devices and, 552 rapid fluid and blood delivery system use and, 553, 554 risk of, 423 Hyperthyroidism, 454-456 definitions of, 454 management and prevention of, 455-456 pathophysiology and causes of, 454-455 signs and symptoms of, 454, 455f, 817t surgery for, 817-819

971

Hyperthyroidism (Continued) thyroid function studies in, 452t, 455t treatment of, 819 true, 454 Hypertrophic cardiomyopathy, characteristics of, 667-668 management of, 669 Hyperventilation, acid-base balance and, 440 for oculocardiac reflex, 696 for traumatic brain injury, 735 intracranial aneurysm rerupture and, 716, 716t, 717 intracranial hypertension and, 594, 702, 702t Hyperviscosity syndrome, 363 Hypervolemia, for treatment of subarachnoid hemorrhage, 721 management of, 64 prevention of, 64-65 rapid fluid and blood delivery system use and, 553, 554 recognition of, 63 risk assessment of, 63 studies of, 63-64, 64t Hyphema, in retrobulbar block, 748 Hypnotic(s), in posterior fossa surgery, 709 Hypoalbuminemia, 438 Hypocalcemia, after thyroid surgery, 818, 819, 820, 821 with massive blood transfusion in children, 680 Hypodipsia, in hypernatremia, 433 Hypoglycemia, definition of, 657 delayed emergence and, 886 in children, 629, 657-658 delayed emergence and, 627 unrecognized, neurologic function and, 658 Hypokalemia, 53-58 causes of, 55 definition of, 53, 53f digitalis toxicity and, 26, 26t effects of, 54, 54t perioperative risks and management of, 56-57, 56t prevention of, 57 Hypomagnesemia, 60-61 hypokalemia with, 57 Hyponatremia, 429-432 causes of, 430t chronic, 432 definition of, 429 delayed emergence and, 886 diagnosis of, 429-430, 431f euvolemic, 430t, 431, 432 humidifier complications and, 544 hypervolemic, 430t, 431, 432 hypo-osmotic, 429, 430, 430t, 431, 432 hypovolemic, 430t, 431, 432 in adrenal insufficiency, 443 postoperative, 431 symptoms of, 429 Hypo-osmolality, hyponatremia with, 431 Hypoparathyroidism, after thyroid surgery, 818, 819, 820, 821 Hypophysial stalk, injury of, 713 Hypotension, α2-agonist–induced, 94, 95, 96 after cardiopulmonary bypass, 352, 353 inotropic drug use for, 11, 12 arterial, definition of, 7 in cardiopulmonary bypass, central neurologic injury and, 341 calcium channel antagonists in anesthesia and, 51 deliberate, after intracranial aneurysm rerupture, 716, 716t complication(s) of, management and prevention of, 857-858

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12:17 PM

Page 972

Index

Hypotension, complications of (Continued) recognition of, 855-856 visual loss as, 693, 855-858, 873 for blood conservation, 297-298 goals of, 855 in spinal surgery, 873-874 techniques of, 855 differential diagnosis of, after psoas compartment block, 257 hemodynamic instability and, 899t, 900, 900t, 901, 901f histamine release and, in children, 625 hypovolemia and, in traumatic brain injury, 733 in abdominal aortic aneurysm repair, 390-391, 391f, 392-393 in adrenal insufficiency, 442, 443 in carcinoid crisis, 814, 815 in laparoscopic surgery, 832, 834 in magnesium sulfate tocolytic therapy, 764 in postanesthesia care unit, 901, 901f in postoperative bleeding, 305 in radical urologic surgery, 847 in retroperitoneal hemorrhage, 257 in spinal cord injury, 739 in spinal surgery, 871, 873-874 in thoracic aortic aneurysm repair, 388 in unclamping of thoracic aorta, 386 intracranial aneurysm rerupture and, 716, 716t, 717-718 intraoperative, after treatment for hypertension, 20 causes of, unrelated to nitroglycerin and sildenafil, 21t management of, 22 ischemic optic neuropathy and, 693, 855-858, 873 ketamine use and, 78-79 local anesthetic–induced, 231, 233 nifedipine with, for tocolytic therapy, 764 normal perfusion pressure breakthrough and, 727 orthostatic, 254, 256 neurolytic celiac plexus block and, 254, 256 refractory, angiotensin II receptor antagonists and, 21 angiotensin-converting enzyme inhibitors and, 21 in RAS-blocked patients on induction of anesthesia, 17, 18 management of, 22 renin-angiotensin-system–antagonist therapy and, 18 succinylcholine use and, in children, 623 supine, hypovolemia and, 63 systemic, complications of, 3 in traumatic brain injury, 733-734, 734f with vasodilator therapy, 3 tourniquet inflation and, 868 treatment of, 7, 18, 22 tricyclic antidepressant toxicity and, 107 vancomycin-induced, 101, 102, 103 vasodilator use and, 5, 6 vasopressors for, 7 venous air embolism and, 704 Hypothalamic-pituitary-adrenal axis, 442, 443f, 444 adrenal insufficiency and, 131, 132 Hypothalamus, injury to, after subarachnoid hemorrhage, 723 regulation of core body temperature by, 663, 664f Hypothermia, 419-422 adverse effects of, 420, 421f, 421t, 665 bradyarrhythmias due to, 333-334

Hypothermia (Continued) causes of, 419t classification of, 419 delayed emergence and, 886 in burn-injured patients, 504, 506 in cardiopulmonary bypass, 341 in pregnant patients, 802, 803 in carotid endarterectomy, 382 in children, 663-665 with massive blood transfusion, 680 in general and regional anesthesia, 419, 420f, 423 risk of, 419-420 in revascularization for peripheral vascular disease, 397 in trauma victims, 730, 736, 830 intracranial aneurysm rerupture and, 716 intraoperative, in cardiopulmonary bypass in pregnant patients, 803 prevention of, 502 stages of, 420 management and prevention of, 420-422, 502, 550-552, 665 physiologic response to, 664, 664f postoperative bleeding and, after cardiac surgery, 306 protective role of, 420 rapid fluid and blood delivery system use and, 553, 554 warming systems for, 420, 550-552 Hypothyroidism, 451-453 bradyarrhythmias due to, 334 causes of, 452 definition of, 451 digitalis toxicity and, 26, 26t management and prevention of, 452-453 thyroid function studies in, 452t, 455t Hypotonic irrigants, in transurethral resection of prostate or bladder, 843, 843t, 844 Hypoventilation. See also Hypercarbia. hypoxemia and, 193 prevention of, 198t Hypovolemia, hypotension with, in traumatic brain injury, 733 in abdominal aortic aneurysm repair, 390, 391, 392 in acute renal failure, 342 in adrenal insufficiency, 444 in burn-injured patients, 505, 506 in psoas compartment block, 259 in trauma victims, 733, 829, 830 management of, 64 nonbarbiturate anesthetics and, 81, 83 prevention of, 64-65, 67 recognition of, 62-63 risk assessment of, 63 studies of, 63, 64t Hypovolemic shock, 347, 444 Hypoxemia, causes of, 193, 194f, 194t, 195f definition of, 877 digitalis toxicity and, 26, 26t effects of, 879t fetal, in fetal distress, 770 in acute respiratory distress syndrome, 347, 348 in children, 637-639 causes of, 637-639, 638t delayed emergence and, 627 management and prevention of, 639 in end-stage renal disease, 463 in morbidly obese, 813 in one-lung ventilation, 365, 368, 369, 370 in postobstruction pulmonary edema, 635 in respiratory insufficiency, 878 intraocular pressure and, 745

Hypoxemia (Continued) intraoperative, with pneumonectomy, 377 management of, 639, 879 maternal, in rapid-sequence induction, 767 prevention of, 198t, 639 pulmonary aspiration and, 642 recognition of, 197, 197t, 637 respiratory failure and, 347 vasodilator use and, 5 vs. hypoxia, 637 Hypoxia, anemic, 195-196, 195f, 196f categories of, 193 circulatory, 197 delayed emergence and, 885, 886 histiocytic, 197 in hepatopulmonary syndrome, 467 in postobstruction pulmonary edema, 213, 215f, 635, 635f, 636 in sepsis, 498 in traumatic brain injury, 733 in venous air embolism, 706 inspiratory and expiratory gas monitoring and, 574 intrauterine, 770. See also Fetal distress. perioperative, 193-198 management and prevention of, 198, 198t patients at risk of, 198 reduction of risk of, 198t pulse oximetry and, 572 vs. hypoxemia, 637 Hypoxic gas mixture, faulty proportioning device and, 521-523 Hysterotomy, midgestation open, 766, 766t I IBMAX, 22t Ibuprofen, action of, 274, 274f gastrointestinal toxicity of, 275, 276 Ibutilide, for perioperative tachyarrhythmias, 323 Idarubicin, 110 metabolism of, 116 Ignition sources, in operating room, 562, 564t Iloprost, actions and side effects of, 4t applications of, 6 Imatinib mesylate (Gleevec), mechanisms, uses, and toxicities of, 113t Imazodan, action and uses of, 22 Imipenem, for nosocomial bacterial pneumonia, 211 Immobilization, thrombosis and, 362, 364 Immune complexes, in acute hemolytic transfusion reaction, 202 Immune response, anesthesia and, 502 in HIV-infected patients, 449 catecholamines and, 8 hepatic necrosis mediated by, 66 herb and nutraceutical effects on, 154t impaired, 499 in cardiopulmonary bypass, 352, 354 in myasthenia gravis, 484 intraoperative angioedema and urticaria and, 427 to NSAIDs, aseptic meningitis and, 276 Immunocompromised patients, blood transfusion in, 295 care of, 500-502 causes of impaired immunity in, 500, 500t management and prevention of complications in, 502 polyradiculopathy in, postpartum, 793 risk assessment in, 501-502 Immunoglobulin A, in allergic reactions to blood transfusions, 203, 204

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Immunoglobulin E, antibodies to, in anaphylactic shock, 97 in latex allergy, 217, 218, 218t, 651 in NSAID allergies, 275 in allergic reactions to blood transfusions, 203, 203t Immunoglobulin G, antibody to, heparin-induced thrombocytopenia and, 292 Immunosuppressive agents, anaphylactic or anaphylactoid reactions associated with, 99t for sarcoidosis, 460 Immunotherapy, for myasthenia gravis, 485 Impedance, 556, 561 Impotence, celiac plexus block and, 254 In vitro contracture test, for malignant hyperthermia, 655 In vitro testing, for anesthetic drugs, 100 Incident reporting, 183, 927, 928 Indinavir, postexposure prophylaxis for HIV with, 447 Indomethacin, action of, 274, 274f for tocolytic therapy in preterm labor, 764, 765 maternal, for EXIT procedure, 609 postoperative, for early extubation anesthesia, 358 Induction, agents used for, anaphylactic or anaphylactoid reactions with, 99t for EXIT procedure, 609 for postoperative nausea and vomiting prevention, 647 in cardiopulmonary bypass in pregnant patients, 803-804 in children, 604-605 with traumatic brain injury, 730 in foreign body aspiration, 755 rapid-sequence, for pulmonary aspiration prevention, 643 intraocular pressure and, 745 risk of maternal hypoxemia in, 767 Infants. See also Fetus; Neonates. anticholinergic toxicity in, 28, 29 atropine overdose in, 30 bradycardia in, in induction of anesthesia, 28 fluid requirements in, calculation of, 658t hypernatremia in, 433 hypoxemia risk in, 637, 638, 638t, 639 myopathy in, succinylcholine administration and, 86 periodic breathing patterns in, 639 postoperative apnea in, 612, 613 postoperative atony in, 611-614 preterm, 763 pulmonary aspiration risk in, 641 Infection(s). See also specific type, e.g., Meningitis. blood transfusion and, 680 bloodstream, central venous catheter–related, 582, 583-585, 583t, 585f, 586f, 587 in burn wounds, 505, 506 in immunocompromised patients, 501 intracranial pressure monitoring and, 593, 594 nosocomial, 210-212 upper respiratory, criteria for, 649 in children, 649-650 laryngospasm and, 599-600 ventricular assist device placement and, 411 with central neuraxial block, 239-241 management of, 240-241 mechanisms of, 239 prevention of, 241 recognition of, 239-240 risk for, 240

Infection(s) (Continued) with continuous perineural local anesthetic infusion, 282, 283 Inflammation, in burn injuries, 504 in systemic inflammatory response syndrome, 497 secondary pulmonary hypertension and, 660 Inflammatory response, after cardiopulmonary bypass, management and prevention of, 354-355 mechanisms of, 352, 353f risk factors for, 353-354 signs and symptoms of, 352, 353 Infliximab, 502t Information, withheld, adverse outcomes and, 942-943 Informed consent, in Alzheimer’s disease patients, 493, 494 medicolegal aspects of, 937, 949 of minors, 944-945 Infraclavicular block, pneumothorax with, 251-253 technique of, 251, 252f Infusion pumps, 549 Inhalation anesthesia, agents used in, for early extubation anesthesia, 358 for prevention of bronchospasm in asthmatics, 190, 191 for emergent cesarean delivery, 772 postoperative apnea in infants and, 613 Inhalation injury, from smoke, in laser surgery, 568 in surgical diathermy, 558 in burn injuries, 504, 505, 505t Injection, intrathecal, after unintended subdural injection, 246-247 unintended, 242-243 neurotoxicity with, 229 intravascular, unintended, 230-234, 233t vs. total spinal anesthesia, 248 of neurolytic solutions, tests for, 254, 256 subdural, unintended, 244-247 Injury(ies), associated with spinal cord injury, 738, 738t, 739 blood vessel, intravascular coagulation and, 361 blood-contaminated, of health care workers, 207, 208 brain, secondary, prevention of, 728, 728t traumatic. See Traumatic brain injury. breathing circuit problems and, 542 burn, 504-507 cervical spine, 177, 737. See also Cervical spine, injury to. traumatic, 828 compressive, cauda equina syndrome and, 227, 228 dental, 181-183 endothelial cell, in preeclampsia, 760 eye, anesthesia-related, 692 corneal, 741-744 open globe, 745-746 postoperative, 692-697 head, 732-736 hyperventilation in, 702 intracranial pressure monitoring and, 591, 593 management of, 734-736, 735f open globe injury and, 745 prevention of, 736 pulmonary edema and, 215 hypothalamus, after subarachnoid hemorrhage, 723

973

Injury(ies) (Continued) inhalation, from smoke, in laser surgery, 568 in surgical diathermy, 558 in burn injuries, 504, 505, 505t laryngeal, 184-185, 577 nerve. See Nerve injury. pressure-related, from tourniquets, 867-870 skin, from arterial tourniquet, 867 in laser surgery, 568 spinal cord, 737-740. See also Spinal cord, injury of. thermal. See also Burn injuries. from humidifier complications, 544 from warming devices, 550-552, 551f, 551t tracheal, 184-185 traumatic. See Trauma. Innominate artery, in cardiopulmonary bypass, 300-301, 300f Inotropic drugs, 11-13 classification of, 11, 11f effects of, 11, 12t in systemic inflammatory response syndrome, 498 management and prevention of complications with, 12-13 Inotropic effects, of etomidate, 81, 82 of ketamine, 78 of propofol, 81, 82 Insufflation, air emboli and, 673 of carbon dioxide, in laparoscopic surgery, 831, 832, 834 Insulin, in diabetic ketoacidosis, 418 in diabetics, regimens for, 417t, 418 in sepsis, for tight glucose control, 499 subcutaneous doses of, 417t Insurance policy issues, in malpractice cases, 934 Intensive care unit, discharge guidelines in, for cardiac patients, 359, 359t mortality risk in, for HIV-infected patients, 449-450 pneumonia in, 210 Interferons, side effects of, 501 Interleukin-1 inhibitors, risks with, 501-502, 502t Interleukin-8, in acute respiratory distress syndrome, 349 Intermittent claudication, in peripheral vascular disease, 394 Internal cardioverter-defibrillators. See also Cardioversion. cardiac risk with, 147 electromagnetic interference and, 404, 404f features of, 399 indications for use of, 400, 401t lithotripsy and, 852 malfunction of, 403-404, 404f surgical diathermy interference with, 556, 557, 558, 559 Interosseous needle, drug delivery by, for intraoperative cardiac arrest, 616, 618f Interscalene nerve block, approaches used for, 249, 249f total spinal anesthesia following, 248-250 Interventional radiology suite, 912, 912f Intra-aortic balloon pump, balloon inflation and deflation of, 409, 410, 410f central neurologic injury and, 340 indications for and contraindications to, 408 management and use of, 410, 410f risk factors for, 409 Intracranial elastance curve, 701, 701f Intracranial hemorrhage, normal perfusion pressure breakthrough and, 724, 726

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Intracranial hypertension, 701-703 in children, after traumatic injury, 729 delayed emergence and, 629 intracranial pressure monitoring and, 591, 593, 594 management and prevention of, 702-703 risk factors for, 701-702 signs and symptoms of, 701 Intracranial pressure, changes in, 701, 701f definition of, 591 delayed emergence and, 886 in brain injury, 733 in vasospasm, 721 increased, in intracranial aneurysm rerupture, 714 in traumatic brain injury, 733 in children, 728, 730 mechanisms of, 701-702 nonbarbiturate anesthetics and, 83 treatment and prevention of, 702-703, 702t, 735 monitoring of. See Intracranial pressure monitoring. normal, 591 Intracranial pressure monitoring, 591-595 advantages and disadvantages of, 593, 593t continuous, 593 intracranial spaces monitored by, 592-593, 592t, 593t management and prevention of complications with, 594 monitors used for, transducer types and location of, 592 use and placement of, 591-592 risks of, 593-594 ventricular, 592-593, 593t Intraocular pressure, anticholinergics and, 30 decrease in, drugs or factors involved in, 745, 745t eye injury and, 692, 745, 745t increase in, drugs or factors involved in, 745, 745t nonbarbiturate anesthetics and, 83 vitreous extrusion and, 694, 695 Intrathecal injection, after unintended subdural injection, 246-247 of lipophilic vs. nonlipophilic drugs, 261 of opioids, for labor and delivery, 262-263 unintended, 242-243 neurotoxicity with, 227, 229 Intravascular injection, unintended, of local anesthetic, 230-234, 233t vs. total spinal anesthesia, 248 Intravascular volume, angiotensin II effects on, 17 in infants and children, massive blood transfusion and, 677, 678 in psoas compartment block, 259 in subarachnoid hemorrhage, 721 Intravenous access, for drug delivery systems, 546-549 in thoracic aortic aneurysm repair, 388 in trauma victims, 829 Intravenous fluids, anaphylactic or anaphylactoid reactions associated with, 99t in radical urologic surgery, 847 in traumatic brain injury, 734, 735t intracranial hypertension and, 702 Intravenous infusion pumps, in magnetic resonance imaging suite, 919 Intravenous solution bags, heated, injury from, 550, 551f, 551t

Intubation. See also under Tube(s). awake, in cervical spine injuries, 179 pulmonary aspiration prevention and, 784 difficult, 161, 162f. See also Airway, difficult. airway examination predictors of, 161, 163t diagnosis of, 161, 162, 163f, 163t, 164, 164t difficult extubation with, 162, 164 endobronchial, 368 introducers for, 162 failed, in emergent cesarean delivery, 772 in obstetric patients, 782 fiberoptic, for difficult airway management, 165-166, 167f, 167t for laryngospasm in children, 602 impossible. See Airway, difficult, cannot ventilate, cannot intubate. in spinal cord injury, 739 nasal, blind, 166, 168, 168t in fiberoptic bronchoscopy, 166, 167t oral, in fiberoptic bronchoscopy, 166, 167f lighted stylet method of, 168-169, 168t tracheal, awake, in cervical spine injuries, 179 dental injury during, 181 for difficult airway management, 161, 162f, 164, 164t, 165-166, 167f, 167t, 168, 168t, 368 in acute respiratory distress syndrome, 350 in cervical spine injuries, 179 in spinal cord injuries, 739 in trauma victims, 730, 734, 829, 829t injury from, 184, 185 postintubation croup and, 631 pulmonary aspiration and, 187, 188, 784 retrograde, 169-170, 170f, 171t via laryngeal mask airway, 169 Iodide, for inhibition of thyroid hormone synthesis, 456 Iodinated radiopaque contrast agent, anaphylactoid reactions to, 100 Iodine, hypothyroidism and, 452 radioactive, for Graves’ disease, 820 Iodophor-in-isopropyl alcohol preparations, in central neuraxial block, 241 Iopanoic acid, for inhibition of thyroid hormone synthesis, 456 Ipecac, syrup of, for poisoning cases, 509, 510t Ipratropium (Atrovent), 29 Irinotrecan, 110 Iron, supplemental, in autologous blood predonation, 296, 297 Irrigants, hypotonic, in transurethral resection of prostate or bladder, 843, 843t, 844 Ischemia, cerebral, delayed emergence and, 629 in carotid endarterectomy, 380-381, 380t, 382 in traumatic brain injury, 733 intracranial pressure and, 702 digital, arterial cannulation and, 579 myocardial, in revascularization for peripheral vascular disease, 397 of intraneural vasculature, nerve injury and, 336-337 of legs, in peripheral vascular disease, 394 of peripheral nerves, 881, 882 pulmonary, pulmonary artery catheter–related, 588 spinal cord, in thoracic aortic aneurysm repair, 387, 388 postpneumonectomy, 379 ventricular reentry and, class I antiarrhythmic drugs and, 36 Ischemic hepatitis, postoperative jaundice and, 807

Ischemic optic neuropathy, in spinal surgery, visual loss with, 856, 857, 873 postoperative, in children, 693 Ischemic pituitary necrosis, antepartum bleeding and, 777 Isoflurane, for intraoperative hypertension, 20 hepatic toxicity and, 66 inflammatory response after cardiopulmonary bypass and, 353 neurophysiologic effects of, 729t teratogenic effects of, 799, 800 Isoproterenol, for bradycardia, 14-15 for drug-induced torsades de pointes, 46 inotropic effects of, 11-12, 12t J Jaundice, obstructive, 808 postoperative, 805-809 classification of, 806-808, 806t diagnosis of, 805-808, 806t intrahepatic causes of, 806-808, 806t management and prevention of, 809 posthepatic causes of, 808 prehepatic causes of, 806 risk assessment of, 808-809 Jaw thrust-chin lift maneuver, for airway obstruction, 179, 601 JCAHO. See Joint Commission on Accreditation of Healthcare Organizations. Jehovah’s Witness patients, 948-950 Jervell and Lange-Nielsen syndrome, 328 Jet ventilation, for management of pulmonary hypertension, 661 Joint Commission on Accreditation of Healthcare Organizations, awareness under anesthesia and, 941 patient misidentification and, 921, 922 quality assurance guidelines of, 927 sedation policies of, 619 Joint replacement surgery, fat embolism syndrome and, 860 Jugular venous bulb oximetric catheter, in traumatic brain injury, 733 K Kaolin-activated clotting time, 291 Kaposi’s sarcoma, daunorubicin for, 110 doxorubicin for, 110 in HIV-infected patients, 448 Kava kava, common uses of/problems with, 156t delayed emergence and, 886 Keratitis, 741, 742 Ketamine, 78-79 as induction agent, 78-79 for detumescence of penile erection, 841 for tricyclic antidepressant toxicity, 107 hypotensive response to, 78-79 in analgesia for opioid-tolerant patients, 280 in children, emergence agitation and, 686 in radiation oncology, 910 preoperative, 684 sedation and, 621 intraocular pressure and, 746 manual infusion dosing regimens for, 549t neurophysiologic effects of, 729t pharmacokinetic properties of, 78-79, 78t Ketanserin, in carcinoid syndrome, 816 Ketoacidosis, diabetic, management of, 417-418, 417t delayed emergence and, 886 pathogenesis of, 415, 416f in acid-base disorders, 437, 439 Kinase II, angioedema and, ACE inhibitors and, 18

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Knee replacement surgery, deep venous thrombosis prophylaxis regimens in, 863 peripheral nerve block for, 267t, 270 psoas compartment block for, 258 thromboembolism and, 364 Knee surgery, outpatient, peripheral nerve block for, 267t, 270 Kyushin, common uses and problems with, 156t L Labeling, of syringes, 924, 924f, 925, 926f Labetalol, actions and side effects of, 4t for cesarean delivery in preeclamptic patients, 761 for electroconvulsive therapy, 904, 905 for hypertension in pregnancy, 761 for rebound hypertension, 95 Labor and delivery, in preeclamptic patients, 760, 761 intrathecal opioids for, 262-263 neurologic injuries in, 789-794 preterm, 763-765 cardiopulmonary bypass in pregnant patients and, 803, 804 nonobstetric surgery in pregnancy and, 799, 800 spinal cord injury with, autonomic hyperreflexia and, 477 trauma in, 779-780, 779t uterine contractions in, 763-764 Laboratory testing, cost containment and, 930 for drug dependence, 119 for substance abuse, 123 Lactate, in acid-base balance, 436, 437t Lactic acidemia, in adrenal insufficiency, 444 Lactic acidosis, cerebral, in carotid endarterectomy, 382 in acid-base disorders, 437, 439 respiratory failure and, 347 Lag monitor, pulse oximetry as, 570 Lambert-Eaton syndrome, 484, 486t differential diagnosis of, 488t Lamin A/C gene, 480 Lamivudine, postexposure prophylaxis for HIV with, 447 Lanreotide, in carcinoid syndrome, 816 Lansoprazole, for prevention of pulmonary aspiration, 643t Laparoscopic surgery, cardiovascular collapse during, 831, 831t complications of, 831-835 differential diagnosis of, 832, 832t management and prevention of, 834-835 recognition of, 832-833 risks with, 833-834 fluid management in, 63, 64 physiologic changes in, 831, 831t safety of in critically ill patients, 834 Laparoscopy, “gasless,” 835 Laryngeal edema, angioedema and, 426, 427 in burn injuries, 504, 505 postintubation croup and, 632 treatment of, 185 Laryngeal mask airway, 168-169 for cervical spine injuries, 179 for cesarean section, 772, 783 for children, 605, 605f in radiation oncology, 910 for prevention of bronchospasm in asthmatics, 191 for trauma victims, 829 intubating, 169 placement of, 576

Laryngeal mask airway (Continued) ProSeal, 169 pulmonary aspiration and, 641-642, 783 Laryngeal nerve, recurrent, 818, 819, 820, 821 superior, 818, 819, 820, 821 Laryngoscope, Bullard, for children, 605 Laryngoscopy, 750-751 dental injury during, 181, 183 difficult, 161, 162f airway examination predictors of, 161, 163t diagnosis of, 161, 162, 163f, 163t, 164, 164t grading systems of, 162f direct, in cervical spine injuries, 179 injuries from, 181, 183, 184, 185 Laryngospasm, airway obstruction with, 600-601, 600f, 601f, 877 in children, 599-602 management and prevention of, 600-602, 600f, 601f, 879 pulmonary edema and, 215, 216 risk factors for, 599-600 signs of, 599 upper respiratory tract infection and, in children, 649-650, 650t Laryngospasm notch, 601 Larynx, angioedema of, ACE inhibitors and, 17-18 competence of, pulmonary aspiration and, 642 in infants, 603, 604f injury to, 184-185, 577 sarcoidosis involving, 457, 458f Laser(s), types of, hazards of, 567, 567t Laser plume, 568 Laser surgery, complications of, 562-565, 567-569 for prostatectomy, 845 of airway, complications with, 750, 751 fire risk with, 562, 563, 563f, 564, 564t, 565, 568, 569 safety issues with, 568-569 Lateral decubitus position, in radical urologic surgery, 846, 847 Latex, substitutions for, 653 Latex allergy, anaphylactic and anaphylactoid reactions and, 98, 99t, 652-653 in children, 651-653 in health care workers, 217-219 management and avoidance of, 219 risk factors for, 218-219 test results for, 218t types of, 217-218, 218t Lavage, bronchopulmonary, for pulmonary aspiration, 642 Lead(s), pacemaker, 399, 400 bipolar and unipolar, 403, 404f Leakage current, 560 in surgical diathermy, 558 Leg(s), in sarcoglycanopathies, 480 revascularization of, for peripheral vascular disease, 394-397 tourniquet effects on, 867-870 Legal considerations. See Medicolegal issues. Lepirudin, for heparin-induced thrombocytopenia in cardiopulmonary bypass, 292 Leukocyte(s), depletion of, inflammatory response after cardiopulmonary bypass and, 354 Leukocyte histamine release test, for anesthetic drugs, 100 Leukocytosis, systemic inflammatory response syndrome and, 497

975

Leukoencephalopathy, progressive multifocal, in AIDS patients, 449 Leukopenia, anthracycline antibiotic action and, 116 Leukotrienes, NSAID action and, 275 Levobupivacaine, maximal plasmal concentrations of, 232t Levodopa, in Parkinson’s disease, 490, 491, 491t Licorice, common uses of/problems with, 156t Lidocaine, dose of, 39t neurotoxicity of, 229 for bronchospasm in asthmatics, 190, 191 for cardiac arrest, in tricyclic antidepressant toxicity, 107 for digitalis toxicity, 26 for epidural anesthesia, 243 for laryngospasm prevention, 602 for spinal anesthesia, 228, 229, 229t inadvertent intrathecal injection of, neurotoxicity of, 228, 229 maximal plasmal concentrations of, 232t vs. bupivacaine, toxicity of, 229, 231, 232 with propofol, for external cardioversion, 907 Ligaments, in cervical spine injury, 177 Light wand, 605 Lighted stylet, oral intubation with, 168-169, 168t, 605 Likelihood ratios, 141, 141t Limb-girdle muscular dystrophy, protein dysfunction in, 479-480 Line isolation monitor, 561 Linens and drapes, in operating room, 563, 565t Linezolid, for methicillin-resistant Staphylococcus aureus infection, 211 Link-25 proportioning system, 518, 521, 521f, 523 Lipase, in pancreatitis, 474 Lipid peroxides, anthracycline antibiotic action and, 116 Lipophilic drugs, intrathecal placement of, 261, 262 neuraxial opioid use and, 262 Liposuction, fat embolism syndrome and, 860 Lithotripsy, anesthesia management with, 851 complications of, 850-852 contraindications to, 851t injuries with, 851 physics of, 850, 850f, 851f undesirable side effects of, 850-851 Liver disease. See also under Hepatic. alcohol-related, 123 hepatic insufficiency as, 466-469 local anesthetic-induced toxicity and, 231 postoperative, 805-809 Liver function studies, 805t, 809 Living wills, 949 L-NAME, in acute respiratory distress syndrome, 350 Local anesthetic(s), allergic reactions to, 233 anaphylactic or anaphylactoid reactions with, 99t cauda equina syndrome and, 227-229 doses of, in morbidly obese, 812 epidural, after psoas compartment block, 258 in analgesia for opioid-tolerant patients, 280 in regional anesthesia, tissue uptake of, 231, 232t neuraxial, unintended injection of, 242, 244, 246, 248 urinary retention and, 838 perineural infusion of, continuous, 282-283 postoperative pain control and, 897

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Local anesthetic(s) (Continued) test doses of, 243 toxicity of, cardiotoxic effects of, 248 in unintended injection, 230-234, 233t into vertebral artery, 248 intrathecal, 242 subdural, 244, 246, 248 neurotoxic effects of, 227-229, 286 systemic, management of, 233 prevention of, 233-234, 233t Long QT syndrome, 38, 38t. See also Q-T interval, prolonged. drug-induced, diagnosis of, 44-45 electrocardiographic features of, 44 management and prevention of, 46 torsades de pointes with, 327, 327f, 328, 328t, 329 ventricular arrhythmias and, 327-330 Loop diuretics, for acute renal failure, 345 for intracranial pressure lowering, 702, 702t Lorazepam, for postoperative delirium, 889 Low birth weight, 763. See also Prematurity. Lumbar epidural anesthesia, in autonomic hyperreflexia, 478 Lumbar plexus, injuries of in childbirth, 790, 791f psoas compartment block and, 258, 259, 260 Lumbar plexus block, 258 posterior, hemorrhagic complications after, 270 Lumbar puncture, spinal hematoma and, 236 Lumbar sympathetic block, hemorrhagic complications after, 270 Lumbosacral nerves, urinary retention and, 837 Lung(s). See also under Pulmonary; Respiratory. dermatomes of, 790, 792f development of, in infants, 638 function of, in cirrhotic patients, 467 in diagnosis of double-lumen tube malposition, 365, 367 in morbidly obese, 810-811, 811t in water-immersion lithotripsy, 851, 851t with massive blood transfusion in children, 680 in one-lung ventilation, 365 inadequate isolation of, prevention of, 369-370 treatment of, 368, 369, 369f inflammatory response in, after cardiopulmonary bypass, 354 sarcoidosis in, 457-458, 457f, 458f small cell carcinoma of, Lambert-Eaton myasthenic syndrome and, 485 volume of, pulmonary vascular resistance and, 316 Lung disease, cavitary, in HIV-infected patients, 448 chronic, 316 parenchymal, secondary pulmonary hypertension and, 660 pulmonary hypertension and, 316, 660, 660t ventricular assist device placement and, 411 Lung injury, acute, transfusion-related, 203, 205, 205t oxygen flush and, 524, 525t ventilation-induced, in acute respiratory distress syndrome, 349 Lung transplantation, for sarcoidosis, 460 Lupus anticoagulant, 363 Lymph node(s), in HIV infection and AIDS, 446, 447f retroperitoneal dissection of, complications of, 846-849

Lymphadenopathy, hilar, in sarcoidosis, 459f Lymphocytes, in HIV infection, 446 Lymphoid follicular hyperplasia, thymic, in myasthenia gravis, 484 Lymphoid tissue, upper airway, in neonates, 603, 604f Lymphoma, in AIDS and HIV-infected patients, 448, 449 non-Hodgkin’s, 110 M Ma huang, common uses and problems with, 155t Macroshock, 560 Magnesium, 59-61 compounds of, 59t in cardiac surgery patients, 360 in cellular function, 59, 59t in therapeutics, 59-60 normal concentrations of, 59, 59t Magnesium sulfate, for acquired long QT syndrome, 329 for adrenalectomy, 825 for cesarean delivery in preeclamptic patients, 761 for drug-induced torsades de pointes, 46 for hypertensive emergencies, 825 for prevention of seizures in labor in preeclamptic patients, 760, 761 for tocolytic therapy, 764 postpartum headache with, 797 uterine contractions and, 763 Magnet, on cardiac rhythm management devices, 559 Magnetic resonance imaging, anesthesia for, 918-920, 918t, 919t cardiac rhythm management devices and, precautions with, 405 contraindications to, 918, 918t for central neurologic injury, 339-340 for cervical spine injuries, 178 for epidural abscess, 240, 240f for pancreatitis, 474 in children, 620 Malignant hyperthermia, 423, 424 carbon dioxide absorbents and, 535 clinical manifestations of, 654, 654t complications of, 655t differential diagnosis of, 655t in children, 654-656 in muscular dystrophy, 481, 482 management of, 656, 656t pathophysiology of, 654 prevention of, 656 risk factors for, 654-655 succinylcholine use and, in children, 623, 624, 625 vs. thyrotoxicosis, 455 Malignant Hyperthermia Association of the United States, 655 Mallampati class, difficult intubation and laryngoscopy and, 161, 163t Malpractice, alleged, 933-935 causes of, 933t discovery process in, 934t stages in lawsuit of, 934t trial process in, 934t notification of insurance carrier of, in adverse incidents, 943 Mandibulofacial dysostosis, difficult airway in, 603f, 605 Mannitol, for acute renal failure, 345 for brain tissue water, 594 for intracranial pressure, 702, 702t

Mannitol (Continued) for thoracic aortic aneurysm repair, 388 for traumatic brain injury, 735 intracranial aneurysm rerupture and, 717, 718 Marijuana, abuse of, 122, 124-125 consequences of, 125 treatment of, 126, 126t Marinol (dronabinol), for marijuana abuse, 126 Mass(es), intracerebral or extracerebral, intracranial pressure and, 701 mediastinal, anterior, 372, 670-672 complications with, 372-375 compression of heart or pulmonary artery with, 374, 375 management and prevention of, 375 risk factors in, 374-375 superior vena cava syndrome with, 373, 375 tracheobronchial tree compression with, 372-373, 373f, 373t, 374f, 375 posterior fossa, 709 space-occupying, intracranial pressure and, 594 Mass reflex, 477 in chronic spinal cord injury, 739 Mass spectrometry, 575 Masseter spasm, succinylcholine use and, in children, 623, 624, 625 Mast cells, in angioedema and urticaria, 426 Mean arterial pressure, 7 deliberate hypotension and, 855, 856 spinal cord injury and, 873 tourniquet use and, 868 Mechanical assist devices, 407-411 classification of, 407, 407t complications with, 410-411 indications for and contraindications to, 407, 408-409 risk assessment with, 409 uses of, 407-408 Mechanical ventilation. See Ventilators, mechanical. Meconium, in amniotic fluid, 770 Mediastinal mass(es). See Mass(es), mediastinal. Mediastinal tube, monitoring of, 305, 306 Mediastinum, anatomy of, 372f definition of, 670 irradiation of, anthracycline antibiotic–induced cardiotoxicity and, 117 widened, in trauma victims, 828 Medical records, privacy of, 944 Medicolegal issues, 921-950 cost containment in, 930-931 do-not-resuscitate orders in operating room and, 946-947 hostile-combative behavior and, 936-938 Jehovah’s Witness patients and, 948-950 of litigation by anesthesiologists, 927 of nerve injuries from tourniquets, 867 patient confidentiality and, 944-945 patient misidentification and, 921-923 quality assurance and, 927-929 syringe swaps and, 924-926 withheld information or misinformation and, 942-943 MEDLINE, latex reactions recorded in, 217, 217t Medulla. See Brainstem. Medulloblastoma, pediatric, 909t Meloxicam, 274, 274f, 275 Memantine, in Alzheimer’s disease, 494

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Meningitis, aseptic, NSAID allergy and, 276 central neuraxial blockade and, 239-241 postpartum headache with, 797 signs of, 239-240 Mental retardation, in Duchenne’s and Becker’s muscular dystrophy, 479, 480 Mental status, after cardiopulmonary bypass, 352 emergence agitation and, 685 in head injury, 732 in intracranial hypertension, 701 in retrobulbar block, 748 Meperidine, anaphylactic and anaphylactoid reactions and, 98, 99t for shivering prevention, 422 monoamine oxidase inhibitors given with, 105 toxicity of, in analgesia for opioid-tolerant patients, 280 Mepivacaine, maximum plasma concentrations of, 232t Meralgia paresthetica, 790 Mesenteric traction syndrome, in abdominal aortic aneurysm repair, 391 Metabolic acidosis, 437 acute respiratory distress syndrome and, 348 in children, delayed emergence and, 627-628 in diabetic ketoacidosis, 418 tourniquet release and, 868 treatment of, 439, 439f Metabolic alkalosis, 437 treatment of, 439-440, 440f Metabolic disorders, bradyarrhythmias due to, 333-334 coexisting disease with, 415-441 delayed emergence and, 886 in children, 627, 629 in HIV drug treatment, 447-448 postpartum headache with, 797 Metabolic rate, cerebral, central neurologic injury and, 340 Metaraminol, for detumescence of penile erection, 841 Methadone, conversion to, in opioid-tolerant patients, 279t, 280, 281 Methemoglobin, pulse oximetry and, 197, 571, 572t Methemoglobinemia, local anesthetic-induced, 231, 232-233 Methicillin-resistant Staphylococcus aureus infection, antibiotics for, 210, 211 Methimazole, for inhibition of thyroid hormone synthesis, 456 Methionine, nitrous oxide and, 69 Methohexital, in electroconvulsive therapy, 904 manual infusion dosing regimens for, 549t Methotrexate, mechanisms, uses, and toxicities of, 113t Methoxyflurane, nephrotoxicity induced by, 67 Methylcellulose drops, for corneal protection, 743, 744 Methylcobalamin, 69 Methylene blue, pulse oximetry and, 571, 572t Methylergonovine, for treatment of uterine atony, 781 3-Methylfentanyl, 120 Methylmethacrylate, embolic injury with, 865-866 Methylparaben, 233 Methylprednisolone, glucocorticoid and mineralocorticoid potencies of, 132t in acute spinal cord injury, 739, 740 in trauma victims, 829 Methylxanthines, adenosine and, 35

Metoclopramide, for postoperative nausea and vomiting, 646t for pulmonary aspiration, 188, 643t, 784 potential complications of, 135 receptor site affinity of, 134t side effects of, 135t Metocurine, dose, clearance, and side effects of, 624t Metronidazole, complications of, 102t Mexiletine, dose of, 39t Mibefradil, adverse drug reactions with, 51 Microdialysis catheter, 733 Microinfarction, 310 Microlaryngoscopy, 750-751 Microorganisms, gram-negative, antibiotics for, 211 in nosocomial pneumonia, 210 skin, central venous catheter–related infection and, 584, 586f Microshock, 558, 560 Micturition reflex, normal, 836-837, 836t Midazolam, delayed emergence and, 627 dose of, 80t, 549t for early extubation anesthesia, 358 for electroconvulsive therapy, 905 for emergence agitation in children, 686 for external cardioversion, 907 for seizures, 233 for status epilepticus, 201 for TURP syndrome, 844 hemodynamic, respiratory and other effects of, 81, 81t, 82 mechanism of action of, 80 pharmacokinetic properties of, 80, 80t preoperative, in children, 684 Midbrain structures, 708 Migraine headache, drugs for, Q-T interval prolongation by, 328t postpartum, 795-796, 798t Milrinone, action and uses of, 22 as inotropic drug, 11, 12, 12t with epinephrine, for low cardiac output after cardiopulmonary bypass, 12 Mineralocorticoid deficiency, in adrenal insufficiency, 443 Mini-mental status examination, 493t Minors. See also Children. consent for treatment of, 937 medical decision making for, 949 medical records of, privacy of, 944 Miscarriage, bleeding with, 774, 776t, 777t Misinformation, adverse outcomes and, 942-943 Misoprostol, 276, 781 Mitochondrial dysfunction, HIV drug treatment and, 448 Mitotane, 110 Mitoxantrone, 110 Mitral regurgitation, ventricular assist device placement and, 411 Mitral stenosis, ventricular assist device placement and, 411 Mitral valve disease, vasodilator drugs for, 3 Mivacurium, 89t, 90 in children, 626 dose, clearance, and side effects of, 624t in electroconvulsive therapy, 904 Mobitz heart block, bradycardia and, 333, 333f Moclobemide, with morphine or synthetic opioids, 105 Monitoring, cardiorespiratory, postoperative apnea in infants and, 614 cerebral, for placement of surgical shunt, 380-381, 380t electronic, cardiac arrest and, 615

977

Monitoring (Continued) fetal, electronic, 770, 772f in cardiopulmonary bypass in pregnant patients, 803 in emergent cesarean delivery, 771 in ex utero intrapartum therapy, 608, 769 in nonobstetric surgery in pregnancy, 800 in open fetal surgery, 768 maternal, in cardiopulmonary bypass in pregnant patients, 804 in nonobstetric surgery in pregnancy, 800 neurophysiologic techniques of, 871-872, 871t, 872f, 872t, 873 of arterial blood pressure, 579-580 of awareness under anesthesia, 940 of burn-injured patients, 507 of central venous pressure, 582-587, 582t of complications of sedation, 620, 620t of core body temperature, 421-422, 423 of deliberate hypotension, 857 of electroconvulsive therapy, 903 of embolization procedures, 913 of esophagus, by transesophageal echocardiography, 577-578 of humidifier complications, 544, 545 of inspiratory and expiratory gases, 574-576 of intracranial pressure, 591-595 of laparoscopic surgery, 833 of magnetic resonance imaging suite, 918-919, 919t of morbidly obese patients, 812 of oxygen delivery, by pulse oximetry, 570-572 of posterior fossa surgery, 709, 710 of pulmonary artery pressure, 588-590, 761-762, 762t of respiratory depression, 73 of revascularization for peripheral vascular disease, 396 of spinal cord surgery, 871-872, 871t, 872f, 872t, 873 of traumatic brain injury, 730, 733 of use of warming devices, 665 of venous air emboli, 673-675, 673f, 674f, 706, 706f Monoamine oxidase inhibitors, in Parkinson’s disease, 491, 491t meperidine with, 105-106 nonhydrazine, 106 Monoclonal antibodies, in heparin-induced thrombocytopenia in cardiopulmonary bypass, 293 Monro-Kellie hypothesis, 591 Moricizine, dose of, 39t Morphine, anaphylactic and anaphylactoid reactions and, 98, 99t conversion to methadone of, in opioid-tolerant patients, 279t, 280 inflammatory response after cardiopulmonary bypass and, 353 intrathecal, 261, 262, 263t complications of, 72-73, 72t for early extubation anesthesia, 358 with monoamine oxidase inhibitors, complications of, 105 Mortality, cardiac risk and, 147, 148t hyperglycemia and, 417 in abdominal aortic aneurysm repair, 392, 392t in acute renal failure, 344-345 in acute respiratory distress syndrome, 349-350 in cirrhosis, 468

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Mortality (Continued) in drug overdose, 120, 121 in early vs. late extubation after cardiac surgery, 357, 357t in fat embolism syndrome, 860 in HIV patients in intensive care unit, 449-450 in immune-mediated transfusion reactions, 203t, 204 in laryngeal and tracheal injuries, 185 in morbidly obese patients, 810 in myxedema, 452 in obstetric patients, 783 in premature infants, 763 in seizure disorders, 201 in subarachnoid hemorrhage, 715t, 720 in trauma-related surgery, 827 maternal, in emergent cesarean delivery, 772 Motilin, in pregnancy, 782 Motor block, in continuous perineural local anesthetic infusion, 283 Motor evoked potentials, in spinal cord surgery, 871, 871t, 872, 872t, 873 in thoracic aortic aneurysm repair, 387, 388 Mucosal barriers, cardiopulmonary bypass and, 352 Motor weakness, in acute porphyria, 75, 76 of lower extremities and trunk, celiac plexus block and, 254 Müller’s maneuver, 215 modified, 634 Multiorgan system failure. See also Multiple organ dysfunction. acute respiratory distress syndrome and, 350 in cholecystectomy in cirrhotic patients, 808 Multiple endocrine neoplasia, adrenal tumors and, 822 Multiple organ dysfunction. See also Multiorgan system failure. criteria for, 498t immunosuppression and, 502 Multiple organ dysfunction syndrome, systemic inflammatory response syndrome and, 496-499 Muscarinic receptors, anticholinergic actions and, 28-29, 30 Muscle(s), biopsy of, for malignant hyperthermia, 655 bulbar, in myasthenia gravis, 484 calcium release in, in malignant hyperthermia, 654 extraocular, in myasthenia gravis, 484 oculocardiac reflex and, 695, 696t injury of, from arterial tourniquet, 867 leg, in sarcoglycanopathies, 480 skeletal, opiate-induced rigidity of, 174-175 smooth, bronchial, 189 relaxation of, sildenafil and, 21 vasodilators and, 3 vascular contraction of, magnesium and, 59 weakness of, in myasthenic disorders, 484 Muscle relaxants. See also Neuromuscular blocking agents. awareness under anesthesia and, 939, 940 depolarizing, complications with, 623 in children, 623-626 dose, clearance, and side effects of, 624t in electroconvulsive therapy, 904 in magnesium sulfate tocolytic therapy, 764 in opiate-induced muscle rigidity, 175 in patients with porphyria, 76 in traumatic brain injury in children, 730 nondepolarizing, 89-91 agents potentiating action of, 89-90 complications with, 623-626

Muscle relaxants (Continued) for rapid-sequence induction in open globe injury, 745, 746 in muscular dystrophy, 481, 482 intraocular pressure and, 695 long-acting vs. short- or intermediateacting, 89t, 90 prolonged neuromuscular block with, management of, 90-91 prevention of, 91 risk of, 89-90 recovery times from, 89t routes of metabolism or elimination of, 90t Muscular dystrophy, 479-482 cardiomyopathy in, 480-481 classification of, 479-481 diagnosis of, 479 extracellular matrix proteins in, 480 management and prevention of, 482 plasma membrane–associated proteins in, 479-480 proteins with enzymatic activity in, 480 recognition of, 481 risks with, 481-482 Myasthenia gravis, 484-485, 486t differential diagnosis of, 488t Myasthenic disorders, 484-489 acetylcholine in, 484, 485f classification of, 484, 486t-488t Myelination, methionine deficiency and nitrous oxide anesthesia and, 69 Myeloneuropathy, vitamin B12 deficiency and, 69 Myeloproliferative disease, management of, 364 thrombosis and, 362-363, 364 Myelosuppression, anthracycline antibiotic action and, 116 Myloclonic seizures, 200 Myocardial contractility, in cardiomyopathy, 668 in hyperkalemia, 57 inotropic drug use and, 11 Myocardial effects, of hyperkalemia, 53-54 of propofol, 81 of subarachnoid hemorrhage, 723 Myocardial infarction, history of, perioperative cardiac risk and, 148-149, 148t ventricular tachycardia and, 320 hyperglycemia and, 417 in abdominal aortic aneurysm repair, 391 in carotid endarterectomy, 382 perioperative, in cardiac surgery, 309-311 postpneumonectomy, 378 risk factors for, 147-149, 148t, 320 transmural, recognition of, 309 ventricular assist device placement and, 408 Myocardial ischemia, catecholamine-induced tachyarrhythmias and, 9 clonidine withdrawal and, 95 in abdominal aortic aneurysm repair, 390, 391, 392, 393 in revascularization for peripheral vascular disease, 397 in thoracic aortic aneurysm repair, 388 nitroprusside and, 314 perioperative, 20 in cardiac surgery, 309-311 management of, 310-311, 310t recognition of, 309 risk factors for, 310, 310t postoperative, volatile anesthetics and, 900 Myoglobin, in anemic hypoxia, 196, 196f Myoglobinuria, succinylcholine use and, in children, 624

Myopathic disease, succinylcholine use and, in children, 624, 625 Myopathy, to HIV drug treatment, 447 Myosin, in uterine contractions, 763 Myotonic dystrophy, cardiac conduction defects in, 480, 481, 482 Myxedema, definition of, 451 diagnosis of, 452, 452t management and prevention of, 452-453 symptoms and pathophysiology of, 451-452 Myxedema coma, 451-453 N Nabumetone, action of, 274, 274f, 275 N-acetylcysteine, for prevention of acute renal failure, 345 Nalbuphine, for reversal of respiratory depression, 263 Naloxone, 128-130 clinical parameters of, 128, 128t delayed emergence and, 886 in children, 629, 630t dose of, 128, 129t for opiate reversal, 73 for respiratory depression reversal, 263 side effects of, 128, 129, 130 Naltrexone, for opioid-addicted physicians, 121 Naproxen, action of, 274, 274f gastrointestinal toxicity of, vs. rofecoxib, 275, 276 Narcotics, for early extubation anesthesia, 358 intraoperative, reversal of, 215 monoamine oxidase inhibitors with, complications of, 105-106 overdose of, pulmonary edema and, 215 Narcotics Anonymous, 126 National Institute for Clinical Excellence (NICE), preoperative test guidelines of, 145 Natriuretic peptides, actions and side effects of, 4t Natural products, and synthetic congeners, 110 Naturopathy, 150 Nausea and vomiting, neuraxial opioids and, 72, 73, 262 physiology of, 644, 645f postoperative, 134-136 after tonsillectomy, 688, 689-690, 691 antiemetics for, 645, 646t, 647, 892t. See also Antiemetic drugs. complications with, 891-892, 892t effects of, 644 in children, 644-648 in intracranial hypertension, 701 in laparoscopic surgery, 832 intractable, 890-892 management of, 265, 644-645, 646f multimodal analgesic techniques and, 265 prevention of, 136, 645, 646t, 647-648 risk factors for, 644, 645t, 890-891, 891t, 894t unanticipated hospital admission and, 894, 895 with syrup of ipecac for poisoning, 509, 510t Nebulizers, problems with, 544-545 Neck. See Spine, cervical. Necrosis, fulminant hepatic, 66-68 ischemic pituitary, antepartum bleeding and, 777 skin, arterial cannulation and, 579 Needle(s), injury with, avoidance of, 208 in peripheral nerve block, 285-286 post–HIV exposure prophylaxis and, 447 insertion of, for injection of neurolytic solutions, 254, 256

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Needle(s), insertion for (Continued) in psoas compartment block, 260 in retrograde tracheal intubation, 170, 170f in transtracheal jet ventilation, 170, 172f interosseous, drug delivery by, 616, 618f spinal, post–dural puncture headache and, 224, 224f, 226 Negligence, 933 by anesthesiologist, 942, 943 in syringe swaps, 925 statute of limitations on, 943 Neonates. See also Infants. intraoperative hyperglycemia in, 658 persistent pulmonary artery hypertension of, 659 retinopathy of prematurity and, 694 shunting in, hypoxemia and, 639 upper airway in, 603, 604f venous air emboli in, 675 Neoplasm, intracranial, postpartum headache with, 796 Neostigmine, for residual neuromuscular block, in Lambert-Eaton myasthenic syndrome, 489 glycopyrrolate and, 30 postoperative nausea and vomiting and, 647 Nephrectomy, radical, complications of, 846-849 Nephritis, interstitial, NSAID action and, 275 Nephron, acute renal failure and, 342, 343f Nephropathy, pigment, acute renal failure and, 344, 345 Nephrotic syndrome, 275, 276 Nephrotoxicity, acute renal failure and, 345 methoxyflurane-induced, 67 Nerve(s), common peroneal, 790, 791f, 792f, 792t compression of root, 239 femoral, block of, for outpatient knee surgery, 267t injuries of in childbirth, 790, 792t laryngeal, after thyroid surgery, 818, 819, 820, 821 lateral femoral cutaneous, 790, 792t lumbosacral plexus, dermatomes of, 790, 792f urinary retention and, 837 obturator, injuries of, 790, 792t, 847-848 peripheral, blood supply of, 286 local anesthetic selection and, 286 phrenic, in unintended intrathecal injection, 243 vs. pneumothorax, 251 radial, injury of, with tourniquet use, 867, 869 sciatic, 790, 791f, 792t splanchnic, in celiac plexus block, 254 tibial, injuries of in childbirth, 790, 792t trochlear, 708 ulnar, injuries of, 336, 881-883, 882f, 883f Nerve block, continuous, perineural local anesthetic infusion in, 282-283 interscalene, 248-250 approaches used for, 249, 249f neuraxial. See Neuraxial blockade. of peripheral nerves. See Peripheral nerve block. Nerve conduction, needle trauma and, 286 Nerve entrapment syndrome, 882 Nerve injury, double-crush concept of, 286 from peripheral nerve block, 285-287 from tourniquets of extremities, 867-870 in childbirth, 790, 791f, 792f, 792t in radical urologic surgery, 847-848, 849

Nerve injury (Continued) in regional anesthesia, 285-287 in spinal surgery, 871, 873 neurapraxic, tourniquet use and, 867, 869, 870 of laryngeal nerves, after thyroid surgery, 818, 819, 820, 821 of peripheral nerves, 285-287, 336-338 causes of, 336 diagnosis of, 336 in childbirth, 790, 792t ischemic, 881, 881f, 882, 883 management and prevention of, 337-338 postoperative complications with, 881-884 risk factors for, 336-337, 337t preexisting, regional anesthesia and, 286-287 Nerve root, compression of, 239 Nerve stimulator, in peripheral nerve block, 266, 267f, 286, 287 for detection of prolonged neuromuscular block, 89, 90, 91 in psoas compartment block, 258, 260 Nesiritide, for prevention of acute renal failure, 345 Neural control, of voiding, 836-837, 836t Neurally mediated syndromes, pacing for, 401t, 402 Neurapraxia, 867, 869, 870, 881 Neuraxial blockade, bradyarrhythmias due to, 333 celiac plexus block and, 254-256 central, 223-260 infectious complications of, 239-241 spinal anesthesia and, cauda equina syndrome and, 227-229 post–dural puncture headache with, 223-226 unintended intrathecal injection and, 242-243 unintended subdural injection and, 244-247 deliberate hypotension and, 857 in anticoagulated patients, ASRAPM guidelines for, 271, 271t in obstetric patients, neurologic complications with, 789 interscalene nerve block and, 248-250 local anesthetics in, systemic toxicity of, 230-234 urinary retention and, 838 opioids in, side effects of, 261-264 postoperative pain control and, 897 psoas compartment block and, 257-260 spinal hematoma and, 235-238 heparinization and, 236, 864 supraclavicular block and, pneumothorax and, 251-253 Neuritis, idiopathic brachial, 336 Neuroblastoma, pediatric, 909t Neurocardiogenic syncope, pacing for, 402 Neurocognitive testing, for detection of central neurologic injury, 339 Neuroexcitation, delayed, with propofol and etomidate, 82 nonbarbiturate anesthetic use and, 83 Neurofibrillary tangles, in Alzheimer’s disease, 493 Neurokinin-1 receptor antagonists, for emesis, 136 Neuroleptic antipsychotic drugs, for postoperative delirium, 889 Neuroleptic malignant syndrome, with antiemetic drugs, 136

979

Neurologic complications, from celiac plexus block, 254, 255f from central nervous system impairment, 339-341 from continuous perineural local anesthetic infusion, 282, 283 from neuraxial blockade, 235 from peripheral nerve injury, 336-338 from psoas compartment block, 259-260 from regional anesthesia, 285-287 peripartum, 789-794 management and prevention of, 793-794 recognition of, 789 risk assessment with, 790-793, 791f-793f, 792t Neurologic dysfunction, after subarachnoid hemorrhage, 715 in acute porphyria, 75 in cervical spine injuries, 177 in children, hypoglycemia and, 658 in HIV-infected patients, 449 in hyperthermia, 424 in spinal epidural abscess or meningitis, 239, 240 inflammatory response after cardiopulmonary bypass and, 354 Neurolytic solutions, in celiac plexus block, 254, 255f injection of, tests for, 254, 256 Neuromuscular blockade, herb and nutraceutical effects on, 154t monitoring of, 91 residual, delayed emergence and, 886 hypercarbia and, 878-879 in airway obstruction, 877 residual unrecognized, 90 reversal of, for postoperative nausea and vomiting prevention, 647 succinylcholine use and, 85, 86, 87. See also Succinylcholine. in children, 623, 625 Neuromuscular blocking agents. See also Muscle relaxants. anaphylactic and anaphylactoid reactions and, 98, 99t for opiate-induced muscle rigidity, 175 in awareness under anesthesia, 939 nondepolarizing, 89-91 in myasthenia gravis, 489 Neuromuscular junction hypersensitivity, in spinal cord injury, 738 Neurons, calcium channel function and, 50 Neuropathy. See also Nerve injury; Neurologic dysfunction. ischemic optic. See Ischemic optic neuropathy. peripheral nerve, local anesthetic selection and, 286 management and prevention of, 883-884 postoperative, 881-884 risk assessment of, 881-883, 882f, 882t, 883f postpartum, AIDS-related, 793 diabetic, 793 Neurosurgery, 701-740 in children, 728-731 Neurotmesis, 881 Neurotoxicity, local anesthetic–induced, cauda equina syndrome and, 227-229 nitrous oxide–induced, 69-71 case reports of, 69, 70t Neurotransmitters, brainstem, antiemetic drug action and, 134t

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Page 980

Index

Neurovascular sheath cannulation, complications with, 269-270 Neutrophil(s), injury of, in acute respiratory distress syndrome, 349 Newborn. See also Infants; Neonates. persistent pulmonary artery hypertension of, 659 Nicaraven, for prevention of vasospasm, 722 Nicardipine, actions and side effects of, 4t for autonomic hyperreflexia, 478 for cesarean delivery in preeclamptic patients, 761 for electroconvulsive therapy, 904 for hypertension, 314, 824 in pregnancy, 761 for induced hypotension, 873 for intracranial aneurysm rerupture, 716 for tocolytic therapy, 765 Nicotinic signs, with anticholinesterase poisoning, 30 Nifedipine, for autonomic hyperreflexia, 478 for hypertension in pregnancy, 761 for tocolytic therapy, 765 Nimodipine, for prevention of vasospasm, 721-722 Nitrates, sildenafil and, 20, 21 Nitric oxide, actions and side effects of, 4t for pulmonary vasodilatation without systemic vasodilatation, 5-6 in erectile dysfunction, 21 inhaled, for acute respiratory distress syndrome, 350 for pulmonary hypertension, 317, 661 overproduction of, hypotension and, 7 phosphodiesterase-5 inhibitors and, 20 sildenafil and, 21 Nitrogen, exhaled, venous air embolism and, 674, 675 Nitroglyceride, for induced hypotension, 873 Nitroglycerin, actions and side effects of, 4t for adrenalectomy, 825 for cesarean delivery in preeclamptic patients, 761 for electroconvulsive therapy, 904, 905 for hypertension, 313-314 for myocardial ischemia, 310 phosphodiesterase-5 inhibitors and, 20, 21 sildenafil and, 21, 22 Nitroprusside, for hypertension, 313-314 for intracranial aneurysm rerupture, 716 Nitrous oxide, for postoperative nausea and vomiting, 647 in EXIT procedure, 609, 610 in inspired and expired gases, monitoring of, 574 in operating room, fire risk and, 565t pipeline supply of, 515, 516 proportioning systems for oxygen and, 518, 520, 521-523 risk assessment with, 69, 70 scavenging systems for, 540 intracranial hypertension and, 703 maternal, in open fetal surgery, 768 neurophysiologic effects of, 729t neurotoxicity of, 69-71 case reports of, 69, 70t management of, 70-71 prevention of, 71 risk assessment with, 69, 70 teratogenic effects of, 799, 800 venous air emboli and, 676, 704, 707, 788 Nizatidine, 93 N-methyl-D-aspartate, in Alzheimer’s disease, 494

Nonbarbiturate anesthetics, 80-83 complications with, management of, 83 prevention of, 83 selection of, 81-82, 83 Non-Hodgkin’s lymphoma, doxorubicin for, 110 Nonketotic hyperosmolar syndrome, 415 Non-nucleoside reverse transcriptase inhibitors, for HIV infection, 447, 448t Nonopioids, dependence on, 119-121 Nonsteroidal anti-inflammatory drugs (NSAIDs), action of, 273, 273f allergy to, 275 chronic use of, 273-277 for postoperative pain control, 897 for prevention of neuraxial opioid complications, 263 in cardiac surgery patients, 359 side effects of, 273-275, 274f, 274t spinal hematoma and, 236, 237, 237t Norepinephrine, adrenal tumors and, 822 as inotropic drug, 11, 12t for acute renal failure, 345 for hypothermia, 663 for pulmonary hypertension, 317 for sepsis, 498 side effects of, 8, 8t Normal perfusion pressure breakthrough, after arteriovenous malformation resection, 724-727 management and prevention of, 726-727 pathophysiology of, 724-725 recognition of, 726 risks of, 726 Normocarbia, in carotid endarterectomy, 382 Normoglycemia, in carotid endarterectomy, 382 in central neurologic injury, 340 Normothermia, in carotid endarterectomy, 382 in intracranial aneurysm rerupture, 716 in pulmonary hypertension, 317 in revascularization for peripheral vascular disease, 397 in traumatic brain injury, 730, 735-736 Normovolemia, for prevention of vasospasm, 721 North American Dräger proportioning systems, 521, 522f, 523 Nosocomial pneumonia, diagnosis of, 210-212 Nuclear protein, in muscular dystrophy, 480 Nucleoside analogue reverse transcriptase inhibitors, for HIV infection, 447, 448, 448t Nursing staff, 73, 448t, 647 Nutraceuticals, 150 common uses of, 155t, 156t perioperative management of, 151, 154 risk assessment for, 151 side effects of, 151, 152t-154t use of, 150-151 O Obesity, definition of, 810 morbid, lithotripsy and, 852 risk assessment in, 810-812, 811t, 812t surgery in, 810-813 management of, 812-813 Obstetrics and gynecology, 759-804 Obstructive sleep apnea, in morbidly obese, 811 in muscular dystrophy, 481 sedation in children and, 620 tonsillectomy and, 688, 688t, 689, 690, 691 Obturator nerve, injuries of, in childbirth, 790, 792t in radical urologic surgery, 847-848 Occurrence screening, in quality assurance program, 927-928

Octreotide acetate, in carcinoid syndrome, 815, 816 Oculocardiac reflex, in children, 695-696, 696f, 696t in retrobulbar block, 748 Oculomotor nerve, 708 in intracranial hypertension, 701 Odontoid hypoplasia, 176 Ohmeda anesthesia machine, scavenging system of, 540, 541f Ohmeda Tec 6 vaporizer, 531 Ointments, flammable, in operating room, 563, 565t OKT3, toxicity of, 501 Olanzapine, for postoperative delirium, 889 Oliguria, acute renal failure and, 342 hypovolemia and, 63 in preeclampsia, 760 Ombudsman, 943 Omeprazole, for pulmonary aspiration prevention, 643t Ondansetron, for postoperative nausea and vomiting, 645, 646t, 647 for prevention of neuraxial opioid complications, 263 receptor site affinity of, 134t side effects of, 135t Open-heart procedures, 340, 463 Operating room, do-not-resuscitate orders in, 946-947 efficiency of, delayed emergence and, 629 electric shock in, 560, 561 explosions in, 562-566 fires in, 562-566 nitrous oxide in, fire risk and, 565t pipeline supply of, 515, 516 proportioning systems for, 518, 520, 521-523 scavenging systems for, 540 temperature in, hypothermia prevention and, 665 Ophthalmic complications, in children, 692-697 Ophthalmology, 741-749. See also Eye(s). Opioids, anaphylactic or anaphylactoid reactions associated with, 99t dependence on, 119-121. See also Opioids, tolerance of. complications of, 120-121 death rate in, 120-121 epidural. See Opioids, neuraxial. equianalgesic conversion doses of, 279t for patients with porphyria, 76 intrathecal. See Opioids, neuraxial. midazolam and, 81 muscle rigidity with, airway difficulty with, 174-175 neuraxial, complications of, 72-73, 72t, 263, 263t for labor and delivery, 262-263 nausea and vomiting with, 262 pruritus with, 262 respiratory depression with, 261-262, 262t sedation with, 262 side effects of, 261-264 urinary retention with, 262 neurophysiologic effects of, 729t postoperative nausea and vomiting and, 647 postoperative pain control and, 897 reversal of, 128, 129t synthetic, with monoamine oxidase inhibitors, 105 tolerance of, 278-281 adjunctive medications with, 280

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Opioids, tolerance of (Continued) definitions of, 278, 278t discharge instructions for patients with, 280 drug addiction and, 280-281 management of, 279-280, 279t risk of, 278-279 toxicity of, in analgesia for opioid-tolerant patients, 280 Optic globe, open, injuries of, 745-746 penetration of, in retrobulbar block, 748 Optic neuropathy, ischemic postoperative, in children, 693 in spinal surgery, visual loss with, 856, 857, 873 Orbit, cross-section of, 743f Organ dysfunction, after cardiopulmonary bypass, 352-355 criteria for, 498t of multiple organs, acute respiratory distress syndrome and, 350 criteria for, 498t immunosuppression and, 502 in cholecystectomy in cirrhotic patients, 808 systemic inflammatory response syndrome and, 496-499 Organ transplantation, infection risk in, 501 Organophosphates, poisoning with, 30 Oropharynx, angioedema of, ACE inhibitors and, 17-18 Orthopedic surgery, 855-874 outpatient, anesthesia and analgesia in, 265 peripheral nerve block for, 265-268 advantages of, 266 contraindications to, 266 methods of, 266, 267t prevention of complications with, 268 thromboembolism risk and, 364, 862-864 Orthopnea, in revascularization procedures, 396 tracheal narrowing and, 374 Orthostatic hypotension, neurolytic celiac plexus block and, 254, 256 Osmolality, of fluids, intracranial hypertension and, 702 plasma, in hypernatremia, 433 measurement of, 429-430 Osmotic cathartic, for poisoning, 509 Osmotic demyelination syndrome, 432 Outcomes, adverse, misinformation and, 942-943 Outpatient surgery, anesthesia and analgesia in, 265 goals for, 265 orthopedic, peripheral nerve block for, 265-268 unanticipated hospital admission for, 894 Oxazolidinone, for methicillin-resistant Staphylococcus aureus infection, 211 Oxidizers, in operating room, fire hazard with, 562, 563, 565t Oximetry, pulse. See Pulse oximetry. venous, jugular bulb, 720 Oxycodone, acetaminophen with, toxicity of, 280 equianalgesic conversion doses of, 279t Oxygen. See also Hypoxemia; Hypoxia. alveolar-arterial partial pressure difference of, hypoxemia and, 194t arterial pressure of, pulse oximetry and, 570, 570f consumption of. See Oxygenation. for opiate-induced respiratory depression, 73 for sarcoidosis, 460

Oxygen (Continued) for venous air embolism, 707 hemoglobin affinity for, by age, 637t hyperventilation with, after intracranial aneurysm rerupture, 716, 716t in operating room, fire risk and, 562, 563, 564, 565, 565t pipeline failure of, algorithm for, 516, 517f contamination or pressure errors in, 515, 516 crossover errors in, 515 proportioning device of, of anesthesia machine, 518, 520, 521-523, 521f, 522f reduced level of. See Hypoxia. in systemic inflammatory response syndrome, 497 inspired, high concentrations of, perioperative infection and, 502 low concentrations of, 193. See also Hypoxia. monitoring of, 574, 575t myocardial, myocardial ischemia and, 310, 310t, 311 response to, hypoxemia and, 194t Oxygen cascade, 194f Oxygen delivery, deliberate hypotension and, 855 inotropic drug use and, 11 monitoring of, by pulse oximetry, 570-572 organ, assessment of, 197t perioperative hypoxia and, prevention of, 198t tissue, assessment of, 197t vasopressor therapy and, 9 Oxygen flush, flowmeter malfunction and, 520 valve of, 524-525, 524f, 525f, 525t, 532 Oxygen free radicals, anthracycline antibiotic action and, 116 Oxygen Ratio Controller proportioning system, 518, 521, 522f, 523 Oxygen saturation, brain, in traumatic brain injury, 733 in hypoxemia, 637 jugular venous, 702 pulse oximetry and, 570, 570f, 571 tourniquet release and, 868 Oxygen sensor, 515 Oxygen tension, blood, in children and infants, 637t brain, in traumatic brain injury, 702, 733 retinopathy of prematurity and, 694 Oxygenation. See also Oxygen. fetal, in fetal distress, 770 in acute respiratory distress syndrome, 350 in anaphylactic or anaphylactoid reactions, 99 in burn-injured patients, 506-507 in hyperthermia, 423 in infants, 638 in pregnancy, cardiovascular bypass and, 802-803, 803f in nonobstetric surgery, 800 monitoring of, 570-572 ASA standards for, 576 myocardial, intra-aortic balloon pump and, 409 postobstruction pulmonary edema and, 215 preinduction, 159 vs. ventilation, pulse oximetry and, 571 Oxygenator, in cardiopulmonary bypass, 303, 304 Oxygen-hemoglobin dissociation curve, 571f anemic hypoxia and, 195-196, 195f in neonates, hypoxemia and, 639 Oxytocin, for uterine atony, 780-781

981

P P waves, in bradycardia, 331, 332 in heart block, 14, 14f Pacemakers, cardiac risk and, 147 features of, 399 for bradycardia, 331-332 for muscular dystrophy, implanted, 481 interference with, by surgical diathermy and electrocautery, 556, 558, 559 electromagnetic, 404, 404f leads of, 399, 400, 561 lithotripsy and, 852 malfunction of, 402-404, 404f Pacing, antitachycardia, 399, 403 biventricular, indications for, 402 dual-chamber, 334 for intraoperative bradycardia in heart transplant patients, 16 for long QT syndrome, 329 in pacemakers and internal cardioverter-defibrillators, 399 overdrive, for drug-induced torsades de pointes, 46 permanent, indications for, 400, 401t temporary, 399-400 for congenital long QT syndrome, 329 indications for, 400, 400t with surgical diathermy or electrocautery, 559 transcutaneous or transvenous, for calcium channel antagonist toxicity, 51 transesophageal, for bradyarrhythmias due to general anesthesia or surgery, 333 Packed red blood cells, in antepartum bleeding, 777 in subarachnoid hemorrhage, 720 indications for, in children, 678, 679t Pain. See also Analgesia. abdominal, in pancreatitis, 473 assessment of, 896, 896t in acute porphyria, 74, 76 in continuous perineural local anesthetic infusion, 283 management of, 261-288, 896-897, 897t for prevention of myocardial ischemia, 311 for prevention of nosocomial pneumonia, 211 in drug abusers, 280 in opioid-tolerant patients, 279-280, 279t opioids for, 883. See also Opioids. postoperative respiratory insufficiency and, 880 neck, in cervical spinal injuries, 177 postoperative, after tonsillectomy, 688, 689-690, 691 apnea in infants and, 614 delirium and, 888 emergence agitation and, 685 multimodal analgesic techniques and, 265 myocardial ischemia and, 311 pulmonary hypertension and, 317, 318 respiratory insufficiency and, 880 tourniquet use and, 868, 869 unanticipated hospital admission and, 894, 895 uncontrolled, 896-898 “Pain and spasm” syndrome, histamine release and, 101 Pancreatic cancer, celiac plexus block and, 254 Pancreatitis, acute, 473-476 causes of, 473, 473t, 474t definition of, 473

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Pancreatitis, acute (Continued) grading of, 474-475, 474t, 475t management of, 475-476 prevention of, 476 signs and symptoms of, 473-474, 474t necrotizing, sterile or infected, 476 Pancuronium, 89t, 90 for rapid-sequence induction in open globe injury, 745-746 in children, dose, clearance, and side effects of, 624t Pantoprazole, for prevention of pulmonary aspiration, 643t Papaverine, 22t angioplasty with, for vasospasm, 721 Papilledema, in intracranial hypertension, 701 Papillotomy, in acute pancreatitis, 475 Para-aminobenzoic acid (PABA), allergic reactions to, 233 Paralysis, spinal cord, postpneumonectomy, 379 Paramagnetic analyzers, 575 Paraplegia, in thoracic aortic aneurysm repair, 387, 388 lithotripsy and, 852 neurolytic celiac plexus block and, 256 Parasympathetic activity, bronchial smooth muscle tone and, 189 urinary retention and, 838 Parathyroid hormone, 818, 819 Paravertebral block, to interscalene nerve block, 249, 249f Parents, medical decision making for children by, 949 presence of during anesthesia induction in child, 683 Paresis, hemidiaphragmatic, vs. pneumothorax, 251 Paresthesia, in childbirth, 792, 793 persistent, 285-287 Parkinson’s disease, 490-492 drugs contraindicated in, 491-492, 491t drugs used in, 490-492, 491t Paroxetine (Paxil), 108 Paroxysmal atrial tachycardia, with atrioventricular heart block, digitalis toxicity and, 25 Paroxysmal supraventricular tachycardia. See also Wolff-Parkinson-White syndrome. anticholinergic-induced, adenosine and, 31 causes, prevention and treatment of, 322t electrocardiographic features of, 320t with ventricular preexcitation, 324, 325, 326 Partial thromboplastin time, in infants and children, 677 Patient(s), autonomy of, 944, 946, 947, 949 awake, neurologic assessment of, for detection of cerebral ischemia, 380-381, 380t awareness of, under anesthesia, 939-941 competent adult, medical decisions by, 949 confidentiality of, 944-945 education of, for early extubation anesthesia, 358 hostile-combative, 936-938 identification of, errors in, 921-923 recommended rules for, 922 incompetent, consent for treatment of, 937 in emergencies, 949 medical decision making by, 949 informed consent of, medicolegal aspects of, 937 of Alzheimer’s disease patients, 493, 494 of minors, 944-945 Jehovah’s Witness, 948-950 minor, consent for treatment by, 937

Patient(s) (Continued) medical decision making by, 944-945, 949 medical records of, 944 population of, variability in, 141, 142 pregnant. See Pregnancy. privacy rights of, 944 Patient Bill of rights, 944 Patient state analyzer, awareness under anesthesia and, 940 Patient-controlled analgesia, in drug abusers, 280 in opioid-tolerant patients, 279-280, 279t Peak expiratory flow rate, in children, 374 Pediatric advanced life support protocol, intraoperative cardiac arrest and, 616 Peer review, in quality assurance program, 928 Penicillin G, complications of, 102t Penile erection, intraoperative, 840-842 management of, 841, 841t prevention of, 841-842 mechanism of, 840 Pentoxifylline, phosphodiesterase selectivity of, 22t Peptic ulcers, gastric prostaglandins and, 273 NSAIDs and, 276 Pergolide, in Parkinson’s disease, 490, 491t Peribulbar block, for regional anesthesia of eye, 749 Pericardial effusion, respiratory complications and, 374 Pericardial tamponade, central venous catheter–related, 582t Pericarditis-myocarditis syndrome, anthracycline antibiotics and, 116 Perineural tissue, uptake of local anesthetic in, 231, 232t Periodontal disease, in preoperative anesthetic examination, 183 Peripheral nerve(s), blood supply of, 286 injury of, 285-287, 336-338 causes of, 336 diagnosis of, 336 in childbirth, 790, 792t ischemic, 881, 881f, 882, 883 management and prevention of, 337-338 postoperative complications with, 881-884 risk factors for, 336-337, 337t local anesthetic selection and, 286 stimulation of, 266, 267f, 286, 287 for detection of prolonged neuromuscular blockade, 89, 90, 91 Peripheral nerve block, anticoagulant therapy and, 269-272 benefits of, 269, 269t for orthopedic outpatient surgery, advantages of, 266 contraindications to, 266 methods of, 266, 267t prevention of complications with, 268 risks of, 266 hemorrhage with, 269-270, 270t management and prevention of, 271-272, 271t in patients with coagulopathies, 272 nerve damage after, 285-286 vascular injury with, 270 Peripheral vascular surgery, 394-397 complications of, 394 management of, 396-397 prevention of, 397 risks with, 394, 396 Permeability pulmonary edema, 348 Pernicious anemia, nitrous oxide anesthesia and, 69

Peroneal nerve, common, in childbirth, 790, 791f, 792f, 792t Perphenazine, for postoperative nausea and vomiting, 646t, 647 pH, alpha-stat, in cardiopulmonary bypass, 341 delayed emergence and, 886 gastric, in pulmonary aspirate, 641, 642, 783, 784 hyperkalemia and, 55 in diabetic ketoacidosis, 418 of stored blood, 680, 680t pulmonary vascular resistance and, 316 serum, 436 Pharmacokinetics, automated drug delivery systems and, 548, 548f, 549 Pharmacotherapy, in cardiopulmonary bypass, central neurologic injury and, 341 Phase II block, succinylcholine and, 85, 86, 87 Phenergan, sedation in children and, 620, 621 Phenothiazines, potential complications of, 136 receptor site affinity of, 134t side effects of, 135t Phenoxybenzamine, for adrenalectomy with pheochromocytoma, 826 Phentolamine, actions and side effects of, 4t Phenylephedrine, for α2-agonist–induced hypotension, 95 Phenylephrine, for detumescence of penile erection, 841 maternal, in open fetal surgery, 768 side effects of, 8, 8t Phenytoin, dose of, 39t Pheochromocytoma, adrenalectomy for, medical and anesthetic management in, 825 risks of, 823 tumor removal in, 825-826 presentation and diagnosis of, 822, 823t, 824t Phosphate, in acid-base balance, 436, 437t replacement of, in diabetic ketoacidosis, 418 Phosphodiesterase inhibitors, 20-23 for myocardial ischemia, 311 selectivity of, 22, 22t Phosphodiesterase-3 inhibitors, action and uses of, 22 after cardiopulmonary bypass, 12, 12t inotropic drugs as, 11, 11t Phosphodiesterase-4 inhibitors, action and uses of, 22 Phosphodiesterase-5 inhibitors. See also Sildenafil. intraoperative myocardial ischemia and, 20-22 Phospholipase A2, in pancreatitis, 473 Phospholipase C, muscarinic receptor stimulation and, 28 Phospholipids, platelet, in coagulation cascade, 361 Phrenic nerve, in unintended intrathecal injection, 243 vs. pneumothorax, 251 Physical dependence, definition of, 278t Physicians, drug dependence in, on nonopioids, 122-127 on opioids, 119-121 treatment of, 125-126 Physiologic imbalance, coexisting disease and, 415-441 delayed emergence and, 627 Physostigmine, delayed emergence and, 887 in children, 630, 630t for emergence agitation in children, 686 for postoperative delirium, 889 Pia mater, anatomy of, 242 deliberate hypotension and, 856 Pickwickian syndrome, in morbidly obese, 810

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Page 983

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Pigment nephropathy, acute renal failure and, 344, 345 Pipecuronium, dose, clearance, and side effects of, 624t Pipeline, components of, 515, 516f failure of, 515, 515t Pituitary necrosis, ischemic, antepartum bleeding and, 777 Pituitary tumors, diabetes insipidus and, 712-713 suprasellar, 712, 713 transsphenoidal approach to, 712 Placenta, retained, extraction of, 780 postpartum hemorrhage with, 779, 779t Placenta accreta, 774 Placenta previa, 774, 775f, 776t, 777t Placental abruption, 775, 776t, 777t Plasma, fresh frozen, for coagulation factor deficiencies, 308 transfusion with, 679t Plasma cholinesterase, succinylcholine use and, in children, 623, 624 Plasma membrane–associated proteins, in muscular dystrophy, 479-480 Plasma osmolality, 429 in hypernatremia, 433 measurement of, 429-430 Plasmapheresis, preoperative, in myasthenia gravis, 489 Platelet(s), COX-1 and COX-2 metabolism and, 274 dysfunction of, in end-stage renal disease, 462-463, 464 in hypothermia, 420 postoperative bleeding after cardiac surgery and, 306, 308 phospholipid of, in coagulation cascade, 361 transfusion of, 306, 308, 679t Platinum coordination complexes, 110 Pleural line, white visceral, in pneumothorax, 252, 252f Pleural space, 251, 252 “Plumb-bob approach,” pneumothorax and, 252 Pneumatic compression devices, for prevention of deep venous thrombosis, 863 Pneumocephalus, postpartum headache with, 797 Pneumocystis jirovecii pneumonia, in HIVinfected patients, 448-449 Pneumomediastinum, in one-lung ventilation, 365 Pneumonectomy, complications after, 376-379, 377t management and prevention of, 377-379 indications for, 376-377 patient selection for, 376, 377f right-sided vs. left-sided, 376-377 Pneumonia, aspiration, postobstruction pulmonary edema and, 635 bacterial, 210-212 diagnosis of, 210 in HIV-infected patients, 448-449 management and prevention of, 211 risk factors for, 210-211 in immunocompromised patients, 501 nosocomial, 210-212 Pneumocystis jirovecii, in HIV-infected patients, 448-449 ventilator-associated, 210 Pneumonitis, aspiration, in children, 641-643 in pregnancy, 767 chemical, in parturients, 782-785 Pneumoperitoneum, carbon dioxide–induced, in laparoscopic surgery, 831, 833, 834

Pneumothorax, central venous catheter–related, 582 in hypoxemia, 878 in laparoscopic surgery, 833, 834 management of, 253 physiologic changes in, 253 recognition of, 251-252 supraclavicular and infraclavicular block with, 251-253 surgically induced, in radical urologic surgery, 846, 848 tension, in laparoscopic surgery, 833, 834 intraoperative cardiac arrest and, 616 pressure in breathing circuit and, 542 risk of, 253 Poisoning, anticholinesterase, vs. anticholinergic toxicity, 29-30 antidotes for, 509, 510t complications from, 508-512 management of, 509-511, 510t, 511t prevention of, 511 Polymethylmethacrylate bone cement, embolic injury with, 865-866 Polypeptides, in carcinoid syndrome, 815t Polyuria, causes of, other than diabetes insipidus, 712t definition of, 66 in diabetes insipidus, 712, 713 Pons. See Brainstem. Porphobilinogen, acute porphyria attacks and, 470, 470f, 471 Porphyria(s), acute, 74, 75t anesthetic management of, 76-77, 76t causes of, 470, 471t drug safety with, 76t, 77 inheritance of, 74, 75 management and prevention of, 76-77, 76t, 471-472 prevalence of, 75 recognition of, 74-75, 470-471, 471t risk assessment for, 75-76, 470, 471, 471t symptoms of, 74-75, 75t acute intermittent, 74, 75t barbiturate-induced, 74-77 δ-aminolevulinic acid dehydratase–deficient, 74, 75t hereditary coproporphyria, 74, 75t variegate, 74, 75t Porphyria cutanea tarda, barbiturate-induced, 74 Porphyrias, 470-472 heme synthesis and, 470, 470f Porphyric crisis, 74, 75t Porphyrins, synthesis of, 74, 74f Portopulmonary hypertension, in hepatopulmonary syndrome, 467 Position (patient), in acute respiratory distress syndrome, 350 in cardiac surgery, peripheral nerve injury and, 337 in laparoscopic surgery, 831, 831t, 833, 834 in morbidly obese patients, 813 in nosocomial pneumonia, 211 in orthostatic hypotension, 254 in post–dural puncture headache, 224 in posterior fossa surgery, 710, 710t in radical urologic surgery, 846-847, 848, 849 in spinal cord injury, 739, 873 in traumatic brain injury, 735 in children, 730 in unintended intrathecal injection, 243 in venous air embolism, 673, 676, 704, 705t, 706, 708, 709, 788 intraoperative, cervical spine injuries and, 179

983

Position (patient) (Continued) eye protection and, 693 in burn-injured patients, 507 prone, in spinal surgery, postoperative visual loss and, 693-694, 856, 857, 873 semisitting, for management of airway edema, 879, 880 sitting, venous air embolism and, 708, 709 supine, compressed tracheobronchial tree in, 373f Trendelenburg, in radical urologic surgery, 846, 847, 849 in spinal surgery, postoperative visual loss and, 856, 857 Positive end-expiratory pressure (PEEP), for venous air embolism prevention, 707 in acute respiratory distress syndrome, 350, 351 in one-lung ventilation, 369 in postobstruction pulmonary edema, 215, 216 in sepsis, 498 Positive pressure ventilation, for opiate-induced respiratory depression, 73 in laparoscopic surgery, 834 tension pneumothorax in, 253 Positron emission tomography (PET), for diagnosis of vasospasm, 719 Postanesthesia care unit, 877-902 delayed emergence and, 885, 886 hypoxemia in, in infants and children, 639 Postconceptual age, postoperative apnea and, 611, 612f, 613, 613f Post–dural puncture headache, clinical features of, 223 epidural blood patch for, in HIV-infected patients, 449 management of, 224-226, 225f postpartum, 797 spinal anesthesia and, 223-226 Posterior fossa, anatomy of, 708 lesions of, effects of, 708 surgical approach to, 708-709 vs. supratentorial lesions, 708, 710 surgery on, 708-711 management of, 710 monitoring in, 709, 710 surgical stimulation of, 708 Posterior lumbar plexus block, hemorrhagic complications after, 270 Postintubation croup, in children, 631-632 Postobstruction pulmonary edema. See Pulmonary edema, postobstruction. Postoperative nausea and vomiting. See Nausea and vomiting, postoperative. Postpartum headache, 795-798 classification of, 795t management of, 796, 798t migraine-type, 795-796, 798t secondary, 796-797, 798t tension-type, 796, 798t Postpneumonectomy syndrome, 378 Post-tourniquet syndrome, 868, 869, 870 Potassium, intracellular vs. extracellular, hyperkalemia and, 55, 56, 464, 464t hypokalemia and, 55 magnesium modulation of, 59, 59t rapid changes in serum levels of, arrhythmias and, 56 release of, in cervical spine injuries, 179 with succinylcholine, 85, 85t, 86 replacement, 57 in diabetic ketoacidosis, 418

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Page 984

Index

Potassium (Continued) serum, electrocardiographic changes and, 462, 463t in acute hyperkalemia, 464, 464t Potassium channel blockers, 44-46 risk of torsades de pointes and, 45 Potassium chloride, for digitalis toxicity, 26 intravenous administration of, 57 Potassium iodide, for inhibition of thyroid hormone synthesis, 456 for thyroid storm, 820 P-Q interval, in hyperkalemia, 54 Pramipexole, in Parkinson’s disease, 490, 491t Preanesthetic evaluation, computerized, 146 false-positive tests in, 141-143 inadequate or missing test results in, 144-146 Prednisolone, glucocorticoid and mineralocorticoid potencies of, 132t Prednisone, dose of, response to short ACTH test and, 131 for anaphylactic or anaphylactoid reactions, 100 glucocorticoid and mineralocorticoid potencies of, 132t Preeclampsia, diagnosis of, 759, 760t magnesium infusion and, 59, 60, 61 management of, anesthetic, 761 obstetric, 760-761 postpartum headache with, 797 prevention of, 761-762 recognition of, 759 risks with, 759-760 Pregnancy, anaphylactoid syndrome of, 786 anesthetic risks in, 766-767, 799 antepartum bleeding in, 774-778 aspiration risk in, 782-785, 782t bleeding in, ectopic, 774, 776t, 777t unclassified, 775-776, 776t blood volume changes in, 776-777 cardiac output in, 777 cardiopulmonary bypass during, 802-804 embolic events in, 786-788 headache in, 796 HIV or AIDS in, complications with, 449 hypertensive disorders of, 759-762, 759t medical decision making in, 949 neurologic complications in, 789-794 nonobstetric surgery during, 799-800 physiologic changes during, anesthesia and, 799 refusal of medical therapy in, ethical issues with, 949 thromboembolic disease and, 362, 363-364 Preload, in cardiomyopathy, 668 Premarin, for bleeding in uremic patients, 464 Prematurity. See also Preterm labor. apnea of, 611, 612 central apnea and, hypoxemia and, 639 postoperative apnea and apnea of, 611, 612 retinopathy of, 694 risks with, 763 Premedication, in children, 604, 684 for radiation oncology, 910 in muscular dystrophy, 482 in pregnant patients, for cardiopulmonary bypass, 803 for EXIT procedure, 609 in uncooperative patients, 937 with anticholinergics, 28 Preoperative interview, in uncooperative patients, 937-938 Preoperative testing, cost containment and, 930

Pressure, at contact point, thermal injury from warming devices and, 550-551, 551f, 551t, 552 breathing circuit, scavenging system and, 540-542 carotid stump, for detection of cerebral ischemia, 381 from tourniquets, 867 intrapleural, negative, postobstruction pulmonary edema and, 213, 214f, 214t, 215, 215f pulmonary artery, monitoring of, 588-590 Preterm labor, 763-765 assessment of, 763 cardiopulmonary bypass in pregnant patients and, 803 definition of, 763 magnesium infusion and, 59, 60, 61 nonobstetric surgery in pregnancy and, 799, 800 Priapism, 840-842 causes of, 840t Prilocaine, methemoglobinemia and, 232-233 Privacy, of patient, 944 Proarrhythmias, class I antiarrhythmic drug–induced, 38 class III antiarrhythmic drug–induced, 45 definition of, 36 ventricular, class I antiarrhythmic drugs and, 36-39 Procainamide, dose of, 39t for atrioventricular reciprocating tachycardia in WPW syndrome, 326 Procarbazine, 110 Prochlorperazine, receptor site affinity of, 134t side effects of, 135t Procyclidine, in Parkinson’s disease, 491, 491t Prokinetic agents, for prevention of pulmonary aspiration, 643t Promethazine, for postoperative nausea and vomiting, 646t, 647 receptor site affinity of, 134t side effects of, 135t Prone position, spinal surgery in, postoperative visual loss and, 693-694, 856, 857, 873 Propafenone, dose of, 39t Propofol, dose of, 80t for early extubation anesthesia, 358 for electroconvulsive therapy, 904 for emergence agitation in children, 686 for external cardioversion, 907 for induction, for prevention of bronchospasm in asthmatics, 190, 191t for neuraxial opioid complications, 263 for Parkinson’s disease, 491t, 492 for patients with porphyria, 76 for prevention of intracranial aneurysm rerupture, 718 for seizures, 233 for status epilepticus, 201 for traumatic brain injury, 735 hemodynamic, respiratory, and other effects of, 81, 81t in children, 82, 621, 686, 910 inflammatory response after cardiopulmonary bypass and, 353 infusion of, continuous, in peripheral nerve block technique, 268 manual, 549t mechanism of action of, 80 neurophysiologic effects of, 729t nonanesthesiologist use of, 621 opioids and, 82

Propofol (Continued) pharmacokinetic properties of, 80t, 81 selection of, 81t, 82 Proportioning device, oxygen, of anesthesia machine, 518, 520, 521-523, 521f, 522f Propoxyphene, in analgesia for opioid-tolerant patients, 280 Propranolol, for hyperthyroidism or thyroid storm, 456 interaction of with diltiazem, 48, 49t Propylthiouracil, after thyroid storm, 820 for inhibition of thyroid hormone synthesis, 456 Prostacyclin, applications of, 6 COX-2 selective antagonists and, 274, 275-276 for pulmonary vasodilatation without systemic vasodilatation, 6 inhaled, for pulmonary hypertension, 317 Prostaglandin F2α, for postpartum hemorrhage, 781 Prostaglandin synthetase inhibitors, in tocolytic therapy, 764-765 Prostaglandins, in carcinoid syndrome, 815t in uterine contractions, 763-764 NSAID action and, 273, 273f, 274 with vascular smooth muscle relaxing effect, actions and side effects of, 4t Prostate, transurethral resection of (TURP), 843-845 venous drainage of, 846, 847f Prostatectomy, laser surgery for, 845 radical, complications of, 846-849 Protamine, complications with, 293 for heparin reversal after cardiopulmonary bypass, 293 intraoperative, pulmonary hypertension and, 318 Protease inhibitors, for HIV infection, 447, 448, 448t Protein(s), in carcinoid syndrome, 815t in muscular dystrophy, 479, 480 Protein binding, delayed emergence and, 886 Protein C, activated, in sepsis, 499 resistance to, 362 deficiency of, 362, 363, 364 Protein kinases, in muscular dystrophy, 480 Protein S, deficiency of, 362, 363, 364 in coagulation process, 361 Proteinuria, in preeclampsia, 760 Prothrombin, gene mutation in, 362 in coagulation cascade, 361 Prothrombin complex concentrate, for coagulation factor deficiencies, 308 Prothrombin time, after cardiac surgery, postoperative bleeding and, 306 in infants and children, 677 postoperative hepatic dysfunction and, 805 Proton pump inhibitors, for prevention of pulmonary aspiration, 188, 643t Pruritus, neuraxial opioids and, 72, 73, 262 Pseudoaddiction, 278t, 279 Pseudoaneurysm, risk factors for, pulmonary artery catheter–related, 589, 589t Pseudocholinesterase, abnormal, block with, management of, 87 screening for, 87 succinylcholine use and, 85, 86-87, 86t in children, 623, 624, 625 variant forms of, 86t, 87 Pseudohypertrophy, in Duchenne’s muscular dystrophy, 479 Pseudohyponatremia, 429, 430t Pseudotumor cerebri, postpartum headache with, 797

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Psoas compartment block, complications of, 257-260 Psychiatric disorders, delayed emergence and, 885 Psychological trauma, in children, 682-684, 683f Psychotropic drugs, in Alzheimer’s disease, 494 Pulmonary artery, catheter in, for management of cirrhosis, 468 for pulmonary hypertension diagnosis, 316 for venous air embolism detection, 674-675 postpneumonectomy confusion about, 379 risks with, 588-589, 589t, 590 compensatory hypertension in, vasodilator drugs for, 3 compression of, with mediastinal mass, 374, 375 perforation of, 588-589 rupture of, 588-589, 589t, 590 Pulmonary artery occlusion wedge pressure, in acute respiratory distress syndrome, 348 Pulmonary artery pressure, in abdominal aortic aneurysm repair, 390, 390f monitoring of, 588-590 in preeclampsia, 761-762, 762t normal values for, 659 pulmonary hypertension and, 315, 316, 659 venous air embolism and, 704 Pulmonary aspiration, 186-188 in morbidly obese, 811-812, 811t in parturients, 782-785 in trauma victims, 828 management of, 783-784, 784t prevention of, 784-785 risk of, 641, 783 signs and symptoms of, 782-783, 783t Pulmonary capillary wedge pressure, in abdominal aortic aneurysm repair, 390, 390f Pulmonary edema. See also Cor pulmonale. after cardiopulmonary bypass, 352 categories of, 348-349 in burn-injured patients, 507 in hypoxemia, 878 maternal risk of, in fetal intrauterine surgery, 767 mixed, acute respiratory distress syndrome and, 348-349 negative-pressure, in children, 602 noncardiogenic, in transfusion-related acute lung injury, 203 postobstruction, 213-216 causes of, 635 chest radiographs of, 634f differential diagnosis of, 213, 215, 688 in children, 634-636 management and prevention of, 215-216, 636 pathogenesis of, 213, 214f, 214t, 215f, 634-635, 635f risk factors for, 215, 635-636 signs of, 213 time course of, 213 postoperative, after tonsillectomy, 688, 689, 690, 690f, 691 postpneumonectomy, 377-378 primary, 62 secondary, 62 with excess fluid therapy, 62 Pulmonary embolism, after orthopedic surgery, 862-864 diagnosis of, 862 management of, 863 in hypoxemia, 878 in pregnancy, 786, 786t, 787, 788 massive, 869, 870

Pulmonary embolism (Continued) pathophysiologic effects of, 363 postpneumonectomy, 378 preventive measures for, 364 treatment of, 364 venous air, in children, 675 Pulmonary function testing, in children, 374 Pulmonary hypertension, fat embolism syndrome and, 860 in cardiomyopathy, 668 in children, 659-662 pharmacologic management of, 317-318 postoperative, 315-318 causes of, 315-316, 315t classification of, 315 management of, 316-318, 317t prevention of, 318 risk factors for, 315-316, 315t primary, 659 pulmonary disease and, ventricular assist device placement and, 411 secondary, 315-316 causes of, 659-661, 659t, 660t workup for, 659, 660t vasodilator use and, 3, 5, 6 Pulmonary infarction, pulmonary artery catheter–related, 588, 589t Pulmonary insufficiency, chronic, pneumonectomy and, 377 Pulmonary ischemia, pulmonary artery catheter–related, 588 Pulmonary thromboembolism, tourniquet use and, 868 Pulmonary toxicity, of amiodarone, anesthetic agents and, 45, 46 Pulmonary vascular disease, structural changes with, 660, 660t Pulmonary vascular resistance, in cardiomyopathy, 668 increased, 3, 661 inotropic drug use and, 11, 12 normal, 659 pulmonary hypertension and, 315, 316, 659, 660 reduction of, 316, 317, 317t vasodilator use and, 5, 6 Pulse, detection of, by pulse oximetry, 570 Pulse generator, in temporary pacemakers, external, 399 implantable, 399-400 Pulse oximetry, 570-572 complications of, 572t fetal, in open fetal surgery, 768 for venous air embolism, 675, 705 improved outcomes and, 933 in children, delayed emergence and, 627 in EXIT procedure, 609 in hypoxemia, 637, 878, 880 intraoperative cardiac arrest and, 615 operator limitations of, 571-572 oxygen status and, 197 technologic limitations of, 570-571 Pump-oxygenator, failure of, in cardiopulmonary bypass, 303-304 infusion, 549 obstructed venous return to, 301 portable infusion, in peripheral nerve block analgesia, 266 Pupil(s), in brain injury assessment, 732 Purkinje fibers, in bradycardia, 331, 332 Pyrexia. See also Hyperthermia. in traumatic brain injury, 734 Pyridostigmine, for myasthenia gravis, 489

985

Q Q waves, in myocardial infarction, 309 QRS complex, in hyperkalemia, 54 in hypokalemia, 54 narrow, in atrioventricular reciprocating tachycardia, 324, 324f, 325, 326 in heart block, 40 wide, in heart block, 40 tricyclic antidepressant action and, 106 with ventricular preexcitation, 324, 324f, 325, 326 QRS tachycardia, adenosine for, 32, 32f, 33 Q-T interval, in hypokalemia, 54 prolonged. See also Long QT syndrome. drugs prolonging, 44, 45 factors predisposing to, 38, 38t polymorphic ventricular tachycardia and, 36, 37 torsades de pointes and, 327, 327f, 328, 328t, 329 Q-Tc interval, normal length of, 327 second-generation H1-blocker effects and, 93 Quality assurance, 927-929 definition of, 927-928 Quality management, 928, 929 Quality of life issues, do-not-resuscitate orders and, 946 Quincke needle, 224f Quinidine, dose of, 39t R Radial artery, cannulation of, 579, 580, 580f Radial nerve, injury of, tourniquet use and, 867, 869 Radiation, of heat energy, 663 Radiation oncology, in children, 909-911 Radiation suite, inspection of, 909-910 Radiation therapy, anthracycline antibiotic– induced cardiotoxicity and, 117 in patients with cardiac rhythm management devices, 405 Radioallergosorbent test (RAST), for anesthetic drugs, 100 for angioedema or urticaria, 427 Radiofrequency ablation, cardiac rhythm management devices and, 405 of cardiac conduction pathways, 915, 915f Radiofrequency identification, for patient identification, 923 Radiography, chest, in acute respiratory distress syndrome, 348f in child with anterior mediastinal mass, 670, 671 in pancreatitis, 474 in pneumothorax, 252 in sarcoidosis, 457-458, 458t one-lung ventilation and, 370 for detection of unintended subdural injection, 244 of cervical spine injuries, 177-179, 178f Radiology, interventional, inspection of radiology suite by anesthesiologist and, 912, 912f retroperitoneal hemorrhage and, 257 Radiosurgery, stereotactic, normal perfusion pressure breakthrough and, 726 Railroad tracking, 244, 245f, 246f Rain-out, 544, 545 Raman scattering, 575 Ramipril, 20, 21 Random drug testing, 121, 123, 127 Ranitidine, 93 for prevention of pulmonary aspiration, 188, 643t

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Index

Ranson’s criteria, in acute pancreatitis, 474, 474t Rapacuronium bromide, in children, bronchospasm and, 624, 625, 626 Rapid fluid and blood delivery devices, complications with, 553-554 Rasagiline, in Parkinson’s disease, 491t Rebleeding, with intracranial aneurysm rupture after subarachnoid hemorrhage, 714-718 Receptor(s), acetylcholine, succinylcholine administration and, 86 cell surface adenosine, adenosine’s effects and, 32 drug interactions with, delayed emergence and, 886 muscarinic, anticholinergic actions and, 28-29 subtypes of, 28 α Receptors, catecholamine effects on, 8 β Receptors, agonists of, for myocardial ischemia, 311 catecholamine effects on, 8 Recombinant factor VIIa, in massive blood transfusion in children, 678 Recombinant hirudin, 364 Recumbency, urinary retention and, 837 Red blood cells, autotransfusion devices and, 679 packed, an antepartum bleeding, 777 for subarachnoid hemorrhage, 720 indications for in children, 678, 679t “Red man” syndrome, 101, 103t Reflux disease, gastroesophageal, in infants, pulmonary aspiration and, 641 in morbidly obese patients, 811t, 812 pulmonary aspiration and, 186, 187 Regional anesthesia. See also specific type, e.g., Neuraxial blockade. cauda equina syndrome in, 227-229 celiac plexus block in, 254-256 chronic NSAID use and, 273-277 continuous, in analgesia for opioid-tolerant patients, 280 deep venous thrombosis prophylaxis regimens in, 864 for Alzheimer’s disease, 494 for autonomic hyperreflexia, 478 for bronchospasm prevention in asthmatics, 191 for detection of cerebral ischemia, 380-381, 380t for emergent cesarean delivery, 772-773 for muscular dystrophy, 482 for myasthenia gravis, 489 for nonobstetric surgery in pregnancy, 800 for orthopedic outpatient surgery, 266 for perioperative management of cirrhosis, 468 for peripheral vascular disease, 394, 395t, 396 heat redistribution in, 664, 664f interscalene nerve block in, complications of, 248-250 local anesthetic systemic toxicity in, 230-234 ocular, retrobulbar block in, 747-749 opioid tolerance and, 278-281 pain management in, acute and chronic, 261-288 perineural local anesthetic infusion in, 282-283 peripheral nerve block in. See Peripheral nerve block. persistent paresthesia in, 285-287 post-dural puncture headache in, 223-226 postoperative apnea in infants and, 613 psoas compartment block in, 257-260 spinal hematoma in, 235-238 supraclavicular and infraclavicular block in, 251-253

Regurgitation, in children, 643 Religious considerations, blood transfusions and, 948 Remifentanil, for early extubation anesthesia, 358 for electroconvulsive therapy, 904 manual infusion dosing regimens for, 549t muscle rigidity induced by, airway difficulties with, 174-175 plasma concentration of, infusion duration and, 546-547, 546f, 547f Renal blood flow, acute renal failure and, 345 calcium channel antagonists and, 51 Renal disease, end-stage. See End-stage renal disease. Renal dysfunction, after cardiopulmonary bypass, 352, 353 digitalis toxicity and, 26, 26t NSAID toxicity and, 276 preexisting, acute renal failure and, 344 ventricular assist device placement and, 409 Renal effects, of hyperglycemia, 417 of NSAIDs, 274-275, 274t Renal failure. See also Acute renal failure. anesthetic-induced, management and prevention of, 68 definition of, 66 hyperkalemia and, 55 hypermagnesemia and, 60 in cardiac surgery patients, 360 inflammatory response after cardiopulmonary bypass and, 353, 354 insufficient fluid therapy and, 62 nonoliguric, 66, 342 postoperative, risk factors for, 67 Renal insufficiency, α2-agonist–induced hypotension and, 95 definition of, 66 Renal papillary necrosis, NSAID action and, 275 Renal perfusion pressure, acute renal failure and, 345 Renin-angiotensin system, drugs affecting, 17-19, 17f Reperfusion injury, in acute respiratory distress syndrome, 348 inflammatory response after cardiopulmonary bypass and, 353 Respiratory acidosis, 436-437 in laparoscopic surgery, 831 treatment of, 439 Respiratory alkalosis, 437 acute respiratory distress syndrome and, 347 treatment of, 439 Respiratory complications. See also under Lung(s); Pulmonary. in burn-injured patients, 506-507 in cervical spine injuries, 177 in hematoma after thyroid surgery, 818, 819, 820-821 in HIV drug treatment, 447, 448-449 in morbidly obese, 810-811, 811t in muscular dystrophy, 481, 482 in radical urologic surgery, 846-847, 848, 849 in transfusion-related acute lung injury, 203 in upper respiratory tract infection, hospital admission and, 894 in children, 649-650, 650t, 894 laryngospasm and, 599-600 posterior fossa surgery and, 708, 709, 710 progressive, postobstruction pulmonary edema and, 213 Respiratory depression, delayed, 72-73 delayed emergence and, 886 early, 72 flumazenil and, 128, 129, 130 midazolam and, 81

Respiratory depression (Continued) neuraxial opioids and, 72-73, 261-262, 262t propofol and, 81, 82 risk factors for, 261-262, 262t Respiratory effects, of early extubation after cardiac surgery, 356, 357t Respiratory failure. See also Acute respiratory distress syndrome (ARDS). chronic hypoxemic, in sarcoidosis, 460 postoperative, 347-351 postpneumonectomy, 377 Respiratory insufficiency, definition of, 877 in posterior fossa surgery, 709, 710 opiate-induced, chest wall rigidity and, 174-175 postoperative, 877-880 causes of, 877-878, 878t management and prevention of, 879-880 presentation of, 877-879 risk assessment of, 879, 879t Respiratory paralysis, in unintended intrathecal injection, 243 Respiratory tract, humidification devices and, for hypothermia prevention, 665 upper, infections of, in children, 649-650, 650t, 894 laryngospasm and, 599-600 unintended hospital admission and, 894 Restrictive cardiomyopathy, characteristics of, 668 management of, 669 Resuscitation, cardiopulmonary, cardiac arrest and, 615, 616 do-not-resuscitate orders and, 946-947 maternal, with amniotic fluid embolism, 788 training for, 616 fluid. See Fluid resuscitation. Retinoblastoma, pediatric, systemic complications of, 909t Retinopathy of prematurity, 694 Retrobulbar block, 747-749 anatomic factors in, 748, 748f complications with, 747-748, 747t management and prevention of, 749 risk factors for, 748-749 indications for/contraindications to, 747 technique of, 748 Retroperitoneal hemorrhage, lumbar sympathetic block and, 270 management and prevention of, 259-260, 259t recognition of, 257, 257t risk of, 258-259, 258t, 259f with psoas compartment block, 257-260 Retroperitoneal space, vascular supply of, 258, 259f Revascularization, of legs, for peripheral vascular disease, 394-397 Reversal agents, 128-130 for delayed emergence, 886, 887 Reverse T3, 451 Revised trauma score, 827, 828t Rewarming, central neurologic injury and, 340 Rhabdomyolysis, hyperkalemia and, 55 succinylcholine use and, in children, 623, 624, 625 Rhabdomyosarcoma, pediatric, systemic complications of, 909t Rheumatoid arthritis, biologic agents for, 501-502, 502t cervical spine instability and, 176-177 Rib fractures, in trauma victims, 828 Ribavirin, side effects of, 501 Risk management, 928, 943 Ritodrine, for tocolytic therapy, 764

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Rocuronium, 89t complications with, in children, 623, 624t for early extubation anesthesia, 358 for opiate-induced muscle rigidity, 175 for rapid-sequence induction in open globe injury, 745 Rofecoxib (Vioxx), action of, 274, 274f toxicity of, 275, 276 Rolipram, 22, 22t Romano-Ward syndrome, 328 Ropinirole, in Parkinson’s disease, 490, 491t Ropivacaine, cardiotoxicity of, 232 maximal plasmal concentrations of, 232t Rotigitine, in Parkinson’s disease, 490, 491t Rule of nines, 506t S S/5 ADU anesthesia machine, electronic proportioning system of, 522, 523 Sacral plexus, injuries of in childbirth, 790, 791f Safety issues, with anesthesia breathing circuit, 529-530, 530t with anesthesia machine, 542 with breathing circuit, 542 with carbon dioxide absorbers, 536 with electrical equipment in operating room, 561 with flowmeters, 520 with humidifiers, 545 with laser surgery, 568-569 with mechanical ventilators, 539 with oxygen flush valve, 525 with patient warming devices, 552 with pipeline gas supplies, 516-517 with proportioning systems, 523 with pulse oximetry, 571 with rapid fluid and blood delivery system use, 554 with saline monitoring lines, 561 with sevoflurane, 536 with surgical diathermy and electrocautery, 558-559 with vaporizers, 533 Saline, for treatment of post–dural puncture headache, 225-226 hypertonic, for hyponatremia, 432 for management of TURP syndrome, 844 for treatment of traumatic brain injury, 735 monitoring lines for, safety issues with, 561 normal, acid-base balance and, 440 Sandostatin LAR, in carcinoid syndrome, 816 Santorini’s plexus, 846, 847, 847f Sarcoglycanopathies, protein dysfunction in, 480 Sarcoidosis, 457-461 cardiac findings in, 458, 459 diagnosis of, 457-458, 457f, 458f, 458t management of, 459-460 multisystem presentation of, 458, 459t prevention of, 460-461 risk assessment in, 458-459 Sarcomeric protein, in muscular dystrophy, 480 Sarcoplasmic reticulum, in malignant hyperthermia, 654, 656 Saw palmetto, common uses of/problems with, 156t Scalene node biopsy, in sarcoidosis, 459 Scapular fractures, in trauma victims, 828 Scavenging systems, in anesthesia machines, 540-542 Sciatic nerve, injuries of, from tourniquet use, 867, 869 in childbirth, 790, 791f, 792t Sciatic nerve block, for outpatient knee surgery, 267t

Scoliosis, in muscular dystrophy, 482 postpneumonectomy, 379 Scopolamine. See also Anticholinergic agents. action of, 28 awareness under anesthesia and, 940 effects of, 28-29, 29t emergence agitation and, 686 for postoperative nausea and vomiting, 646t potential complications of, 136 receptor site affinity of, 134t side effects of, 135t γ-Secretase, in Alzheimer’s disease, 493 Sedation, complications of, management and prevention of, 621-622 recognition of, 620, 620t risk of, 620-621 conscious, 619 deep, 619, 619t complications of, 620, 620t definitions of, 619 for postoperative nausea and vomiting prevention, 647 in Alzheimer’s disease, 494 in children, 619-622 guidelines for, 621, 622 nonanesthesiologist use of, 621 preoperative, 684 institutional policies of, 619, 621 mild, 619 moderate, 619, 619t complications of, 620, 620t neuraxial opioids and, 72, 262 with antiemetic drugs, 135, 136 with benzodiazepines, flumazenil reversal and, 128, 129, 130 Sedation team, 621 Sedatives, delayed emergence and, 885-886 in posterior fossa surgery, 709 preoperative, in children, 684 Seizures, after subarachnoid hemorrhage, 722 flumazenil-induced, 129 generalized, classification of, 200 in acute porphyria, 75, 76 in children, delayed emergence and, 629 intracranial aneurysm rerupture and, 716, 717t local anesthetic–induced, 230 management of, 233 risk of, 231, 231t magnesium sulfate for, in preeclamptic patients in labor, 760 partial, classification of, 200 pathologic mechanism of, 200 pharmacotherapy for, 200, 201 tricyclic antidepressant toxicity and, 106 Selective serotonin reuptake inhibitors (SSRIs), 107-108 adverse drug reactions with, 108 Selegiline, in Parkinson’s disease, 491, 491t Self-harm, emergence agitation in children and, 686 Sellick’s maneuver, 188 Senile plaques, in Alzheimer’s disease, 493 Sensory deficits, in cardiac surgery patients, 336 of lower extremities and trunk, celiac plexus block and, 254 Sentinel events, 927, 928 Separation anxiety, in children, 682, 683f, 684, 685 Sepsis, acute gram-negative, HIV drug treatment and, 448 acute renal failure and, 344 criteria for, 496, 497t

987

Sepsis (Continued) definition of, 496, 497t hyperglycemia and, 658 in burn wounds, 505, 506 inflammatory response after cardiopulmonary bypass and, 354 postoperative jaundice and, 806, 807 pulmonary artery, pulmonary artery catheter–related, 589 systemic inflammatory response syndrome and, 496-499 vs. hypothyroidism, 452 Septic shock, adrenal insufficiency and, 444 cortisol levels with, 131 definition of, 496, 497t hydrocortisone in, 9 replacement doses of steroids with, 132 Septicemia, in TURP syndrome, 844 Septostomy, atrial, for pulmonary hypertension in children, 661 Serine protease inhibitors, inflammatory response after cardiopulmonary bypass and, 354 Serotonin. See also Selective serotonin reuptake inhibitors (SSRIs). in carcinoid syndrome, 814, 815 monoamine oxidase inhibitors and, 105 Serotonin receptor antagonists, for treatment of neuraxial opioid complications, 263 potential complications of, 135-136 Serotonin syndrome, 107 Sertraline (Zoloft), 108 Serum test, for latex, 218t Sevoflurane, carbon dioxide absorbents and, 534, 535, 535f, 536 fire risk and, 563 for early extubation anesthesia, 358 for oculocardiac reflex in children, 696 heart block and, 40 hepatic toxicity and, 66 inflammatory response after cardiopulmonary bypass and, 353 neurophysiologic effects of, 729t Sheehan’s syndrome, antepartum bleeding and, 777 Shivering, in children and infants, 665 in hypothermia, in anesthetized patients, 664 in pulse oximetry, 570, 571 postoperative, 422 Shock, anaphylactic, 97 electrical, rapid fluid and blood delivery system use and, 553, 554 hemorrhagic, in retroperitoneal hemorrhage, 257 hypovolemic, in adrenal insufficiency, 444 respiratory failure and, 347 in obstetric hemorrhage, 776t, 778 in trauma victims, 829 septic, definition of, 496, 497t spinal, 177 systemic inflammatory response syndrome and, 497 treatment of, 440, 829 vasodilatory, supplementary arginine vasopressin for, 9 Shock(s), biphasic waveforms of, 399 internal cardioverter-defibrillator malfunction and, 403 Shock lung, 62 Shunt(s), in left-sided thoracotomy, 386 in newborn, hypoxemia and, 639 placement of, in carotid endarterectomy, 380-381, 380t

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Page 988

Index

Shunt(s) (Continued) right-to-left, hypoxemia and, 193, 195, 195f, 639 ventriculoperitoneal, after subarachnoid hemorrhage, 722 Shunting, intracardiac, postpneumonectomy, 378-379 Sick sinus syndrome, management of, 334 Sildenafil, for erectile dysfunction, 21 for pulmonary hypertension, 21, 661 intraoperative myocardial ischemia and, 20-22 nitroglycerin and, 20, 21 phosphodiesterase selectivity of, 22t prevention of drug-drug interactions with, 22-23 safety of, 22-23 Single-photon positron emission tomography (SPECT), for diagnosis of vasospasm, 719 Sinoatrial exit block, 40 Sinoatrial node conduction, adenosine effects on, 32-33, 34 block of, 332 calcium channel antagonist effects on, 40, 48, 49f, 50 in bradycardia, 331, 332f Sinus bradycardia, 40, 41, 231, 331, 332f, 334. See also Bradycardia. management of, 334 oculocardiac reflex and, in children, 695, 696f Sinus node dysfunction, pacing for, 401t, 402 Sinus tachycardia. See Tachyarrhythmias; Tachycardia. Sinus thrombosis, postpartum headache with, 796 Sinusitis, postpartum headache with, 797 Sipple’s syndrome, adrenal tumors and, 822 Sitting position, in posterior fossa surgery, 710, 710t venous air embolism and, 705t, 706 in posterior fossa surgery, 708, 709 Skin, central venous catheter–related infection and, 584, 586f herb and nutraceutical effects on, 154t hyperpigmentation of, in adrenal insufficiency, 442 hypothermia prevention and, 664-666 injury of, from arterial tourniquet, 867 from laser surgery, 568 necrosis of, arterial cannulation and, 579 Skin preparations, flammable, 563, 564t, 565, 565t Skin tests, for anesthetic drugs, 100 for angioedema or urticaria, 427 for latex, 218t Sleep apnea, obstructive, in morbidly obese, 811 in muscular dystrophy, 481 sedation in children and, 620 tonsillectomy and, 688, 688t, 689, 690, 691 Small cell carcinoma, of lung, Lambert-Eaton myasthenic syndrome and, 485 Smoke inhalation, from laser surgery, 568 from surgical diathermy, 558 in burn injuries, 504, 505, 505t Smoking, case history of, 122 consequences of, 125 marijuana, 124 secondhand, laryngospasm and, 600 symptoms of, 123-124 treatment of, 126, 126t Smooth muscle, bronchial, 189 relaxation of, sildenafil and, 21 vasodilators and, 3 vascular contraction of, magnesium and, 59

Soda lime, carbon dioxide absorption by, 534536, 535f Sodium, in diabetic ketoacidosis, 418 in hypernatremia, 433, 434, 434t in hyponatremia, 429-432 replacement of, 432 in metabolic acidosis, 437 in prerenal syndrome, 344 urinary, in hypovolemia, 63 Sodium bicarbonate, for acute renal failure, 346 for hyperkalemia, 57 Sodium bisulfite, chemical injury with, in obstetric patients, 790 Sodium citrate, for pulmonary aspiration, 188, 643t Sodium iodide, for inhibition of thyroid hormone synthesis, 456 Sodium nitroprusside, actions and side effects of, 4t for adrenalectomy, 825 for autonomic hyperreflexia, 478 for cesarean delivery in preeclamptic patients, 761 for hypertensive emergencies, 824 for induced hypotension, 873 for myocardial ischemia, 311 Sodium thiopental, for seizures, 233 Somatosensory evoked potentials, in cerebral ischemia, 381 in peripheral nerve injury, 336 in spinal cord surgery, 871-872, 871t, 872f, 872t, 873 in thoracic aortic aneurysm repair, 387, 388 monitoring of, 709 in cervical spine injuries, 179 Spectrophotometry, infrared absorption, 575 Sphincter(s), external urethral, 836, 837 internal urethral, 836, 837 Spina bifida, surgery for, latex allergy and, 651, 652, 653 Spinal abscess. See Epidural abscess. Spinal anesthesia, continuous, cauda equina syndrome and, 227 guidelines for, 228, 228t failed, repeat injection after, 227, 228-229 for emergent cesarean delivery, 771-772 intraoperative penile erection and, 841 lidocaine, prevention of neurotoxicity with, 229, 229t neurologic injury with, in childbirth, 793 post–dural puncture headache with, 223-226 total, after interscalene nerve block, 248 causes of, 248, 248t differential diagnosis of, 248 management and prevention of, 249-250, 249f presentation of, 248 risk of, 248-249, 249t Spinal arteries, in thoracic aortic aneurysm repair, 387, 387f Spinal cord, blood supply of, 387, 387f obstetric neurologic injuries and, 790, 793f cervical, injuries of, 177. See also Spine, cervical, injuries of. compression of, 239 dysfunction of, epidural abscess and, 239 urinary retention and, 837 edema of, in thoracic aortic aneurysm repair, 387 injury of, 737-740 acute, injuries associated with, 738, 738t recent surgery and, 739 ventilatory compromise with, 738, 738t autonomic dysreflexia and, 477, 853-854

Spinal cord, injury of (Continued) chronic, anesthesia for surgery in, 739 complications with, 737-739, 738t management and prevention of, 739, 740 recognition of, 737 ischemia or paralysis of, postpneumonectomy, 379 protection of, in thoracic aortic aneurysm repair, 387-388, 387f, 388t unintended injection of, 242-243, 244-247 Spinal hematoma, 235-238 differential diagnosis of, 235-236, 235t management of, 237 neuraxial blockade and, neurologic dysfunction with, 235 thromboembolism prophylaxis and, 864 prevention of, 237-238 risk of with anticoagulants, 236-237 Spinal interbody cages, 856 Spinal shock, 177 Spinal shock syndrome, 737 Spinal surgery, complications of, 871-874 management and prevention of, 873-874 recognition of, 871-872 risks with, 872, 872t, 873t in prone position, postoperative visual loss and, 693-694, 855-858, 873 Spine, cervical, collar for, 177, 829 injuries of, 177, 737 assessment of, 179 computed tomography of, 178 diagnostic algorithm for, 178f immobilization of, 177, 829 in children, 729 magnetic resonance imaging of, 178 management of, 179-180 radiographic evaluation of, 177-179, 178f signs of, 177 traumatic, 734, 828, 829 instability of, 176-180 Splanchnic nerves, in celiac plexus block, 254 “Splinting,” hypercarbia and, 878 Sprotte needle, 224f SSRIs (selective serotonin reuptake inhibitors), 107-108 adverse drug reactions with, 108 St. John’s wort, adverse drug reactions with, 109 as antidepressant, 108-109 common uses and problems with, 156t components of, 108-109 delayed emergence and, 109, 886 Standard of care, 935t Stanford classification, of aortic dissection, 384 Starling curve, in adult, neonate, and fetus, 767, 767f Starling equation, 214f, 635 Statins, postpneumonectomy cardiac complications and, 378 Status epilepticus, 201 Stellate ganglion block, left, for congenital long QT syndrome, 329 Sterile technique, for epidural abscess, 241 Sternal retraction, brachial plexus injury and, 337 Steroids. See Corticosteroids. Stewart-Fencl-Gilfix method, in acid-base analysis, 438, 438f Strabismus surgery, oculocardiac reflex in, in children, 695, 696f, 696t Streptococcus aureus, methicillin-resistant (MRSA), in nosocomial pneumonia, 210, 211 Streptozotocin, mechanisms, uses, and toxicities of, 114t

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Stress, adrenal insufficiency and, 442 cardiopulmonary bypass and, 313 cortisol levels with, 131 hypothyroidism and, 452 in anesthesia for patients with long QT syndrome, 329 in neonates, secondary pulmonary hypertension and, 660 in Wolff-Parkinson-White syndrome, 326 surgical, central neurologic injury and, 339 in revascularization for peripheral vascular disease, 394 systemic inflammatory response syndrome and, 496, 497 thyroid crisis and, 454, 455 Stress test, cardiac, 148-149 carotid endarterectomy and, 381, 382 in revascularization for peripheral vascular disease, 397 Stridor, postextubation, postobstruction pulmonary edema and, 213 postintubation croup and, 631, 632 treatment of, 185 Stroke, after coronary artery bypass grafting, 339 carotid endarterectomy and, 380-382 hyperglycemia and, 417 in cardiac surgery patients, 360 Stroke volume, in cardiomyopathy, 668 Strong ion difference, in acid-base balance, 436, 437t, 440 ST-T waves, in carotid endarterectomy, 382 in myocardial infarction, 309 Subarachnoid block, in autonomic hyperreflexia, 478 in cesarean delivery in preeclamptic patients, 761 Subarachnoid hemorrhage, complications with, 714t intracranial aneurysm rupture and, 714-718 vasospasm and, 717, 719-723 Subarachnoid space, 242. See also Intrathecal injection. local anesthetic in, neurotoxicity and, 227, 229 Subconjunctival anesthesia, with intravenous sedation, for regional anesthesia of eye, 749 Subdural injection, unintended, 244-247 management and prevention of, 247 risk of, 244, 246 vs. total spinal anesthesia, 248 Subdural space, 246 Subglottic edema, postintubation croup and, 631, 632 Subsidiary atrial bradycardia, 331 Substance abuse. See also Drug dependence. denial of, 125 in physicians, 120, 122-127 in poisoning cases, 508 postpartum headache with, 797 screening tests for, 123, 123t Substantia nigra, in Parkinson’s disease, 490 Sub-Tenon’s block, for regional anesthesia of eye, 749 Succinylcholine, 22t as anesthetic adjunct, 85-87 complications with, 85, 85t conditions predisposing to, 85, 85t in children, 623-626 management and prevention of, 87 delayed emergence and, 886 for laryngospasm in children, 601-602 hyperkalemia and, 55, 57 in burn-injured patients, 507 in cervical spine injuries, 179, 738 in children, complications with, 623-626

Succinylcholine (Continued) dose, clearance, and side effects of, 624t for laryngospasm, 601-602 with undiagnosed muscular dystrophy, 481 in cirrhosis, 468 in electroconvulsive therapy, 904 in muscular dystrophy, 481, 482 in myasthenia gravis, 489 in opiate-induced muscle rigidity, 175 intraocular pressure and, 695, 745 labeling for, 625, 626f Sucralfate, for prevention of nosocomial pneumonia, 211 Suctioning, bronchoscopic, pulmonary aspiration and, 187 for prevention of nosocomial pneumonia, 211 for pulmonary aspiration in children, 642 intraoperative, for capturing shed blood, 296 pericardial, postoperative bleeding and, 306 Sudden infant death syndrome, 612, 613 Sufentanil, intrathecal placement of, 72, 261, 262 manual infusion dosing regimens for, 549t muscle rigidity induced by, airway difficulties with, 174-175 plasma concentration of, infusion duration and, 546-547, 546f, 547f Sulfamethoxazole-trimethoprim, for Pneumocystis jirovecii pneumonia, 448 Sulfonamides, porphyrias and, 471t, 472 Sulindac, blood pressure and, 274 Sumatriptan, for treatment of post–dural puncture headache, 225 Superior vena cava syndrome, 373, 375 anterior mediastinal masses and, 671 Superoxide anion radicals, anthracycline antibiotic action and, 116 Supine hypotensive syndrome, 767, 768 Supraclavicular block, pneumothorax with, 251-253 technique of, 251, 251f Supraglottic airway devices, 168-169 Supraventricular tachycardia, 334 adenosine for, 32, 34, 35, 43 in children, catheter ablation for, 915, 916 emergent cardioversion for, 907 in postanesthesia care unit, 902 paroxysmal. See Paroxysmal supraventricular tachycardia. reentrant, adenosine for, 43 Surfactant instillation, in acute respiratory distress syndrome, 350 Surgery, bradyarrhythmias and, 333 cardiac risk stratification for, 148t cortisol levels in, 131 delay or cancellation of, false-positive test results and, 142 missing or inadequate test results and, 144 do-not-resuscitate orders and, 946-947 emergency, in spinal cord injury, 739 general, 805-835 hyperkalemia and, 55 in dialysis-dependent patients, 463-464 in HIV-infected patients, 449 in morbidly obese patients, 810-813 nonobstetric, during pregnancy, 799-800 posterior fossa, 708-711 postoperative apnea in infants and, 612 potassium disorders and, 56-57, 56t spinal cord injury and, 737, 739. See also Spinal cord, injury of; Spine, cervical, injuries of. thoracic, 365-379 thromboembolic disease and, 362, 363t, 364 transurethral, 843-845

989

Surgery care team, for intraoperative cardiac arrest, 616 Surgical diathermy, complications with, 556-559 unipolar and bipolar, 556-557 Suspension laryngoscopy, 750 Swallowing, foreign body aspiration and, 754 Sympathectomy, in revascularization for peripheral vascular disease, 394 Sympathetic activity, anticholinergic action and, 28 in autonomic hyperreflexia, 477 ketamine and, 78 Sympatholysis, in celiac plexus block, 254 with α2-agonists, 95 β-Sympathomimetic drugs, for calcium channel antagonist toxicity, 51 Synaptic vesicles, in congenital myasthenic syndromes, 485 Synaptotagmin, in Lambert-Eaton myasthenic syndrome, 485 Syncope, in congenital and acquired long QT syndrome, 328, 329 neurally mediated, pacing for, 402 Syndrome of inappropriate antidiuretic hormone secretion, causes of, 430t diagnosis of, 429, 431, 431f SSRI use and, 108 Syringe swaps, 924-926 in awareness under anesthesia, 939 Systemic inflammatory response syndrome, 348 criteria for, 496, 496t multiple organ dysfunction syndrome and, 496-499 risk of, 496-497 sepsis and, 496-499 Systemic vascular resistance, 315 inotropic drug effects on, 11, 12 T T cells, CD4, 446, 447f T waves, in hyperkalemia, 54 Tachyarrhythmias. See also Tachycardia. atrial, postpneumonectomy, 378 catecholamine vasopressor–induced, 8-9 implanted cardioverter-defibrillators for, indications for, 401t, 402 in laparoscopic surgery, 832, 834 perioperative, 319-323 causes of, 320, 321t, 322t definition of, 319 diagnosis of, 319, 320t electrocardiographic features of, 319, 320t management and prevention of, 321t, 322t, 323 risk factors for, 319-320, 323 pheochromocytoma and, 823, 824f stable, cardioversion for, 905 unstable, cardioversion for, 905, 907-908 ventricular, after subarachnoid hemorrhage, 723 ventricular preexcitation with, 324-326. See also Wolff-Parkinson-White syndrome. Tachycardia. See also Tachyarrhythmias. adenosine for, 32, 34 anticholinergic toxicity and, 30, 31 as atrioventricular junctional rhythm, 320t, 321t atrioventricular reciprocating, 324, 324f, 325, 326. See also Wolff-Parkinson-White syndrome. bidirectional ventricular, digitalis toxicity and, 25 cardioversion for, 32, 34

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Tachycardia (Continued) digitalis-induced, 24, 24f, 25. See also Digitalis. for treatment for bradycardia in heart transplant patients, 16 hemodynamic instability and, 899t, 900, 900t, 901-902 hypertension with, β-blockers for, 314 in postanesthesia care unit, 901-902 in radical urologic surgery, 847 in revascularization for peripheral vascular disease, 397 nonparoxysmal atrioventricular junctional, digitalis-induced, 24, 24f, 25 paroxysmal, 319 paroxysmal atrial with atrioventricular heart block, 25 reentrant, 43 radiofrequency ablation in, 915 sensing and discrimination for, in pacemakers, 399 supraventricular, 334 adenosine for, 32, 34, 35, 43 in children, catheter ablation for, 915, 916 emergent cardioversion for, 907 in postanesthesia care unit, 902 paroxysmal. See Paroxysmal supraventricular tachycardia. reentrant, 43 treatment of, 32 vasodilator use and, 6 ventricular. See Ventricular tachycardia. wide QRS, 324, 324f Tacrolimus, toxicity of, 501 Team approach, in fast-track cardiac anesthesia, 356 in intraoperative cardiac arrest, 616 in sedation of children, 621-622 Teeth, damage to, classification of, 181 consequences of, 182 management and prevention of, 182-183 preanesthetic evaluation and, 181 preexisting, 181 nomenclature and numbering system of, 182f protective devices for, 183 Temperature. See also Thermoregulation; Warming devices. ambient, in operating room, 421 body. See Body temperature. of fluids, in hypothermia prevention, 665-666 Tension headache, postpartum, 796, 798t Tension pneumothorax, in laparoscopic surgery, 833, 834 intraoperative cardiac arrest and, 616 pressure in breathing circuit and, 542 risk of, 253 Teratogenesis, anesthetic drugs and, 799 maternal cardiac disease and, 802 Terbutaline, for detumescence of penile erection, 841 for tocolytic therapy, 764 Test(s), accuracy of, 141 benefits vs. harm of, 145 evidence-based medical care and, 145 false-positive, 141-143 inadequate or missing, 144-146 incorrectly performed, 141, 142 preanesthetic, guidelines for, 145-146, 145t precision of, 141 predictive value of, 141, 141t preoperative, focused, 145 selection of, outcome and, 144, 145 sensitivity of, 141

Test(s) (Continued) specificity of, 141 stress, perioperative cardiac risk and, 148-149 tilt, 63 unnecessary, 143 Tetrahydrocannabinol, blood, for substance abuse testing, 123 THC concentration, in marijuana, 124 Theophylline, for adenosine-induced proarrhythmias, 34, 34f Therapeutic interventions, anesthesia for, 903-920 Thermal injury, 504-507. See also Burn injuries. from warming devices, 550-552, 551f, 551t to tracheobronchial tree, from humidifier complications, 544 Thermogenesis, in hypothermia, 663-664 Thermoregulation, anticholinergic effects on, 30, 31 hypothalamic, in awake and anesthetized pediatric patients, 663-665, 664f in anesthesia, 419, 420f, 423 perioperative, in infants and children, 664-665, 664f Thiazide diuretics, for acute renal failure, 345 Thienopyridine derivatives, spinal hematoma and, 236-237, 237t Thin-layer chromatography, for drug dependence, 119 for substance abuse testing, 123 Thiopental, for early extubation anesthesia, 358 for intracranial aneurysm rerupture, 716 inflammatory response after cardiopulmonary bypass and, 353 neurophysiologic effects of, 729t Thirst, in hypernatremia, 433 Thoracic aortic aneurysm, 384-389 classification of, 384, 384f, 385f recognition of, 384-386, 385t risk assessment of, 386 signs and symptoms of, 385t surgical repair of, management of, 388 risks with, 386-388, 389 Thoracic surgery, 365-379 Thoracostomy, tube, tension pneumothorax and, 253 Thorazine, sedation in children and, 620, 621 Thrombin, in coagulation cascade, 361 Thrombocytopenia, anthracycline antibiotic action and, 116 heparin-induced, 291-292 in preeclampsia, 760, 761 non-heparin immune-associated, in cardiopulmonary bypass, 292 Thromboelastography, computerized, postoperative bleeding and, 306 Thromboembolic complications, of orthopedic surgery, 862-864 diagnosis of, 862 management of, 863 prevention of, 863-864 risk factors for, 862-863, 862t, 863t Thromboembolism. See also Hypercoagulable disorders. arterial and venous, 363 in pregnancy, 787 in radical urologic surgery, 848, 849 risk factors for, 270, 270t surgery and, 362, 363t, 364 tourniquet use and, 868 Thrombogenic effects, of NSAIDs, 274, 274f, 274t, 275-276 Thrombolysis, 361

Thrombolytic drugs, in central neuraxial techniques, ASRAPM guidelines for, 271t Thrombomodulin, in coagulation process, 361 Thromboplastin, tissue, in coagulation cascade, 361 Thromboprophylaxis, spinal hematoma and, 236 Thrombosis, 361-364 central venous catheter–related, 583t cerebral venous, postpartum headache with, 796 deep venous. See Deep venous thrombosis. heparin-induced thrombocytopenia with, 292 indwelling vascular catheters and, 364 of radial artery, 579, 580f secondary pulmonary hypertension and, 660 Thromboxane A2, 273f, 274 Thrombus, after carotid endarterectomy, 381 formation of, 361 intra-aortic balloon pump and, 409 Thymectomy, for myasthenia gravis, 485, 489 Thymoma, in myasthenia gravis, 484 Thyroid function studies, in thyroid disorders, 452t, 455t Thyroid hormone, deficiency of, 452 prevention of synthesis of, 456 regulation and activity of, 451 replacement of, for myxedema coma, 452-453 Thyroid storm, 454-456 after thyroid surgery, 817, 818, 818t, 819-820 causes of, 454, 455 definition of, 454 diagnosis of, 455, 455t management and prevention of, 455-456, 819-820 pathogenesis of, 817-818 Thyroid surgery, complications of, 817-821 Thyroiditis, Hashimoto’s, 452 Thyroid-stimulating hormone, 451 Thyrotoxic crisis, 454, 455 Thyrotoxicosis, 454, 455, 455t, 819 differential diagnosis of, 455 management and prevention of, 455-456 signs and symptoms of, 817, 818t Thyrotoxicosis factitia, 454 Thyrotropin, 451 Thyrotropin-releasing hormone, 451 Thyroxine (T4), in hypothyroidism, 451 replacement doses of, 452 Tibial nerve, injuries of in childbirth, 790, 792t Ticlopidine, peripheral nerve block and, hemorrhagic complications with, 270 spinal hematoma and, 236-237, 237t Tidal volume, in acute respiratory distress syndrome, 350 Tidalafil, 21. See also Sildenafil. Tilt test, positive, 63 Tirilazad, in prevention of vasospasm, 722 Tirofiban, in cardiac surgery patients, 359 in heparin-induced thrombocytopenia in cardiopulmonary bypass, 293 Tissue factor, 361 Tissue factor pathway inhibitor, in coagulation process, 361 Tissue oxygen tension monitor, in traumatic brain injury, 733 Tissue perfusion, thermal injury from warming devices and, 550-551, 551t Tissue plasminogen activator, for treatment of subarachnoid hemorrhage, 720 Tissue thromboplastin, 361 Tissue-type plasminogen activator, 361 Titan gene, 480

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Tobacco abuse. See also Smoking. case history of, 122 consequences of, 125 symptoms of, 123-124 treatment of, 126, 126t Tobacco smoke, secondhand, laryngospasm and, 600 Tocainide, dose of, 39t Tocolytic therapy, 763, 764-765 for retained placenta or uterine inversion, 780 in cardiopulmonary bypass in pregnant patients, 804 in fetoscopic surgery, 769 in open fetal surgery, 768 Tolcapone, in Parkinson’s disease, 490, 491, 491t Tolerance, of drugs, definition of, 119, 120, 278, 278t of opioids, 120, 278-281 discharge instructions for, 280 Tongue, in airway obstruction, 877 Tonic-clonic seizures, 200 Tonsillar hypertrophy, sedation in children and, 620 Tonsillectomy, hospital admission after, criteria for, 691t in children, 688-691 Topotecan, 110 Torsades de pointes, 327-330 acquired long QT syndrome and, 327, 328, 329 adenosine and, 33 causes of, 327, 328t conditions predisposing to, 38, 38t congenital long QT syndrome and, 328, 329 drug-induced, class I antiarrhythmic drugs and, 36, 37, 37f class III antiarrhythmic drug–induced, 45, 46 management and prevention of, 46, 328t electrocardiographic features of, 327f, 328 hypomagnesemia and, 59, 60 management and prevention of, 39, 46, 329 prolonged Q-T interval and, 44-45, 327, 328, 329 risk factors for, 328, 328t second-generation H1-blocker effects and, 93 Tort, intentional, 943 Total artificial heart, 407 Total intravenous anesthesia, automated drug delivery systems and, 549 in myasthenai gravis, 489 in pipeline supply failure, 516 Tourniquet(s), of extremities, 867-870 inflation time and pressure limits for, 869, 870 injuries from, management and prevention of, 870 recognition of, 868-869 risks for, 869-870, 869t local injuries from, 867-868 post-tourniquet syndrome and, 868-869, 870 safety factors for, 870 systemic effects from, 868 peripheral nerve ischemia and, 882 Toxic ingestion, complications from, 508-512 Toxicity, of local anesthetics, cardiovascular, 230-231 central nervous system, 230 systemic, 230-234 opioid, in analgesia for opioid-tolerant patients, 280 organ, volatile anesthetics and, 66-68 Toxidromes, in poisoning cases, 509, 509t Toxoplasmosis, cerebral, in AIDS patients, 449

Trachea, early extubation of, after cardiac surgery, 356-360 guidelines for, 359t management of, 358-359, 359t prevention of complications with, 359-360 risk factors for, 359t extubation of, postobstruction pulmonary edema and, 216 in infants and children, airway obstruction and, 374 anatomy of, 638 injury of, 184-185 intubation of, awake, in cervical spine injuries, 179 difficult, 161, 162f, 165-166, 167f, 167t. See also Airway, difficult. airway examination predictors of, 161, 163t assessment of, 368 dental injury with, 181 diagnosis of, 161, 162, 163f, 163t, 164, 164t difficult extubation with, 162, 164 introducers for, 162 in acute respiratory distress syndrome, 350 in cervical spine injuries, 179 in spinal cord injury, 739 in trauma victims, 730, 734, 829, 829t injury from, 184, 185 postintubation croup and, 631, 632 pulmonary aspiration during, 187, 188, 784 retrograde, 169-170, 170f, 171t via laryngeal mask airway, 169 stenosis of, 184, 185f Tracheobronchial tree, anatomy of, 369, 370f compression of, 372-373, 373f, 373t, 374f causes of, 373t management of, 375 thermal injury to, from humidifier complications, 544 Tracheostomy, 170 in trauma victims, 829 Tracheotomy, in cervical spine injuries, 179 Train-of-four stimulation, for detection of prolonged neuromuscular blockade, 89, 90, 91 Trandolapril, 52 Tranexamic acid, for early extubation anesthesia, 358 for hereditary angioneurotic edema, 427 for prevention of intracranial aneurysm rerupture, 716 for reduction of blood loss after cardiac surgery, 307t in pregnant patients, 803 Transaminases, postoperative hepatic dysfunction and, 806 Transbronchial biopsy, in sarcoidosis, 458 Transcranial Doppler ultrasonography, 720 Transesophageal echocardiography, complications with, 577-578 for abdominal aortic aneurysm repair, 390 for acute respiratory distress syndrome, 348-349 for aortic dissection, 299f for cardiopulmonary bypass in pregnant patients, 804 for early extubation anesthesia, 359 for pulmonary embolism, 862 for venous air embolism, 674, 674f, 705 in cardiopulmonary bypass, 339, 340 inotropic drug use and, 11, 12

991

Transfusion reaction(s), 202-205. See also Blood transfusion(s). acute hemolytic, 202, 203t, 204, 205, 205t acute lung injury as, 203, 203t, 204, 205, 205t allergic, 203, 203t, 204, 205, 205t delayed hemolytic, 203-204, 203t, 205, 205t febrile nonhemolytic, 202-203, 203t, 204, 205, 205t identification of, 202, 202t, 204 immune-mediated, features of, 202, 202t, 203, 203t, 204 management of, 204, 205t prevention of, 205 management of, 204, 205t prevention of, 205 Transtracheal jet ventilation, cricothyrotomy with, 170-171, 172f, 172t Transurethral resection of bladder tumor (TURB), 843 Transurethral resection of prostate (TURP), 843. See TURP syndrome. Transurethral surgery, complications of, 843-845 Trauma. See also Injury(ies). altered level of consciousness in, 177 blunt, 827 dental, in general anesthesia, 181 during delivery, postpartum hemorrhage and, 779-780, 779t ethanol ingestion and, 508 hyperkalemia and, 55 intubation, 185. See also Intubation; Trachea, intubation of. ocular. See Eye(s), injuries of. oropharyngeal, in transesophageal echocardiography, 577, 578 penetrating, 694-695, 695t, 827 postoperative jaundice and, 806, 807 prevention of, 830 psychological, in children, 682-684, 683f respiratory failure and, 347 scoring systems for, 827-828, 828t spinal cord injury and, 737, 738 surgery for, complications of, 827-830 management of, 829-830 presurgical preparation in, 828-829 urinary retention and, 837 Traumatic brain injury. See also Head injury. cerebral perfusion pressure and, 591 definition of, 732 in children, 728-731 assessment of, 728-729 management of, 729-731 prevention of, 731 risks with, 729 intracranial pressure monitoring and, 593 management of, 594, 729-731, 734-736, 735t prevention of, 731, 736 primary, 732-733, 732t risk assessment in, 733-734, 733t, 734f secondary, 733, 733t Treacher Collins syndrome, difficult airway in, 603f, 605 Trendelenburg position, in radical urologic surgery, 846, 847, 849 spinal surgery in, postoperative visual loss and, 856, 857 Triage scoring systems, 827, 828t Trial, in malpractice cases, 934 Trichloroethylene, carbon dioxide absorbents and, 535, 536 Tricyclic antidepressants, 106-107 mechanism of action of, 106 overdose of, flumazenil and, 128, 129, 130 toxicity of, management and prevention of, 107

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Index

Trihexyphenidyl, in Parkinson’s disease, 491, 491t Triiodothyronine (T3), 451 replacement doses of, 452 Trimethoprim-sulfamethoxazole, complications from, 102t Trochlear nerve, 708 Troponins, cardiac, in myocardial infarction and ischemia, 309-310 Trypsin, in pancreatitis, 473 Tryptase, in anaphylaxis, 98 serum, in latex allergy, 652 Tube(s), chest, drainage from, 305, 306 for prevention of tension pneumothorax, 253 double-lumen, in left-sided thoracotomy, 386 endobronchial, double-lumen, complications with, 368, 368t malposition of, 365-366, 365f, 366f, 367f, 368, 369f placement of, 365, 365f suggested sizes of, 370 single-lumen, in one-lung ventilation, 368 endotracheal. See also Trachea, intubation of. care of, prevention of nosocomial pneumonia and, 211, 212 fiberoptic, 165-166, 168 fire risk with, 562, 563, 564, 565, 568, 569 in blind nasal intubation, 168, 168t in retrograde tracheal intubation, 170, 171t introducer for, 162 lighted stylet, 168-169 medications delivered by, for intraoperative cardiac arrest, 616 placement of, monitoring of, 576 postintubation croup and, 631, 632 removal of, 162, 164 securing of, in burn-injured patients, 507 “softened,” in fiberoptic nasal intubation, 166 esophageal-tracheal Combitube, 169 gastric, for prevention of pulmonary aspiration, 188 laryngeal, 169 Univent, in left-sided thoracotomy, 386 Tube thoracostomy, tension pneumothorax and, 253 Tuberculosis, disseminated, in HIV-infected patients, 448 d-Tubocurarine, dose, clearance, and side effects of, 624t “Tubular washout therapy,” for acute renal failure, 345 Tubules, renal, in acute renal failure, 342, 343f, 344 Tumor(s). See also Cancer; Mass(es). adrenal, 822 adrenalectomy and, 823, 824f medical and surgical management for, 825-826 brain, in children, 728-731 postpartum headache with, 796 carcinoid, complications of, 814-816 embolization of, in radical nephrectomy, 847 in children, systemic complications of, 909t Tumor necrosis factor-α, in acute respiratory distress syndrome, 349 inhibitors of, 501-502, 502t Tuohy needle, for epidural blood patch, 226 Turmeric root, common uses and problems with, 156t TURP syndrome, 843-845 clinical features of, 843, 844t delayed emergence and, 886 management and prevention of, 844-845 pathophysiology of, 844t risks with, 844

T-wave changes, hyperkalemia and, 58 Tyrosine kinase, in myasthenia gravis, 484 U Ulcers, duodenal, 93 gastric prostaglandins and, 273 peptic, from NSAIDs, 276 risk factors for, 275 Ulnar nerve, injuries of, 336, 881-883, 882f, 883f Ultrasonography, Doppler, for vasospasm, 720 for venous air embolism, 674, 675, 705, 787 for identification of fetal abnormalities, 607 Umbilical cord, in ex utero intrapartum therapy, 769 Univent tube, for lung isolation, in one-lung ventilation, 368 Universal precautions, 208, 208t, 447 Upper respiratory infections, criteria for, 649 in children, 649-650 unanticipated hospital admission and, 894 laryngospasm and, 599-600 Urapidil, actions and side effects of, 4t Urea, renal function and, 342-343 Uremia, platelet disorders and, in end-stage renal disease, 462-463, 464 Urinary bladder. See Bladder. Urinary retention, anticholinergics and, 30, 31 autonomic dysreflexia and, 853, 854 neuraxial opioids and, 72, 262 postoperative, 836-839 causes of, 837 management and prevention of, 838-839, 838t risk factors for, 837-838, 837t Urine, concentrated, in diabetes insipidus, 712, 713 in hypernatremia, 433 in acute porphyria, 75 in hypovolemia, 63 sodium level and, 63 tests of, for substance abuse, 123, 123t Urologic surgery, 836-854 radical, complications of, 846-849 management and prevention of, 848-849 recognition of, 846-848 risks with, 848 Urticaria, and angioedema, 426-428 in transfusion reaction, 204 management and prevention of, 427-428 recognition of, 426-427 risks of, 427 Uterine artery, in fetal intrauterine surgery, 767 Uteroplacental blood flow, in fetal intrauterine surgery, 767-768 in preeclampsia, 760 Uterus, atony of, blood loss in, 779, 779t in EXIT procedure, 609, 610 contractions of, in labor, 763-764 spinal cord injury with, autonomic hyperreflexia and, 477 inversion of, blood loss with, 779t, 780 rupture of, bleeding with, 775, 776t, 777t, 779t, 780 V Vaccination, against H. influenzae type B, 216 against hepatitis B, 468 against infectious disease, 208 Valerian, common uses and problems with, 156t delayed emergence and, 886 Van Slyke equation, 437 Vancomycin, complications of, 101-104, 102t, 103t infusion rate and, 103 management and prevention of, 103-104

Vancomycin (Continued) desensitization protocols for, 104 for methicillin-resistant Staphylococcus aureus infection, 211 with volatile anesthetics, 101-102, 103t Vaporizers, design of, 531, 533 freestanding, 532, 533 liquid agent in patient breathing circuit and, 532, 532t, 533 overfilling and tipping of, 531-532, 533 problems with, 531-533 pumping effect of, 532, 533 Vapors, anesthetic, monitoring of, 574, 575 flammable, in operating room, 563, 565t Vardenafil, 21. See also Sildenafil. Vasa previa, bleeding in, 774, 775, 776t, 777t Vascular insufficiency, tourniquet use and, 869, 870 Vascular resistance, systemic, 315 inotropic drug effects on, 11, 12 Vascular smooth muscle, contraction of, magnesium and, 59 relaxation of, by vasodilators, 3 Vascular surgery, 380-397 of peripheral vascular system, 394-397 Vascular tone, angiotensin II effects on, 17 Vasculature. See Blood vessels. Vasoactive drugs, 3-19 Vasoactive substances, secondary pulmonary hypertension and, 660 Vasoconstriction, cutaneous, in hypothermia, 663-665 Vasoconstrictors, 7-9 in lidocaine spinal anesthesia, neurotoxicity and, 229 inotropic drugs as, 11, 11t, 12 urinary retention and, 838 Vasodilatation, adenosine and, 32 in autonomic hyperreflexia, 477 in cardiopulmonary bypass in pregnant patients, 804 in magnesium sulfate tocolytic therapy, 764 with nifedipine, 764 rewarming, 422 systemic, with vasodilator therapy, 3 Vasodilators, 3-6 action of, 3 complications with, 3, 5, 6 for detumescence of penile erection, 841 for hypertension, 313-314 for intravenous or inhalational administration, 4t, 5t for rebound hypertension, 95 ideal properties of, 3 in cross-clamping of thoracic aorta, 386, 388 in traumatic brain injury, 734, 734f inotropic drugs as, 11, 11t management of, 5-6 Vasopressin, aqueous, for antidiuretic hormone replacement, 713 in sepsis, 498 in subarachnoid hemorrhage, 721 in systemic inflammatory response syndrome, 498 in tricyclic antidepressant toxicity, for cardiac arrest, 107 side effects of, 8t with inotropic drug use after separation from cardiopulmonary bypass, 12 Vasopressors, 7-9. See also Catecholamine(s). effects of, 7, 8t in cardiopulmonary bypass in pregnant patients, 804 in hypothyroidism, 453

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Vasopressors (Continued) in systemic inflammatory response syndrome, 498 in treatment of subarachnoid hemorrhage, 721 management and prevention of complications with, 9 monoamine oxidase inhibitors and, 105 risk assessment with, 8 Vasospasm, 717, 719-723 acute hydrocephalus and, after subarachnoid hemorrhage, 722 cerebral, intracranial aneurysm rerupture and, 717, 719-723 diagnosis of, 719-720, 719t management of, 720-721, 720t prevention of, 721-723, 721t risks with, 720 Vaughan-Williams classification, of antiarrhythmic drugs, 37 Vecuronium, 89t dose, clearance, and side effects of, in children, 624t for opiate-induced muscle rigidity, 175 for rapid-sequence induction in open globe injury, 745, 746 in open fetal surgery, 768 Vegetarians, cobalamin deficiency in, 70 Vein(s), ascending lumbar, in retroperitoneal space, 258, 259f injury of, from arterial tourniquet, 868 segmental lumbar, in retroperitoneal space, 258, 259f Venous air embolism, 704-707. See also Air embolism. central venous catheter–related, 582t in children, 629, 673-676 in posterior fossa surgery, 708, 709, 710 in pregnancy, 786, 787, 787t, 788 management and prevention of, 675-676, 706-707 monitoring for, 673-675, 673f, 674f, 706, 706f rapid fluid and blood delivery system use and, 553, 554 recognition of, 553, 704-705 risk factors for, 705-706, 705t terminology of, 673 Venous compression, jugular manual, for prevention of venous air embolism, 707 Venous congestion, of head and neck, postoperative visual loss and, 856 Venous gas embolism, massive, in cardiopulmonary bypass, 302-303, 302f in laparoscopic surgery, 832, 834 Venous oximetry, jugular bulb, 720 Venous stasis, 361, 362 Venous thromboembolism, 363 risk factors for, 270-271, 270t Venous thrombosis, cerebral, postpartum headache with, 796 deep. See Deep venous thrombosis. preventive measures for, 364 Ventilation. See also under Breathing; Respiratory. bag-mask positive pressure, for airway obstruction management, 601 facemask, difficult, 159 diagnosis of, 161, 162, 163f, 163t, 164, 164t patient factors with, 159, 161t signs of, 161t for pulmonary hypertension, 316, 661 impossible, airway management with. See Airway, difficult. in burn-injured patients, 506-507

Ventilation (Continued) in radical urologic surgery, 846-847, 848, 849 in spinal cord injury, 738, 738t in trauma victims, 829 mechanical. See also Ventilators. in systemic inflammatory response syndrome, 498 nosocomial pneumonia and, 210-212 positive-pressure, for opiate-induced respiratory depression, 73 tension pneumothorax and, 253 pressure-controlled, in laparoscopic surgery, 834 monitoring of, ASA standards for, 576 one-lung, 365-370 complications of, 368t management of, 368-369 prevention of, 369-370 in left-sided thoracotomy, 386 vs. oxygenation, pulse oximetry and, 571 Ventilation-induced lung injury, in acute respiratory distress syndrome, 349 Ventilation-perfusion defects, hypoxemia and, 193, 194f in fat embolism syndrome, 859 in venous air embolism, 706 prevention of, 198t Ventilation-perfusion scan, for pulmonary embolism, 786 Ventilator support, in acute respiratory distress syndrome, 350 in burn-injured patients, 507 in opiate-induced respiratory depression, 73 in systemic inflammatory response syndrome, 498 Ventilators. See also Breathing circuit of anesthesia machine. manual, mechanical ventilator problems and, 539 mechanical, bellows leak and, 538 electrical or mechanical failure and, 538 equipment failure with, 537 fresh gas flow and, 538 humidifiers and, 543, 543f inspiratory-expiratory ratio and, 538 management of, 539, 539f operator error or misuse with, 537 pressure limit and, 537 problems with, 537-539 settings for, vasodilator use and, 5 tidal volume or respiratory rate settings and, 537 ventilator alarms and, 528f, 538 ventilator-manual switch and, 537 Ventricular arrhythmias, class I antiarrhythmic drugs and, 36-39 digitalis-induced, magnesium infusions for, 59, 60 in restrictive right ventricular cardiomyopathy, 668 long QT syndrome and, 327-330 tricyclic antidepressant toxicity and, 107 triggered, hypomagnesemia and, 59, 60 Ventricular assist devices, 407 indications for, 408 management and use of, 410-411 risk factors for, 409 types of, 408 Ventricular dilatation, after subarachnoid hemorrhage, 722 Ventricular fibrillation, 319 after cardioversion for atrial fibrillation, 908 causes, prevention, and treatment of, 322t

993

Ventricular fibrillation (Continued) electric shock and, 560 electrocardiographic features of, 320t Ventricular flutter, 319 causes, prevention, and treatment of, 322t electrocardiographic features of, 320t Ventricular muscle fibers, in bradycardia, 332 Ventricular preexcitation, tachyarrhythmias with, 324-326. See also Wolff-ParkinsonWhite syndrome. Ventricular premature beats, adenosine and, 33 class I antiarrhythmic drugs and, 36 Ventricular reentry, ischemia-related, class I antiarrythmic drugs and, 36 Ventricular septal hypertrophy, asymmetrical, 25 Ventricular tachycardia, adenosine and, 33 cardiac disorders associated with, 320 causes, prevention and treatment of, 322t digitalis toxicity and, 25 electric shock and, 560 electrocardiographic features of, 320t in postanesthesia care unit, 902 monomorphic, 319, 319f nonsustained, class I antiarrhythmic drugs and, 36 polymorphic, 44 prolonged Q-T intervals and, 36, 37, 327, 327f, 329. See also Torsades de pointes. Ventriculoperitoneal shunt, after subarachnoid hemorrhage, 722 Verapamil, 48-52. See also Calcium channel blockers. actions and side effects of, 4t β-blockers used with, heart block and, 41-42, 42t cardiac conduction and, 50, 51 for coronary artery disease, 52 for hypertension, 52, 314 for tachyarrhythmias, heart block and, 40 in Wolff-Parkinson-White syndrome, 326 Vertebral artery, local anesthetic injection into, 248 Vincristine, mechanisms, uses, and toxicities of, 114t, 115t Vioxx, toxicity of, 275, 276 Viral disease, blood transfusion and, 295 Viral hepatitis, in perioperative management of cirrhosis, 468 Virchow’s triad, 361 in pregnancy, 362 Visceral pleural line, white, 252, 252f Visual loss, open globe injury and, 745 postoperative, delirium and, 888 in children, 693-694 in spinal surgery, 873 with deliberate hypotension, 855-858 Vital signs, delayed emergence and, 885 in brain injury assessment, 732-733 Vitamin(s), deficiency states of, dietary and herbal regimens and, 151 Vitamin B12, deficiency of, nitrous oxide and, 69, 70 risk of, 70 Vitamin E, common uses and problems with, 155t for prevention of intracranial aneurysm rerupture, 718 Vitreous humor, loss of, in children, 694-695 in retrobulbar block, 748 Vocal cords, assessment of, 818 dysfunction of, 184 in transesophageal echocardiography, 577 paralysis of, after thyroid surgery, 818, 819, 820, 821 Voiding, neural control of, 836-837, 836t

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Volume status, determination of, 430 in postanesthesia care unit, 899 Vomiting. See Nausea and vomiting. Vomiting center, 890, 891f von Hippel-Lindau syndrome, adrenal tumors and, 822 von Recklinghausen’s disease, adrenal tumors and, 822 Von Willebrand’s factor, secondary pulmonary hypertension and, 660 W Wake-up test, spinal cord injury and, 873 Warfarin, in cardiopulmonary bypass in pregnant patients, 803 in central neuraxial techniques, ASRAPM guidelines for, 271t in joint replacement surgery, 864 oral, for prevention of deep venous thrombosis, 863 protein C and protein S deficiency and, 364 spinal hematoma and, 236, 237, 237t Warming. See also Hypothermia; Thermoregulation. active and passive, in anesthesia, 665-666 Warming devices, for hypothermia prevention, 665 risks from, 550-552, 551f, 551t Water. See also Edema.

Water (Continued) brain, hyponatremia and, 429, 430f treatment of, 594 chemical properties of, acid-base balance and, 436, 437t deficit of, in hypernatremia, 433, 434, 434t disorders of homeostasis of, 429-435 excess, humidifier complications and, 544 in adrenal insufficiency, 443 replacement, in children, calculation of, 658t Water blanket devices, 552 Waves, cannon a, 319 δ, in Wolff-Parkinson-White syndrome, 324, 325 Wenckebach heart block, bradycardia and, 333, 333f Wheezing. See also Bronchospasm. nonbronchospastic, causes of, 189t Whitacre needle, 224f Whole bowel irrigation, for poisoning, 509 Wilms’ tumor, systemic complications of, 909t Winnie’s approach to interscalene nerve block, 249, 249f Withdrawal syndromes. See also Drug(s), withdrawal from. with herbs and nutraceuticals, 154t

Withdrawal syndromes (Continued) with substance abuse, 125 Wolff-Parkinson-White syndrome, 324-326 anticholinergic toxicity and, 30 digitalis and, 25 features of, 325 management and prevention of, 326 non-DHP calcium channel antagonists and, 51 radiofrequency ablation for, 915, 915f, 916 risk factors for, 325 Women, headache in, 796 Wound(s), debridement of, in burn-injured patients, 506 Wound hematoma, after carotid endarterectomy, 381 in airway obstruction, 877-878, 879 Wristbands, patient misidentification and, 923 X Xenon 133, for measurement of cerebral blood flow, 380, 381 Z Zaprinast, phosphodiesterase selectivity of, 22t Zeroing, of intracranial pressure monitor, 591-592 Zidovudine, for HIV infection, in obstetric patients, 449 postexposure prophylaxis for, 447