Rural Surgery: Challenges and Solutions for the Rural Surgeon

Rural Surgery

 

Matthias W. Wichmann • David C. Borgstrom Nadine R. Caron • Guy Maddern (Editors)

Rural Surgery Challenges and Solutions for the Rural Surgeon

Editors Matthias W. Wichmann, FRACS Department of General Surgery Mount Gambier General Hospital and Flinders University Rural Medical School 276-300 Wehl Street North Mount Gambier, SA 5290 Australia [email protected] David C. Borgstrom, MD, FACS Department of Surgery Bassett Medical Center One Atwell Road Cooperstown, NY 13326 USA [email protected]

Nadine R. Caron, MD, MPH, FRCSC University of British Columbia-Northern Medical Program Prince George, BC Canada [email protected] Guy Maddern, MD Department of Surgery The Queen Elizabeth Hospital 28 Woodville Rd Woodville South, SA 5011 Australia [email protected]

The following figures are published with the kind permission of the respective owner Figures: 4.1, 4.3, 4.4, 4.5, 7.2, 7.3, 12.1, 12.3, 14.1, 14.2, 15.1, 15.2, 15.3, 30.1, 30.2, 30.3, 37.1, 37.2, 39.1, 39.2, 39.3, 39.4, 40.1, 40.2, 40.3, 40.4, 40.5, 53.1, 53.2, 53.3, 53.5, 61.1, 61.2, 61.4, 63.1, 63.2 Jauch K-W, Mutschler W, Wichmann MW (2007), Chirurgie Basisweiterbildung, Springer-Verlag, Berlin, Heidelberg

ISBN  978-3-540-78679-5     e-ISBN  978-3-540-78680-1 DOI  10.1007/978-3-540-78680-1 Springer Heidelberg Dordrecht London New York Library of Congress Control Number: 2011923337 © Springer-Verlag Berlin Heidelberg 2011 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is ­concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant ­protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Cover design: eStudioCalamar, Figueres/Berlin Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)

To Juliane, Antoinette, Jakobus, and Evangelia – thank you for taking me “down under”! Matthias W. Wichmann To Donna, Catherine, and Samantha. Thank you for your love, confidence, and support. David C. Borgstrom To our fellow rural surgeons around the world. Guy Maddern To Gary F. Purdue† (1945–2010) – gifted surgeon, friend, humanitarian. David C. Borgstrom

 

Preface

We are very pleased to present our contribution to the developing field of rural surgery. Rural surgery requires the surgeon to always be prepared for a procedure or an intervention that he or she might not have done or seen either frequently or recently – this is the best definition of the challenge facing rural surgery. It does summarize well what the challenges of daily work for rural surgeons can be. These challenges become more complex due to the fact that expert support or advice and the technology requirements that often accompany them are frequently far away or not available. With this textbook on rural surgery we want to provide up-to-date information for senior as well as junior surgeons working in nonmetropolitan hospitals around the world. The book is a guide to get through the challenges of starting a surgical practice in a rural environment and can provide the scientific background for the routine work of the experienced rural surgeon. The book also aims to assist surgeons who provide locum services and may not always be used to working alone in a new environment. We hope that this book will become a valuable companion for surgeons working in the field of rural surgery around the world. The editors started to work on this project in 2007 when David Borgstrom came to present at the Annual Scientific Meeting of the Provincial Surgeons of Australia (PSA) in Whyalla (sp) (South Australia). Matthias Wichmann, Guy Maddern, and David Borgstrom agreed to edit a textbook on rural surgery based on the recent experience of one of the Australian editors (MW) who at that time was just beginning to adjust to the challenge and rewards of a rural surgical practice after moving to Australia from Germany. Nadine R. Caron soon joined the editorial team and we started to collect contributing authors around the world. We are very grateful to all the contributing authors for their input into this textbook. Their expertise and knowledge will help to make rural surgeons more comfortable with difficult situations and treatment decisions in our daily practice and serve as a resource for the future rural surgeons who will pursue this rewarding career. The editors would also like to express their gratitude to the team of the SpringerVerlag in Germany. From the start the publisher was very supportive of the idea to edit a book on rural surgery. We are especially thankful to Mrs. Stephanie Benko and Mrs. Rosemarie Unger and Mrs. Dakshinamoorthy Mahalakshmi for their help and assistance.



vii

viii

Preface

We trust that you will enjoy this book and that it will be a valuable support for your work in rural surgery. Mount Gambier, SA, Australia

Matthias W. Wichmann, FRACS

Contents

Part I  Challenges of Rural Surgery   1 Rural Surgical Education: The Australian Approach . . . . . . . . . . . . . . Guy Maddern and Matthias W. Wichmann

3

  2 Surgery for Rural America . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . David C. Borgstrom

5

  3 Surgery in Rural Canada: Challenges and Possible Solutions . . . . . . . Nadine R. Caron and Stephen J. Pinney

7

Part II  Pre- and Postoperative Care



  4 Fundamentals of Surgical Oncology . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hanno Niess, Karl-Walter Jauch, and Christiane J. Bruns

17

  5 Palliative Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Matthias W. Wichmann

27

  6 Fiber Optic Endoscopy: Bronchoscopy . . . . . . . . . . . . . . . . . . . . . . . . . Matthias W. Wichmann and Fritz W. Spelsberg

31

  7 Fiber Optic Endoscopy: Gastroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . Matthias W. Wichmann and Fritz W. Spelsberg

35

  8 Fiber Optic Endoscopy: Colonoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . Matthias W. Wichmann and Fritz W. Spelsberg

41

  9 Endoscopy for Rural Surgeons: ERCP . . . . . . . . . . . . . . . . . . . . . . . . . . Ian C. Roberts-Thomson

47

10 Rigid Endoscopy: Cystoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mark Lloyd and John Miller

51

ix

x

Contents

11 Rural Surgical Audit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . David A.K. Watters

55

12 Acute Pain Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Edmund A.M. Neugebauer, Astrid Althaus, and Christian Simanski

67

13 Prophylaxis of Venous Thromboembolism . . . . . . . . . . . . . . . . . . . . . . . Robert A. Fitridge and Simon McRae

77

14 Nutrition of the Surgical Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Florian Brackmann, Wolfgang H. Hartl, and Peter Rittler

85

15 Surgical and Hospital-Acquired Infections . . . . . . . . . . . . . . . . . . . . . . Wolfgang Böcker and Wolf Mutschler

99

16 Antimicrobial Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 Christian P. Schneider and Beatrice Grabein 17 Preoperative Risk Assessment in Rural Surgery . . . . . . . . . . . . . . . . . . 133 Teresa Bueti, Munawar Rana, and Matthias W. Wichmann 18 Perioperative Fluid Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Peter Rittler and Wolfgang H. Hartl 19 Analgesia and Sedation in Intensive Care . . . . . . . . . . . . . . . . . . . . . . . 145 Christian Waydhas

Part III  Operative Care 20 Anti-reflux Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 Glyn Jamieson 21 Gastric Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 Matthias W. Wichmann 22 Gallbladder Surgery: Laparoscopic Cholecystectomy and Management of Bile Duct Stones in the Rural Setting . . . . . . . . . . 169 Harsh A. Kanhere and Andrew D. Strickland 23 Liver Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181 Faud Alkhoury, Christine Vancott, and Randall Zuckerman 24 Pancreatic Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187 Markus Trochsler, Thomas Satyadas, and Harsh A. Kanhere

Contents

xi

25 Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 Martin Bruening 26 Surgery of the Spleen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 Matthias W. Wichmann 27 Complications After Bariatric Surgery . . . . . . . . . . . . . . . . . . . . . . . . . 205 Brent White 28 Appendicitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217 Kerstin S. Schick and Johannes N. Hoffmann 29 Bowel Obstruction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 Saukat T. Esufali 30 Diverticulitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231 Matthias W. Wichmann and Karl-Walter Jauch 31 Therapy of Sepsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237 Johannes N. Hoffmann 32 Bowel Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245 Peter Hewett and Cu Tai Lu 33 Rectal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251 Peter Hewett 34 Stoma Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255 Nick Rieger 35 Acute Abdominal Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259 Hajir Nabi 36 Gastrointestinal Bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267 Friesen W. Randall 37 Mesenteric Ischaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275 Heinrich Stiegler, Florian Brackmann, and Laura Holzner 38 Management and Surgery of Inflammatory Bowel Diseases . . . . . . . . 281 William Roediger 39 Proctology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289 Alexander Herold and Laura Holzner 40 Abdominal Wall Hernias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299 Reinhold A. Lang and Martin K. Angele

xii

41 Thyroid Surgery for the Community General Surgeon . . . . . . . . . . . . 309 Anthony J. Chambers and Janice L. Pasieka 42 Parathyroid Surgery in the Non-Tertiary Center . . . . . . . . . . . . . . . . . 315 Anthony J. Chambers and Janice L. Pasieka 43 Adrenal Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323 Marlon A. Guerrero and Wen Shen 44 Breast Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331 David Walsh 45 Skin Cancer: Current Surgery for This Common Problem . . . . . . . . . 341 R. Gwyn Morgan 46 Pediatric Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351 Thao T. Marquez, Mara B. Antonoff, and Daniel A. Saltzman 47 Vascular Surgery: Acute Limb Ischaemia . . . . . . . . . . . . . . . . . . . . . . . 359 Mark Hamilton 48 Vascular Surgery: Management of the Diabetic Foot . . . . . . . . . . . . . . 369 Mark Hamilton 49 Minor Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375 Eric Mooney

Part IV  Relevant Orthopaedics for General Surgeons 50 Simple Orthopaedic Procedures and Common Diagnoses . . . . . . . . . . 389 David Wysocki and René Zellweger 51 Carpal Tunnel Release . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 407 Hajir Nabi 52 Dupuytren’s Contracture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411 Barney McCusker 53 Hand Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415 Andreas Frick and Christiane G. Frick

Part V  Other Relevant Operative Specialities for General Surgeons 54 Rural Obstetrics and Gynaecology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425 Colin Weatherill

Contents

Contents

xiii

55 Urological Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433 John Miller, Clair Whelan, and Kulendran Sivapragasam 56 Otolaryngologic Emergencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451 Cynthia Bonatucci Fisher

Part VI  Emergency Care 57 Airway Management: A Surgical Perspective . . . . . . . . . . . . . . . . . . . . 465 Adrian Anthony 58 Management of the Severely Injured . . . . . . . . . . . . . . . . . . . . . . . . . . . 483 Adrian Anthony 59 Rural Burn Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 501 Gary F. Purdue† and Brett D. Arnoldo 60 A Guide to Neurotrauma for the Rural Surgeon . . . . . . . . . . . . . . . . . . 507 David Omahen and Stephen J. Hentschel 61 Abdominal Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 529 Wolfgang E. Thasler 62 Trauma Surgery: Neck Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535 Harsh A. Kanhere and Robert A. Fitridge 63 Open Extremity Fractures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 541 Ekkehard Euler 64 Traumatic Injuries of the Spine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 547 Rudolf Beisse and Christoph Siepe 65 Trauma Surgery, Orthopaedic – Pelvic Fracture . . . . . . . . . . . . . . . . . . 555 Tim Pohlemann, Daniel Köhler, and Christopher Tzioupis 66 Trauma Surgery: Vascular Emergencies . . . . . . . . . . . . . . . . . . . . . . . . 563 Robert A. Fitridge and Mark Hamilton 67 Thoracic Emergencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 571 Christian Müller Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 577

 

Part Challenges of Rural Surgery

I

 

1

Rural Surgical Education: The Australian Approach Guy Maddern and Matthias W. Wichmann

1.1 Introduction Recruiting and maintaining a “critical mass” of the medical workforce within rural centers is a difficult challenge for the Australian society. Australia is one of the most urbanized societies on Earth, and the majority of the population (83%) lives in and around a small number of major cities that are mainly localized on the coastline. Until now, working in medicine in rural Australia appears to be attractive to only a few Australians and has been supported by a substantial number of healthcare providers who are educated and trained outside Australia. To address this significant and growing problem, all the major universities throughout Australia have established so-called Rural Medical Schools in order to expose students to rural medicine at a young age, hoping to retain a significant fraction of these students within the rural medical workforce. Various colleges of medical specialties have also introduced dedicated training programs that aim at recruiting and possibly retaining medical specialists in rural Australia. Whether or not these new concepts of medical teaching account for long-term success remains to be determined. Early

G. Maddern Department of Surgery, The Queen Elizabeth Hospital, 28 Woodville Rd, Woodville South, SA 5011, Australia e-mail: [email protected] M.W. Wichmann (*) Department of General Surgery, Mount Gambier General Hospital and Flinders University Rural Medical School, 276-300 Wehl Street North, Mount Gambier, SA 5290, Australia e-mail: [email protected]

results and the growing interest of students to participate in rural education, however, suggest a promising and encouraging beginning.

1.2 Rural Surgical Training in Australia Surgical training in Australia has been restructured and is now run within the Surgical Education and Training (SET) Program. Within the SET program, trainees are selected directly into one of the nine specialty training programs (cardiothoracic, general, neurosurgery, orthopedic, ENT, pediatric, plastic/reconstructive, urology, vascular). Length of training varies between 5 and 7  years depending on the specialty, and trainees can then present for fellowship examination. The earliest point at which an application can be made for the first year of training (SET1) is during Postgraduate Year 2 (PGY2). Trainees applying for general surgical training have the option to enroll into the Rural Surgical Training Program (RSTP), which has been introduced to enable early recruitment of trainees into the rural surgical workforce. The RSTP allows trainees to undertake a flexible program that includes regional, rural, and remote practice. Trainees within RSTP have access to a network of rural surgeons and mentor assistance, and receive additional financial assistance for conferences and training courses. Each trainee is allocated a mentor, who is responsible for helping the trainee develop a comprehensive training program, and who serves as a guide and counselor during the surgical training period. Rural trainees must complete the standard general surgical training program and can present for the fellowship exam in General Surgery at the completion of

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_1, © Springer-Verlag Berlin Heidelberg 2011

3

4

their 5-year program. Rural surgical education aims to equip the trainee for both metropolitan and rural surgical practice, but aims at trainees who have a rural background or have prior rural medical experience. The selection process for trainees who are interested in rural surgery and those who are not is the same. This selection involves a semi-structured interview, assessment of curriculum vitae, and evaluation of referee and supervisor reports. During recent years, Australia has relied on a large number of international medical graduates to maintain surgical services in rural and remote areas. In 2007, RSTP had produced 38 graduates since its commencement in 1998. In view of these figures, it is no surprise that foreign medical graduates currently represent a large fraction of the rural surgical workforce. Recent evidence suggests that a sustainable and safe service requires a minimum of three general ­surgeons within a rural surgical center. One model of addressing this workforce challenge is to bring rural surgeons into a network relationship with city institutions that allows for continuing professional development, access to locum cover, forum for quality assurance, and auditing as well as ongoing contact with students and trainees. Some centers are remote, but of insufficient size to support more than one general surgeon. If only serviced by one surgeon, they would need to be on call

G. Maddern and M.W. Wichmann

365 days a year. To deal with this problem, some towns have rotating surgeons from the city work in the town for 7 days and then return to the city to be replaced by another fresh surgeon for the following week. This model has been highly successful and well received by the patients of general practitioners. Provision of reliable locum support has also been successfully used to allow solo surgical practitioners to have respite and enable attendance at professional meetings. These efforts combined with major city hospitals offer a viable way forward. This combined with the joint efforts of universities, as well as the Australasian College of Surgeons, may result in a higher proportion of Australian graduates working in rural surgery in the years to come.

Recommended Reading Bruening, M.H., Maddern, G.J.: Surgical undergraduate education in rural Australia. Arch. Surg. 137, 794–798 (2002) Campbell, G.: Rural surgical training in Australia. ANZ J. Surg. 77, 922–923 (2007) Gough, I.: President’s perspective. Surgical News 10, 3–4 (2009) Green, A.: Maintaining surgical standards beyond the city in Australia. ANZ J. Surg. 73, 232–233 (2003) Maddern, G.J.: Rural general surgical placement: a necessity not an option. ANZ J. Surg. 73, 975 (2003)

2

Surgery for Rural America David C. Borgstrom

It is estimated that 60 million Americans live in rural areas far removed from urban and suburban health care. Health care and surgical care for rural America is at a crisis. Rural Americans are, in general, older, sicker, poorer, and less educated than their urban and suburban counterparts. Infant mortality and injuryrelated mortality is greater, there is less insurance and fewer physicians per capita, and it is estimated that there is 20–30% less overall medical service for rural and remote Americans. As the economics of health care evolve, the constraints on rural America become even greater. Many rural hospitals are closing at a time when it is more and more clear that the general surgeon is the economic engine that drives the rural hospital and the rural hospital is quite often the economic engine of the rural community. To compound this problem, the number of surgeons per capita in rural America indicates this population is underserved and it is estimated there will continue to be a significant shortage of surgeons needed to practice in rural areas. Further, with the aging of the baby boomer population, the segment of America growing the fastest is those aged 65 and over. In this group of patients, it is estimated the general surgery workload is three times greater than in those of a younger age. As health care evolves, fewer and fewer surgeons in general surgery training programs are electing to remain in general surgery. Currently, only about 35–40% of residents completing US general surgery education

D.C. Borgstrom Department of Surgery, Bassett Medical Center, One Atwell Road, Cooperstown, NY 13326, USA e-mail: [email protected]

programs elect to go into practice where general ­surgery is part of their practice and of those, only 13% are electing to go into rural surgery locations. Student interest in these opportunities has declined, and there are fewer female students interested. General surgeons in rural America are by and large male, over 50 years of age; they are much more likely to be international medical graduates and are seeking earlier retirement than their urban/suburban counterparts. Where the estimated age of retirement used to be near 70, it is now around 62 years of age. Economic issues of lower reimbursement, technology advances, increased liability costs and culture diversity concerns of family make this a problem that is getting worse. The crisis is further compromised because of the fact that most Americans who live in rural America do not like the big city and would much prefer to get their health care away from urban areas. Fortunately, there is increasing recognition of this crisis, not only in the lay press, but also in organizations such as the Association of Program Directors in Surgery and the American College of Surgeons. There is now a recognized need to refocus efforts to not only train surgeons to feel qualified to care for this broad diversity of surgical need, but also to make it appealing both from an economic standpoint and an academic standpoint. The American Association for the Surgery Trauma has developed an acute care surgical fellowship in conjunction with a surgical critical care fellowship. While the intent of this at first glance is to develop mechanisms to care for the acute presentation of surgical disease in large academic medical centers, the diversity of experience is well designed for surgeons who are interested in providing surgical care for rural America.

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_2, © Springer-Verlag Berlin Heidelberg 2011

5

6

Finally, there are several institutions that have recognized the need to not only provide an experience in rural surgery practice, but also diversity training. The Oregon Health and Science University’s Department of Surgery has a program to introduce residents to a rural surgery practice as an alternative to spending time in a research lab. The University of North Dakota program also facilitates experiences for its residents to spend considerable time in a rural setting. Bassett Healthcare, in Cooperstown, New York, through the Mithoefer Center for Rural Surgery, provides fellowship opportunities for surgeons who have completed

D.C. Borgstrom

their traditional general surgery curriculum who have interest in additional training that will allow them ­better to care for rural America. Surgical care for rural America is at a crossroads. There is declining interest and increasing need. Fortunately, there are organizations that have recognized the critical nature of the concern and are attempting to develop programs that will not only make it appealing for newly trained surgeons, but to also provide them the training necessary to feel qualified to provide the broad array of surgical expertise necessary to care for rural America.

3

Surgery in Rural Canada: Challenges and Possible Solutions Nadine R. Caron and Stephen J. Pinney

3.1 Introduction

3.2 How Do We Define “Rural Canada”?

The provision of timely and quality surgical services is a persistent challenge in rural Canada. As they work to provide rural surgical services, health-care providers, administrators, and policy makers confront considerable obstacles. With almost 10 million km2, Canada is the second-largest country in the world. However, its population density ranks in the lowest 5% of countries – 95% of the land in Canada is rural. Despite this, only about 20% of Canadians live in rural areas as defined by a community having a population of less than 10,000. These geographic factors alone produce inherent challenges, which are increased by the economic, socio-cultural, and political issues facing rural communities: rationalization of health-care resources to regional centers, relatively high poverty rates, plus issues in health status disparities, most of which are often associated with aboriginal populations. While these challenges are longstanding and difficult to overcome, the stress on the health-care system and the rural populations it serves creates an impetus for change. This chapter outlines the challenges in training for and providing rural surgery in Canada and suggests possibilities for creative solutions.

In the context of surgical practice, we define “rural” as communities whose small population and/or remote geographic location usually requires surgeons to maintain a broad practice with minimal clinical support and ­limited access to technical resources. In Canada, this most commonly refers to communities with one to two general surgeons and populations of less than 10–20,000 people.

N.R. Caron (*) University of British Columbia-Northern Medical Program Prince George, BC, Canada e-mail: [email protected] S.J. Pinney Department of Orthopaedics, St. Paul’s Hospital, 1081 Burrard St. Room C323, Vancouver, BC V6Z 1Y6, Canada e-mail: [email protected]

3.3 Challenges There are multiple challenges to providing highquality surgical services in rural Canada. These include (1) the limited number of practicing general surgeons; (2) the fact that skills needed for a rural surgical practice are increasingly de-emphasized in Canadian surgical training programs; (3) difficulties in recruiting and retaining surgeons to rural communities; (4) limited resources for establishing or maintaining surgical services and practices; and (5) poor integration and coordination of existing surgical services.

3.3.1 The Limited Number of Practicing General Surgeons Rural communities face a stark challenge: Few physicians choose careers in rural surgery. We will explore the causes for this shift in detail later, but let us begin with two key facts: Surgeons in rural locations are almost exclusively general surgeons, and the number

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_3, © Springer-Verlag Berlin Heidelberg 2011

7

8

of general surgeons in Canada is decreasing. Quite simply, more general surgeons have retired than have entered the Canadian work force over the past decade [1, 2]. With fewer graduates entering general surgery practice, it becomes difficult to find enough of them to meet the needs of rural Canadian communities.

3.3.2 Skills Needed for a Rural Surgical Practice Are Increasingly De-emphasized in Canadian Surgical Training Programs Another, more subtle shift has occurred as well: The culture of present-day surgical training in North America encourages subspecialization as opposed to the generalist training once well incorporated in standard General Surgery residencies [3]. Of those completing General Surgery training, a significant number now choose subspecialization, bypassing the option of rural surgery practice in favor of post-residency fellowships based on anatomic association, clinical etiology, technology utilized or age-related patient populations. It is estimated that up to 70% of graduates from Canadian general surgery residencies ­pursue postgraduate fellowships. This has limited the number of surgeons who can provide the wide range of surgical procedures required in rural Canada. A generation ago, a graduating ­general surgeon would feel comfortable performing a variety of common procedures in a range of disciplines such as caesarian sections, emergency craniotomy “burr holes”, skin grafting, draining peri-tonsillar abscesses, and stabilizing basic fractures. Today’s graduating general surgeons often have little hands-on experience performing these type of procedures and therefore many new surgeons do not feel comfortable performing the breadth of procedures that are needed in a rural community. One reason for this is program planning, the process whereby residency training programs structure observation, training, and hands-on learning. In many Canadian residency programs, general surgery residents no longer experience rotations in urology, obstetrics/ gynecology, plastic surgery, neurosurgery, and orthopedics. If they do, such rotations typically occur in the junior residency years when the focus of training is not on procedural competency but on understanding core

N.R. Caron and S. Pinney

surgical principles. Indeed, the only “off-service” rotation (not general surgery or one of its subspecialties) mandated by the Royal College of Physicians and Surgeons of Canada is Critical Care Medicine. General surgery residents spend their senior years focusing on subspecialty general surgery such as hepatobiliary, colorectal, or minimally invasive surgery, among a long list of others. They become comfortable and competent performing complex surgeries as part of a team at a tertiary center, but often have little experience performing a wide variety of the more basic surgical procedures in other disciplines on their own. Like most people, surgeons become comfortable with what they have been trained to do, in an environment they are familiar with and as a result, often distance themselves from the concept of rural practice. A further reason for this move toward subspecialization is role modeling, a factor that education specialists recognize as one of the most powerful teaching tools [3, 4]. Students model themselves on what they see, and surgery residents at major training programs in Canada tend to encounter subspecialists at greater frequency and significantly longer in duration than general surgeons due to their urban-based training. These individuals serve as role models for those training to be general surgeons; implicitly, this fosters the trend toward subspecialization that has made it so ­difficult to train generalists and recruit such surgeons to rural practices. Finally, we must consider that most training programs are situated in large urban centers. During the five or more years that it takes residents to train, they often become comfortable in this type of setting, developing friendships and/or partnerships, and building lives that make it difficult for them to move to a rural community when they finish their training.

3.3.3 Difficulties in Recruiting and Retaining Surgeons Rural Canadian communities face further challenges in recruiting and retaining surgeons, including (a) lower patient volumes to maintain subspecialty skills [3] and (b) the perception that rural surgical practices require demanding on-call schedules. First, as we have seen, surgeons increasingly choose to pursue subspecialization after their general training.

9

3  Surgery in Rural Canada: Challenges and Possible Solutions

Having done so, they often wish to maintain a focused practice that does not extend significantly beyond their field of expertise. Such a scope of practice is neither predictable nor easily obtained in the rural environment, helping to explain why most subspecialty-trained surgeons do not move to rural locations. For rural general surgeons who have not pursued subspecialty training, their low case volume for subspecialty care creates increased pressure to transfer patients requiring elective care in subspecialty fields to regional or tertiary centers. This can limit the scope of rural elective general surgery and often adds to the stress of emergent surgical care [3]. Concerns regarding daunting emergency on-call responsibilities pose a further challenge. Surgeons in small rural communities simply do not have many local colleagues with whom to share on-call workload and this all too often correlates with increased frequency of formal and informal on-call schedules. While small populations may translate to less afterhours work when on-call, rural surgeons grapple with community expectations that they be available for urgent matters. As well, they face the considerable stress of caring for patients with challenging clinical presentations in the absence of colleague support, both medical and surgical. As a result, quality of life issues and professional burnout pose real concerns for surgeons practicing in rural areas [5].

3.3.4 Limited Resources for Establishing or Maintaining Surgical Services and Practices Ironically, government policies often discourage surgeons from pursuing rural surgery practices, as infrastructure funding for hospitals, labs, and imaging facilities tends to favor regionalization. From the ­government’s perspective, it makes sense to concentrate physical and human resources in larger centers. However, this means that surgeons wanting or needing to practice with access to these facilities and resources (especially subspecialists) will naturally be drawn to larger regional centers. For surgeons in rural communities, regionalization often means finding themselves (and their patients) hours away from well-equipped and well-staffed regional centers.

3.3.5 Poor Integration and Coordination of Existing Surgical Services Practical issues within the health-care delivery system further undermine the potential for a more widespread distribution of general surgeons. For example, many general surgeons would prefer not to practice as sole practitioners, preferring the freer lifestyle provided by a shared practice, but the catchment base in most rural communities is not large enough to keep more than one surgeon busy. In addition, many of the resources required to sustain a full surgical practice that meets clinical guidelines and public expectations such as CT scanners, MRIs, and laboratories are not available in rural centers.

3.3.6 Summary of Challenges A variety of forces are thus combining to undermine Canada’s ability to provide high-quality surgical care in rural areas. Fewer general surgeons are being trained and those who do graduate often are not prepared to provide the breadth of surgical procedures required in a rural community. In addition, trainees have limited exposure to rural surgery and few role models to encourage them to choose a rural surgery practice. The prospect of a demanding on-call schedule and professional isolation with the lack of colleagues may also act as additional deterrents. Combined with limited funding for infrastructure and the lack of an integrated system for providing surgical care, these factors have lessened the ability of rural communities to recruit and retain surgeons.

3.4 Possible Solutions To provide surgery in rural communities, you need both surgeons and the human and physical resources that support them: nursing, anesthesia, operating rooms, imaging equipment, and laboratory support. Despite the many problems associated with providing high-quality surgical care to rural populations in Canada – problems of surgical training, recruitment, workload, isolation, regionalization – there are practical strategies that would increase the number of surgeons

10

willing to work in such communities and significantly improve the structures that support them there. These strategies include (1) using educational and program planning principles to encourage residents to pursue rural surgery practices; (2) optimizing the use of telemedicine as a means of providing clinical care and clinical teaching; (3) using a systems-based approach to improve integration between communities; (4) training some general practitioners to perform basic surgical procedures and provide initial trauma stabilization; and (5) utilizing physician extenders (PEs) to extend the range of surgeons in rural practices; and (6) increasing financial incentives for rural surgeons.

3.4.1 Invoking Educational and Program Planning Principles In order to train a new generation of surgeons ready to take up practice in rural Canada, medical programs will need to apply educational and program planning principles in a strategic fashion. Education principles that will facilitate this change include (a) role modeling; (b) outcome-based education; (c) utilizing the central role of evaluation; (d) target training to planned scope of practice and avoid “extraction education”; and (e) ensuring active learning. Program planning principles will also be essential to ensure that resources exist to support our current and future rural surgeons.

3.4.1.1 Role Modeling Role modeling is a critical educational tool that could be deployed to encourage more surgeons to consider rural practices. Surgical trainees – indeed, all trainees – are acutely influenced by role models [4]. In fact, what trainees observe teaches them far more than any lecture that they hear or paper that they read. If surgical trainees are not exposed to surgeons who have flourishing and enjoyable rural practices, very few graduates are likely to attempt this type of practice, especially given current trends toward regionalization. To encourage young ­surgeons to pursue rural careers, residency training ­programs must provide direct, sustained exposure to surgeons providing high-quality care in rural communities. Importantly, physicians chosen as role models should be ones who enjoy their work. Such role models would be most effectively used in conjunction with a student population that itself had

N.R. Caron and S. Pinney

roots in rural Canada. Although growing up in a rural community does not guarantee that individuals will stay in a rural community once they are trained, it does increase the likelihood of this happening. Medical schools and surgical residency programs should therefore actively encourage candidates who have grown up in rural communities and should try to match them with mentors who both model and speak about the attractions of rural surgical practice.

3.4.1.2 The Principle of Outcome-Based Education The principle of outcome-based education suggests that training for any profession should be dictated by what one actually needs to be able to do in practice [6]. This is the premise underlying the CanMEDS initiative that attempts to identify the knowledge, skills, and personal qualities that physicians graduating from Canadian medical schools should have [7]. This in turn demands that those in charge of the medical school curriculum create learning experiences so that their graduates will have the desired attributes. The same principle can be applied to training general surgeons for a rural surgery practice. For those destined to be general surgeons in rural practices, this means performing core surgical procedures in an appropriate spectrum of specialties without tertiary and quaternary resources. For medical schools interested in producing surgeons ready to practice in rural Canada, this means thinking carefully about what common clinical scenarios such physicians are likely to encounter and ­creating learning experiences that will allow them to provide these services within quality standards.

3.4.1.3 Appreciating Evaluation’s Central Role in Learning Appreciating evaluation’s central role in learning is critical during surgeons’ training and after they start practice. People tend to base their actions on how they are evaluated [8]. In this context, we are referring to “evaluation” in the broadest sense of the word. If a goal of residency training is to encourage more graduates into rural practices, then the content they are taught and upon which they are evaluated should reflect this. If medical school exams and assessments include content related to rural surgery, they will encourage mastery of such issues, regardless of students’ ultimate

11

3  Surgery in Rural Canada: Challenges and Possible Solutions

practice type or location. Such content might involve patient transfers (the decision-making process and optimizing the transfer itself); telephone consultations; the spectrum of clinical approaches to the pathology; and clinical scenarios within the curriculum that will be based on resources available and how to differentiate such approaches. For trainees planning an urbanbased practice, the curriculum should generate an understanding of the challenges of rural surgical care and the responsibilities of referral centers to assist when human or technical resources are needed.

3.4.1.4 Over Education or “Extraction Education” Over education or “extraction education” is a negative principle that should be kept in mind by program planners as they promote the expansion of rural surgery. Essentially, as individuals become more highly trained, they usually gain more career opportunities. In the field of surgery, individuals with higher degrees of training (i.e., general surgeons with subspecialty training) commonly pursue non-rural positions. This suggests a potential benefit of training rural surgeons locally and at a level appropriate to what is needed for the rural practice. This will likely translate into less subspecialty rotations in fields least likely to be required in rural surgery such as hepatobiliary, complex pediatric surgery, or transplantation and more broad based training in preparation for the case loads expected in rural hospitals. This highlights the need for distributed training sites for surgical rotations in targeted or specific communities, where surgeons would master what they need for specific practices. Such targeted training has achieved a degree of success in General practitioner (GP) surgery training in Canada and other parts of the world. GP surgeons acquire the ability to perform a limited scope of identified surgical interventions with additional training dictated by a specific community needs such as skin grafts, hand ­procedures, tubal ligations, or others. A basic curriculum with additional procedures tailored to the community tends to enhance physician retention.

3.4.1.5 Active Learning Active learning refers to the principle that learning happens most effectively when learners are physically and/or intellectually engaged in the learning process [9]. It facilitates efficient learning and optimizes

retention of information and skills. Activities with a physical component, especially real or simulations of real events, can be very helpful to facilitate active learning. The “hands-on” approach to many aspects of surgical training is an example of active learning. It is a richer, more powerful mode of learning than the passive learning that, unfortunately, is the usual modality in continuing medical education (CME). To ensure maximum effect, education programs designed to ­foster skills essential to rural surgical practice should deploy active learning principles at every level, from residency to CME.

3.4.2 Telemedicine Telemedicine represents a unique opportunity to address some of the problems in providing surgical services to rural Canadian communities. For the purposes of this chapter, we define telemedicine as the use of live interactive video and audio feeds via the internet to facilitate either clinical care or health-care education from a distance. With recent advances in computing power, digital video, and internet technology, an increasing number of Canadian rural communities can now take advantage of this resource. There are three broad ways that telemedicine is used: (a) physicians diagnosing and in some instances treating patients from afar; (b) specialist physicians helping nonspecialist physicians manage complicated cases in their home community; and (c) providing interactive education to rural health-care providers. Each of these could dramatically improve surgical care in rural communities if the systems and culture are ­created to optimize how telemedicine is used.

3.4.2.1 Physicians Diagnosing and in Some Instances Treating Patients from Afar It is increasingly common in Canada for specialist surgeons to assess patients via telemedicine. This has expanded access to specialist physicians to a much broader segment of the population. Imagine a patient in British Columbia whose GP has identified a lung mass and begun a basic workup at the local hospital. Previously, such a patient was then required to travel 3  h or more each way to be seen by a specialist in

12

thoracic surgery. This often required either a multiday trip or more likely, multiple day trips with associated expenses and thereby served to create a barrier to care. Often, patients are forced to avoid or delay these journeys for health-care access because of time, money, weather, or employment restrictions, among others. With telemedicine, patients can show up for an “appointment” at their local hospital and be assessed via telemedicine by a thoracic surgeon who is often hours away. These visits are often facilitated by a local nurse who collects all of the patient’s test results, reviews the patients’ history, and may even help carry out a basic physical exam under the direction of the consulting surgeon. In many instances, telemedicine either allows the patient to be managed locally or, if surgery is indicated, it can be done in one trip with the knowledge that the patient has been worked up prior to the procedure. Postoperative follow-up care can also benefit from this system. There are obvious limitations to this type of telemedicine as physicians cannot perform a hands-on examination. However, this type of telemedicine could serve to dramatically expand access to specialist care in a number of cases. Perhaps the biggest barrier to wide-scale implementation of this type of care is the traditional medical culture. Providing care via the internet may feel different to many surgeons and especially unnatural to more senior or less technologically savvy physicians. However, given the tremendous potential to extend care to a wide segment of the Canadian population that presently does not have access to specialist treatment, it is an approach that physicians and administrators should ­pursue vigorously.

3.4.2.2 Expert Physicians Helping Nonexpert Physicians Manage Complicated Cases in Their Home Community Telemedicine can also enable urban physicians and/or subspecialists to aid physicians in a rural area. Physi­ cians now commonly use video links to help rural ­colleagues manage a trauma patient, treat patients with acute coronary syndrome, or appropriately manage any patient with a complex problem. This use of telemedicine is likely to be more easily embraced as it represents an extension of traditional rural practice. For several generations of Canadian rural physicians, the telephone has served as a lifeline to expert

N.R. Caron and S. Pinney

consults. The ability to share images and live video feeds dramatically improves the accuracy and extent of care that can be provided via real-time physician-to­physician communications. This use of telemedicine can be done as easily as sending an x-ray image via a cell phone. However, for more involved interactions, a video linkup and a coordinated program for accessing expert physicians should be instituted. 3.4.2.3 Providing Interactive Education to Health-Care Providers Finally, telemedicine promises to make regular continuing medical education (CME) practical and economical for physicians practicing in rural communities. The ability to obtain and maintain core knowledge and skills and to learn about medical advances is particularly critical for rural physicians. However, attending a CME program requires extended travel time, cost, and time away from practices where few locums are available. Distance learning via telemedicine provides a potential solution to these problems. Interactive lecture presentations can now be easily presented online in the form of webinars. Even a coordinated curriculum providing a comprehensive review of a broad topic can now be provided online via distance learning complete with instructors, regular feedback, and examinations. These tools now make it much more manageable for rural physicians to keep knowledge and skills up-to-date.

3.4.3 Systems-Based Solutions Even if medical schools and their surgical residencies were to train a new generation of surgeons for rural Canada, many of the barriers to high-quality surgical care would still exist. These barriers stem from systemic or organizational issues. A trauma victim requiring a general surgeon, an orthopedic surgeon, and a CT scan may have to visit three different hospitals, each hours apart. These are problems that compromise care and the solutions to these issues require organizational or system changes that need to be instituted by the administrators of the overall health system. These are changes that require vision, creativity, and leadership and should be done without automatically defaulting to the regionalization approach where all resources are simply removed. However, as Canada

13

3  Surgery in Rural Canada: Challenges and Possible Solutions

has a coordinated single-payer health system, these changes, while difficult, are not impossible.

3.4.4 Training General Practitioners (GPs) As Surgeons Training some general practitioners (GPs) to perform certain basic surgical procedures and provide initial trauma stabilization could prove to be a vital element of improved surgical care in rural communities. However, what procedures could be appropriately ­performed by GPs and how GPS should be trained and certified continue to be debated. Currently, there is only one formal GP surgery training site in Canada, which was initiated 2 years ago. Training rural GPs in Advance Trauma and Cardiac Life Support (ATLS and ACLS) is practical and indeed existing pathways for this training already exist. Extending this to training GPs to provide basic anesthesia and perform basic surgical procedures such as Caesarian sections, appendectomies, endoscopies, and applying external fixation to long-bone fractures would be a practical next step for GPs who are committed to learning, and maintaining these skills. As might be expected, there is some resistance from specialist surgeons to training GP surgeons. However, the benefits to rural communities are potentially profound and examples exist in Canada. For example, the ability for a mother to have a caesarian section (C/S) performed locally would have a dramatic effect on obstetrical care in a community. Indeed, obstetrical care in British Columbia, Canada is in crisis. As less obstetricians (specialist surgeons) set up practice in rural communities, there are more expectations that the local general surgeons provide C/S capacity. However, as stated previously, less general surgeons are going to rural communities and even less are trained in C/S skills. GP surgeons often fill this gap but the lack of training programs and opportunities limits new GP surgeons in filling these roles. Therefore, GPs who previously managed obstetrical patients are now relinquishing their privileges in this area due to lack of surgical backup that then adds to an already stressful practice pattern. For those GP’s that maintain obstetric care in the face of all limitations, they now have extensive call duties that has led to burnout and either moving to a center with surgical obstetrical backup or being forced to quit obstetrics

care. Ultimately, it is patient care that suffers. Many pregnant patients would be able to stay in their home communities and deliver their babies locally rather than travel away from their family and friends – and at their own expense – to await the birth of their child in a strange community. Similarly, early intervention in trauma and urgent cases such as appendicitis would improve outcomes and decrease cost. If standardized programs, real-time mentoring from specialists, and close monitoring of performance were established, such training could substantially expand surgical care in rural Canadian communities.

3.4.5 Utilizing Physician Extenders (PEs) to Extend the Range of Surgeons in Rural Practices The use of physician extenders (PEs) such as nurse practitioners (NPs) and physicians’ assistants (PAs) offers practicing surgeons the chance to increase the number of patients that receive their care. NPs are already used in many rural communities and physicians’ assistants now practice in some Canadian provinces. There are three general ways that PEs can improve access and care in rural communities. All are predicated on the PE being well-trained and working closely under guidance from physicians. One model involves the PE working directly with a surgeon to substantially increase the volume of patients that the surgeon can see without decreasing the quality of care. With appropriate training and division of labor, it is not uncommon for a competent well-trained PE to nearly double a surgeon’s clinic volume. This would be extremely beneficial when one of the limitations and stressors of clinical practice for rural surgeons is workload and expectations to meet it. For this to occur, the surgeon or physician overseeing the PE must spend the time, often 2–6 months, to adequately train the PE about his/her practice. In addition, often the practice itself needs to be modified so as to facilitate a greater flow of patients. Changes may include opening up a separate clinic schedule for the PE as well as training the individuals who schedule patients so that the ­delegation of patients between physician and PE is organized for optimal efficiency. Another model uses well-trained PEs to provide patient care in emergency rooms and urgent-care

14

facilities under guidance from a physician. This type of PE work could allow surgeons in a rural community to avoid burnout knowing that they have someone to help manage on-call referrals. For communities trying to recruit and retain a surgeon or surgeons, a team of well-trained and proactive PEs can have a positive impact on a surgeon’s lifestyle. GP surgeons have also demonstrated this positive effect in a mixedmodel where they work in the same community with a specialist colleague. This in turn makes it more likely that surgeons will stay in the community in question. Finally, many communities use NPs to provide independent patient care. This allows many rural communities to provide basic medical care locally. This model can work very well provided the PE is well trained and is integrated into the wider medical system. The ability for the NP to have a network of physicians (including the most proximal rural surgeon) that they can call to help facilitate and expedite patient care is important. A coordinated program using PEs has the very real potential of extending meaningful health care to many rural Canadians who are presently not able to adequately access the health-care system.

3.4.6 Financial Incentives Finally, surgeons choosing a rural practice will need to be rewarded financially. Perhaps the most practical way to do this is to ensure that adequate operating time is available for rural surgeons. This does require an increased financial commitment from the government and therefore can be a challenge. However, if programs to increase the provision of surgical care are funded with appropriate incentives, they can serve as a tool to recruit and retain surgeons in rural areas and thereby improve surgical care.

3.5 Conclusion The challenge of providing surgical care in rural Canada is real. Factors undermining the provision of surgical care in rural Canada include: an overall shortage of general surgeons; residency training programs that have relatively few role models for promoting the

N.R. Caron and S. Pinney

virtues of a rural practice; persistent difficulties in recruiting and retaining surgeons in rural communities; and limited resources for establishing and maintaining a coordinated surgical service. However, with these ­challenges come opportunities to develop creative solutions and the Canadian health-care system in many ways is well positioned to enact many of these solutions. These solutions include better education and role modeling to promote rural surgery as a career choice; incorporation of telemedicine to expand and improve care in rural communities; making systematic organizational changes to improve the delivery of surgical care in rural areas; training GP surgeons to provide some basic surgical care; and utilizing physician extenders to expand the delivery of surgical care. Applying potential solutions will require innovative leadership and a vision that what is needed, is possible.

References   1. Pong, R.W., Lemire, F., Tepper, J.: Physician retirement in Canada: what is known and what needs to be done. Paper prepared for the 10th international medical workforce ­conference in Vancouver, British Columbia, Canada, http:// www.cranhr.ca/pdf/10_retCAN.pdf, March 2007   2. Scott, I.M., Matejcek, A.N., Gowans, M.C., Nut Diet, M., Wright, B.J., Brenneis, F.R.: Choosing a career in surgery: factors that influence Canadian Medical students’ interest in pursuing a surgical career. Can. J. Surg. 51(5), 371–377 (2008)   3. Rinker II, C.F.: Meeting the needs of rural general surgeons: the ACS subcommittee on rural surgery. Bull. Am. Coll. Surg. 90(8), 13–18 (2005)   4. Kenny, N., Mann, K., MacLeod, H.: Role modeling in physicians’ professional formation: reconsidering an essential but untapped educational strategy. Acad. Med. 78(12), 1203–1210 (2003)   5. Shanafelt, T.D., Balch, C.M., Bechamps, G.J., Russell, T., Dyrbye, L., Satele, D., Collicott, P., Novotny, P.J., Sloan, J., Freischlag, J.A.: Burnout and career satisfaction among American surgeons. Ann. Surg. 250(3), 463–471 (2009)   6. Frank, J.R., Danoff, D.: The CanMEDS initiative: implementing an outcomes-based framework of physician competencies. Med. Teach. 29(7), 642–647 (2007)   7. Royal College of Physicians and Surgeons of Canada CanMEDS website: http://rcpsc.medical.org/canmeds/ index.php Accessed/edited date feb 4, 2011   8. Reznick, R.K., MacRae, H.: Teaching surgical skills – changes in the wind. N. Engl. J. Med. 355, 2664–2669 (2006)   9. Norman, G.R., Schmidt, H.G.: The psychological basis of problem-based learning: a review of the evidence. Acad. Med. 67, 557–565 (1992)

Part Pre- and Postoperative Care

II

 

4

Fundamentals of Surgical Oncology Hanno Niess, Karl-Walter Jauch, and Christiane J. Bruns

4.1 Introduction The proceedings in characterization of molecular changes in tumour cells have led to widespread acceptance of the hypothesis that on the cellular level cancer is a genetic disease. Rapid progressions in the field of molecular biology are increasingly suggesting that the transformation of a normal cell to a malignant cell is a multi-step process. This transformation of the cell could be a result of multiple gene mutations, gene amplifications, changes in transcriptional and translational activity and constant over-activation on protein level. The accumulation of gene mutations mostly takes place in genes that are crucial for normal cellular growth. Essentially, one distinguishes between two classes of genes that are important for the development of a tumour: protooncogenes/oncogenes, which positively influence tumour growth; and tumour ­suppressor genes, which negatively influence tumour growth. In sporadically occurring tumours, these mutations are acquired in somatic cells (somatic mutation) whereas in inheritable tumours, the gene mutations are passed on over the germline (germline mutation) and thus the mutations are existent in all cells of the body. Therefore, the fields of molecular genetics and tumour biology play an important role in the elucidation of malignant diseases, and are of increasing relevance in medical diagnostics, and in the near future, also in tumour therapy.

H. Niess, K.-W. Jauch, and C.J. Bruns (*) Department of Surgery, University Hospital Grosshadern, Marchioninistr. 15, 81377 Munich, Germany e-mail: [email protected]

4.2 Basic Molecular Genetics in the Context of Tumour Formation Most sporadically occurring colorectal carcinomas emerge from polyps within 5–10  years in the framework of the so-called adenoma–carcinoma sequence (Fig. 4.1) [1]. In the course of the adenoma–carcinoma sequence, mutations and losses of certain alleles, e.g. FAP, Ki-ras, DCC, p53, accumulate within a normal mucosal cell. Within 5–10 years, these damaged alleles can turn a mucosal cell into an adenoma and finally into an invasive carcinoma. In sporadically occurring ductal pancreatic carcinoma, one can retrace a form of sequence that is similar to the adenoma–carcinoma sequence. Through molecular triggers, normal ductal pancreatic tissue develops into intraductal papillary mucinous neoplasms (IPMNs), then into pancreatic intraepithelial neoplasms (PanIN), and finally into an invasive ductal pancreatic carcinoma [2]. The genetic cause for this sequence is, on the one hand, loss of chromosomes on which potential tumour suppressor genes are located, e.g. loss of 1p, 6q, 9p, 12q, 17p, 18q and 21q. On the other hand, genetic alterations of genes such as k-ras, p16, cyclin D1, p53, MTS1, BRCA2 or SMAD4 sustain the ­progression of the pancreatic cancer sequence. Familial adenomatous polyposis (FAP) is an example of an inheritable disease with a detectable genetic defect that predisposes for tumour development. One can identify a defect in the so-called APC gene. However, only 1% of the cases of colorectal carcinoma are based on the existence of FAP. FAP has an autosomal dominant inheritance with nearly complete penetrance. It is characterized by the early appearance of multiple colorectal polyps, which inevitably leads to the formation of colorectal carcinomas in the young adult.

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_4, © Springer-Verlag Berlin Heidelberg 2011

17

18

H. Niess et al.

Normal mucosa

Mutation/ allele loss FAP gene

Mutation Ki-ras Tubular adenoma

5–10 years

Loss of DCC Adenoma with severe atypia

Adenocarcinoma Mutation/ allele loss p53 gene

3–5 years

Fig. 4.1  Adenoma–carcinoma sequence in colorectal carcinoma

In 80% of the cases, there is a germline mutation of the APC gene, which leads to a functional inactivation of the gene product. Certain mutations of the APC gene result in an attenuated form of FAP in which patients develop fewer tumours at a later time point [3]. Hereditary nonpolyposis colorectal cancer (HNPCC) represents another inheritable tumour disease. It is characterized by colorectal adenocarcinomas in patients with less than ten polyps and an early manifestation age (less than 50 years). It is also characterized by the location of the carcinoma, usually proximal to the left colic flexure (about 70% of the cases), and frequent metachronal and synchronal occurrence of the colorectal carcinomas. HNPCC is inherited in an autosomal dominant manner with a penetrance of a colorectal carcinoma of about 85–90% up to the age of 70. Additionally, genetic carriers have an elevated risk of developing carcinoma of the endometrium, stomach, ovaries, breast, small bowel, hepatobiliary tract, urothelium and brain. In about 44–86% of HNPCC families, one can detect a germline mutation in a DNA-mismatch-repair (MMR-) gene such as hMLH1 or hMSH2, rarely also hMSH6, hPMS1 or hPMS2. MMR-genes encode for proteins that correct faults in DNA replication. Loss of function of the

MMR-genes by inactivating mutations leads to the accumulation of DNA errors, which can be detected as microsatellite instability (MSI) in 85–95% of HNPCCassociated tumours [4].

4.3 Goals of Surgical Oncology Depending on their objective, the principles of surgical oncology are distinguishable between curative and palliative procedures [5]. Surgery with curative intentions has the objective of healing the patient by means of tumour excision and prevention of a relapse. Occasionally, additional nonsurgical tumour-specific measures are applied preoperatively (neoadjuvant) or postoperatively (adjuvant). Surgery and non-operative measures performed with palliative intentions have the purpose of preventing or alleviating symptoms or, generally put, to improve the quality of life in incurable situations (see Chap. 5). Cytoreductive surgery has the purpose of removing the major part of tumour tissue (also called debulking) to improve the initial situation for additional tumourdestructive treatments.

4  Fundamentals of Surgical Oncology

To what extent even a tumour resection, which was started with primarily curative intentions, leads to healing or fulfills a palliative purpose, depends on the type, localization and stage of the tumour disease as well as the type of surgery performed and other ­factors. A crucial point within this scenario also is the biology of the tumour, which until now could be manipulated only to a limited degree.

4.4 Curative Surgical Oncology Bearing in mind the patient’s quality of life, the topmost objectives of surgical oncology in a multimodal setting are clearance of the tumour and low procedurerelated morbidity and mortality. The fundamentals in oncological surgery with curative intentions are: 1. Tumour excision within healthy tissue, including potentially afflicted neighbouring structures 2. The removal of the regional lymphatic drainage according to the anatomy 3. The avoidance of intraoperative tumour cell spread To ensure the tumour excision within healthy tissue in parenchymal organs, tumours of the soft tissue and tumours of the GI tract, one needs to remove a circumferential safety margin around the macroscopically viewable tumour. The size of the safety margin differs between the specific types of organ tumours and depends on its growth characteristics and respective tumour stage. In early tumour stages, maintaining the respective safety margin is easier than at later stages, and thus the rate of locoregional tumour recurrences increases with increasing tumour stages. In case of doubt, frozen sections performed during surgery may help to confirm clear safety margins. The existence of metastases does not necessarily exclude from performing a curative surgical intervention. However, the prerequisites for a curative procedure in metastatic disease are that the primary tumour and all metastases need to be removable, and that there would be no residual metastases after the surgery. Certainly all these requirements must be achieved with a justifiable operative risk. Resection of distant metastases is performed ­primarily for metastases of colorectal carcinoma and sarcomas of the soft tissue located in lung and liver. In individual cases, it appears to be justified to also

19

consider resection of distant metastases of renal cell carcinoma and malignant melanoma. Anatomic structures are of great importance in the selection of the resection layer. The resection layer in the curative excision of rectal carcinoma serves as a classic example: the complete removal of the mesorectum is achieved by preparation inside the avascular layer between the parietal pelvic fascia and the visceral pelvic fascia (Waldeyer’s fascia in dorsal position and Denonvillier’s fascia in ventral position). This step is, besides maintaining a sufficient dorsal safety margin, crucial to obtaining a surgical clearance that is adequate to the spatial extent of the tumour [6]. Another example of an adequately radical tumour excision is the compartment resection for soft tissue tumours as the complete removal of a tumour-afflicted muscle group [7]. With increasing tumour expansion, the probability of lymph node involvement by the tumour increases as well. Generally, there is a constant, anatomically definable route of lymphatic drainage for each organ. Elective and prophylactic lymph node dissection within the framework of surgical oncology is performed because of the fact that lymph node metastases are often only detected during histopathological ­examination. Therefore, the tumour-dependent regional lymphatic drainage system is completely removed, and in most of the cases, this needs to be performed en bloc with the removal of the primary tumour itself. The elective lymph node dissection is carried out for diagnostic reasons to evaluate the tumour stage and to estimate the prognosis. In certain tumours (e.g. breast cancer, gastric cancer), the lymph node status is a decisive prognostic parameter [8]. Furthermore, the lymph node status serves as a criterion for adjuvant therapeutic measures (colorectal cancer, breast cancer) [9]. Concerning the extent of the lymph node dissection in a curative setting, removal of the first lymph node station of the respective tumour-afflicted organ is acceptable. Assuming that some patients might profit from an extended surgical removal of further lymph node stations, this is justified only in cases where it does not increase the operative risk. The concept of sentinel lymph node biopsy has evolved under the assumption of a constant lymphatic drainage. This means that the findings in the first draining lymph node (the sentinel lymph node) are representative for the whole regional lymph node section. In certain tumour entities, the decision of removing or leaving the regional lymph node section is based on the findings in the sentinel lymph node. Breast cancer

20

and malignant melanoma are the tumour entities where most experience with sentinel lymph node biopsies exists. Few reports do also exist about initial results for tumours of the gastrointestinal tract [10]. If lymph node infiltration is evident prior to surgery, the lymph node removal is called selective or therapeutic lymph node dissection. In patients with infiltration of the tumour into anatomically neighbouring structures, one should aim for their removal together with the primary tumour (multivisceral en bloc resection). This is because loosening possible adhesions between the tumour and its neighbouring structures might lead to opening of the tumour capsule and thus dissemination of tumour cells. The decision on the extent of the surgical procedure should be made individually based upon the quality of life, the operative risk, and the overall prognosis under consideration of the tumour biology. For example, colon cancer with infiltration of the neighbouring small intestine, bladder, adnexa or uterus is preferably removed via en bloc resection without loosening tumour adhesions or examining frozen sections [11]. In contrast to this stands the strategy of pretreatment of, e.g. rectal carcinoma in a neoadjuvant setting with radio-chemotherapy to minimize and devitalize the tumour. This leads to the possibility of a subsequent resection, which can be less extensive and thus less risky with regard to impaired quality of life (colostomy, neo-bladder, sexual dysfunction) [12]. In oncological standard procedures as for example in colorectal cancer, the surgeon not only removes the primary tumour with its respective safety margin and regional lymphatic tissue but also tries to ligate the draining veins as early as possible. This serves the purpose of preventing haematogenous tumour cell dissemination and is called the ‘no-touch-isolation-technique’. In laparoscopic oncological procedures, the prevention of tumour cell dissemination is achieved by covering the surgical incisions with foil when retrieving the tumour from the abdomen. Metastases implanted into the skin after removal of incidental gall bladder carcinoma have been described and these patients usually require additional surgery including excision of the port sites.

4.5 Palliative Surgical Oncology Despite curative objectives, only 50% of the patients with tumours of the gastrointestinal tract can be healed. In the other half of the patients with tumours of the GI

H. Niess et al.

tract, a surgical approach can only be considered as being palliative. The role of palliative surgical oncology is improvement of quality of life in patients with incurable disease by alleviating or abolishing tumour-related symptoms. In a broader sense, palliative surgical oncology has a prophylactic character by preventing the appearance of complications in advanced tumour disease and maintaining acceptable quality of life for the patients as long as possible. Palliative surgery includes the following procedures: removal of the primary tumour despite existence of distant metastases (e.g. colorectal carcinoma with distant metastases to prevent bowel obstruction or ­haemorrhage), small bowel anastomoses to bypass a tumour-induced bowel obstruction, colostomies, endoscopic procedures and procedures that prepare for ­supportive measures (e.g. port implantation). However, for gastric outlet stenosis produced by a locally advanced distal gastric carcinoma, the ­palliative distal gastric resection and thus removal of the tumour is superior to a gastro-enterostomy as bypass procedure, this of course only if the procedure comes with a justifiable perioperative risk for the patient. Further examples of palliative tumour resection include the lobectomy in abscessing advanced lung cancer or mastectomy in ulcerating metastasized breast cancer. Under certain circumstances, lifethreatening complications of a tumour disease may justify extended tumour resections in case the emergency situation can only be mastered by surgery, even if they involve a substantially increased risk (e.g. gastrectomy in massive bleedings from gastric cancer with distant metastases). Endocrinologically active non-resectable tumours justify procedures to downsize the tumour and thus alleviate symptoms and improve quality of life. However, in advanced tumours, often the only remaining option is to perform procedures that leave the tumour in situ. Besides surgery, other ­possible procedures are medicinal treatment, endoscopic or interventional radiology procedures, and radiotherapy. The selection of the correct procedure depends on the degree of impairment of quality of life by the tumour, the expected prognosis, the risk of the procedure and the patient’s wishes. Supportive measures are especially relevant in incurable situations. Among those are adequate pain therapy and nutritious support.

21

4  Fundamentals of Surgical Oncology

4.6 Surgical Oncology as Part of a Multimodal Tumour Therapy Today surgical oncology usually is part of a multimodal interdisciplinary concept of tumour therapy. A multimodal approach includes classic procedures such as surgery, chemotherapy and radiotherapy. However, nowadays it also includes interventional radiology procedures such as chemoembolization, radiofrequency ablation, as well as systemic molecular biology approaches so-called targeted therapy. The respective multimodal treatment and the order of the different procedures should be discussed in an interdisciplinary tumour board and ascertained for each patient on an individual basis. Locally advanced rectal carcinoma (T3-4, N1) represents a typical example of a multimodal treatment approach. Before undergoing surgery (anterior rectosigmoid resection, low anterior resection, abdominoperineal resection), patients receive neoadjuvant radiochemotherapy, which is continued as systemic adjuvant chemotherapy after surgery. In doing so, the prognosis of these patients has been substantially improved and the risk of local recurrent tumour is significantly decreased [13]. Furthermore, the rate of sphincter-preserving surgery in tumours near the anal sphincter has been increased without impairment of the oncological radicality. To allow for local resectability in pancreatic cancer, similar approaches such as neoadjuvant radiochemotherapy are applied. Moreover, approaches from mole­ cular biology such as anti-angiogenic therapy (e.g. Bevacizumab in metastasized colorectal cancer) or thyrokinase inhibitors (e.g. Erlotinib in advanced ­pancreatic cancer) may be part of the multimodal treatment. The overall goal of multimodal oncological therapy is to improve the prognosis of each individual patient with the underlying tumour disease under consideration of the prognostic factors.

4.6.1 Established Prognostic Factors From many clinical trials the following prognostic factors relevant for therapy in oncology have evolved: • R-status (residual tumour status) • pTNM status

• Grading • Lymph node ratio (number of lymph nodes diseased/ number of lymph nodes removed) • Perioperative complications (nutritious status, total blood loss, need for blood transfusions, infections) • Tumour-specific experience of the treating centre (‘high volume hospitals’)

4.6.1.1 Residual Tumour Status (R-Status) The R0 status (no residual tumour) should relate to the primary tumour, its respective lymphatic drainage pathway and, if applicable, distant metastases. • Absolute R0 resection: All three dimensions of the primary tumour and the lymphatic drainage are free of tumour (lymph node ratio < 0.2) • Relative R0 resection: All three dimensions of the primary tumour and the lymphatic drainage are free of tumour but with an insufficient size of safety margins (lymph node ratio > 0.2) • R1 resection: Microscopic tumour residual • R2 resection: Macroscopic tumour residual

4.6.1.2 TNM Classification The TNM classification allows for an anatomic description of the tumour spread. T describes the extent of the primary tumour: • T0: No indications of a primary tumour (CUP: cancer of unknown primary) • Tis/Ta: The tumour has not infiltrated other tissue; these tumours usually go along with a good prognosis • T1, 2, 3 or 4: Increasing size of the tumour/infiltration of certain tissue layers in hollow organs/infiltration of adjacent organs • Tx: No statement about the primary tumour possible N describes the existence or absence of regional lymph node metastases: • N0: No evidence for lymph node infiltration • N1, 2 or 3: Increasing lymph node infiltration; classification into ipsilateral or contralateral affliction and mobility, as well as in relation to the primary tumour and number of positive lymph nodes • Nx: No statement on lymph node affliction possible

22

M describes the existence or absence of distant metastases: • M0: No evidence for distant metastases • M1: Distant metastases present • Mx: No statement on distant metastases possible

4.6.1.3 Grading/Histomorphologic Features Further addenda to describe the tumour are histomorphologic features such as Grading (G1–G4): Histomorphologic feature describing the state of differentiation of the tumour tissue • G1 = well differentiated; which means that the tumour tissue resembles the tissue of origin closely • G4 = undifferentiated; the tissue of origin is only detectable by ultrastructural or immunohistochemical analysis L0/L1: Invasion into lymph vessels or tumour cell emboli inside lymph vessels; contact to the lymph ­vessel wall is not necessary for the diagnosis V0/V1/V2: Invasion into veins (none/microscopic/ macroscopic) Sx/S0, 1, 2 or 3: Serum tumour markers; these are only registered in malignant testicular cancer (Sx: not available/examined; S0 = normal, S1–3 = at least one marker elevated) 4.6.1.4 Certainty of the Diagnostic Findings Adding the descriptor ‘C’ to the respective TNM category creates the possibility to denote certainty of the diagnostic findings. • C1: General examination methods such as physical examination or standard x-ray, etc. • C2: Special examination methods such as ERCP, CT, MRT, etc. • C3: Results of the surgical exploration, cytology or biopsy • C4: Insights from the surgical resection, the histopathologic examination; equivalent to the pTNM classification • C5: Insights from the autopsy including histopathologic results

H. Niess et al.

4.6.1.5 UICC-Staging In the framework of staging tumour diseases, several TNM categories are summarized into one UICC stage according to their prognosis. UICC stage

pTNM categories

Stage 0

TisN0M0

Stage I

T1, T2, N0, M0

Stage II

T3, T4, N0, M0

Stage III

Any T, N1, N2, M0

Stage IV

Any T, any N, M1

The UICC stages indicate that the size of the primary tumour is not the decisive factor for prognosis of the patients but the lymphatic and haematogenous dissemination (stage II vs. stage III). 4.6.1.6 Minimum Number of Lymph Nodes to Be Examined in Tumours of the GI Tract To be able to give an applicable statement on the lymph node status of the respective gastrointestinal tumour for the TNM classification, the examination of a minimum number of lymph nodes is required (Table 4.1). The lymph node ratio is calculated from the proportion of tumour-positive lymph nodes to the total number of lymph nodes removed.

Table 4.1  Required minimum numbers of lymph nodes to be removed Localization of the tumour

Minimum number of lymph nodes to be removed

Stomach

15

Colon, rectum

12

Pancreas

10

Liver, gall bladder, extrahepatic biliary tract

3

23

4  Fundamentals of Surgical Oncology

4.6.1.7 Perioperative Management One important factor that influences the outcome of oncological operations is the preoperative nutritional status of the patient [14]. Tumour cachexia is mostly accompanied by a poor protein synthesis by the liver and thus leads to immunosuppression. This status of impaired healing can then lead to infection and sepsis in the postoperative period. Immunosuppression on the one hand, and paracrine or endocrine effects of stress factors (IL-6, TNF-a, NFkB, etc.), growth factors (epidermal growth factor [EGF], vascular endothelial growth factor [VEGF], etc.) secreted by the remaining immune-competent cells on the other hand support angiogenesis and cell proliferation and thus lead to stimulation of tumour growth. Hence, performing surgery with a low rate of complications is also a factor relevant to prognosis (Fig. 4.2). A similar prognostic factor has been established in intraoperative blood loss and the amount of blood products given [15]. Apart from the early detection and correction of co-morbidities (cardiovascular and pulmonary risk factors, diabetes, renal failure, liver failure, preceding operations, etc.), the preparation of the tumour patient for surgery includes the optimization of his nutritional status. This is achieved by substituting calories, vitamins, trace elements, etc., depending on the extent of malnourishment. If necessary, total parenteral

nutrition with simultaneous application of oral immunonutrition is given over a period of 5–7 days before surgery.

4.7 Influence of Surgery on Metastasization Especially in colorectal cancer – but also in other tumours of the gastrointestinal tract – it has been discovered that the primary tumour possesses the ability to produce anti-angiogenic substances (e.g. angiostatin), which inhibit the outgrowth of micrometastases, for example in the liver, to macrometastases. These substances are secreted amongst others by the primary tumour and reach the liver by bloodstream. Thus, they act as endocrine substances. As long as the primary tumour remains in place micrometastases will form. However, they will also remain in their micrometastatic state because the decisive proangiogenic stimulus needed for a macroscopic outgrowth is suppressed amongst others by these substances secreted by the primary tumour [16]. This phenomenon of invisible, asymptomatic tumour cell spread is called ‘dormant disease’. As soon as the primary tumour has been surgically removed, the suppressing anti-angiogenic effect is absent and

Cell proliferation TNFa, NFkB IL-6

Immune cells VEGF, EGF, etc. Angiogenesis

Fig. 4.2  Influence of postoperative complications on tumour growth

For example, anastomotic insufficiency, peritonitis, sepsis

Immunosuppression

Tumour growth

24

H. Niess et al.

Fig . 4.3  ‘Tumour dormancy’ – antiangiogenic effects of the primary tumour on existing micrometastases Micrometastases

The primary tumour secretes antiangiogenic substances (endostatin, angiostatin)

Macrometastases

Discontinuation of antiangiogenic substances leads to growth of the metastases

Primary tumour

Before resection of the primary tumour

the micrometastases are able to generate an ‘angiogenic phenotype’. This leads to tumour cell proliferation and formation of visible, possibly symptomatic macrometastases (Fig. 4.3). Multimodal concepts of therapy, e.g. surgery with subsequent chemotherapy, are necessary to prevent such developments. Modern anti-angiogenic drugs and strategies might also be helpful to avoid the outgrowth of micrometastases.

4.8 Tumour Angiogenesis One decisive step for tumour growth as well as for the process of tumour cell spread is the creation of a sufficient vascular network inside the tumour and its surrounding tissue. Tumours that are smaller than 1 mm in diameter obtain their nutrients and oxygen by the process of diffusion. The larger the tumour becomes the more its growth is dependent on adequate formation of new vasculature. The transition of a microscopic tumour, which is not detectable by the established clinical examination methods into a macroscopic, clinically detectable mass is called the ‘angiogenic switch’ [17].

After resection of the primary tumour

The development of new vasculature in tumours is partially supported by the production and secretion of pro-angiogenic factors by the tumours itself, and partially by the production and secretion of ­pro-angiogenic factors in the surrounding tissue. Ultimately, the formation of new vasculature depends on the interaction between stimulating and inhibitory angiogenic factors produced by the tumour and its surrounding tissue. Presumably, the production of a multitude of pro-angiogenic factors is necessary to sustain vascular formation. The initiation of angiogenesis (Fig.  4.4) then leads to an exponential tumour growth. A very important pro-angiogenic factor is the ‘vascular endothelial growth factor’/‘vascular permeability factor’ (VEGF/VPF). The receptors for the growth factor VEGF are almost exclusively expressed on endothelial cells. After binding to their receptors, VEGF and others exert pro-angiogenic effects in terms of endothelial cell proliferation, degradation of extracellular matrix, endothelial cell migration, tube formation, and finally development of a tumour vessel system. Furthermore, in particular, VEGF acts as a survival factor for endothelial cells under hypoxia stress. A parameter used in many tumour systems to measure the influence of pro-angiogenic

25

4  Fundamentals of Surgical Oncology Tumour angiogenesis

Small localized tumour < 1 mm3

Tumour can now grow and spread

VEGF, bFGF, IL-8, HIF-1a, etc. molecule

Blood vessel

Fig. 4.4  Tumour angiogenesis

factors is the so-called microvessel density. To some extent, the microvessel density correlates with the degree and progression of the tumour disease and the general prognosis.

References   1. Schackert, H.K., Gebert, J., Ansorge, W., Herfarth, C.: Molecular principles of carcinogenesis. Significance of prevention and early detection of solid malignant tumors. Chirurg 64(9), 669–677 (1993)   2. Biankin, A.V., Kench, J.G., Dijkman, F.P., Biankin, S.A., Henshall, S.M.: Molecular pathogenesis of precursor lesions of pancreatic ductal adenocarcinoma. Pathology 35(1), 14–24 (2003)   3. Abdel-Rahman, W.M., Pletomaki, P.: Molecular basis and diagnostics of hereditary colorectal cancer. Ann. Med. 36(5), 379–388 (2004)   4. Chung, D.C., Rustgi, A.K.: The hereditary nonpolyposis colorectal cancer syndrome: genetics and clinical implications. Ann. Intern. Med. 138(7), 560–570 (2003)   5. Junginger, Th., Schlag, P.M.: Prinzipien der Chirurgischen Tumortherapie. Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Chirurgischen Arbeitsgemein­ schaft Onkologie (CAO) der Deutschen Gesellschaft für Chirurgie. Kurzgefasste Interdisziplinäre Leitlinien 2002. 3. Auflage (2005)   6. Heald, R.J., Häsband, E.M., Ryall, R.D.: The mesorectum in rectal cancer surgery – the clue to pelvic recurrence? Br. J. Surg. 69, 613–616 (1982)

  7. Enneking, W.F., Spanier, S.S., Malawer, M.M.: The effect of the anatomic setting on the results of surgical procedures for soft parts sarcoma of the thigh. Cancer 47, 1005–1022 (1981)   8. Hölzel, D., Engel, J., Schmidt, M., Sauer, H.: Modell zur primären und sekundären Metastasierung beim Mammakarzinom und dessen klinische Bedeutung. Strahlenther. Onkol. 1, 10–23 (2001)   9. Junginger, Th, Hossfeld, D.K., Sauer, R.: Aktualisierter Konsensus der CAO, AIO und ARO zur adjuvanten Therapie bei Kolon- und Rektumkarzinom von 1.7.1998. Dtsch. Ärztebl. 96, 698–700 (1999) 10. Tsioulias, G.J., Wood, ThF, Morton, D.L., Bildnik, A.J.: Lymphatic mapping and focused analysis of sentinel lymph nodes upstage gastrointestinal neoplasms. Arch. Surg. 135, 926–932 (2000) 11. Hohenberger, W., Meyer, Th: Grundzüge der chirurgischen Onkologie. Zbl. Chir. 125, W39 (2000) 12. Budach, W., Hoffmann, W., Bamberg, M.: Stellenwert der Radiochemotherapie beim Rektumkarzinom. Verdauungsk­ rankh 16, 156–166 (1998) 13. Smith, D.E., Muff, N.S., Shetabi, H.: Combined preoperative neoadjuvant radiotherapy and chemotherapy for anal and rectal cancer. Am. J. Surg. 151(5), 577–580 (1986) 14. Klek, S., Kulig, J., Szczepanik, A.M., Jedrys, J., Kolodziejczyk, P.: The clinical value of parenteral immunonutrition in surgical patients. Acta Chir. Belg. 105(2), 175–179 (2005) 15. Takemura, M., Osugi, H., Higashino, M., Takada, N., Lee, S., Kinoshita, H.: Effect of substituting allogenic blood transfusion with autologous blood transfusion on outcomes after radical oesophagectomy for cancer. Ann. Thorac. Cardiovasc. Surg. 11(5), 293–300 (2005)

26 16. Hahnfeldt, P., Panigrahy, D., Folkman, J., Hlatky, L.: Tumor development under angiogenic signalling: a dynamical ­theory of tumor growth, treatment response, and postvascular dormancy. Cancer Res. 59(19), 4770–4775 (1999)

H. Niess et al. 17. Udagawa, T., Fernandez, A., Achilles, E.G., Folkman, J., D’Amato, R.J.: Persistence of microscopic human cancers in mice: alterations in the angiogenic balance accompanies loss of tumor dormancy. FASEB J. 16(11), 1361–1370 (2002)

5

Palliative Surgery Matthias W. Wichmann

5.1 Introduction Palliative surgery is an important part of surgical ­decision-making and should be carried out in agreement with a treatment decision based on the individual patient’s decision for his or her end-of-life treatment. The surgical team must try to identify the treatment goals together with the patient and the patient’s family – these may vary in patients with identical diagnosis and prognosis and it is important that the surgeon does not base the decision on what appears possible, but on what the patient has expressed as primary palliative treatment goals. It is also important to note and to explain, that palliative treatment does not aim to prolong life but to provide best possible symptom control (pain, nausea and vomiting, intestinal obstruction, ­dyspnoea). Obviously, palliative (surgical) care also does not aim to actively reduce the patient’s life expectancy. In the author’s view, palliative surgical care should be a team decision with the patient and his/her family in the center and a number of team members including (palliative care) nurses and allied health, social workers, psychologist, pain service, surgeons and palliative care physicians. In the rural setting, not all of these important contributors to palliative care may be available, which makes the role of the team leader (surgeon, if admitted under his/her care) even more important. For the rural surgeon, it is also important to consider that extensive surgery may require High Dependency Unit (HDU) or even Intensive Care Unit (ICU) admission which may M.W. Wichmann Department of General Surgery, Mount Gambier General Hospital and Flinders University Rural Medical School, 276-300 Wehl Street North, Mount Gambier, SA 5290, Australia e-mail: [email protected]

not be available in the patient’s hometown, and therefore would require transfer away from the patient’s family. This is an important factor for most patients, and must be discussed prior to surgical intervention. It is also important to consider that operative morbidity is common (up to 40%) after palliative surgery and that a number of patients (10%) require additional surgery for the morbidity.

Palliative care is a team approach aiming at best ­possible symptom control during end-of-life treatment and focusing only on the patient’s/patient’s family decision regarding the priorities of treatment goals.

5.2 Surgical Palliative Procedures Malignant obstruction of the trachea or main bronchi: These lesions are usually suitable for bronchoscopic intervention including stent insertion, argon plasma beam coagulation, or laser ablation (see Chap. 6). Significant bleeding which cannot be controlled via bronchoscopy may require palliative resection of the affected lobe. Esophageal cancer: If a malignancy of the esophagus is not resectable due to advanced disease, most patients will receive palliative radio-chemotherapy under the care of medical and radiation oncology. In this setting surgical intervention may become necessary in terms of endoscopic stenting or endoscopic placement of a feeding gastrostomy (PEG) (see Chap. 7). Palliative resection of an advanced esophageal cancer is usually not recommended due to the significant morbidity and the range of endoscopic treatment options.

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_5, © Springer-Verlag Berlin Heidelberg 2011

27

28

Gastric cancer: If the patient is fit for surgery, p­ alliative gastrectomy, or partial gastrectomy should always be considered first since these procedures offer best palliation and symptom control compared to endoscopic treatment or bypass surgery. If a resection is not possible, a gastro-jejunostomy (Roux-en-Y) as a palliative bypass should be constructed for malignant gastric outlet obstruction. Since the patient usually is less mobile and spends a lot of time in bed, an anastomosis at the posterior wall of the stomach should be preferred unless the underlying malignancy precludes sufficient mobilization of the stomach. Passage of a nasogastric tube through the anastomosis may improve the symptoms of postoperative paresis of the upper gastrointestinal tract. At the time of surgery, a feeding jejunostomy should also be considered. If a bypass cannot be constructed, a feeding jejunostomy plus a venting PEG are the author’s treatment of choice for malignant gastric ­outlet obstruction. Pancreatic cancer: Only 30% of all pancreatic ­cancers are resectable at the time of diagnosis. Surgical palliation therefore is an important part of pancreatic surgery. The decision for palliation very often must be made during explorative surgery when a pancreatic cancer which was considered resectable is shown to be non-resectable. The life expectancy in these patients is short (approximately 6 months) and surgical morbidity must be low. Biliary bypass surgery can be done using the gall bladder (cholecysto-jejunostomy) provided the gall bladder has flow into the common bile duct (can be probed via the cystic duct). If access to the common duct is good, a choledocho-jejunostomy or hepaticojejunostomy should be preferred. After removal of the gall bladder a cholangiogram can be done prior to construction of a side-to-side anastomosis between a Roux-en-Y jejunal limb and the common hepatic duct or the common bile duct. Duodenal obstruction may not be present at the time of initial surgery but frequently develops prior to the patient’s death from pancreatic cancer. We, therefore, suggest to also construct a side-to-side gastro-jejunostomy within the same surgery to avoid a repeat intervention at a later point in time when duodenal obstruction has developed. If preoperative staging indicates a non-resectable disease, palliative treatment may also be possible using endoscopic stents (metallic stents) which are introduced via ERCP (see Chap. 9). Gall bladder/bile duct cancer: Surgical palliation of non-resectable disease can be done using a

M.W. Wichmann

Roux-en-Y jejunal limb bypass or endoscopic stenting (usually metallic stents). There appears to be no survival advantages of either of the two approaches. In patients where endoscopic stent placement is not possible due to previous surgery or due to tumor growth, a percutaneous drainage is possible and even a percutaneous stent insertion can be attempted. We try to avoid ongoing percutaneous drainage wherever possible due to significant pain and discomfort resulting from a drain in the liver. Small bowel cancer: Non-resectable small bowel cancer can usually be treated using entero-enteric bypasses with side-to-side anastomosis between nonaffected parts of the small bowel. We prefer a two-layer running suture anastomosis with absorbable sutures. Colon cancer: Patients suffering from non-resectable large bowel cancer usually present with bowel obstruction. Non-resectability may result from the extent of tumor disease or the patient’s general health. Endoscopic stenting of the tumor stenosis has been shown to effectively treat the bowel obstruction and can be used as a bridging procedure prior to definite resection (after adequate resuscitation of the patient) or as a sole treatment if the patient is not considered/suitable for additional resection of the cancer. Stenting, however, does require a lumen which can be passed with the guide wire. If no rest-lumen can be identified, endoscopic stenting is not an option and palliative stoma (loop-colostomy) formation or bypass construction may be the only treatment options. Rectal cancer: Low rectal cancer may not be suitable for endoscopic stenting in view of the possibility to cause fecal incontinence and severe perineal pain. This has to be decided based on the exact position of the tumor and the length of the required stent. Good results can be obtained with stents within the rectosigmoid junction, although recent reports also suggest the option of pain-free stenting within 5 cm from anal verge. Obstructing lesions in the mid-rectum and lower third of the rectum usually require formation of a loopcolostomy for adequate palliation. Uncontrolled bleeding from rectal cancers can very often be managed endoscopically (injection, argon beam, laser, stent), or may require palliative resection even if complete clearance of the tumor cannot be achieved. Malignant ureteric obstruction: Retrograde stenting of the ureter is the treatment of choice, but may not be possible in all patients. If the retrograde approach fails, a percutaneous nephrostomy should be performed which may allow for antegrade stent placement.

29

5  Palliative Surgery

In view of the significant number of patients treated for non-resectable upper GI tract or large bowel cancer, the rural surgeon should be familiar with the technique of endoscopic stent application and a selection of endoscopic stents should be available in a rural center with an active endoscopy unit.

to sustain life and provide care regardless of whether the treatment is appropriate and compassionate given the condition of the patient. This makes palliative surgery a very challenging and interesting field of surgical decision-making.

Recommended Reading 5.3 Summary Palliative surgery is a very demanding part of our work and should ideally be part of a team approach to the patient’s end-of-life treatment. The patient’s wishes regarding this part of his or her life must guide any decision made by the treating team. With regard to this, it is of utmost importance to be aware of the fact that technological advancements have provided the means

Cady, B., Miner, T., Morgentaler, A.: Part 2: Surgical palliation of advanced illness: what’s new, what’s helpful. J. Am. Coll. Surg. 200, 281–290 (2005) Coustasse, A., Quiroz, T., Lurie, S.G.: To the bitter end: disparities in end-of-life care. J. Hosp. Mark. Public Relations 18, 167–185 (2008) Dunn, G.P.: Palliative surgery. In: Walsh, D. (ed.) Palliative Medicine, pp. 535–540. Elsevier Saunders, Philadelphia (2009) Tilney, H.S., Lovegrove, R.E., Purkayastha, S., et al.: Comparison of colonic stenting and open surgery for malignant large bowel obstruction. Surg. Endosc. 21, 225–233 (2007)

 

6

Fiber Optic Endoscopy: Bronchoscopy Matthias W. Wichmann and Fritz W. Spelsberg

6.1 Introduction Practical knowledge and experience with bronchoscopy are of relevance not only for interventions within the trachea and the lung, but also for interventions within intensive care. With regard to this, bronchoscopy is not only a diagnostic but also a therapeutic tool. The anatomy of the bronchial system is illustrated in Fig. 6.1.

1

6.2 Instruments Flexible bronchoscopy, preferably with a video-­ bronchoscope, is the standard procedure with an instrument measuring approximately 5–6 mm in diameter. At the tip, the instrument can be flexed in two directions and it usually has one working channel (2.8–3.2 mm). Rigid bronchoscopy has few indications only, e.g., massive bleeding, foreign body removal.

M.W. Wichmann (*) Department of General Surgery, Mount Gambier General Hospital and Flinders University Rural Medical School, 276-300 Wehl Street North, Mount Gambier, SA 5290, Australia e-mail: [email protected] F.W. Spelsberg Department of Surgery, University of Munich – Campus Grosshadern, Marchioninistr. 15, 81377 Munich, Germany

2 4

3

7

8 9

5 6

1 - trachea 2 - carina 3 - right main bronchus 4 - right superior lobe bronchus 5 - right middle lobe bronchus 6 - right inferior lobe bronchus 7 - left main bronchus 8 - left superior lobe bronchus 9 - left inferior lobe bronchus

Fig. 6.1  Diagram of the tracheo-bronchial system for documentation of bronchoscopic findings

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_6, © Springer-Verlag Berlin Heidelberg 2011

31

32

M.W. Wichmann and F.W. Spelsberg

6.3 Patient Preparation Prior to the procedure, elective patients should be fasted for at least 6 h and anticoagulants should be stopped as indicated (7  days for aspirin, clopidogrel, warfarin, 24 h for low-molecular heparin). Atropine (0.5 mg sc) can be given as pre-medication, and following local anesthesia of the nasopharynx (spray, inhalation), i.v. sedation (midazolam 3–5  mg, propofol 2  mg/kg  bw) should be given. Intraoperative monitoring of oxygen saturation and liberal application of oxygen with a mask are mandatory. The bronchoscope can be introduced through the nose (or mouth) under vision. In ventilated patients, the bronchoscope is advanced through the endotracheal tube or laryngeal mask. Within the trachea, additional topical local anesthesia should be applied with a pump spray via the working channel.

6.4 Indications Common indications for bronchoscopy are summarized in Table 6.1.

6.5 Diagnosis and Treatment of Haemoptysis Any form of haemoptysis must be investigated with a bronchoscope. Preoperative investigations have to differentiate true haemoptysis from pseudo-­haemoptysis, which is caused by bleeding in the nasopharynx or the upper gastrointestinal tract. True haemoptysis usually Table 6.1  Indications for bronchoscopy Preoperative Intraoperative

has bright red foamy blood and the patient suffers from significant dyspnea and coughing. Mortality of this condition is as high as 80%, depending on the underlying cause. Table  6.2 summarizes the most common causes of haemoptysis. Around 90% of pulmonary bleedings originate from the bronchial arteries and 5% come from the pulmonary vessels, which means that the systemic arterial blood pressure is relevant for the severity of the bleeding. Patients with haemoptysis are initially managed with oxygen administration, chest elevation or positioning on the affected body side (if known). Blood, circulating volume, and coagulation factors should be substituted as needed. Patients who are not compromised with regard to blood pressure and oxygenation should first have a computed tomography (or chest X-ray if not available). Patients with compromised blood pressure despite substitution should be intubated early, and then require urgent bronchoscopy. Cave: Patients with pulmonary bleeding are ­primarily endangered due to hypoxia and not due to blood loss. In patients with massive bleeding, a rigid bronchoscopy may become necessary in order to directly occlude the bleeding bronchus. Following intubation, the bleeding source or at least the side of bleeding has to be established to allow for separate ventilation of the non-affected lung (intubation of

Postoperative

Intervention

Hoarseness

Intubation

Atelectasis

Aspiration

Persistent cough

Position control of ventilation tube

Anastomotic leakage

Foreign body

Dyspnea, stridor

Control of tracheal anastomosis

Bronchial stump leakage

Stenosis

Haemoptysis

Anastomotic stenosis

Tracheo-malacia

Histology needed

Follow-up

Lavage

Esophageal cancer

Fistula

Tracheal rupture

Palliation

33

6  Fiber Optic Endoscopy: Bronchoscopy Table 6.2  Causes for haemoptysis Neoplastic Infectious

Cardiovascular

Traumatic

Others

Cancer

Tuberculosis

Embolus

Iatrogenic

Bronchiectasis

Metastasis

Pneumonia

Cardiac failure

Trauma

Endometriosis

Carcinoid

Abscess

Aneurysm

Sarcoidosis

Fungal

Wegener’s granulomatosis

Cystic fibrosis

Behcet’s syndrome Systemic lupus erythematosus

the main bronchus or usage of a double lumen tube). After securing the ventilation, a balloon can be used to selectively occlude the bleeding bronchus if this can be identified. Bronchoscopy also allows for ablation of malignant lesions and associated bleeding complications using laser therapy, argon-plasma coagulation, diathermy and cryosurgery. Furthermore, cold water and topical agents for vasoconstriction (adrenalin) can be used for bleeding control. In specialized centers, radiological embolization of the bleeding vessel may be possible using superselective catheters. If these interventions are not available or not successful, emergency surgery may be necessary.

6.6 Bronchoscopy-Assisted Intubation Conventional intubation may be impossible due to a number of causes (i.e., immobile cervical spine due to inflammatory processes/autoimmune disease, fractures of the cervical spine, enlarged thyroid, ENTcancer) and bronchoscopic assistance may be necessary. Usually, the ventilation tube is passed over the bronchoscope and this is then passed through the nose or the mouth into the trachea being subsequently used as a “guide-wire” for the passage of the ventilation tube. The correct position of the tube can then be visualized prior to withdrawal of the bronchoscope.

6.7 Percutaneous Puncture Tracheostomy Patient requiring long-term ventilation may require a tracheostomy, which can be constructed using a percutaneous dilatation tracheostomy kit. The bronchoscope

is placed into the trachea to confirm correct positioning of the guide wire following puncture of the trachea between the second and third cartilage and subsequent dilatation of the opening to fit a tracheal ventilation tube. It is important to note that percutaneous puncture tracheostomy carries significant risks of laceration of surrounding tissues and intraoperative complications and should not be performed by a novice without an assistant experienced in percutaneous puncture tracheostomy.

6.8 Bronchoscopic Treatment of Atelectasis Due to pain and inadequate mobilization, hypoventilation of one or several segments of the lung (atelectasis) can be observed after thoracic as well as abdominal surgery. This condition may require bronchoscopic intervention if patient positioning and physiotherapy do not resolve the problem. Bronchoscopy is much less traumatic than blind catheter aspiration of the lung, and allows for selective aspiration of the mucous as well as topical application of a mucolytic agent (acetylcysteine).

6.9 Treatment of Tracheo-Bronchial Stenosis Stenosed segments of the tracheo-bronchial system are a dangerous condition and cause significant discomfort for the patient due to dyspnea, retention pneumonia, bleeding, and coughing. Malignant, non-operable lesions require endoluminal therapy using laser or

34

argon-plasma coagulation as well as stenting or after loading therapy since systemic chemotherapy and radiation therapy usually do not have a sufficient local effect on the stenosis within the tracheo-bronchial system. Bronchoscopic re-canalization of the respiratory tract can be a life-saving palliative intervention in these situations. Stents may also be useful for the treatment of tracheo-malacia and for the closure of fistulas between the trachea and the esophagus (malignant or postoperative). A number of various stents are available for these indications.

6.10 Complications During bronchoscopy, hypoxia and hypercapnia can develop, especially in patients with compromised lung function. Furthermore, laryngeal or bronchial spasms and arrhythmias can be observed due to the intervention. Laceration of the trachea and/or bronchi can cause bleeding or perforation of these structures.

6.11 Rigid Laryngoscopy This procedure allows direct assessment of the ­oropharynx (base of tongue, vallecula, epiglottis), pharynx proper, larynx (vocal cords), and proximal

M.W. Wichmann and F.W. Spelsberg

trachea. The endoscope is inserted into the back of the mouth and delivers a magnified view of the laryngeal structures using an angled lens system. The procedure usually requires intubation and allows for detailed vision, biopsy and manipulation of all structures in the pharynx and larynx. Rigid laryngoscopy may be especially useful for removal of large foreign bodies, bleeding control and can also help to better visualize pathology within the upper third of the esophagus (i.e., endoscopic pouch repair). Rigid laryngoscopy carries a higher risk of soft tissue laceration, vocal cord edema and bleeding than flexible laryngoscopy and should not be carried out without proper training.

Recommended Reading Freitag, L.: Interventional endoscopic treatment. Lung Cancer 45, S235–S238 (2004) Rowe, L.D.: Otolaryngology – head and neck surgery. In: Doherty, G.M. (ed.) Current Surgical Diagnosis and Treatment, pp. 967–973. McGraw-Hill, New York (2006)

7

Fiber Optic Endoscopy: Gastroscopy Matthias W. Wichmann and Fritz W. Spelsberg

7.1 Introduction Flexible endoscopy is a significant part of the everyday workload of most general surgeons. The ongoing development of this technology has contributed to ­significant reduction of access trauma in most surgical specialties as well as in general surgery. Flexible endoscopy is part of preoperative assessment and treatment planning; it allows for intraoperative evaluation of the surgical site (i.e., anastomosis after resection, width of esophagus after fundoplication) and is part of the management of post-operative complications (i.e., stenting of fistulas, dilatation of stenoses, washout of anastomotic leakage). The endoscopic treatment of early stages of gastro-­intestinal cancers has been established, as well as the useful application of flexible endoscopy during so-called rendezvous procedures with minimal invasive surgery (i.e., resection of gastro-intestinal stroma tumors). Moreover, interventional endoscopy plays a major role in the palliative treatment of a number of advanced tumors within the ­gastro-intestinal tract and allows for ­maintenance of normal food passage and control of local complications such as blood loss or fistula formation.

M.W. Wichmann (*) Department of General Surgery, Mount Gambier General Hospital and Flinders University Rural Medical School, 276-300 Wehl Street North, Mount Gambier, SA 5290, Australia e-mail: [email protected] F.W. Spelsberg Department of Surgery, University of Munich – Campus Grosshadern, Marchioninistr. 15, 81377 Munich, Germany

7.2 Upper Gastro-Intestinal Tract Endoscopy/Gastroscopy 7.2.1 Indications Flexible endoscopy of the upper gastro-intestinal tract is indicated when a known or suspected disease of the esophagus, stomach, or duodenum requires further investigation. Common indications for endoscopy of the upper gastro-intestinal tract are listed in Table 7.1.

7.2.2 Patient Preparation and Technique of Examination The patient needs to be informed about the risks and indication for the endoscopy and should be fasted for a minimum of 6 h. Anticoagulation therapy does not need to be stopped unless a more invasive intervention than biopsy is planned. The procedure is carried out with the patient lying on the left side. Usually, local anesthetics can be applied with a spray into the larynx (Xylocaine spray). Local anesthesia should not be applied in a not-fasted emergency patient since it increases the risk of aspiration. If the patient is sedated (Midazolam 3–5  mg i.v. or Disoprivan 50–70  mg bolus + maintenance boli of 10–30  mg i.v.), pulseoxymetry is mandatory for monitoring. The use of Disoprivan also requires the presence of a second ­physician during the investigation. The need of sedation for upper GI endoscopy can be discussed with the patient prior to surgery and should consider the

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_7, © Springer-Verlag Berlin Heidelberg 2011

35

36

M.W. Wichmann and F.W. Spelsberg

Table 7.1  Indications for upper gastro-intestinal endoscopy Preoperative Intraoperative

Post-operative

Intervention

Dysphagia

Localization (tumor, bleeding site)

Stenosis

Palliation

Reflux disease

Inspection of anastomosis/suture

Anastomotic leakage

Dilatation

Bleeding

Rendezvous

Postop. hemorrhage

Polypectomy

Suspected cancer

Ischemia

Feeding tube/PEG

Histology needed

Ulcer, gastritis

Foreign body removal

Staging

Follow-up

expected pathology, length of intervention, experience of the investigator, as well as the patient with similar previous interventions and the local infrastructure. The patient needs to have a bite guard introduced into the mouth to avoid damage of the gastroscope during the investigation. The endoscope is then advanced under vision, which allows for a detailed inspection of the esophagus, cardia (from above and in inversion), and stomach as well as parts I (bulbus duodeni) and II (pars descendens duodeni) of the duodenum. Biopsy forceps are used to collect specimens under vision from the upper GI tract for histopathological evaluation as well as Helicobacter pylori testing.

7.2.3 Bleeding Control Within the Upper Gastro-Intestinal Tract Endoscopic control of bleeding lesions within the upper GI tract is successful in more than 90% of all patients. A number of treatment options have been described, and their availability may vary in different locations. Most common causes of bleeding within the upper GI tract are ulcers of the stomach or the duodenum. Endoscopic treatment of these bleeding lesions is indicated for an actively bleeding ulceration (Forrest I), ulceration with a visible vessel (Forrest IIa) and ulceration with an adhering blood clot (Forrest IIb) (see Table 7.2 for the Forrest classification). With ongoing treatment of hemorrhagic shock, interventional endoscopy is the most important diagnostic and possibly therapeutic intervention and needs to be done as early as possible. To protect the patient from aspiration, an early intubation must be considered. Actively bleeding ulcers are treated with irrigation using ice-cold water and identification of the bleeding lesion. Subsequently, the ulcer is injected with a mixture of adrenaline (1 mg; 1:1,000) and normal saline (10 ml).

If available, fibrin glue depots should be injected into the base of the ulcer immediately adjacent to the bleeding vessel. If a vessel can be clearly identified, clipapplication should be considered as well. The risk of recurrent bleeding is highest (30%) during the first 72 h after treatment, and can be reduced to 5–15% with the endoscopic intervention and additional medical treatment (proton pump inhibitor therapy 40  mg i.v. three times/day or as continuous infusion). The usefulness of a routine control endoscopy at 24 h after the initial treatment is under constant debate. The authors are not in favor of this and prefer on-demand treatment. Approximately 10% of upper gastro-intestinal tract bleedings come from esophageal varices. The prognosis of this condition mainly depends on successful bleeding control. Endoscopic banding of esophageal varices is standard of care for this condition. Varicose veins of the gastric fundus should be injected with a mixture of histoacryl and lipiodol. Eighty percent to 90% of all bleeding variceses can be treated successfully with endoscopy. Failed treatment requires positioning of a SengstakenBlakemore or of a Linton-Nachlass tube into the esophagus. This tube has to be decompressed every 6–12 h to avoid pressure ulcers within the esophagus. Medical treatment can be done with Terlipressin or Somatostatin in cases of failed endoscopy, or in addition to endoscopic treatment. Table 7.2  Forrest classification of upper GI bleeding I: Active bleeding •

Ia: Spurting blood

•

Ib: Oozing blood

II: Signs of previous bleeding • IIa: Visible, non-bleeding vessel • IIb: Blood clot in ulcer • IIc: Blood-covered ulcer III: Ulcer without signs of previous bleeding

37

7  Fiber Optic Endoscopy: Gastroscopy

Mallory–Weiss tears usually do not require endoscopic treatment and the bleeding stops without ­intervention. Dieulafoy lesions and gastric cancers are the underlying cause for upper GI bleedings in less than 5%. Diffuse bleeding may be difficult to treat and usage of Argon beam coagulation can be helpful (if available), otherwise cold water instillation into the stomach can also help to reduce the amount of blood loss. Figure 7.1 shows the endoscopic appearance of various lesions causing upper gastrointestinal bleedings.

stomach against the abdominal wall and avoids ­dislocation of the tube • Direct puncture of the stomach under vision, placement of two holding stitches to fix the stomach to the abdominal wall, placement of a feeding catheter into the stomach The most commonly used procedure is the pull-through technique with a thread and transoral introduction of the feeding tube.

7.3 Percutaneous Endoscopic Gastrostomy (PEG)

7.4 Endoscopic Treatment of Anastomotic Leakage or Stenosis

Endoscopic placement of an enteral feeding tube through the abdominal wall has become standard of care for a number of conditions causing dysphagia (i.e., neurological disorders, malignant disease). Two different techniques have been described:

Following esophageal resection up to 30% of the patients can suffer from anastomotic leakage. Endoscopy can be useful for diagnosis and treatment (debridement, fibrin glue application, stent insertion) of this dangerous condition.

• Puncture of the stomach under endoscopic view, introduction of a thread through the needle and pull-through of the thread with the gastroscope into the patient’s mouth, joining of the thread with the feeding tube and pull-through of the thread with the feeding tube into the stomach, an anvil places the

Endoscopic evaluation done by an experienced investigator is safe at any point in time after upper GI surgery, without resulting in an increased risk of perforation or anastomotic leakage

Fig. 7.1  Endoscopic appearance of lesion causing upper gastrointestinal bleeding. (a) Chronic ulcer of the anterior wall of the duodenal cap; (b) severe hemorrhagic gastritis without erosions; (c) bleeding from the apex of a stromal tumor (leiomyoma) in

the fundus of the stomach; (d) close-up view of a bleeding Dieulafoy lesion in the fundus of the stomach (Pictures courtesy of Professor Ian C. Roberts-Thomson, Queen Elizabeth Hospital, Adelaide)

38

M.W. Wichmann and F.W. Spelsberg

Fig. 7.1  (continued)

Stenosis of the passage through the upper GI tract can be treated under vision with balloon dilatation (Through The Scope, TTS) or using Guillard-SavaryBougies with a guide wire placed through the working channel of the endoscope. A very short stenosed segment can also be treated with radial incisions (Truong technique). Usually any form of treatment requires more than one intervention to achieve long-lasting success.

a

Fig. 7.2  Inoperable esophageal cancer (a) prior to stent placement; (b) after stent placement of a partially covered metal stent

7.4.1 Palliative Tumor Treatment Inoperable stenosing cancers of the esophagus or cardia and the mediastinum, as well as recurrent disease after tumor resections within the upper GI tract, can be treated with a variety of stents (Figs. 7.2a, b). In some cases an anti-reflux stent can be applied to avoid reflux of gastric contents (Fig. 7.3a–c).

b

39

7  Fiber Optic Endoscopy: Gastroscopy

a

b

Fig. 7.3  (a–c) Release of a self-expanding metal stent under image intensifier control

Recommended Reading Hung, W.K., Li, V.K., Chung, C.K., et  al.: Randomized trial comparing pantoprazole infusion, bolus and no treatment on gastric pH and recurrent bleeding in peptic ulcers. ANZ J. Surg. 77, 677–681 (2007)

c

 

8

Fiber Optic Endoscopy: Colonoscopy Matthias W. Wichmann and Fritz W. Spelsberg

8.1 Introduction Flexible endoscopy of the large bowel has significantly improved diagnosis and preoperative evaluation as well as post-operative care and palliation for almost all diseases of the large bowel and rectum. Colonoscopy, therefore, is part of pre-operative assessment and treatment planning, allows for intraoperative evaluation of the surgical site (i.e., anastomosis after resection, localization of pathology if not identified preoperatively) and is part of the management of post-operative complications (i.e., dilatation of stenoses, washout of anastomotic leakage). The endoscopic treatment of advanced polyps or early colon cancers (endoscopic mucosectomy) has been established, as well as the useful application of flexible endoscopy during so-called rendezvous procedures with minimal invasive surgery (i.e., laparoscopic resection of advanced polyps). Moreover, interventional endoscopy plays a major role in the palliative treatment of a number of advanced non-resectable tumors within the large bowel and allows for maintenance of normal food passage and control of local complications such as blood loss or fistula formation. As part of complete colonoscopy, an attempt should be made to also visualize the terminal ileum, although recent studies do not indicate that routine intubation of the ileum during surveillance colonoscopy offers any clinical advantage. The ileocaecal valve, as well as the

orifice of the appendix should, however, be clearly visualized and documented with a picture (Figs. 8.1 and 8.2). Withdrawal time after intubation of the caecum should be at least 7  min, with double passage of each colonic

Fig. 8.1  Endoscopic view of ileocaecal valve and appendiceal orifice

M.W. Wichmann (*) Department of General Surgery, Mount Gambier General Hospital and Flinders University Rural Medical School, 276-300 Wehl Street North, Mount Gambier, SA 5290, Australia e-mail: [email protected] F.W. Spelsberg Department of Surgery,University of Munich – Campus Grosshadern, Marchioninistr. 15, 81377 Munich, Germany

Fig. 8.2  Endoscopic view of colon polyp

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_8, © Springer-Verlag Berlin Heidelberg 2011

41

42

M.W. Wichmann and F.W. Spelsberg

Table 8.1  Indications for colonoscopy Preoperative Intraoperative

Post-operative

Intervention

Lower GI tract bleeding

Localization of lesion

Leakage

Polypectomy

Search for and localization of tumor

Control of suture

Stenosis

Dilatation

Inflammatory bowel disease

Rendezvous

Hemorrhage

Bleeding control

Histology needed

Decompression of pseudo-obstruction (Ogilvie syndrome)

Palliation

Unclear diarrhea

Ischemia

Invagination

Surveillance (>50 years)

Follow-up

Decompression

flexure during withdrawal of the colonoscope. Inversion in the ampulla of the rectum should also be documented with a picture, and allows for an orientation with regard to pathology of the anal canal. To complete the investigation of the anal canal, a proctologic examination (inspection, digital palpation, rigid proctoscopy) should be added. Indications for colonoscopy are listed in Table 8.1.

Table  8.2  Regimen for bowel preparation (Mount Gambier General Hospital) Laxative combination • GlycoPrep-C® (70 g) sachet: polyethylene glycol • 2 PicoPrep® (15.5 g) sachets: Na picosulfate Two days before examination • Stop eating brown bread, cereals, vegetables, and fruits

To clearly identify the exact localization of a pathologic finding within the rectum and distal sigmoid colon, a rigid rectoscopy is required. This procedure allows to exactly measure the distance from the dentate line, which is of relevance for preoperative planning, as well as discussion of neo-adjuvant treatment for rectal cancer (below the peritoneal flexion). Virtual colonoscopy (computed tomography colo­ no­scopy) is an attractive alternative for flexible colonoscopy in case of a failed or incomplete procedure. It, however, also requires a bowel preparation and significant air insufflation into the large bowel, and does not allow for a biopsy or polypectomy.

8.2 Patient Preparation and Technique of Examination A thorough bowel preparation is mandatory for adequate visualization of the entire large bowel. A number of various protocols have been established for this, and all of them require the patient to also follow a diet for at least 24  h prior to the investigation (an example for

• Do not eat anything with seeds in it • Do not eat any yellow cheese One day before examination • Drink at least one glass of clear fluid each hour • No solid foods and no milk products allowed, drink approved clear liquids (see below) only • Laxatives – First dose: 1 pm – add the entire contents of one sachet of PicoPrep in a glass of warm water and stir until dissolved; drink mixture slowly but completely – Second dose: 4 pm – make up sachet of GlykoPrep-C (70 g) with 1 L of water; drink the fluid within approximately 1 h – Third dose: 7 pm – add the entire contents of one sachet of PicoPrep in a glass of warm water and stir until dissolved; drink mixture slowly but completely Approved clear liquids (may not contain red or purple colorings): water, clear bullion, apple juice, grape juice, plain jelly, black tea/coffee, clear sports drinks, carbonated beverages, clear fruit cordials

bowel preparation is listed in Table  8.2). The major advantage of polyethylene-glycol-based iso-osmolar solutions (e.g., Golytely®, Klean-Prep®) when compared to saline solutions (Fleet®) is the option to also use them for patients with impaired cardiac or renal function.

43

8  Fiber Optic Endoscopy: Colonoscopy

The procedure should be done using a fully flexible video-colonoscope with forward vision and a maximum viewing angle of 140°. Most colonoscopes have one to two working channels and are approximately 13 mm in diameter. The working length is 130 cm and the image gives a 1:20 enlargement of the visualized bowel. The use of so-called video-zoom colonoscopy with special lens systems allows for 1:100 enlargement, and the practicability of this is still under investigation. The use of special dyes and filters to visualize early neoplastic changes of the mucosa is also being investigated. The large-scale use of these techniques will most likely be limited due to the related costs and the additional time required for these procedures.

Cave: In high-risk patients (cardiac valve replacement, previous infectious endocarditis, leaking ­cardiac valves), antibiotic prophylaxis should be given to prevent bacterial endocarditis after the colonoscopy. Sedation of the patient (midazolal 3–5 mg i.v. and/or disoprivan 50–70 mg i.v. + maintenance boli 10–30 mg i.v.) with mandatory monitoring using pulse-oxymetry may be necessary. The investigation is started with the patient in left lateral position and the knees bent. During difficult investigations a repositioning (on the back or even on the front) of the patient or manual fixation of the bowel (pressure from the left lateral abdominal wall toward the center of the abdomen) by an assistant may be necessary. As mentioned above, the colonoscopy should clearly visualize the caecum and in specific cases (inflammatory bowel disease) the intubation of the terminal ileum is necessary. Figure 8.1 shows the ileocaecal valve as well as the appendiceal orifice as indicators of a complete colonoscopy. The learning curve for adequate completion of diagnostic colonoscopy has been established to be in the area of 150 procedures.

8.3 Polypectomy 8.3.1 Risk of Malignancy Adenomatous polyps of the large bowel are ­neoplasias which carry the potential to progress to a ­malignant ­disease (adenoma–carcinoma sequence). ­Approxi­mately

5% of large bowel polyps are thought to progress to large bowel cancers. High-grade dysplasia within a polyp is a risk factor for the development of colorectal cancer. Patient age, number, and size of the polyps as well as the fraction of villous adenomas are relevant for the risk of malignancy. Approximately 90% of all polyps in the large bowel are either tubular or tubulovillous in nature, and only 10% are pure villous adenomas. The risk of malignancy increases from 4% in tubulovillous adenomas <1  cm to 7% in adenomas measuring 1–2 cm and 46% in lesions larger than 2 cm. If a polyp is detected via rectoscopy, an additional colonoscopy must be carried out since additional polypoid lesions can be found in up to 40% of these patients.

8.3.2 Procedure Endoscopic excision of a large polyp (>1  cm) (Fig.  8.2) requires an adequate coagulation system (INR 1.4, PTT < 2× normal value, platelet count > 50,000/mm3), optimal bowel preparation, and risk-adjusted indication (risk of perforation and possible need for emergency surgery vs. elective bowel resection). Removal of the polyp is done using a diathermy snare, with the option of prior injection of adrenaline (1 mg, 1:1,000) mixed with normal saline (10  ml) to prevent bleeding, and to float the polyp off the mucosa (especially for flat and broad-based lesions). After polypectomy, clips may be applied for bleeding control and to close the mucosa to prevent secondary perforation of the bowel wall. Polyps smaller than 5 mm should be removed using a biopsy forceps, since diathermy would alter the tissue too much for adequate histological evaluation. Very large polyps may require removal in several pieces (piecemeal technique) or even with several procedures. Histological evaluation of these piecemeal specimens can be very difficult, and complete clearance of the advanced polyp cannot always be achieved. This must be considered when discussing the option of bowel resection after biopsy and tattooing of the advanced polyp. Figure 8.3 shows the polypectomy site of a large polyp before and after clip application for haemostasis and prevention of bowel perforation. Figure  8.4 shows a colon cancer as detected by colonoscopy. Figure 8.5 shows the endoscopic appearance of different colonic polyps.

44

M.W. Wichmann and F.W. Spelsberg

a

b

Fig. 8.3  Endoscopic view of polypectomy site before (a) and after (b) clip application

8.3.3 Follow-up After complete removal of a polyp, follow-up should be done at 3–6 months, then at 3–5-year intervals. The author’s approach is slightly less aggressive with a repeat colonoscopy following polypectomy scheduled after 12  months (villous adenoma < 12  months). Surveillance colonoscopies are needed to be scheduled for:

Fig. 8.4  Endoscopic view of colon cancer

Aim of the procedure must be complete excision and complete retrieval of the polyp since up to 8% of all removed polyps contain parts of invasive carcinomas which may be missed if only ­partial excision is done, or part of the polyp is lost for histological examination.

• Familial hereditary non-polyposis colorectal cancer: every 1–2 years starting at age 20–30, annually after 40 years • First-degree relative with colon cancer/adenomatous polyp: start at age 40, then every 10 years • Personal history of polyps: every 3–5 years • Personal colon cancer history: 3–6  months after treatment, then every 3–5 years • Inflammatory bowel disease: every 1–2  years, beginning at any age • Family history of familial adenomatous polyposis (AFP): annual

8.3.4 Complications Destruction of the tumor using diathermy, laser, or argon-plasma coagulation should not be done because they do not allow for pathological evaluation. These techniques are of relevance, however, for palliation, and can restore normal fecal passage.

The complication rate of diagnostic colonoscopies is very low (<0.2%) and the associated mortality is <0.01%. The most common complications are cardiopulmonary problems (usually due to sedation) and bleeding episodes (<0.02%). Perforations usually occur

45

8  Fiber Optic Endoscopy: Colonoscopy Fig. 8.5  Endoscopic appearance of various colonic polyps. (a) Typical small polyp; (b) polyp on a large stalk; (c) typical flat polyp, 2 cm in diameter; (d) large polyp, 4 cm in diameter. Endoscopic resection of polyps (c) and (d) is often difficult and such patients may be best referred to specialized endoscopy centers (Pictures courtesy of Professor Ian C RobertsThomson, Queen Elizabeth Hospital, Adelaide)

within the recto-sigmoid junction or the sigmoid colon and have an incidence of less than 0.05%. Abdominal pain and discomfort is usually due to the insufflation of air – ongoing discomfort, however, requires exclusion of a perforation (abdominal X-ray, computed tomography). Therapeutic colonoscopies carry slightly higher complication rates with regard to bleeding (1–2%) and perforation (0.1–0.3%). The mortality rate is 0.05%.

(pain treatment ± antibiotic treatment) after radiological exclusion of a perforation. Should a ­perforation occur, it usually requires surgical intervention, although a conservative approach (nil per mouth, i.v. antibiotics) can be considered if the bowel ­preparation was very good, no cancerous lesion has been detected and the patient is not on regular corticosteroids.

8.4 Postpolypectomy Syndrome

8.5 Treatment of Anastomotic Leakage or Stenosis

Following polypectomy a transient episode of pain with local peritonism, fever, and raised white blood cell count can be observed without evidence of full thickness wall necrosis or perforation. This condition is believed to result from a localized peritonitic reaction to the polypectomy, and should be treated conservatively

After low anterior rectal resection, up to 30% of patients suffer from a leakage at the level of the anastomosis. In some cases, a wait-and-see policy with endoscopic washout and fibrin-glue application can be followed, whereas more severe cases may require endoscopic vacuum-assisted closure. This procedure uses the

46

principle of vacuum-assisted wound healing with a drainage connected to special foam which is being introduced through the area of leakage and drains into a suction bottle. This foam needs to be replaced endoscopically every 3–4 days and allows outpatient treatment of this severe complication of rectal surgery. The stenosis of an anastomosis within the colon or rectum can be treated using similar techniques as in the upper GI tract with balloon dilatation, Guillard-Savary, or Hegar bougies.

8.5.1 Palliative Treatment Patients with non-resectable large bowel cancer can benefit from endoscopic stent placement through the malignant stenosis. This can be done as a definitive procedure or as a bridging procedure allowing for ­adequate resuscitation prior to palliative or curative bowel resection.

M.W. Wichmann and F.W. Spelsberg

Recommended Reading Iqbal, C.W., Cullinane, D.C., Schiller, H.J., et  al.: Surgical management and outcome of 165 colonoscopic perforations from a single institution. Arch. Surg. 143, 701–707 (2008) Lee, S.H., Chung, I.K., Kim, S.J., et al.: An adequate level of training for technical competence in screening and diagnostic colonoscopy: a prospective multicenter evaluation of the learning curve. Gastrointest. Endosc. 67, 683–689 (2008) Tilney, H.S., Lovegrove, R.E., Purkayastha, S., et al.: Comparison of colonic stenting and open surgery for malignant large bowel obstruction. Surg. Endosc. 21, 225–233 (2007) Weidenhagen, R., Gruetzner, K.U., Wiecken, T., et  al.: Endoscopic vacuum-assisted closure of anastomotic leakage following anterior resection of the rectum: a new method. Surg. Endosc. 22, 1818–1825 (2008) Goldenberg, E.A., Khaitan, L., Huang, I.-P., Smith, C.D., Lin, E.: Surgeon-initiated screening colonoscopy program based on SAGES and ASCRC recommendations in a general surgery practice. Surg. Endosc. 20(6), 964–966 (2006)

9

Endoscopy for Rural Surgeons: ERCP Ian C. Roberts-Thomson

9.1 Introduction ERCP is an endoscopic procedure that involves cannulation of the ampulla of Vater and use of radiologic contrast to outline biliary and pancreatic ducts. The technique was first described from centers in the USA and Japan between 1968 and 1970, soon after the introduction of fiberoptic endoscopes. In 1974, a group from Germany described endoscopic sphincterotomy for bile duct stones and, in 1979, a different German group described the use of endoscopic stents for malignant bile duct obstruction. Despite these impressive developments, widespread adoption of the technique was relatively slow as the procedure was technically demanding and associated with significant complications. Even today, ERCP is performed by only a minority of gastroenterologists or surgeons and, in Australia, is largely restricted to major city hospitals.

9.2 Training Training in endoscopy has always been an issue for surgeons. In Australia and many other countries, surgical trainees have only had limited access to endoscopy training as the majority of training has been conducted in medical departments. Furthermore, for surgeons, training in endoscopy has only been a relatively small part of the total training experience. In contrast, the development of skills in endoscopy is a

I.C. Roberts-Thomson Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, 28 Woodville Rd, Woodville South, SA 5011, Australia e-mail: [email protected]

major focus for advanced trainees in gastroenterology and hepatology. In relation to training for ERCP, particular issues are low case loads (even in some tertiary centers) and the possibility of lower success rates and higher frequencies of complications when procedures are solely or largely performed by trainees. In Australia, most of the training in ERCP is performed in medical departments in tertiary hospitals. A formal “recognition of training” certificate is provided by a national group after appropriate references and documentation of 200 procedures performed independently. In most tertiary centers, this will only be achieved after a minimum of 2 years of training.

9.3 Indications There have been major changes in the indications for ERCP over the last 30 years. For example, ERCP was widely used for the diagnosis of biliary and pancreatic disorders in the 1980’s but is now largely restricted to ­therapeutic procedures for bile duct stones, biliary and pancreatic cancer, and miscellaneous biliary disorders. The major reason for this change is the introduction of  various non-invasive procedures including upper abdominal ultrasound (US), computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP) and endoscopic US. Of these, only upper abdominal US and CT will be readily available to most rural surgeons. Current indications for ERCP are summarized in Table 9.1. At present, the majority of bile duct stones are treated by endoscopic biliary sphincterotomy and endoscopic extraction (Fig. 9.1). These stones may be diagnosed before cholecystectomy, by an intraoperative cholangiogram during cholecystectomy or because

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_9, © Springer-Verlag Berlin Heidelberg 2011

47

48

I.C. Roberts-Thomson

Table  9.1  Indications for endoscopic retrograde cholangio­ pancreatography Diagnostic

Confirm bile duct stones Confirm ampullary neoplasms Define post-operative biliary disorders Define pancreatic fistulae Confirm sclerosing cholangitis

Therapeutic

Biliary sphincterotomy for bile duct stones Biliary stents for malignant obstruction Biliary sphincterotomy for post-­ cholecystectomy pain Management of benign biliary strictures Management of post-operative biliary fistulae Pancreatic stents for pancreatic fistulae Endoscopic drainage of pancreatic pseudocysts Extraction of pancreatic duct stones

Fig. 9.1  Images of bile duct stones taken at ERCP. (a) Single small calculus; (b) multiple stones and one larger calculus; (c) multiple irregular stones and at least one large stone; (d) a single

of the development of early or late manifestations after cholecystectomy. Features of bile duct stones prior to cholecystectomy include abdominal pain and changes in liver enzymes, obstructive jaundice, cholangitis and changes in liver enzymes without pain. After surgery, bile duct stones should be suspected when there is persisting pain with changes in liver enzymes, the development of jaundice or the development of a biliary fistula, usually through the cystic duct stump. Patients diagnosed with bile duct stones months or years after cholecystectomy present in a similar way to those with bile duct stones prior to cholecystectomy. For biliary and pancreatic cancer, endoscopic procedures largely involve the insertion of biliary stents in patients with obstructive jaundice. However, ­diagnostic ERCP can have a role, particularly when US or CT images show obstruction close to the duodenal wall without an associated mass. Some of these patients have cancer of the ampulla of Vater while others have periampullary or duodenal cancer. Endoscopic US is also being increasingly used to assess the size and extent of spread of pancreatic and biliary neoplasms

huge calculus. Sphincterotomy and stone extraction is likely to be successful in (a) and (b) but (c) and (d) will be challenging, even for experts

49

9  Endoscopy for Rural Surgeons: ERCP

and, if surgery seems unlikely, to obtain tissue for assessment by aspiration cytology. At present, tissue obtained by this technique has greater sensitivity and specificity for the diagnosis of cancer than diagnostic procedures at ERCP including brush cytology of ductal strictures and duct biopsy. Other miscellaneous indications for diagnostic and therapeutic ERCP include the diagnosis and endoscopic management of post-operative biliary strictures and sclerosing cholangitis. Diagnostic and therapeutic procedures have also been promoted for pancreatic pseudocysts, chronic pancreatitis, pancreatic trauma and pancreatic ascites, but endoscopic management should be restricted to experts. Another issue is that of biliary-type pain after cholecystectomy (without stones). If medical therapy fails, endoscopic sphincterotomy should be restricted to experts as selective cannulation of the bile duct is sometimes difficult and there is a higher than expected frequency of pancreatitis after the procedure.

9.4 Preparation and Sedation Patients should fast for at least 3 h prior to the ­procedure. Satisfactory sedation can usually be achieved with meperidine (pethidine) and midazolam but some practitioners routinely use propofol with help from anaesthetists or anaesthetic assistants. However, unconscious sedation does limit the use of positional changes that may facilitate the interpretation of ductal images. Theoretically, meperidine is preferable to fentanyl as the latter drug induces a greater degree of spasm in the sphincter of Oddi.

9.5 Endoscopic Stents for Malignant Biliary Obstruction Patients with malignant biliary obstruction can be treated with endoscopic stents, palliative bypass ­surgery or more radical surgery with the potential for cure. Ideally, management in individual patients should be discussed in a multi-disciplinary setting that includes surgeons and oncologist. Endoscopic stents

are likely to be the preferred form of therapy in patients with advanced disease and in those who are elderly (>85  years) or with significant comorbidities. Stents can be composed of either plastic or metal (nitinol or stainless steel). Conventional 10-French plastic stents are relatively cheap, remain patent for 3–4 months and can usually be readily replaced by repeat ERCP. In contrast, metal stents are more expensive and remain patent for a longer period. However, most metal stents are impossible to remove endoscopically and, in the event of stent occlusion, options include a second metal stent within the original stent or a plastic stent within the metal stent. In practice, plastic stents are often used in patients whose survival seems likely to be short while metal stents are used in those whose anticipated survival is > 4–6 months. An additional issue is the use of plastic stents to relieve jaundice prior to radical surgery. Advocates of this policy point to the avoidance of urgent procedures and a possible improvement in patient outcomes. Others who prefer to avoid pre-operative stents are concerned by stent-induced changes in ducts and a possible increase in post-operative infections. This issue has not been entirely resolved, although a recent randomized trial showed that pre-operative stents did not improve patient outcomes when the pre-operative serum bilirubin was < 250 mmol/l (14.6 mg/dl).

9.6 Complications The major complication of ERCP is the development of pancreatitis. This has been defined in a number of different ways but the clinical issue is pain after the procedure that is accompanied by a rise in the serum amylase to >300–500 U/l. The frequency of this complication ranges from 1% to almost 25% in unselected series but should be 7% or less. Several studies have shown higher risks for pancreatitis when procedures are performed by endoscopists with low case-loads. Other risk factors for pancreatitis include difficulties with cannulation, use of precut techniques, female gender and procedures on patients with recurrent ­pancreatitis or post-cholecystectomy pain. As various pharmacological agents have failed to reduce the risk of pancreatitis after ERCP, minimization of risk

50

continues to depend on appropriate case selection and a meticulous endoscopic technique. Less common complications after ERCP include duodenal bleeding after endoscopic sphincterotomy, cholangitis and duodenal perforation.

9.7 ERCP in a Rural Setting Competence at ERCP is largely determined by the quality and duration of training and by ongoing experience. The minimal case-load for maintenance of ERCP skills has not been defined but may be 50 cases/year. This is the approximate case-load that would be generated from a population of 50,000 people. Although ERCP in Australia is largely performed by gastroenterologists, there are some notable exceptions including rural surgeons. However, a significant issue for surgical trainees is access to ERCP training in large metropolitan hospitals.

Recommended Reading Coelho-Praghu, N., Baron, T.H.: Endoscopic retrograde cholangiopancreatography in the diagnosis and management of cholangiocarcinoma. Clin. Liver Dis. 14, 333–348 (2010)

I.C. Roberts-Thomson Davids, P.H., Groen, A.K., Rauws, E.A., Tytgat, G.N., Huibregtse, K.: Randomised trial of self-expanding metal stents versus polyethylene stents for distal malignant biliary obstruction. Lancet. 340, 1488–1492 (1992) de Groen, P.C., Gores, G.J., LaRusso, N.F., Gunderson, L.L., Nagorney, D.M.: Biliary tract cancers. N. Eng. J. Med. 341, 1368–1378 (1999) Freeman, M.L., Nelson, D.B., Sherman, S., et al.: Complications of endoscopic biliary sphincterotomy. N. Engl. J. Med. 335, 909–918 (1996) Moss, A.C., Morris, E., Leyden, J., MacMathuna, P.: Malignant distal biliary obstruction: a systematic review and metaanalysis of endoscopic and surgical bypass results. Cancer Treat. Rev. 33, 213–221 (2007) Roberts-Thomson, I.C.: Endoscopic sphincterotomy of the papilla of Vater: An analysis of 300 cases. Aust. N.Z. J. Med. 14, 611–617 (1984) Takagi, K., Ikeda, S., Nakagawa, Y., et al.: Retrograde pancreatography and cholangiography by fiber duodenoscope. Gastroenterology 59, 445–452 (1970) van den Gaag, N., Rauws, E.A.J., van Eijck, C.H.J., et  al.: Preoperative biliary drainage for cancer of the head of the pancreas. N. Engl. J. Med. 362, 129–137 (2010) Varadarajulu, S., Eloubeidi, M.A.: The role of endoscopic ultrasonography in the evaluation of pancreatico-biliary cancer. Surg. Clin. North Am. 90, 251–263 (2010)

Rigid Endoscopy: Cystoscopy

10

Mark Lloyd and John Miller

10.1 Introduction Cystoscopy is the endoscopic inspection of the lower urinary tract. Cystoscopy includes the endoscopic visualization of the urethra and bladder. Cystoscopy is a useful procedure for evaluation of urinary symptoms or signs including haema­turia, reduced urinary flow, urinary frequency and urgency. The male urethra is divided into penile, bulbar, membranous and prostatic urethra while the female urethra is quite short. The bladder includes base, dome, ureteric orifices and trigone. Cystoscopy may be achieved by use of the rigid cystoscope or the more recent flexible cystoscope. Rigid cystoscopy is usually performed under a general anaesthetic, particularly in the male, due to the discomfort associated with introducing the instrument. Rigid cystoscopy may be performed under local anaesthetic in the female owing to the short urethra. Flexible cystoscopy is performed under topical local anaesthetic gel. It provides a rapid and convenient assessment of the lower urinary tract. The advantage of rigid cystoscopy is the superior vision and the ability to introduce a biopsy forceps in order to biopsy any abnormal area. Any area of bleeding may be diathermied by use of the monopolar diathermy lead – which may also be used to stop bleeding from any site of bladder biopsy.

M. Lloyd (*) and J. Miller Department of Surgery, The Queen Elizabeth Hospital, 28 Woodville Rd, Woodville South, SA 5011, Australia e-mail: [email protected]

10.2 Indications Cystoscopy is indicated for evaluation of lower urinary tract symptoms, haematuria, bladder lesions, stones and bladder outflow obstruction. A cystoscopy is recommended for evaluation of all cases of haematuria – particularly gross haematuria, and ongoing microscopic haematuria, particularly in those with significant microscopic haematuria, which is variously defined as over 5–10 red cells detected under light microscopy per high power field. All smokers with any degree of haematuria should undergo cystoscopy due to the high risk of transitional cell carcinoma. Other risk factors for neoplasia of the urothelium include exposure to petrochemical products, solvents and herbicides and pesticides. Recurrent urinary tract infection may also be investigated with a cystoscopy. Surveillance cystoscopy following treatment for transitional cell carcinoma of the bladder is mandatory and is initially repeated frequently to check for recurrences and following this annually.

10.3 Patient Preparation Prior to initial cystoscopy it is useful to obtain an ultrasound of the urinary tract and bladder and it is recommended to obtain a urine microscopy and culture to exclude infection and to quantify any haematuria. Urine cytology is particularly useful to check for any malignant cells in the urine, which is suggestive of transitional cell carcinoma. An active urinary infection is a contraindication to cystoscopy not only as the cloudy urine impedes vision but also due to the risk of sepsis particularly if the urothelium is breached.

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_10, © Springer-Verlag Berlin Heidelberg 2011

51

52

Antibiotic prophylaxis is at the clinician’s discretion but must be given if infection is suspected or if the patient is at risk in the event of bacteraemia (prosthetic heart valve especially).

10.4 Findings Transitional cell carcinoma appears as a papillary or solid mass in the bladder or urethra – this may be biopsied or referred primarily to an urologist for management. Cystitis appears as a diffuse inflammatory reaction of the bladder wall and is usually indicative of infection; however, the differential diagnosis includes carcinoma in situ (appearing as flat red areas in the bladder) and other forms of cystitis (interstitial cystitis, postradiotherapy and haemorrhagic cystitis). Bladder outflow obstruction is suggested by a benign prostatic hyperplasia (which may also be a common cause of haematuria if the cystoscopy is otherwise negative) or a tight bladder neck with muscular hypertrophy. Benign prostatic hyperplasia is indicated by a large prostate with lobes meeting and obstructing the prostatic urethra. Bladder outflow obstruction may be associated with bladder stones – which are easily seen with cystoscopy – small stones may be washed out – larger stones should be treated endoscopically at a tertiary centre. The ureteric orifices should be inspected and normally lie symmetrically opposite at the corners of the trigone – the ridge running transversely from one to the other aids identification and is termed the interureteric bar. The observation of a ureteric jet of urine is helpful for location and aids in excluding obstruction. Haematuria from a ureteric orifice is indicative of ­unilateral ureteric or renal pathology. Ureteric orifices may be cannulated with an openended ureteric catheter. A retrograde pyelogram may be obtained by the instillation of 10 ml of radio-opaque contrast to confirm the position. This may also be performed prior to difficult abdominal/pelvic surgery – a size 6 or 4 French catheter is used for this purpose. Cystoscopy may be performed intraoperatively to check for bladder or ureteric injury – this is suggested by the presence of blood on introduction of the ­cystoscope. A thorough evaluation of the bladder, ­presence or absence of ureteric jets should be done. Retrograde pyelogram or the instillation of methylene blue may also be performed.

M. Lloyd and J. Miller

During cystoscopy a urethral stricture may be detected – this may be impassable if dense but often is a flimsy stricture which can be dilated with the cystoscope. A stricture may be dilated with urethral sounds; however, the possibility of urethral injury and false passage should be borne in mind. Cystoscopy is not complete without a digital rectal examination as early prostate cancer sometimes presents with a prostatic nodule and is usually asymptomatic. It is also a useful way of assessing prostatic size.

10.5 Technique Cystoscopy is performed using a 21 or 23 French sheath and a 30° and 70° optical Hopkins rod telescope. The light source is usually halogen and the telescope is connected to a single or triple chip camera. Single chip cameras are perfectly suitable for cystoscopy. Cystoscopy can be combined with endoscopic ­surgery on the lower urinary tract. This requires the introduction of a resectoscope using a 26 or 28 French sheath. Usually this is a dual lumen sheath which features continuous flow to allow any blood to be washed away by fluids keeping the operative view clear with good light transmission. Using this sheath resection of a bladder tumour may be performed using an electrocautery resecting loop. Transurethral resection of the prostate may also be ­performed. Both procedures can be complicated by significant bleeding and hence the need for a continuous flow of irrigation fluid. Irrigation fluid may be saline, water or glycine; however, glycine must be used if diathermy is to be employed. Glycine is composed of amino-acetic acid and is used to allow transmission of an electrical current only through the instrument used and not through the fluid itself. Its osmolarity is greater than water but less than plasma. Saline does not allow diathermy to be used and water is hypotonic and can cause problems if absorbed in significant quantities. Glycine too can cause problems with excessive absorption usually occurring during TURP – this is termed TURP syndrome – it is characterized by dilutional hyponatraemia and expansion of the extracellular fluid space. The syndrome is commonly detected by a confusional state – if untreated it may lead to cerebral oedema, seizures and coma.

53

10  Rigid Endoscopy: Cystoscopy

10.6 Complications Complications which can be observed after cystoscopy include: • False passage – without careful visualization the urethra may be perforated – this can occur at the level of the bulbar urethra. The management is placement of catheter into the true passage and into the bladder. • Bleeding from biopsy or resection sites – this is managed by diathermy and subsequent catheterization. • TURP (Trans Urethral Retrograde Prostatectomy) syndrome – managed by fluid restriction, diuretics and occasionally hypertonic saline intravenously. • Sepsis – managed by appropriate antibiotic therapy and catheter drainage. • Post-operative urinary retention or clot retention. Clearly, the best management is prevention by careful instrumentation of the sterile urinary tract together with antibiotic prophylaxis. Cystoscopy may be accompanied by prostatic biopsy if required – the indications for this are an ­elevated PSA or the presence of a suspicious prostatic nodule. Prostatic biopsy is performed by a trucut needle biopsy utilizing a spring-loaded biopsy device. The needle biopsy may be finger guided using great care

not to injure one’s finger! Most biopsies are now ­performed using a transrectal ultrasound probe which allows good visualization of the prostate and accurate needle placement for biopsy. Six to 12 biopsies are taken of the peripheral zone of the prostate where ­prostatic carcinoma is most likely to appear. This procedure may be accompanied by sepsis and therefore antibiotic prophylaxis for all patients is required together with an enema to empty the rectum before ultrasound is employed. Any anticoagulation must be ceased as for all surgery on the urinary tract. Endoscopy of the lower urinary tract is safe in terms of a diagnostic procedure. Operative endoscopy may be accompanied by ­complications for which the surgeon should be ready – bleeding, urinary retention and sepsis remain the most common.

Recommended Reading Hanno, P., Malkowicz, S.P., Wein, A.: Clinical Manual of Urology. McGraw-Hill, New York (2001) Tanagho, E.A., McAninch, J.W.: Smith’s General Urology Lange Clinical Medicine/McGraw-Hill, New York (2007) Wein, A.J., Kavoussi, L.R., Novick, A.C., Partin, A.W.: Campbell-Walsh Urology Review Manual, 9th edn. Saunders, Mosby (2007)

 

Rural Surgical Audit

11

David A.K. Watters

11.1 Definitions Surgical audit can be defined as ‘the systematic, ­critical analysis of the quality of surgical care that is reviewed by peers against explicit criteria or recognised standards, and then used to further inform and improve surgical practice’ [1, 2]. A briefer definition might be, ‘am I doing what I think I am doing?’ and ‘am I doing it as well as others?’ Surgical audit addresses the structure (access, efficiency), process (protocols, documentation and patient journey) and outcomes (mortality, morbidity, disability, improvement) of care. To be effective, surgical audit involves a feedback loop where issues identified by audit and peer review are reported, solutions are found, changes occur and the outcome of those changes are further monitored. Surgeons and their teams need to reflect on performance, and then engage the relevant stakeholders in devising and communicating improvements in care [2]. In recognition of the value of participating in surgical audit and peer review, many surgical colleges and hospitals have made such auditing a mandatory component of continuing professional development [3]. Mortality audits are specifically designed to learn from deaths, though there is a wide variability of mortality rates between specialties. The Royal Australasian College of Surgeons (RACS) regards participation in the Australia New Zealand Audit of Surgical Mortality (ANZASM) as an aspect of clinical governance,

a separate component from audit and peer review in maintaining professional standards [3]. Surgical audits may include one’s whole practice (all cases whether operated on or not), or focus on a specific procedure, presenting problem or outcome.

11.2 Performing a Surgical Audit in the Rural Context Rural surgeons tend to have a broader clinical practice than their metropolitan colleagues. Country towns often struggle to attract and retain a surgical workforce, so specialists are often isolated. Despite their isolation, such specialists still need to perform a regular surgical audit and obtain a review by peers. The models adopted for peer review vary according to ­circumstance and are discussed below. An audit must be complete (contain all cases for the particular condition or time frame), accurate and honest. The focus and period of the audit need to be defined. For example, all cases of colorectal surgery for years x–y; alternatively, all cases managed for time period z. Six monthly audits are commonly timed in training hospitals to coincide with registrar rotations. Yearly audits may be just as appropriate for the isolated rural surgeon or for an audit focused on one ­problem or group of procedures.

11.2.1 What Data to Collect? David A.K. Watters Department of Surgery, University of Melbourne and Barwon Health, Geelong Hospital, Geelong, VIC 3220, Australia e-mail: [email protected]

The data collected needs to identify what procedures were done on what sort of patients (risk, urgency, comorbidities) and the outcome of those procedures.

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_11, © Springer-Verlag Berlin Heidelberg 2011

55

56

D.A.K. Watters

Table 11.1  Minimum and expanded data sets advised for whole practice audit Minimum data set

Expanded data set

Name (or initials)

a

ID (or case record number)a

Admission type

Date of birth (age calculated) Sex

Presenting problem

Final diagnosis

Comorbidities

Admission date

Wound infection risk

Discharge date

ASA grading

Operation/procedure performed

Indication for operation

Operation date

Type of anaesthetic

Operation urgency

Operating magnitude

Complications and grade (Table 11.2)

Pathology information and diagnosis

Surgeon identifiera

Outcome/discharge type

Information that is private and not for release beyond the surgical unit responsible for care Source: RACS Surgical Audit and Peer Review Guide, 3rd edn.

a

The minimum and expanded datasets recommended by the Royal Australasian College of Surgeons (RACS) are shown in Table 11.1 [1, 2]. The expanded data set enables better risk stratification, which may facilitate ‘comparing with known standards’. The age of a patient, urgency of procedure, stage of disease and comorbidities are key aspects of stratifying the risk of morbidity and mortality. Some specialties have established scoring systems. Specialist data sets may also be appropriate for specific procedures. The recording of comorbidities is difficult to achieve retrospectively, and the American Society of Anaesthetists (ASA) status may be a reasonable alternative. In colorectal audits conducted by rural surgeons, a count of two or more comorbidities was associated with worse outcomes. Table 11.2 shows the comorbidities used by the Elixhauser [4] and Charlson [5] classifications, the latter list carrying a score. The third column shows complications (Clavien) [6] to provide useful drop-down menus to record comorbidities and grade complications. Risk stratification of the condition of the patient is essential to compare outcomes if like is to be compared with like. Trainee surgeons may also collect data about the supervision level and the learning impact of the case.

Trainee logbooks should prepare the trainee for a lifetime of surgical audit and not be simply a list of procedures without outcomes, learning or pathology data [7]. The Supervision Levels recommended for trainee logbooks are: S1: Surgeon Mentor Scrubbed S2: Surgeon Mentor in Theatre S3: Surgeon Mentor Available A1: Assisting Surgeon Mentor A2: Assisting Surgeon Registrar

11.2.2 How to Collect the Data for Audit The earliest and simplest surgical audits were conducted on paper. Paper-based audit require considerable discipline to consistently record the cases, often in a notebook. The more cases, the more challenging becomes the sorting and arranging of the information and its analysis. For these reasons, most surgeons ­prefer to record their data in an electronic format on a computer or personal digital assistant (PDA). The simplest software is to use a spreadsheet such as Excel (www.microsoft.com). Spreadsheets are limited in the number of columns that can be seen on the screen at any one time and are best for logbooks of activity with a limited number of characters in each cell. The best audit programs are based on a database that facilitates searching, summarising and calculations. Many examples of successful surgical audit have employed programs such as Filemaker Pro (www.filemaker.com), Microsoft Access (www.microsoft.com) or HanDbase (www.ddhsoftware.com). Google spreadsheets are another option. What is important is that a program is user friendly and, once the data is entered, the software can be used to generate useful reports without too much extra work. All of the available programs require a template for data entry to be created. Data entry is facilitated by a value list of common conditions such as is shown for the list of comorbidities and complications (Table 11.2). A free downloadable program using Filemaker Pro has been created by the author and is available from the RACS website, http://www.racs. edu.au/racs/fellows/cpd-recertification/cpd-resourcesand-tools/david-watters-surgical-audit-tool. The above hyperlink will lead you to a program that has been used by many rural surgeons but it is still only one

57

11  Rural Surgical Audit Table 11.2  Useful comorbidities and complications for drop-down value lists Cardiovascular

Elixhauser

Charlson (score)

Clavien complications (grade)

Congestive heart failure

Congestive heart failure (1)

Atrial fibrillation

Arrhythmia

Metabolic

Valvular heart disease

Acute MI (1)

Hypertension

Cerebrovascular disease (1)

Peripheral vascular disease

Peripheral vascular disease (1)

Diabetes uncomplicated

Diabetes (1)

Diabetes complicated

Diabetes complications (2)

Tachyarrhythmia requiring B blocker (2) Bradyarrhythmia requiring pacemaker (3) Heart failure leading to low output syndrome (4) Cardiac insufficiency after myocardial infarction (4d)

Obesity Liver

Hepatic disease

Liver disease (1) Severe liver disease (3)

Renal

Renal failure

Pulmonary

Pulmonary circulatory disorders

Neurological

Renal disease (2)

Renal insufficiency requiring dialysis (4) Atelectasis requiring physiotherapy (1)

Chronic pulmonary disease

Pulmonary disease (1)

Pneumonia requiring antibiotics treated on ward (2)

Paralysis

Paraplegia (2)

TIA requiring anticoagulants (2)

Other neurological Cancer

Urinary tract infection requiring antibiotics (2) Reoperation for ureteric injury (3)

Postoperative stroke (4)

Solid tumour without metastasis

Cancer (2)

Metastatic cancer

Metastatic cancer (3)

Lymphoma Other general

AIDS Weight loss Drug abuse Alcohol abuse Psychosis Depression

HIV (6)

Anastomotic leak requiring surgery (3) Necrotising pancreatitis (4) Wound infection opened at bedside (1) Wound infection requiring antibiotic therapy (2) Wound dehiscence requiring OT closure (3) Transient confusion (1)

Rhematoid arthritis/collagen vascular diseases Fluid and electrolyte abnormality Coagulopathy Blood loss anaemia Deficiency anaemia In Australia and the UK, obesity is defined as BMI >25 (= overweight) and >30 (= high risk). Patients with dementia are given ‘other neurological disorder’ but it may be worth adding this. Acute myocardial infarction needs to be defined and I recommend this is within the preceding 30 days

58

example to be considered. Verification should focus on what data are missing or inaccurate. Larger databases (clinical information systems) may be used to generate the data required for audit in individual hospitals (e.g. CORDis in Geelong/Victoria (AUS)).

D.A.K. Watters

centre and present the audit to the surgeons there. It is ideal if those who work in the referral centre, usually a city, have some appreciation of the context of rural practice. There may also be specific procedures, such as ERCP, that would be more appropriate to report through a focused audit and present to peers in a major centre to which the more complex cases would normally be referred [8, 9].

11.2.3 How to Prepare an Audit Surgical audit should review both the workload and the outcomes. The relevant outcomes vary according to procedure and specialty. A whole practice audit such as is often carried out by general surgeons in a rural hospital should include in its outcomes all major complications, unplanned reoperations, unplanned readmissions and mortalities. Most surgeons are assisted by a data and presentation checklist (Fig.  11.1). Problem cases should be presented with enough detail so that the peers have enough information on which to assess the clinical decision-making. For example, a single slide for each case that contains the age, sex, presentation, risk, procedure and the clinical course leading up to the adverse event. A PowerPoint template for surgical audit (Fair Dinkum Audit) can be downloaded from the RACS website, www.surgeons. org/media/16117/PSAauditpostertemplate.ppt.

11.3.1 Conduct of the Meeting A surgical audit meeting should generally not identify names of patients and be conducted in an open, honest but not aggressive way. The purpose of the meeting is to report, review and reflect, not to name and blame. The surgical peer review meeting should have a chairperson who is independent of the team presenting the audit. The chairperson should record the issues, effect on patient or hospital recommendations, action to be taken by whom and when (Fig. 11.3). It is a local decision whether only surgeons are present or whether anaesthetists, surgical ward/operating nurses and hospital managers are present. Certain technical issues arising may only require discussion within the craft group but other events will only be able to be addressed at a service or hospital-wide level. The Director of Surgery should normally be invited and will act as a means of communication between clinician and managers.

11.3 Peer Review An isolated rural surgeon may not have a local peer who practices in their specialty. Although there will be value in presenting one’s audits to other specialists, it is also important to present to at least two other surgeons in the same speciality. This can be achieved by teleconference, or by the peers agreeing to meet face to face every few months. Another alternative is for the audit to be presented at a conference where peers will be present. This method has been used by the Provincial Surgeons of Australia, using a standard poster template (Fig. 11.2) available from, www. surgeons.org/media/16117/PSAauditpostertemplate.ppt. A third model used by some centres in South Australia is for the rural surgeon to visit the referral

11.4 Reporting Surgical Outcomes Outcome reporting requires some degree of risk stratification as patients have individual risks of complications or mortality (Table 11.2). The simplest means is to use ASA [10], or a count of comorbidities from the list in Table 11.2. The use of POSSUM [11, 12] is complex, challenging and usually beyond the enthusiasm of general surgeons except in the research context [10]. The assessment and appropriate measurement of actual outcome varies from procedure to procedure though the principles are the same for all operations. The various specialties need to determine by consensus what the outcome indicators for operations within

11  Rural Surgical Audit Unit X, Surgeons A, B,C, Audit time period: date Y to date Z 1 Surgical caseload 1.1.Total Admissions 1.2 Total Operations 1.2.1 Sub-classified by emergency (1.2.1a), urgent 1.2.1b or elective (1.2) 1.2.2 Number of Complex, Major, Moderate and Minor operations Subclassified by emergency, urgent or elective where appropriate 1.3 Final diagnosis of non-operated admissions – table with numbers and a column that includes plan or outcomes 1.4 Types of Operation – table Tables Subclassified by specialty groups (e.g. endoscopies, breast, endocrine, colorectal, upper GI, etc.) 2 Morbidity and mortality (quality indicators) 2.1 Number of complications and classified by 2.1.1 Severity of complications into grades 1, 2, 3 according to their effect on the patient and the treatment required (see minimum dataset) 2.1.2 Type of complication 2.1.3 Rates for different procedures (see Table 3) Bile leak after cholecystectomy Recurrent laryngeal nerve palsy rate for thyroidectomy Colonoscopies should include completion rates and polypectomy rates Clinical Indicators may include unplanned overnight stay (for day case) as a quality of care indicator (The numerator is the number of complications or relevant performance indicator for each group. The Denominator is the total number of procedures.) 2.2 Number of unplanned readmissions 2.3 Number of unplanned re-operations 2.4 Number of unplanned ICU readmissions 2.5 Transfers to a higher level of care 2.6 Near misses 2.7 Incident reports 2.8 Complaints 2.9 Number of mortalities (= type 4 complication in minimum dataset) Sub-classify as avoidable, unavoidable and expected, unexpected 3 Case details Each readmission, re-operation, ICU readmission, transfer, mortality, type 3 complication and case of interest should be discussed with at least the following information (advise one slide per case): Age and sex Final diagnosis Reason for Readmission/re-operation/ICU readmission/transfer What was done (investigations, procedures etc) Complications, adverse events (with analysis) Outcome 4 What can be done differently? 4.1 Issues/events to report 4.2 Lessons learned 4.3 Recommendations for improvement

Fig. 11.1  Checklist of information, which might be included in a surgical audit presentation (Adapted from [2])

59

60

Fig. 11.2  Fair Dinkum Audit template. Designed by David Watters and accessible from www.surgeons.org

D.A.K. Watters

61

11  Rural Surgical Audit Fig. 11.3  Suggested format for a chairperson’s report of a surgical audit meeting [1, 2]. The report will normally have a row for each issue. The table above is taken from the RACS Surgical Audit and Peer Review Guide [3] and Watters et al. [2]

For Surgical Units OPQ Surgeon(s) ABC Dates Y to Z Chairman Mr H Issue

Effect on patient and hospital

their field are. Vascular surgeons may use limb salvage rates after femoropopliteal bypass rates or stroke rates after carotid endarterectomy. Cardiothoracic surgeons employ mortality, rebleeding and deep sternal infection rates to monitor outcomes. A colorectal surgeon will report outcomes based on mortality, anastomotic leak and unplanned reoperation rates. Death may occur so infrequently in some specialties (e.g. plastic surgery) that mortality rates bear no relationship to performance. Plastic surgeons often use take rates of a split skin graft, or adequacy of excision margins for skin cancers. Appropriate outcome indicators are shown in Table 11.3, which also lists some actual performance results achieved by rural surgeons. It is ideal if surgical outcomes can be classified as either a success or a failure. When this can be done, cumulative summation (CUSUM) analysis can be applied to give visual feedback on performance (Fig.  11.4). CUSUM involves a time plot of attempts against an agreed binary target. Cumulative failure means that each failure is recorded as an upstroke on a cumulative failure chart where the horizontal axis is number of attempts (procedures) and the vertical axis records failures; a success is recorded as a horizontal line. CUSUM and cumulative failure charts are visual and useful for feedback to surgeons, units and services on performance. They measure variation in small samples and allow for early detection of small aberrations, natural variations and procedural performance trends (Fig. 11.5) [13, 14].

11.4.1 Complications Complications should be graded according to their effect on the patient. Grade 1 complications are those that have little effect on the patient and do not significantly delay discharge from hospital. They include

Recommendation

Action by whom and when

Final outcome of report

wound erythema, postoperative retention that responds to catheterisation and trial of void, minor fluid and electrolyte derangements. Grade 2 complications are those that prolong postoperative stay or cause the patient ­significant suffering. Examples include a scrotal haematoma after inguinal herniorrhaphy, major wound infection, pneumonia and deep venous thrombosis. Grade 3 complications include those that require major intervention such as radiological drainage (for a collection), nutritional support (for prolonged ileus or intestinal fistula to be treated conservatively), and cardiac stenting. Unplanned reoperations, or ICU admission are other examples. Death is a Grade 4 complication. An alternative is the Clavien Classification of surgical complications, which has five grades (Table 11.2). Grade 1 complications are minor and include wound infections opened at the bedside. Blood transfusion and TPN are included under Grade 2 together with other complications requiring pharmacological treatment. Grade 3 requires surgical, endoscopic or radiological intervention. Grade 4 requires ICU care for a lifethreatening complication and single organ (4a) or multiorgan (4b) failure. Death is a Grade 5 complication.

11.4.2 Adverse Events and Incidents An adverse event is defined as unintentional harm (to the patient) arising from an episode of healthcare and not due to the disease process itself. Surgical adverse events include unplanned reoperation, unplanned readmission, medication errors and side effects, falls, pressure ulcers, hospital acquired infection and inadvertent injury during surgery. Adverse events occur in around 10% of general surgical cases. The rates vary between specialties. Adverse events need to be reported through both a hospital incident reporting system and through surgical audit. Each adverse event can be graded using

62

D.A.K. Watters

Table 11.3  Key performance indicators for rural surgery Specific procedures Performance indicator

Expected result (derived from consensus or literature)

Actual results (reported by Rural craft Group Audit or SCARS)

Thyroid surgery

Recurrent laryngeal nerve palsy (requires pre- and postoperative cord visualisation)

<2% permanent, <5% temporary

Long-term results not available, temporary palsy = 1.5%

Total thyroidectomy

Hypoparathyroidism

Permanent < 5%

Long-term results not available

Temporary < 30%

Temporary = 17%

Elective laparoscopic cholecystectomy

Bile leak rate prolonging stay (>48 h)

<5%

1.2%

Elective lap cholecystectomy

Bile leak requiring intervention

<2%

1%

Elective lap cholecystectomy

Conversion after elective surgery

<5–10%

6.7%

Elective lap cholecystectomy

Unplanned ERCP after completing cholecystectomy laparoscopically

<2%

0.6%

Elect Lap Chole

Bile duct injury

<1%

0.4%

Colorectal resection

Anastomotic leak after elective resection

<3%

3/136 Anterior 1/135 Right

Colorectal resection

Mortality after elective surgery

<3%

1/136 Anterior SCARS: 2.8%

Colorectal resection

Mortality after emergency surgery

<10%

SCARS 8.3%

Breast cancer surgery

DCIS and no axillary surgery

>90%

Not reported

Breast cancer surgery

Invasive cancer with axillary staging surgery

>90%

Not reported

Breast cancer surgery

Referral for radiotherapy after breast conservation surgery for invasive cancer and DCIS

>85%

Not reported

Breast cancer surgery

Offering or prescribing hormonal treatment for oestrogen receptor positive tumours

>85%

Not reported

Breast cancer surgery

Clear margins for breast conserving surgery invasive cancers and DCIS

>95%

Not reported

Inguinal hernia repair

Postoperative pain >3/12 requiring referral to a pain clinic

<3%

Not reported

Inguinal hernia repair

Scrotal haematoma

<2%

0.6%

The SCARS project was a voluntary audit of 877 colorectal operations by 67 rural and regional surgeons. The Rural Craft Group Audit in Australia has amassed over 3,000 cases for inguinal hernia, thyroidectomy, cholecystectomy and colorectal and breast cancer surgery. The presence of more than two comorbidities raised the overall mortality (elective and emergency) from 4.6% to 16.4% [16]

a Severity Assessment Code (Fig. 11.6) on the basis of its effect on the patient or hospital service, and the likelihood of it recurring. Adverse events require honest and frank discussion with patient and/or their family. Patients who have suffered unintentional harm deserve to have their suffering

acknowledged with empathy, and apology should be offered without necessarily admitting any fault. Adverse events offer an opportunity to improve the system of healthcare if the response to their occurrence is positive. They require investigation in an atmosphere of ‘noblame’ with engagement of the major stakeholders.

63

11  Rural Surgical Audit 10

8

6 Cumulative Failure

Fig. 11.4  (a, b) CUSUM and cumulative failure chart for vocal cord palsy after thyroidectomy. On the top the cumulative failure chart (a) shows two permanent vocal cord palsies represented as steps but performance remains acceptable. The corresponding CUSUM chart on the below (b) shows acceptable performance travelling with the two failures represented by the saw teeth. The trend of the performance line is downwards from the horizontal

4

2 0

1

21

41

61 81 101 121 141 161 181 201 221 241 261 281 301 Case number

1

21 41 61 81 101 121 141 161 181 201 221 241 261 281 301 Case number

−2 −4 0.5 0 −0.5

CUSUM

−1 −1.5 −2 −2.5 −3 −3.5 −4

Limited Adverse Occurrence Screening of healthcare (LAOS) was introduced in a rural hospital to identify opportunities to improve the system. Alan Wolff and Jo Bourke [15] were able to demonstrate reduced adverse outcomes by reviewing and responding to unplanned readmissions, prolonged length of stay, mortalities and return to theatre. The technique could be replicated in any rural hospital. A sentinel event is defined as ‘a relatively infrequent, clear-cut event that occurs independently of a patient’s condition; it commonly reflects hospital systems and process deficiencies’. Sentinel events are catastrophic and include operating on the wrong site or side, retained swabs or instruments after ­surgery, ABO incompatibility and gas embolism. At hospital and department of health level, they require early reporting (within days), detailed investigation, often with root cause analysis, and verifiable system changes.

11.5 Rural Surgical Craft Group (Australia) The ability to provide evidence of performance has driven the rural and regional surgeons of Australia to establish their own database. Commonwealth of Australia funding was obtained to support surgical audits in a number of regional and remote centres. Over 3,000 operations and their outcomes were entered during the first two phases of the project and a third phase is ongoing. The findings have confirmed the ­earlier results of SCARS for colorectal surgery – that rural and remote surgeons have acceptable outcomes (Table  11.3). There will always be some cases that should be referred to a specialist centre, for example low rectal cancers. It is to be hoped that the performance of rural surgeons will be measurable (and so defendable) by being able to compare their results with the database and so compare with ‘known standards’.

64

a

D.A.K. Watters

b

Cumulative failure graph

8

Cusum graph

10

5

4 2

Cusum

Cumulative failure

6

0

0

–2

–5

–4 –6

0

10 Attempt number

20

–10

0

10 Attempt number

20

Probably acceptable Definitely acceptable Probably unacceptable Definitely unacceptable

Fig. 11.5  (a, b) CUSUM and cumulative failure plots for anastomotic leak after the last 20 large bowel procedures. Cumulative failure graph (left) showing possibly unacceptable performance in colorectal surgery anastomotic leak rate. The corresponding

CUSUM graph on the right shows a tendency to rise rather than drop below the line. This particular surgeon reflected on their performance and subsequently had much fewer anastomotic leaks, indicative of the value of feedback on performance

Event classification Consequences/ISR Catastrophic (1)

Major (2)

Moderate (3)

Minor (4)

Almost certain

1

1

1

3

Likely

1

1

2

3

Occasional

1

2

3

4

Unlikely

2

2

3

4

Rare

3

3

3

4

Likelihood

Fig. 11.6  Classification of incidents and adverse events Reporting incidents into an incident reporting system such as RiskMan is assisted by grading the injury severity which is based on its effect and likelihood of recurrence. Hospital risk registers enable management to prioritise and formulate strategies to address the most important risks

ISR = Injury Severity Risk

11  Rural Surgical Audit

65

11.6 Conclusion

Comorbidity Index predicted in-hospital mortality. J. Clin. Epidemiol. 57, 1288–1294 (2004)   6. Dindo, D., Demartines, N., Clavien, P.A.: Classification of surgical complications. Ann. Surg. 240, 205–213 (2004)   7. Watters, D., Green, A., van Rij, A.: Requirements for trainee logbooks. ANZ J. Surg. 76(3), 181–184 (2006)   8. Watters, D.A., Knight, R.E.: Isolated specialists: how many procedures do they need to carry out and how do we measure whether they are competent? ANZ J. Surg. 78(9), 731–732 (2008)   9. Dundee, P.E., Chin-Lenn, L., Syme, D.B., Thomas, P.R.: Outcomes of ERCP: prospective series from a rural centre. ANZ J. Surg. 77, 1013–1017 (2008) 10. Bowles, T.A., Sanders, K.M., Colson, M., Watters, D.A.: Simplified risk stratification in elective colorectal surgery. ANZ J. Surg. 78, 24–27 (2008) 11. Copeland, G.P.F.A.U., Jones, D.F.W., Walters, M.: POSSUM: a scoring system for surgical audit. Br. J. Surg. 78, 355–360 (1991) 12. Tekkis, P.P., et al.: Development of a dedicated risk-adjustment scoring system for colorectal surgery (colorectal POSSUM). Br. J. Surg. 91, 1174–1182 (2004) 13. Bowles, T., Watters, D.: Time to CUSUM: simplified reporting of outcomes in colorectal surgery. ANZ J. Surg. 77(7), 587–591 (2007) 14. Yap, C., Colson, M., Watters, D.: Cumulative sum techniques for surgeons: a brief review. ANZ J. Surg. 77(7), 583–586 (2007) 15. Wolff, A.M., Bourke, J., Campbell, I.A., Leembrugen, D.W.: Detecting and reducing hospital adverse events. Med. J. Aust. 174, 621–625 (2001) 16. Birks, D.M., Gunn, I.F., Birks, R.G., Strasser, R.P.: Colorectal surgery in rural Australia: SCARS; a surgeonbased audit of workload and standards. ANZ J. Surg. 71, 154–158 (2001)

The principles of surgical audit are the same wherever a surgeon is based. The challenges of peer review can be overcome even by isolated practitioners. Rural Surgeons in Australia and New Zealand have demonstrated their willingness and ability to participate in craft group audit. The data so far accumulated suggests that rural performance is more than satisfactory. Userfriendly tools to assist with data collection and presentation have been developed.

References   1. Royal Australasian College of Surgeons.: Surgical audit and peer review guide, 3rd edn. Melbourne, Australia. Available from www.surgeons.org (2008)   2. Watters, D., Green, A., van Rij, A.: Guidelines for surgical audit in Australia and New Zealand. ANZ J. Surg. 76(1–2), 78–83 (2006). Review   3. Royal Australasian College of Surgeons.: Continuing ­professional development information manual 2007–2009, Melbourne, Australia. Available from www.surgeons.org (2006)   4. Elixhauser, A., Steiner, C., Harris, D.R., Coffey, R.M.: Comorbidity measures for use administrative data. Med. Care 36, 8–27 (1998)   5. Sundarajan, V., Henderson, T., Perry, C., Muggivan, A., Quan, H., Ghali, W.A.: New ICD-10 version of the Charlson

 

Acute Pain Management

12

Edmund A.M. Neugebauer, Astrid Althaus, and Christian Simanski

Pearls and Pitfalls

›› Pain management is an interdisciplinary task

›› Sufficient pain management is a prerequisite

›› ›› ›› ›› ›› ››

››

for enhanced patient recovery and for a ­reduction in postoperative morbidity and mortality. Pain assessment and documentation (‘fifth vital sign’) are fundamental prerequisites for adequate pain management. Opioids remain the fundamental group of analgesic drugs for the treatment of moderate-to-severe pain. Co-analgesics support the action of analgesics but are not sufficient alone for postoperative pain relief. Peripheral nerve blocks have the main advantage of not compromising patient alertness. Local analgesics are very effective in epidural analgesia. Epidural local anaesthetics lead to a decreased incidence of pulmonary infection and complications overall compared with opioids. Treatment of acute pain should be procedurespecific and treatment should be adapted to the measured pain intensity reported by the patient.

E.A.M. Neugebauer (*), A. Althaus, and C. Simanski Department of Medicine, University of Witten/Herdecke, Ostmerheimer Straße 200, 51109 Cologne, Germany e-mail: [email protected]

››

requiring close liaison with all personnel involved in the care of the patient. Use of evidence-based clinical practice guidelines are recommended and should be adapted locally.

Acute pain management is a basic human right (Professor M. I. Cousins, President, Australian and New Zealand College Anaesthetists)

Although major efforts have been taken to improve acute pain management in recent years, we are still far away in meeting this basic human right. In the USA and Europe, the results of studies dedicated specifically to both medical and postoperative patients in academic hospitals have shown unequivocally that pain remains undertreated. Insufficient pain management originates from organizational problems, time constraints in daily clinical routine, little motivation to change daily clinical routine, complexity of pain management, difficulties in assessing pain intensity, and insufficient knowledge of pain management. However, pain should not be an accompanying phenomenon of medical treatments. Adequate techniques (epidural analgesia, epidural catheter, patient-controlled analgesia, etc.) and effective analgesics exist and, in principle, the possibilities for adequate pain management are available to all. An adequate pain therapy is an important prerequisite for enhanced patient recovery, and will reduce the postoperative risk of morbidity and mortality. Moreover, a significant reduction in long-term morbidity can be achieved since moderate-to-severe

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_12, © Springer-Verlag Berlin Heidelberg 2011

67

68

acute pain has been demonstrated as an independent predictor for chronic postoperative pain. Adequate pain therapy is cost-effective; it is associated with a decrease in both intensive care and overall hospital stay. Studies have shown that up to 70% of patients present to the hospital because of acute pain. Furthermore, they associate the success of medical treatment with the relief of pain and it is of significant value from the patients’ perspective. Pain is therefore considered an ideal parameter for the evaluation of the quality of in-hospital care.

12.1 Definitions Pain, as defined by the International Association for the Study of Pain, is ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’. Pain is subjective and is an individual, multifactorial experience influenced by culture, previous pain events, mood, beliefs, and an ability to cope. Acute pain is defined as ‘pain of recent onset and probable limited duration’. It usually has an identifiable temporal and causal relationship to injury (trauma, operation) or disease (colic, peritonitis, etc.). Chronic pain persists commonly beyond the time of healing of an injury (>3–6 months) and frequently has no clear identifiable cause. Acute and chronic pain may represent a continuum.

E.A.M. Neugebauer et al.

Spinal cord level: Once transducted into electrical stimuli, conduction of neuronal action potentials into afferent input and dorsal horn outputs follows. This signal conduction is called transmission in the spinal cord. The processing of pain on its way from excitation to perception is subject to several transformations. Tissue damage such as that associated with infection, inflammation, or ischemia, produces an array of chemical mediators (algetic substances such as prostaglandins, histamine, etc.) which can sensitize nociceptors to increase pain perception. This increase in sensitivity is termed peripheral sensitization, which can also lead to central sensitization. In addition to the excitatory processes, inhibitory modulation occurs within the dorsal horn. Central projecting level: A peripheral pain signal which reaches the central nervous system after transduction, transmission, and transformation needs to be translated into pain perception. The areas of the brain involved are the limbic system, cortex (e.g., cingulate cortex, insula, prefrontal cortex), and thalamus. The perception and experience of pain is multifactorial and is further influenced by psychological and environmental factors of each individual. Figure 12.1 gives a schematic representation of the nociceptor pathway.

Pain perception and experience

Cortex thalamus

Transformation

12.2 Pathophysiological and Pharmacological Basics Pain development and transduction involves multiple interacting peripheral and central mechanisms. The understanding of principles is important for the choice of medical treatments, and will therefore be summarized briefly. The basis of each central nervous system function is the excitation–response relationship. Peripheral level: Acute pain starts by tissue injury caused by mechanical, thermal, or chemical excitation. The detection of noxious stimuli requires activation of peripheral sensory organs (nociceptors) and transduction of the energy into electrical signals for conduction to the central nervous system. Nociceptive afferents are distributed widely throughout the body (skin, muscle, joints, viscera, meninges).

Sympatic conduction and modulation

Spinal cord

Transformation Actions potentials Transmission Receptor potentials Transduction Mechanical, thermal, chemical stimuli

Fig. 12.1  Schematic representation of the nociceptor pathway

69

12  Acute Pain Management

12.3 Analgesic Drugs For adequate pain management, it is necessary to be familiar with the main mechanisms of pain relief by the different analgesic drugs. Analgesic drugs can be subdivided into five major categories (Table 12.1).

12.3.1 Non-opioid Analgesics The basic action of most non-opioids (nonsteroidal anti-inflammatory drugs – NSAIDs) is the inhibition of the cyclooxygenase (COX) enzymes. Two subtypes of COX enzymes have been identified – the constitutive COX-1 and the ‘inducible’ COX-2, and now a COX-3 is being investigated. Many of the effects of NSAIDs can be explained by inhibition of prostaglandin synthesis in peripheral tissues, nerves, and the central nervous system. Prostaglandins have many physiological

functions including gastric mucosal protection, renal tubular function, intrarenal vasodilatation, bronchodilatation, and production of endothelial prostacyclin. Such physiological roles are mainly regulated by COX-1 and are the basis for many of the adverse effects associated with NSAID use. Tissue damage results in COX-2 ­production, leading to synthesis of prostaglandins that result in pain and inflammation. NSAIDs are nonselective COX inhibitors that inhibit both COX-1 and COX-2 with a wide spectrum of analgesic, anti-inflammatory, antipyretic effects. Aspirin acetylates inhibit COX irreversibly but NSAIDs are reversible inhibitors of enzymes. The COX-2 inhibitors (e.g., parecoxib) have been developed to inhibit selectively the inducible form. Arylacid derivatives (diclofenac) and aryl propionic derivates (ibuprofen) are nonselective COX-inhibitors. Para­cetamol (acetaminophen) and metamizol have additional central effects. A combination of paracetamol and NSAIDs has additive effects on postoperative analgesia. Figure 12.2 illustrates the nociceptive pathway and therapeutic options of pain relief.

Table 12.1  Categories of analgesic drugs

• Non-opioids • Opioids

12.3.2 Opioids

• Local anaesthetics

Opioids remain the central group of analgesic drugs for the treatment of moderate-to-severe acute pain and transmit their action via different types of receptors.

• Co-analgesics • Adjuvant drugs

Fig. 12.2  Nociceptive pathway and therapeutic options of pain relief

Hypothalamus/thalamus limbic system

Opioids/antidepressants (colitis, crohn, surgery of carcinoma)

Cortical translation

Opioids (thorax/esophageal/pancreas operations)

Spinal cord/brainstem

Non-opioids (in combination with COX-inhibitors in major operation, i.e., colon)

Afferent nerve conduction

Local anesthetics (inguinal hernia repair)

Nociceptor

COX-Inhibitors, NSAID’s (basic medication)

70

Opioids can be differentiated into pure m-agonists (morphine, oxycodone, fentanyl, tramadol), mixed agonists–antagonists (antagonistic at m-receptors and agonistic at k- and s-receptors, e.g., pentazocine, tilidine), partial agonists with high affinity and small intrinsic activity at m-receptors (buprenorphine), and pure antagonists (at m-, k-, and s-receptors) such as naloxone. The opioid receptors are located mostly at structures that are involved in transmission, transformation, and translation of afferent signals. A high density is found in the limbic system, the thalamus, the pons region, and the substancia gelatinosa in the dorsal horn. Clinically meaningful side effects are doserelated; once a threshold dose is reached, every 3–4 mg increase of morphine-equivalent dose per day is associated with one additional adverse event. The most significant adverse effects are sedation, pruritus, nausea, and vomiting. The risk can be reduced significantly by parallel application of NSAIDs and/or adjuvant drugs. In the management of acute pain, one opioid is not superior to others but some opioids appear more effective in some patients than others.

12.3.3 Local Anaesthetics Local anaesthetics exert their effects as analgesics by impeding neuronal excitation and/or conduction. Shortduration local anaesthetics (lignocaine, plasma half-life 90  min) have to be differentiated from long-duration local anaesthetics (bupivacaine, ropivacaine). The local anaesthetic effect primarily depends on the site of administration, the dose administered, and the presence or absence of vasoconstrictors. Local application of 20 ml 0.25% bupivacaine in the area of trocar incision sites in laparoscopic cholecystectomy or colectomy reduces significantly postoperative pain intensity. Local anaesthetics are very effective in epidural analgesia. The quality of pain relief from low-dose epidural infusion (bupivacaine 0.1%, ropivacaine 0.2%) is improved consistently from the addition of adjuvants such as ­opioids. The concept of fast-track recovery benefits most from the application of an epidural.

E.A.M. Neugebauer et al. Table 12.2  Co-analgesics and their main functions Antidepressant

Increase function of inhibitory transmitter (e.g., serotonin, noradrenalin, i.e., aminotryptiline)

Anticonvulsive

Supportive in neuropathic pain syndro­ mes (e.g., carbamacepine, gabapentin)

Muscle relaxant

Supportive in muscle pain and spasms (e.g., benzodiazepine)

Corticosteroid

Anti-inflammatory (e.g., dexamethasone)

Bisphosphonate

Supportive in bony pain syndromes after metastasis of tumours (e.g., clodronate, pamidronate)

However, they are extremely helpful in combination with opioids and NSAIDs, and can reduce postoperative analgesic requirements. Adjuvant drugs are mainly used to decrease side effects of analgesic drugs such as emesis, vomiting, and constipation. Co-analgesics can be classified as follows (Table 12.2): Antidepressants decrease the awareness of pain and enhance the functioning of inhibiting neurotransmitters (serotonin, noradrenalin). Beside their antidepressant effect, they also have analgesic properties. Anticonvulsants: Carbamazepine, clonazepam and gabapentin are the most common agents used in the treatment of neuropathic pain. Tonicity reducing medication (i.e., benzodiazepines) is used in the treatment of painful muscle tension and spasm. The mode of action of most substances remains unknown. Corticosteroids inhibit the formation of cytokine, leukotriene, prostaglandin and macrophage activating interferon-g, and suppress the formation of inflammatory processes. Bisphosphonates have a repressive effect on bone absorption and are particularly used in the therapy of bone pain and osteolytic bone metastasis. Adjuvants can be divided into antiemetics and lax­ atives and are used to manage anxiety and side eff­ects of analgesic therapy, i.e., nausea, vomiting, and constipation.

12.3.4 Co-analgesics and Adjuvant Drugs

12.3.5 General Pain Management

Co-analgesics support the action of analgesics but are not sufficient alone for postoperative pain management.

The surgeon has a special responsibility in the treatment of pain. Aside from pharmacological interventions,

71

12  Acute Pain Management

consideration should be given to the possibility of intervention before, during, and after surgery to optimize pain management. All procedures should be performed under the philosophy of avoiding pain wherever possible (minimal invasive techniques, positioning, etc.). Drains should be avoided and wound closure should be performed preferably with absorbable sutures. Postoperatively, a whole array of preventive measures should be considered with respect to reducing pain and associated complications: early rehabilitation (fasttrack), wound management, physio­therapy, cold/heat, massage techniques, and removal of lines and drains as soon as possible.

but with adhesive tape. The patient’s position while being operated can also influence the emergence of postoperative pain; patients, who are operated in a dorsal position, i.e., abdominal operations, have less postoperative pain in the back if they have a pillow beneath their knees during the treatment. During prolonged operations, it is mandatory to put the patient in a position that avoids pressure on exposed body parts because this might lead to nerve damage or a compartment syndrome with additional pain (head of the fibula, sulcus ulnaris on the elbow, popliteal fossa during lithotomy position).

12.5 Intraoperative Interventions 12.4 Preoperative Interventions Preoperatively, the surgeon has to provide evidencebased information to the patient regarding the type of disease, available treatment options, and procedurerelated postoperative pain management. The information about possible upcoming pain should neither evoke unrealistic expectations nor fear. Adequate procedural information can reduce anxiety and has an advantageous influence on the patient’s pain assessment. The knowledge about the possibility to influence the pain sensation in a positive way enhances the pain tolerance and this in turn reduces the use of analgesics. By contrast, insecurity about the operation and possible upcoming pain can increase the fear of the operation. A high level of anxiety and unrealistic beliefs can in turn increase postoperative pain. The placebo-effect plays an important role, and should be used within the frame of positive and realistic information. Patient information and training regarding coping and relaxation strategies have been shown to reduce pain and distress. The patients should be convinced that their pain is of utmost importance to the treating team and that they can also contribute to the success of pain management (patient as partner/co-therapist). Information about the different possible pain therapies need to be adapted to the patient’s experiences. The patient needs to be informed about side effects and alternative pain treatments. Smaller interventions and wound care should be done using local anaesthetics. If children are treated, a sufficient wound adaptation can be achieved without a needle

Intraoperatively, the choice of the operative procedure and of the access is essential to reduce postoperative pain. Minimal invasive operative procedures have been established especially for operations of the appendix, gallbladder, groin hernia, and colon and constitute well-validated methods with significantly less post­ operative pain than the conventional procedures. Transversal incisions cause less pain than vertical ­incisions in laparotomies, and skin incisions via diathermy cause less pain than the conventional scalpel. Further ­pos­sibilities to reduce pain can be achieved by defining strict indications for the usage of drains and tubes. Usually, it  can be abstained from placing subcutaneous suction drains. Suture material can also influence postoperative pain. Absorbable sutures avoid painful removal.

12.6 Postoperative Interventions Surgeons can alleviate postoperative pain by using ­adequate bandages. Very tight or unneeded bandage have to be avoided. Tuberosities need sufficient cushioning when orthotics or orthopaedic casts are applied. The early mobilization of patients with the assistance of nursing staff or physiotherapists can help to avoid postoperative complications. By means of a stepwise augmentation of exposure and sufficient analgesia, excessive demands can be avoided. Newer ‘fast track concepts’ schedule the patient’s mobilization to a chair already 5 h after the operation. Physical treatment and adjuvant medications can be used in addition to alleviate pain.

72

If catheters, drains, and tubes are not needed anymore, they should be removed immediately. Analgesia can decrease physiologic reactions to surgical complications (fever, muscular defence). Thus, the surgeon has to be informed about increasing pain and use of analgesics.

12.7 Medical Interventions 12.7.1 Peripheral Nerve Blockade The main advantage of using peripheral nerve block techniques as compared to systemic drug therapy (see below) is that the use of local anaesthetics does not compromise patient alertness and allows pain-free mobilization. Peripheral nerve blocks may be used for diagnostic and therapeutic purposes. Important technical issues include the technique of nerve location, the type of catheter equipment, the amount of drug, and the duration of drug efficacy. Following localization of the nerve, a continuous block can be initiated. Local anaesthetics such as lidocaine, mepivacaine, or prilocaine are effective for 2  h whereas bupivacaine and ropivacaine can produce pain relief for up to 12  h. Adjuvant techniques may prolong the duration of action. For example, wound infiltration with a longacting local anaesthetic agent provides effective analgesia following inguinal hernia repair but not for open cholecystectomy or hysterectomy. Continuous femoral nerve blockade provides postoperative analgesia and functional recovery superior to intravenous morphine with fewer side effects and comparable to epidural analgesia following knee joint replacement surgery. Both single injection and continuous application carry the risk of neurological injury, intravascular injection, dislodgment, haematoma, and infection. The incidence of neurological injury following peripheral nerve blocks is 0.02–0.4%.

12.7.2 Epidural Analgesia Epidural analgesia (i.e., the provision of pain relief by continuous administration of pharmacological agents into the epidural space via an indwelling catheter) has

E.A.M. Neugebauer et al.

become a widely used technique for the management of acute pain after surgery and trauma. Regardless of the analgesic agent used, location of catheter, or the type of surgery, it provides better pain relief than parenteral opioid administration. Improved pain relief with epidural local anaesthetics leads to a decreased incidence of pulmonary infection and other pulmonary complications overall when compared with systemic opioids. The combination of a low concentration of local anaesthetic and opioid is superior to either of the drugs alone. The addition of small amounts of adrenaline (epinephrine) to such mixtures improves analgesia and reduces systemic opioid consumption. Administration of a local anaesthetic into the thoracic epidural space results in improved bowel recovery, while this benefit cannot be observed with lumbar drug administration. Adverse effects are uncommon but include permanent neurological damage, which is reported at 0.05–0.0005%, and epidural haematoma (0.0005%). Others include respiratory depression (1–15%) and hypotension (5–10%).

12.7.3 Systemic Analgesia Necessary prerequisites for patient-orientated systemic pain therapy are good knowledge and understanding of the cause of pain (inflammatory, spasm, type of operation or operative access, anxiety, or depression of the patient), the anatomy and pain transduction, and, based on this information, the necessary surgical, physical, psychological, or medical therapy. Whereas chronic pain treatment starts with non-pharmacological techniques (psychotherapy, TENS, etc.) followed by mild non-opioid analgesics, and, subsequently, strong opioids, the treatment of acute pain follows the reverse order (Fig. 12.3). Strong opioids combined with NSAIDs are used as first-line therapy to control pain when intensity is highest. Analgesic drugs given by the intravenous route have a more rapid onset of action compared with most other routes of administration. Titration of opioid therapy for severe acute pain is best achieved using intermittent intravenous bolus doses (2–3 mg of morphine at 5 min intervals until relief of pain). Relative or absolute overdosing (also rapid injection) may lead to complications and side effects independent of the opioid used. However, the risk of overdosing with resultant respiratory depression is not

73

12  Acute Pain Management “Reversed” WHO-pain ladder for acute pain therapy (Non-opioids always as basic medication) Strong opioids Moderate opioids Non-opioids

WHO pain ladder for chronic pain therapy Strong opioids Moderate opioids Non-opioids

Fig.  12.3  WHO pain ladder of acute and therapeutic pain therapy

an issue as long as the patient continues to experience pain. If it occurs, sufficient antagonists (naloxon 0.4 mg) should always be available and the sedation level should be assessed in parallel. Continuous infusion of opioids in the general ward setting is not recommended because of the increased risk of respiratory depression compared with other methods of parenteral opioid administration. Non-opioid analgesics have an antipyretic and antiinflammatory effect. They should be administered either solely (such as after minor operations) or in combination with opioids. Opioid and non-opioid drugs can be administered systemically by a number of different routes. The choice of route is determined by various factors including the overall condition of the patient but also by the ease of use, accessibility, speed of analgesic onset, duration of action, and patient acceptability. In general, the principle of individualization of dose and dosing intervals should apply to the administration of all analgesic drugs, whatever the route. Frequent assessment of the patient’s pain and their response to treatment rather than strict adherence to a given dosing regimen is required if adequate analgesia is to be obtained. Oral administration is straightforward, noninvasive, has good efficacy in most settings, and has a high patient acceptability. Other than in the treatment of severe

acute pain, it is the route of choice for most analgesic drugs provided that there is no contraindication to its use. After major operations or trauma, the aim should be to change to the oral route as quickly as possible. The analgesic efficacy varies from one pain model to another and the administration of analgesics should be procedure-specific. Although still used commonly, intramuscular injection of analgesic agents is no longer recommended because of the significant risk of abscess formation, nerve lesions, and necrosis. Subcutaneous injection shares the same problem as intramuscular administration that absorption may be impaired in situations of poor perfusion. This leads to inadequate early analgesia and late absorption of the drug depot when perfusion is reestablished. Rectal administration of drugs is useful when other routes are unavailable. Transdermal routes for opioid administration (fentanyl or buprenorphine patches) are not recommended for acute pain management due to safety concerns (respiratory depression) and the difficulties in short-term dose adjustments that may be required for titration. The general rule is that the patient should determine their analgesic requirement within given limitations for all routes of administration. Patient-controlled analgesia (PCA) refers to methods of pain relief that allow the patient to self-administer small doses of an analgesic agent as required. This is not necessarily associated only to the use of programmable infusion pumps. Adequate analgesia needs to be obtained prior to commencement of PCA. Initial instructions for bolus doses should take into account individual patient factors such as history of prior opioid use and patient age. Individual prescriptions may need to be adjusted and drug concentrations should be standardized within each institution to reduce programming errors. A background infusion is not recommended in acute pain management.

12.8 Non-medical Interventions Regarding severe postoperative pain pharmacological treatment is the first-line therapy. This can be complemented by nonmedical interventions including special nursing and physiotherapeutic techniques, psychological interventions, acupuncture, and contra-irritation techniques. All these procedures not only feature little or no side effects, but also provide the patient with attention and personal care.

74

12.8.1 Nursing and Physiotherapy Within the postoperative therapy procedures such as general mobilization (exercises in bed, helping the patient to get up and walk around), demonstration of rather pain-free motion sequences, pain-free breathing and coughing techniques, tension-release techniques, active or passive motion exercises, techniques of massage, and special positioning of the patient should always be considered. Postoperative cooling therapy is advisable after orthopaedic surgical treatment. A recently conducted meta-analysis including six randomized studies revealed a significant analgesic effect in favour of patients who were treated with cooling after an arthroscopic cruciate ligament repair compared to the control group. In body areas with poor blood supply, for example, in vascular surgical patients, however, a cooling therapy is contraindicated.

12.8.2 Psychological Interventions Preoperatively, a combination of different cognitivebehavioural strategies has been proven to reduce pain and anxiety. Psychological interventions should also be integrated in the postoperative pain management; their efficacy is well-validated not only in the treatment of chronic pain but also in the therapy of acute pain. Cognitive-behavioural techniques as distraction, cognitive revaluation, and positive visualization have turned out to alleviate pain. Other strategies as imagination techniques, hypnosis, and relaxation exercises can reduce the degree of postoperative pain and the use of analgetics. Cognitive-behavioural techniques within the preoperative setting are not time-consuming and can be implemented promptly after the operation.

E.A.M. Neugebauer et al.

effects have been demonstrated after meniscus operations, thoracotomies, and shoulder joint operations.

12.8.4 Acupuncture Acupuncture has been proven to be effective and ­efficient in the treatment of certain chronic pain ­syndromes, whereas in postoperative pain high level evidence is still missing. In total hip replacement and arthroscopic shoulder joint surgery the use of analgetics was reduced by applying acupuncture. Regarding postoperative side effects (nausea, vomiting), a metaanalysis revealed a significant effect of P6 acupuncture compared to the application of fake acupuncture.

12.9 Assessment and Documentation of Acute Pain Pain assessment and documentation are fundamental prerequisites for adequate pain management. Regular assessment leads to improved pain management. Under routine clinical conditions, measurement of pain intensity is sufficient and should be performed by visual analogue or numerical rating scales. Self-reporting of pain should be used whenever appropriate as pain is by definition a subjective experience. In the pre- and postoperative setting scoring should include static (rest) and dynamic (pain on sitting, coughing) measurements at least two times a day and following treatment of pain to determine efficacy. The score should be documented in the patient’s charts as the ‘fifth vital sign’. Uncontrolled or unexpected pain requires reassessment of the diagnosis and consideration of alternative causes for pain.

12.8.3 Contra-Irritation Techniques

12.10 Organization of Acute Pain Management

The contra-irritation technique is based on the ­gate-control theory. After certain kinds of operations the additional application of a transcutaneous elec­trical nerve stimulation (TENS) with an intensity below the pain threshold (15  mA) can reduce the ­postoperative pain intensity as well as the need for analgetics. Positive

Pain management is an interdisciplinary undertaking. Successful management of acute pain requires close liaison with all personnel involved in the care of the patient and should include surgeons, anaesthesiologists, and nurses. Effective acute pain management will only result from appropriate education and organizational structures

75

12  Acute Pain Management

for the delivery of pain relief. Clear-cut responsibilities between disciplines are mandatory and this may differ between countries or even hospitals. Effective organizational structures for the delivery of pain relief are often more important than the anal­gesic techniques themselves. In some institutions, acute pain services (APS) are responsible for managing more advanced methods of pain relief such as PCA and ­epidural analgesia. There is a wide diversity of APS structures (from low-cost nurse-based through to multidisciplinary services) with different responsibilities. A recent review of publications analyzing the effectiveness of APS concluded that its implementation is associated with a significant improvement of pain relief with a possible reduction of postoperative nausea and vomiting. Marked improvements in conventional methods of pain relief can be expected by the introduction of evidence-based clinical practice guidelines. However, it is the implementation of guidelines and not their development which remains the greatest obstacle to their use. Professional bodies in a number of countries have published guidelines for the management of acute pain. A procedure-specific approach is highly recommended such as the online PROSPECT group (www.postoppain.org). Resource availability, staff with pain management expertise, and the existence of formal quality assurance programmes to monitor pain management are positive predictors of compliance with guidelines. Official guidelines need to be adapted for individual hospital requirements and the ward nurses play the most significant role in local adaptation. With their support, and that of clinical management and directors of surgical departments, we have been successful in translating national guidelines on acute pain management into the ‘Initiative Pain Free Clinic’. The Cologne City Hospital Merheim was the first in Germany to receive board certification by an external organization. This initiative served as a role model for other hospitals in

improving the organization of acute pain management with resultant benefit to the patients and the hospital.

Recommended Reading American Society of Anesthesiologists: Practice guidelines for acute pain management in the perioperative setting. An updated report by the American Society of Anesthesiologists Task Force on acute pain management. Anesthesiology 100, 1573–1581 (2004) Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine: Acute pain management: scientific evidence, 2nd edn. National Health and Medial Research Council. http://www.nhmrc.gov.au/publications/subjects/clinical.htm (2005) Ballantyne, I.S., Carr, D.B., de Ferranti, S., et al.: The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials. Anaesth. Analg. 86, 598–612 (1998) Kehlet, H.: Multimodal approaches to control postoperative pathophysiology and rehabilitation. Br. J. Anaesth. 78, 606– 617 (1997) Kehlet, H., Gray, A.W., Bonnett, F., et al.: A procedurespecific systematic review and consensus recommendations for postoperative analgesia following laparoscopic cholecystectomy. Surg. Endosc. 19, 1396–1415 (2005) Neugebauer, E.: Initiative Schmerzfreie Klinik: (k)eine vision. Schmerz 19, 557 (2005) Laubental, H., Neugebauer, E., et al.: The German guidelines on the treatment of acute perioperative and posttraumatic pain. www.leitlinien.net-AWMF0041 Neugebauer, E., Hempl, K., Sauuerland, S.T., et al.: Situation der perioperativen Schmerztherapie in Deutschland: Ergebnisse einer reprasentativen, anonymen Umfrage von 1000 chirurgischen. Kliniken Chirurg 69, 461–466 (1998) Veterans Health Administration D.o.D.: Clinical practice guideline for management of postoperative pain. http://www.oqp. med.va.gov/cqg/PAIN/PAIN_base.htm (2002) Werner, M.U., Søholm, L., Rotbøll-Nielssen, P., et al.: Does an acute pain service improve postoperative outcome. Anaesth. Analg. 95, 1361–1372 (2002) Zhao, S.Z., Chung, F., Hanna, P., et al.: Dose-response relationship between opioids use and adverse effects after ambulatory surgery. J. Pain Symptom Manage. 28, 35–46 (2004)

 

Prophylaxis of Venous Thromboembolism

13

Robert A. Fitridge and Simon McRae

13.1 Prevention of VTE

13.1.2 Methods of Thromboprophylaxis

13.1.1 Incidence of VTE in Hospitalised Patients

Both mechanical and pharmacological methods of thrombo­prophylaxis have been clearly demonstrated in a number of studies to decrease the risk of DVT and pulmonary embolus (PE), including fatal events, as well as being cost effective. The choice of approach is predominantly determined by the absolute risk of VTE associated with a particular procedure. Generally, pharmacological prophylaxis has been shown to be more effective than mechanical methods alone, with the former reducing the risk of VTE by at least 60–70% in most patient groups.

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in our community, with an annual incidence of 1–2 per 1,000 individuals. ­App­roximately 50% of episodes of VTE are related to recent hospital admission, with an almost equal contribution from surgical and non-surgical patients. Without thromboprophylaxis, the incidence of DVT in hospitalised patients is significant (Table  13.1). As expected, variation is seen between different patient categories, with the incidence highest in patients undergoing major orthopaedic procedures and experiencing major trauma. The reported incidence of VTE is influenced by the method utilised to screen for events. Venography detects all events, including asymptomatic isolated distal DVT, and studies using this method give the highest reported rate. However, the incidence of  clinically significant symptomatic events in most ­studies has been shown to be directly proportional to the venographic incidence of VTE (approximately ­tenfold less).

R.A. Fitridge (*) and S. McRae Department of Surgery, The Queen Elizabeth Hospital, 28 Woodville Rd, Woodville South, SA 5011, Australia e-mail: [email protected], [email protected]

13.1.2.1 Currently Available Methods of DVT Prophylaxis General Measures The importance of general measures such as adequate hydration of hospital inpatients, and early mobilisation while recovering from their illness or surgery should not be underestimated, although these measures have not been extensively studied. Mechanical Methods Mechanical methods include graduated compression stockings (GCS), intermittent pneumatic compression devices (IPC) and venous foot pump (VFP). The most obvious advantage of mechanical prophylaxis over pharmacological methods is that there is no increased risk of bleeding associated with the former. This is particularly important in patients who are at high risk of bleeding or procedures where post-operatively bleeding is particularly catastrophic, e.g. neurosurgery.

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_13, © Springer-Verlag Berlin Heidelberg 2011

77

78

R.A. Fitridge and S. McRae

Table 13.1  Risk of DVT without prophylaxis Condition Incidence (%) Major abdominal general surgery

15–30

Major trauma

40–80

Stroke

20–50

Patients in high dependency/ intensive care units

30–50

Table 13.2  Forms of DVT prophylaxis General

Early mobilisation Mechanical methods

Pharmacological Methods of Prophylaxis A number of pharmacological methods of VTE prophylaxis are now available. Unfractionated heparin (UFH) has been used for VTE prophylaxis for a number of decades, and is normally given at a dose of 5,000 units of sodium heparin twice or three times daily. Lowmolecular-weight heparin (LMWH) is a chemically or enzymatically modified form of UFH, which is generally given as a once-daily dose. LMWH has been shown to be more effective than UFH for a number of indications including prevention of DVT post major orthopaedic ­surgery, major trauma and ischaemic stroke, and current guidelines reflect these findings. Warfarin is still widely utilised for prophylaxis post major orthopaedic surgery in North America, and can also be used in other patient groups if extended prophylaxis is indicated (Table 13.2).

Graduated compression stockings (GCS) Intermittent pneumatic compression devices (IPC)

Pharmacological methods

The use of IPC devices alone has been shown to be effective in decreasing the risk of VTE in a number of surgical patient groups [1], and therefore, this approach should be utilised in moderate- or high-risk patients in whom anticoagulant therapy is contra-indicated. IPC is also often used as an adjunctive measure in addition to pharmacological methods in patients at particularly high risk of venous thromboembolism, an approach supported by the findings of a recent Cochrane review [2]. A recent systematic review suggested that use of graduated compression stockings results in up to a 50% reduction in all episodes of DVT; however, the data regarding the role of stockings in preventing the more clinically significant proximal DVT was inconclusive. There is ongoing debate about the effectiveness of knee-high GCS in comparison to full-length or thigh-high stockings, with the available data being inconclusive. However, frequent inappropriate application and poor patient compliance with full length stockings may limit their effectiveness in real life.

Adequate hydration

Unfractionated heparin Low-molecular-weight heparin Selective factor Xa inhibitor (Fondaparinux) Warfarin

A number of new antithrombotic agents that selectively inhibit specific activated clotting factors are presently or are soon to become available for use in patients requiring thromboprophylaxis. Fondaparinux is an injectable selective indirect inhibitor of factor Xa that has now been available for some years. Combined data from a number of trials has demonstrated that Fondaparinux is more effective in preventing VTE following major orthopaedic surgery than LMWH, at the expense of a slight increase in bleeding risk which has probably resulted in limited uptake of this agent. Renal clearance is the method of elimination of lowmolecular-weight heparin and Fondaparinux. In a setting of a creatinine clearance of <30 ml/min, a reduction in the calculated dose of low-molecular-weight heparin or Fondaparinux should be considered. Alternative agents should be considered in patients with more marked renal impairment. Due to the frequent age-related decrease in creatinine clearance, particular care should be taken when using these agents in very elderly. Significant interest has surrounded the development of a number of new oral agents likely to be used for both prevention and treatment of VTE. Rivaroxaban is an oral direct factor Xa inhibitor that has been shown to be more effective than the LMWH enoxaparin in preventing VTE following hip and knee arthroplasty, with similar bleeding rates. Dabigatran is an oral direct thrombin inhibitor that appears to be as effective as LMWH in preventing VTE following orthopaedic ­surgery. Both agents have been recently approved in a number of health jurisdictions for the above indications.

79

13  Prophylaxis of Venous Thromboembolism

13.1.3 Inferior Vena Caval Filters There is ongoing debate regarding what constitutes appropriate use of inferior vena cava (IVC) filters. There is general agreement that IVC filter use is appropriate in patients with recent (within 1 month) symptomatic VTE requiring more than brief interruption of therapeutic anticoagulation. All other indications are open to debate, largely due to the lack of evidence for or against their use in other circumstances. Most controversial is the use of filters in trauma patients at high risk of VTE in whom anticoagulant therapy is contraindicated. The availability of temporary IVC filters able to be retrieved has no doubt contributed to the increase in filter use in recent years. However, it is not uncommon for these planned temporary devices to be unable to be retrieved, and clinicians should therefore consider that temporary IVC filters may in fact remain in-situ indefinitely, with their presence associated with a long-term increase in risk of DVT.

13.1.4 Risk Stratification for VTE As mentioned above, the risk of developing VTE can be stratified on the basis of both patient-related ­co-morbidities and procedure-related risks. Table 13.3 summarises these risk factors. Whilst it is possible to assess the risk for an individual patient, a more straightforward approach is to use simplified protocols, risk Table 13.3  Risk factors for venous thromboembolism [3] Patient related

Previous DVT or PE Cancer Immobility, e.g. CVA Oestrogen therapy (HRT or OCP)

stratifying patients primarily on the basis of their planned surgical procedure/or primary underlying medical condition and modify this only if a number of further risk factors are present. Figure  13.1 and Table 13.4 show contemporary protocols for prophylaxis based on risk developed by the ANZ Working Party on the Management and Prevention of Venous Thromboembolism and the American College of Chest Physicians. It is recommended that all health institutions adopt similar guidelines, with or without local modification as appropriate. Risk assessment should be performed in all patients at admission to hospital, if not already done so at surgical pre-assessment.

13.1.5 Current Compliance with VTE Prophylaxis Guidelines A number of studies have demonstrated inadequate adherence to guidelines for provision of VTE prophylaxis. Individuals can be risk stratified regarding their risk of developing DVT or PE on the basis of both patient-related co-morbidities and procedure-related risks. The ENDORSE trial [6] assessed over 68,000 surgical and medical inpatients in 32 countries of whom 45% were categorised as surgical. This study found that 64% of surgical and 42% of medical patients were considered to be at-risk of VTE. However, only 59% of surgical and 40% of medical individuals considered atrisk were receiving appropriate prophylaxis. A number of strategies have been demonstrated to improve the uptake of appropriate prophylaxis protocols, including the use of pre-printed order forms attached to admission bundles, computer reminders, and ongoing audit and feedback [7]. Adherence to VTE prophylaxis protocol guidelines is one appropriate measure for quality of care audit in contemporary surgical practice.

Thrombophilia Obesity Inflammatory conditions, e.g. inflammatory bowel disease Surgical procedure related

Hip, knee, lower limb orthopaedic surgery Laparoscopic surgery Cancer surgery

13.2 Diagnosis of Venous Thromboembolic Events Despite appropriate prophylaxis, there is still a small but definite risk of developing a VTE event during or soon after hospitalisation. Subjective diagnosis of both DVT and PE is often inaccurate, and therefore, an

STEP 1

†Additional VTE Risk Factors immobility, thrombophilia, oestrogen therapy, pregnancy or puerperium, active inflammation, strong family history of VTE and/or obesity.

*Major surgery: intra-abdominal surgery or any surgery > 45 minutes duration

• All other surgery

Fig. 13.1  Surgical VTE prophylaxis guide [4]

R I S K

L O W E R

R • Other surgery with prior VTE and/or active cancer I S K • Major surgery* age > 40 years

• Hip fracture surgery

H • Hip or knee arthroplasty I • Major trauma G H

Assess Patient Risk

Surgical VTE Prophylaxiss Guide

Prescribe: enoxaparin 40mg daily or dalteparin 5000U daily or for orthopaedic surgery fondaparinux 2.5mg daily (commence 6-8 hrs post-op) Duration 5-10 days EXCEPT 28-35 days for hip arthroplasty

Prescribe: enoxaparin 20mg daily or dalteparin 2500U daily or LCUH 5000 BD or TDS Duration 5-10 days

Consider LMWH or LDUH if addtional risk factors † Duration until hospital discharge

YES No anticoagulant

NO

YES No anticoagulant

NO

YES No anticoagulant

Duration 5-10 days EXCEPT 28-35 days for hip fracture surgery

or dalteparin 5000U daily or LCUH 5000 TDS or for hip fracture surgery fondaparinux 2.5mg daily (commerce 6-8 hrs post-op)

NO Prescribe: enoxaparin 40mg daily

YES No anticoagulant

NO

Renal impairment with LMWH - see manufacturer’s product information

Contraindication to anticoagulant prophylaxis Active bleeding / high risk of bleeding eg. haemophilia, thrombocytopenia (platelet count <50 × 10° /L), history of GI bleeding Severe hepatic disease (INR > 1.3) / adverse reaction to heparin On current anticoagulation Other eg. very high falls risk and palliative management.

Are there any contraindications to anticoagulant prophylaxis? (see below)

Are there any contraindications to anticoagulant prophylaxis? (see below)

Are there any contraindications to anticoagulant prophylaxis? (see below)

Are there any contraindications to anticoagulant prophylaxis? (see below)

Assess for Anticoagulant Prophylaxis

STEP 2

For ALL patients undergoing surgery or when surgery is imminent

Apply IPC and/or GCS

Apply GCS and/or IPC

Apply GCS and/or IPC

Consider GCS

YES Observe closely for VTE

NO

YES Observe closely for VTE

NO

YES Observe closely for VTE

NO

YES Observe closely for VTE

NO

LMWH - Low Molecular Weight Heparin LDUH - Low Dose Unfractionated Heparin GCS - Graduated Compression Stockings IPC - Intermittent Pneumatic Compression VTE - Venous Thromboembolism

Contraindication to Mechanical prophylaxis Severe peripheral arterial disease: Resent skin graft Severe peripheral neuropathy: Severe leg deformity

Are there any contraindication to mechanical prophylaxis? (see below)

Are there any contraindication to mechanical prophylaxis? (see below)

Are there any contraindication to mechanical prophylaxis? (see below)

Are there any contraindication to mechanical prophylaxis? (see below)

STEP 3

Assess Mechanical Prophylaxis

80 R.A. Fitridge and S. McRae

81

13  Prophylaxis of Venous Thromboembolism Table 13.4  Levels of thromboembolism risk and recommended thromboprophylaxis for patients in hospital [5] Levels of risk Approximate DVT risk Suggested thromboprophylaxis without thromboprophylaxis options (%)a Low risk

<10

Minor surgery in mobile patients

No specific thromboprophylaxis Early and “aggressive” ambulation

Medical patients who are fully mobile Moderate risk

10–40

Most general, open gynaecologic or urologic surgery patients

LMWH (at recommended doses), unfractionated heparin bd or tds, fondaparinux

Medical patients, bed rest or sick Moderate VTE risk plus high bleeding risk High risk

Mechanical thromboprophylaxisb 40–80

Hip or knee arthroplasty, hip fracture surgery Major trauma, spinal cord injury

LMWH (at recommended doses), fondaparinux, oral vitamin K antagonist (INR2-3)

Mechanical thromboprophylaxisb

High VTE risk plus high bleeding risk Rates based on objective diagnostic screening for asymptomatic DVT in patients not receiving thromboprophylaxis b Mechanical thromboprophylaxis includes IPC or VFP and/or GCS; consider switch to anticoagulant thromboprophylaxis when high bleeding risk decreases a

objective approach to diagnostic testing is required. Diagnostic algorithms combining non-invasive tests have largely replaced the previous invasive gold standards of venography and pulmonary angiography. Given the falling proportion of patients referred with suspected VTE that have the diagnosis objectively confirmed (as low as 10–15% in recent series), these algorithms have attempted to limit the need for diagnostic imaging while maintaining patient safety. The probability of individual patient’s having the diagnosis of VTE being confirmed can be stratified using clinical prediction rules, the most widely used of which are the DVT and PE Wells’ scores (Tables 13.5 and 13.6). In patients with a low pre-test probability (Wells score < 2, DVT unlikely), a negative sensitive D-dimer test, a product of the breakdown of crosslinked fibrin by plasmin, can be used to exclude DVT or PE without performing diagnostic imaging. Patients with either a high pre-test probability of VTE or a positive D-dimer test should proceed to diagnostic imaging, and as the majority of patients having undergone recent surgery will fall into one of these two categories, such algorithms are less useful in this patient population. Compression ultrasonography (CUS) is the commonly used diagnostic imaging test performed for suspected DVT. This technique is accurate for ruling in or

ruling out proximal DVT (popliteal and above). There is more debate regarding the accuracy (particularly the specificity) of CUS in the diagnosis of isolated calf vein or distal DVT, with diagnostic accuracy related to both the quality of the ultrasound machine as well as being operator dependent. While a negative complete compression ultrasound (examining proximal and distal vessels) has been shown to safely exclude DVT in most patients, where the clinician is highly suspicious of acute DVT but the initial study is negative, it is reasonable to repeat the imaging in 4–7 days to detect an initial small thrombus that may have subsequently propagated. Current imaging techniques for PE include ventilation/perfusion (V/Q) scanning, and increasingly spiral computerised tomographic pulmonary angiography (CTPA). A V/Q scan is reported on the presence or absence of mismatched perfusion defects. A high probability scan (the presence of a segmental sized or larger mismatched perfusion defect) is diagnostic of PE and justifies initiation of treatment, while a normal perfusion scan safely excludes PE. All other test results should be considered non-diagnostic, and further investigation is required. A non-diagnostic scan is more likely in patients with pre-existing lung pathology, and therefore, CTPA should be the investigation

82

R.A. Fitridge and S. McRae

Table 13.5  Diagnostic algorithm for patients with episode of suspected first deep vein thrombosis Patient with suspected DVT

Assess Pre-test Probability using the Well’s Prediction Rule (see below)

“DVT unlikely” (score < 2)

“DVT likely” (score ? 2)

Proceed directly to diagnostic imaging in these patients.

D-dimer test

Negative D-dimer

Compression Ultrasonography (CUS)

Positive D-dimer

NEGATIVE

POSITIVE

DVT confirmed Proceed to treatment algorithm

DVT excluded

Table 13.6  Wells et al. [8] score for the diagnosis of DVT Clinical characteristic Score Active cancer (ongoing or Rx within 6 months)

1

Paralysis, paresis or recent plaster immobilisation

1

Recently bedridden for >3 days or surgery within 12 weeks (requiring general anaesthetic)

1

Previously documented DVT or PE

1

Localised tenderness along the distribution of the deep venous system

1

Entire leg swelling

1

Calf swelling at least 3 cm larger than the asymptomatic leg (measured 10 cm below the tibial tuberosity)

1

Pitting oedema confined to the symptomatic leg

1

Alternative diagnosis as least as likely as DVT

−2

Interpretation: Score < 2 = DVT unlikely; score ³ 2 = DVT likely

*Do not perform D-Dimer if (a) Anticoagulation for > 24 h (b) Symptoms lasting > 14 days (c) Patient is pregnant

of choice in this group. A filling defect in a segmental level or more proximal pulmonary artery on spiral CTPA is diagnostic of PE and justifies treatment. A number of recent studies have shown that it is safe to withhold anticoagulation in patients with a normal CTPA. CTPA has the additional advantage of having the potential to detect alternative causes of chest pain in patients with suspected PE.

13.3 Management of Venous Thromboembolic Events 13.3.1 Calf Vein Thrombosis The majority of post-surgical DVTs will be isolated to the calf veins below the level of the politeal vessel (isolated distal DVT). These may often be asymptomatic, but can on occasion result in significant discomfort

83

13  Prophylaxis of Venous Thromboembolism

and swelling. Left untreated, approximately 10–25% of isolated distal DVTs will extend into the proximal veins, increasing the risk of PE. Calf vein thrombosis that is going to extend proximally normally does so within 1 week. There are no clear consensus guidelines at present for management of calf vein DVT. Based on the above natural history, a number of potential therapeutic approaches are reasonable. These include: (a) Symptomatic treatment alone with the performance of repeat ultrasonography at 1 week to detect those thrombi that have extended proximally and therefore require therapeutic anticoagulation. (b) Therapeutic anticoagulation for a 6–12  week period. This approach is likely to be appropriate in patients with ongoing risk factors (e.g. malignancy) or with more extensive thrombi. (c) Although not widely studied, many clinicians may utilise a shorter period of anticoagulation such as 2 weeks of LMWH, reassessing for progression at the end of this period with a repeat ultrasound.

13.3.2 Proximal DVT Traditionally, individuals have been formally anticoagulated with intravenous heparin and Warfarin. This approach required a period of in-hospital stay until the INR has been stabilised. Currently, patients who are judged to be reliable who do not have marked obstructive symptoms, and who do not have marked iliofemoral thrombus, can be managed as an outpatient utilising once-daily subcutaneous LMWH until they are therapeutically anticoagulated with Warfarin. This approach requires adequate community nursing support so that regular INRs can be taken and also lowmolecular-weight heparin can be injected where the patient is unable to do so. A recent Cochrane review found that there is a lower risk of bleeding associated with the use of LMWH than intravenous UFH, and that the risk of recurrent thrombotic events was also lower. Based on the protocols used in the initial clinical trials establishing their efficacy, both LMWH or UFH should be given for a minimum of 5 days, with the requirement that the INR is ³2 on two occasions 24  h apart prior to parenteral anticoagulation being ceased.

13.3.3 Duration of Anticoagulation The duration of anticoagulation is a balance between the risk of recurrent VTE once anticoagulation is ceased, and the risk of major bleeding whilst on warfarin (which is 2–3% per year in most series). The best predictor of recurrence risk is the presence or absence of a provoking risk factor at the time of the initial event. Isolated distal DVT is also associated with a lower risk of recurrent thrombosis. Based on these facts, the following broad recommendations can be made on duration of treatment: (a) Isolated distal DVT – 6–12 weeks (annual risk of recurrence < 3%) (b) Proximal DVT or PE associated with a major provoking risk factor (i.e. major surgery or trauma) – 3–6 months (annual recurrence risk ~ 3%) (c) Proximal DVT or PE with minor provoking risk factor (medical illness, oral contraceptive pill usage, travel) – 6 months (annual recurrence risk ~ 3–5%) (d) Unprovoked proximal DVT or PE – minimum of 6  months treatment, consideration of long-term therapy (annual recurrence risk ~ 10%) Repeat imaging should be performed at the cessation of anticoagulation to obtain a new baseline that can be used for comparison with future sc0ans. Patients with unprovoked events or with events at a young age, or with a strong family history should be considered for thrombophilia testing, as some conditions (protein C and protein S deficiencies, antithrombin deficiency and anti-phospholipid antibody syndrome) may require long-term anticoagulation due to a significant increase in risk of recurrent events. The role of new predictors of recurrence such as D-dimer testing and the presence of residual changes on imaging are still being evaluated.

References   1. MacLellan, D.G., Fletcher, J.P.: Mechanical compression in the prophylaxis of venous thromboembolism. ANZ J. Surg. 77, 418–423 (2007)   2. Kakkos, S.K., Caprini, J.A., Geroulakos, G., et al.: Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism in high-risk patients (review). Cochrane Database Syst. Rev. 8(4), CD005258 (2008)

84   3. McRae, S.J., Ginsberg, J.S.: In the diagnosis of deep-vein thrombosis and pulmonary embolism. Curr. Opin. Anaesthesiol. 19(1), 44–51 (2006)   4. Australia and New Zealand Working Party on the Management and Prevention of Venous Thromboembolism: Prevention of venous thromboembolism: best practice guidelines for Australia and New Zealand, 4th edn. Health Education and Management Innovations, Sydney (2007)   5. Geerts, W.H., Bergqvist, D., Pineo, G.F., et al.: Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th edn.). Chest 133, 381–453 (2008)

R.A. Fitridge and S. McRae   6. Cohen, A.T., Tapson, V.F., Bergmann, J.F., et  al.: Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-­ sectional study. Lancet 371(9610), 387–394 (2008)   7. Tooher, R., Middleton, P., Pham, C., et  al.: A systematic review of strategies to improve prophylaxis for venous thromboembolism in hospitals. Ann. Surg. 241(3), 397–415 (2005)   8. Wells, P.S., Anderson, D.R., Rodger, M., et al.: Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N. Engl. J. Med. 349(13), 1227–1235 (2003)

Nutrition of the Surgical Patient

14

Florian Brackmann, Wolfgang H. Hartl, and Peter Rittler

14.1 Changes of the Substrate Metabolism After Surgical Disturbance of Homeostasis 14.1.1 Basic Principles The hormonal changes after surgical trauma represent the essential basis for the adjustment of the substrate metabolism during this period. Catabolism, i.e. breakdown of all existing substrate depots in the body, is the main process. Initially, this represents a reasonable physiological reaction to provide the organism with elements for energy production and composition of important functional proteins. Thus, enhanced lipolysis in the adipose tissue leads to increased release of free fatty acids, which can, on the one hand, be used as an alternative substrate for the non-obligatory carbohydrate-dependent tissues (skeletal muscles), and represent, on the other hand, energy sources for the accelerated metabolism in the liver. Parallel to the restricted carbohydrate utilization in the skeletal muscles, a pronounced protein breakdown takes place here as well. By that, released amino acids fulfil mainly two purposes: on one side, the gluco­ neogenetic amino acids can be drawn on for the accelerated production of glucose in the liver; on the other side, the nitrogen carriers released from the skeletal muscles

F. Brackmann Department of General Surgery, Mount Gambier General Hospital, 276-300 Wehl Street North, Mount Gambier, SA 5290, Australia W.H. Hartl, and P. Rittler (*)  Department of Surgery, Campus Großhadern, Marchioninistr. 15, 81377 Munich, Germany e-mail: [email protected]; [email protected]

are essential for wound healing. In this context, the supply of the gastrointestinal tract with certain amino acids (glutamine) is worth mentioning. Glutamine-dependent repair mechanisms are said to limit the extent of integrity disturbance within the g­ astrointestinal tract. The main site of metabolic changes after trauma or surgery is the liver. Here carbohydrates from gluconeogenesis and glycolysis are released into the blood. The accelerated hepatic production of glucose together with the peripheral insulin resistance lead to hyperglycaemia, which helps to optimize the glucose supply and by that the glucose intake and energy metabolism in the obligatory glucose-dependent tissues (immunocompetent cells, fibroblasts) (Figs. 14.1 and 14.2). Utilization of endogenously released amino acids for glyconeogenesis leads to irrevocable loss of nitrogen in the form of urea from the body. This loss of nitrogen equates to a loss of body proteins and is the biochemical correlate of the decrease of muscle mass. After elective surgical procedures, and with uncomplicated postoperative recovery, the maximum of ­metabolic changes occurring in the course of the ­post-aggression syndrome will be seen within the first 2  weeks after surgical disturbance of homeostasis. The insulin resistance with concomitant hyperglycaemia reaches its peak within the first 48  h, while the decrease in body proteins will have its maximum after 2 weeks. Accordingly, the protein metabolism recovers only very slowly.

Replenishment of body protein supply can only be expected 3–6 months after extensive surgical procedure without complications or trauma. The body weight does not reach the initial level before a similar period of time either.

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_14, © Springer-Verlag Berlin Heidelberg 2011

85

86

F. Brackmann et al.

Lipolyse

Free fatty acids Keytone bodies Glucose Glycogenesis Lactate, Pyruvate Alanine, Glutamine

Urea

Proteolysis

Urea Balance Fig. 14.1  Substrate flow in the post-aggression metabolism

Glycerol 30g

114g

Glycogen Glucose 320g

3C

8g

76g

Blood cells 130g Wound

104g Lactate

Urea in the urine

Alanine, Lactate Gluamine

80g Amino acids

Fig. 14.2  Glucose ­regeneration during stress

14.2 Metabolic Particularities of the Intensive Care Patient With persistent Systemic Inflammatory Response Syn­ drome (SIRS) or severe sepsis, the severe disturbance of the carbohydrate metabolism with hyperglycaemia and insulin resistance remains because of the ongoing hormonal activation. Under such conditions very high

carbohydrate concentrations might -if untreated- have negative consequences for the patient’s prognosis due to immunosuppressive effects. Furthermore, there is a striking protein catabolism. Mainly four mechanisms seem to be initially responsible for this prolonged massive loss of proteins: • Immobilization of the patient • Release of catabolic hormones

87

14  Nutrition of the Surgical Patient

• Regularly seen hypercatabolism with increased metabolic rate • Activation of certain cytokines In long-term courses, another important mechanism to trigger and maintain the prolonged protein catabolism is the pathological change in the peripheral and central nervous system. This so-called septic neuropathy (in 70–90% of all intensive care patients) is associated with peripheral neuropathy and signs of axonal degeneration. Subsequently, functional denervation develops, which leads to drastic increase of protein breakdown. More than 90% of the critically ill patients show atrophy of the skeletal muscles (necrosis of muscle, intracellular lipid deposits). Another central finding with almost all intensive care patients is the increasing fatty degeneration of the liver caused by imbalance between fatty acid intake, fatty acid oxidation and fatty acid administration through VLDL-triglycerides. Protein catabolism leads to defective VLDL-triglyceride synthesis or secretion as well.

14.3 Nutritional Status and Caloric Demand Nutritional therapeutic measures are essential to ­minimise complications and achieve the best possible quality of life in the preoperative, intraoperative and postoperative period including the rehabilitation phase. For all measures, appropriate consideration of nutritional supply and status is required.

14.4 Assessment of Nutritional Status Today, reliable assessment of the nutritional status has to be regarded as a necessary component and prerequisite of any efficient nutritional therapy. Particularly severely malnourished patients are affected by increased perioperative morbidity and therefore benefit most from adequate nutritional therapy. Basic details regarding nutritional status are body height and weight to calculate the BMI (Body-Mass

Index), and inquiring about weight loss. The BMI is mainly established to classify overnutrition (moderate > 25, definite > 30, massive > 40). To assess under-/ malnourishment, it is only valid for chronic severe under-/malnourishment (BMI < 18.5), but not to detect short-term under-/malnourishment in acute conditions like malignancies, etc., and in cases of previously existing overnutrition. From a clinical point of view it has been proven as useful to classify patients as normally nourished, moderately undernourished or severely undernourished: • Considered as moderately undernourished are those patients that have lost 10–15% of their body weight preoperatively and concurrently have hypoalbuminaemia or disturbances in other body systems. • Severe undernourishment equals weight loss of 15% or more. In practice, assessment of the nutritional status based on the so-called Subjective Global Assessment (SGA) or the Nutritional Risk Screening 2002 (NRS 2002) has become widely accepted. This method mainly consists of taking accurate medical history, physical examination and estimation of the current energy demand of the individual patient. SGA allows making rough nutritional classifications of individual patients by discriminating between • Well nourished • Moderately undernourished • Severely undernourished The variables for the SGA are listed in Fig.  14.3. Special attention is paid to changes in body weight, alterations in nutritional intake, gastrointestinal disorders, physical activity and the underlying disease with its relation to nutritional demand. Furthermore, in the physical examination, loss of subcutaneous fat and clinically evident muscular atrophy are recorded. Additionally, ankle and flank oedema as well as ascites are to be noted. No defined numeric algorithm is used to get an appropriate SGA classification. Rather, a categorization on a basis of subjective evaluation is performed. In spite of this subjectivity, a clear correlation between SGA and prognosis of the surgical patient is found. This only applies for preoperative assessment, though; there is still no precise method for postoperative surveillance or intensive care patients available.

88 Fig. 14.3  Variables of the “Subjective global Assessment” (SGA)

F. Brackmann et al. A. History 1. Weight change Overall loss in past 6 months: – amount = # ___________ kg; – % loss = # ____________ Change in past 2 weeks: – ___________________ increase, – ___________________ no change, – ___________________ decrease. 2. Dietary intake change (relative to normal) ___________ No change, ___________ Change ___________ duration = # ___________ weeks type: – ___________ suboptimal liquid diet, – ___________ full liquid diet – ___________ hypocaloric liquids, – ___________ starvation. 3. Gastrointestinal symptoms (that persisted for >2 weeks) ___________ none, ___________ nausea, ___________ vomiting, ___________ diarrhea, ___________ anorexia. 4. Functional capacity ___________ No dysfunction (e.g., full capacity), ___________ Dysfunction ___________ duration = # ___________ weeks. type: __________________ working suboptimally, __________________ ambulatory, __________________ bedridden. 5. Disease and its relation to nutritional requirements Primary diagnosis (specify) ___________________________________________ Metabolic demand (stress) : – ____________ no stress, – ____________ low stress, – ____________ moderate stress, – ____________ high stress. B. Physical (for each trait specify: 0 = normal, 1+ = mild, 2+ = moderate, 3+ = severe). # ______________________________ loss of subcutaneous fat (triceps, chest) # ______________________________ muscle wasting (quadriceps, deltoids) # ______________________________ ankle edema # ______________________________ sacral edema # ______________________________ ascites C. SGA rating (select one) __________________ A = Well nourished __________________ B = Moderately (or suspected of being) malnourished __________________ C = Severely malnourished Select appropriate category with a checkmark, or enter numerical value where indicated by “#”

Besides those general diagnostics that should always be done in specific situations as in chronic diseases (e.g. liver cirrhosis, chronic pancreatitis, immunosuppression), or severe undernourishment (tumours, Crohn’s disease), problem-oriented diagnostic investigations

(serum albumin level, short-lived functional proteins, 24  h urine-creatinine excretion, bioelectrical impedance analysis [BIA]) can be carried out to detect and distinguish protein deficiency or specific nutritional deficiencies.

89

14  Nutrition of the Surgical Patient

14.5 Estimating the Perioperative Caloric Demand Postoperatively, fluid and electrolyte supply has to be aligned to calorie and substrate supply. For that, it is necessary to determine the patient’s energy demand first. You start with the basic energy metabolic rate, that can be calculated approximately according to Harris and Benedikt for the healthy person based on body weight, age, gender and height. In clinical routine, the basic metabolic rate can be calculated by Stein and Levine’s rule of thumb (basic energy metabolism [kcal]/day = 24 × kg bodyweight). Generally, it can be assumed that caloric demand immediately after elective procedures is equivalent to the metabolic rate at rest. After mobilizing the patient the rate increases about 10%. Hence, only fluids and electrolytes are given on the day of surgery. Administration of vitamins and trace elements during this period is not necessary. From the first day on calories should be administered preferably orally or enterally via a tube. If this is not possible, glucose and amino acids can be administered parenterally for a few days. Parenteral nutrition is only required for patients who cannot be fed orally or enterally after 1 week.

Note:  Caloric deficiency always leads in the medium term to under-/malnourishment and increases the risk for complications or delayed rehabilitation. Therefore, especially after resolving the acute phase sufficient nutrition and, where required, additional energy- and protein-rich drinking supplements should be administered.

14.6.1 Oral Nutrition Usually, products for oral nutrition are supplied by the hospital kitchen. Apart from mainly liquid diet (tea, soup, biscuits, oral drinking supplements with high calorieand protein concentration), there are more preparations with different consistencies and fibre ­concentrations (filtered diet, light diet, full diet). Oral food intake should be the rule. Drinking ­supplements can be used as additive measures in case of inadequate oral food intake especially for severe under-/malnourishment and during the postoperative period. Studies established the merit of such measures for old patients after hip fractures or after gastrectomy.

14.6.2 Enteral Nutrition Substrates are administered enterally in case of dysphagia or malfunctioning of the upper gastrointestinal tract (stomach/oesophagus). For enteral nutrition, fabricated balanced diets are used that meet all the patient’s needs regarding nutrients, trace elements, electrolytes and vitamins. Most of them are suitable as full nutrition but are more expensive than normal hospital diet. Nutrient defined diets (NDD) have to be distinguished from chemically defined diets (CDD) (Table 14.1). For catabolic patients NDDs with higher caloric density and higher protein content are available to provide protein rich nutrition (1.3–1.5 g/kg bodyweight/day). For uncomplicated long-term feeding and in case of unrestricted gastrointestinal functioning, NDDs containing fibre can be used. Here diets containing insoluble fibre (cellulose) and diets with soluble fibre (prebiotics: pectin, agar, mucilage, oligofructose) can be distinguished.

14.6.3  Diets Adapted to Metabolism 14.6 Substrates for Perioperative Nutrition Perioperative feeding can be done orally, enterally or parenterally. Accordingly, there are commercial products for all three modalities.

So-called diets adapted to metabolism are designed for patients with specific organic diseases and in­­ sufficiencies as well as for situations with metabolic peculiarities: • Diabetes diet • Diets with immunomodulatory effects

90

F. Brackmann et al.

Table 14.1  Nutrient defined and chemically defined diets Nutrient defined diets (NDD) Composition

Chemically defined diets (CDD)

Carbohydrates in form of oligo- and polysaccharides (50–60%)

Amino acids, tripeptides or oligopeptides

Intact protein from milk, soy, egg albumin and meat protein (15–20%) Lipids from vegetable oil

Low in lipids

Essential fatty acids Saturated fatty acids (short-chain, medium-chain and long-chain fatty acids) Low in fibre

Free of fibre

Properties

High molecular

Low molecular slightly hyperosmolar because of osmotically active protein hydrolysate

Location of resorption

Entire GI tract

Jejunum and Ileum

Application

For normal digestion and resorption performance

For global impairments of the intraluminal hydrolyse capacity and resorption (e.g. exclusive jejunal feeding)

• Liver-adapted tube diets • Kidney-adapted diets

14.6.4 Parenteral Nutrition

Diabetes diets contain reduced amounts of carbohydrates and an increased fraction of unsaturated fatty acids and help to control glycaemia and reduce insulin demand. Immunomodulating diets contain substrates like Glutamine, Arginine, Omega-3-fatty acids and nucleotides that have been shown to have certain immunomodulatory effects. In general, the aim is to dampen the hyperinflammatory processes which occur within SIRS and sepsis, and to strengthen the specific immune system on the other side. Glutamine is supposed to have further positive effects on gastrointestinal tract function. Liver-adapted tube diets contain specific amino acid patterns. The goal of this modification is to restore normal plasma aminograms in patients with liver failure, especially patients with hepatic encephalopathy, who have increased plasmatic levels of aromatic amino acids and methionine, but decreased levels of branched chain amino acids. Therefore, diets enhanced with branched chain amino acids can help to improve this amino acid imbalance. Patients with marginally impaired kidney function can benefit from kidney-adapted diets with a reduced proportion of nitrogen and a high proportion of essential amino acids or adapted electrolyte compositions.

In case of malfunction of the lower GI tract (small bowel/large bowel) feeding has to be parenteral. It should be hypocaloric for the first week after surgical trauma and normo (iso-) caloric in the second week. For both, the early (day 1–3) and the late (day 4–6) postoperative phase, commercialised infusion solutions are available which take the specific ­metabolic demands of each phase into account (Table 14.2). If electrolyte- or water imbalances occur in the late postoperative period, it is necessary to combine single solutions of amino acids and sugar according to the above principles instead of using the amino acid carbohydrate solutions. The concentrations of sugar solutions range between 10% and 40% and allow isocaloric nutrition for patients with such dysfunctions. Of course, the amounts of carbohydrates administered in such manner have to be adjusted to the extent of the post-aggression metabolism. Additionally, it is necessary to combine this with separate amino acid solutions that usually contain 10% synthetic crystalline amino acids. Those solutions are generally composed of 40–50% essential amino acids, the rest being non-essential amino acids.

91

14  Nutrition of the Surgical Patient Table 14.2  Infusion solution for the different phases of parenteral postoperative nutrition Hypocaloric nutrition in the early postoperative phase

Hypocaloric nutrition in the late postoperative phase

Complete isocaloric parenteral nutrition

Timing

Day 1–3 after surgery

Day 4–6 after surgery

From day 7 after surgery

Composition and properties

Slightly hypertonic (700–800 mosm/l)

High osmolarity (1,300 mosm/l)

High osmolarity (>1,300 mosm/l)

Low caloric density (0.3–0.4  kcal/ml)

High caloric density (0.6–0.7 kcal/ml)

High caloric density (1–1.2 kcal/ml)

5% glucose, 3.5% amino acids and electrolyte proportioned to the maintenance dose

Carbohydrates, amino acids, trace elements, electrolytes, proportioned to the increased protein- (1–1.2 g/kg body weight/ day) and carbohydrate demand (4 g/kg body weight/day)

Amino acid-carbohydratelipid-combination solutions or amino acid-carbohydratesolutions with lipids separate

Amount of infusion

40 ml/kg bodyweight/day

25–30 ml/kg bodyweight/day

Way of application

Peripheral venous line

Central venous line

14.6.5  Parenteral Application of Lipids For complete isocaloric parenteral nutrition hyperosmolaric amino acid/carbohydrate/lipid combination solutions are available. Lipids, however, can also be administered as a separate part of parenteral nutrition. Because of its high caloric density (2  kcal/ml), only small amounts of lipids are sufficient to administer adequate amounts of calories. At present, there are five different infusion solutions for the application of lipids with different compositions. As a general rule these solutions contain 20% of lipids in 250 ml: • Lipid emulsions based on soy bean oil (20  g fat/100 ml with 52% linoleic acid) • MCT/LCT-solutions: soy bean or coconut oil (so-called medium chain triglycerides); 10  g soy bean oil/100  ml with 10  g coconut oil/100  ml in physical mixture • Structured lipids: same composition as MCT/LCTsolutions, not physically but biochemically mixed • Lipid emulsions based on soy bean and olive oil with 4 g soy bean oil/100 ml (equal to 18% linoleic acid) and 16 g olive oil/100 ml • Preparations with higher fractions of omega-3 fatty acids (fish oil) Linoleic acid plays an important role as it is the precursor substance of arachidonic acid, which many

Central venous line

inflammatory mediators (prostaglandins, leucotrienes) with immunosuppressive functions are made from. To reduce these effects, new solutions contain considerably smaller amounts of linoleic acids (higher proportions of MCT or olive oil). Furthermore, infusion solutions with higher fractions of omega-3 fatty acid might have positive immunologic effects due to the decreased synthesis of immunosuppressive prostanoids.

14.6.6 Special Preparations for Patients with Organ Dysfunctions Similarly to enteral nutrition, there are also specific preparations of parenteral nutrition to compensate for organ dysfunctions. The so-called kidney solutions contain only essential and few semi-essential amino acids. Since increasingly damaging effects of urea concentrations above 100 mg/ dl can be expected, administration of daily proteins has to be cut down to one-third of the calculated daily intake if haemofiltration/dialysis is meant to be postponed. With this nutritional regime, production of urea is lower than with carbohydrate supply only. Yet in case of longer-lasting renal failure, resumption of isocaloric nutrition with full amino acid supply is preferable. For patients with hepatic encephalopathy and ammoniac concentrations of more than 100  mg/dl,

92

special liver solutions exist for parenteral administration that contain higher fractions of branched chained amino acids (see above).

14.6.7. Supply of Glutamine, Vitamins and Trace Elements Nowadays, special amino acid solutions which include glutamine in the form of dipeptides (in combinations or single solutions) are available. So far, amino acid solutions did not contain glutamine, because glutamine is instable in solution. Linking glutamine to alanine or glycine makes parenteral supply possible as well. Especially intensive care patients (see below) show a distinct glutamine deficiency both in their plasma and in their muscle tissue. Postoperative application of vitamins and trace elements is only required in cases of long-term parenteral nutrition. Preparations that contain the most important trace elements (chrome, copper, iron, manganese, fluorine, molybdenum, selenium and zinc) exist and are usually administered daily. Water-soluble vitamins can be given additionally (thiamine, riboflavin, pyridoxine, pantothenic acid, ascorbic acid, biotin, folic acid, cyanocobalamine). The administration of lipophilic vitamins (vitamin A, D2, K and E) can be done parenterally as well, if the patient receives lipids intravenously in the context of nutritional therapy. If the patient does not receive lipids intravenously, the same vitamins can alternatively be administered in specially processed normal saline.

14.7 Preoperative Nutritional Therapy 14.7.1 Indication Indication for preoperative nutritional therapy is moderate-to-severe malnourishment for all patients with elective procedures. It has been shown that pre-existing, relevant undernourishment leads to a perioperative shift of fluids into the “third space”, is associated with muscle weakness, significantly interferes with wound healing and leads to pronounced immunodeficiency. All of these phenomenons significantly increase postoperative morbidity and mortality. By enforcing

F. Brackmann et al.

aggressive preoperative nutritional therapy over a period of at least 1 week, postoperative complications can be reduced by 20–35%. A further indication for preoperative nutrition is given in tumour patients prior to big visceral operations, even if no relevant undernourishment is present. Drinking supplements with immunomodulatory substances are used for this purpose during a period of 5–7 days before surgery. This kind of nutritional therapy is usually carried out up to the evening before surgery, and decreases the perioperative morbidity by reducing infectious complications.

14.7.2 Calorie Supply Tumour patients who are not undernourished preoperatively receive additive immunomodulatory supplements with 500–1,000 cal. The amount of administered calories for undernourished patients is not based on the expected current metabolic rate but should be hypercaloric. Here 30–40 kcal/kg body weight/day non-protein calories should be administered with one-third given in the form of lipids. Proteins should be given in the amount of 1–1.5 g/kg body weight/day. Ideally, this calorie intake can be achieved with oral supplements high in protein. Only in cases of dysphagia or high risk of aspiration, enteral nutrition (nutrient defined diet) is used. Only if oral/enteral nutrition is impossible or insufficient, it becomes reasonable to use complete parenteral nutrition with balancing of vitamin- and trace element deficiencies over the period of one week. The efficiency of these measures is shown by an increase of short-lived functional proteins (prealbumin, retinol binding protein) in the circulation.

14.8 Postoperative Nutritional Therapy 14.8.1 Indication Postoperative oral food intake should be started as soon as possible and gradually increased according to the conditions of post-aggression metabolism. In case

93

14  Nutrition of the Surgical Patient

of insufficient swallowing and/or gastrointestinal functioning artificial alimentation has to be considered. Indication for artificial feeding (enteral/parenteral) is given • for all patients who are undernourished preoper­ atively • for patients who have no signs of undernourishment but are expected not to receive oral food intake for more than 7 days or only food intake not covering their full demand In these patients alimentation should be started after surgery without delay. Parenteral nutrition is indicated only in cases with absolute contra-indications for enteral nutrition. Possible indications are: • Bowel obstruction with relevant impairment of passage • Persistent intestinal leakage • Paralytic ileus • Severe shock with circulatory instability In all other cases it is recommended to at least try to use enteral nutrition (gastric/jejunal). If the intestinal passage is only partly restricted, enteral nutrition should be combined with parenteral nutrition to cover caloric demands. Even for patients with gastrointestinal anastomosis, generally a discontinuation of oral/enteral food intake is not necessary. The gradual build-up of diet should be adapted to the patient’s tolerance. After anastomosis of the small bowel, colon and rectum, oral/enteral food intake can be started on the first day post op. For anastomosis of the upper gastrointestinal tract (oesophagus resection, gastrectomy), enteral food intake through a tube inserted distal to the anastomosis or specific catheter jejunostomy during the first days is recommended. Even a small fraction of caloric intake is beneficial. Small bowel mucosa enterocytes need glutamine from an enteral source.

Early enteral diet build-up decreases the risk of infection and at the same time shortens the length of hospital stay.

14.8.2 Oral/Enteral Calorie Intake Basic requirement for any kind of oral/enteral therapy is a sufficient passage and resorption of the administered substrates. In addition, the following has to be considered: • Capacity of passage in the GI tract • Type of surgical procedure After all thoracic and orthopaedic procedures, light diet can be started immediately after operation provided the GI tract is intact. After abdominal surgery, without harming the integrity of the intestinal tract, oral build-up of diet can be started on the first postoperative day as well. After feeding mainly liquids for a short period, diet can be switched over to light, low-fibre food already on the second postoperative day. Here the supplied amount of calories has to be adapted to the characteristics of the post-aggression metabolism – as it is done in parenteral nutrition. After surgery in the lower GI tract, diet build-up is slightly held up and then started with liquid nutrition in the first 2 days followed by the normal diet build-up as described.

The actual intake of the supplied calories has to be monitored carefully to avoid unexpected calorie deficiency.

After procedures in the upper GI tract, especially ­gastric or oesophageal resections, feeding is done by ­special, intraoperatively placed tubes (catheter jejunostomy). Special enteral nutritional solutions (see above) are administered, starting with 250  ml continuously for 24 h on the first day post op. If oral feeding cannot be achieved sufficiently, infusions are carefully increased over the next days by 250  ml/24  h every 1–2 days until the caloric demand of 24 kcal/kg bodyweight is reached. If patients after thoracic, vascular or orthopaedic surgery or extraintestinal abdominal procedures are not capable of taking food orally, enteral feeding via nasogastric tube is started early. Here, too, diet buildup is done gradually, starting at 500  ml on the first

94

F. Brackmann et al.

postoperative day. The intake is increased by 500 ml/ day until the caloric optimum is reached. There is strong evidence that especially patients after big visceral tumour surgeries or severe polytrauma, benefit from postoperative enteral feeding. If there is a need for long-term enteral feeding (>4  weeks), changing to a transcutanous tube (e.g. PEG) is recommended. A further specific feature applies for oncologic patients. It is suggested to continue feeding of the ­preoperative immunomodulatory tube nutrition postoperatively. In case of uncomplicated progress, a period of 5–7 days is sufficient for that.

14.8.3 Parenteral Calorie Intake Following the immediate postoperative period, and after estimating the calorie- and water demand, it is also important to assess the fraction of protein- and non-protein calories in the total calorie intake. The healthy adult needs approximately 0.8  g protein/kg body weight/day. Patients after big ­surgical interventions need between 1 and 1.2  g protein/kg body weight/day depending on the extent of their disease.

The main focus of postoperative nutritional therapy has to be on sufficient supply of proteins. Based on a demand of 1 g/kg body weight/day an amount of 4 kcal/kg body weight/day should be administered in form of amino acids during the entire postoperative period.

The additional amount of carbohydrates and lipids depends on the calculated energy demand and the expected metabolic impairment. Therefore, only 50–60% of the estimated calorie demand is administered between the first and third postoperative day, i.e. 12  kcal/kg body weight/day (according to Stein and Levine). Deducting the administered amount of protein calories from that (4  kcal/kg body weight/day) results in a daily amount of carbohydrates of about

8 kcal/kg body weight/day (equal to 2 g carbohydrates/ kg body weight/day). Remission of the post-aggression syndrome and increase in substrate metabolism can be expected between day 4 and 6 post operation, if no complications occur. During that period about three-fourths of the amount of calories calculated as basic metabolic rate is administered, i.e. about 18  kcal/kg body weight/day. Deduction of the protein calories results in an amount of carbohydrates of about 13 kcal/kg body weight/day. Beginning with the seventh postoperative day, it is possible to use complete isocaloric nutrition with amino acids/proteins (1.5  g/kg body weight/day), carbohydrates (4  g/kg body weight/day) and lipids, usually increasing the amount of lipid calories from 0.5 to 1 g (= 5 respectively 10 kal/kg/day). The dosage is approached to the calculated calorie demand while careful attention is given to the level of blood glucose and triglycerides. If long-term parenteral feeding is to be expected, the daily maintenance dose of vitamins and trace elements should be administered from the first day after surgery.

14.8.4 Complications of Early Oral/ Enteral Nutrition Early oral/enteral nutrition is not generally without risks, and if complications occur morbidity is significantly increased (Table 14.3). Nonetheless, taking all positive and negative effects into account, there is still an advantage for patients to be fed orally/enterally early during the postoperative course. However, in certain clinical situations considerable variations of the usual gastrointestinal tract motility occur (mainly gastric emptying). Repeat high residual volumes of the stomach when aspirating through the nasogastric tube are the best indicators of functional failure of gastric emptying. The reason for this is ­multifactorial: sepsis, acute hyperglycaemia, autonomous neuropathy, catecholamines, beta2-mimetics and analgosedation. In this case, motility enhancing drugs (metroclopramid, erythromycin) should be used. Another unintentional effect is the increase of the gastric pH. This leads to weakening of the gastric acid barrier (especially due to antacid therapy) and therefore to ascension of bacteria and colonisation of the

95

14  Nutrition of the Surgical Patient Table 14.3  Complications and concomitant symptoms of early postoperative oral/enteral feeding Complications

Possible causes and risk factors

Functional impairment of gastric emptying

Mostly extra-gastric, primary or concomitant disease •  Severe systemic disease •  Acute hyperglycaemia •  Autonomous neuropathy •  Drug effects

Hospital acquired pneumonia

Ascension of bacteria and fungi as a consequence of elevation of the gastric pH

Diarrhoea

Intestinal primary or concomitant disease, often multifactorial •  Infections of the GI tract • Motility-, resorption- or passage impairments

Passage impairments in small- or large bowel

Intestinal or extraintestinal primary or concomitant disease • Decrease of blood circulation in the abdomen •  Infection of the GI tract •  Drug effects

oesophagus and pharynx. Micro-aspirations can develop which increases the risk of hospital-acquired pneumonia. Stopping the feeding during the night allows the gastric pH to fall and restores the acid barrier. The most common complication of enteral feeding is diarrhoea. The cause of diarrhoea is multifactorial and the composition of the feeding solution only rarely is the reason for this problem. Critical pathomechanisms are infectious diseases of the intestinal tract and impairment of motility, resorption or blood supply. The antibiotic-induced pseudomembranous colitis has to be considered as a differential diagnosis as well. The diarrhoea can be treated by reducing the flow, changing the nutritional regime or modality or by changing the antibiotics. In severe cases (haemorrhagic colitis) a total feeding pause might be indicated. Apart from impairment of motility in the upper GI tract, passage failures in the small and large bowel are relevant. The combined small-/large-bowel ileus has to be differentiated from the isolated large-bowel ileus (Ogilvie-syndrome, pseudo obstruction of the colon). If this condition cannot be fixed with mechanical means (enema, endoscopic aspiration) or

by administration of prokinetics, oral/enteral therapy must be changed to a total parenteral regime.

14.8.5 Practice of Enteral Nutrition To commence enteral feeding some kind of access to the GI tract has to be established, usually using transnasal tubes. For nasogastric feeding tubes with the largest tolerated lumen (12–14 charriere) should be used, this also allows for decompression of the stomach. If the upper GI tract will not work for a foreseeable period of time, a catheter jejunostomy should be performed during surgery. Alternatively, it can be considered to place nasojejunal tubes endoscopically. This offers simple and secure access to the upper small bowel and can also be used to bypass an insufficient anastomosis after gastrectomy/oeso­ phagectomy. In principal, two different modalities of application are available: continuous administration, or bolus feeding of 50–300 ml. In general, continuous administration is better tolerated leading to a higher energy- and substrate supply, since the rate of treatment limiting diarrhoea and aspirations is smaller. On the other hand, acute blockage can be missed which could lead to a life-threatening aspiration.

In case of uncertain tube function, bolus feeding is preferable since the nursing staff can check the amount of residual volume in the stomach before every application and reduce the amount of feeding if necessary.

14.9 Particularities of Nutrition in Critically Ill Patients 14.9.1 Substrates Immunomodulatory tube nutrition for patients with surgical sepsis is not indicated at present regardless of the severity of the disease. Especially pro- and

96

F. Brackmann et al.

anti-inflammatory reactions to nutrition play a role here, although this impact has not been clearly specified. In patients with total parenteral feeding, glutamine in form of dipeptides (20 g/day) should be added. This prevents common glutamine deficiencies and the ­associated immunodeficiency. On a long-term basis, a decrease in mortality has been reported. The main focus of nutritional therapy in the intensive care patient is to prevent protein catabolism. Patients with severe SIRS or sepsis lose between 1.2 and 1.4  kg of protein in a period of about 3  weeks (mainly skeletal muscles), which is approximately 13% of the baseline. The amount of calorie intake in relation to the total metabolic rate hardly influences protein catabolism. Even large amounts of protein intake, can only reduce protein catabolism, but not fully prevent it. The optimal daily intake of proteins is about 1.5 g protein/kg body weight/day. Larger amounts do not have positive effects on protein metabolism. The different feeding modalities certainly play a role in reducing protein loss. Enteral feeding, for example, can almost halve the protein loss of intensive care patients within 10 days compared to isocaloric parenteral feeding.

14.9.2 Caloric Demand The vast majority of intensive care patients is supplied sufficiently with a conservative calorie administration of 21–25 kcal/kg body weight/day (depending on the amount of physical activity and analgosedation). Calorie administration at this level is a trade-off between trying to compensate losses as far as possible and reducing toxic side effects on the other hand.

14.9.3 Additive Pharmacotherapy Because of the well-known adverse effects of ­hyperglycaemia to the immune system, rigid control of the blood glucose level is mandatory. Plasma glucose

levels in intensive care patients should not exceed 150 mg/ dl. Hyperglycaemia needs to be treated with insulin therapy, possibly with continuous insulin infusion via a perfusor and close monitoring.

14.9.4 Metabolic Monitoring At present, a reliable and easy-to-use method to clinically estimate the protein demand of the individual surgical patient does not exist. It is possible to minimise the daily protein loss for most of the elective surgical patients by administration of 1–1.2  g/kg body weight/day protein. This can be increased to 1.5 g/kg body weight/day in intensive care patients. Creatinine or urea concentrations are only very limited indicators for an increasing protein catabolism. However, measuring those serum concentrations is necessary to early detect toxic levels of these metabolites in acute renal failure and to initiate adequate therapeutic measures if needed. After overcoming sepsis, protein intake can be increased up to an amount where urea levels are within the upper normal range. To monitor lipid utilization, it is necessary to measure plasma triglyceride concentrations in regular intervals. This helps to detect impairments of lipid metabolism at an early stage. Malfunctioning of the carbohydrate metabolism can be diagnosed by measurements of blood glucose levels several times per day (blood glucose profile). The electrolyte demand of the patient is usually determined by measurements of their serum concentrations. To detect real deficiencies of the so-called micronutrients (trace elements, vitamins) indirect functional tests would be required which are complicated and cannot be performed in practice. Therefore, patients at risk are usually administered appropriate vitamins and trace elements prophylactically in regular intervals.

Recommended Reading Alberda, C., Gramlich, L., Jones, N., Jeejeebhoy, K., Day, A.G., Dhaliwal, R., Heyland, D.K.: The relationship between nutritional intake and clinical outcomes in critically ill patients: results of an international multicenter observational study. Intensive Care Med. 35(10), 1728–1737 (2009)

14  Nutrition of the Surgical Patient Braga, M., Gianotti, L., Nespoli, L., Radaelli, G., Di Carlo, V.: Nutritional approach in malnourished surgical patients: a prospective randomized study. Arch. Surg. 137, 174–180 (2002a) Braga, M., Gianotti, L., Vignali, A., Carlo, V.D.: Preoperative oral arginine and n-3 fatty acid supplementation improves the immunometabolic host response and outcome after colorectal resection for cancer. Surgery 132, 805–814 (2002b) Griesdale, D.E., de Souza, R.J., van Dam, R.M., Heyland, D.K., Cook, D.J., Malhotra, A., Dhaliwal, R., Henderson, W.R., Chittock, D.R., Finfer, S., Talmor, D.: Intensive insulin ­therapy and mortality among critically ill patients: a meta-­analysis including NICE-SUGAR study data. CMAJ 180, 821–827 (2009)

97 Jones, N.E., Heyland, D.K.: Implementing nutrition guidelines in the critical care setting: a worthwhile and achievable goal? JAMA 300, 2798–2799 (2008) Kondrup, J., Rasmussen, H.H., Hamberg, O., Stanga, Z., Ad Hoc ESPEN Working Group: Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clin. Nutr. 22, 321–336 (2003) Sorensen, J., Kondrup, J., Prokopowicz, J., Schiesser, M., Krähenbühl, L., Meier, R., Liberda, M., EuroOOPS study group: EuroOOPS: an international, multicentre study to implement nutritional risk screening and evaluate clinical outcome. Clin. Nutr. 27, 340–349 (2008)

 

Surgical and Hospital-Acquired Infections

15

Wolfgang Böcker and Wolf Mutschler

15.1 Background 15.1.1 Basic Concepts

3. Non-abscessing infections (e.g., fasciitis, peritonitis) 4. Posttraumatic infections (e.g., osteomyelitis following open fracture) 5. Postoperative surgical site infections (e.g., wound infection, abdominal wall abscess)

15.1.1.1 Infection, Infectious Disease, and Inflammation An infection is defined by the invasion and reproduction of bacteria, viruses, fungi, parasites, prions, or viroids within the human body. Whether the invading pathogen leads to a clinical manifestation of an infectious disease depends on the number and virulence of the pathogen as well as on the resistance of the patient. The host responds to the infection with an inflammation.

15.1.1.2 Surgical Infections Surgical infections have to be either treated by an operation or have been caused by a surgical intervention. Surgical infection can be divided into five different groups: 1. Primary abscessing infections (e.g., furuncle, carbuncle) 2. Secondary abscessing infections (e.g., liver abscess)

W. Böcker University of Munich, The Queen Elizabeth Hospital, 28 Woodville Rd, Woodville South, SA 5011, Australia e-mail: [email protected] W. Mutschler (*) Hospital of University of Munich, Ludwigs-MaximiliansUniversity, Nussbaumstrasse 20, 80336 Munich, Germany e-mail: [email protected]

15.1.1.3 Diagnosis of Surgical Infections Surgical infections primarily present with clinical symptoms. The clinical presentation on the body surface is one or more cardinal symptoms of inflammation: 1. Rubor (= redness) 2. Calor (= heat) 3. Tumor (= swelling) 4. Dolor (= pain) 5. Functio laesa (= impaired function) Infections of deep sites (e.g., abdominal abscess, implants) can initially have a complete lack of local symptoms and are sometimes difficult to diagnose. Systemic symptoms such as chills and fever may be present. Leukocytosis and elevated erythrocyte sedimentation rate (ESR) may be the only signs. Deep infections often need additional diagnostic tools such as CT scan, MRI, or PET scan. Scintigram may be helpful to diagnose infections of artificial joints and osteosynthesis materials. Sometimes needle aspiration with cells count and microbiology culture may give the final clue.

15.1.1.4 Infection Defense The goal of the body’s immune system is the elimination or inactivation of the invading organism. There are

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_15, © Springer-Verlag Berlin Heidelberg 2011

99

100

several physiological protective mechanisms which prevent the invasion of pathogens: 1. Intact body surface 2. Adequate tissue perfusion 3. Physiological bacterial colonization The human body responds to infection with a congenital unspecific and an acquired specific immune system. Several factors can lead to a failure or dysfunction of the immune system. Apart from congenital immune defects, acquired immune defects can impair the immune response: 1. Accompanying disease (e.g., diabetes, HIV, malignoma, hematological disease) 2. Medication (e.g., steroids, immunosuppressants) 3. Nicotine use 4. Older age 5. Bad general condition and malnutrition Several local factors favor an infection: 1. Opening of body surface (traumatic or operative) 2. Limited blood perfusion 3. Unfavorable wound conditions (necrosis, compromised blood perfusion) 4. Inadequate wound care (late wound closure, hematoma, long surgery time) 5. Implantation of foreign bodies (i.v. access, peritoneal dialysis catheter, long stay of drains, osteosynthesis material, endoprostesis, valves) Studies have also shown a coincidence of surgical site infections with remote site infections. Therefore, prior to elective surgery (e.g., joint replacement), these infections should be treated first.

15.1.1.5 Principles of Therapy The surgical therapy of infections consists of: 1. Operative treatment 2. Correction of the acquired immune defect (if possible) 3. Systemic antimicrobial therapy First-line treatment is early surgery with incision, removal of necrosis, and placement of a drain. This is particularly true for abscesses (Ubi pus ibi evacua!). One exception is an intra-abdominal abscess, which may be successfully treated by drainage alone. For

W. Böcker and W. Mutschler

local antimicrobial therapy, antiseptics can be used. Local application of antibiotics should be avoided because of the generation of resistance. Cooling by alcohol packing may suppress the inflammation. Systemic antimicrobial therapy is indicated (see Chap. 16): 1. With generalized infection (fever, chills) 2. With particular dangerous infections (e.g., gas ­gangrene, mediastinitis, pneumonia, sepsis) 3. As prophylactic perioperative measure (inserting implants and prosthesis; procedures, which are accompanied by an increased risk of infection: e.g., gastrointestinal tract surgery; operations on neck, eye, and breast) Systemic antibiotic therapy alone for abscessing infection is not recommended, since the pathogens cannot be reached by the drugs. Moreover, the treatment with antimicrobial drugs alone would prolong the course of infection.

15.1.2 Prevention of Surgical Infections 15.1.2.1 Hygiene The goal of hygienic measures is the prevention of ­surgical and nosocomial infections. With hygiene ­measures on patients, infection rates can be reduced. Mupirocin ointment is effective as a topical agent for eradicating S. aureus from the nares of colonized patients. Preoperative shaving of the surgical site the night before an operation is associated with a significantly higher risk of surgical site infections. Therefore, shaving immediately before the operation is recommended. Several antiseptic agents are available for preoperative preparation of skin at the incision site. Alcohol-containing products, iodophores (e.g., povidone-iodine), and chlorhexidine gluconate are the most commonly used agents. Hygiene measures with patient contact using masks, gloves, and gowns protect the patient as well as the surgical team. To prevent wound infections with dressing changes, aseptic measure should be used. Hygiene measures in the operating room which have been shown to be effective are the use of ventilation, routine cleaning of surfaces, the usage of drapes, and sterilization of surgical instruments. Positive

101

15  Surgical and Hospital-Acquired Infections

pressure prevents airflow to enter from less clean areas into the operating room.

15.1.2.2 Asepsis and Antisepsis In general, septic and aseptic surgeries can be discriminated. If possible, patients with and without wound infections should be separated on the ward and in the operating room. In aseptic surgeries, no pathogens are released. The postoperative risk of infection is significantly below 5%. Rigorous adherence to the principles of asepsis by all scrubbed personnel is the foundation of surgical site infection prevention. During septic procedures, a massive release of pathogens can be observed. Antisepsis describes the use of antiseptic agents in order to reduce the numbers of pathogens. Members of the surgical team who have direct contact with the sterile operating field or sterile instruments used in the field wash their hands and forearms by performing a traditional procedure known as scrubbing. This happens immediately before donning sterile gowns and gloves. Alcohol or povidone-iodine is considered the gold standard for surgical hand preparation. Surgical hand disinfection is a two step process: 1. Thorough cleaning underneath fingernails (usually with a brush) 2. Scrubbing at least for 3–5 min After performing the surgical scrub, hands should be kept up and away from the body (elbows in flexed position) so that antiseptic agent runs from the tips of the fingers toward the elbows. Jewelries and artificial nails have to be removed before scrubbing.

15.1.2.4 Antimicrobial Prophylaxis Surgical antimicrobial prophylaxis is used as a single i.v. administration of an antimicrobial agent just before the start of an (elective) procedure (within 30  min prior to  skin incision). Contaminated wounds often require longer duration of prophylaxis. Antimicrobial agents are used as intravenous infusions to reduce the microbial burden of intraoperative contamination to a level that cannot overwhelm host defenses. Serum and tissue levels should be maintained during the whole procedure. Antimicrobial prophylaxis is an evidence-based measure to reduce postoperative infections in a number of ­procedures (e.g., joint replacement, gastrointestinal surgery). The choice of the antimicrobial agent depends on the most likely pathogens (e.g., joint replacement: S. aureus, coagulase-negative Staphylococci, gram-negative bacilli; appendectomy: gram-negative bacilli, anaerobes). 15.1.2.5 Hospital-Acquired Infections Nosocomial infections are acquired in medical institutions and affect 4–10% of all inpatients and 25% of intensive care patients. Most common infections are pneumonia, upper respiratory tract, urinary tract, and wound infections as well as sepsis. Typical pathogens are Enterococcus spp., Staphylococcus aureus, coagulase-negative staphylococci, Escherichia coli, Pseudomonas aeroginosa, and fungi. A major problem with hospital-acquired infection is the prevalence of resistance against many different antimicrobial agents (multiple drug resistance), which has to be addressed with the choice of the antimicrobial agent. 15.1.2.6 Surveillance of Nosocomial Infections

15.1.2.3 Surgical Technique Excellent surgical technique is widely believed to reduce the risk of surgical site infections. Such techniques include gentle tissue handling, removing devitalized tissues, eradicating dead space, preserving adequate blood supply, preventing hypothermia, avoiding inadvertent entries into a hollow viscus, and appropriately managing the postoperative incision. All foreign bodies including suture material, prosthesis, and drains promote infections. Drains are effective in evacuating ­postoperative hematoma or seroma, which – if present – increases the risk for surgical site infection.

Many countries have implemented regulations that require hospitals to conduct surveillance of particular nosocomial infections. These measures are not only meant to identify outbreaks with pathogens that have multiple drug resistance, but also to identify an increa­sed incidence of surgical site infection of certain surgical procedures. MRSA is the most common pathogen with multiple drug resistance and most frequently observed in intensive care, trauma surgery, and vascular surgery wards. If there is an increased incidence of nosocomial infection, certain measures (screening, education, changes in hygiene procedures) have to be followed. A routine screening of all patients and personnel has not been recommended.

102

15.1.2.7 Management of MRSA (MethicillinResistant Staphylococcus aureus) Methicillin-resistant Staphylococcus aureus is a feared pathogen in nosocomial infections. These are asso­ciated with higher morbidity and mortality. The prevalence has increased significantly over the last few years. Patients at risk for MRSA (positive history, transfer from an institution with high prevalence, contact with MRSA carrier, chronically ill patient) have to be isolated until negative screening results are available. Colonized or infected patients have to be isolated. Personnel have to disinfect hands and wear gloves, mask, and gowns, which all remain in the room before leaving. All instruments (e.g., stethoscope, ECG, ultrasound) have to be disinfected. Daily cleaning of surfaces in the patient’s room is required. Patient’s blankets and pillows are washed daily. Elective surgeries should be avoided, and small procedures should be conducted in the patient’s room. Major surgeries should be performed in the septic operating room, and at the end of the daily operating program. Treatment of MRSA is done according to the sensitivity testing (e.g., vancomycin). The nares of colonized patients are treated effectively with Mupirocin ointment (3× daily, at least for 3 days). For eradication of skin colonization, whole body washings with antiseptic agents are performed. Also colonized personnel have to be eradicated and should not have patient contact before. Isolation of MRSA-colonized patients can be lifted, when 3  days after completion of treatment three consecutive smears are negative.

15.2 Surgical Infections 15.2.1 Bacterial Infections 15.2.1.1 Introduction Bacterial infection can be discriminated by different criteria: 1. Anatomically (skin: furuncle, fascia: necrotizing fasciitis) 2. Pathogen (Staphylococcus ssp., Streptococcus ssp., etc.) 3. Urgency of surgical intervention (urgent: furuncle; emergency: necrotizing fasciitis) 4. Extent of infection (local: abscess; diffuse: fasciitis)

W. Böcker and W. Mutschler

5. Degrees (uncomplicated infection; complicated infection: larger surgical intervention necessary, extension in deep soft tissues or severe comor­bidity) 6. Growing condition (aerobe, anaerobe) 7. Pus generation In clinical practice, infections are separated into aerobic and anaerobic infections.

15.2.2 Aerobic Infections 15.2.2.1 Abscess Definition: A collection of pus which accumulated in a tissue cavity formed on the basis of an infectious process. Abscesses can develop in any kind of solid tissue, but are most frequently localized on the body surface (e.g., needle abscess). More rarely abscesses are found within inner organs (brain, tonsils, teeth, liver). Typical pathogens are Staphylococcus, E.coli, and mixed infection. Symptoms: Cardinal symptoms of inflammation. Sometimes fluctuation can be observed near the body surface. A pulsating pain is typical. Therapy: Surgical drainage of the abscess is usually indicated once the abscess has developed from a harder serous inflammation to a softer pus stage. This is expressed in the Latin medical aphorism: Ubi pus, ibi evacua (“where there is pus, evacuate it”). Curettage, flushing, and local antiseptic agents clean the cavity. In addition, drains are frequently placed. With smaller localized abscesses, antimicrobial agents are not required. Needle aspiration of the abscess as only treatment is the exception, e.g., with placement of pigtail-catheter in intra-abdominal abscesses.

15.2.2.2 Empyema Definition: Infection in a preformed cavity with a missing initial necrosis. Localization: pericardium, gallbladder, pleura, and joints. Pathogens: Staphylococcus ssp., Streptococcus ssp., N. gonorrhoeae, E. coli, Proteus, anaerobic organisms, frequently mixed flora. Symptoms: Depend on localization. Shortness of breath and thoracic pain are seen with pleural- and pericardial empyema. Abdominal pain with gallbladder empyema. Swelling and redness with joint empyema. Fever and chills. Therapy: Incision, flushing, removal (where possible, e.g., gallbladder), drainage, and systemic

103

15  Surgical and Hospital-Acquired Infections

antimicrobial therapy are the major steps of adequate surgical intervention.

extensive necrosis. Therapy: Excision of necrosis. All abscesses have to be drained. Frequently antimicrobial therapy is necessary. Consider underlying undiagnosed immune suppression.

15.2.2.3 Furuncle Definition: Skin infection starting from hair follicles with localized accumulation of pus (Fig.  15.1). Localization: All hairy body surfaces. Pathogen: Staphylococcus ssp. Symptoms: Classical symptoms of inflammation. Can be very painful. Therapy: Most furuncles run their course within 1 week. Soaking the furuncle with warm water can help to alleviate the pain and hasten draining the pus. Incision is rarely necessary and only performed with local pus accumulation. Antimicrobial agents are only necessary in severe cases and with generalized spread (furunculosis). Always consider underlying immune suppression (e.g., undiagnosed diabetes, malnutrition with vitamin deficiency).

Definition: Acute Streptococcus infection of the skin and subcutaneous tissue (Fig. 15.2). Localization: Most frequently face and extremities. Pathogen: Streptococcus pyogenes. Symptoms: Patients typically develop symptoms including high fevers, chills, and general illness within 48 h of the initial infection. Characteristically, the erythematous skin lesion enlarges rapidly and has a sharply demarcated raised edge (Fig. 15.3). Therapy: Antimicrobial therapy, immobilization, cold dressing. Search for skin ulcerations (e.g., between toes) and consider immune suppression.

15.2.2.4 Carbuncle

15.2.2.6 Phlegmon

Definition: Confluent skin infection originating from several furuncles. Localization: Preferably neck, back, and buttocks. Pathogen: Staphylococcus ssp. Symptoms: Pain with pressure and redness of skin, sometimes with

Definition: Diffuse and infiltrating infection. Due to special enzymes (hyaluronidase, streptokinase), pathogens spread in the interstitial soft tissue (Fig.  15.2). Loca­lization: Skin, intermuscular

Folliculitis

Boil

15.2.2.5 Erysipelas

Carbuncle

Fig. 15.1  Folliculitis, furuncle and carbuncle are distinguished by the extent of infection. These skin infections are most frequently caused by Staphylococcus ssp. infection

104

W. Böcker and W. Mutschler

Epidermis

Dermis

Subcutaneous tissue Fascia Muscle

Erysiplas

Phlegmon

Necrotizing fasciitis

Fig.  15.2  Erysipelas are infection of the dermis. Phlegmon extents with special enzymes into the soft tissue of the subcutis. Necrotizing infections are even more aggressive and invade the through fascia into the muscle

15.2.2.7 Gangrene

Fig. 15.3  Typical clinical presentation of erysipelas. This acute Staphylococcus pyogenes infection characteristically enlarges rapidly and has a sharply demarcated raised edge

and intramuscular, mediastinal, and retroperitoneal. Pathogens: Strepto­coccus ssp., Staphylococcus ssp., Proteus, anaerobes (Bacterioides), enterobacteria, sometimes mixed flora. Symptoms: Depend on type of pathogen and localization. Frequently diffuse redness and swelling is found. Fever and leukocytosis. Therapy: Antimicrobial therapy is mandatory. In severe cases, immediate surgical intervention is necessary. Eradicate the source.

Definition: Complication of necrosis caused by infection and/or ischemia. A necrosis without inflammation is called mummification. Localization: Most frequently lower extremities. Less frequent other soft tissues: Fournier’s gangrene (severe spontaneous gangrene of scrotum with high morbidity and mortality). Pathogens: Anaerobes, saprogenic microorganisms, frequently mixed flora. Symptoms: Extended necrosis with black to gray-green discoloration, fecal smell, often without pain. The toxic products formed by bacteria are absorbed and can cause systemic manifestation of septicemia as well as death. Therapy: Removal of all necrotic tissue. Amputation of extremities is often necessary. Improvement of vascular perfusion is essential.

15.2.2.8 Necrotizing Infection Definition: Live-threatening and fast progressing infection with necrosis of fascias and muscle (Fig.  15.2). Pathogens: Streptococcus (Streptococcus gangrene, necrotizing fasciitis, Streptococcus myositis), Staphylococcus (necrotizing fasciitis), Clostridium (myositis, cellulitis), sometimes mixed flora. Localization: Infections extend along subcutis, fascia, and muscle septums. Symptoms:

105

15  Surgical and Hospital-Acquired Infections

Severe pain and characteristic livid red discoloration of the skin. With progression development of necrosis. Fast development of a septic picture with multiple organ failure. Therapy: Immediate surgical intervention with extended debridement is essential. With delayed surgical intervention, mortality exceeds 50%. Intensive care treatment is usually needed. Systemic antimicrobial therapy with broad-spectrum antibiotics. Hyperbaric oxygen therapy (HOT) has significantly reduced fatality rates. After debridement, wounds are left open and closure may be attempted after second look operation. Vacuum-assisted closure can be considered after complete surgical removal of all necrotic tissues.

15.2.2.9 Panaris and Paronychia Definition: Infection of the nail fold or wall. Symptoms: Initially redness and severe pressure pain. Later development of an abscess. Therapy: In early stages, finger bath and local anti-inflammatory treatment with immobilization. Abscesses must be drained.

15.2.2.10 Bursitis Definition: Acute or chronic inflammation of a bursa. Commonly caused by repeated movement and excessive pressure. Carries a high risk of infection with open injuries. Localization: Typically in exposed positions (elbow and knee). Pathogens: In open injuries, Streptococcus and Staphylococcus. Symptoms: Pain, redness, swelling, and fluctuation. Therapy: Surgical excision of the bursa in case of purulent bursitis and in open injuries. Immobilization.

15.2.3 Anaerobic Infections 15.2.3.1 Tetanus Definition: Wound infection caused by bacteria which secrete a neurotoxin (tetanospasmin). As the infection progresses, the released neurotoxin causes characteristic muscle spasms. In some countries, the disease is notifiable. Localization: Any contaminated wound. Pathogen: Clostridium tetani. Symptoms: After an

incubation time of 3–60  days (typically 1–2  weeks) initial unspecific general symptoms. Thereafter, a characteristic sequence of symptoms: muscle spasm in the jaw (trismus or lockjaw), facial spasm (risus sardonicus), followed by difficulty to swallow and rigidity of calf and pectoral muscle. Spasms shape the body into a characteristic hyperlordosis called opisthotonus. Symptoms may last for several weeks, if left untreated. Therapy: Until now, only symptomatic treatment is available. Therefore, tetanus prophylaxis is very important. In addition to adequate wound care to avoid anaerobe wound condition, prophylaxis by immunization is essential. With existing pre-immunization, refreshment is ­necessary with tetanus toxoid every 5  years. With no  pre-immunization, a simultaneous immunization with tetanus toxoid and passive immunization with human anti-tetanospasmin immunoglobulin or tetanus immunoglobulin is crucial.

15.2.3.2 Gas Gangrene Definition: Bacterial tissue infection with gas-producing pathogens. Rapidly progressing and lifethreatening infection. Typically, the environmental bacteria enter through contaminated wounds and expand in anaerobic environments. The organism not only produces gas, but also secretes powerful exotoxins. Localization: Soft tissues. Pathogens: Clostridium perfringens (90%) and other Clostridium species. Symptoms: Extremely painful, rapidly progressing wound infection. Charac­teristically crepitation on palpation. Drainage of black-blood-stained fluid, foamy, sweet-rotten smelling secretion. The affected muscles appear gray-red. Sometimes, on X-ray, the gas can be seen. The general condition of the patient rapidly deteriorates with sepsis and multiple organ failure. Therapy: Must start immediately with clinical suspicion. Leaving this condition untreated always ends with the patient’s death. Surgical interventions with extended debridement have to counteract anaerobe wound conditions. If necessary, affected extremities have to be amputated. Antimicrobial therapy has to start with suspicion. Even with surgery and antimicrobial therapy, mortality still is up to 40%. With hyperbaric oxygen therapy (HOT), mortality rates can be decreased to 20–25% and amputation rates can be decreased by 70%.

 

Antimicrobial Therapy

16

Christian P. Schneider and Beatrice Grabein

16.1 Introduction Antimicrobial agents are widely used pharmaceuticals in hospital and outpatient care. They are causal therapeutic agents and their rational use can decrease antibiotic resistance, and therefore, hospital stay and treatment costs. However, due to increased quality standards and cost pressure for public health services, these requirements can only be achieved if up-to-date infectious disease management strategies have been implemented. Although guidelines and recommendations from several associations and institutions were included in this chapter, it is important to note that rational empiric antibiotic therapy underlies continuous alterations. Therefore, therapeutic recommendations can only capture basic principles. Often various therapeutic options are available, and the therapeutic spectrum is not always comparable in different countries or institutions. Various treatment options help to avoid allergic reactions and allow to choose antibiotic agents according to the individual patient’s risk profile.

C.P. Schneider (*) Department of Surgery, University Hospital Munich, Ludwig-Maximilians University Munich, Campus Großhadern, Marchioninistr. 15, 81377 Munich, Germany e-mail: [email protected] B. Grabein Max von Pettenkofer-Institute for Hygiene and Clinical Microbiology, Ludwig-Maximilans University Munich, Campus Großhadern, Marchioninistr. 15, 81377 Munich, Germany e-mail: [email protected]

16.2 Basic Principles of Antimicrobial Therapy Characterization of antibiotics, pharmacokinetics, efficacy, antibiotic resistance, and side effects (Table 16.1). The antibiotic agents described were selected with specific consideration of their importance in the surgical field.

16.3 Penicillins The classification of penicillins is based on their chemical structure. Different chemical constitutions imply varying effects against pathogens and their beta-­ lactamases. Penicillins are bactericidal due to blockade of bacterial transpeptidases which are important for the peptidoglycan synthesis in the bacterial cell wall. Benzylpenicillins, aminopenicillins, and isoxazolylpenicillins are available in parenteral and enteral pharmaceutical forms, whereas acylaminopenicillins can only be administered intravenously. Penicillins are approved for treatment of systemic and local infections with various gram-positive and gram-negative pathogens. A wider range of pathogens can be treated via combination of penicillins with a beta-lactamase inhibitor.

16.3.1 Pharmacokinetics Penicillins generally exhibit a medium to high plasma concentration while their half-life is in the low to middle range (0–10 h). They reside mostly in the extracellular space with a low relative distribution volume of 0–0.4 L/kg. The rate of metabolization is low,

M.W. Wichmann et al. (eds.), Rural Surgery, DOI: 10.1007/978-3-540-78680-1_16, © Springer-Verlag Berlin Heidelberg 2011

107

108

C.P. Schneider and B. Grabein

Table 16.1  Antimicrobial agents for parenteral application Groups Subgroups Drugs Penicillins

Maximum dosage

Benzylpenicillin

Benzylpenicillin

10 million units q4–6 h

Aminopenicillin

Ampicillin

2 g q8h

Aminopenicillin/BLI

Amoxicillin/clavulanate

2.2 g q8h

Ampicillin/sulbactam

3 g q8h

Carboxypenicillin/BLI

Ticarcillin/clavulanate

3.1 g q4–6 h

Acylaminopenicillins

Piperacillin

4 g q8h

Mezlocillin

4–5 g q8h or 10 g q12h

Acylaminopenicillin/BLI

Piperacillin/tazobactum

4.5 g q8h

Isoxazolylpenicillins

Flucloxacillin

2 g q4–6 h

Oxacillin

4–8 g q4–6 h

First generation

Cephazolin

2 g q8h

Second generation

Cefuroxime

1.5 g q8h

Cefotiam

2 g q8h

Cefotaxime

2 g q8h

Ceftriaxone

2 g q12h

Third generation with anti-pseudomonal activity

Ceftazidime

2 g q8h

Fourth generation

Cefepime

2 g q8–12 h

Fifth generation

Cefoxitine

2 g q8h

Group 1

Imipenem

1 g q8h

Group 2

Meropenem

1 g q8h

Ertapenem

1 g q24h

Doripenem

500 mg q8h

Aztreonam

2 g q6–8 h

Ofloxacin

400 mg q12h

Ciprofloxacin

400 mg q8h

Group 3

Levofloxacin

500 mg q12h

Group 4

Moxifloxacin

400 mg once daily

Erythromycin

1 g q6h

Clarithromycin

500 mg q12h

Azithromycin

500 mg once daily

Vancomycin

15–20 mg/kg BW q12h

Teicoplanin

400 mg q12h on day 1,and than 400 mg once daily

Lipopeptide

Daptomycin

4 mg/kg BW once daily

Aminoglycoside

Amikacin

15 mg/kg BW once daily

Gentamicin

5–7 mg/kg BW once daily

Netilmicin

5–7 mg/kg BW once daily

Tobramycin

5–7 mg/kg BW once daily

Cephalosporins

Third generation

Carbapenems

Ungrouped Monobactams Fluroquinolones

Macrolide

Glycopeptide

Group 2

109

16  Antimicrobial Therapy Table 16.1  (continued) Groups Subgroups

Drugs

Maximum dosage

Oxazolidinone

Linezolid

600 mg q12h

Lincosamide

Clindamycin

600 mg q8h

Streptogramin

Quinupristin/dalfopristin

7.5 mg/kg BW q8h

Tetracycline

Doxycyclin

200 mg q24h on day 1, and than 100 mg once daily

Glycylcycline

Tigecycline

100 mg q24h on day 1, and than 50 mg once daily

Ansamycins

Rifampicin

10 mg/kg BW once daily, (maximum 900 mg/day)

Nitroimidazole

Metronidazole

500 mg q8h

Fosfomycine

Fosfomycin

4–8 g q8h

Sulfonamide/ Benzylpyrimidine

Co-trimoxazol

960 mg q12h

q every, h hours, kg kilogram, g gram, mg milligram, BW body weight, BLI beta-lactamase inhibitor

and penicillins are mainly eliminated via the kidneys through tubular secretion. Isoxazolylpenicillins have a high plasma protein–binding capacity and low tissue distribution compared to the other penicillins. The best time-dependent efficacy kinetics can be reached if drug concentrations at the site of infection are above the minimum inhibitory concentration and therefore short treatment intervals are necessary.

16.3.2 Efficacy and Indication The efficacy of penicillins is dependent on their chemical structure. It ranges from small spectrum (Penicillin G) and extends to broad-spectrum efficacy if combined with beta-lactamase inhibitors (Piperacillin-Tazobactam). Application of Penicillin G is limited to Strep­ tococcus species (spp.), Pneumococci, Meningococci, and some anaerobic pathogens (Clostridium spp., Actinomyces spp.) and should not be given as a single agent if a serious infection is present. Nevertheless, Penicillin G is still the first choice for erysipelas and treatment of infections with Streptococcus and Pneumococcus if cultures do not reveal mixed pathogens. Aminopenicillins have a broad-spectrum efficacy. They are very effective against Enterococcus and some gram-negative pathogens. Aminopenicillins are approved for treatment of endocarditis and meningitis. In combination with beta-lactamase inhibitors, their spectrum is extended to infections with several other gram-positive

and gram-negative pathogens, including infections of the upper respiratory tract, urinary tract, abdomen, genitals, skin, and soft tissue. Isoxazolylpenicillins have a narrow spectrum only and are useful against Staphylococcus including those strains producing penicillinase. Possible indications are endocarditis, arthritis, infection of the skin and soft tissue as long as the Staphylococcus strain is not resistant against methicillin. Acylaminopenicillins are broad-spectrum antibiotics and include gram-positive and gram-negative aerobic and anaerobic pathogens. Piperacillin also covers infections with Pseudomonas aeruginosa. In combination with beta-lactamase inhibitors, they are also effective against various beta-lactamase-producing pathogens. Indications are infections of nearly all organ systems. Piperacillin-Tazobactum can be used as rational empiric antibiotic therapy for serious infections.

16.3.3 Antibiotic Resistance Resistance of Streptococcus and Pneumococcus against penicillin is still low at approximately 2% of the isolates, but can reach up to 30% in some countries. The resistance rate of Escherichia coli against aminopenicillins increased within the last years to more than 50%. The efficacy of piperacillin-tazobactam against Pseudomonas aeruginosa is still sufficient. The fraction of oxacillin-resistant Staphylococcus aureus (MRSA) is continuously increasing. It ranges

110

C.P. Schneider and B. Grabein

from approximately 15% of Staphylococcus aureus isolates from hospital patients in some European countries to more than 60% in the United States. The antibiotic resistance rate for Staphylococcus epidermidis and coagulase-negative Staphylococcus is commonly more than 70%.

16.3.4 Side Effects (Table 16.2) Allergic reactions can be observed in 0.7–10% of all patients treated with penicillins and occur particularly after repeated applications. These hypersensitive reactions are characterized by nausea, vomitus, bronchospasm, and hypotonia. Delayed allergic reactions can appear 7–10  days after administration of penicillins with fever, urticaria, lymph node swelling, and hemolytic anemia, defined as Type III hypersensitivity reactions (Arthus type). Neurotoxicity can arise only after application of high dosage of penicillins (80–100  Mio. IU/day). Additionally, pseudoallergic skin reactions may occur after treatment with aminopenicillins if a concomitant viral infection is present (mononucleosis). Antibiotic therapy with isoxazolylpenicillins can increase liver enzymes.

16.4 Cephalosporins Cephalosporins are grouped into basic and broadspectrum cephalosporins. They are generally classified into five groups. Cephalosporins are bactericidal, and their pharmacokinetic characteristics are comparable to penicillins. Agents of groups 1 and 2 are effective against Staphylococci which decreases in groups 3–5. In contrast, substances of groups 2–5 have increasing efficacy against gram-negative pathogens. Additionally, cephalosporins possess a good efficacy against pathogens producing beta-lactamase based on their stability against various kinds of bacterial beta-lactamases.

16.4.1 Pharmacokinetics Most cephalosporins are eliminated unmodified via the kidneys, and their mean half-life is 2 h in patients with normal renal function. Their distribution in the different body compartments is also similar to those of penicillins. Only ceftriaxone (group 3a) reveals an extended half-life of 8 h, and therefore, a single daily application is sufficient. Moreover, approximately 50% of ceftriaxone is excreted via the biliary system.

Table 16.2  Side effects of penicillin treatment and alternative treatment options Cross-reactivity between beta-lactam antibiotics Penicillins

® First-generation cephalosporins

1.7–5.6%

® Second-generation cephalosporins ® Third-generation cephalosporins Penicillins

® Carbapenems

~50%

Penicillins, cephalosporins

® Aztreonam

Rarely

Cephalosporins

® Carbapenems

Lowly

Ceftazidime

® Aztreonam

Commonly

Staphylococcus spp.

Clindamycin, doxycyclin, glycopeptide, linezolid, macrolide, rifampicin

Alternative antimicrobial substances Gram-positive bacteria

Streptococcus spp. Pneumococcus Gram-negative bacteria

Escherichia coli Enterobacteriaceae

Aminoglycoside, aztreonam, fluoroquinolones, doxycycline

111

16  Antimicrobial Therapy

16.4.2 Efficacy and Indication

16.4.4 Side Effects

In general, all cephalosporins are ineffective against Enterococci and methicillin-resistant Staph­ylococci. Substances of the first generation ­(cephazolin) have a good efficacy against methicillin-sensible Staphy­ lococci and Streptococci, but are weak against gramnegative pathogens. Cepha­losporins of the second generation (cefuroxime, cefotiam) have an extended spectrum against gram-negative bacteria and con­ tinuing activity against gram-positive pathogens. ­Third-generation cephalosporines (cefotaxime, ceftriaxone) have a broad-spectrum with excellent activity against gram-negative bacteria but decreasing effects against Staphylococci. In addition, ceftazidime (third generation with anti-pseudomal activity) and cefepime (fourth generation) exhibit anti-pseudomonal activity. Cefepime also has good efficacy against Staphylococci, Streptococci and beta-lactamase-producing bacteria compared to ceftazidime. Furthermore, cephalosporins of the fifth generation (cefoxitine) are effective against anaerobic pathogens. Cephalosporins are approved for treatment of various kinds of infections, including infections of the respiratory and urinary tracts, bones and joints, genitals, skin and soft tissue. Cefotiam and cephalosporins of the third to fifth generation are also approved for infections of the biliary tract and abdomen. In addition, cephalosporins of the first, second, third, and fifth generation are used as prophylactic antibiotics during the perioperative phase.

Possible side effects are comparable to those of penicillins, but allergic reactions are fewer. Increased liver enzymes and gastrointestinal discomfort occur in 5–10% of all treated patients. Augmented risk of bleeding may appear if anticoagulants are given simultaneously with cefoxitin. Therapeutic administration of ceftriaxone can rarely lead to shadows in the ultrasound of the gall bladder which is called transitory ­biliary pseudolithiasis.

16.4.3 Antibiotic Resistance High rates of antibiotic resistance for second-generation cephalosporins can be detected in Enterobacter spp., Citrobacter, and indol-positive strains of the Proteus group. Since several years, increasing antibiotic resistance rates up to 28% can be observed in Escherichia coli isolated from ICU patients. Isolates of Klebsiella pneumoniae and Escherichia coli producing extendedspectrum-beta-lactamases (ESBL) cause antibiotic resistance against third- and fourth-generation cephalosporins ranging from 4–8% up to 55% (South America) in hospitalized patients.

16.5 Carbapenems Carbapenems are also beta-lactam antibiotics with bactericidal efficacy due to inhibition of the bacterial cell wall synthesis. They are divided into two groups with group 1 consisting of imipenem and group 2 of meropenem and ertapenem. Carbapenems, especially those of group 1, are broad-spectrum antibiotics approved for the treatment of serious life-threatening infections and empiric therapy in patients receiving immunosuppressive medication.

16.5.1 Pharmacokinetics The distribution volume of carbapenems is small and mainly extracellular. Protein-binding capacity is more than 90% for ertapenem, while imipenem and meropenem have much lower capacities with 20% and 2%, respectively. In part, carbapenems are metabolized and predominately eliminated via the kidneys. Ertapenem has a longer plasma half-life of 4 h compared to the other carbapenems.

16.5.2 Efficacy and Indications Carbapenems are broad-spectrum antibiotics, and their efficacy includes almost all bacteria including anaerobic pathogens, except for Enterococcus facium, methicillin-resistant Staph­ylococci, and Stenotropho­ monas maltophilia. Doripenem is very effective against

112

C.P. Schneider and B. Grabein

Pseudomonas aeruginosa, Enterobacteriaceae, and Acinetobacter spp. which are resistant against other antimicrobial drugs. The efficacy of ertapenem is different with no effects against Pseudomonas aeruginosa, Acinetobacter spp., and Enterococci. Carbabenems are approved for the treatment of serious pneumonia, intra-abdominal infections, sepsis, and infections of the skin and soft ­tissue and for empiric therapy in neutropenic patients.

16.6.1 Pharmacokinetics

16.5.3 Antibiotic Resistance

16.6.2 Efficacy and Indication

Currently, antibiotic resistances including Entero­ bacteriaceae are rare. It has been shown that some Klebsiella species are resistant against carbapenems due to release of carbapenem-hydrolyzing metallobeta-lactamases. Although the efficacy of carbapenems is still good, infections with Pseudomonas aeruginosa, Burkholderia cepacia, or other non-­fermenting bacteria in hospitalized and/or immunosuppressed patients demonstrate increased rates of resistance.

Aztreonam has strong activity against susceptible gram-negative bacteria, including Pseudomonas aerug­ inosa. It is approved for treatment of pneumonia, skin and soft tissue infections, complicated and uncomplicated urinary tract infections, gynecologic infections, and intra-abdominal infections and septicemia caused by gram-negative bacteria in combination with anaerobic coverage.

16.5.4 Side Effects

The distribution volume of aztreonam is low, but sufficient levels can be reached in urine; bile; and pleural, pericardial, and synovial fluids. Approximately 56% is bound to plasma proteins and the plasma half-life is 2 h. Aztreonam is not metabolized and is mainly excreted via glomerular filtration and tubular secretion as unchanged drug.

16.6.3 Antibiotic Resistance

Mild gastrointestinal symptoms can be observed in 5–10% of all treated patients. Allergic reactions occur rarely with less than 3%.

Anaerobic bacteria, Acinetobacter spp., Burkholderia cepacia-complex, Stenotrophomonas maltophilia, and gram-positive pathogens are generally resistant against aztreonam.

16.6 Monobactams

16.6.4 Side Effects

The only available monobactam is aztreonam. The mechanism of action is similar to beta-lactams. It is stable against some beta-lactamases. Aztreonam is bactericidal through inhibition of mucopeptide synthesis in the bacterial cell wall, and thereby blocking peptidoglycan crosslinking. It is only active against gram-negative bacteria. Aztreonam displays good efficacy against Entero­bacteri­ aceae and non-lactose fermenters including Pseudomonas aeruginosa. There is limited cross-reactivity between aztreonam and other beta-lactam antibiotics, and it is generally considered safe to administer aztreonam to patients with hypersensitivity to penicillins.

Side effects include injection site reactions, rash, ­gastrointestinal disorder, and rarely toxic epidermal necrolysis. There may be drug-induced eosinophilia.

16.7 Fluroquinolones Fluoroquinolones are divided into four groups. Group one has no clinical relevance and clinical relevant agents are ciprofloxacin, ofloxacin and norfloxacin (group 2), levofloxacin (group 3), and moxifloxacin

113

16  Antimicrobial Therapy

(group 4). They can be administrated parenterally as well as orally due to their excellent acid stability. Fluroquinolones are bactericidal through inhibition of bacterial DNA-gyrases which are important for the nucleotide acid synthesis.

strains. Escherichia coli has resistance rates from 7% up to 20% of all isolates, Staphylococcus aureus from 15% up to 60% (mostly MRSA isolates) and Pseudomonas aeruginosa from 10% up to 30% against ciprofloxacin.

16.7.1 Pharmacokinetics

16.7.4 Side Effects

The relative distribution volume of all fluoroquinolones is large with 2 up to 41  L/kg and they penetrate excellently into various tissues. Their plasma protein– binding capacities add up to <40%. The half-life varies between 3 and 4 h for ciprofloxacin and norfloxacin, 7–8 h for ofloxacin and levofloxacin, and >10 h for moxifloxacin. Therefore, their intervals of administration differ. Levofloxacin and ofloxacin are eliminated via renal secretion while ciprofloxacin and norfloxacin also are eliminated via the liver and intestines. Moxifloxacin is almost completely eliminated via ­conjugation reactions.

Side effects after treatment with fluoroquinilones are present in 4–10% of all patients. Common symptoms are gastrointestinal irritation, affection of the CNS with sleep disturbances and obnubilation. Reactions of the skin are rare, but UV exposure should be avoided due to the phototoxic effects of all fluoroquinolones. Caution is needed in patients with tendon degeneration, since tendon ruptures have been described after administration of fluoroquinolones. Additionally, prolongation of the QTc-interval has been observed after therapy with fluroquinolones.

16.7.2 Efficacy and Indications Fluoroquinolones are approved for the treatment of infections of the urinary tract, ENT and respiratory tract, abdomen, genitals, bones, skin and soft tissues as well as for serious systemic infections (i.e., sepsis). Ciprofloxacin, ofloxacin, and norfloxacin (group 2) have a good efficacy against gram-negative bacteria (Enterobacteriaciae, Hemophilus influencae, Pseudomonas aeruginosa) and a considerably lower effectiveness in the gram-positive field (Staphylococci, Pneumococci, and Enterococci). Levofloxacin (group 3) has better and moxifloxacin (group 4) much better effects against gram-positive and atypical pathogens. Moxifloxacin has a poor effectivity against Pseudomonas aeruginosa but the antibiotic spectrum of moxifloxacin also includes anaerobic bacteria.

16.7.3 Antibiotic Resistance In recent years, antibiotic resistance rates against fluroquinolones are on the rise in all relevant bacterial

16.8 Macrolides The most commonly used macrolides are erythromycin, clarithromycin, and azithromycin which can be applied parenterally, while roxithromycin can only be given enterally. The mechanism of action of macrolides is inhibition of bacterial protein biosynthesis by binding reversibly to the subunit 50S of the bacterial ribosome, thereby inhibiting translocation of peptidyl-tRNA. This action is mainly bacteriostatic, but can be bactericidal in high concentrations. Macrolides tend to accumulate within leukocytes, and therefore, they become transported to the site of infection. Presently, their use in the surgical field is limited.

16.8.1 Pharmacokinetics The half-life of macrolides ranges from 2.5 h for erythromycin, 2–5 h for clarithromycin, 12 h for roxithromycin, and >14 h for azithromycin. The distribution volume varies considerably from 0.7 L/kg BW for erythromycin up to 25 L/kg BW for azithromycin. Erythromycin is predominantly metabolized by demethylation in the

114

liver. The main elimination route of macrolides is via the biliary tract, and a small fraction via the urine (<4.5%).

16.8.2 Efficacy and Indications Macrolides are approved for the treatment of infections of the upper airways, ENT field and the urinary tract caused by Streptococci, Pneumococci, Chlamydia, Legionella, Mycoplasma, and Ureaplasma. Entero­ bacteriaceae and Pseudomonas spp. are generally resistant against macrolides. Macrolides represent an alternative treatment option for infections with Strep­ tococci (scarlet fever, erysipelas) in patients with an allergy to penicillins.

16.8.3 Antibiotic Resistance

C.P. Schneider and B. Grabein

the addition of new units to the peptidoglycan. Glycopeptides are only effective against gram-positive bacteria. They are considered as reserve option for the treatment of infections with multi-resistant gram-positive pathogens, as their efficacy in beta-lactam-susceptible pathogens is worse than that of the beta-lactams.

16.9.1 Pharmacokinetics Glycopeptides have a time-dependent therapeutic effect and are distributed only within the extracellular space. Therefore, their distribution volume is very small. In addition, their ability to penetrate into tissue is limited. The half-life of vancomycin ranges from 6 to 8 h and for teicoplanin from 70 to 100 h. Teicoplanin has a much higher protein-binding capacity with 90% compared to vancomycin with 55%. Glycopeptides are eliminated via renal secretion. Therapeutic drug monitoring is mandatory during treatment with glycopeptides because pharmacokinetics vary largely between individuals.

Antibiotic resistance rates of Pneumococci against macrolides range at approximately 20%.

16.9.2 Efficacy and Indication 16.8.4 Side Effects Macrolides, mainly erythromycin and clarithromycin, have a class effect of QT prolongation which can lead to torsade de pointes. Macrolides exhibit enterohepatic recycling which can lead to recurrence of the product in the system, causing nausea, gastrointestinal disorder, and increase in liver enzymes. Local reactions at the site of application (phlebitis) are frequent. Furthermore, treatment with macrolides can cause vertigo.

16.9 Glycopeptides The glycopeptides vancomycin and teicoplanin are only available for parenteral application because they are not absorbed after oral intake. This class of drugs inhibits the synthesis of cell walls in susceptible microbes by inhibiting peptidoglycan synthesis. They bind to the amino acids within the cell wall preventing

Glycopeptides are very effective against various infections with gram-positive pathogens (Staphylococci, Streptococci, and Enterococci), such as endocarditis, pneumonia, bone infection, infection of the kidneys, and serious systemic infections (sepsis). Importantly, glycopeptides are the first-line antimicrobial agent for infections with multi-resistant Staphylococci (MRSA and MRCNS) and Enterococci.

16.9.3 Antibiotic Resistance Antibiotic resistance of methicillin-resistant Staphy­ lococcus aureus and Enterococcus faecalis against glycopeptides is still very rare but can be occasionally observed for Staphylococcus epidermidis. In contrast, antibiotic resistance of Enterococcus faecium against glycopeptides can be seen frequently with varying profiles of resistance against both vancomycin and teicoplanin. The resistance rates can reach up to 30% which usually occurs in intensive care patients.

16  Antimicrobial Therapy

115

16.9.4 Side Effects

(including glycopeptide-resistant Enterococci (GRE)), Staphylococci (including methicillin-resistant Staphy­ lococcus aureus), Streptococci, and corynebacteria. Daptomycin is approved for skin and skin structure infections caused by gram-positive infections, Staphy­ lococcus aureus bacteremia, and right-sided S. aureus endocarditis. In lung tissue, daptomycin becomes ­rapidly inactivated by surfactant, and ­therefore, daptomycin is ineffective in pneumonia treatment.

Glycopeptides are usually given as an infusion and can cause tissue necrosis and phlebitis at the injection site if administered too rapidly. Indeed pain at the site of injection is a common adverse event. One of the side effects is called “Red man syndrome,” an idiosyncratic reaction to bolus administration, caused by histamine release. Some other side effects of vancomycin are nephrotoxicity including renal failure and interstitial nephritis, blood disorders including neutropenia, deafness, and gastrointestinal disorder (reversible after termination of treatment).

16.10 Lipopeptides Daptomycin represents the first antibiotic agent of this new antibiotics class. Daptomycin has a distinct mechanism of action, disrupting multiple aspects of bacterial cell membrane function dependant on calcium integration into cytoplasmic cell membrane. It appears to bind to the membrane and cause rapid depolarization, resulting in a loss of membrane potential leading to inhibition of protein, DNA, and RNA syntheses, which results in bacterial cell death.

16.10.3 Antibiotic Resistance Antibiotic resistance against daptomycin has been observed only in few cases.

16.10.4 Side Effects Side effects commonly seen after administration of daptomycin are elevation of creatinine kinase, gastrointestinal disorders (constipation, nausea, diarrhea, vomiting, dyspepsia, abdominal pain, decreased appetite, stomatitis, and flatulence), pain at the site of administration, headache, and insomnia.

16.10.1 Pharmacokinetics 16.11 Aminoglycosides Half-life of daptomycin is 7–9 h and more than 90% binds to plasma proteins. Elimination takes place in 78% via renal secretion and 5% are egested via feces. Adjustment of dosage in older patients and patients with mild-to-moderate liver dysfunction (Child-Pugh classes A and B) is not necessary but administration intervals extend up to 48 h in patients with renal failure (creatinine clearance <30 mL/min, hemodialysis, and peritoneal dialysis).

16.10.2 Efficacy and Indications Daptomycin is active against gram-positive bacteria only. It has proven in vitro activity against Enterococci

The most important substances of this antibiotic class are amikacin, gentamicin, netilmicin, and tobramycin all of which can be administrated parenterally only. Tobramycin may be given in a nebulized form as well. Aminoglycosides demonstrate rapid bactericidal effects through irreversibly binding to the bacterial 30S ribosomal subunit (amikacin works by binding to the 50S subunit), inhibiting the translocation of the peptidyl-tRNA from the A-site to the P-site, and also causing misreading of mRNA, leaving the bacterium unable to synthesize proteins vital to its growth. Indications are serious infections with gram-negative bacteria and also in combination with beta-lactam antibiotics therapy of endocarditis caused by gram-positive cocci (Enterococci and Streptococci) due to synergistic

116

effects. However, the decision to use aminoglycosides must be made carefully due to their poor tissue distribution and high nephrotoxicity.

16.11.1 Pharmacokinetics Aminoglycosides are almost exclusively distributed within the extracellular space. Therefore, their distribution volume is low with a short half-life of approximately 2 h in patients with normal kidney function. Since the therapeutic ratio of aminoglycosides is low, drug monitoring is mandatory particularly if renal function is impaired. A daily single application time point of the total dosage has been established for all aminoglycosides because of comparable antimicrobial activity and reduced nephrotoxicity compared to administration in three smaller dosages.

C.P. Schneider and B. Grabein

16.11.4 Side Effects Aminoglycosides have potential nephrotoxic and ­ototoxic side effects which are cumulatively and dose dependant. They also interfere with neuromuscular signaling, and therefore, they should not be given if patients suffer from Myasthenia gravis. Allergic reactions, blood disorders, and impaired liver function are side effects which can occasionally be observed after treatment with aminoglycosides.

16.12 Oxazolidinone Linezolid is the only agent of this new antibiotic class and can be given orally as well as i.v. Oxazolidinones are protein synthesis inhibitors and stop growth and reproduction of bacteria by disrupting translation of messenger RNA (mRNA) into proteins in the ribosome. Linezolid is considered bacteriostatic against most organisms, but has some bactericidal activity against Streptococci.

16.11.2 Efficacy and Indications Aminoglycosides are primarily used for treatment of infections involving aerobic, gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter as well as Staphylococci. In general, they should be given in combination with other antimicrobial substances, preferably with beta-lactam antibiotics due to synergistic effects. The therapeutic administration of aminoglycosides is approved for the treatment of serious infections (sepsis), fever in neutropenic patients, Pseudomonas infections in patients with cystic fibrosis (also for inhalation), and endocarditis. Amikacin is also effective against gram-negative pathogens with resistance against gentamicin and tobramycin.

16.11.3 Antibiotic Resistance Antibiotic resistance develops fast because of decreased accumulation of the substances in bacteria and loss of binding affinity. Additionally, inactivation of aminoglycosides takes place through enzyme induction via acetylation, adenylation, and phosphorylation of the drugs.

16.12.1 Pharmacokinetics Linezolid has a high bioavailability which is independent of the application route (orally or intravenously). Linezolid has low plasma protein–binding capacity (approximately 31%, but highly variable) and a volume of distribution at steady state of around 40–50  L. The tissue distribution is generally good and half-life averages around 5–7 h. Linezolid is metabolized in the liver, by oxidation of the morpholine ring, without involvement of the cytochrome P450 system, and is eliminated mainly via renal secretion (85%).

16.12.2 Efficacy and Indications Linezolid is effective against all clinically important gram-positive bacteria, notably Enterococcus faecium and Enterococcus faecalis (including vancomycin-­ resistant Enterococci), Staphylococcus aureus (including

117

16  Antimicrobial Therapy

methicillin-resistant Staphylococcus aureus, MRSA), Streptococcus agalacticae, Streptococcus pneumoniae, Streptococcus pyogenes, the viridans group Streptococci, and Listeria monocytogenes. It is also highly active in vitro against several mycobacteriae.

The elimination half-life is 1–5 h. Clindamycin is ­primarily eliminated by hepatic metabolism (80%) and the metabolites are excreted via the urine.

16.13.2 Efficacy and Indications 16.12.3 Antibiotic Resistance Resistance rates have remained stable and extremely low, less than 0.5% of isolates in general, and less than 0.1% of S. aureus samples.

16.12.4 Side Effects Common side effects of linezolid include diarrhea, headache, nausea, vomiting, rashes, constipation, altered taste perception, and discoloration of the tongue. In particular, a decrease in leukocyte and platelet counts can be observed after long-term use of linezolid, and therefore, in these patients, repeated blood counts are mandatory.

16.13 Lincosamides Clindamycin can be given parenterally and orally. It has a bacteriostatic effect and interferes with bacterial protein synthesis (in a similar way to erythromycin, azithromycin, and chloramphenicol), by binding preferentially to the 50S subunit of the bacterial ribosome. Clindamycin is usually used to treat infections with gram-positive anaerobic bacteria.

16.13.1 Pharmacokinetics Approximately 90% of an oral dose of clindamycin is absorbed from the gastrointestinal tract and it is widely distributed throughout the body, excluding the central nervous system. Adequate therapeutic concentrations can be achieved in bone. There is also active uptake into white blood cells, most importantly neutrophils.

Clindamycin has good efficacy against Staphylococci, Streptococci, gram-positive anaerobic bacteria, Bacter­ oides spp., and Mycoplasma pneumoniae. Clindamycin is used primarily to treat infections caused by susceptible anaerobic bacteria, including infections of the respiratory tract, skin and soft tissue infections, as well as peritonitis. It is also used to treat bone and joint infections, particularly those caused by Staphylococcus aureus.

16.13.3 Antibiotic Resistance Resistance rates for clindamycin range at 10% for blood isolates of Staphylococcus aureus, 30% for coagulasenegative Staphylococcus, and 10–20% for Bacteroides spp. Additionally, resistance rates of MRSA and MRSE continue to rise.

16.13.4 Side Effects Common side effects associated with clindamycin therapy, which can be observed in more than 1% of patients include diarrhea, pseudomembranous colitis, nausea, vomiting, abdominal pain or cramps, increased liver enzyme, rash, and/or itch. High doses (both ­intravenous and oral) may cause a metallic taste, and topical application can cause contact dermatitis.

16.14 Streptogramins Streptogramins are cyclic peptides and are available as a fixed combination of dalfopristin (70%) and quinupristin (30%). Both agents have bacteriostatic effects and have bactericidal effects in combination with a ­distinct post-antibiotic effect. The combination of

118

quinupristin/dalfopristin is only available for parenteral application. Quinupristin binds to the 50S ribosomal subunit and prevents elongation of the polypeptide. Dalfopristin binds to a nearby site, changes the conformation of the 50S ribosomal subunit, and enhances the binding of quinupristin by a factor of about 100. Quinupristin/dalfopristin is effective against all clinically relevant gram-positive bacteria, notably multi-resistant staphylococci (MRSA) and glycopeptide-resistant Enterococcus faecium. The use of quinupristin/dalfopristin should be limited to infections with gram-positive bacteria where no other antibiotics are effective.

16.14.1 Pharmacokinetics Quinupristin/dalfopristin has a medium distribution ­volume, and their half-lives range from 1 to 3 h. They are mainly metabolized in the liver and eliminated via the biliary tract. The protein-binding capacity varies from 55–78% for quinupristin to 11–26% for dalfopristin.

C.P. Schneider and B. Grabein

recommended. Other frequent side effects include arthralgia and myalgia, gastrointestinal disorder (nausea, diarrhea, or vomiting), headache, and increased liver enzymes. Quinupristin/dalfopristin also interferes with the cytochrome P450 enzyme system in the liver.

16.15 Tetracyclines Tetracyclines are a group of broad-spectrum antibiotics which have lost their general usefulness due to the development of bacterial resistance. Despite this, they remain the treatment of choice for some specific indications. The clinically most relevant agent of this antibiotic group is doxycycline which can be administered parenterally and orally. Tetracyclines generally have bacteriostatic effects through inhibition of protein synthesis by binding to the 30S ribosomal subunit in the mRNA translation complex. The treatment spectrum covers gram-positive and gram-negative bacteria.

16.14.2 Efficacy and Indications The use of Quinupristin/dalfopristin is limited to infections with gram-positive cocci, including multi-resistant Staph­ylococci (MRSA) and glycopeptide-resistant Enterococcus faecium (VRE). The drug combination should not be used against Enterococcus faecalis. Quinupristin/dalfopristin is approved for the treatment of infections of the lung, skin, and soft tissues and all infections caused by glycopeptide-resistant Enterococ­ cus faecium.

16.14.3 Antibiotic Resistance Enterococcus faecalis, anaerobic and aerobic gramnegative bacteria are resistant against streptogramins.

16.14.4 Side Effects Allergic reaction at the application site is common and administration via a central venous catheter is

16.15.1 Pharmacokinetics The distribution of doxycycline is mainly intracellular, and it penetrates well into all tissues. The halflife ranges from 10 to 20 h. Doxycycline is partly metabolized in the liver and eliminated via feces and urine.

16.15.2 Efficacy and Indications Nowadays, the use of doxycycline is limited to few indications. It is frequently used to treat infections caused by Chlamydia (trachoma, psittacosis, salpingitis, urethritis and L. venereum infection), Mycoplasma, Rickettsia (typhus, Rocky Mountain spotted fever), brucellosis, and spirochetal infections (borreliosis, syphilis, and Lyme disease). In general, approved indications for the use of doxycycline are infections of the upper and lower respiratory tracts, the bile tract, and pelvic inflammatory disease.

119

16  Antimicrobial Therapy

16.15.3 Antibiotic Resistance The local resistance rates differ significantly, and there is a lack of published data. Resistance rates range from 10% to 20% for gram-positive bacteria and are higher in the gram-negative field.

16.15.4 Side Effects Treatment with doxycycline can cause stomach or bowel upsets. Of particular note is a possible photosensitive allergic reaction which increases the risk of sunburn. Allergic reactions and hepatotoxicity are rarely seen.

resistant strains of Acinetobacter baumannii, and isolates of Klebsiella pneumoniae and Escherichia coli producing AmpC-beta-lactamases or extended-spectrumbeta-lactamases (ESBL). Currently, the drug is licensed for the treatment of skin and soft tissue infections as well as intra-abdominal infections.

16.16.3 Antibiotic Resistance In general, tigecycline has no activity against Pseudomonas spp., Proteus spp., and Burkholderia cepacia. Antibiotic resistance against usually susceptible bacteria has been observed only in few cases so far.

16.16.4 Side Effects 16.16 Glycylcyclines Tigecycline is the first clinically available drug in a new class of antibiotics called the glycylcyclines and has a similar structure as the tetracyclines. Tigecycline has a bacteriostatic effect and is a protein synthesis inhibitor by binding to the 30S ribosomal subunit of bacteria.

16.16.1 Pharmacokinetics Tigecycline has a long half-life of 25–42 h, and it has a large distribution volume. It is eliminated via kidneys (33%) and liver (60%) without modification. No dose adjustment is needed for patients with impaired kidney or liver function (Child-Pugh-Stadium A and B). Tigecycline does not interact with the cytochrome P450 enzyme system in the liver.

16.16.2 Efficacy and Indications Tigecycline is active against many gram-positive bac­ teria, gram-negative bacteria, anaerobes, mycoplasma and chlamydiae. It is also active against methicillinresistant Staphylococcus aureus (MRSA), multi-drug

The most common side effects of tigecycline are ­gastrointestinal disorders (diarrhea, nausea, and vomiting). Increased serum bilirubin can also be rarely observed.

16.17 Ansamycins Rifampicin can be administered intravenously as well as orally. It has bacteriostatic and bactericidal effects on proliferating cells which depend on the administered dose as well as the activity of the bacteria. Rifampicin inhibits DNA-dependent RNA polymerase in bacterial cells by binding to its beta-subunit, thus preventing transcription to RNA and subsequent translation into proteins. It has a good efficacy against tuberculosis as well as in combination with other antibiotics against multi-resistant gram-positive bacteria.

16.17.1 Pharmacokinetics Rifampicin has a high distribution throughout the body, and reaches effective concentrations in many organs and body fluids, including the cerebrospinal fluid. About 60–90% of the drug is bound to plasma proteins. The half-life of rifampicin ranges from 6 to 7 h

120

and depends on the duration of therapy because selfinduction by the agent causes increased metabolization rate. Approximately 7% of the administered drug is excreted unchanged through the urine; urinary elimination, however, accounts for 30% while 60–65% of the administered dosage is excreted via the feces.

C.P. Schneider and B. Grabein

as well as orally. It has a high bactericidal activity against anaerobic bacteria because it is taken up by diffusion and then inhibits protein synthesis via binding to DNA.

16.18.1 Pharmacokinetics 16.17.2 Efficacy and Indications Apart from the “typical use” for the treatment of myco­ bacterium infections, including tuberculosis and ­leprosy, rifampicin has a role in combination with glycopeptides or other antibiotics for the treatment of infections with Staphylococci (including methicillinresistant strains), Streptococci, and Enterococci if ­susceptibility is confirmed.

16.17.3 Antibiotic Resistance Rifampicin resistance develops quickly during monotherapy. Primary resistances against Mycobacterium tuberculosis and meningococci are rare.

Metronidazole has a medium distribution volume, and its half-life ranges from 6 to 8 h. The agent is partially bound to plasma proteins (10–20%), and after metabolization, it is eliminated mainly via renal excretion (60–80%).

16.18.2 Efficacy and Indications Metronidazole is approved for treatment of infections caused by anaerobic bacteria (including meningitis and brain abscess). It is used in combination for perioperative prophylaxis. Metronidazole is further indicated for the treatment of protozoal infections due to Entamoeba histolytica, Giardia lamblia (Giardiasis), and Tricho­ monas vaginalis. Metronidazole has also been proven to be effective for the treatment of pseudomembranous colitis caused by Clostridium difficile.

16.17.4 Side Effects The more common unwanted effects include hepatotoxicity, gastrointestinal disorder, and altered blood counts. Rifampicin is an effective liver enzymeinducer, promoting the upregulation of hepatic cytochrome P450 enzymes, and therefore, increasing the rate of metabolism of many other drugs that are cleared by the liver through these enzymes.

16.18.3 Antibiotic Resistance Primary resistance among anaerobic bacteria is rarely seen. Some strains of Helicobacter pylori have developed resistance against metronidazole.

16.18.4 Side Effects 16.18 Nitroimidazoles Metronidazole is the most important nitroimidazole and it is used mainly in the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa. Metronidazole has an excellent bioavailability and can be administered parenterally

Common side effects include nausea, diarrhea, and a metallic taste in the mouth. Therapy with metronidazole can be associated with leucopenia, neutropenia, and increased risk of peripheral neuropathy. Consump­ tion of alcohol should be avoided while using metronidazole because a significant alcohol intolerance can develop.

121

16  Antimicrobial Therapy

16.19 Fosfomycin

16.20 Co-trimoxazole

Fosfomycin can be given parenterally and orally, but the enteral form (Fosfomycin-Trometamol) is only approved for the treatment of urinary tract infections. Fosfomycin is an antimetabolite of phosphoenolpyruvate in the enzymatic synthesis of bacterial cell wall components and has bactericidal activity. Fosfomycin is active against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa, but resistance develops rapidly under monotherapy.

Co-trimoxazole is a sulfonamide antibacterial combination of trimethoprim and sulfamethoxazole and is used for the treatment of a variety of gram-positive and gram-negative bacterial infections. Trimethoprim and sulfamethoxazole inhibit successive steps in the folate synthesis pathway. Each component alone exhibits bacteriostatic effects, but together they have bactericidal effects.

16.20.1 Pharmacokinetics 16.19.1 Pharmacokinetics Fosfomycin is distributed selectively in the extracellular space, and therefore, its distribution volume is small. Fosfomycin does not bind to plasma proteins and is eliminated unmodified via the urinary tract.

Co-trimoxazole is distributed in the intra- and extracellular spaces, and its tissue distribution volume is low for sulfamethoxazole and medium for trimethoprim. Seventy percent of sulfamethoxazole and 45% of trimethoprim are bound to plasma proteins, and their half-lives range from 10 to 12 h. Co-trimoxazole is partly metabolized and then excreted via the urine.

16.19.2 Efficacy and Indications 16.20.2 Efficacy and Indications Fosfomycin is effective against Staphylococci, grampositive and gram-negative bacteria. Its use is approved for infections in different locations (particularly bone and meninges) as long as susceptibility of the pathogen has been proven.

16.19.3 Antibiotic Resistance Resistance rapidly develops under monotherapy due to spontaneous mutations.

16.19.4 Side Effects Gastrointestinal disorder and pain at the application site are often seen during fosfomycin therapy. Attention must be paid to the high sodium chloride content of the solution.

Co-trimoxazole is effective against gram-positive and gram-negative bacteria and is predominantly used for the treatment of infections with Stenotr­ ophomonas maltophilia, Pneumocystis jiroveci (formerly Pneumocystis carinii) and in combination with other drugs for infections with methicillin-resistant Staphylococcus aureus. It can be effective in a variety of upper and lower respiratory tract infections, renal and urinary tract infections (UTI), and can be used for long-term prophylaxis of UTI in patients at risk.

16.20.3 Antibiotic Resistance Escherichia coli, Salmonella, Shigella, and other Enterobacteriacae have developed increased resistance rates during recent years.

122

C.P. Schneider and B. Grabein

16.20.4 Side Effects Administration of high dosages of co-trimoxazole can be associated with gastrointestinal disorders, crystalluria (formation of crystals and excretion in the urine), and acute renal failure. Serious adverse effects including Stevens–Johnson syndrome, myelosuppression, mydriasis, agranulocytosis, and hepatitis are rarely seen.

16.21 Characterization of Antifungals (Table 16.3), Pharmacokinetics, Efficacy, Resistance, and Side Effects (Table 16.4)

fungal infection is often difficulty. Verification of fungi in primarily sterile material or histological detection of invasiveness in bioptic material may represent distinct markers of invasive fungal infections. Local and systemic fungal infections are often seen in patients with diminished immunological competence, for example after organ transplantation. Additionally, biological selection of fungi occurs after long-term antibiotic therapy, and therefore, critical ill patients are at increased risk of IFI. If fungal infections are assumed or established, in particular with molds (e.g., Asper­ gillus spp.), antifungal therapy must be given for ­significantly longer periods of time compared to antibacterial therapy. Efficacies of important antifungal drugs in the clinical setting are summarized in Table 16.4.

16.21.1 Introduction

16.22 Polyenes

Invasive fungal infections (IFI) only play a minor role in the surgical field. Microbiological detection of fungi (e.g., Candida spp.) is common but is usually due to colonization of the host. Under these circumstances, antifungal treatment is usually not indicated. Nonethe­ less, differentiation between colonization and invasive

Amphotericin B is available for parenteral application as well as an oral preparation. It may also be given in a nebulized form and for topical application, for example intra-abdominal irrigation. A liposomal formulation of amphotericin B for injection has been developed which exhibits fewer side effects (particularly nephrotoxicity)

Table 16.3  Systemic antifungal agents for parenteral and oral applications Group Drugs Maximum dosage Intravenously

Orally

Polyene

Amphotericin B Amphotericin B liposomal

1–1.5 mg/kg BW once daily 3–5 mg/kg BW once daily

n/a n/a

Azole

Fluconazole

10 mg/kg BW once daily

10 mg/kg BW once daily

Itraconazole

200 mg q12–24 h

200 mg q12–24 h

Voriconazole

6 mg/kg BW q12h on day 1, and then 3–4 mg/kg BW q12h

400 mg q12h on day 1, and then 200 mg q12h

n/a

400 mg q12h

Posaconazole Fluorinated pyrimidine

Flucytosine

25–37.5 mg/kg BW q6h

n/a

Echinocandins

Caspofungin

70 mg once daily on day 1, and then 50 mg once daily

n/a

Anidulafungin

200 mg once daily on day 1, and then 100 mg once daily

n/a

Micafungin

150 mg once daily

n/a

n/a non-applicable to reach therapeutic systemic levels, q every, h hours, BW body weight

123

16  Antimicrobial Therapy Table 16.4  Antifungals’ efficacy

Pseudallescheria

Zygomycetes

?

Dermatophyte

Aspergillus flavus

?

Cryptococcus neoformans

Aspergillus fumigatus

Amphotericin B

Candida krusei

Polyene

Candida glabrata

Drugs

Candida tropicalis

Candida albicans

Group

Amphotericin B liposomal Azole

Fluconazol

R

Itraconazol

R

R

Voriconazol Posaconazol Fluorinated

Flucytosin

pyrimidine Echinocandins

Caspofungin Anidulafungin Micafungin

No efficacy

Effective

R = potentially resistant ? = efficacy unclear

while having similar efficacy. Nystatin is only available as oral preparation. Amphotericin B antagonizes the sterol synthesis, the main component of fungal cell membranes, forming a transmembrane channel that leads to potassium leakage and fungal cell death. Polyene antifungal agents have a broad-spectrum efficacy which covers Candida and Aspergillus spp., except Scedosporium (Pseudallescheria) spp.

16.22.1 Pharmacokinetics Amphotericin B and Nystatin are not absorbed after oral intake. After parenteral application, amphotericin B binds up to 90% to plasma proteins and its half-life ranges to about 20 h. The highest tissue concentration

can be reached in the liver while its concentration is lower in the lungs and kidneys, but can increase up to 65% of plasma concentration in pleural, peritoneal, and synovial fluids if infection is present. The distribution into the cerebrospinal fluid is marginal. Amphotericin B is slowly eliminated via the kidneys over several days, and it cannot be removed via dialysis.

16.22.2 Efficacy and Indications Amphotericin B is approved for the treatment of serious systemic fungal infections including peritonitis, sepsis, meningitis, and endocarditis. The oral preparation can be used for intestinal decontamination and therapy of thrush or other topical forms of candidiasis.

124

16.22.3 Resistance Development of resistance under amphotericin B therapy is uncommon, and only individual reports have been published indicating primary resistance of some Candida strains.

16.22.4 Side Effects Nephrotoxicity is a frequently reported side effect, and it is much milder when the liposomal formulated amphotericin B is used. Frequently, a serious acute reaction after infusion (1–3 h later) can be noted consisting of high fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea, and tachypnea. Other possible side effects include thrombophlebitis at the application site, several forms of anemia and other hematological problems as well as backache.

16.23 Azoles Systemic applicable antifungal agents of this group are fluconazole, itraconazole, voriconazole, and posaconazole, which are chemically different azole derivates with imidazole or triazole structure. Inhibition of the fungal enzyme 14a-demethylase which produces ergosterol (an important component of the fungal plasma membrane) is the common mode of action. All azole derivates also inhibit cytochrome P450 enzyme system and parts of the human steroid synthesis. Therefore, careful patient evaluation must look for possible interactions with other medications. Fluconazole, itraconazole, and voriconazole can be given parenterally and orally, while posaconazole is only available for oral administration. The effectiveness varies significantly among the azole derivates. Fluconazole is highly effective against several Candida species, but shows poor activity against Candida glabrata and no effect against Candida krusei and molds. Itraconazole has similar efficacy across Candida spp. and is additionally active against Aspergillus spp. Voriconazole also covers Candida glabrata, Candida krusei, Fusarium

C.P. Schneider and B. Grabein

spp., and Scedosporium spp. Posaconazole, the most recent azole derivate, also has good efficacy against Zygomycetes.

16.23.1 Pharmacokinetics Fluconazole is well absorbed after oral intake, and its half-life reaches up to 25 h. Plasma protein–binding capacity of fluconazole is low with approximately 12%. It penetrates well into various tissues and reaches high concentrations in urine, saliva, sputum, and cerebrospinal fluids. Most of the administered fluconazole (60–80%) is eliminated unmodified via the kidneys. Itraconazole is also well absorbed after oral intake, particularly if taken together with alimentation. However, the bioavailability varies individually, and therefore, drug monitoring is necessary to modify the dosage and reach therapeutic levels. Intraconazole has a half-life of 24 h and is nearly 99% bound to plasma proteins. It does not penetrate into the cerebrospinal fluid and neither renal failure nor dialysis has an impact on intraconazole serum levels. Voriconazole is almost completely absorbed after oral intake. Its half-life ranges from 6 up to 12 h and approximately 60% is bound to plasma proteins. The cerebrospinal fluid level of this drug can reach nearly 50% of plasma levels. Most of the drug (95%) is metabolized in the liver, 80% is then excreted via the urine (2% unmodified), and 20% via the feces. Posaconazole is slowly absorbed after oral intake which depends on the fat content of the nutrition. Posaconazole has a high distribution volume and a medium half-life of 35 h. Almost 98% of the drug is bound to plasma proteins and the major proportion is eliminated via the feces, while 15% is removed via the urine.

16.23.2 Efficacy and Indications Fluconazole is widely used for the treatment of fungal infections caused by Candida albicans and tropicalis while itraconazole i