W. Joost Wiersinga Christopher W. Seymour Editors

Handbook of Sepsis W. Joost Wiersinga Christopher W. Seymour Editors 123 Handbook of Sepsis W. Joost Wiersinga Christopher W. Seymour Editors Handbook of Sepsis Editors W. Joost Wiersinga Christopher W. Seymour University of Amsterdam University of Pittsburgh Amsterdam Pittsburgh The Netherlands Pennsylvania USA ISBN 978-3-319-73505-4 ISBN 978-3-319-73506-1 (eBook) https://doi.org/10.1007/978-3-319-73506-1 Library of Congress Control Number: 2018935395 © Springer International Publishing AG, part of Springer Nature 2018 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. 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Printed on acid-free paper This Springer imprint is published by the registered company Springer International Publishing AG part of Springer Nature The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Preface Sepsis is one of the most common deadly diseases. Despite its remarkable incidence, and despite the progress which has been made in understanding this complex syndrome, for both clinicians at the bedside and scientists at the bench many key questions remain unanswered. In order to address this unmet need, we now present the first edition of the Handbook of Sepsis. This practically oriented book provides an up-to-date overview of all significant aspects of the pathogenesis of sepsis and its management. Readers will find information on the involvement of the coagulation and endocrine systems during sepsis and on the use of biomarkers to diagnose sepsis and allow early inter- vention. International clinical practice guidelines for the management of sepsis are presented, and individual chapters focus on aspects such as fluid resuscitation, vaso- pressor therapy, response to multiple organ failure, antimicrobial therapy, and adjunctive immunotherapy. The closing section looks forward to the coming decade, discussing novel trial designs, sepsis in low- and middle-income countries, and emerging management approaches. The book is international in scope, with contri- butions from leading experts across the world. It will be of value to professionals/ practitioners that take care of patients with severe infections in all fields of medicine in addition to those who are in training or study sepsis in depth. We would like to thank all our colleagues who all worked hard and full of enthu- siasm on each and every chapter of this book. In this respect, the continued support of members of the European Sepsis Academy, the Surviving Sepsis Campaign guidelines committee, the European Society of Clinical Microbiology and Infectious Diseases, and the International Sepsis Forum has been truly inspiring. In addition, we gratefully acknowledge the continued and wonderful support of the editorial staff at Springer Nature. At the end, we do hope that this handbook can make a small contribution to the further improvement of care for patients with sepsis who present with this devastating syndrome on emergency departments, wards, and intensive care units in all corners of the world. Amsterdam, The Netherlands W. Joost Wiersinga Pittsburgh, PA, USA Christopher W. Seymour March 2018 v Contents Part I Sepsis: An Overview 1 What Is Sepsis? �� 3 Luuk Giesen and Mervyn Singer 2 The Epidemiology of Sepsis . 15 Hallie C. Prescott Part II The Pathogenesis of Sepsis 3 Pathogenesis of Sepsis �� 31 Tjitske S. R. van Engelen, W. Joost Wiersinga, and Tom van der Poll 4 The Coagulation System in Sepsis �� 45 Marcel Levi 5 The Endocrine System in Sepsis . 61 Nicholas Heming, Sivanthiny Sivanandamoorthy, Paris Meng, and Djillali Annane 6 Sepsis Biomarkers �� 81 Jean-Louis Vincent and Christophe Lelubre Part III Sepsis Management 7 International Clinical Practice Guidelines �� 97 Radu Postelnicu, Andrew Rhodes, and Laura Evans 8 Fluids in Sepsis . 113 James R. Anstey, Adam M. Deane, and Rinaldo Bellomo 9 Vasopressors in Sepsis. 127 Julian Arias Ortiz and Daniel De Backer 10 Management of Multiorgan Failure in Sepsis . 139 Ithan D. Peltan and Samuel M. Brown 11 Sepsis Management: Importance of the Pathogen �� 159 Russell J. McCulloh and Steven M. Opal vii viii Contents 12 Antimicrobial Therapy �� 185 Thierry Calandra and Benoît Guery 13 Adjunctive Immunotherapy �� 201 G. P. Leijte, M. Kox, and P. Pickkers Part IV Sepsis in the Coming Decade 14 Novel Trial Design in Sepsis �� 217 Christopher W. Seymour and Derek C. Angus 15 Sepsis in Low- and Middle-Income Countries �� 231 Luciano Cesar Pontes Azevedo and Flavia Ribeiro Machado 16 Sepsis: The Road Ahead �� 253 Jianfeng Xie and Craig M. Coopersmith Part I Sepsis: An Overview What Is Sepsis? 1 Luuk Giesen and Mervyn Singer 1.1 Introduction Sepsis is an enigmatic clinical syndrome that arises when a patient reacts adversely to an infection and develops organ dysfunction as a consequence. It can affect practically all organ systems, though the organs involved and the degree of dysfunction will vary markedly between patients. It can lead to death in a high propor- tion of cases. Sepsis is now officially defined as a dysregulated host response to an infection, causing life-threatening organ dysfunction [1]. This new definition, and accompa- nying clinical criteria, will hopefully provide a stronger, more consistent base to better inform incidence, outcomes and research. The nature of sepsis is extremely complex, and the disease course can differ markedly between patients. As yet, sepsis cannot be determined with certainty in many cases. Diagnosis often relies upon clinician gestalt as definitive microbiological evidence of a precipitating infection is often absent. Moreover, attempts to find a magic cure for sepsis have been fruitless [2]. This is, in large part, due to a highly variable biological phenotype, even in patients presenting with similar clinical features. Management is mainly supportive at present with resuscitation, organ support and eradication of the underlying infection with antibiotics ± source control [2]. On a more positive note, our understanding of sepsis has profoundly increased, and better diagnostics are being developed to aid identification and target the dosing and timing of therapeutic interventions. In the developed world, sepsis has an incidence of 2.5 million patients per year and a mortality rate of approximately 650,000 patients per year (when corrected for the new definition using only recent data) [3]. This would translate to roughly 19 million cases of sepsis a year globally, with approximately 5 million deaths [3]. This estimation is probably wildly inaccurate, as there is a general lack of L. Giesen, M.D. · M. Singer, M.D., F.R.C.P.(Lon) (*) Bloomsbury Institute of Intensive Care Medicine, University College London, London, UK e-mail: [email protected] © Springer International Publishing AG, part of Springer Nature 2018 3 W. J. Wiersinga, C. W. Seymour (eds.), Handbook of Sepsis, https://doi.org/10.1007/978-3-319-73506-1_1 4 L. Giesen and M. Singer comprehensive epidemiological data in low- and middle-income countries. The lack of good primary care, adequate infection prevention, timely antibiotic treat- ment, poor staffing levels and adequate critical care provision account for a com- pletely different situation in these countries. The World Health Organization provides additional insights into this conundrum. While the WHO does not yet monitor sepsis, it does track communicable diseases. According to WHO data, three infectious diseases were in the top ten causes of death worldwide in 2015: lower respiratory disease, diarrheal disease and tuberculosis with a combined mortality of 7.3 million people [4]. The majority of these fatalities occur in developing countries. It is likely that most die from sepsis as infection without organ dysfunction cannot

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