Mechanisms of attention and attentional impairment

Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information Brain Disorders in Critical Illness Mechanisms, Diagnosis, and Treatment © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information Brain Disorders in Critical Illness Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens Associate Professor, Department of Anesthesiology and Critical Care Medicine; Associate Professor of Neurology, Neurosurgery and Radiology-Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA Tarek Sharshar Professor, Department of Intensive Care Medicine, Raymond Poincaré Hospital, University de Versailles Saint-Quentin-en-Yvelines, Garches, France; Laboratory of Histopathology and Animal Models, Francois Jacob Centre, Institut Pasteur, Paris, France E. Wesley Ely Professor of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine and the Geriatric Research Education Clinical Center (GRECC) of Tennessee Valley Veterans Affairs Healthcare System, Nashville, TN, USA © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information University Printing House, Cambridge CB2 8BS, United Kingdom Published in the United States of America by Cambridge University Press, New York Cambridge University Press is part of the University of Cambridge. It furthers the University’s mission by disseminating knowledge in the pursuit of education, learning, and research at the highest international levels of excellence. www.cambridge.org Information on this title: www.cambridge.org/9781107029194 © Cambridge University Press 2013 This publication is in copyright. Subject to statutory exception and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published 2013 Printed in the United Kingdom by TJ International Ltd. Padstow Cornwall A catalogue record for this publication is available from the British Library ISBN 978-1-107-02919-4 Hardback Cambridge University Press has no responsibility for the persistence or accuracy of URLs for external or third-party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. ............................................................................................... Every effort has been made in preparing this book to provide accurate and up-to-date information which is in accord with accepted standards and practice at the time of publication. Although case histories are drawn from actual cases, every effort has been made to disguise the identities of the individuals involved. Nevertheless, the authors, editors and publishers can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation. The authors, editors and publishers therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this book. Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use. © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information Contents List of contributors Foreword xiii Jesse Hall Introduction xv page viii Section 1. Epidemiology and Outcomes 1. The epidemiology of critical illness brain dysfunction 1 Raoul Sutter and Robert D. Stevens 2. Cognitive dysfunction following critical illness 15 Ramona O. Hopkins and James C. Jackson 3. Psychiatric disorders following critical illnesses 23 Dimitry S. Davydow 8. Mechanisms of attention and attentional impairment 68 Paolo Bartolomeo 9. Neurology of sleep and sleep disorders 76 Robert D. Sanders, Stefan D. Gurney, Jamie W. Sleigh, and Mervyn Maze 10. Neural basis of fear and anxiety 84 Odile Viltart and Christel C. Vanbesien Section 3. Biological Mechanisms 4. Functional status and quality of life after critical illness 30 Sanjay V. Desai, Nathan E. Brummel, and Dale M. Needham 11. Experimental models of cognitive dysfunction in infection and critical illness 97 Colm Cunningham 5. Delirium and dementia: unraveling the complex relationship 39 Margaret Pisani 12. Neurobiological effects of systemic physiological and metabolic insults 108 Jean-Francois Payen, Gérard Audibert, and Nicolas Bruder Section 2. Behavioral Neurology in the ICU 13. Cerebral ischemia and reperfusion Raymond C. Koehler 119 6. Cognitive reserve 49 Richard E. Temes, Robert S. Wilson, Lisa L. Barnes, and David A. Bennett 14. Brain perfusion and autoregulation in systemic critical illness 129 Martin Siegemund and Luzius A. Steiner 7. Neurology of consciousness impairments 59 Benjamin Rohaut, Frédéric Faugeras, and Lionel Naccache 15. Delirium and neurotransmitter dysfunction 139 Willem A. van Gool v © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information Contents Section 5. Preventative and Therapeutic Interventions 16. Neuromodulatory and neurotoxic effects of sedative agents 150 Jean Mantz and Souhayl Dahmani 27. Environmental modification Yoanna Skrobik 17. Neuroimmunological cross-talk in critical illness 160 Robert Dantzer and Keith W. Kelley 28. New paradigms in sedation of the critically ill patient 285 Christopher G. Hughes and Pratik P. Pandharipande 18. Inflammatory mechanisms in chronic neurodegenerative disease: the impact of microglia priming 172 V. Hugh Perry 29. Pharmacological management of delirium 294 Dustin M. Hipp and E. Wesley Ely 19. The neuroendocrine response to critical illness 181 David Luis and Djillali Annane 20. Autonomic dysfunction in SIRS and sepsis 192 Jeremy D. Scheff, Panteleimon D. Mavroudis, Steve E. Calvano, Stephen F. Lowry, and Ioannis P. Androulakis 21. Sepsis-induced neuronal dysfunction and death 200 Sadanand M. Gaikwad, Catherine N. Widmann, and Michael T. Heneka 22. Neuroimmunomodulation in sepsis 208 Marion Griton and Jan Pieter Konsman 30. Pharmacogenomics and cerebral dysfunction 305 Yoanna Skrobik 31. Early physical and occupational therapy 316 John P. Kress 32. Rehabilitation after critical illness Richard D. Griffiths and Christina Jones 321 Section 6. Clinical Encephalopathy Syndromes 33. Drug-induced encephalopathy Bruno Mégarbane Section 4. Diagnosis of Brain Dysfunction 329 34. Metabolic encephalopathies: inborn errors of metabolism causing encephalopathies in adults 344 Frederic Sedel 23. Clinical neurological assessment of the critically ill patient 219 Raoul Sutter, Tarek Sharshar, and Robert D. Stevens 24. Bedside assessment of delirium in critically ill patients 229 Alawi Luetz and Claudia D. Spies 25. Electroencephalography and evoked potentials in critically ill patients Matthew A. Koenig and Peter W. Kaplan 279 241 26. Neuroimaging of delirium 257 Karen J. Ferguson and Alasdair M. J. MacLullich 35. Encephalopathy associated with alcohol or drug withdrawal 354 Felix Kork and Claudia D. Spies 36. Posterior reversible encephalopathy syndrome (PRES): the essential elements 362 Walter S. Bartynski and Hebah M. Hefzy 37. Hypoxic-ischemic encephalopathy 373 Fabio Silvio Taccone and Alain Cariou vi © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information Contents 38. Sepsis-associated encephalopathy 381 Romain Sonneville, C. Rauturier, F. Verdonk, F. Chretien, and Tarek Sharshar 39. Seizures and status epilepticus in critical illness 391 Brandon Foreman and Jan Claassen 40. Encephalopathy and coma in acute and chronic liver failure 403 Julia Wendon and Jennifer Ryan 41. Neurological complications of cardiac surgery: stroke, encephalopathy, and cognitive decline 410 Rebecca F. Gottesman, Maura A. Grega, Guy M. McKhann, and Ola A. Selnes Glossary 419 Index 424 Color plate section is between pp. 240 and 241. vii © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information Contributors Ioannis P. Androulakis Department of Biomedical Engineering, Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, and Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA Djillali Annane Service de reanimation, hospital Raymond Poincaré (AP-HP), University of Versailles SQY, Garches, France Gérard Audibert Department of Anesthesiology and Critical Care, Nancy University Hospital, Nancy, France Lisa L. Barnes Departments of Behavioral Sciences and Neurological Sciences, and Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA Paolo Bartolomeo INSERM-U 975, Centre de Recherche de l’Institut du Cerveau et de la Moelle Epinière (CRICM) et Université Pierre et Marie Curie (UPMC), Groupe Hospitalier Pitié-Salpêtrière, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Fédération de Neurologie, Paris, France; Department of Psychology, Catholic University, Milan, Italy Walter S. Bartynski Department of Radiology and Radiological Science, Division of Neuroradiology, Medical University of South Carolina, Charleston, SC, USA David A. Bennett Professor of Neurological Sciences, Department of Neurological Sciences and Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA Nicolas Bruder Department of Anesthesiology and Critical Care, Marseille University Hospital, Marseille, France Nathan E. Brummel Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt School of Medicine, Nashville, TN, USA Steve E. Calvano Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA Alain Cariou Medical Intensive Care Unit, AP-HP, Cochin Hospital, Paris, and Paris Descartes University and Sorbonne Paris Cité Medical School, Paris, France F. Chretien Unité “Histopathologie Humaine et Modèles Animaux,” Département Infection et Epidémiologie, Institut Pasteur, Paris, and University of Versailles Saint-Quentin-en-Yvelines, Garches, France Jan Claassen Division of Neurocritical Care, Neurological Institute of New York, Columbia University Medical Center, New York, NY, USA Colm Cunningham Trinity College Institute of Neuroscience and School of Biochemistry and Immunology, Trinity College Dublin, Republic of Ireland Souhayl Dahmani AP-HP, Robert Debré University Hospitals, INSERM-U 676, Paris Diderot University, Paris, France viii © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information List of contributors Robert Dantzer Department of Symptom Research, MD Anderson Cancer Center, Houston, TX, USA Dimitry S. Davydow Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA Sanjay V. Desai Division of Pulmonary and Critical Care Medicine, The Johns Hopkins University, Baltimore, MD, USA E. Wesley Ely Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine and the Geriatric Research Education Clinical Center (GRECC) of Tennessee Valley Veterans Affairs Healthcare System, Nashville, TN, USA Frédéric Faugeras INSERM, ICM Research Center, UMRS 975, Paris, and AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Departments of Neurophysiology and Neurology, Paris, France Karen J. Ferguson Neuroimaging Research Fellow, School of Clinical Sciences, University of Edinburgh, UK Brandon Foreman Comprehensive Epilepsy Center, Neurological Institute of New York, Columbia University Medical Center, New York, NY, USA Sadanand M. Gaikwad Department of Neurology, Clinical Neuroscience Unit, University of Bonn, Bonn, Germany Rebecca F. Gottesman Department of Neurology, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA Maura A. Grega Research Nurse Program Coordinator, The Johns Hopkins University, Baltimore, MD, USA Richard D. Griffiths Emeritus Professor of Medicine (Intensive Care), Whiston Hospital and Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK Marion Griton CNRS UMR 5536 Magnetic Resonance of Biological Systems, Victor Segalen Bordeaux 2 University, Bordeaux, France Stefan D. Gurney Magill Department of Anaesthesia, Intensive Care, and Pain Medicine, and Department of Anaesthetics, Intensive Care and Pain Medicine, Chelsea & Westminster Hospital, Imperial College London, UK Hebah M. Hefzy Department of Neurology, Henry Ford Hospital, Detroit, MI, USA Michael T. Heneka Department of Neurology, Clinical Neuroscience Unit, University of Bonn, Bonn, Germany Dustin M. Hipp Vanderbilt University School of Medicine, Nashville, TN, USA Ramona O. Hopkins Department of Psychology and Neuroscience Center, Brigham Young University, Provo, UT, and Department of Medicine, Pulmonary and Critical Care Division, Intermountain Medical Center, Murray, UT, USA Christopher G. Hughes Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA James C. Jackson Division of Allergy, Pulmonary, and Critical Care Medicine, and Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, TN, USA Christina Jones Nurse Consultant, Intensive Care Rehabilitation, Intensive Care Unit, Whiston Hospital, Prescot, Merseyside, and Honorary Reader, Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK Peter W. Kaplan Department of Neurology, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA Keith W. Kelley Department of Immunophysiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA ix © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information List of contributors Raymond C. Koehler Department of Anesthesiology and Critical Care Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA Jean Mantz Department of Anesthesia and Critical Care, Beaujon-Paris Val de Seine University Hospitals, Paris, France Matthew A. Koenig Neurocritical Care, Neuroscience Institute, The Queen’s Medical Center, Honolulu, HI, USA Panteleimon D. Mavroudis Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, USA Jan Pieter Konsman CNRS UMR 5536 Magnetic Resonance of Biological Systems, Victor Segalen Bordeaux 2 University, Bordeaux, France Mervyn Maze Department of Anesthesia & Perioperative Care, University of California San Francisco, San Francisco, CA, USA Felix Kork Department of Anaesthesiology and Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany Bruno Mégarbane Medical and Toxicological Critical Care Unit, Lariboisière Hospital, Paris Diderot University, INSERM U705, Paris, France John P. Kress Department of Medicine, Section of Pulmonary and Critical Care, University of Chicago, Chicago, IL, USA Stephen F. Lowry Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA Lionel Naccache INSERM, ICM Research Center, UMRS 975, Paris; AP-HP, Groupe Hospitalier PitiéSalpêtrière, Departments of Neurophysiology and Neurology, Paris; University Paris 6, Faculté de Médecine Pitié-Salpêtrière, Paris, France Alawi Luetz Department of Anaesthesiology and Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany Dale M. Needham Outcomes After Critical Illness and Surgery (OACIS) Group, Division of Pulmonary and Critical Care Medicine, and Department of Physical Medicine and Rehabilitation, The Johns Hopkins University, Baltimore, MD, USA David Luis Service de reanimation, hospital Raymond Poincaré (AP-HP), University of Versailles SQY, Garches, France Pratik P. Pandharipande Vanderbilt University School of Medicine, Anesthesia Service, VA TVHS, Nashville, Nashville, TN, USA Alasdair M. J. MacLullich Department of Geriatric Medicine, University of Edinburgh, and Honorary Consultant in General and Geriatric Medicine, Royal Infirmary of Edinburgh, UK Jean-Francois Payen Department of Anesthesiology and Critical Care, Grenoble University Hospital, Grenoble, France Guy M. McKhann Johns Hopkins University School of Medicine, Baltimore, MD, USA V. Hugh Perry Experimental Neuropathology, Centre for Biological Sciences, University of Southampton, Southampton, UK x © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information List of contributors Margaret Pisani Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT, USA Martin Siegemund Department of Anaesthesia, Critical Care and Prehospital Emergency Medicine, State Hospital AG, Baden, Switzerland C. Rauturier Unité “Histopathologie Humaine et Modèles Animaux,” Département Infection et Epidémiologie, Institut Pasteur, Paris, and University of Versailles Saint-Quentin-en-Yvelines, Garches, France Yoanna Skrobik Département de soins intensifs, Maisonneuve-Rosemont Hospital, and Critical Care Medicine, University of Montreal, Montreal, Quebec, Canada Benjamin Rohaut Departments of Neurology and Intensive Care Unit, ICM Research Center INSERM UMRS 975 and Université Pierre et Marie Curie (Paris VI), Pitié-Salpêtrière Hospital, Paris, France Jennifer Ryan Division of Mucosal Biology and Transplantation Institute of Liver Studies, Kings College London, Kings College Hospital, London, UK Robert D. Sanders Magill Department of Anaesthesia, Intensive Care, and Pain Medicine; Department of Anaesthetics, Intensive Care, and Pain Medicine, Chelsea & Westminster Hospital, Imperial College London, and Department of Leukocyte Biology, National Heart and Lung Institute, Imperial College London, London, UK Jeremy D. Scheff Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, USA Frederic Sedel Department of Neurology, Reference Center for Lysosomal Diseases, Neurometabolic Function Unit, Pitié-Salpêtrière Hospital, AP-HP, Paris, and Université Pierre et Marie Curie (Paris VI), Paris, France Ola A. Selnes Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD, USA Tarek Sharshar Department of Intensive Care Medicine, Raymond Poincaré Hospital, University Versailles SaintQuentin-en-Yvelines, Garches, France; Laboratory of Histopathology and Animal Models, Francois Jacob Centre, Institut Pasteur, Paris, France Jamie W. Sleigh Department of Anaesthesia, University of Auckland, Waikato Hospital, Hamilton, New Zealand Romain Sonneville Department of Intensive Care Medicine and Infectious Diseases, Hôpital Bichat-Claude Bernard, Université Diderot-Paris 7, Paris; Unité “Histopathologie Humaine et Modèles Animaux,” Département Infection et Epidémiologie, Institut Pasteur, Paris; University of Versailles Saint-Quentin-en-Yvelines, Garches, France Claudia D. Spies Department of Anesthesiology and Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Campus Virchow Klinikum und Campus Charité Mitte, Berlin, Germany Luzius A. Steiner Department of Anesthesia, University Hospital Center and University of Lausanne, Lausanne, Switzerland Robert D. Stevens Departments of Anesthesiology and Critical Care Medicine, and Department of Neurology, Neurosurgery and Radiology-Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA Raoul Sutter Departments of Anesthesiology and Critical Care Medicine, and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Fabio Silvio Taccone Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Bruxelles, Belgium xi © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information List of contributors Richard E. Temes Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA Versailles Saint-Quentin-en-Yvelines, Garches, France Willem A. van Gool Department of Neurology, Academic Medical Centre, Amsterdam, the Netherlands Odile Viltart University Lille Nord de France/USTL (Sciences & Technologies, Lille 1), and INSERM UMR 837, Plasticity and Development of Postnatal Brain, Place de Verdun, Lille, France Christel C. Vanbesien University Lille Nord de France/USTL (Sciences & Technologies, Lille 1), and INSERM UMR 837, Molecular events associated to early stages of Parkinson’s disease, Place de Verdun, Lille, France Julia Wendon Division of Mucosal Biology and Transplantation, Institute of Liver Studies, Kings College London, Kings College Hospital, London, UK F. Verdonk Unité “Histopathologie Humaine et Modèles Animaux,” Département Infection et Epidémiologie, Institut Pasteur, Paris, and University of Catherine N. Widmann Department of Neurology, Clinical Neuroscience Unit, University of Bonn, Bonn, Germany Robert S. Wilson Rush Alzheimer’s Disease Center, Rush University, Chicago, IL, USA xii © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information Foreword Jesse Hall, MD Professor of Medicine, Anesthesia & Critical Care, Section Chief, Pulmonary and Critical Care Medicine, University of Chicago, Chicago, TL, USA As patients emerge from the terror and abyss of early life-threatening illness, many critical care physicians have learned the wisdom of asking them – or their loved ones when the patient cannot interact and communicate – a simple but probing question: “What do you hope will be achieved by our treatments here in the intensive care unit?” Unfortunately the question is more often asked in those circumstances that lead care providers to predict that the chances for survival and recovery are becoming remote. I believe that if we asked this more routinely, of those dramatically improving and hence lifting our pride in the power of our healing, as well as those dying and bringing us to acknowledge the limitations of our interventions and engaging our commitment to provide comfort to all, the answer would be fairly straightforward and akin to: “To return to my life as I knew it” or “To be myself again.” In my experience our patients and their families show extraordinary realism and resilience. What they mean by those simple statements are not first and foremost that their hearts, and lungs, and kidneys, and limbs all return to their level of function before devastating illness or injury, although this is of course a deep wish. Yes, we discuss whether the dialysis machine or mechanical ventilator will be temporary and if it is to be eventually withdrawn what the path to liberation will entail. But their most fervent wish is to have their loved one return home. And in addition to their return to home and community and job, that they would be the same person, with the personal history, memories, ability to interact, personality and personhood that they recently left behind. In the hierarchy of all of the organs that we discuss on rounds each day when we use our organ- and problem-based approach to organize our findings and plans, they wish most to have their brains back. Paradoxically, this pre-eminent priority embedded in their simple answers to our question is often precisely what we are least able to address, because we lack insight into what has happened to their brain in the course of critical illness, and what the arc of recovery might be. There are reasons the field of critical care medicine has found itself lacking in response to this patient-oriented outcome and priority. We are a young field of medicine, which arose in response to technology expansion and its geographic concentration in hospital units. Early means were developed and refined by pioneers of the field to halt lethal organ failure, to provide an opportunity to diagnose and treat underlying diseases and return patients to an increasingly stable state. We learned that the interplay of these disease processes and our life-support systems was complex and we wisely chose to define critical illness syndromes characterizing the state of our patients, such as the Systemic Inflammatory Response Syndrome. Careful exploration of organ function under our watch taught us that even when the patient became ill from a seemingly localized problem, such as an inflamed pancreas, coagulation, liver, renal, lung, and brain dysfunctions were more often than not present. We assumed, perhaps overly optimistically, that these organ dysfunctions seemingly acquired during critical illness would be shed if the fundamental problem was properly identified and treated, at least if our patient did not march inexorably into a dreaded state of refractory multi-system organ failure. Because our healthcare systems lack ideal longitudinal care and follow-up – in fact far from ideal for either patients or care providers – our early hopeful supposition that conditions such as ICU delirium would be temporary and shed as the patient improved was not much tested before our own eyes. However, our increasing success in treating life-threatening illness generated large populations of survivors of critical illness, and this reality coupled with the dedication and insight of early investigators describing long-term outcomes from critical illness have challenged our early halcyon projections of recovery from presumed temporary brain dysfunction. Seminal studies of patients recovering from the acute respiratory distress syndrome (ARDS), understandably focusing upon serial lung function improvement over time, described xiii © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information Foreword major neurocognitive and neuropsychiatric problems persisting for years after the lung injury that so captured our attention, even when a clear and defined structural brain injury appeared absent. It was most often these deficits of the brain and psyche that precluded patients from returning to the full aspects of their premorbid lives, and which dominated their assessment of the quality of their lives. Somewhat late to the table for the reasons stated above, a large multi-disciplinary group of investigators has arisen across the world, bringing the perspectives and tools of critical care medicine, neurology, psychology, psychiatry, pharmacology, neuroimaging, and rehabilitation medicine to this clinical problem. A handful of descriptive studies has now exploded in only a few years to become literally hundreds of publications defining, describing, and exploring the mechanisms of brain dysfunction acquired during and persisting after diverse critical illnesses. Accordingly, it is timely for the creation of a textbook to summarize where we are in this nascent field, and what the best paths to further study and treatment of our patients might be. Brain Disorders in Critical Illness, created by senior editors Robert Stevens, Tarek Sharshar, and Wes Ely, is a tour de force in the pursuit of this mission. The assembled authors are leaders from the fields of inquiry needed to address the central questions that have arisen about brain dysfunction in critical illness. The reader will be presented with an organization of material that is logical and thorough. It begins with a section on the epidemiology and outcomes that have been increasingly described in the literature based upon longitudinal study of critically ill patients. It then moves to a series of chapters describing behavioral neurology in the ICU, a necessary preamble to then describe biological mechanisms for dysfunction of the central nervous system with emphasis on those mechanisms most plausibly operative during the diverse insults that produce critical illness. A series of chapters then address the dilemma of diagnosis. We are still at a point of determining if there are truly unique types of injury occurring during typical treatments in the ICU, or whether we are witnessing injuries akin to those previously described during other processes (e.g., cardiopulmonary bypass, hypoxia, anesthesia), and how we may assemble tools and then definitions to identify at-risk patients during their ICU stay for special attention downstream. While we certainly are early in the course of even understanding this problem (or how many different problems the general observations will yield), the next section addresses some early studies of promising means of preventing and even treating brain dysfunction in the critically ill. Finally, the last section describes those relatively specific encephalopathies (e.g., hepatic encephalopathy, sepsis) that have been the subjects of study in their own right in the past. Emerging fields benefit enormously from thoughtful pauses that inventory existing information, organize findings into comprehensible frameworks, offer new paradigms for understanding what has been described, and at least name the demon when there are large gaps challenging our understanding. This textbook provides those valuable contributions to the field of critical care medicine, and the authors are to be commended for their accomplishments. It is my hope the book will stimulate as much new thought and discovery as it reviews, and if so it will be poised for an even more exciting second edition in the near future. xiv © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment Edited by Robert D. Stevens, Tarek Sharshar and E. Wesley Ely Frontmatter More information Introduction Tarek Sharshar, E. Wesley Ely, and Robert D. Stevens In recent years there has been widespread acknowledgment that critical illness has a fundamental neurological dimension. A broad body of work has demonstrated that severe illnesses, possibly in conjunction with practices and interventions in the ICU, are responsible for neurological complications which have a major impact on short- and long-term outcome. This neurological burden is almost certainly an indirect product of intensive care itself, with increasing numbers of patients surviving to the recovery phase of critical illness. Scientific exploration of the relevance and impact of ICU-acquired neurological disorders has been led by an initially small, but rapidly expanding, group of dedicated researchers. An illustration of this process is the work on delirium which started with observational studies and now includes large, multicenter randomized trials. Delirium is a complex and fascinating syndrome as its pathophysiology, expression, and severity is heavily dependent on the underlying disorder (e.g., sepsis, hepatic failure), while understanding of its biological mechanisms draws on concepts from neurology, neuropharmacology, neuroimmunology, and the cognitive neurosciences. The association between delirium and age- or disease-associated cognitive impairment is clearly reciprocal, possibly implicating subtle shifts between chronic and acute neuroinflammatory states. Another illustration is anoxic-ischemic encephalopathy resulting from cardiac arrest, which has been the object of a major research effort mobilizing intensivists, neurologists, neurophysiologists, and neuroradiologists in order to develop prognostic models and to assess therapeutic strategies. Anoxic-ischemic encephalopathy is also a clinical paradigm for understanding the biology of consciousness and consciousness disorders. Critical illnesses are life-threatening disturbances of homeostasis. The central nervous system is a major regulator of homeostasis, responding to physiological challenges via behavioral, neuroendocrine, autonomic, and neuroinflammatory responses. A major task for research in critical illness is to understand the fundamental differences between adaptive and maladaptive homeostatic responses, a task which will require rigorous scientific evaluation of interactions between immunological, endocrine, and autonomic systems. Knowledge of these interactions is likely to yield breakthroughs in the treatment of life-threatening diseases such as sepsis, ARDS, and their associated neurological sequelae. Collectively, constructs elaborated in this book underscore the central relevance of neuroscience in the realm of critical care medicine, not only for clinicians in the ICU who are routinely facing acute neurological syndromes, but also for clinical and translational researchers who are evaluating novel therapeutic interventions and innovative methods to map brain perturbations via advances in neuroimaging and electrophysiology. This book provides an overview of brain disorders in critical illness, of which delirium and anoxicischemic encephalopathy are emblematic. But the overarching goal is to construct a biological framework for understanding these disorders. It is our conviction that insights and methods developed in neuroscience will be the main driver of scientific progress in the neurology of critical illness. We would like to extend our deepest appreciation to each author for having enthusiastically accepted to contribute to this book. As editors of this “first-ever textbook” synthesizing Brain Disorders in Critical Illness we look forward to advances in care that will bring more complete healing to our patients globally as they emerge from ICUs and put the pieces of their lives back together. xv © in this web service Cambridge University Press www.cambridge.org