Mechanisms of attention and attentional impairment

Brain Disorders in CriticalIllnessMechanisms, Diagnosis, and Treatment

www.cambridge.org© in this web service Cambridge University Press

Cambridge University Press978-1-107-02919-4 - Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and TreatmentEdited by Robert D. Stevens, Tarek Sharshar and E. Wesley ElyFrontmatterMore information

http://www.cambridge.org/9781107029194

http://www.cambridge.org


Brain Disorders in CriticalIllnessMechanisms, Diagnosis, and TreatmentEdited by

Robert D. StevensAssociate 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 SharsharProfessor, 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 ElyProfessor of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicineand the Geriatric Research Education Clinical Center (GRECC) of Tennessee Valley Veterans Affairs Healthcare System, Nashville, TN, USA






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 ofeducation, learning, and research at the highest international levels of excellence.

www.cambridge.orgInformation on this title: www.cambridge.org/9781107029194

© Cambridge University Press 2013

This publication is in copyright. Subject to statutory exceptionand to the provisions of relevant collective licensing agreements,no reproduction of any part may take place without the writtenpermission 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 ofURLs 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 andup-to-date information which is in accord with accepted standards and practiceat 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 theinformation contained herein is totally free from error, not least because clinicalstandards are constantly changing through research and regulation. The authors,editors and publishers therefore disclaim all liability for direct or consequentialdamages resulting from the use of material contained in this book. Readersare strongly advised to pay careful attention to information provided by themanufacturer of any drugs or equipment that they plan to use.






Contents

List of contributors page viiiForeword xiiiJesse HallIntroduction xv

Section 1. Epidemiology andOutcomes

1. The epidemiology of critical illnessbrain dysfunction 1Raoul Sutter and Robert D. Stevens

2. Cognitive dysfunction following criticalillness 15Ramona O. Hopkins and James C. Jackson

3. Psychiatric disorders following criticalillnesses 23Dimitry S. Davydow

4. Functional status and quality of life aftercritical illness 30Sanjay V. Desai, Nathan E. Brummel, and DaleM. Needham

5. Delirium and dementia: unraveling thecomplex relationship 39Margaret Pisani

Section 2. Behavioral Neurologyin the ICU

6. Cognitive reserve 49Richard E. Temes, Robert S. Wilson, LisaL. Barnes, and David A. Bennett

7. Neurology of consciousnessimpairments 59Benjamin Rohaut, Frédéric Faugeras,and Lionel Naccache

8. Mechanisms of attention and attentionalimpairment 68Paolo Bartolomeo

9. Neurology of sleep and sleepdisorders 76Robert D. Sanders, Stefan D. Gurney, JamieW. Sleigh, and Mervyn Maze

10. Neural basis of fear and anxiety 84Odile Viltart and Christel C. Vanbesien

Section 3. Biological Mechanisms11. Experimental models of

cognitive dysfunction in infection andcritical illness 97Colm Cunningham

12. Neurobiological effects ofsystemic physiological and metabolicinsults 108Jean-Francois Payen, Gérard Audibert, andNicolas Bruder

13. Cerebral ischemia and reperfusion 119Raymond C. Koehler

14. Brain perfusion and autoregulationin systemic critical illness 129Martin Siegemund and Luzius A. Steiner

15. Delirium and neurotransmitterdysfunction 139Willem A. van Gool

v






16. Neuromodulatory and neurotoxiceffects of sedative agents 150Jean Mantz and Souhayl Dahmani

17. Neuroimmunological cross-talk in criticalillness 160Robert Dantzer and Keith W. Kelley

18. Inflammatory mechanisms in chronicneurodegenerative disease: the impact ofmicroglia priming 172V. Hugh Perry

19. The neuroendocrine response to criticalillness 181David Luis and Djillali Annane

20. Autonomic dysfunction in SIRS andsepsis 192Jeremy D. Scheff, Panteleimon D. Mavroudis,Steve E. Calvano, Stephen F. Lowry, and IoannisP. Androulakis

21. Sepsis-induced neuronal dysfunction anddeath 200Sadanand M. Gaikwad, Catherine N. Widmann,and Michael T. Heneka

22. Neuroimmunomodulation in sepsis 208Marion Griton and Jan Pieter Konsman

Section 4. Diagnosis of BrainDysfunction

23. Clinical neurological assessment of thecritically ill patient 219Raoul Sutter, Tarek Sharshar, and RobertD. Stevens

24. Bedside assessment of delirium in criticallyill patients 229Alawi Luetz and Claudia D. Spies

25. Electroencephalography andevoked potentials in critically ill patients 241Matthew A. Koenig and Peter W. Kaplan

26. Neuroimaging of delirium 257Karen J. Ferguson and Alasdair M. J. MacLullich

Section 5. Preventative andTherapeutic Interventions

27. Environmental modification 279Yoanna Skrobik

28. New paradigms in sedationof the critically ill patient 285Christopher G. Hughes and PratikP. Pandharipande

29. Pharmacological managementof delirium 294Dustin M. Hipp and E. Wesley Ely

30. Pharmacogenomics and cerebraldysfunction 305Yoanna Skrobik

31. Early physical and occupationaltherapy 316John P. Kress

32. Rehabilitation after critical illness 321Richard D. Griffiths and ChristinaJones

Section 6. ClinicalEncephalopathy Syndromes

33. Drug-induced encephalopathy 329Bruno Mégarbane

34. Metabolic encephalopathies: inbornerrors of metabolism causingencephalopathies in adults 344Frederic Sedel

35. Encephalopathy associated with alcoholor drug withdrawal 354Felix Kork and Claudia D. Spies

36. Posterior reversibleencephalopathy syndrome (PRES):the essential elements 362Walter S. Bartynski and Hebah M. Hefzy

37. Hypoxic-ischemic encephalopathy 373Fabio Silvio Taccone and Alain Cariou

Contents

vi






38. Sepsis-associated encephalopathy 381Romain Sonneville, C. Rauturier,F. Verdonk, F. Chretien, and Tarek Sharshar

39. Seizures and status epilepticus in criticalillness 391Brandon Foreman and Jan Claassen

40. Encephalopathy and coma in acute andchronic liver failure 403Julia Wendon and Jennifer Ryan

41. Neurological complications of cardiac surgery:stroke, encephalopathy, and cognitivedecline 410Rebecca F. Gottesman, Maura A. Grega, GuyM. McKhann, and Ola A. Selnes

Glossary 419Index 424

Color plate section is between pp. 240 and 241.

Contents

vii






Contributors

Ioannis P. AndroulakisDepartment of Biomedical Engineering, Departmentof Chemical and Biochemical Engineering, RutgersUniversity, Piscataway, and Department of Surgery,UMDNJ-Robert Wood Johnson Medical School, NewBrunswick, NJ, USA

Djillali AnnaneService de reanimation, hospital Raymond Poincaré(AP-HP), University of Versailles SQY, Garches,France

Gérard AudibertDepartment of Anesthesiology and Critical Care,Nancy University Hospital, Nancy, France

Lisa L. BarnesDepartments of Behavioral Sciences and NeurologicalSciences, and Rush Alzheimer’s Disease Center, RushUniversity Medical Center, Chicago, IL, USA

Paolo BartolomeoINSERM-U 975, Centre de Recherche de l’Institut duCerveau et de la Moelle Epinière (CRICM) etUniversité Pierre et Marie Curie (UPMC), GroupeHospitalier Pitié-Salpêtrière, Paris, France; AP-HP,Groupe Hospitalier Pitié-Salpêtrière, Fédération deNeurologie, Paris, France; Department of Psychology,Catholic University, Milan, Italy

Walter S. BartynskiDepartment of Radiology and Radiological Science,Division of Neuroradiology, Medical Universityof South Carolina, Charleston, SC, USA

David A. BennettProfessor of Neurological Sciences, Departmentof Neurological Sciences and Rush Alzheimer’sDisease Center, Rush University Medical Center,Chicago, IL, USA

Nicolas BruderDepartment of Anesthesiology andCritical Care, Marseille University Hospital,Marseille, France

Nathan E. BrummelDivision of Allergy, Pulmonary and Critical CareMedicine, Vanderbilt School of Medicine, Nashville,TN, USA

Steve E. CalvanoDepartment of Surgery, UMDNJ-RobertWood Johnson Medical School, New Brunswick,NJ, USA

Alain CariouMedical Intensive Care Unit, AP-HP, CochinHospital, Paris, and Paris Descartes University andSorbonne Paris Cité Medical School, Paris, France

F. ChretienUnité “Histopathologie Humaine et ModèlesAnimaux,” Département Infection et Epidémiologie,Institut Pasteur, Paris, and University of VersaillesSaint-Quentin-en-Yvelines, Garches, France

Jan ClaassenDivision of Neurocritical Care, Neurological Instituteof New York, Columbia University Medical Center,New York, NY, USA

Colm CunninghamTrinity College Institute of Neuroscience and Schoolof Biochemistry and Immunology, Trinity CollegeDublin, Republic of Ireland

Souhayl DahmaniAP-HP, Robert Debré University Hospitals,INSERM-U 676, Paris Diderot University, Paris,France

viii






Robert DantzerDepartment of Symptom Research, MD AndersonCancer Center, Houston, TX, USA

Dimitry S. DavydowDepartment of Psychiatry and Behavioral Sciences,University of Washington, Seattle, WA, USA

Sanjay V. DesaiDivision of Pulmonary and Critical CareMedicine, The Johns Hopkins University,Baltimore, MD, USA

E.Wesley ElyDivision of Allergy, Pulmonary, and Critical CareMedicine, Vanderbilt University School of Medicineand the Geriatric Research Education Clinical Center(GRECC) of Tennessee Valley Veterans AffairsHealthcare System, Nashville, TN, USA

Frédéric FaugerasINSERM, ICM Research Center, UMRS 975, Paris,and AP-HP, Groupe Hospitalier Pitié-Salpêtrière,Departments of Neurophysiology and Neurology,Paris, France

Karen J. FergusonNeuroimaging Research Fellow, School of ClinicalSciences, University of Edinburgh, UK

Brandon ForemanComprehensive Epilepsy Center, NeurologicalInstitute of New York, Columbia University MedicalCenter, New York, NY, USA

Sadanand M. GaikwadDepartment of Neurology, ClinicalNeuroscience Unit, University of Bonn, Bonn,Germany

Rebecca F. GottesmanDepartment of Neurology, Johns Hopkins BayviewMedical Center, Baltimore, MD, USA

Maura A. GregaResearch Nurse Program Coordinator, The JohnsHopkins University, Baltimore, MD, USA

Richard D. GriffithsEmeritus Professor of Medicine (Intensive Care),Whiston Hospital and Department of MusculoskeletalBiology, Institute of Ageing and Chronic Disease,Faculty of Health and Life Sciences, University ofLiverpool, Liverpool, UK

Marion GritonCNRS UMR 5536 Magnetic Resonance of BiologicalSystems, Victor Segalen Bordeaux 2 University,Bordeaux, France

Stefan D. GurneyMagill 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. HefzyDepartment of Neurology, Henry Ford Hospital,Detroit, MI, USA

Michael T. HenekaDepartment of Neurology, Clinical NeuroscienceUnit, University of Bonn, Bonn, Germany

Dustin M. HippVanderbilt University School of Medicine, Nashville,TN, USA

Ramona O. HopkinsDepartment of Psychology and Neuroscience Center,Brigham Young University, Provo, UT, andDepartment of Medicine, Pulmonary and CriticalCare Division, Intermountain Medical Center,Murray, UT, USA

Christopher G. HughesDepartment of Anesthesiology, Vanderbilt UniversitySchool of Medicine, Nashville, TN, USA

James C. JacksonDivision of Allergy, Pulmonary, and Critical CareMedicine, and Center for Health Services Research,Vanderbilt University School of Medicine, Nashville,TN, USA

Christina JonesNurse Consultant, Intensive Care Rehabilitation,Intensive Care Unit, Whiston Hospital, Prescot,Merseyside, and Honorary Reader, Institute of Ageingand Chronic Disease, Faculty of Health and LifeSciences, University of Liverpool, Liverpool, UK

Peter W. KaplanDepartment of Neurology, Johns Hopkins BayviewMedical Center, Baltimore, MD, USA

Keith W. KelleyDepartment of Immunophysiology, University ofIllinois at Urbana-Champaign, Urbana, IL, USA

List of contributors

ix






Raymond C. KoehlerDepartment of Anesthesiology and Critical CareMedicine, School of Medicine, The Johns HopkinsUniversity, Baltimore, MD, USA

Matthew A. KoenigNeurocritical Care, NeuroscienceInstitute, The Queen’s Medical Center,Honolulu, HI, USA

Jan Pieter KonsmanCNRS UMR 5536 Magnetic Resonance of BiologicalSystems, Victor Segalen Bordeaux 2 University,Bordeaux, France

Felix KorkDepartment of Anaesthesiology andIntensive Care Medicine, Charité –Universitätsmedizin Berlin, Campus VirchowKlinikum and Campus Charité Mitte, Berlin,Germany

John P. KressDepartment of Medicine, Section of Pulmonaryand Critical Care, University of Chicago, Chicago,IL, USA

Stephen F. LowryDepartment of Surgery, UMDNJ-Robert WoodJohnson Medical School, New Brunswick, NJ, USA

Alawi LuetzDepartment of Anaesthesiology andIntensive Care Medicine, Charité –Universitätsmedizin Berlin, Berlin, Germany

David LuisService de reanimation, hospital Raymond Poincaré(AP-HP), University of Versailles SQY, Garches,France

Alasdair M. J. MacLullichDepartment of Geriatric Medicine, Universityof Edinburgh, and Honorary Consultant in Generaland Geriatric Medicine, Royal Infirmary ofEdinburgh, UK

Guy M. McKhannJohns Hopkins University School of Medicine,Baltimore, MD, USA

Jean MantzDepartment of Anesthesia and Critical Care,Beaujon-Paris Val de Seine University Hospitals,Paris, France

Panteleimon D. MavroudisDepartment of Chemical andBiochemical Engineering, Rutgers University,Piscataway, NJ, USA

Mervyn MazeDepartment of Anesthesia & Perioperative Care,University of California San Francisco, SanFrancisco, CA, USA

Bruno MégarbaneMedical and Toxicological Critical Care Unit,Lariboisière Hospital, Paris Diderot University,INSERM U705, Paris, France

Lionel NaccacheINSERM, ICM Research Center, UMRS 975,Paris; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Departments ofNeurophysiology and Neurology, Paris;University Paris 6, Faculté de MédecinePitié-Salpêtrière, Paris, France

Dale M. NeedhamOutcomes After Critical Illness and Surgery(OACIS) Group, Division of Pulmonaryand Critical Care Medicine, andDepartment of Physical Medicine andRehabilitation, The Johns Hopkins University,Baltimore, MD, USA

Pratik P. PandharipandeVanderbilt University School of Medicine,Anesthesia Service, VA TVHS, Nashville,Nashville, TN, USA

Jean-Francois PayenDepartment of Anesthesiology andCritical Care, Grenoble University Hospital,Grenoble, France

V. Hugh PerryExperimental Neuropathology, Centre forBiological Sciences, University of Southampton,Southampton, UK


x






Margaret PisaniPulmonary and Critical Care Medicine,Yale University School of Medicine, NewHaven, CT, USA

C. RauturierUnité “Histopathologie Humaine etModèles Animaux,” DépartementInfection et Epidémiologie, InstitutPasteur, Paris, and University ofVersailles Saint-Quentin-en-Yvelines,Garches, France

Benjamin RohautDepartments of Neurology and Intensive Care Unit,ICM Research Center INSERM UMRS 975 andUniversité Pierre et Marie Curie (Paris VI),Pitié-Salpêtrière Hospital, Paris, France

Jennifer RyanDivision of Mucosal Biology and TransplantationInstitute of Liver Studies, Kings College London,Kings College Hospital, London, UK

Robert D. SandersMagill Department of Anaesthesia, IntensiveCare, and Pain Medicine; Department of Anaesthetics,Intensive Care, and Pain Medicine, Chelsea &Westminster Hospital, Imperial College London,and Department of Leukocyte Biology, NationalHeart and Lung Institute, Imperial College London,London, UK

Jeremy D. ScheffDepartment of Biomedical Engineering, RutgersUniversity, Piscataway, NJ, USA

Frederic SedelDepartment of Neurology, Reference Center forLysosomal Diseases, Neurometabolic FunctionUnit, Pitié-Salpêtrière Hospital, AP-HP, Paris, andUniversité Pierre etMarie Curie (Paris VI), Paris, France

Ola A. SelnesDepartment of Neurology, The Johns HopkinsHospital, Baltimore, MD, USA

Tarek SharsharDepartment of Intensive Care Medicine, RaymondPoincaré Hospital, University Versailles Saint-Quentin-en-Yvelines, Garches, France; Laboratory ofHistopathology and Animal Models, Francois JacobCentre, Institut Pasteur, Paris, France

Martin SiegemundDepartment of Anaesthesia, Critical Care and Pre-hospital Emergency Medicine, State Hospital AG,Baden, Switzerland

Yoanna SkrobikDépartement de soins intensifs,Maisonneuve-Rosemont Hospital, and CriticalCare Medicine, University of Montreal, Montreal,Quebec, Canada

Jamie W. SleighDepartment of Anaesthesia, University ofAuckland, Waikato Hospital, Hamilton, New Zealand

Romain SonnevilleDepartment of Intensive Care Medicine andInfectious Diseases, Hôpital Bichat-ClaudeBernard, Université Diderot-Paris 7, Paris;Unité “Histopathologie Humaine et ModèlesAnimaux,” Département Infection etEpidémiologie, Institut Pasteur, Paris; Universityof Versailles Saint-Quentin-en-Yvelines, Garches,France

Claudia D. SpiesDepartment of Anesthesiology andIntensive Care Medicine, Charité –Universitätsmedizin Berlin, Campus VirchowKlinikum und Campus Charité Mitte, Berlin,Germany

Luzius A. SteinerDepartment of Anesthesia, University Hospital Centerand University of Lausanne, Lausanne, Switzerland

Robert D. StevensDepartments of Anesthesiology and Critical CareMedicine, and Department of Neurology,Neurosurgery and Radiology-Radiological Sciences,Johns Hopkins University School of Medicine,Baltimore, MD, USA

Raoul SutterDepartments of Anesthesiology and Critical CareMedicine, and Department of Neurology, JohnsHopkins University School of Medicine, Baltimore,MD, USA

Fabio Silvio TacconeDepartment of Intensive Care, Erasme Hospital,Université Libre de Bruxelles, Bruxelles, Belgium


xi






Richard E. TemesDepartment of Neurological Sciences, Rush UniversityMedical Center, Chicago, IL, USA

Willem A. van GoolDepartment of Neurology, Academic Medical Centre,Amsterdam, the Netherlands

Christel C. VanbesienUniversity Lille Nord de France/USTL(Sciences & Technologies, Lille 1), and INSERMUMR 837, Molecular events associated to earlystages of Parkinson’s disease, Place de Verdun,Lille, France

F. VerdonkUnité “Histopathologie Humaine etModèles Animaux,” DépartementInfection et Epidémiologie, InstitutPasteur, Paris, and University of

Versailles Saint-Quentin-en-Yvelines,Garches, France

Odile ViltartUniversity Lille Nord de France/USTL (Sciences &Technologies, Lille 1), and INSERM UMR 837,Plasticity and Development of Postnatal Brain, Placede Verdun, Lille, France

Julia WendonDivision of Mucosal Biology and Transplantation,Institute of Liver Studies, Kings College London,Kings College Hospital, London, UK

Catherine N. WidmannDepartment of Neurology, Clinical NeuroscienceUnit, University of Bonn, Bonn, Germany

Robert S. WilsonRush Alzheimer’s Disease Center, Rush University,Chicago, IL, USA


xii






ForewordJesse Hall, MDProfessor 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 earlylife-threatening illness, many critical care physicianshave learned the wisdom of asking them – or theirloved ones when the patient cannot interact and com-municate – a simple but probing question: “What doyou hope will be achieved by our treatments here inthe intensive care unit?” Unfortunately the question ismore often asked in those circumstances that lead careproviders to predict that the chances for survival andrecovery are becoming remote. I believe that if weasked this more routinely, of those dramaticallyimproving and hence lifting our pride in the powerof our healing, as well as those dying and bringing usto acknowledge the limitations of our interventionsand engaging our commitment to provide comfort toall, the answer would be fairly straightforward andakin to: “To return to my life as I knew it” or “To bemyself again.”

In my experience our patients and their familiesshow extraordinary realism and resilience. What theymean by those simple statements are not first andforemost that their hearts, and lungs, and kidneys,and limbs all return to their level of function beforedevastating illness or injury, although this is of coursea deep wish. Yes, we discuss whether the dialysismachine or mechanical ventilator will be temporaryand if it is to be eventually withdrawn what the path toliberation will entail. But their most fervent wish is tohave their loved one return home. And in addition totheir return to home and community and job, thatthey would be the same person, with the personalhistory, memories, ability to interact, personality andpersonhood that they recently left behind. In the hier-archy of all of the organs that we discuss on roundseach day when we use our organ- and problem-basedapproach to organize our findings and plans, they wishmost to have their brains back.

Paradoxically, this pre-eminent priority embeddedin their simple answers to our question is often preciselywhat we are least able to address, because we lack insightinto 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 hasfound itself lacking in response to this patient-orientedoutcome and priority.We are a young field ofmedicine,which arose in response to technology expansion and itsgeographic concentration in hospital units. Early meanswere developed and refined by pioneers of the field tohalt lethal organ failure, to provide an opportunity todiagnose and treat underlying diseases and returnpatients to an increasingly stable state. We learnedthat the interplay of these disease processes and ourlife-support systems was complex and we wisely choseto define critical illness syndromes characterizing thestate of our patients, such as the Systemic InflammatoryResponse Syndrome. Careful exploration of organfunction under our watch taught us that even whenthe patient became ill from a seemingly localized prob-lem, such as an inflamed pancreas, coagulation, liver,renal, lung, and brain dysfunctions were more oftenthan not present. We assumed, perhaps overly optimis-tically, that these organ dysfunctions seeminglyacquired during critical illness would be shed if thefundamental problem was properly identified and trea-ted, at least if our patient did not march inexorably intoa dreaded state of refractorymulti-system organ failure.

Because our healthcare systems lack ideal longitu-dinal care and follow-up – in fact far from ideal foreither patients or care providers – our early hopefulsupposition that conditions such as ICU deliriumwould be temporary and shed as the patient improvedwas not much tested before our own eyes. However,our increasing success in treating life-threatening ill-ness generated large populations of survivors of crit-ical illness, and this reality coupled with the dedicationand insight of early investigators describing long-termoutcomes from critical illness have challenged ourearly halcyon projections of recovery from presumedtemporary brain dysfunction. Seminal studies ofpatients recovering from the acute respiratory distresssyndrome (ARDS), understandably focusing uponserial lung function improvement over time, described

xiii






major neurocognitive and neuropsychiatric problemspersisting for years after the lung injury that so cap-tured our attention, even when a clear and definedstructural brain injury appeared absent. It was mostoften these deficits of the brain and psyche that pre-cluded patients from returning to the full aspects oftheir premorbid lives, and which dominated theirassessment of the quality of their lives.

Somewhat late to the table for the reasons statedabove, a large multi-disciplinary group of investigatorshas arisen across the world, bringing the perspectivesand tools of critical care medicine, neurology, psych-ology, psychiatry, pharmacology, neuroimaging, andrehabilitation medicine to this clinical problem. Ahandful of descriptive studies has now exploded inonly a few years to become literally hundreds of pub-lications defining, describing, and exploring the mech-anisms of brain dysfunction acquired during andpersisting after diverse critical illnesses. Accordingly,it is timely for the creation of a textbook to summarizewhere we are in this nascent field, and what the bestpaths to further study and treatment of our patientsmight be. Brain Disorders in Critical Illness, created bysenior editors Robert Stevens, Tarek Sharshar, andWes Ely, is a tour de force in the pursuit of this mission.

The assembled authors are leaders from the fieldsof inquiry needed to address the central questions thathave arisen about brain dysfunction in critical illness.The reader will be presented with an organization ofmaterial that is logical and thorough. It begins with asection on the epidemiology and outcomes that havebeen increasingly described in the literature basedupon longitudinal study of critically ill patients. Itthen moves to a series of chapters describing behav-ioral neurology in the ICU, a necessary preamble to

then describe biological mechanisms for dysfunctionof the central nervous system with emphasis on thosemechanisms most plausibly operative during thediverse insults that produce critical illness. A series ofchapters then address the dilemma of diagnosis. Weare still at a point of determining if there are trulyunique types of injury occurring during typical treat-ments in the ICU, or whether we are witnessing injur-ies akin to those previously described during otherprocesses (e.g., cardiopulmonary bypass, hypoxia,anesthesia), and how we may assemble tools andthen definitions to identify at-risk patients duringtheir ICU stay for special attention downstream.While we certainly are early in the course of evenunderstanding this problem (or how many differentproblems the general observations will yield), the nextsection addresses some early studies of promisingmeans of preventing and even treating brain dysfunc-tion in the critically ill. Finally, the last sectiondescribes those relatively specific encephalopathies(e.g., hepatic encephalopathy, sepsis) that have beenthe subjects of study in their own right in the past.

Emerging fields benefit enormously from thought-ful pauses that inventory existing information, organ-ize findings into comprehensible frameworks, offernew paradigms for understanding what has beendescribed, and at least name the demon when thereare large gaps challenging our understanding. Thistextbook provides those valuable contributions to thefield of critical care medicine, and the authors are to becommended for their accomplishments. It is my hopethe book will stimulate as much new thought anddiscovery as it reviews, and if so it will be poised foran even more exciting second edition in the nearfuture.

Foreword

xiv






IntroductionTarek Sharshar, E.Wesley Ely, and Robert D. Stevens

In recent years there has been widespread acknowledg-ment that critical illness has a fundamental neurologicaldimension. A broad body of work has demonstrated thatsevere illnesses, possibly in conjunction with practicesand interventions in the ICU, are responsible for neuro-logical complications which have a major impact onshort- and long-term outcome. This neurological burdenis almost certainly an indirect product of intensive careitself, with increasing numbers of patients surviving tothe recovery phase of critical illness. Scientific explora-tion of the relevance and impact of ICU-acquired neuro-logical disorders has been led by an initially small, butrapidly expanding, group of dedicated researchers.

An illustration of this process is the work on delir-ium which started with observational studies and nowincludes large, multicenter randomized trials. Deliriumis a complex and fascinating syndrome as its patho-physiology, expression, and severity is heavily depend-ent on the underlying disorder (e.g., sepsis, hepaticfailure), while understanding of its biological mech-anisms draws on concepts from neurology, neuro-pharmacology, neuroimmunology, and the cognitiveneurosciences. The association between delirium andage- or disease-associated cognitive impairment isclearly reciprocal, possibly implicating subtle shiftsbetween chronic and acute neuroinflammatory states.

Another illustration is anoxic-ischemic encephalop-athy resulting from cardiac arrest, which has been theobject of a major research effort mobilizing intensivists,neurologists, neurophysiologists, and neuroradiologistsin order to develop prognostic models and to assesstherapeutic strategies. Anoxic-ischemic encephalopathyis also a clinical paradigm for understanding the biologyof consciousness and consciousness disorders.

Critical illnesses are life-threatening disturbances ofhomeostasis. The central nervous system is a major

regulator of homeostasis, responding to physiologicalchallenges via behavioral, neuroendocrine, autonomic,and neuroinflammatory responses. A major task forresearch in critical illness is to understand the funda-mental differences between adaptive and maladaptivehomeostatic responses, a task whichwill require rigorousscientific evaluation of interactions between immunolog-ical, endocrine, and autonomic systems. Knowledge ofthese interactions is likely to yield breakthroughs in thetreatment of life-threatening diseases such as sepsis,ARDS, and their associated neurological sequelae.

Collectively, constructs elaborated in this bookunderscore the central relevance of neuroscience inthe realm of critical care medicine, not only for clini-cians in the ICU who are routinely facing acute neuro-logical syndromes, but also for clinical andtranslational researchers who are evaluating noveltherapeutic interventions and innovative methods tomap brain perturbations via advances in neuroimag-ing and electrophysiology.

This book provides an overview of brain disordersin critical illness, of which delirium and anoxic-ischemic encephalopathy are emblematic. But theoverarching goal is to construct a biological frame-work for understanding these disorders. It is our con-viction that insights and methods developed inneuroscience will be the main driver of scientificprogress in the neurology of critical illness. Wewould like to extend our deepest appreciation to eachauthor for having enthusiastically accepted to contrib-ute to this book. As editors of this “first-ever textbook”synthesizing Brain Disorders in Critical Illness we lookforward to advances in care that will bring more com-plete healing to our patients globally as they emergefrom ICUs and put the pieces of their lives backtogether.

xv






Mechanisms of attention and attentional impairment

Documents

Transcript of Mechanisms of attention and attentional impairment