44 Update in Intensive Care and Emergency Medicine

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Edited by J.-L. Vincent

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E. Abraham M. Singer (Eds.)

Mechanisms of Sepsis-Induced Organ Dysfunction and Recovery

With 48 Figures and 22 Tables

123

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Series Editor

Prof. Jean-Louis Vincent

Head, Department of Intensive Care Erasme University Hospital Route de Lennik 808, 1070 Brussels Belgium

jlvincen@ulb.ac.be

Volume Editors Edward Abraham, MD University of Colorado Health Sciences Center

Division Pulmonary & Critical Care Medicine

E. Ninth Avenue 4200 80262 Denver, CO USA

Mervyn Singer, MD University College Hospital Bloomsbury Institute of Intensive Care

Division Medicine Gower Street, WC1E 6BT London

United Kingdom

ISSN 0933-6788

ISBN-10 3-540-30157-7 Springer Berlin Heidelberg New York ISBN-13 978-3-540-30157-8 Springer Berlin Heidelberg New York

Library of Congress Control Number: 2006929196

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Table of Contents

Setting the Scene . . . . 1 J.L. Vincent

The Inflammatory Response

Genetics and Severe Sepsis . . . . 17 J. Texereau, V. Lemiale, J.-P. Mira

Cell Signaling Pathways of the Innate Immune System

During Acute Inﬂammation . . . . 35 S.M. Opal, P.A. Cristofaro

Early-Onset Pro-inﬂammatory Cytokines . . . . 55 C. Kaech, T. Calandra

The Signiﬁcance of HMGB1, a Late-Acting Pro-inﬂammatory Cytokine . . . . 67 E. Abraham

Nitric Oxide . . . . 77 J. Carré, M. Singer, S. Moncada

Involvement of Reactive Oxygen and Nitrogen Species

in the Pathogenesis of Acute Lung Injury . . . . 97 S. Matalon, I.C. Davis, J.D. Lang Jr

Heat Shock Proteins in Inﬂammation . . . 113 Z. Bromberg, Y.G. Weiss, C.S. Deutschman

Fibrosis in the Acute Respiratory Distress Syndrome . . . 123 D.C.J. Howell, R.C. Chambers, G.J. Laurent

Resolution of Inﬂammation . . . 137 G. Bellingan

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VI Table of Contents

The Cellular Immune Respone

Compartmentalized Activation of Immune Cells During Sepsis

and Organ Dysfunction . . . 161 J.-M. Cavaillon, M. Adib-Conquy

The Neutrophil in the Pathogenesis

of Multiple Organ Dysfunction Syndrome . . . 183 Z. Malam, J.C. Marshall

The Role of the Macrophage . . . 203 J. Pugin

The Role of the Endothelium . . . 211 W.C. Aird

Differential Effects of Pro-Inﬂammatory Mediators

on Alveolar Epithelial Barrier Function . . . 229 M.A. Matthay, J.-W. Lee

Mechanisms and Pathways of Dysfunction

Macrocirculatory Disturbances . . . 239 D. De Backer

The Microcirculation Is a Vulnerable Organ in Sepsis . . . 249 P.W.G. Elbers, C. Ince

The Cholinergic Anti-inﬂammatory Pathway:

Connecting the Mind and Body . . . 263 C.J. Czura, S.G. Friedman, K.J. Tracey

Coagulation in Sepsis . . . 273 W.J. Wiersinga, M. Levi, T. van der Poll

The Role of Insulin and Blood Glucose Control . . . 287 L. Langouche, I. Vanhorebeek, G. Van den Berghe

Dysfunction of the Bioenergetic Pathway . . . 299 M. Singer

Metabolic Pathways . . . 311 O. Rooyackers, J. Wernerman

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Table of Contents VII

Cell Death and Acute Lung Injury . . . 321 T.R. Martin, N. Hagimoto, G. Matute-Bello

Mechanisms of Immunodepression after Central Nervous System Injury . . . 335 C. Meisel, H.-D. Volk

Organ-specific Mechanisms of Dysfunction

Pulmonary Dysfunction . . . 353 N.S. MacCallum, G.J. Quinlan, T.W. Evans

The Gut . . . 369 M.P. Fink

Endogenous Danger Signals in Liver Injury:

Role of High Mobility Group Box Protein-1 . . . 383 A. Tsung, G. Jeyabalan, T.R. Billiar

Sepsis-induced Acute Renal Failure and Recovery . . . 393 M. Raghavan, R. Venkataraman, J.A. Kellum

Sepsis-Induced Brain Dysfunction . . . 407 C. Guidoux, T. Sharshar, D. Annane

Myocardial Depression in Sepsis and Septic Shock . . . 415 A. Kumar, J.E. Parrillo

Skeletal Muscle . . . 437 R.D. Grifﬁths, T. Bongers, A. McArdle

Subject Index . . . 449

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Contributors

Abraham E

Department of Medicine University of Alabama 1530 3rd Ave S

Birmingham, AL 35294-0012 USA

Adib-Conquy M

UP Cytokines & Inﬂammation Institut Pasteur

28 rue Dr Roux 75015 Paris France

Aird WC

Molecular Medicine

Beth Israel Deaconess Medical Center RW-663

330 Brookline Avenue Boston, MA 02215 USA

Annane D

Service de Réanimation Hospital Raymond Poincaré 104 Boulevard Raymond Poincaré 92380 Garches

France

Bellingan G

Center for Respiratory Research University College London Rayne Institute

University St London, WC1E 6JJ United Kingdom

Billiar TR

Department of Surgery

University of Pittsburgh School of Medicine 20 Lothrop Street

Presbyterian Hospital F1200 Pittsburgh, PA 15213 USA

Bongers T

Division of Metabolic and Cellular Medicine School of Clinical Science

Duncan Building, UCD University of Liverpool Liverpool, L69 3GA United Kingdom

Bromberg Z

Department of Anesthesia and Critical Care Medicine Hadassah Hebrew University School of Medicine

Jerusalem 91120 Israel

Calandra T

Infectious Diseases Service Department of Medicine

Centre Hospitalier Universitaire Vaudois 1011 Lausanne

Switzerland

Carré J

Wolfson Institute of Biomedical Research University College of London

Gower Street London, WC1E 6BT United Kingdom

Cavaillon JM

UP Cytokines & Inﬂammation Institut Pasteur

28 rue Dr Roux 75015 Paris France

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X Contributors

Chambers RC

Center for Respiratory Research The Rayne Institute

5 University Street London, WC1E 6JJ United Kingdom

Cristofaro PA

Infectious Diseases Division Memorial Hospital of RI 111 Brewster Street Pawtucket, RI 02860 USA

Czura CJ

Laboratory of Biomedical Science North Shore-LIJ Research Institute 350 Community Dr.

Manhasset, NY 11030 USA

Davis IC

Department of Anesthesiology University of Alabama 1530 3rd Avenue South Birmingham, AL 35294 USA

De Backer D

Department of Intensive Care Medicine Erasme University of Brussels Hospital Route de Lennik 808

1070 Brussels Belgium

Deutschman CS

Department of Anesthesiology and Critical Care Medicine

University of Pennsylvania School of Medicine Dulles 781A/HUP

3400 Spruce Street

Philadelphia, PA 19104-4283 USA

Elbers PWG

Department of Anesthesiology, Intensive Care and Pain Management St. Antonius Hospital

Koekoekslaan 1 Postbus 2500 3430 EM Nieuwegein Netherlands

Evans TW

Department of Intensive Care Medicine Royal Brompton Hospital

Sydney Street London, SW3 6 NP United Kingdom

Fink MP

Departments of Critical Care Medicine, Surgery, Pharmacology and Pathology University of Pittsburgh School of Medicine Room 616 Scaife Hall

3550 Terrace Street Pittsburgh, PA 15261 USA

Friedman SG

Laboratory of Biomedical Science North Shore-LIJ Research Institute 350 Community Drive

Grifﬁths RD

Guidoux C

Service de Réanimation Hospital Raymond Poincaré 104 Boulevard Raymond Poincaré 92380 Garches

France

Hagimoto N

Pulmonary Research Labs, 151L VA Puget Sound Medical Center 1660 S. Columbian Way Seattle, WA 98108 USA

Howell DCJ

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Contributors XI

Ince C

Clinical Physiology Academic Medical Center Meibergdreef 9

1105 AZ Amsterdam Netherlands

Jeyabalan G

Kaech C

Infectious Diseases Service Department of Medicine

Centre Hospitalier Universitaire Vaudois 1011 Lausanne

Switzerland

Kellum JA

Department of Critical Care Medicine 615 Scaife Hall

University of Pittsburgh 3550 Terrace Street Pittsburgh, PA 15261 USA

Kumar A

Section of Critical Care Medicine Health Sciences Center, GE706 820 Sherbrooke St

Winnipeg, Manitoba R3A 1R9 Canada

Lang JD Jr

Langouche L

Department of Intensive Care Medicine Katholieke Universiteit Leuven Herestraat 49

3000 Leuven Belgium

Laurent GJ

Lee JW

Department of Medicine and Anesthesia Cardiovascular Research Institute University of California

505 Parnassus Avenue San Francisco, CA 94143-0624 USA

Lemiale V

Medical Intensive Care Unit Groupe Hospitalier Cochin – St Vincent de Paul

René Descartes University – Paris V 27 rue du Faubourg St Jacques 75679 Paris Cedex 14 France

Levi M

Academic Medical Center Department of Internal Medicine Meibergdreef 9, Room G2-130 1105 AZ Amsterdam Netherlands

MacCallum NS

Sydney Street London, SW3 6NP United Kingdom

Malam Z

Sepsis Research Laboratory St. Michael’s Hospital

4th Floor Bond Wing, Rm. 4-007 30 Bond Street

Toronto, ON M5B 1W8 Canada

Marshall JC

Sepsis Research Laboratory St. Michael’s Hospital

4th Floor Bond Wing, Rm. 4-007 30 Bond Street

Toronto, ON M5B 1W8 Canada

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XII Contributors

Martin TR

Matalon S

Matthay MA

Department of Medicine and Anesthesia Cardiovascular Research Institute University of California

505 Parnassus Avenue San Francisco, CA 94143-0624 USA

Matute-Bello G

McArdle A

Meisel C

Institute of Medical Immunology

Universitätsmedizin Charité Campus Mitte Schumanstrasse 20/21

10117 Berlin Germany

Mira JP

Medical Intensive Care Unit Groupe Hospitalier Cochin – St Vincent de Paul

Moncada S

Wolfson Institute of Biomedical Research University College of London

Opal SM

Infectious Diseases Division Memorial Hospital of RI 111 Brewster Street Pawtucket, RI 02860 USA

Parrillo JE

Cardiovascular and Critical Care Services Cooper University Hospital

One Cooper Plaza Camden, NJ 08103 United States

Pugin J

Department of Intensive Care Medicine University Hospital

Rue Micheli-du-Crest 1211 Geneva 14 Switzerland

Quinlan GJ

Sydney Street London, SW3 6 NP United Kingdom

Raghavan M

Rooyackers O

Dept of Anesthesiology and Intensive Care Medicine K32

Karolinska University Hospital Huddinge 14186 Stockholm

Sweden

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Contributors XIII

Sharshar T

Service de Réanimation Hôpital Raymond Poincaré 104 Boulevard Raymond Poincaré 92380 Garches

France

Singer M

Bloomsbury Institute of Intensive Care Medicine

Wolfson Institute of Biomedical Research University College London

Texereau J

Cochin Institute of Molecular Genetics Groupe Hospitalier Cochin –

St Vincent de Paul

Tracey KJ

Laboratory of Biomedical Science North Shore-LIJ Research Institute 350 Community Dr.

Tsung A

Van den Berghe G

3000 Leuven Belgium

van der Poll T

Vanhorebeek I

3000 Leuven Belgium

Venkataraman R

Vincent JL

Department of Intensive Care Medicine Erasme University of Brussels Hospital Route de Lennik 808

1070 Brussels Belgium

Volk HD

Institute of Medical Immunology

Universitätsmedizin Charité Campus Mitte Schumanstrasse 20/21

10117 Berlin Germany

Weiss YG

Department of Anesthesiology and Critical Care Medicine

University of Pennsylvania School of Medicine Dulles 781A/HUP

3400 Spruce Street

Philadelphia, PA 19104-4283 USA

Wernerman J

Dept of Anesthesiology and Intensive Care Medicine

K32

Karolinska University Hospital Huddinge 14186 Stockholm

Sweden

Wiersinga WJ

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Common Abbreviations

ALI Acute lung injury

APACHE Acute physiology and chronic health evaluation ARDS Acute respiratory distress syndrome

BAL Bronchoalveolar lavage CNS Central nervous system

DIC Disseminated intravascular coagulation HMGB High mobility group box protein ICAM Intercellular adhesion molecule ICU Intensive care unit

IFN Interferon IL Interleukin

IL-1ra Interleukin-1 receptor antagonist LPS Lipopolysaccharide

MAPK Mitogen-activated protein kinase MHC Major histocompatibility complex MOF Multiple organ failure

NF-κ^B Nuclear factor-kappa B NO Nitric oxide

NOS Nitric oxide synthase PAF Platelet activating factor PMN Polymorphonuclear leukocyte ROS Reactive oxygen species

SIRS Systemic inﬂammatory response syndrome TGF Transforming growth factor

TLR Toll-like receptor TNF Tumor necrosis factor