Table Of Content18
Update in Intensive Care
and Emergency Medicine
Edited by J.-L.Vincent
K. Reinhart K. Eyrich
C. Sprung (Eds.)
Sepsis
Current Perspectives
in Pathophysiology and Therapy
With 109 Figures and 56 Tables
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Hong Kong Barcelona
Budapest
Series Editor
Prof. Dr. Jean-Louis Vincent
Clinical Director, Department ofIntensive Care
Erasme University Hospital
Route de Lennik 808, 1070 Brussels, Belgium
Volume Editors
Prof. Dr. Konrad Reinhart
Direktor der Klinik fur Anasthesiologie und Intensivtherapie
Klinikum der Friedrich Schiller-Universitat Jena
BachstraBe 18,07740 Jena, FRG
Prof. Dr. Klaus Eyrich
Klinik fUr Anasthesiologie und operative Intensivmedizin
Universitatsklinikum Steglitz der FU Berlin
Hindenburgdamm 30, 12200 Berlin, FRG
Prof. Dr. Charles Sprung
Department ofAnesthesiology and Critical Care Medicine
Hadassah Hebrew University, Medical Center
P. O. Box 12000,91120Jerusalem, Israel
ISBN-13: 978-3-642-85038-7 e-ISBN-13: 978-3-642-85036-3
001: 10.1007/978-3-642-85036-3
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Preface
Sepsis is still the leading cause of death in surgical and general
intensive care units. Although our knowledge of this complex
syndrome has increased in recent years, it is still far from com
plete. New therapeutic approaches have been developed. Some
did not fullfill the high expectations for their use in clinical prac
tice; others are still under clinical evaluation.
It is the aim ofthis monograph to offer basic information on the
etiology, definition, pathophysiology, prevention and therapy of
sepsis and septicshockto both theclinician and the scientist. We
believe that it presents an extensive overview that may help the
clinician to better understand and treat sepsis and septic shock.
We also hope that this work will give some directions for future
research both in the clinical field as well as the laboratory.
Jena, Berlin, Jerusalem, K.Reinhart
February 1994 K. Eyrich
C.Sprung
Table of Contents
I. Definition/Prognosis
Sepsis and Septic Shock: Update on Definitions
(Jo-L.Vincent) 3
0 0 0 0 0 0 0 0 0 0 0 0 ••••••••
Clinical Manifestations and Prognostic Indicators in Sepsis
(R. C.Bone) ... 16
0 • • • • • • • • • • • • • • • • • • •
What Determines Prognosis in Sepsis? Evidence for
a Comprehensive Individual Patient Risk Assessment
Approach to the Design and Analysis of Clinical Trials
(W.A.Knaus, D.P.Wagner, F.E.Harrell, Jr.
and E.A.Draper) ... 23
0 •••••••• 0 • 0 • • • • ••
A Scoring System for Multiple Organ Dysfunction
Syndrome
(Jo C.Marshall) .. 38
0 •••••••••••• 0 • 0 0 • 0 0 • • ••
II. Pathogenesis
Endotoxemia and Sepsis: Important Roles for
Lipopolysaccharide Binding Protein and CD14
in Endotoxin Signal Transduction
(K.F.Bruin, M.A.M. von der M6hlen and
S.JoH. van Deventer) ... o. 53
0 • • 0 • • • • • • • • • •
The Function and Potential Therapeutic Value
ofLipopolysaccharide Binding Protein During Gram
Negative Sepsis: Recombinant Expression and
Promoter Studies
(R.R. Schuman, N. Lamping, C.Kirschning, H.Po Knopf
and F.Herrmann) 391
0 •••••••
VIII Table ofContents
Bacterial Exotoxins and Sepsis
(w.Seeger, H.Schiitte, F.Grimminger, N.Suttorp
and B.Bhakdi) . . . . . . . . . . . . . . . . .. .... .. 61
Bacterial Translocation: Myth versus Reality
(M.D.Pasquale, M.D.Cipolle and F.B.Cerra) . . . . . . .. 86
Tumor Necrosis Factor and Other Cytokines
in Septic Syndrome
(B.Beutler) . . . . . . . . . . . . . . . . . . . . ... 107
Role of Oxygen Free Radicals in the Pathophysiology
of Sepsis
(M. Kretzschmar) 122
ill. Pathophysiology
Cardiocirculation in Sepsis
(F.Bloos and W.J. Sibbald) ...... 139
A Current View of Oxygen Supply Dependency
(S.M.Cain) 150
Sepsis and Nutritional Blood Flow
(M.D.Menger, B.Vollmar and K.Messmer) ........ 163
Endothelial Cell Function in the Critically III
(J.-L.Vincent, J. C.Preiser, G.Friedman and H.Zhang) . . . 174
Sepsis and Cellular Metabolism
(0. Gutierrez) 181
IV. Monitoring
Monitoring of O Transport and Tissue Oxygenation
2
in Septic Shock
(K.Reinhart, L.Hannemann, A.Meier-Hellmann and
M.Specht) 193
v. Therapy
Sepsis-Related Problems in Pediatric Patients
(J.A.Hazelzet and R.deGroot) 217
Table ofContents IX
Definitions and Therapy of Sepsis
(R.C.Bone) . . 228
Role of Surgical Intervention in the Prevention
and Therapy of Sepsis
(W Teichmann, B.Herbig and M.Weidner) 239
Antibacterial Treatment of Sepsis
(D.Adam and B.Gerlach) .... . 246
Diagnostic and Therapeutic Approach in Invasive Fungal
Infections of Intensive Care Unit Patients
(M.Petri, H.Lode and T.Schaberg) ..... . . . . . . . . . 256
Fluid Therapy in Sepsis
(WI.Sibbald) . . ... 266
Influence of Catecholamines on Regional Perfusion
and Tissue Oxygenation in Septic Shock Patients
(A.Meier-Hellmann and K.Reinhart) .. . . . . . . . .. 274
Metabolic Changes in Sepsis - Can the Host Response
be Influenced Metabolically?
(M.Georgieff, T.Schricker and B.Kugler) 292
VI. New Therapeutic Approaches
Is there a Place for Monoclonal Antibodies
Against Endotoxin in the Therapy of Sepsis?
(L.Eidelman and C.L.Sprung) 307
Endotoxin in Septic Shock
(Z.M.N. Quezada, C.Natanson and WD.Hoffman) 314
Tumour Necrosis Factor as a Therapeutic Target in Sepsis
(S.Sriskandan andI.Cohen) 337
Tumor Necrosis Factor-Neutralization with a Specific
Monoclonal Antibody
(M.Kluge and M.Kaul) . . . . . . . . . . . . . . . . . . . . . 349
X Table ofContents
Cardiovascular Effects of Repeated Administration of the
F(ab')z Fragment of an Anti-tumor Necrosis Factor-a
Monoclonal Antibody in Patients with Severe Sepsis
(P.Boekstegers, S.WeidenhOfer, R.Zell, G.Pilz, E.Holler,
T Kapsner, M.Kaul, f. Kempeni and K.Werdan) . 357
Modulating Effects ofPentoxifylline on Cytokine
Release Syndromes
(F U. Schade and P.Zabel) . .. 371
The Treatment of Sepsis with Interleukin-1 Receptor
Antagonist
(s.M.Opal, C.f. Fisher, fr. and f. Pribble) .. , ... 382
The Function and Potential Therapeutic Value
of Lipopolysaccharide Binding Protein During Gram
Negative Sepsis: Recombinant Expression and
Promoter Studies
(R.R. Schuman, N. Lamping, C.Kirschning, H.P. Knopf
and F Herrmann) . 391
Platelet-Activating Factor: Pathophysiological Changes
and Therapeutic Implications in Sepsis
(f. F Dhainaut, f. P.Mira and L.Fierobe) . . . . . . . . 397
Potential of Oxyradical Scavengers in the Therapy
ofSepsis
(f.f. Zimmerman) 414
N-Acetylcysteine in Sepsis
(c.Spies and K.Reinhart) ... 425
Immunoaugmentation: A Contribution to Prophylaxis
and Treatment of Sepsis?
(E.Faist, A.Markewitz, R.Maier and S. Lang) ..... 443
What Is Certain in the Treatment with Immunoglobulins?
(H. G.Kress) 449
Arachidonic Acid Metabolism in Sepsis: What is the Role
of Cyclooxygenase Inhibition?
(G.R.Bernard) 464
Table ofContents XI
Improvement ofMonocyte Function - A New Therapeutic
Approach?
(W.D.Docke, U.Syrbe, A.Meinecke, C.Platzer, A.Makki,
K.Asadullah, C.Klug, H.Zuckermann, P.Reinke,
H.Brunner, R.vonBaehrand H.D. Volk) . 473
From Localized Angioedema to Generalized Capillary
Leak Syndrome
(B. Eisele and U.De/vos) 501
Potential for Gene Therapy in the Treatment of Sepsis
(K.L.Brigham, A.E. Canonico, J.T Conary, B.0.Meyrick
and H.Schreier) 528
VII. Specific Therapeutic Aspects
Step-by-Step Treatment of Acute Respiratory
Distress Syndrome
(K.Lewandowski, R.Rossaintand K.J.Falke) . . 539
Perfluorocarbons as an Alternative Respiratory Medium
(A.S. TiitUncii and B.Lachmann) 549
Subject Index 565
List of Contributors
Prof Dr. med. Dr. rer. nat. Prof R.C.Bone, MD
D.Adam The Medical College ofOhio,
Vorstand der Abteilung Toledo
flir Antimikrobielle Therapie 3000Arlington Avenue
und Infektionsimmunologie Toledo, OH43699-0008, USA
Dr. von Haunersches Kinderspital
der UniversitiH
Prof K.L.Brigham, MD
LindwurmstraBe 4
Centerfor Lung Research
80337 Miinchen, FRG
DepartmentofMedicine
Vanderbilt University School
ofMedicine
Prof G.R.Bernard, MD Nashville,TN 37232, USA
Division ofPulmonary and Critical
CareMedicine
K.F.Bruin
Centerfor Lung Research
DepartmentofInflammation
Vanderbilt University
Research, AMCHospital
Nashville,TN37232-2650, USA
University ofAmsterdam
Medical Center
Meibergdreef9
Prof B.Beutler, MD 1105 AZ Amsterdam,
Research Laboratories
The Netherlands
Howard Hughes Medical Institute
5353 Harry Hines Boulevard
Dallas,TX75235-9050,USA Prof s.M.Cain, MD, PhD
DepartmentofPhysiology
and Biophysics
University ofAlabama
Dr. med. F.Bloos
at Birmingham
The Richard Ivey Critical Care
Birmingham, AL35294-0005, USA
Trauma Centre
Victoria Hospital Corporation
375South Street Prof F.B.Cerra, MD
London, Ontario NGA 4G5, Department ofSurgery
Canada UniversityofMinnesota
406Harvard Street Southeast
Minneapolis, MN55455, USA
Dr. med. P.Boekstegers
Medizinische Klinik I Prof Dr. med. J.Cohen
Ludwig-Maximilians-Universitat Directorofthe Department of
Miinchen Infectious Diseases&Bacteriology
Klinikum GroBhadern Hammersmith Hospital
Marchionistr. 15 Du Cane Road
81377Miinchen, FRG London W12 ONN, UK
