Kernaussagen Sepsis ist die systemische Reaktion auf eine Infektion, wobei als zentrale Komponenten dieser Reaktion Entzündungsmechanismen, Gerinnungsaktivierung, Endotheldysfunktion und Mikrozirkulationsschaden in Wechselwirkung treten. Resultat ist in vielen Fällen eine vitale Bedrohung des Organismus durch Multiorgandysfunktion und -versagen. Der Kenntnisstand über die zentralen Pathomechanismen der Sepsis ist in den letzten Jahren enorm gewachsen. Neue, aus diesem Wissen heraus abgeleitete Therapieansätze erbrachten im Rahmen klinischer Studien nur begrenzte Therapieerfolge, ohne die hohe Letalität bei Sepsis entscheidend zu senken.
Literatur
1
Cohen J.
The immunopathogenesis of sepsis.
Nature.
2002;
420
885-891
2
Lavoie P M, Thibodeau J, Erard F, Sekaly R P.
Understanding the mechanism of action of bacterial superantigens from a decade of research.
Immunol Rev.
1999;
168
257-269
3
Dinges M M, Schlievert P M.
Role of T-cells and gamma interferon during induction of hypersensitivity to lipopolysaccharide by toxic shock syndrome toxin 1 in mice.
Infect Immun.
2001;
69
1256-1264
4
Rangel-Frausto M S, Pittet D, Costigan M. et al .
The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study.
JAMA.
1995;
273
117-123
5
Tiruppathi C, Naqvi T, Sandoval R. et al .
Synergistic effects of tumor necrosis factor-alpha and thrombin in increasing endothelial permeability.
Am J Physiol Lung Cell Mol Physiol.
2001;
281
L958-968
7
Tilg H, Trehu E, Atkins M B. et al .
Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55.
Blood.
1994;
83
113-118
8
Neviere R R, Cepinskas G, Madorin W S. et al .
LPS pretreatment ameliorates peritonitis-induced myocardial inflammation and dysfunction: role of myocytes.
Am J Physiol.
1999;
277
H885-892
12
Linderkamp O, Ruef P, Brenner B. et al .
Passive deformability of mature, immature, and active neutrophils in healthy and septicemic neonates.
Pediatr Res.
1998;
44
946-950
15
Eichelbrönner O, Sielenkämper A, Cepinskas G. et al .
Endotoxin promotes adhesion of human erythrocytes to human vascular endothelial cells under conditions of flow.
Crit Care Med.
2000;
28
1865-1870
17 Finney S J, Evans T W. Pathophysiology of sepsis: the role of nitric oxide. In: Vincent JL, Carlet J, Opal SM (eds) The Sepsis Text. Boston, Dordrecht, London; Kluwer Academic Publishers 2002: 211-230
18
Ellis C G, Bateman R M, Sharpe M D. et al .
Effect of a maldistribution of microvascular blood flow on capillary O(2) extraction in sepsis.
Am J Physiol Heart Circ Physiol.
2002;
282
H156-164
20
Nelson D P, Samsel R W, Wood L D, Schumacker P T.
Pathological supply dependence of systemic and intestinal O2 uptake during endotoxemia.
J Appl Physiol.
1988;
64
2410-2419
21
Sielenkämper A W, Yu P, Eichelbrönner O. et al .
Diaspirin cross-linked Hb and norepinephrine prevent the sepsis-induced increase in critical O(2) delivery.
Am J Physiol Heart Circ Physiol.
2000;
279
H19 22-1930
22
Brealey D, Karyampudi S, Jacques T S. et al .
Mitochondrial dysfunction in a long-term rodent model of sepsis and organ failure.
Am J Physiol Regul Integr Comp Physiol.
2004;
286
R491-497
23
Kantrow S P, Taylor D E, Carraway M S, Piantadosi C A.
Oxidative metabolism in rat hepatocytes and mitochondria during sepsis.
Arch Biochem Biophys.
1997;
345
278-288
24
Anning P B, Sair M, Winlove C P, Evans T W.
Abnormal tissue oxygenation and cardiovascular changes in endotoxemia.
Am J Respir Crit Care Med.
1999;
159
1710-1715
25
Hotchkiss R S, Rust R S, Dence C S. et al .
Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F]fluoromisonidazole.
Am J Physiol.
1991;
261
R965-972
26
Boekstegers P, Weidenhofer S, Kapsner T, Werdan K.
Skeletal muscle partial pressure of oxygen in patients with sepsis.
Crit Care Med.
1994;
22
640-650
27
Lorenz E, Mira J P, Frees K L, Schwartz D A.
Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock.
Arch Intern Med.
2002;
162
1028-1032
28
Wichmann M W, Inthorn D, Andress H J, Schildberg F W.
Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome.
Intensive Care Med.
2000;
26
167-172
29
Meduri G U, Headley S, Kohler G. et al .
Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time.
Chest.
1995;
107
1062-1073
30
Schutte H, Lohmeyer J, Rosseau S. et al .
Bronchoalveolar and systemic cytokine profiles in patients with ARDS, severe pneumonia and cardiogenic pulmonary oedema.
Eur Respir J.
1996;
9
1858-1867
32
Fischer L G, Freise H, Hilpert J H, Wendholt D, Lauer S, van Aken H, Sielenkämper A W.
Modulation of hypoxic pulmonary vasoconstriction is time and NO dependent in a peritonitis model of sepsis.
Int Care Med.
2004;
30
1821-1828
33 Vallet B. The gut in sepsis. In: Vincent JL, Carlet J, Opal SM (eds) The Sepsis Text. Boston, Dordrecht, London; Kluwer Academic Publishers 2002: 645-664
34
Levy M M, Fink M P, Marshall J C. et al .
2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference.
Intensive Care Med.
2003;
29
530-538
36
Rivers E, Nguyen B, Havstad S. et al .
Early goal-directed therapy in the treatment of severe sepsis and septic shock.
N Engl J Med.
2001;
345
1368-1377
39
Bernard G R, Vincent J L, Laterre P F. et al .
Efficacy and safety of recombinant human activated protein C for severe sepsis.
N Engl J Med.
2001;
344
699-709
40
Annane D, Sebille V, Charpentier C. et al .
Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.
JAMA.
2002;
288
862-871
