Intensivmedizin up2date 2005; 1(1): 9-20
DOI: 10.1055/s-2004-826111
Allgemeine Prinzipien der Intensivmedizin
© Georg Thieme Verlag KG Stuttgart · New York

Pathophysiologie der Sepsis (mit Videos)

Andreas  Sielenkämper,, Lars  Fischer, Hendrik  Freise, Hugo  Van Aken
Further Information

Publication History

Publication Date:
05 July 2006 (online)

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
  • 6 Aird W C. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome.  Blood. 2003;  101 3765-3777
  • 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
  • 9 Nomura F, Akashi S, Sakao Y. et al . Cutting edge: endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface toll-like receptor 4 expression.  J Immunol. 2000;  164 3476-3479
  • 10 Lam C, Tyml K, Martin C, Sibbald W. Microvascular perfusion is impaired in a rat model of normotensive sepsis.  J Clin Invest. 1994;  94 2077-2083
  • 11 Sielenkämper A W, Meyer J, Kloppenburg H. et al . The effects of sepsis on gut mucosal blood flow in rats.  Eur J Anaesthesiol. 2001;  18 673-678
  • 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
  • 13 Yodice P C, Astiz M E, Kurian B M. et al . Neutrophil rheologic changes in septic shock.  Am J Respir Crit Care Med. 1997;  155 38-42
  • 14 Scharte M, Fink M P. Red blood cell physiology in critical illness.  Crit Care Med. 2003;  31 S651-657
  • 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
  • 16 Vallet B. Endothelial cell dysfunction and abnormal tissue perfusion.  Crit Care Med. 2002;  30 S229-234
  • 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
  • 19 Ince C, Sinaasappel M. Microcirculatory oxygenation and shunting in sepsis and shock.  Crit Care Med. 1999;  27 1369-1377
  • 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
  • 31 Sylvester J T. Hypoxic pulmonary vasoconstriction: a radical view.  Circ Res. 2001;  88 1228-1230
  • 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
  • 35 Freise H, Bruckner U B, Spiegel H U. Animal models of sepsis.  J Invest Surg. 2001;  14 195-212
  • 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
  • 37 Van den Berghe G, Wouters P, Weekers F. et al . Intensive insulin therapy in the critically ill patients.  N Engl J Med. 2001;  345 1359-1367
  • 38 Marik P E, Raghavan M. Stress-hyperglycemia, insulin and immunomodulation in sepsis.  Intensive Care Med. 2004;  30 748-756
  • 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

Priv.-Doz. Dr. A. Sielenkämper

Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin · Universitätsklinikum Münster

Albert-Schweitzer-Str. 33 · 48129 Münster

Phone: 0251 8347255

Fax: 0251 8348667

Email: sieland@uni-muenster.de