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Immunmodulierende Therapien bei der Sepsis: Irrwege der Vergangenheit?

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Diagnostik und Intensivtherapie bei Sepsis und Multiorganversagen

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Trotz kontinuierlicher medizinischer Fortschritte in den letzten Jahrzehnten bleibt die Mortalität der Sepsis weiterhin unakzeptabel hoch. In multiplen Phase-III-Studien wurden in den letzten Jahren spezifische immunmodulatorische Ansätze bei der Sepsis getestet (Anti-Endotoxin-Antikörper, Anti-Zytokin-Antikörper, Zytokinrezeptorantagonisten, Cyclooxygenaseinhibitoren usw.) mit dem Ziel, die proinflammatorische Immunantwort zu blockieren. Diese Strategien waren erfolglos. Wesentliche Aspekte der Sepsispathophysiologie (Redundanz der Systeme, Phasen der Immunantwort bei der Sepsis, Beseitigung des auslösenden Agens, Gerinnungsbeteiligung) wurden nicht beachtet.

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Literatur

  1. Abraham E, Raffin TA ( 1994) Sepsis therapy trials: continued disappointment or reason for hope? JAMA 271:1876

    Article  PubMed  CAS  Google Scholar 

  2. Dellinger RP (2003) Cardiovascular management of septic shock. Crit Care Med 31:946–955

    Article  PubMed  Google Scholar 

  3. Hoffmann JN, Faist E (1996) Neue Therapieansätze bei der Sepsis. In: Bünte H, Junginger T (ed) Jahrbuch der Chirurgie 1996. Biermann, Zülpich, p 101–112

    Google Scholar 

  4. Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874

    Article  Google Scholar 

  5. Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Penzes I, Kübier A, Knaub S, Keinecke H-O, Heinrichs H, Schindel F, Juers M, Bone RC, Opal SM (2001) High-dose antithrombin III in severe sepsis a randomized controlled trial. JAMA 286:1869–1878

    Article  PubMed  CAS  Google Scholar 

  6. Bernard GR, Vincent J-L, Laterre P-F, La Rosa SP, Dhainaut J-F, Lopez-Rodriguez A, Steingrub JS, Garber GE, Heiterbrand JD, Ely EW, Fisher CJ and for the PROWESS study group (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709

    Article  PubMed  CAS  Google Scholar 

  7. Abraham E, Reinhart K, Opal SM for the Optimist Trial Study Group (2003) Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: A randomized controlled trial. JAMA 290:238–247

    Article  PubMed  CAS  Google Scholar 

  8. Hotchkiss RS, Karl IE (2003) The pathophysiology and treatment of sepsis. N Engl J Med 348:138–150

    Article  PubMed  CAS  Google Scholar 

  9. Thijs LG (2000) Coagulation inhibitor replacement in sepsis is a potentially useful clinical approach. Crit Care Med 28:S68–S73

    Article  PubMed  CAS  Google Scholar 

  10. Opal SM (2000) Phylogenetic and functional relationship between coagulation and the innate immune response. Crit Care Med 28:S77–S80

    Article  PubMed  CAS  Google Scholar 

  11. Glück T, Opal SM, Rossaint R, Schölmerich J (2003) Entwicklungen in der Sepsistherapie und aktuelle Behandlungskonzepte. Intensivmed 40:392–411

    Article  Google Scholar 

  12. Eichacker PQ, Parent C, Kalil A, Esposito C, Cui X, Banks SM, Gerstenberger EP, Fitz Y, Danner RL, Natanson C (2002) Risk and the efficacy of antiinflammatory agents retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med 166: 1197–1205

    Article  PubMed  Google Scholar 

  13. Wiedermann CJ, Hoffmann JN, Juers M, Ostermann H, Kienast J, Briegel J, Strauss R, Keinecke H-O, Warren BL, Opal SM (2004) High dose antithrombin III in the treatment of severe sepsis in patients with a high risk of death: efficacy and safety. Crit Care Med submitted

    Google Scholar 

  14. Hoffmann JN, Inthorn D, Jauch KW (2003) Antiinflammatorische Therapie in der Sepsis. Chirurg 74:587–588

    Article  PubMed  CAS  Google Scholar 

  15. Vincent J-L (2004) Endpoints in sepsis trials: More than just 28-day mortality? Crit Care Med 32:S209–S213

    Article  PubMed  Google Scholar 

  16. Esmon CT (1999) Inflammation, Sepsis, and coagulation. Haematologica 84:254–259

    PubMed  CAS  Google Scholar 

  17. Dellinger RP (2003) Inflammation and coagulation: implications for the septic patient. Clinical Infectious Diseases 36:1259–1265

    Article  PubMed  Google Scholar 

  18. Parrillo JE (1993) Pathogenetic mechanisms of septic shock. N Engl J Med 328:1471–1477

    Article  PubMed  CAS  Google Scholar 

  19. Glusa E (1992) Vascular effects of thrombin. Semin Thromb Hemost 18: 296–304

    Article  PubMed  CAS  Google Scholar 

  20. Johnson K, Aarden L, Choi Y, De Groot E, Creasey AA (1996) The proinflammatory cytokine response to coagulation and endotoxin in whole blood. Blood 87:5051–5060

    PubMed  CAS  Google Scholar 

  21. Esmon CT (2000) The protein C pathway. Crit Care Med 28:S44–S48

    Article  PubMed  CAS  Google Scholar 

  22. van der Poll T, Levi M, Hack CE, ten Cate H, van Deventer SJ, Eerenberg AJ, de Groot ER, Jansen J, Gallati H, Buller HR et al (1994) Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees. J Exp Med 179: 1253–1259

    Article  PubMed  Google Scholar 

  23. van Deventer SJ, Buller HR, ten Cate JW, Aarden LA, Hack CE, Sturk A (1990) Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood 76: 2520–2526

    PubMed  Google Scholar 

  24. Lamy M, Deby-Dupont G (1995) Is sepsis a mediator-inhibitor mismatch? Intensive Care Med 21:S250–S257

    Article  PubMed  Google Scholar 

  25. Bone RC (1992) Modulators of coagulation. A critical appraisal of their role in sepsis. Arch Intern Med 152:1381–1389

    Article  PubMed  CAS  Google Scholar 

  26. Inthorn D, Hoffmann JN, Hartl WH, Mühlbayer D, Jochum M (1997) Antithrombin III supplementation in severe sepsis: beneficial effects on organ dysfunction. Shock 8:328–334

    Article  PubMed  CAS  Google Scholar 

  27. Inthorn D, Hoffmann JN, Hartl WH, Mühlbayer D, Jochum M (1998) Effect of antithrombin III supplementation on inflammatory immune response in patients with severe sepsis. Shock 10:90–96

    Article  PubMed  CAS  Google Scholar 

  28. Souter P, Thomas S, Hubbard AR, Poole S, Roemisch J, Gray E (2001) Antithrombin inhibits LPS-induced tissue factor and interleukin-6 production by mononuclear cells, human umbilical vein endothelial cells, and whole blood. Crit Care Med 29:134–139

    Article  PubMed  CAS  Google Scholar 

  29. Hoffmann JN, Vollmar B, Inthorn D, Schildberg FW, Menger MD (2000) Antithrombin reduces leukocyte adhesion during chronic endotoxemia by modulation of the cyclooxygenase pathway. Am J Physiol 279:C98–C107

    CAS  Google Scholar 

  30. Hugh TE (1986) Biochemistry and biology of anaphylatoxins. Complement 13:111

    Google Scholar 

  31. Huey R, Hugli TE (1985) Characterization of a C5a receptor on human polymorphonuclear leukocytes. J Immunol 135:2063–2068

    PubMed  CAS  Google Scholar 

  32. Vangerow B (1996) Clinical improvement after administration of Cl-esterase inhibitor in two patients with SIRS and capillary leakage syndrome. Intensive Care Med 22(S3):367

    Google Scholar 

  33. Fourrier F, Chopin C, Goudemand J, Hendrycx S, Caron C, Rime A, Marey A, Lestavel P (1992) Septic shock, multiple organ failure, and disseminated intravascular coagulation. Compared patterns of antithrombin III, protein C, and protein S deficiencies. Chest 101:816–823

    Article  PubMed  CAS  Google Scholar 

  34. Taylor FBJ, Chang A, Esmon CT, D’Angelo A, Vigano DA, Blick KE (1987) Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest 79:918–925

    PubMed  CAS  Google Scholar 

  35. Taylor FBJ (1994) Studies on the inflammatory-coagulant axis in the baboon response to E. coli: regulatory roles of proteins C, S, C4bBP and of inhibitors of tissue factor. Prog Clin Biol Res 388:175–194

    PubMed  CAS  Google Scholar 

  36. Esmon CT (2000) Introduction: are natural anticoagulants candidates for modulating the inflammatory response to endotoxin? Blood 95:1113–1116

    PubMed  CAS  Google Scholar 

  37. Hoffmann JN, Vollmar B, Laschke M, Inthorn D, Fertmann J, Schildberg FW, Menger MD (2004) Microhemodynamic and cellular mechanisms of activated protein C action during endotoxemia. Crit Care Med 32:1011–1017

    Article  PubMed  Google Scholar 

  38. de Jonge E, Dekkers PE, Creasey AA, Hack CE, Paulson SK, Karim A, Kesecioglu J, Levi M, van Deventer SJ, van der Poll T (2000) Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia. Blood 95:1124–1129

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Chirurgische Klinik und Poliklinik, Ludwig-Maximilians-Universität München, Klinikum Großhadern Marchioninistr. 15, 81377, München, Germany

    Priv.-Doz. Dr. med. J. N. Hoffmann

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  1. Priv.-Doz. Dr. med. J. N. Hoffmann
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  1. Einheit für Multidisziplinäre Intensivmedizin (EMI), Universitätsklinikum Leipzig AÖR, Liebigstr. 20, 04104, Leipzig

    Lothar Engelmann

  2. Klinikum Hildesheim, Weinberg 1, 31134, Hildesheim

    Hans-Peter Schuster

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Hoffmann, J.N. (2006). Immunmodulierende Therapien bei der Sepsis: Irrwege der Vergangenheit?. In: Engelmann, L., Schuster, HP. (eds) Diagnostik und Intensivtherapie bei Sepsis und Multiorganversagen. Steinkopff. https://doi.org/10.1007/978-3-7985-1729-5_15

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  • DOI: https://doi.org/10.1007/978-3-7985-1729-5_15

  • Publisher Name: Steinkopff

  • Print ISBN: 978-3-7985-1728-8

  • Online ISBN: 978-3-7985-1729-5

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