Mediatoren und ihre Antagonisten in der Schocktherapie

  • E. Neugebauer
  • A. Leuchleuthner
  • A. Dietrich
  • S. Saad
  • D. Rixen
Part of the Deutsche Gesellschaft für Chirurgie book series (DTGESCHIR, volume 1991)

Zusammenfassung

Von gegenwärtig mehr als 150 beschriebenen Schockmediatoren sind als kausal beteihgt (Anwendung der Koch-Dale-Kriterien in Verbindung mit Entscheidungsbäumen) bisher nur die Mediatoren Histamin, C5a, ß-Endorphin, Tumornekrosefaktor (TNF), Thromboxan B2, Plättchenaktivierender Faktor (PAF) und die Sauerstoffradikale gesichert. Während experimentelle Studien mit Hemmstoffen der Mediatorwirkungen meist überzeugend sind, steht der positive Nachweis in klinischen Studien außer für Histamin (Anaphylaktischer Schock) noch aus. Von Kombinationstherapien mit Hemmstoffen gegen verschiedene kausale Mediatoren kann für die Zukunft der größte Nutzen erwartet werden.

Schlüsselwörter

Schockmediatoren kausale Rolle Hemmstoffe experimentelle/ klinische Ergebnisse 

Mediators and Their Antagonists in Shock Therapy

Summary

The list of shock mediators currently comprises more than 150 candidates. A careful analysis using the criteria of Koch-Dale together with decision trees for exclusion of bias revealed that only histamine, C5a, ß-endorphin, tumor necrosis factor (TNF) thromboxane B2, platelet-activaring factor (PAF), and oxygen free radicals are shown to be causally associated with shock symptoms. Although experimental studies with inhibitors of these mediators were convincing, there is still a lack of evidence under chnical conditions (exception histamine: anaphylactic shock). Combinations of antagonists against different causal mediators are the most promising future approaches.

Key words

Shock mediators Cause-effect relationship Inhibitors Experimental/ Clinical results 

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References

  1. 1.
    Baumgartner JD (1990) Monoclonal anti-endotoxin antibodies for the treatment of gram-negative bacteremia and septic shock. Eur J Clin Microbiol Infect Dis 9:711–716PubMedCrossRefGoogle Scholar
  2. 2.
    Hack CE, Thijs LG (1991) The orchestra of mediators in the pathogenesis of septic shock: A review. In: Vincent JL (ed) Update. Springer, Berlin Heidelberg New York Tokyo, pp 232–246Google Scholar
  3. 3.
    Skarvan K (1989) Mediatoren beim Trauma. Med Welt 45:525–532Google Scholar
  4. 4.
    Neugebauer E, Lorenz W, Schirren J, Dietrich A (1988) Mediatoren in der Pathogenese des septischen Schocks — Eine Standortbestimmung. In: Reinhart K, Eyrich K (eds) Sepsis — Eine interdisziplinäre Herausforderung. Springer, Berlin Heidelberg New York Tokyo, pp 222–236Google Scholar
  5. 5.
    King LS (1957) Dr. Koch’s postulate. J Hist Med Alhed Sci 7:350–361Google Scholar
  6. 6.
    Neugebauer E, Lorenz W, Maroske D, Barthlen W (1987) Mediatoren beim septischen Schock; Strategien zu ihrer Sicherung und zur Einschätzung ihrer kausalen Bedeutung. Chirurg 58:470–481PubMedGoogle Scholar
  7. 7.
    Neugebauer E, Lorenz W, Maroske D, Barthlen W, Ennis M (1987) The role of mediators in septic/endotoxic shock. A meta-analysis evaluating the current status of histamine. Theor Surg 2:1–28Google Scholar
  8. 8.
    Ziegler EJ, McCutchan JA, Fierer J (1982) Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Echerichia coh. N Engl J Med 307:1225–1230PubMedCrossRefGoogle Scholar
  9. 9.
    Ziegler EJ, Fischer CJ, Sprung CL (1981) Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin — a randomized, double-blind, placebo-controlled trial. N Engl J Med 324:429–436CrossRefGoogle Scholar
  10. 10.
    Novick D, Engelmann H, Wallach D, Rubinstein M (1989) So luble cytokine receptors are present in normal human urine. J Exp Med 170:1409–1414PubMedCrossRefGoogle Scholar
  11. 11.
    Neugebauer E, Lorenz W, Beckurts T, Maroske D, Merte H (1987) Significance of histamine formation and release in the development of endotoxic shock: Proof of current concepts by randomized controlled studies in rats. Rev Infect Dis 9:585–593CrossRefGoogle Scholar
  12. 12.
    Lorenz W, Röher HD, Doenicke A, Ohmann C (1984) Histamine release in anaesthesia and surgery: a new method to evaluate its chnical significance with several types of causal relationship. Clin Anaesthesiol 2:403–426Google Scholar
  13. 13.
    Rixen D, Leuchleuthner A, Saad S, Buschauer A, Nagelschmidt M, Thoma S, Rink A, Neugebauer E (1991) Beneficial effect of H2-Agonism and Hj-Antagonism in endotoxic shock? Circ Shock 34:133Google Scholar
  14. 14.
    Neugebauer E, Beckurts T, Lorenz W, Maroske D, Merte H, Horeyseck G, Dietz W (1986) Induced histidine decarboxylase in endotoxic shock: Identifiaction of the enzyme in rat liver and influence of its inhibitors on survival parameters. Agents Actions 18:23–29PubMedCrossRefGoogle Scholar
  15. 15.
    Stevens JH, O’Hanley P, Shapiro JM, Mihm FG, Satoh PS, Collins JA, Raffin TA (1986). Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates. J Chn Invest 77:1812–1816CrossRefGoogle Scholar
  16. 16.
    Bengtsson A, Redl H, Heideman M, Schlag G (1992) Complement in septic shock. In: Neugebauer E, Holaday JW (eds) Handbook for mediators in septic shock. CRC Press, (in Vorbereitung)Google Scholar
  17. 17.
    Holaday JW, Faden AI (1978) Naloxone reversal of endotoxin hypotension suggests role of endorphins in shock. Nature 275:450PubMedCrossRefGoogle Scholar
  18. 18.
    Holaday JW, Long JB, Martinez-Arizala A, Chenitts A, Reynolds DG, Gurll N (1989) Effects of TRH in circulatory shock and central nervous system ischemia. Ann NY Acad Sci 353:380–389Google Scholar
  19. 19.
    Peters WP, Johnson MW, Friedmann PA (1981) Pressor effect of naloxone in septic shock. Lancet 1:529PubMedCrossRefGoogle Scholar
  20. 20.
    Groeger JA, Carton GC, Howland WS (1983) Naloxane in septic shock. Crit Care Med 11:650PubMedCrossRefGoogle Scholar
  21. 21.
    Hughes GS (1984) Naloxane and methylprednisolone sodium succinate enhance sympathomedullary discharge in patients with septic shock Life. Science 35:2319Google Scholar
  22. 22.
    DeMaria A, Craven DE, Heffernan JJ (1985) Naloxone versus placebo in treatment of septic shock. Lancet 1:1363–1365PubMedCrossRefGoogle Scholar
  23. 23.
    Michie HR, Wilmore DW (1990) Sepsis, signals and surgical sequelae. Arch Surg 125:531–536PubMedCrossRefGoogle Scholar
  24. 24.
    Tracey KJ, Fong Y, Hesse DG (1987) Anti-cachectin/TNF antibodies prevent the fatal sequelae of experimental bacteremia in primates. Nature 330:662–664PubMedCrossRefGoogle Scholar
  25. 25.
    Exley AR, Cohen J, Buurman W (1990) Monoclonal antibody to TNF in severe septic shock. Lancet 1:1275–1276CrossRefGoogle Scholar
  26. 26.
    Bernard G, Reines HD, Metz CA, Halushka PV, Swindell SB, Higgins SB, Wright PE, Watts CA (1988) Effects of a short course of Ibuprofen in patients with severe sepsis. AST 138Google Scholar
  27. 27.
    Braquet P, Paubert-Braquet M, Koltai H, Bourgain R, Bussolino F, Hosford D (1989) Is there a case for PAF antagonists in the treatment of ischemic states? Trends Pharmacol Sci 10:23–30PubMedCrossRefGoogle Scholar
  28. 28.
    Gerdin B, Haglund U (1992) Possible Involvment of oxygen free radicals (OFR) in shock and shock related states. In: Neugebauer E, Holaday JW (eds) Handbook of Mediators in Septic Shock., CRC Press (in Vorbereitung)Google Scholar
  29. 29.
    Neugebauer E, Bouillon B, Dietrich A, Lechleuthner A (1989) Cortison-Standards und neue Tendenzen: Notfallindikation Schock. Münch Med Wochenschr 131:907–911Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • E. Neugebauer
    • 1
  • A. Leuchleuthner
  • A. Dietrich
  • S. Saad
  • D. Rixen
  1. 1.Biochemische und Experimentelle AbteilungII. Chirurgischer Lehrstuhl Universität zu KölnKöln 91Bundesrepublik Deutschland

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