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Sepsis and MODS - What Is Wrong and What Is Right

  • A. Gullo
  • G. Berlot
Conference paper

Abstract

Despite major advances in the knowledge of the pathophysiologic mechanisms responsible of the develoment of sepsis and its related consequences, namely Multiple Organ Dysfunction Syndrome (MODS) and Failure (MOF), the mortality rate of septic patients remains high. Although this can be attributed to a number of factors, including the underlying diseases, a more advanced age of the affected patients, the appearance of antibiotic-resistant bacterial strains, etc., nevertheless it is surprising and somewhat disappointing that the clinical applications of the basic researches carried results far below the expectations [1]. Then, it appears rather logical to wonder a) if the measures developed to contrast sepsis, MODS and MOF on the basis of these experimental results are effective and b) if the main indicator used to assess the effectiveness of these approaches (namely the survival at a predetermined interval of time) is fully appropriate.

Keywords

Septic Shock Systemic Inflammatory Response Syndrome Septic Patient Multiple Organ Dysfunction Syndrome Platelet Activate Factor Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Bernard GR (1995) Sepsis trials. Am J Resp Crit Care Med 102:4–10Google Scholar
  2. 2.
    Rackow EC, Astiz ME (1991) Pathophysiology and treatment of septic shock. JAMA 266: 548–554PubMedCrossRefGoogle Scholar
  3. 3.
    Berlot G, Vincent JL (1992) Cardiovascular effects of cytokines. Clin Intens Care 3:199–205Google Scholar
  4. 4.
    Davies MG, Hagen PO (1997) Systemic inflammatory response syndrome. Br J Surg 84: 920–935PubMedCrossRefGoogle Scholar
  5. 5.
    Moldawer LL (1994) Biology of proinflammatory cytokines and their antagonist. Crit Care Med 22:S3–S7PubMedGoogle Scholar
  6. 6.
    Bone RC (1996) Sir Isaac Newton, Sepsis, SIRS and CARS. Crit Care Med 24:1125–1136PubMedCrossRefGoogle Scholar
  7. 7.
    Christman JW, Holden EP, Blackwell TS (1995) Strategies for blocking the systemic effects of cytokines in the sepsis syndrome. Crit Care Med 23:955–963PubMedCrossRefGoogle Scholar
  8. 8.
    Ziegler EJ, McCuchan JA, Fierer J et al (1982) Treatment of gram-bacteremia and shock with human antiserum to a mutant Escherichia coli. New Engl J Med 307:1225–1230PubMedCrossRefGoogle Scholar
  9. 9.
    Lachman E, Pitsoe SB, Gaffin SL (1984) Antilypolisaccharide immunotherapy in the management of septic shock of obstetrical and gynecological origin. Lancet 1:981–983PubMedCrossRefGoogle Scholar
  10. 10.
    Fomsgaard A, Baek L, Foomsgard JS et al (1988) Preliminary study in treatment of septic shock patients with antilypolisaccharide IgG with from blood donors. Scand J Infect Dis 21:697–708CrossRefGoogle Scholar
  11. 11.
    Talan DA (1993) Recent developments in our understanding of sepsis: evaluation of antiendotoxin antibodies and biological response modifiers. Ann Emer Med 22:1871–1990CrossRefGoogle Scholar
  12. 12.
    Greenman RL, Schein RMH, Martin MA et al (1991) A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of Gram-sepsis. JAMA 266: 1097–1102PubMedCrossRefGoogle Scholar
  13. 13.
    Ziegler EJ, McCutchan JA, Fierer J et al (1991) Treatment of Gram-bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double blind, placebo controlled trial. N Engl J Med 324:429–436PubMedCrossRefGoogle Scholar
  14. 14.
    Bone RC, Balk RA, Fein AM et al (1995) A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled study. Crit Care Med 23:994–1006PubMedCrossRefGoogle Scholar
  15. 15.
    Cunnion RE (1992) Clinical trials of immunotherapy for sepsis. Crit Care Med 20:721–723PubMedCrossRefGoogle Scholar
  16. 16.
    Silva AT, Bayston KF, Cohen J (1990) Prophylactic and therapeutic effects of a monoclonal antibody to tumour necrosis factor-alfa in experimental Gram-shock. J Inf Dis 162:421–427CrossRefGoogle Scholar
  17. 17.
    Exley AR, Cohen J, Buurman WA et al (1990) Monoclonal antibody to TNF in severe septic shock. Lancet 335:1275–1277PubMedCrossRefGoogle Scholar
  18. 18.
    Vincent JL, Bakker J, Marecaux G et al (1992) Administration of anti TNF antibodies improves left ventricular function in septic shock patients: results of a pilot study. Chest 101: 810–815PubMedCrossRefGoogle Scholar
  19. 19.
    Dhainaut JFA, Vincent JL, Richard C et al (1995) DP 571, a humanized antibody to tumour necrosis factor-alpha: safety, pharmacokinetics, immune response, and influence of the antibody on cytokine concentrations in patients with septic shock. Crit Care Med 23:1461–1469PubMedCrossRefGoogle Scholar
  20. 20.
    Cohen J, Carlet J for the INTERSEPT group (1996) INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-α in patients with sepsis. Crit Care Med 24:1431–1440PubMedCrossRefGoogle Scholar
  21. 21.
    Rheinhart K, Wiegand-Lohnert C, Grimminger F et al (1996) Assessment of the safety and efficacy of the monoclonal anti-tumour necrosis factor antibody fragment, MAK 195F, in patients with sepsis and septic shock: a multicenter, randomized, placebo-controlled, dose ranging study. Crit Care Med 24:733–742CrossRefGoogle Scholar
  22. 22.
    Granowitz EV, Santos AA, Poutsaka DD et al (1991) Production of Interleukin-1 receptor antagonist during experimental endotoxemia. Lancet 1338:1423–1424CrossRefGoogle Scholar
  23. 23.
    Dinarello CA (1991) The proinflammatory cytokines Interleukin-1 and Tumor Necrosis Factor and treatment of septic shock syndrome. J Inf Dis 163:1177–1184CrossRefGoogle Scholar
  24. 24.
    Ohlsson K, Bjork P, Bergenfeldt M et al (1990) Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature 343:550–552CrossRefGoogle Scholar
  25. 25.
    Arend WP (1991): Interleukin 1 receptor antagonist: a new member of Interleukin 1 family. J Clin Invest 88:1445–1451PubMedCrossRefGoogle Scholar
  26. 26.
    Fisher E, Marana MA, Van Zee KJ et al (1992) Interleukin-1 receptor antagonist improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia. J Clin Invest 89:1551–1557CrossRefGoogle Scholar
  27. 27.
    Fisher CJ, Slotman GJ, Opal SM et al (1994) Initial evaluation of human recombinant Interleukin 1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open label, placebo-controlled multicentre trial. Crit Care Med 22:12–21PubMedGoogle Scholar
  28. 28.
    Fisher CJ, Dhainaut JF, Opal SM et al (1994) Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double blind, placebo-controlled trial. JAMA 271:1836–1843PubMedCrossRefGoogle Scholar
  29. 29.
    Knaus WA, Harrell FE, LeBreque JF et al (1996) Use of predicted risk of mortality to evaluate the efficacy of anticytokine therapy in sepsis. Crit Care Med 24:46–56PubMedCrossRefGoogle Scholar
  30. 30.
    Opal SM, Fisher CJ, Dhainaut JFA et al (1997) Confirmatory Interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double blind, placebo-controlled, multicenter trial. Crit Care Med 25:1115–1124PubMedCrossRefGoogle Scholar
  31. 31.
    Bazzoni F, Beutler B (1996) Seminars in Medicine at the Beth Israel Hospital, Boston: The Tumour Necrosis factor ligand and receptor families. New Engl J Med 34:1717–1725Google Scholar
  32. 32.
    Sorkine P, Setton A, Halpern P et al (1995) Soluble tumour necrosis factor receptors reduce bowel ischemia-induced lung permeability and neutrophil sequestration. Crit Care Med 23: 1377–1381PubMedCrossRefGoogle Scholar
  33. 33.
    Van Zee KJ, Kohno T, Fisher E et al (1992) Tumour necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumour necrosis factor alpha in vitro and in vivo. Proc Natl Acad Sci USA 89:4845–4849PubMedCrossRefGoogle Scholar
  34. 34.
    Mohler KM, Torrance DS, Smith CA et al (1993) Soluble tumour necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol 151:1548–1561PubMedGoogle Scholar
  35. 35.
    Fisher CJ, Agosti JA, Opal SM et al (1996) Treatment of septic shock with the tumor necrosis factor receptonFc fusion protein. New Engl J Med 334:1697–1702PubMedCrossRefGoogle Scholar
  36. 36.
    Abraham E, Glauser MP, Butler T et al (1997) p55 Tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock. A randomized controlled multicenter trial. JAMA 277:1531–1538PubMedCrossRefGoogle Scholar
  37. 37.
    Goldie AS, Fearon KC, Ross JA et al (1995) Natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome. JAMA 274:172–177PubMedCrossRefGoogle Scholar
  38. 38.
    Bone RC (1992) Phospholipids and their inhibitors: a critical evaluation of their role in the treatment of sepsis. Crit Care Med 20:884–890PubMedCrossRefGoogle Scholar
  39. 39.
    Lefer A (1989) Significance of lipid mediators in shock states. Circ Shock 27:3–12PubMedGoogle Scholar
  40. 40.
    Sun X, Hsueh W (1988) Bowel necrosis induced 6y tumour necrosis factor in rats is mediated by platelet activating factor. J Clin Invest 81:1328–1331PubMedCrossRefGoogle Scholar
  41. 41.
    Sun X, Hsueh W, Torre-Amione G (1990) Effects of in vivo priming on endotoxin induced hypotension and tissue injury: the role of PAF and tumour necrosis factor. Am J Pathol 136: 949–956PubMedGoogle Scholar
  42. 42.
    Thompson WA, Coyle S, Van Zee K et al (1994) The metabolic effects of platelet activating factor in endotoxemic man. Arch Surg 129:72–79PubMedCrossRefGoogle Scholar
  43. 43.
    Dhainaut JFA, Tenaillon A, Le Tulzo Y et al (1994) Platelet-activating factor antagonist BN 52021 in the treatment of severe sepsis: a randomized, double-blind, placebo-controlled, multicenter clinical trial. Crit Care Med 22:1720–1728PubMedGoogle Scholar
  44. 44.
    Zeni F, Freeman B, Natanson C (1997) Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med 25:1095–1100PubMedCrossRefGoogle Scholar
  45. 45.
    Bollaert PE, Charpentier C, Levy B et al (1998) Reversal of late septic shock with supraphysi-ologic doses of hydrocortisone. Crit Care Med 26:645–650PubMedCrossRefGoogle Scholar
  46. 46.
    Pinsky MR, Vincent JL, Deviere J et al (1993) Serum cytokine levels in human septic shock: relation to multiple system organ failure and mortality. Chest 103:565–575PubMedCrossRefGoogle Scholar
  47. 47.
    Calandra T, Baumgartner JD, Grau GE et al (1990) Prognostic values of tumour necrosis fac-tor/cachectin, interleukin-1, interferon-alpha, and interferon gamma in the serum of patients with septic shock. J Infect Dis 161:982–987PubMedCrossRefGoogle Scholar
  48. 48.
    Cain BS, Meldrum DR, Harken AH, McIntyre (1998) The physiologic basis for anticytokine clinical trials in the treatment of sepsis. J Am Coll Surg 186:337–350PubMedCrossRefGoogle Scholar
  49. 49.
    Fassbender K, Pargger H, Muller W, Zimmerli W (1993) IL-6 and acute phase protein concentrations in surgical intensive care unit patients: diagnostic sign in nosocomial infection. Crit Care Med 21:1175–1180PubMedCrossRefGoogle Scholar
  50. 50.
    Waage A, Aasen AO (1992) Different role of cytokine mediators in septic shock related to meningococcal disease and surgery. Immunology 127:221–230Google Scholar
  51. 51.
    Calandra T, Gerain J, Heumann D et al (1991) High circulating levels of interleukin-6 in patients with septic shock evolution during sepsis, prognostic value and interplay with other cytokines. Am J Med 91:23–29PubMedCrossRefGoogle Scholar
  52. 52.
    Wakefield CH, Barclay GR, Fearon KCH et al (1998) Proinflammatory mediator activity, endogenous agonists and the systemic inflammatory response in intra-abdominal sepsis. Br J Surg 85:818–825PubMedCrossRefGoogle Scholar
  53. 53.
    Dandona P, Nix D, Wilson MF et al (1994) Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab 79:1605–1608PubMedCrossRefGoogle Scholar
  54. 54.
    Assicot M, Gendrel D, Carsin H et al (1993) High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 341:515–518PubMedCrossRefGoogle Scholar
  55. 55.
    Mimoz O, Benoist JF, Edouard AR et al (1998) Procalcitonin and C-reactive protein during the early postraumatic systemic inflammatory response syndrome. Intens Care Med 24: 185–188CrossRefGoogle Scholar
  56. 56.
    Cavaillon JM, Munoz C, Fitting C et al (1992) Circulating cytokines: the tip of the iceberg? Circ Shock 38:145–152PubMedGoogle Scholar
  57. 57.
    Sprung CL, Eidelman LA, Pizov R et al (1997) Influence of alterations in forgoing life-sustaining treatment practices on clinical sepsis trial. Crit Care Med 25:383–387PubMedCrossRefGoogle Scholar
  58. 58.
    Tanaka N, Murata A, Ken-ichi U et al (1995) Interleukin 1 receptor antagonist modifies the changes to vital organs induced by acute necrotizing pancreatitis in a rat experimental model. Crit Care Med 23:901–908PubMedCrossRefGoogle Scholar
  59. 59.
    Moreland LA, Baumgartner SW, Schiff MH et al (1997) Treatment of rheumatoid arthritis with a recombinant human tumour necrosis factor receptor (p75)-Fc fusion protein. New Engl J Med 337:141–147PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia, Milano 1999

Authors and Affiliations

  • A. Gullo
  • G. Berlot

There are no affiliations available

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