Advertisement

Anti-Inflammatory Therapy in Sepsis

  • Jonathan Sevransky
  • Charles Natanson
Part of the Perspectives on Critical Care Infectious Diseases book series (CCID, volume 2)

Abstract

Despite advances in supportive care and medical technology, the mortality rate from sepsis remains high (35–50%) (1). It is the most common cause of death in non-cardiac intensive care units, and the incidence appears to be rising (2). Over the last 20 years, prevailing thought has attributed much of the morbidity and mortality of sepsis to an overexuberant host inflammatory response to bacteria or bacterial products. In preclinical studies, agents designed to limit this host pro-inflammatory response showed promising effects, prompting numerous clinical trials.

Keywords

Septic Shock Sepsis Syndrome Soluble Tumor Necrosis Factor Receptor Hyperdynamic Septic Shock Bradykinin Antagonist 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Wheeler, AP, and GR. Bernard. Treating patients with severe sepsis. N Eng J Med 1999;340:207–214.CrossRefGoogle Scholar
  2. 2.
    Linde-Swirbe, WT, DC. Angus, J. Carcillo, et al. Age specific incidence and outcome of sepsis in the US. Crit Care Med 1999;27:A33.CrossRefGoogle Scholar
  3. 3.
    Hartman, F. A., and W. J. M. Scott. Protection of adrenalectomized animals against bacterial intoxication by an extract of the adrenal cortex. J Exp Med 1932;55:63–69.PubMedCrossRefGoogle Scholar
  4. 4.
    Sacks, M. S. Fulminating septicemia associated with purpura and bilateral adrenal hemorrhage (Waterhouse-Friderichsen Syndrome); report of two cases with review of the literature. Ann Int Med 1936:1105–1114.Google Scholar
  5. 5.
    Hinshaw, L. B., L. T. Archer, and B. K. Beller-Todd. Survival of primates in LD100 septic shock following steroid/antibiotic therapy. J Surg Res 1980;28:151–170.PubMedCrossRefGoogle Scholar
  6. 6.
    Fabian, T. C., and R. Patterson. Steroid therapy in septic shock. Survival study in a laboratory model. Am Surgeon 1982;48:614–617.PubMedGoogle Scholar
  7. 7.
    Hinshaw, L. B., B. K. Beller-Todd, L. T. Archer, et al. Effectiveness of steroid antibiotic treatment in primates administered LD100 Eschericia coli. Ann Surg 1981;194:51–56.PubMedCrossRefGoogle Scholar
  8. 8.
    Hinshaw, L. B., D. J. Flournoy, L. T. Archer, et al. Recovery from lethal Escherichia coli shock. Surg Gyn Ob 1979; 149:545–553.Google Scholar
  9. 9.
    White, G. L., L. T. Archer, B. K. Beller-Todd, et al. Increased survival with methylprednisolone treatment in canine endotoxin shock. J Surg Res 1978;25.Google Scholar
  10. 10.
    Beller-Todd, B. K. L. T. Archer, R. Passey, et al. Effectiveness of modified steroid-antibiotic therapies for lethal sepsis in the dog. Arch Surg 1983;118:1293–1299.CrossRefGoogle Scholar
  11. 11.
    Bennett, I. L., M. Finland, M. Hamborger, et al. The effectiveness of hydrocortisone in the management of severe infection. JAMA 1963;183:462–465.CrossRefGoogle Scholar
  12. 12.
    Luce, J. M., A. B. Montgomery, J. D. Marks, et al. Ineffectiveness of high-dose methylprednisolone in preventing parenchymal lung injury and improving mortality in patients with septic shock. Am Rev Respir Dis 1988;138:62–68.PubMedCrossRefGoogle Scholar
  13. 13.
    The Veterans Administration Systemic Sepsis Cooperative Study Group. Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med 1987;317:653–658.CrossRefGoogle Scholar
  14. 14.
    Bone, R., C. Fisher, T. Clemmer, et al. A controlled trial of high dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 1987;317:653–658.PubMedCrossRefGoogle Scholar
  15. 15.
    Sprung, C., P. Caralis, E. Marcial, et al. The effects of high dose corticosteroids in patients with septic shock. N Eng J Med 1984;311:1137–1143.CrossRefGoogle Scholar
  16. 16.
    Thompson, W. L, H. T. Gurley, B. A. Lutz, et al. Inefficacy of glucocorticoids in shock (double-blind study). Clin Res 1976;24:258A.Google Scholar
  17. 17.
    Schumer, W. Steroids in the treatment of clinical shock. Ann Surg 1976;184:133–139.CrossRefGoogle Scholar
  18. 18.
    Klastersky, J., R. Cappell, and L. Debusscher. Effectiveness of betamethasone in management of severe infections. N Eng J Med 1971;284:1248–1250.CrossRefGoogle Scholar
  19. 19.
    Cronin, L., D. J. Cook, and J. Carlet. Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med 1997;23:1430–1439.CrossRefGoogle Scholar
  20. 20.
    Lefering, R., and E. A. Neugebauer. Steroid controversy in sepsis and septic shock: a meta-analysis. Crit Care Med 1995;23:1294–1303.PubMedCrossRefGoogle Scholar
  21. 21.
    Zeni, F., B. Freeman, and C. Natanson. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med 1997;25:1095–1100.PubMedCrossRefGoogle Scholar
  22. 22.
    Schumer, W. Steroid in the treament of clinical septic shock. Arch Surg 1976;184: 537–541.Google Scholar
  23. 23.
    The Veterans Association Systemic Sepsis Cooperative Study Group. Effect of high dose glucocorticoid therapy on mortality in patients with clinical signs of sepsis. N Engl J Med 1987;317:653–658.CrossRefGoogle Scholar
  24. 24.
    Meduri, G., and G. Chrousos. Duration of glucocorticoid treatment and outcome in sepsis. Chest 1998;114:355–359.PubMedCrossRefGoogle Scholar
  25. 25.
    Bollaert, P.-E., C. Charpentier, B. Levy, et al. Reversal of late septic shock in with supraphysiologic doses of hydrocortisone. Crit Care Med 1998;26:645–650.PubMedCrossRefGoogle Scholar
  26. 26.
    Briegel, J., H. Forst, M. Hallar, et al. Stress doses of hydrocortisone reverse hyperdynamic septic shock: A prospective, randomized, double-blind, single center study. Crit Care Med 1999;27:723–732.PubMedCrossRefGoogle Scholar
  27. 27.
    Chawla, K., Y. Kupfer, I. Goldman, et al. Hydrocortisone reverses refractory septic shock. Crit Care Med 1999;27:A33.CrossRefGoogle Scholar
  28. 28.
    ACCP SCCM Consensus Conference Committee. American College of Chest Physicians/ Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Critical Care Medicine 1992;20:864–874.CrossRefGoogle Scholar
  29. 29.
    Abraham, E., R. Wunderink, H. Silverman, et al. Efficacy and safety of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis syndrome. A randomized, controlled, double-blind multi-center clinical trial. TNF-alpha MAb Sepsis Study Group. JAMA 1995;273:934–941.PubMedCrossRefGoogle Scholar
  30. 30.
    Cohen, J., and J. Carlet. Intersept: An international, multicenter, placebo controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. Crit Care Med 1996;24:1431–1440.PubMedCrossRefGoogle Scholar
  31. 31.
    Abraham, E., A. Anzueto, G. Guterrez, et al. Double-blind randomized controlled trial of monoclonal antibody to human tumor necrosis factor in human septic shock. Lancet 1998;351:929–933.PubMedGoogle Scholar
  32. 32.
    Clark, M., L. Plank, A. Connolly, et al. Effect of a chimeric antibody to tumor necrosis factor alpha on cytokine and physiologic responses in patients with severe sepsis. A randomized clinical trial. Crit Care Med 1998;26:1650–1659.PubMedCrossRefGoogle Scholar
  33. 33.
    Rheinhart, K., C. Wiegland-Lohnart, F. Grimmanger, et al. Assessment of the safety and efficacy of the monoclonal antitumor necrosis factor antibody-fragment MAK 19F in patients with sepsis and septic shock: a multicenter, randomized placebo-controlled study. Crit Care Med 1996;24:733–742.CrossRefGoogle Scholar
  34. 34.
    Kay, C. A. Can better measures of cytokine responses be obtained to guide cytokine inhibition? Pressentation and handout Washington DC, Cambridge Health Institutes February 20-1, 1996.Google Scholar
  35. 35.
    Dhainaut, J., J. Vincent, C. Richard, et al. CD571, a humanized antibody to tumor necrosis factor-alpha: safety, pharmacodynamics, immune responses and influence of the antibody on cytokine concentrations in patients with septic shock. Crit Care Med 1995;21:1461–1469.CrossRefGoogle Scholar
  36. 36.
    Fisher, C., S. Opal, J. Dhainaut, et al. The CB006 Sepsis Syndrome Study Group. Crit Care Med 1993;21:318–327.PubMedCrossRefGoogle Scholar
  37. 37.
    Abraham, E., M. Glauser, T. Butler, et al. P55 tumor nerosis factor receptor fusion protein in the treatment of patients with septic shock. JAMA 1997;277:1531–1538.PubMedCrossRefGoogle Scholar
  38. 38.
    Abraham, E. Immunomodulatory therapy in sepsis: failure in clinical trials or critical thinking. International Conference, American Thoracic Society, Chicago, Illinois Tuesday April 28, 1998.Google Scholar
  39. 39.
    Fisher, C., J. Agosti, S. Opal, et al. Treatment of septic shock with the tumor necrosis factor receptor Fc fusion protein. N Engl J Med 1997;334:1697–1702.CrossRefGoogle Scholar
  40. 40.
    Fisher, C., G. Slotman, S. Opal, et al. Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open label, placebo controlled clinical trial. Crit Care Med 1994;22:12–21.PubMedGoogle Scholar
  41. 41.
    Opal, S., C. Fisher, F. Dhainaut, et al. Confirmatory interleuken-1 receptor antagonist in severe sepsis: a phase III, randomized double-blind, placebo controlled,multi-center trial. Crit Care Med 1997;25:1115–1124.PubMedCrossRefGoogle Scholar
  42. 42.
    Fisher, C., J. Dhainaut, and S. Opal. Recombinant human interleukin-1 receptor antagonist in the treatment of patients with the sepsis syndrome. JAMA 1994;271:1836–1848.PubMedCrossRefGoogle Scholar
  43. 43.
    Dhainaut, J., A. Tenaillon, Y. deTulzo, et al. Platelet-activating factor receptor antagonist BN 52021 in the treatment of severe sepsis: A randomized, placebo controlled, multi-center clinical trial. Crit Care Med 1994;22:1720–1728.PubMedGoogle Scholar
  44. 44.
    Dhainaut, J., A. Tenaillon, M. Hemmer, et al. The confirmatory platelet-activating factor receptor antagonist trial in patients with severe gram negative bacterial sepsis: a multi-center, randomized, placebo controlled, multicenter trial. Crit Care Med 1998;26:1963–1971.PubMedCrossRefGoogle Scholar
  45. 45.
    Rodell, T., and C. Foster. Sepsis data show negative trend in second phase II sepsis trial. Press Release. Cortec, Inc, 7000 North Broadway, Denver CO 80821 July 18, 1995.Google Scholar
  46. 46.
    Fein, A., G. Bernard, G. Criner, et al. Treatment of severe systemic inflammatory response syndrome and sepsis with a novel bradykinin antagonist, deltibant (CP-0127): results of a randomized, double-blind, placebo controlled trial. JAMA 1997;277:482–487.PubMedCrossRefGoogle Scholar
  47. 47.
    Jacobs, E., M. Soulsby, R. Bone, et al. Ibuprofen in canine endotoxin shock. J Clin Invest 1982;70:536–571.PubMedCrossRefGoogle Scholar
  48. 48.
    Wright, P. E., and G. R. Bernard. Mechanisms of late hemodynamic and airway dynamic responses to endotoxin in awake sheep. Am Rev Resp Dis 1989;140:672–678.PubMedCrossRefGoogle Scholar
  49. 49.
    Bernard, G., A. Wheeler, J. Rüssel, et al. The effects of ibuprofen on the physiology and survival of patients with sepsis. The ibuprofen in sepsis study group. N Engl J Med 1997;336:912–918.PubMedCrossRefGoogle Scholar
  50. 50.
    Haupt, M., M. Jastremski, T. Clemmer, et al. Effect of ibuprofen in patients with severe sepsis; a randomized, double-blind multi-center trial. Crit Care Med 1991;19:1339–1347.PubMedCrossRefGoogle Scholar
  51. 51.
    Sevransky, J. E., and C. Natanson. An analysis of clinical trials of mediator-specific anti-inflammatory agents. Sepsis 1999;3:11–19.CrossRefGoogle Scholar
  52. 52.
    Natanson, C., C. Esposito, and S. M. Banks. The siren’s song of confirmatory sepsis trials; selection bias and sampling error. Crit Care Med 1998;26:1927–1931.PubMedCrossRefGoogle Scholar
  53. 53.
    Natanson, C., P. W. Eichenholz, and R. L. Danner. Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock. J Exp Med 1989; 169:823–832.PubMedCrossRefGoogle Scholar
  54. 54.
    Suffredini, A. F., R. E. Fromm, M. M. Parker, et al. The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med 1989;321:280–287.PubMedCrossRefGoogle Scholar
  55. 55.
    Natanson, H. W., Suffredini AF, Eichacker PQ, and Danner RL. Selected Treatment Strategies for Septic Shock Based on Proposed Mechanisms of Pathogenesis. Ann Int Med 1994;120:771–783.PubMedGoogle Scholar
  56. 56.
    Ziegler, E. J., J. A. McCutchan, and J. Fierer. Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Esherichia coli. N Engl J Med 1982;307:1225–1230.PubMedCrossRefGoogle Scholar
  57. 57.
    Ziegler, E. J., C. J. Fisher, and C. L. Sprung. Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. New Engl J Med 1991;324:429–436.PubMedCrossRefGoogle Scholar
  58. 58.
    The J5 Study Group. Treatment of severe infectious purpura in children with human plasma from donors immunized with Esherichia coli J5: a prospective double-blind study. J Infect Dis 1992; 165:695–701.CrossRefGoogle Scholar
  59. 59.
    Calandra, T., M. P. Glauser, J. Schellekens, et al. Treatment of gram-negative septic shock with human IgG antibody to Escherichia coli J5; a prospective, double-blind, randomized trial. J Infect Dis 1988;158:312–319.PubMedCrossRefGoogle Scholar
  60. 60.
    Greenman, R. L., R. M. H. Scein, and M. A. Martin. A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. JAMA 1991;266:1097–1102.PubMedCrossRefGoogle Scholar
  61. 61.
    Bone, R. C., R. A. Balk, and A. M. Fein. A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled trial. Crit Care Med 1995;23:994–1006.PubMedCrossRefGoogle Scholar
  62. 62.
    McClosky, R. V., R. C. Straube, C. Sanders, et al. Treatment of septic shock with human monoclonal antibody HA-1A. Ann Int Med 121: 1–5, 1994.Google Scholar
  63. 63.
    McCutchan, J. A., J. L. Wolf, E. L. Ziegler, et al. Ineffectiveness of single-dose human antiserum to core glycolipid (Esherichia coli J5) for prophylaxis of bacteremic, gramnegative infection in patients with prolonged neutropenia. J Suisse de Medecine 1983;113(s):40–55.Google Scholar
  64. 64.
    The Intravenous Immunoglobulin Collaborative Study Group. Prophylactic intravenous administration of standard immune globulin compared with corelipopolysaccaride immune globulin in patients at high risk of post-surgical infection. N Engl J Med 1992;327:234–240.CrossRefGoogle Scholar
  65. 65.
    Baumgartner, J. D., D. Heumann, J. Gerain, et al. Association between protective efficacy of anti-lipopolysaccharide (LPS) antibodies and suppression of LPS-induced tumor necrosis factor alpha and interleukin 6. Comparison of O side chain-specific antibodies with core LPS antibodies. J Exp Med 1990; 171:889–896.PubMedCrossRefGoogle Scholar
  66. 66.
    Baumgartner, J. D. Immunotherapy with antibodies to core lipopolysaccharide: a critical appraisal. Infect Dis Clinics NA 1991;5:915–917.Google Scholar
  67. 67.
    Aiki, H., M. Kodama, T. Tani, et al. Treatment of sepsis by extracorporeal elimination of endotoxin using polymyxin B-immobilized fiber. Am J Surgery 1994;167:412–4171994.CrossRefGoogle Scholar
  68. 68.
    Bernard GR, Reines HD, Haluska DV. Prostacyclin and thromboxone A2 formatica is increased in human sepsis syndrome: effects of cyclooxygenase inhibition. Am Rev Respir Dis 1991;144:1095–1101.PubMedCrossRefGoogle Scholar
  69. 69.
    Lucas CE, Ledgerwood AN. The cardiopulmonary response to massive doses of steroids in patients with septic shock. Arch Surg 1984;119:537–541.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Jonathan Sevransky
    • 1
  • Charles Natanson
    • 1
  1. 1.Johns Hopkins University and the National Institutes of HealthUSA

Personalised recommendations