Sepsis trials: What have we learned?

Clinical Pulmonary Medicine

Volumn 6, Issue 6, 1999, Pages 367-377

  DePietro, Michael R ^a   Natanson, Charles ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

Anti inflammatory agents; Multisystem organ failure; Oxygen delivery; Sepsis

Indexed keywords

ANTIINFLAMMATORY AGENT; BRADYKININ ANTAGONIST; CPO 127; DEXAMETHASONE; GINKGOLIDE B; GLUCOCORTICOID; HYDROCORTISONE; IMMUNOGLOBULIN; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; LIPOPOLYSACCHARIDE; MAK 195F; METHYLPREDNISOLONE; PROSTAGLANDIN INHIBITOR; TUMOR NECROSIS FACTOR ALPHA ANTIBODY; TUMOR NECROSIS FACTOR ANTIBODY; TUMOR NECROSIS FACTOR RECEPTOR; UNCLASSIFIED DRUG;

ARTICLE; CLINICAL RESEARCH; CLINICAL TRIAL; HUMAN; INFLAMMATION; INTENSIVE CARE; META ANALYSIS; MULTIPLE ORGAN FAILURE; PATHOPHYSIOLOGY; SEPSIS; SEPTIC SHOCK;

EID: 0032749947     PISSN: 10680640     EISSN: None     Source Type: Journal    
DOI: 10.1097/00045413-199911000-00006     Document Type: Article

References (89)

1. Parillo J. Management of septic shock, present and future. Ann Intern Med 1991;115:451-2.
2. Sands KE, Bates DW, Lanken PN, et al. Epidemiology of the sepsis syndrome in eight academic medical centers. Academic Medical Center Consortium Sepsis Project Working Group. JAMA 1997;278:234-40.
3. Increase in National Hospital Discharge Survey rates for septicemia - United States, 1979-1987. MMWR Morb Mortal Wkly Rep 1990;39: 31-4.
4. Cipolle MD, Pasquale MD, Cerra FB. Secondary organ dysfunction: from clinical perspectives to molecular mediators. Crit Care Med 1993;9:261-98.
5. Grum CM. Cells in crisis: cellular bioenergetics and inadequate oxygenation in the intensive care unit. Chest 1992;102:329-30.
6. Freeman BD, Natanson C. Clinical trials in sepsis and septic shock in 1994 and 1995. Curr Opin Crit Care 1995;1:349-57.
7. Nelson DP, Beyer C, Samsel RW, et al. Pathologic supply dependence of oxygen uptake during bacteremia in dogs. J Appl Physiol 1987;63:1487-9.
8. Haupt MT, Gilbert EM, Carlson RW. Fluid loading increases oxygen consumption in septic patients with lactic acidosis. Am Rev Respir Dis 1985;131:912-6.
9. Kaufman BS, Rackow EC, Falk JL. The relationship between oxygen delivery and consumption during fluid resuscitation of hypovolemic and septic shock. Chest 1984;85:336-40.
10. Shoemaker WC, Montgomery ES, Kaplan E, Elwyn D. Physiologic patterns in surviving shock patients. Arch Surg 1973;106:630-8.
11. Ronco JJ, Fenwick JC, Tweedle M, et al. Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and nonseptic humans. JAMA 1993;270:1724-30.
12. Ronco JJ, Fenwick JC, Wiggs BR, et al. Oxygen consumption is independent of increases in oxygen delivery by dobutamine in septic patients who have normal or increased plasma lactate. Am Rev Respir Dis 1993;147:25-31.
13. Chittock DR, Russell JA. Oxygen delivery and consumption during sepsis. Clin Chest Med 1996;17:263-75.
14. Russell JA, Phang PT. The oxygen delivery/ consumption controversy. Approaches to management of the critically ill. Am J Respir Crit Care Med 1994;149:533-7.
15. Cain SM. Oxygen delivery and uptake in dogs during anemic and hypoxic hypoxia. J Appl Physiol 1977;42:228-34.
16. Bland RD, Shoemaker WC, Cobb JC. Hemodynamic and oxygen transport patterns in surviving and nonsurviving postoperative patients. Crit Care Med 1985;13:85-90.
17. Shoemaker WC, Appel P, Kram H, et al. Prospective trial of supranormal values of survivors as therapeutic goals in high risk patients. Chest 1988;94:1176-86.
18. Flemming A, Bishop M, Shoemaker WC, et al. Prospective trial of supranormal values as goals of resuscitation in severe trauma. Arch Surg 1992;127:1175-81.
19. Bishop M, Shoemaker WC, Appel P, et al. Prospective, randomized trial of survivor values of cardiac index, oxygen delivery, and oxygen consumption as resuscitation end-points in severe trauma. J Trauma 1995;38: 780-7.
20. Boyd O, Grounds R, Bennett E. A randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery in high risk surgical patients. JAMA 1993;270:2699-702.
21. Yu M, Levy MM, Smith P, et al. Effects of maximizing oxygen delivery on morbidity and mortality in critically ill patients: a prospective randomized controlled study. Crit Care Med 1993;21:830-8.
22. Tuschmidt J, Freid J, Astiz M, et al. Elevation of cardiac output and oxygen delivery improves outcome in septic shock. Chest 1992; 102:116-20.
23. Guiterrez G, Palizas T, Doglio G, et al. Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients. Lancet 1992;339:195-9.
24. Hayes M, Timmins A, Yau E, et al. Evaluation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994;330: 1717-22.
25. Gattinoni L, Brazzi L, Peosi P, et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. N Engl J Med 1994;333:1025-32.
26. Baue AE. The horror autotoxicus and multiple-organ failure. Arch Surg 1992;127:1451-62.
27. Deitch EA. Multiple organ failure. Pathophysiology and potential future therapy. Ann Surg 1992;216:117-34.
28. Rangel-Frausto MS, Pittet D, Costigian M, et al. The natural history of the system inflammatory response syndrome (SIRS). A prospective study. JAMA 1995;273:117-23.
29. Hinshaw LB, Solomon DA, Feeny PC, et al. Hemodynamic and survival effects of methylprednisolone in endotoxic shock. Arch Surg 1967;94:61-6.
30. Ziegler EJ, McCutchan JA, Douglas H, Braude AI. Prevention of lethal pseudomonas bacteremia with epimerase-deficient E. coli antiserum. Trans Assoc Am Physicians 1975;88: 101-8.
31. Ziegler EJ, Douglas H, Braude AI. Human antiserum for prevention of the local shwartzman reaction and death from bacterial lipopolysaccharides. J Clin Invest 1973;52:3236-8.
32. Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effects of endotoxin. Science 1985;229:869-71.
33. Bone RC. The pathogenesis of sepsis. Ann Intern Med 1991;115:457-69.
34. Tracey KJ, Beutler B, Lowry SF, et al. Shock and tissue injury induced by recombinant human cachectin. Science 1986;234:470-4.
35. Dinarello CA. Interleukin-1 and interleukin antagonism. Blood 1991;77:1627-52.
36. Natanson C, Eichacker PQ, Danner RL, et al. Endotoxin and tumor necrosis factor challenges in dogs simulates the cardiovascular profile of human septic shock. J Exp Med 1989;169:823-32.
37. Ohlsson K, Bjork P, Bergenfeldt M, et al. Interleukin-1 receptor antagonist reduces mortality from endotoxic shock. Nature 1990;348:550-2.
38. Tracey KJ, Fong Y, Hesse DG, et al. Anticachectin/TNF monoclonal antibodies prevent septic shock during lethal bactaeremia. Nature 1987;330:662-4.
39. Opal SM, Cross AS, Kelly NM, et al. Efficacy of a monoclonal antibody directed against tumor necrosis factor in protecting neutropenic rats from lethal infection with Pseudomonas aeruginosa. J Infect Dis 1990;161:1048-52.
40. Zeni F, Freeman B, Natanson C. Antiinflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med 1997;25: 1095-100.
41. Natanson C. Reevaluation of antiinflammatory trials in sepsis: a meta-analysis. In: The role of cytokines in systemic and pulmonary medicine. Continuing monograph series. New York, NY: American Thoracic Society, 1997:7-18.
42. Freeman BD, Eichacker PQ, Natanson C. The role of inflammation in sepsis and septic shock: a meta-analysis of both clinical and preclinical trials of antiinflammatory therapies. In: Galin JI, Snyderman R, editors. Inflammation: basic principles and clinical correlates. 3rd ed. Philadelphia, PA: Lippincott-Raven Publishers, 1999:965-76.
43. Natanson C, Esposito CJ, Banks SM. The sirens' song of confirmatory sepsis trials: selection bias and sampling error. Crit Care Med 1998;26:1927-31.
44. Abraham E, Wunderink R, Silverman H, et al. Efficacy and safety of monoclonal antibody to human tumor necrosis factor-α in patients with sepsis syndrome: a randomized, controlled, double-blind, multicenter clinical trial. TNF-α MAb Sepsis Study Group. JAMA 1995; 273:934-41.
45. Abraham E, Anzueto A, Gutierrez G, et al. Double-blind randomised controlled trial of monoclonal antibody to tumor necrosis factor in treatment of septic shock. Lancet 1998;351: 929-33.
46. Cohen J, Carlet J. INTERCEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-α in patients with sepsis. International Sepsis Trial Study Group. Crit Care Med 1996;24:1431-40.
47. Rhinehart K, Wiegand-Lohnart C, Grimminger F, et al. Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor fragment, MAK 195, in patients with sepsis and septic shock: a multicenter, randomized, placebo-controlled, dose ranging study. Crit Care Med 1993;21:318-27.
48. Fisher CJ, Opal SM, Dhainaut JF, et al. Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis. The CB0006 Sepsis Syndrome Study Group. Crit Care Med 1993;21:318-27.
49. Dhainaut JF, Vincent JL, Richard C, et al. CPD57, a humanized antibody to human tumor necrosis factor-α: safety, pharmacokinetics, immune response, and the influence of the antibody on cytokine concentrations in patients with septic shock. CPD571 Sepsis Study Group. Crit Care Med 1995;23:1461-9.
50. Kay CA. Can better measures of cytokine responses be obtained to guide cytokine inhibition? Presented at: Cambridge Health Institute's Designing Better Drugs & Clinical Trials for Sepsis/SIRS: Reducing Mortality to Patients and Suppliers; February 20-21, 1996; Washington, DC.
51. Abraham E. Immunomodulation therapy in sepsis: failure in clinical trials or critical thinking. Presented at: International Conference of the American Thoracic Society; April 28, 1998; Chicago, IL.
52. Fisher CJ, Agosti JM, Opal SM, et al. Treatment of septic shock with the tumor necrosis factor receptor: Fc fusion protein. N Engl J Med 1995;334:1697-702.
53. Abraham E, Glauser MP, Butler T, et al. P55 tumor necrosis factor fusion protein in the treatment of patients with severe sepsis and septic shock. Ro 45-2081 Study Group. JAMA 1997;277:1531-8.
54. Fisher CJ, Dhainaut JF, Opal SM, et al. Recombinant human interleukin-1 receptor antagonist in the treatment of patients with sepsis syndrome. Phase III rhIL-1ra Sepsis Syndrome Study Group. JAMA 1994;272:1836-43.
55. Opal SM, Fisher CJ, Dhainaut JF. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double- blind, placebo-controlled, multicenter trial Crit Care Med 1997;25:1115-24.
56. Fisher CJ, Slotman GJ, Opal SM, et al. Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open label, placebo controlled multicenter trial. Crit Care Med 1994;22:12-21.
57. Bernard GR, Wheeler AP, Russell JA, 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: 912-8.
58. Bernard GR, Reines HD, Halushka PV. Prostacyclin and thromboxane A2 formation is increased in human sepsis syndrome. The effects of cyclooxygenase inhibition. Am Rev Respir Dis 1991;144:1095-101.
59. Haupt MT, Jastremski MS, Clemmer TP, et al. The effects of ibuprofen in patients with severe sepsis: a randomized, double-blind, multicenter study. The Ibuprofen Study Group. Crit Care Med 1991;19:1339-47.
60. Fein AM, Bernard GR, Criner GJ, 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. CP-0127 SIRS and Sepsis Study Group. JAMA 1997;227:482-7.
61. Rodell TC, Foster C. Sepsis data show negative trend in second phase II sepsis trial [press release]. Cortech, Inc., 7000 N Broadway, Denver, CO 80821. July 18, 1995.
62. Dhainaut JF, Tenaillon A, Hemmer M, et al. Confirmatory platelet-activating factor receptor antagonist trial in patients with severe gram-negative bacterial sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. BN 52021 Sepsis Investigator Group. Crit Care Med 1998;26:1963-71.
63. Dhainaut JF, Tenaillon A, Le Tuzlo Y, et al. Platelet activating factor receptor antagonist BN 52021 in the treatment of severe sepsis: a double-blind, randomized, placebo controlled, multicenter clinical trial. BN 52021 Sepsis Study Group. Crit Care Med 1994;22:1720-8.
64. Luce JM, Montgomery AB, Marks ID, 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: 62-8.
65. 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;317:659-65.
66. Bone RC, Fisher CJ, Clemmer TP. A controlled clinical trial of high dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 1987;317:653-8.
67. Sprung CL, Caralis PV, Marcial EG. The effects of high dose corticosteroids in patients with septic shock: a prospective controlled study. N Engl J Med 1984;311:1137-43.
68. Thompson WL, Gurley HT, Lutz BA, et al. Inefficacy of glucocorticoids in shock (double-blind study) [abstract]. Clin Res 1976;24:258A.
69. Lucas CE, Ledgerwood AM. The cardiopulmonary response to massive doses of steroids in patients with septic shock. Arch Surg 1984; 119:537-41.
70. Klastersky J, Cappel R, Debusscer L. Effectiveness of betamethasone in management of severe infections. N Engl J Med 1971;284:1248-50.
71. Cooperative Study Group. The effectiveness of hydrocortisone in the management of severe infection. JAMA 1963;183:462-6.
72. Schumer W. Steroids in the treatment of clinical septic shock. Ann Surg 1976;184:333-41.
73. McCutchan JA, Wolf JL, Ziegler EJ, Braude AI. Ineffectiveness of single-dose antiserum to core glycolipid (E. coli J5) for prophylaxis of bacteremic, gram-negative infections in patients with prolonged neutropenia. Schweiz Med Wochenschr Suppl 1983;14:40-5.
74. Baumgartner JD, Glauser MP, Schellekens J, et al. Prevention of gram negative shock and death in surgical patients by antibody to endotoxin core glycolipid. Lancet 1985;2:59-63.
75. The Intravenous Immunoglobulin Collaborative Study Group. Prophylactic intravenous administration of standard immune globulin as compared with core-lipopolysaccharide immune globulin in patients at high risk of post-surgical infection. N Engl J Med 1992;327:234-40.
76. Calandra T, Glauser MP, Schellekens J, Verhoef J. Treatment of gram negative septic shock with human IgG antibody to E. coli J5, a prospective, double-blind, randomized trial. J Infect Dis 1988;158:312-9.
77. J5 Study Group. Treatment of severe infectious purpura in children with human plasma from donors immunized with Escherichia coli J5: a prospective, double-blind study. J Infect Dis 1992;165:695-701.
78. Ziegler EJ, McCutchan JA, Fierer J, et al. Treatment of gram negative bacteremia and shock with human antiserum to a mutant Escherichia coli. N Engl J Med 1982;307:1225-30.
79. Greenman RL, Schein RM, Martin MA, et al. A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram negative sepsis. The XOMA Sepsis Study Group. JAMA 1991;266:1097-102.
80. Wenzel R, Bone RC, Fein A, et al. Results of a second, double-blind, randomized, controlled trial of anti-endotoxin antibody E5 in gram negative sepsis [abstract]. In: Program and abstracts of tbe 31st Interscience Conference of Antimicrobial Agents and Chemotherapy; 1991:294.
81. Ziegler EJ, Fischer CJ, Sprung CL, et al. Treatment of gram negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo controlled trial. The HA-1A Sepsis Study Group. N Engl J Med 1991;324: 429-36.
82. McCloskey RV, Straube RC, Sanders C, et al. Treatment of septic shock with human monoclonal antibody HA-1A: a randomized, double-blind, placebo controlled trial. CHESS Trial Study Group. Ann Intern Med 1994;121: 1-5.
83. Cronin L, Cook DJ, Carlet J, et al. Corticosteroid treatment for sepsis, a critical reappraisal and meta-analysis of the literature. Crit Care Med 1995;23:1430-9.
84. Lefering R. Steroid controversy in sepsis and septic shock: a meta-analysis. Crit Care Med 1995;23:1294-303.
85. Natanson C, Hoffman WD, Suffredini AF, et al. Selected treatment strategies for septic shock based on proposed mechanisms of pathogenesis. Ann Intern Med 1994;120:771-83.
86. Baumgartner JD. Immunotherapy with antibodies to core lipopolysaccharide: a critical appraisal. Infect Dis Clin North Am 1991;5: 915-27.
87. Corriveau CC, Danner RL. Endotoxin as a therapeutic target in septic shock. Infect Agents Dis 1993;2:35-43.
88. Sevransky JE, Shaked G, Novogrodsky A, et al. Tyrphostin AG 556 improves survival and reduces multiorgan failure in canine Escherichia coli peritonitis. J Clin Invest 1997;99: 1966-73.
89. Leturcq DJ, Moriarity AM, Talbott G, Winn RK, Martin TR, Ulevitch RJ. Antibodies against CD14 protect primates from endotoxin-induced shock. J Clin Invest 1996;98: 1533-8.