Endotoxaemia in Critical Illness: Rapid Detection and Clinical Relevance

  • J. C. Marshall
  • D. M. Foster
  • P. M. Walker
  • A. Romaschin
Conference paper


The emergence of Gram negative organisms as an important cause of infection in critically ill patients is a relatively recent phenomenon. Prior to the development of the first intensive care units, exogenous micro-organisms including Staphylococci, Streptococci, and the tubercle bacillus were the most common infecting species in hospitalised patients [1]. Gram negative infection was first recognized to be a significant clinical problem in the early 1960s [2], and by the conclusion of the decade, had become the dominant and defining cause of septic shock in the intensive care unit [3]. Investigations into the mechanisms of the profound alterations in haemodynamic homeostasis and remote organ function occurring during Gram negative infection focussed on the pathologic role of a constituent of the bacterial cell wall — lipopolysaccharide or endotoxin.


Septic Shock Critical Illness Horseshoe Crab Opsonized Zymosan Negative Infection 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Rogers DE(1959) The changing pattern of life-threatening microbial disease. N Engl J Med 261:677–683PubMedCrossRefGoogle Scholar
  2. 2.
    McCabe WR, Jackson GG(1962) Gram negative bacteremia. Etiology and ecology. Arch Intern Med 110:83–91CrossRefGoogle Scholar
  3. 3.
    Maclean LD, Mulligan WG, Mclean APH et al(1967) Patterns of septic shock in man — a detailed study of 56 patients. Ann Surg 166:543–562PubMedCrossRefGoogle Scholar
  4. 4.
    Sweet MJ, Hume DA(1996) Endotoxin signal transduction in macrophages. J Leuk Biol 60:8–26Google Scholar
  5. 5.
    Marshall JC(1991) The ecology and immunology of the GI tract in health and critical illness. J Hosp Infect 19:7–17PubMedCrossRefGoogle Scholar
  6. 6.
    Ulevitch RJ, Tobias PS(1995) Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin. Ann Rev Immunol 13:437–457CrossRefGoogle Scholar
  7. 7.
    Beutler B, Milsark IW, Cerami AC(1985) Passive immunization against cachectin tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229:869–871PubMedCrossRefGoogle Scholar
  8. 8.
    Ohlsson K, Bjork P, Bergenfeldt M et al(1990) Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature 348:550–552PubMedCrossRefGoogle Scholar
  9. 9.
    Demling RH, Lalonde CC, Jin LJ et al(1986) The pulmonary and systemic response to recurrent endotoxemia in the adult sheep. Surgery 100:876–883PubMedGoogle Scholar
  10. 10.
    Suffredini AF, Fromm RE, Parker MM et al(1989) The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med 321:280–287PubMedCrossRefGoogle Scholar
  11. 11.
    Michie HR, Spriggs DR, Manogue KR et al(1988) Tumor necrosis factor and endotoxin induce similar metabolic responses in human beings. Surgery 104:280–286PubMedGoogle Scholar
  12. 12.
    Fong Y, Marano MA, Moldawer LL et al(1990) The acute splanchnic and peripheral tissue metabolic response to endotoxin in humans. J Clin Invest 85:896–1904CrossRefGoogle Scholar
  13. 13.
    van der Poll T, de Waal Malefyt R, Coyle SM et al(1997) Antiinflammatory cytokine responses during clinical sepsis and experimental endotoxemia: sequential measurements of plasma soluble interleukin(IL)-1 receptor type II, IL-10, and IL-1. J Infect Dis 175:118–122PubMedCrossRefGoogle Scholar
  14. 14.
    Taveira Da Silva AM, Kaulach HC, Chuidian FS et al(1993) Brief report: shock and multiple organ dysfunction after self administration of salmonella endotoxin. N Engl J Med 328: 1457–1460PubMedCrossRefGoogle Scholar
  15. 15.
    Ziegler EJ, McCutchan JA, Fierer J et al(1982) Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. N Engl J Med 307:1225–1230PubMedCrossRefGoogle Scholar
  16. 16.
    Ziegler EJ, Fisher CJ, Sprung CL et al(1991) Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. N Engl J Med 324:429–436PubMedCrossRefGoogle Scholar
  17. 17.
    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-negative sepsis. JAMA 266:1097–1102PubMedCrossRefGoogle Scholar
  18. 18.
    McCloskey RV, Straube RC, Sanders C et al(1994) Treatment of septic shock with human monoclonal antibody HA-1A. A randomized double-blind, placebo-controlled trial. Ann Intern Med 121:1–5PubMedGoogle Scholar
  19. 19.
    Moore GE, Holbein ME, Knochel JP (1995) Exercise-associated collapse in cyclists is unrelated to endotoxemia. Med Sci Sports Exer 27:1238–1242Google Scholar
  20. 20.
    Hurley JC(1995) Endotoxemia: methods of detection and clinical correlates. Clin Microbiol Rev 8:268–292PubMedGoogle Scholar
  21. 21.
    van Deventer SJ, Buller HR, Ten Cate JW et al(1988) Endotoxemia: an early predictor of septicaemia in febrile patients. Lancet 1:605–609PubMedCrossRefGoogle Scholar
  22. 22.
    Casey LC, Balk RA, Bone RC(1993) Plasma cytokines and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med 119:771–778PubMedGoogle Scholar
  23. 23.
    Danner RL, Elin RJ, Hosseini JM et al(1991) Endotoxemia in human septic shock. Chest 99:169–175PubMedCrossRefGoogle Scholar
  24. 24.
    Hurley JC(1992) Antibiotic-induced release of endotoxin: a reappraisal. Clin Infect Dis 15:840–854PubMedCrossRefGoogle Scholar
  25. 25.
    Van Deventer SJH, Ten Cate JW, Tytgat GNJ(1988) Intestinal endotoxemia. Clinical significance. Gastroenterology 94:825–831PubMedGoogle Scholar
  26. 26.
    Riddington DW, Venkatesh B, Boivin CM et al(1996) Intestinal permeability, gastric intra-mucosal pH, and systemic endotoxemia in patients undergoing cardiopulmonary bypass. JAMA 275:1007–1012PubMedCrossRefGoogle Scholar
  27. 27.
    Buttenschoen K, Berger D, Hiki N et al(1996) Plasma concentrations of endotoxin and anti-endotoxin antibodies in patients with multiple injuries: a prospective clinical study. Eur J Surg 162:853–860PubMedGoogle Scholar
  28. 28.
    Winchurch RA, Thupari JN, Munster AM(1987) Endotoxemia in burn patients: Levels of circulating endotoxins are related to burn size. Surgery 102:808–812PubMedGoogle Scholar
  29. 29.
    Kivilaakso E, Valtonen VV, Malkamaki M et al(1984) Endotoxemia and acute pancreatitis: correlation between the severity of the disease and the anti-enterobacterial common antigen antibody titre. Gut 25:1065–1070PubMedCrossRefGoogle Scholar
  30. 30.
    Roumen RMH, Frieling JTM, van Tits HWHJ et al(1993) Endotoxemia after major vascular operations. J Vasc Surg 18:853–857PubMedCrossRefGoogle Scholar
  31. 31.
    Soong CV, Blair PHB, Halliday ML et al(1993) Endotoxemia, the generation of cytokines, and their relationship to intramucosal acidosis of the sigmoid colon in elective abdominal aortic aneurysm repair. Eur J Vasc Surg 7:534–539PubMedCrossRefGoogle Scholar
  32. 32.
    Cooperstock M, Riegle L(1985) Plasma Limulus gelation assay in infants and children: correlation with Gram negative bacterial infection and evidence for “intestinal endotoxemia”. Prog Clin Biol Res 189:329–345PubMedGoogle Scholar
  33. 33.
    Le Moine O, Soupison T, Sogni P et al(1995) Plasma endotoxin and tumor necrosis factor-α in the hyperkinetic state of cirrhosis. J Hepatol 23:391–395PubMedCrossRefGoogle Scholar
  34. 34.
    Lumsden AB, Henderson JM, Kutner MH(1988) Endotoxin levels measured by a chromogenic assay in portal, hepatic and peripheral venous blood in patients with cirrhosis. Hepatology 8:232–236PubMedCrossRefGoogle Scholar
  35. 35.
    Bion JF, Badger I, Crosby HA et al(1994) Selective decontamination of the digestive tract reduces Gram-negative pulmonary colonization but not systemic endotoxemia in patients undergoing elective liver transplantation. Crit Care Med 22:40–49PubMedGoogle Scholar
  36. 36.
    Murphy PA(1967) Quantitative aspects of the release of leukocyte pyrogen from rabbit blood incubated with endotoxin. J Exp Med 126:763–781PubMedCrossRefGoogle Scholar
  37. 37.
    Levin J, Tomasulo PA, Oser RS(1970) Detection of endotoxin in human blood and demonstration of an inhibitor. J Lab Clin Med 75:903–911PubMedGoogle Scholar
  38. 38.
    Tamura H, Obayashi T, Takagi K et al(1982) Perchloric acid treatment of human blood for quantitative endotoxin assay using synthetic chromogenic substrate for horseshoe crab clotting enzyme. Thromb Res 27:51–57PubMedCrossRefGoogle Scholar
  39. 39.
    Rylatt D, Wilson K, Kemp BE et al(1995) A rapid test for endotoxin in whole blood. Prog Clin Biol Res 392:273–284PubMedGoogle Scholar
  40. 40.
    Kollef MH, Eisenberg PR(1997) A rapid qualitative assay to detect circulating endotoxin can predict the development of multiorgan dysfunction. Chest 112:173–180PubMedCrossRefGoogle Scholar
  41. 41.
    Eperon S, De Groóte D, Werner-Felmayer G et al(1997) Human monocytoid cell lines as indicators of endotoxin: comparison with rabbit pyrogen and limulus amoebocyte lysate assay. J Immunol Methods 207:135–145PubMedCrossRefGoogle Scholar
  42. 42.
    Romaschin AD, Harris DM, Ribeiro MB et al(1998) A rapid assay of endotoxin in whole blood using autologous neutrophil-dependent chemiluminescence. J Immunol Methods 212: 169–185PubMedCrossRefGoogle Scholar
  43. 43.
    Schulman KA, Glick HA, Rubin H et al(1991) Cost-effectiveness of HA-1A monoclonal antibody for Gram negative sepsis. JAMA 266:3466–3471PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia, Milano 1999

Authors and Affiliations

  • J. C. Marshall
  • D. M. Foster
  • P. M. Walker
  • A. Romaschin

There are no affiliations available

Personalised recommendations