Klinische Wochenschrift

, Volume 62, Issue 20, pp 986–991 | Cite as

Endotoxemia in intensive care patients: A longitudinal study with the limulus amebocyte lysate test

  • P. C. Fink
  • J. H. Grunert


In patients with severe underlying disease and in polytraumatized patients, clinical signs of septicemia caused by infections with gram-negative bacteria are observed postoperatively with increasing frequency. Using a photometric LAL test, a longitudinal assessment of LAL reactivity on 41 intensive care patients was performed. Postoperatively, all patients developed a septicemia of different severity with body temperatures >38.5° C. Dividing the individual disease course, related to body temperatures, into three phases (A-C) it was found that independent of the severity of septicemia, the majority of patients (38/41) yielded a positive LAL reactivity. In phase B (body temperature >38.5° C) more plasma samples contained LAL-reactive material than in phase A and C (body temperature <38.5° C). A decline of fever (phase B to C) correlated significantly (P < 0.05) with the change from positive to negative LAL reactivity. In patients with high leukocyte counts (15–50 × 109/l) a positive LAL reactivity was found more frequently. The majority of patients (21/27) who survived were transferred with negative LAL reactivity to the general wards. The results suggest that single determinations of LAL reactivity are of limited clinical validity. Using the individual profile of LAL reactivity gained through a longitudinal assessment, data upon the development of the disease course can be obtained.

Key words

Endotoxin Limulus amebocyte lysate test 



Limulus amebocyte lysate




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  1. 1.
    McCabe WR, Jackson GG (1962) Gram-negative bacteremia. I. Etiology and ecology. Arch Int Med 110:83–91Google Scholar
  2. 2.
    Levin J, Poore TE, Young NS, Margolis S, Zauber NP, Townes AS, Bell WR (1972) Gram-negative sepsis: detection of endotoxemia with the limulus test. With studies of associated changes in blood coagulation, serum lipids, and complement. Ann Int Med 76:1–7Google Scholar
  3. 3.
    Hardaway RM (1980) Endotoxemic shock. Dis Colon Rectum 23:597–604Google Scholar
  4. 4.
    Weil MH, Shubin H, Biddle M (1964) Shock caused by gram-netative microorganisms. Analysis of 169 cases. Ann Intern Med 60:384–400Google Scholar
  5. 5.
    Christy JH (1971) Pathophysiology of gram-negative shock. Am Heart J 81:694–701Google Scholar
  6. 6.
    Eiseman B, Beart R, Norton L (1977) Multiple organ failure. Surg Gynecol Obstet 144:323–326Google Scholar
  7. 7.
    Vito L, Dennis RC, Weisel RD, Hechtman HB (1974) Sepsis presenting as acute respiratory insufficiency. Surg Gynecol Obstet 138:896–900Google Scholar
  8. 8.
    Wardle EN (1975) Endotoxinaemia and the pathogenesis of acute renal failure. Q J Med 44:389–398Google Scholar
  9. 9.
    McGowan JE Jr, Barnes MW, Finland M (1975) Bacteremia at Boston City Hospital: Occurrence and mortality during 12 selected years (1935–1972), with special reference to hospital-acquired cases. J Infect Dis 132:316–335Google Scholar
  10. 10.
    Maki DG (1981) Nosocomial bacteremia. An epidemiologic overview. Am J Med 70:719–732Google Scholar
  11. 11.
    Rose R, Huning KJ, Townsend TR, Wenzel RP (1977) Morbidity/mortality and economics of hospital-acquired blood stream infections: a controlled study. South Med J 70:1267–1269Google Scholar
  12. 12.
    Yin ET, Galanos C, Kinsky S, Bradshaw RA, Wessler S, Lüderitz O, Sarmiento ME (1972) Picogram-sensitive assay for endotoxin: Gelation of Limulus polyphemus blood cell lysate induced by purified lipopolysaccharides and lipid A from gram-negative bacteria. Biochim Biophys Acta 261:284–289Google Scholar
  13. 13.
    Fink PC, Lehr L, Urbaschek RM, Kozak J (1981) Limulus amebocyte lysate test for endotoxemia: investigations with a femtogram sensitive spectrophotometric assay. Klin Wochenschr 59:213–218Google Scholar
  14. 14.
    Elin RJ, Knowles R, Barth WF, Wolff SM (1978) Lack of specificity of the Limulus lysate test in the diagnosis of pyogenic arthritis. J Infect Dis 137:507–513Google Scholar
  15. 15.
    Elin RJ, Wolff SM (1973) Nonspecificity of the Limulus amebocyte lysate test: positive reactions with polynucleotides and proteins. J Infect Dis 128:349–352Google Scholar
  16. 16.
    Pekarek R, Wannemacher R, Powanda M, Abeles F (1974) Further evidence that leukocytic endogenous mediator (LEM) is not endotoxin. Life Sci 14:1765–1776Google Scholar
  17. 17.
    Fink PC, Wolkersdorfer RG (1982) Leucoxyte activation of the Limulus amebocyte lysate. In: Watson SW, Levin J, Novitsky TJ (eds) Endotoxins and their detection with the Limulus amebocyte lysate test. Alan R Liss, New York, pp 281–285Google Scholar
  18. 18.
    Prytz H, Holst-Christensen J, Korner B, Liehr H (1976) Portal venous and systemic endotoxaemia in patients without liver disease and systemic endotoxaemia in patients with cirrhosis. Scand J Gastroenterol 11:857–863Google Scholar
  19. 19.
    Wildfeuer A, Heymer B, Schleifer KH, Haferkamp O (1974) Investigations on the specificity of the Limulus test for the detection of endotoxin. App Microbiol 28:867–871Google Scholar
  20. 20.
    Brunson KW, Watson DW (1976) Limulus amebocyte lysate reaction with streptococcal pyrogenic exotoxin. Infect Immun 14:1256–1258Google Scholar
  21. 21.
    Sullivan JD, Watson SW (1974) Factors affecting the sensitivity of Limulus lysate. Appl Environ Microbiol 28:1023–1026Google Scholar
  22. 22.
    Rastogi SC, Seligmann EB, Hochstein HD, Dawsom JH, Farag LG, Marquina RE (1979) Statistical procedure for evaluating the sensitivity of Limulus amebocyte lysate by using a reference lysate. Appl Environ Microbiol 38:911–915Google Scholar
  23. 23.
    Tsuji K, Steindler KA (1983) Use of magnesium to increase sensitivity of Limulus amebocyte lysate for detection of endotoxin. Appl Environ Microbiol 45:1342–1350Google Scholar
  24. 24.
    Weary ME, Donohue G, Pearson FC, Story K (1980) Relative potencies of four reference endotoxin standards as measured by the Limulus amebocyte lysate and USP Rabbit Pyrogen Tests. Appl Environ Microbiol 40:1148–1151Google Scholar
  25. 25.
    Levin J, Tomasulo PA, Oser RS (1970) Detection of endotoxin in human blood and demonstration of an inhibitor. J Lab Clin Med 75:903–911Google Scholar
  26. 26.
    Cooperstock MS, Tucker RP, Baublis JV (1975) Possible pathogenic role of endotoxin in Reye's syndrome. Lancet 1:1272–1274Google Scholar
  27. 27.
    Reinhold RB, Fine J (1971) A technique for quantitative measurement of endotoxin in human plasma. Proc Soc Exp Biol Med 137:334–340Google Scholar
  28. 28.
    Stumacher RJ, Kovnat MJ, McCabe WR (1973) Limitations of the usefulness of the Limulus assay for endotoxin. N Engl J Med 288:1261–1264Google Scholar
  29. 29.
    Elin RJ, Robinson RA, Levine AS, Wolff SM (1975) Lack of clinical usefulness of the Limulus test in the diagnosis of endotoxemia. N Engl J Med 293:521–524Google Scholar
  30. 30.
    Harris NS, Feinstein R (1977) A new Limulus assay for the detection of endotoxin. J Trauma 17:714–718Google Scholar
  31. 31.
    Dixon WJ, Mood AM (1946) The statistical sign test. J Am Statist Assoc 41:557–566Google Scholar
  32. 32.
    McNemar Q (1947) Note on sampling error of the differences between correlated proportions or percentages. Psychometrika 12:153–154Google Scholar
  33. 33.
    Feldman S, Pearson TA (1974) The Limulus test and gram-negative bacillary sepsis. Am J Dis Child 128:172–174Google Scholar
  34. 34.
    Elin RJ (1978) Clinical utility of the Limulus test with blood, CSF and synovial fluid. In: Cohen E (ed) Biomedical applications of the horseshoe crab (Limulidae). Alan R Liss, New York, pp 279–292Google Scholar
  35. 35.
    Harris NS, Feinstein R (1977) Relationship of endotoxemia with clinically defined gram-negative septicemia. Surg Forum 28:23–25Google Scholar
  36. 36.
    Garibaldi RA, Allman GW, Larsen DH, Smith CB, Burke JP (1973) Detection of endotoxemia by the Limulus test in patients with indwelling urinary catheters. J Infect Dis 128:551–554Google Scholar
  37. 37.
    Skarnes RC (1966) The inactivation of endotoxin after interaction with certain proteins of normal serum. Ann NY Acad Sci 133:644–662Google Scholar
  38. 38.
    Freudenberg MA, Bøg-Hansen TC, Back U, Galanos C (1980) Interaction of lipopolysaccharides with plasma high-density lipoprotein in rats. Infect Immun 28:373–380Google Scholar
  39. 39.
    Freudenberg MA, Freudenberg N, Galanos C (1982) Time course of cellular distribution of endotoxin in liver, lungs and kidney of rats. Br J Exp Pathol 63:56–65Google Scholar
  40. 40.
    Bränemark PI, Urbaschek B (1967) Endotoxins in tissue injury. Vital microscopic studies on the effect of endotoxin from E. coli on the microcirculation. Angiology 18:667–671Google Scholar
  41. 41.
    Cuevas P, Fine J (1972) Role of intraintestinal endotoxin in death from peritonitis. Surg Gynecol Obstet 134:953–957Google Scholar
  42. 42.
    Levin J (1982) The Limulus test and bacterial endotoxins: some perspectives. In: Watson SW, Levin J, Novitsky TJ (eds) Endotoxins and their detection with the Limulus amebocyte lysate test. Alan R Liss, New York, pp 7–24Google Scholar
  43. 43.
    Andersen BM, Solberg O (1980) The endotoxin-liberating effect of antibiotics on meningococci in vitro. Acta Pathol Microbiol Scand [B] 88:231–236Google Scholar
  44. 44.
    Goto H, Nakamura S (1980) Liberation of endotoxin from Escherichia coli by addition of antibiotics. Jpn J Exp Med 50:35–43Google Scholar
  45. 45.
    Gelfand JA, Elin RJ, Berry FW, Frank MM (1976) Endotoxemia associated with the Jarisch-Herxheimer reaction. N Engl J Med 295:211–213Google Scholar
  46. 46.
    Nolan JP, Camara DS (1982) Endotoxin, sinusoidal cells, and liver injury. In: Popper H, Schaffner F (eds) Progress in Liver Diseases Vol VII. Grune Stratton, New York, pp 361–376Google Scholar
  47. 47.
    Fink PC, Schultze KD (1982) The polyethylene glycol precipitation technique and the particle-counting immunoassay for detection of circulating immune complex-like material in liver cirrhosis and septicemia. J Lab Clin Med 99:852–865Google Scholar
  48. 48.
    Ruiter DJ, v der Meulen J, Wisse E (1980) Some cell biological and pathological aspects of the endotoxin uptake by the liver. In: Liehr H, Grün M (eds) The Reticuloendothelial System and the Pathogenesis of Liver Disease. Elsevier North-Holland Amsterdam, pp 267–277Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • P. C. Fink
    • 1
    • 2
  • J. H. Grunert
    • 1
  1. 1.Klinische Chemie I im Zentrum Laboratoriumsmedizin der Medizinischen Hochschule HannoverGermany
  2. 2.Zentralkrankenhaus, Institut für Laboratoriumsmedizin — ZentrallaborKliniken der Freien Hansestadt BremenBremenBundesrepublik Deutschland

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