Clinical Recognition and Treatment of Endotoxinemia

  • Joseph G. Sinkovics
Part of the University of South Florida International Biomedical Symposia Series book series (EMISS, volume 18)

Abstract

In health we co-exist with our bowel flora without harm from lipopoly-saccharide endotoxins that the gram-negative constituents of this flora produce and release. The lower intestinal tract of patients entering hospitals becomes rapidly colonized by the nosocomial gram-negative flora dominant in that environment. Green salads, faucets, the vase holding cut flowers at the bedside serve as common sources of colonization without tissue invasion. Breaking through natural barriers (indwelling arterial and venous lines, genitourinary and other catheters, mucosal ulcerations of the oral cavity and gastrointestinal tract), leukopenia (including granulocyto- and lymphocytopenia and depletion of monocytes-macrophages) allow for invasion of tissues and blood stream by gut flora containing also the colonizing nosocomial bacteria (Pseudomonas sp., Serratia sp.). Absorption of endotoxin from the compromised gastrointestinal or genitourinary tracts may occur without actual bacterial invasion of the blood stream. Gram-negative bacteria invading soft tissues and blood produce and release endotoxins. These endotoxins exert diverse and most profound biological effects often cascading relentlessly toward irreversible shock and death.

Keywords

Dopamine Corticosteroid Lipase Pyruvate Prostaglandin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Reference

  1. 1.
    M. J. Stuart, Effect of endotoxin on arachidonic acid release and thromboxane B2 production of human platelets, Am. J. Hemat. 11: 159 (1981).PubMedCrossRefGoogle Scholar
  2. 2.
    J. A. Cook, W. C. Wise, and P. V. Halushka, Elevated thromboxane levels in the rat during endotoxin shock. Protective effect of imidazole, 13-azaprostanoic acid or essential fatty acid deficiency, J. Clin. Invest. 65: 227 (1980).PubMedCrossRefGoogle Scholar
  3. 3.
    R.-J. Xiu, D. E. Hammerschmidt, P. A. Cappo, and H. S. Jacob, Anisodamine inhibits thromboxane synthesis, granulocyte aggregation and platelet aggregation, JAMA 247: 1458 (1982).PubMedCrossRefGoogle Scholar
  4. 4.
    J. R. Fletcher, P. W. Ramwell, and C. M. Herman, Prostaglandins and hemodynamic course of endotoxin shock, J. Surg. Res. 20: 589 (1976).PubMedCrossRefGoogle Scholar
  5. 5.
    E. L. Howes, M. T. Kwok, and D. G. McKay, The effects of indomethacin on the generalized Shwartzman reaction, Am. J. Pathol. 90: 7 (1978).PubMedGoogle Scholar
  6. 6.
    H. M. Tyler, C.A.P.D. Saxton, and M. J. Parry, Administration to man of UK-37248-01, a selective inhibitor of thromboxan synthetase, Lancet 1: 629 (1981).PubMedCrossRefGoogle Scholar
  7. 7.
    D. C. Morrison and R. J. Ulevitch, The effects of bacterial endotoxin on host mediation systems, Am. J. Pathol. 93: 527 (1978).Google Scholar
  8. 8.
    J. A. Robinson, M. L. Klodnycky, H. S. Loeb, M. R. Racic, and R. M. Gunnar, Endotoxin, prekallikrein, complement and systemic vascular resistance, Am. J. Med. 59: 61 (1975).PubMedCrossRefGoogle Scholar
  9. 9.
    J. G. Sinkovics, Project M26/gm 9: Life-threatening infections (endotoxic shock included) in patients with cancer, Research Report, The University of Texas M.D. Anderson Hospital and Tumor Institute, Houston, Texas (1967 and 1972 ).Google Scholar
  10. 10.
    B. Chernow and J. W. Holaday, The pathogenesis of septic shock, JAMA 252: 208 (1984).PubMedCrossRefGoogle Scholar
  11. 11.
    R. D’Amato and J. W. Holaday, Multiple opioid receptors in endotoxin shock: evidence for δ involvement and μ-δ interactions in vivo, Proc. Nat. Acad. Sci. U.S.A. 81: 2989 (1984).Google Scholar
  12. 12.
    B. Mizock, Septic shock. A metabolic perspective, Arch. Int. Med. 144: 579 (1984).Google Scholar
  13. 13.
    F. M. Torti, B. Dieckmann, B. Beutler, A. Cerami, and G. M. Ringold, A macrophage factor inhibits adipocyte gene expression: an in vitro model of cachexia, Science 229: 867 (1985).PubMedCrossRefGoogle Scholar
  14. 14.
    S. Sassa, M. Kawakami, and A. Cerami, Inhibition of the growth and differentiation of erythroid precursor cells by an endotoxin-induced mediator from peritoneal macrophages, Proc. Nat. Acad. Sci. U.S.A. 80: 1717 (1983).CrossRefGoogle Scholar
  15. 15.
    P. H. Pekala, M. Kawakami, C. W. Angus, and D. Lane, Selective inhibition of synthesis of enzymes for de novo fatty acid biosynthesis by an endotoxin-induced mediator from exudate cells, Proc. Nat. Acad. Sci. U.S.A. 80: 2743 (1983).CrossRefGoogle Scholar
  16. 16.
    B. Beutler, I. W. Milsark, and A. G. Cerami, Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin, Science 229: 869 (1985).PubMedCrossRefGoogle Scholar
  17. 17.
    J. G. Sinkovics, Program M27: Infectious and immunological diseases in patients with cancer, Research Report, The University of Texas, M.D. Anderson Hospital and Tumor Institute, Houston, Texas (1974).Google Scholar
  18. 18.
    S. Passe, V. Mike, R. Mertelsmann, T. Cee, and B. Clarkson, Acute nonlymphoblastic leukemia, Cancer 50: 1462 (1982).PubMedCrossRefGoogle Scholar
  19. 19.
    G. N. Hortobagyi, H.-Y. Yap, C. L. Wiseman, G. R. Blumenschein, A. U. Buzdar, S. S. Legha, J. U. Gutterman, E. M. Hersh, and G. P. Bodey, Chemoimmunotherapy for metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, methotrexate, 1-asparaginase, Corynebacterium parvum, and pseudomonas vaccine, Cancer Treatments Reports 64: 157 (1980).Google Scholar
  20. 20.
    H. Shubin and W. H. Weil, Bacterial shock, JAMA 236: 421 (1976).CrossRefGoogle Scholar
  21. 21.
    M. C. Houston, L. Thompson, and D. Robertson, Diagnosis and management, Arch. Int. Med. 144: 1433 (1984).Google Scholar
  22. 22.
    M. M. Parker and J. E. Parrillo, Septic shock: hemodynamics and pathogenesis, JAMA 250: 3324 (1983).PubMedCrossRefGoogle Scholar
  23. 23.
    M. M. Parker, J. H. Shelhamer, S. L. Bacharach, M. V. Green, C. Natanson, T. M. Frederick, B. Damske, and J. E. Parrillo, Profound but reversible myocardial depression in patients with septic shock, Ann. Int. Med. 100: 483 (1984).PubMedGoogle Scholar
  24. 24.
    R. McConn, J. K. Greineder, F. Wasserman, and G.H.J. Clowes, Is there a humoral factor that depresses ventricular function in sepsis? Circ. Shock Sl: 22 (1979).Google Scholar
  25. 25.
    T. R. Poskitt, and P. K. F. Poskitt, Thrombocytopenia of sepsis. The role of circulating IgG-containing immune complexes, Arch. Int. Med. 145: 891 (1985).Google Scholar
  26. 26.
    L. Thomas and R. A. Good, Studies of the generalized Shwartzman reaction. I. General observations concerning the phenomenon, J. Exp. Med. 96: 605 (1952).Google Scholar
  27. 27.
    R. A. Good and L. Thomas, Studies on the generalized Shwartzman reaction. IV. Prevention of the local and generalized Shwartzman reaction with heparin, J. Exp. Med. 97: 871 (1953).PubMedCrossRefGoogle Scholar
  28. 28.
    W. R. McCage, Serum complement levels in bacteremia due to gram-negative organisms, New Eng. J. Med. 288: 21 (1973).CrossRefGoogle Scholar
  29. 29.
    C. A. Stetson and R. A. Good, Studies on the mechanism of the Shwartzman phenomenon. Evidence for the participation of polymorphonuclear leukocytes in the phenomenon, J. Exp. Med. 93: 49 (1951).PubMedCrossRefGoogle Scholar
  30. 30.
    J.S.C. Fong and R. A. Good, Prevention of the localized and generalized Shwartzman reaction by an anticomplementary agent, cobra venom factor, J. Exp. Med. 134: 642 (1971).PubMedCrossRefGoogle Scholar
  31. 31.
    J. G. Sinkovics, Infectious complications of cancer, J. Inter-American Med. 4: 10 (1979).Google Scholar
  32. 32.
    O. Nowel, J. Bernuau, B. Rueff, and J.-P.Benbamou, Hypoglycemia, a common complication of septicemia in cirrhosis, Arch. Int Med. 141: 1477 (1981).CrossRefGoogle Scholar
  33. 33.
    A. Cortez, J. Zito, C. E. Lucas, and S. J. Gerrick, Mechanism of in appropriate polyuria in septic patients, Arch. Surg. 112: 471 (1977).Google Scholar
  34. 34.
    W. L. Henrick, D. Prophet, and J. P. Knochel, Rhabdomyolysis associated with Escherichia coli septicemia, South Med. J. 73: 936 (1980).Google Scholar
  35. 35.
    S. B. Kalish, M. S. Tallman, F. V. Cook, and E. A. Blumen, Polymicrobial septicemia associated with rhabdomyolysis, myoglobinuria and acute renal failure, Arch. Int. Med. 1142: 133 (1982).Google Scholar
  36. 36.
    L. B. Pemberton, Shock lung with massive tracheal loss of plasma, JAMA 237: 2511 (1977).PubMedCrossRefGoogle Scholar
  37. 37.
    J. G. Sinkovics, “Medical Oncology. An Advanced Course,” 2nd Edition, Marcel Dekker, New York (1986).Google Scholar
  38. 38.
    D. Cavanaugh, Septic shock in a pregnant or recently pregnant woman, Postgrad. Med. 62: 62 (1977).Google Scholar
  39. 39.
    R. C. Tarazi, Sympathomimetic agents in the treatment of shock, Ann. Int. Med. 81: 364 (1974).PubMedGoogle Scholar
  40. 40.
    S. Weitzman and S. Berger, Clinical trial design in studies of corticosteroids for bacterial infections, Ann. Int. Med. 81: 36 (1974).PubMedGoogle Scholar
  41. 41.
    J. G. Sinkovics, Severe infectious complications in patients with treated neoplasms, Abstracts XIIIth International Congress of Internal Medicine (1976).Google Scholar
  42. 42.
    J. Klastersky, R. Cappel, and L. Debusscher, Effectiveness of betamethasone in management of severe infections, New Eng. J. Med. 284: 1248 (1971).CrossRefGoogle Scholar
  43. 43.
    W. Schumer, Steroids in the treatment of clinical septic shock, Ann. Surg. 184: 333 (1976).PubMedCrossRefGoogle Scholar
  44. 44.
    J. N. Sheagren, Septic shock and corticosteroids, New Eng. J. Med. 305: 456 (1981).Google Scholar
  45. 45.
    E. H. Kass, High dose corticosteroids for septic shock, New Eng. J. Med. 311: 1178 (1984).CrossRefGoogle Scholar
  46. 46.
    L. B. Hinshaw, Corticosteroids for septic shock, New Eng. J. Med. 312: 510 (1985).Google Scholar
  47. 47.
    C. L. Sprung, P. V. Caralis, E. H. Marcial, M. A. Gelbard, and R. C. Duncan, Corticosteroids for septic shock, New Eng. J. Med. 312: 511 (1985).Google Scholar
  48. 48.
    M. Tapper and D. Armstrong, Bacteremia due to Pseudomonas aeruginosa complicating neoplastic disease: a progress report, J. Inf. Dis. 130 (1974).Google Scholar
  49. 49.
    W. Schumer, Corticosteroid treatment of septic shock, JAMA 253: 3165 (1985).CrossRefGoogle Scholar
  50. 50.
    M. Piccart, J. Klastersky, F. Meunier, H. Lagast, Y. VanLaethem, and D. Weerts, Single drug versus combination empirical therapy for gram-negative bacillary infections in febrile cancer patients with and without granulocytopenia, Antimicrob. Ag. Chemother. 26: 870 (1984).Google Scholar
  51. 51.
    P. A. Pizzo, J. Commers, D. Cotton, J. Gress, J. Hathorn, J. Hiemenz, D. Longo, D. Marshall, and K. J. Robichaud, Approaching the controversies in antibacterial management of cancer patients, Am. J. Med. 76: 436 (1984).PubMedCrossRefGoogle Scholar
  52. 52.
    G. P. Bodey, Antibiotics in patients with neutropenia, Arch. Int. Med. 144: 1845 (1984).Google Scholar
  53. 53.
    V. Fainstein, G. P. Bodey, R. Bolivar, L. Elting, KoB. McCredie, and J.J. Keating, Moxalactam plus ticarcillin or tobramycin for treatment of febrile episodes in neutropenic cancer patients, Arch. Int. Med. 144: 1766 (1984).Google Scholar
  54. 54.
    L. Jadeja, R. Bolivar, V. Fainstein, M. Keating, K. McCredie, M. Hay, and G. P. Bodey, Piperacillin plus vancomycin in the therapy of febrile episodes in cancer patients, Antimicrob. Ag. Chemother. 26: 295 (1985).Google Scholar
  55. 55.
    R. Feld, T. J. Louie, L. Mandell, E. J. Bow, H. G. Robson, A. Chow, A. Belch, L. Miedzinski, A. Rochlis, Y. Pater, and A. Willan, A multi-center comparative trial of tobramycin and ticarcillin vs. moxalactam and ticarcillin in febrile neutropenic patients, Arch. Int. Med. 145: 1083 (1985).CrossRefGoogle Scholar
  56. 56.
    C. R. Smith, R. Ambinder, J. J. Lipsky, B. G. Petty, E. Israel, R. Levitt, E. D. Mellits, L. Rocco, J. Longstreth, and P. S. Lietman, Cefotaxime compared with nafcillin plus tobramycin for serious bacterial infections, Ann. Int. Med. 101: 469 (1984).PubMedGoogle Scholar
  57. 57.
    V. Fainstein, Treatment in the U.S. cancer referral center vs. the community-based facility, in: “Infections in the Cancer Patient: Antimicrobial Therapy Today,” Health Projects International and Glaxo Pharmaceuticals, San Diego (1985).Google Scholar
  58. 58.
    R. Ramphai, B. S. Kramer, and K. H. Rand, Comparison of ceftazidime versus cephalothin-gentamicin-carbenicillin versus ceftazidime plus vancomycin in febrile granulocytopenic patients, in: “Infections in the Cancer Patient: Antimicrobial Therapy Today,” Health Projects International and Glaxo Pharmaceuticals, San Diego (1985).Google Scholar
  59. 59.
    J. Joshi and S. O. Schimpff, Empiric antibiotic therapy for febrile granulocytopenic cancer patients: double β-lactam vs. β-lactam-aminoglycoside regimen that suppresses or preserves alimentary canal anaerobes, in: “Infections in the Cancer Patient: Antimicrobial Therapy Today,” Health Projects International and Glaxo Pharmaceuticals, San Diego (1985).Google Scholar
  60. 60.
    Editorial, Host responses in gram-negative septicemia, Lancet 2: 693 (1982).Google Scholar
  61. 61.
    E. J. Ziegler, J. A. McCutchan, J. Fierer, M. P. Glauser, J. C. Sadoff, H. Douglas, and A. I. Braude, Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli, New Eng. J. Med. 307: 1225 (1982).CrossRefGoogle Scholar
  62. 62.
    J. A. McClutchan and E. J. Ziegler, Treatment with anti-gram-negative antibodies, Lancet 2: 802 (1983).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Joseph G. Sinkovics
    • 1
    • 2
  1. 1.Community Cancer CenterSt, Joseph’s Hospital and University of South Florida College of MedicineTampaUSA
  2. 2.Department of Virology and EpidemiologyBaylor College of MedicineHoustonUSA

Personalised recommendations