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Corticosteroids, nonsteroidal anti-inflammatory drugs, and naloxone in the sepsis syndrome

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Abstract

Corticosteroids have proven to be effective as adjunctive treatment in sepsis and severe typhoid fever when used early and in high doses. If corticosteroids are given in high doses (30 mg/kg), they should be administered in 1–2 doses, and not to exceed 4 total doses within 24 hours. The efficacy of the drug may be diminished in more severe sepsis, but use of corticosteroids in severe sepsis may delay death. If the benefit of corticosteroid use in late sepsis is only to prolong impending death, then steroid administration is probably futile; however, the alternative view is that corticosteroid use may constitute one step in a series leading to shock reversal and recovery. Risks and benefits of corticosteroid use should be tailored to the individual patient with consideration given to the nature and extent of the underlying disease. Although the pathophysiology of the sepsis syndrome remains elusive, new therapeutic regimens may evolve using nonsteroidal anti-inflammatory drugs and neuropeptide antagonists. As with corticosteroids, their application before or early after the onset of shock appears more beneficial; however, the patient population that will benefit most from treatment with these drugs remains, for the most part, unidentified, and more clinical trials are needed.

Résumé

Les corticostéroïdes ont fait leur preuve en tant qu'agent thérapeutique complémentaire quand ils sont employés précocement et à hautes doses dans l'infection et la fièvre typhoïde. Si les corticostéroïdes sont donnés à hautes doses (30 mg/kg), ils doivent être administrés en 1–2 doses et ne jamais dépasser 4 doses par 24 heures. L'efficacité du médicament peut être faible dans les infections graves, il est alors seulement susceptible de retarder le décès. En fait, si l'emploi se limite à ce seul bénéfice, il paraît inutile d'y avoir recours. A l'inverse, la corticothérapie peut représenter une étape utile et efficace du traitement du choc. Les bénéfices et les risques de la corticothérapie doivent être appréciés en fonction de chaque malade et plus particulièrement de la nature et de l'intensité de l'affection dont il est victime. Bien que la physiopathologie du syndrome infectieux reste insaisissable, de nouveaux protocoles thérapeutiques comportant des anti-inflammatoires non stéroïdiens et des antagonistes neuropeptidiques peuvent être employés. Comme pour les corticoïdes leur usage avant ou au début du choc donne les meilleurs résultats. En fait, la population des malades qui peut bénéficier de l'emploi de ces agents médicamenteux n'est pas parfaitement définie et de très nombreux essais cliniques sont indispensables pour définir les meilleures indications.

Resumen

Los corticosteroides han probado ser efectivos como tratamiento adyuvante cuando se utilizan precozmente y en altas dosis en la sepsis y en la fiebre tifoidea grave. Si los corticosteroides son administrados en altas dosis (30 mg/kg), éstos deben darse en 1–2 dosis y no exceder un total de 4 dosis en 24 horas. La eficacia de la droga puede verse disminuida en casos de sepsis mas severa, pero su uso en el estado séptico puede diferir la mortalidad. Si el beneficio del uso de los corticosteroides en sepsis tardía es únicamente el de retardar una muerte inminente, entonces la administración de esteroides sería fútil; sinembargo, la perspectiva alterna es que el uso de corticosteroides constituye un escalón de una serie de eventos que resultan en la reversion del shock y la recuperation. Los riesgos y los beneficios del uso de corticosteroides deben ser ajustados a cada paciente individual con la debida consideración a la naturaleza y gravedad de la enfermedad de base. Aunque la patofisiología del síndrome de sepsis se mantiene elusivo, es previsible que nuevos regimenes terapéuticos puedan ser desarrollados con el uso de drogas anti-inflamatorias no esteroides y antagonistas neuropéptidos. Al igual que con los corticosteroides, su aplicación antes o muy pronto después de la iniciacion del shock parece ser de mayor beneficio; sinembargo, todavía no ha sido posible establecer cual es la población de patientes que se puede beneficiar mayormente de la terapia con estas drogas, y son necesarios mas estudios y ensayos clínicos.

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References

  1. Long, W.M., Pons, G.M., Sprung, C.L.: Metabolic and hormonal responses to injury and sepsis in the critically ill. In Endocrine Aspects of Acute Illness, G.W. Geelhoed, B. Chernow, editors, New York, Churchill Livingstone, 1985, pp. 1–26

    Google Scholar 

  2. Cuthbertson, D.P.: Post-shock metabolic response. Lancet7:433, 1942

    Google Scholar 

  3. Clowes, G.H.A., Vucinic, M., Weidner, M.G.: Circulatory and metabolic alterations associated with survival or death in peritonitis: Clinical analysis of 25 cases. Ann. Surg.163:866, 1966

    Google Scholar 

  4. MacLean, L.D., Mulligan, W.G., McLean, A.P.H., Duff, J.H.: Patterns of septic shock in man—a detailed study of 56 patients. Ann. Surg.166:543, 1967

    Google Scholar 

  5. Siegel, J.H., Greenspan, M., del Guercio, L.R.: Abnormal vascular tone, defective oxygen transport and myocardial failure in human septic shock. Ann. Surg.170:232, 1970

    Google Scholar 

  6. Nishijima, H., Weil, M.H., Shubin, H., Cavanilles, J.: Hemodynamic and metabolic studies on shock associated with gramnegative bacteremia. Medicine52:287, 1973

    Google Scholar 

  7. Siegel, J.H., Goldwyn, R.M., Friedman, H.P.: Pattern and process in the evolution of septic shock. Surgery70:232, 1971

    Google Scholar 

  8. Siegel, J.H.: Pattern and progress in the evaluation of and recovery from shock. In The Aged and High Risk Surgical Patient. Medical, Surgical and Anesthetic Management, J.H. Siegel, P. Chodoff, editors, New York, Grune & Stratton, 1976, p. 381

    Google Scholar 

  9. Hammerschmidt, D.E., White, J.G., Craddock, P.R., Jacob, H.S.: Corticosteroids inhibit complement-induced granulocyte aggregation: A possible mechanism for their efficacy in shock states. J. Clin. Invest.63:798, 1979

    Google Scholar 

  10. Skubitz, K.M., Craddock, P.R., Hammerschmidt, D.E., August, J.T.: Corticosteroids block binding of chemotactic peptide to its receptor on granulocytes and cause disaggregation of granulocyte aggregates in vitro. J. Clin. Invest.68:13, 1981

    Google Scholar 

  11. Sacks, T., Moldow, C.F., Craddock, P.R., Bowers, T.K., Jacob, H.S.: Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes: An in vitro model of immune vascular damage. J. Clin. Invest.61:1161, 1978

    Google Scholar 

  12. Till, G.O., Johnson, K.J., Kanbel, R., Ward, P.A.: Intravascular activation of complement and acute lung injury: Dependency on neutrophils and toxic oxygen metabolites. J. Clin. Invest.69:1126, 1982

    Google Scholar 

  13. Clermont, H.G., Williams, J.S., Adams, J.T.: Steroid effect on the release of lysosomal enzyme phosphatase in shock. Ann. Surg.179:917, 1974

    Google Scholar 

  14. Chi, E.Y., Henderson, W.R., Klebanoff, S.J.: Phospholipase A2-induced rat mast cell arachidonate metabolites. Lab. Invest.47:579, 1982

    Google Scholar 

  15. Herman, A.G.: Introductory remarks about the nomenclature of prostaglandins and their biosynthesis and metabolism. In Cardiovascular Pharmacology of the Prostaglandins, A.G. Herman, P.M. VanHoutte, H. Denolin, A. Goossens, editors, New York, Raven Press, 1982, pp. 1–6

    Google Scholar 

  16. Bult, H., Herman, A.G.: Prostaglandins and circulatory shock. In Cardiovascular Pharmacology of the Prostaglandins, A.G. Herman, P.M. VanHoutte, H. Denolin, A. Goossens, editors, New York, Raven Press, 1982, pp. 327–345

    Google Scholar 

  17. Schein, R.M.H., Long, W.M., Sprung, C.L.: Controversies in the management of sepsis and septic shock: Corticosteroids, naloxone and non-steroidal anti-inflammatory agents. In Perspectives on Sepsis and Septic Shock, W.J. Sibbald, C.L. Sprung, editors, The Society of Critical Care Medicine, 1986, pp. 339–368

  18. Vale, W., Spiess, J., Rivier, C., Rivier, J.: Characterization of a 41 residue ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphin. Science213:1394, 1981

    Google Scholar 

  19. Holaday, J.W., Black, L.E., Long, J.B.: Neuropeptides in shock and trauma. In Endocrine Aspects of Acute Illness, G.W. Geelhoed, B. Chernow, editors, New York, Churchill Livingstone, 1985, pp. 257–284

    Google Scholar 

  20. Weil, M.H., Miller, B.S.: Experimental studies on therapy of circulatory failure produced by endotoxin. J. Lab. Clin. Med.57:683, 1960

    Google Scholar 

  21. White, G.L., Archer, L.T., Beller, B.K., Hinshaw, L.B.: Increased survival with methylprednisolone treatment in canine endotoxin shock. J. Surg. Res.25:357, 1978

    Google Scholar 

  22. Hinshaw, L.B., Beller, B.K., Archer, L.T., Flournoy, D.J., White, G.L., Phillips, R.W.: Recovery from lethalE. coli shock in dogs. Surg. Gynecol. Obstet.149:545, 1979

    Google Scholar 

  23. Coalson, J.J., Benjamin, B.A., Archer, L.T., Beller, B.K., Spaet, R.H., Hinshaw, L.B.: A pathologic study ofEscherichia coli shock in the baboon and the response to adrenocorticosteroid treatment. Surg. Gynecol. Obstet.147:726, 1978

    Google Scholar 

  24. Hinshaw, L.B., Archer, L.T., Beller-Todd, B.K., Coalson, J.J., Flournoy, J., Passey, R., Benjamin, B., White, G.L.: Survival of primates in LD100 septic shock following steroid-antibiotic therapy. J. Surg. Res.28:151, 1980

    Google Scholar 

  25. Hinshaw, L.B., Beller-Todd, B.K., Archer, L.T.: Current management of the septic shock patient: Experimental basis for treatment. Circ. Shock9:543, 1982

    Google Scholar 

  26. Schein, R.M.H., Sprung, C.L.: The use of corticosteroids in the sepsis syndrome. In Critical Care—State of the Art, vol. 7, Society of Critical Care Medicine (in press)

  27. Weitzman, S., Berger, S.: Clinical trial design in studies of corticosteroids for bacterial infections. Ann. Intern. Med.81:36, 1974

    Google Scholar 

  28. Kreger, B.E., Craven, D.E., McCabe, W.R.: Gram-negative bacteremia. IV. Reevaluation of clinical features and treatment in 612 patients. Am. J. Med.68:344, 1980

    Google Scholar 

  29. Sheagren, J.N.: Septic shock and corticosteroids. N. Engl. J. Med.305:456, 1981

    Google Scholar 

  30. Schumer, W.: Steroids in the treatment of clinical septic shock. Ann. Surg.184:333, 1976

    Google Scholar 

  31. Shine, K.I., Kuhn, M., Young, L.S., Tillisch, J.H.: Aspects of the management of shock. Ann. Intern. Med.93:723, 1980

    Google Scholar 

  32. Blaisdell, F.W.: Controversy in shock research: The role of steroids in septic shock. Circ. Shock8:673, 1981

    Google Scholar 

  33. Sprung, C.L., Caralis, P.V., Marcial, E.H., Pierce, M., Gelbard, M.A., Long, W.M., Duncan, R.C., Tendier, M.D., Karpf, M.: The effects of high-dose corticosteroids in patients with septic shock: A prospective, controlled study. N. Engl. J. Med.311:1137, 1984

    Google Scholar 

  34. Hoffman, S.L., Punjabi, N.H., Kumalas, S., Moechtar, M.A., Pulungsih, S.P., Rivai, A.R., Rockhill, R.C., Woodward, T.E., Loedin, A.A.: Reduction of mortality in chloramphenicol treated severe typhoid fever by high-dose dexamethasone. N. Engl. J. Med.310:82, 1984

    Google Scholar 

  35. Bondy, P.K., editor: Metabolic Disease and Control, 8th edition, Philadelphia, W.B. Saunders Co., 1980

    Google Scholar 

  36. Wilson, J.W.: Cellular localization of3H-labeled corticosteroids by electron microscopic autoradiography after hemorrhagic shock. In Steroids and Shock, T.M. Glemm, editor, Baltimore, University Park Press, 1974, pp. 275–299

    Google Scholar 

  37. DeMaria, E.J., Reichman, W., Kenney, P.R., Armitage, J.M., Gann, D.S.: Septic complications of corticosteroid administration after central nervous system trauma. Ann. Surg.202:248, 1985

    Google Scholar 

  38. Weigelt, J.A., Norcross, J.F. Borman, K.R., Snyder, W.H.: Early steroid therapy for respiratory failure. Arch. Surg.120:536, 1985

    Google Scholar 

  39. Sladen, A.: Methylprednisolone. Pharmacologic doses in shock lung syndrome. J. Thorac. Cardiovasc. Surg.71:800, 1976

    Google Scholar 

  40. Sibbald, W.J., Anderson, R.R., Reid, B., Holliday, R.L., Driedger, A.A.: Alveolocapillary permeability in human septic ARDS. Chest79:133, 1981

    Google Scholar 

  41. Sibbald, W.J., Driedger, A.A., Finley, R.J.: High dose corticosteroids in the treatment of pulmonary microvascular injury. Ann. N.Y. Acad. Sci.384:496, 1982

    Google Scholar 

  42. Brigham, K.R., Bowers, R., McKeen, C.: Methylprednisolone prevention of increased lung vascular permeability following endotoxemia in sheep. J. Clin. Invest.67:1103, 1981

    Google Scholar 

  43. Hinshaw, L.B., Solomon, L.A., Erdös, E.G., Reins, B.J.: Effects of acetylsalicylic acid on the canine response to endotoxin. J. Pharmacol. Exp. Ther.157:665, 1967

    Google Scholar 

  44. Halushka, P.V., Wise, W.C., Cook, J.A.: Studies on the beneficial effects of aspirin in endotoxin shock. Am. J. Med.74[Suppl., June 14]:91, 1983

    Google Scholar 

  45. Parratt, J.R., Sturgess, R.M.:E. coli endotoxin shock in the cat; treatment with indomethacin. Br. J. Pharmacol.53:485, 1975

    Google Scholar 

  46. Fletcher, J.R., Ramwell, P.W.: Lidocaine or indomethacin improves survival in baboon endotoxin shock. J. Surg. Res.24:154, 1978

    Google Scholar 

  47. Fletcher, J.R., Ramwell, P.W.:E. coli endotoxin shock in the baboon: Treatment with lidocaine or indomethacin. Adv. Prostaglandin Thromboxane Res.3:183, 1978

    Google Scholar 

  48. Hilton, J.G., Wells, C.H.: Effects of indomethacin and nicotinic acid onE. coli endotoxin shock in anesthetized dogs. J. Trauma16:968, 1976

    Google Scholar 

  49. Tempel, G.E., Cook, J.A., Wise, W.C., Halushka, P.V.: The improvement in endotoxin-induced redistribution of organ blood flow by inhibition of thromboxane and prostaglandin synthesis. Adv. Shock Res.7:209, 1982

    Google Scholar 

  50. Fletcher, J.R., Ramwell, P.W.:E. coli endotoxin shock in the dog; treatment with lidocaine or indomethacin. Br. J. Pharmacol.64:185, 1978

    Google Scholar 

  51. Brigham, K.L., Ogletree, M.L.: Effects of prostaglandins and related compounds on lung vascular permeability. Bull. Europ. Physiopath. Resp.17:703, 1981

    Google Scholar 

  52. Wise, W.C., Cook, J.A., Eller, T., Halushka, P.V.: Ibuprofen improves survival from endotoxic shock in the rat. J. Pharmacol. Exp. Ther.215:160, 1980

    Google Scholar 

  53. Jacobs, E.R., Soulsby, M.E., Bone, R.C., Wilson, F.J. Hiller, F.C.: Ibuprofen in canine endotoxin shock. J. Clin. Invest.70:536, 1982

    Google Scholar 

  54. Bone, R.C., Jacobs, E.R.: Research on ibuprofen for sepsis and respiratory failure. AM. J. Med.77[Suppl. 1A July 13]:114, 1984

    Google Scholar 

  55. Fink, M.P., MacVittie, T.J., Casey, L.C.: Inhibition of prostaglandin synthesis restores normal hemodynamics in canine hyperdynamic sepsis. Ann. Surg.200:619, 1984

    Google Scholar 

  56. Short, B.L., Miller, M.K., Fletcher, J.R.: Improved survival in the suckling rat model of group B streptococcal sepsis after treatment with nonsteroidal anti-inflammatory drugs. Pediatrics70:343, 1982

    Google Scholar 

  57. Snapper, J.R., Hutchinson, A.A., Ogletree, M.L., Brigham, K.L.: Effects of cyclooxygenase inhibitors on the alterations in lung mechanics caused by endotoxemia in the unanesthetized sheep. J. Clin. Invest.72:63, 1983

    Google Scholar 

  58. Goldfarb, R.D., Glenn, T.M.: Regulation of lysosomal membrane stabilization via cyclic nucleotides and prostaglandins: The effects of steroids and indomethacin. In Molecular and Cellular Aspects of Shock and Trauma, A.M. Lefer, W. Schumer, editors, New York, Alan R. Liss, Inc., 1983, pp. 147–166

    Google Scholar 

  59. Butler, R.R., Wise, W.C., Halushka, P.V., Cook, J.A.: Gentamicin and indomethacin in the treatment of septic shock: Effects of prostacyclin and thromboxane A2 production. J. Pharmacol. Exp. Therap.225:94, 1983

    Google Scholar 

  60. Almqvist, P.M., Ekstrom, B., Kuenzig, M., Haglund, U., Schwartz, S.I.: Increased survival of endotoxin-injected dogs treated with methylprednisolone, naloxone and ibuprofen. Circ. Shock14:129, 1984

    Google Scholar 

  61. Wise, W.C., Halushka, P.V., Knapp, R.G., Cook, J.A.: Ibuprofen, methylprednisolone, and gentamicin as conjoint therapy in septic shock. Circ. Shock17:59, 1985

    Google Scholar 

  62. Hughes, G.S.: Naloxone and methylprednisolone sodium succinate enhance sympathomedullary discharge in patients with septic shock. Life Sci.35:2319, 1984

    Google Scholar 

  63. Moncada, S.: Prostacyclin—discovery and biological importance. In Prostaglandins 1984: Research and Clinical Update, Minneapolis, Burgess Publishing Co., 1985, pp. 1–39

    Google Scholar 

  64. Demling, R.H., Smith, M., Gunther, R., Gee, M., Flynn, J.: The effect of prostacycline infusion on endotoxin-induced lung injury. Surgery89:257, 1981

    Google Scholar 

  65. Holaday, J.W., Faden, A.I.: Naloxone reversal of endotoxin hypotension suggests a role of endorphins in shock. Nature275:450, 1978

    Google Scholar 

  66. Peters, W.P., Johnson, M.W., Friedman, P.A., Mitch, W.E.: Pressor effect of naloxone in septic shock. Lancet1:529, 1981

    Google Scholar 

  67. Patton, M.L., Gurll, N.J., Reynolds, D.J., Vargish, T.: Adrenalectomy abolishes and cortisol restores naloxone's beneficial effects on cardiovascular function and survival in canine hemorrhagic shock. Cir. Shock10:317, 1983

    Google Scholar 

  68. Groeger, J.S., Carlon, G.C., Howland, W.S.: Naloxone in septic shock. Crit. Care Med.11:650, 1983

    Google Scholar 

  69. Kaufman, J.J.: Acidosis lowers in vivo potency of narcotics and narcotic antagonists and can even abolish narcotic antagonist activity. Lancet1:559, 1982

    Google Scholar 

  70. Rock, P., Silverman, H., Plump, D., Kecala, Z., Smith, P., Michael, J.R., Summer, W.: Efficacy and safety of naloxone in septic shock. Crit. Care Med.13:28, 1985

    Google Scholar 

  71. Faden, A.I.: Opiate antagonists and thyrotrophic releasing hormone. I. Potential role in the treatment of shock. J.A.M.A.252:1177, 1984

    Google Scholar 

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  1. Section of Critical Care Medicine, Division of General Medicine, Department of Medicine, Veterans Administration Medical Center, University of Miami School of Medicine, Miami, Florida, USA

    William M. Long Ph.D. & Charles L. Sprung M.D.

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Long, W.M., Sprung, C.L. Corticosteroids, nonsteroidal anti-inflammatory drugs, and naloxone in the sepsis syndrome. World J. Surg. 11, 218–225 (1987). https://doi.org/10.1007/BF01656405

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