Use of Corticosteroids in the Severely Ill Patient

  • M. Antonelli
  • M. Passariello
Conference paper


Besides primary and secondary adrenal insufficiency, many medical conditions benefit from the use of corticosteroids because of their anti-inflammatory and immunosuppressive activity. Several mechanisms are involved in the suppression of inflammation by the glucocorticoids, and many remain to be elucidated. Glucocorticoids inhibit the recruitment of leukocytes and monocyte-macrophages into affected areas and the synthesis of a great variety of chemotactic substances and other factors that mediate increased capillary permeability, vasodilatation, and contraction of various nonvascular smooth muscles. All natural and synthetic glucocorticoids act by binding a specific cytoplasmic glucocorticoid receptor. The complex glucocorticoid receptor has the ability to enter the nucleus of the cell and bind specific sites of DNA and control transcription of glucocorticoid-regulated genes. At present the list of substances whose synthesis or release is inhibited by glucocorticoids includes arachidonic acid and its metabolites (prostaglandins and leukotrienes), platelet activating factor (PAF), the nitric-oxide pathway, tumor necrosis factor (TNF) and many interleukins. Glucocorticoids can thus control the synthesis or release of substances involved in onset and evolution of inflammation [1–7].


Septic Shock Acute Respiratory Distress Syndrome Bacterial Meningitis Platelet Activate Factor Typhoid Fever 
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  1. 1.
    Packard BD, Weiler JM (1983) Steroids inhibit activation of the alternative amplification pathway of complement. Infect Immunol 40: 1011–1019Google Scholar
  2. 2.
    Moncada S, Higgs A (1993) The L-arginine-nitric oxide pathwway. N Eng J Med 329: 20022012Google Scholar
  3. 3.
    Hammerschmidt DE, White JG, Graddock PR et al (1979) Corticosteroids inhibit complement-induced granulocyte aggregation: A possible mechanism for their efficacy in shock states. J Clin Invest 63: 798–893Google Scholar
  4. 4.
    Skubits KM, Craddock LR, Hammerschmidt DE et al (1981) Corticosteroids block binding of chemotactic peptide to its receptor on granulocytes and cause disaggregation of granulocyte aggregates in vitro. J Clin Invest 68: 13–20CrossRefGoogle Scholar
  5. 5.
    Dhainaut JF, Mira JP (1993) The role of platelet activating factors in sepsis. In: Gartner JD, Calandra T, Carlet J (Eds) Mediators of sepsis: From pathophysiology to therapeutic approaches. Maurice Rapid Colloquia. Baum, Paris, FlammarionGoogle Scholar
  6. 6.
    Beutler B, Krochin N, Milsark I et al (1986) Control of cachectin (tumor necrosis factor) synthesis: Mechanisms of endotoxin resistance. Science 232: 977–980Google Scholar
  7. 7.
    Parant M, Le Contel C, Parant F et al (1991) Influence of endogenous glucocorticoid on endotoxin-induced production of circulating TNF-alpha. Lymphokine Cytokine Res 10: 265–271PubMedGoogle Scholar
  8. 8.
    Hahn EC, House HB, Rammelkamp CH et al (1951) Effect of cortisone on acute streptococcal infections and post-streptococcal complications. J Clin Invest 30: 274–281PubMedCrossRefGoogle Scholar
  9. 9.
    Bennet IL, Finland M, Hamburger M et al (1963) The effectiveness of hydrocortisone in the management of severe infections. JAMA 183: 462–465CrossRefGoogle Scholar
  10. 10.
    Schumer W (1976) Steroids in the treatment of clinical septic shock (1963). Ann Surg 184: 333–339PubMedCrossRefGoogle Scholar
  11. 11.
    Sprung CL, Caralis PV, Marcial EH et al (1984) The effect of high dose corticosteroids in patients with septic shock. N Eng J Med 311: 1137–1143CrossRefGoogle Scholar
  12. 12.
    The Veterans Administration Systemic Sepsis Cooperative Study Group (1987) Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of sepsis. N Eng J Med 317: 659–665Google Scholar
  13. 13.
    Bone RC, Fisher CJ, Clemmer TP et al (1987) A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Eng J Med 317: 653–658CrossRefGoogle Scholar
  14. 14.
    Luce JM, Montgomery AB, Marks JD et al (1988) Ineffectiveness of high-dose methylprednisolone therapy in preventing parenchymal lung injury and improving mortality in patients with septic shock. Am Rev Resp Dis 138: 62–68PubMedCrossRefGoogle Scholar
  15. 15.
    McGowan JE, Chesney PJ, Crossley KB et al (1992) Guidelines for the use of systemic glucocorticoids in the management of selected infections. J Infect Dis 165: 1–13PubMedCrossRefGoogle Scholar
  16. 16.
    Havens PL, Wendelberg KJ, Hoffmann GM (1989) Corticosteroids as adjunctive therapy in bacterial meningitis. Am J Dis Child 143: 1051–1055PubMedGoogle Scholar
  17. 17.
    Lebel MH, Freij BJ, Syrogiannopulos GA et al (1988) Dexamethasone therapy for bacterial meningitis. N Eng J Med 319: 964–971CrossRefGoogle Scholar
  18. 18.
    Odio CM, Fainzegicht I, Paris M et al (1991) The beneficial effect of early dexamethasone administration in infants and children with bacterial meningitis. N Eng J Med 324: 1525–1531CrossRefGoogle Scholar
  19. 19.
    Hoffman SL, Punjabi NH, Kumala S et al (1984) Reduction of mortality in the chloramphenicol-treated severe typhoid fever by high-dose dexamethasone. N Eng J Med 310: 82–88CrossRefGoogle Scholar
  20. 20.
    Ajao OG, Ajao A, Johnson T (1984) Methylprednisolone sodium succinate in the treatment of typhoid perforation. Trans R Soc Trop Med Hyg 78: 573–576PubMedCrossRefGoogle Scholar
  21. 21.
    Gagnon S, Boota AM, Fischl MA et al (1990) Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A double-blind, placebo-controlled trial. N Eng J Med 323: 1444–1450Google Scholar
  22. 22.
    The National Institute of Health–University of California Expert Panel for Corticosteroids as Adjunctive Therapy for Pneumocystis Pneumonia (1990) Consensus statement on the use of corticosteroids as adjunctive therapy for Pneumocystis pneumonia in the acquired immunodeficiency syndrome. N Eng J Med 323: 1500–1504Google Scholar
  23. 23.
    Lefering R, Neugebauer EAM (1995) Steroid controversy in sepsis and septic shock: A meta-analysis. Crit Care Med 23: 1294–1303Google Scholar
  24. 24.
    Cronin L, Cook DJ, Carlet J et al (1995) Corticosteroid treatment for sepsis: A critical appraisal and meta-analysis of the literature. Crit Care Med 23: 1430–1439Google Scholar
  25. 25.
    Lamberts SWJ, Bruining HA, De Jong FH (1997) Corticosteroid therapy in severe illness. N Eng J Med 337: 1285–1292CrossRefGoogle Scholar
  26. 26.
    Rothwell PM, Udwadia ZF, Lawler PG (1991) Cortisol response to corticotropin and survival in septic shock. Lancet 337: 582–583PubMedCrossRefGoogle Scholar
  27. 27.
    Moran JL, Chapman MJ, O’Fathartaigh MS et al (1995) Hypocortisolemia and adrenocortical responsiveness at onset of septic shock. Intensive Care Med 20: 489–495CrossRefGoogle Scholar
  28. 28.
    Soni A, Pepper GM, Wyrwinski PM et al (1995) Adrenal insufficiency occurring during septic shock: Incidence, outcome and relationship to peripheral cytokine levels. Am J Med 98: 266–271Google Scholar
  29. 29.
    Drucker D, Shandling M (1985) Varial adrenocortical function in acute medical illness. Crit Care Med 13: 477–479PubMedCrossRefGoogle Scholar
  30. 30.
    Jurney TH, Cockrell JL Jr, Lindberg JS et al (1987) Spectrum of serum cortisol response to ACTH in ICU patients: correlation with degree of illness and mortality. Chest 92: 292–295PubMedCrossRefGoogle Scholar
  31. 31.
    Sainsbury JR, Stoddart JC, Watson MJ (1981) Plasma cortisol levels: a comparison between sick patients and volunteers given intravenous cortisol. Anaesthesia 36: 16–21PubMedCrossRefGoogle Scholar
  32. 32.
    Bouachour G, Tirot P, Gouello JP et al (1995) Adrenocortical function during septic shock. Intensive Care Med 21: 57–62PubMedCrossRefGoogle Scholar
  33. 33.
    Bouachour G, Roy PM, Guiraud MP (1995) The repetitive short corticotropin stimulation test in patients with septic shock. Ann Intern Med 123: 962PubMedGoogle Scholar
  34. 34.
    Briegel J, Forst H, Hellinger H et al (1991) Contribution of cortisol deficiency during septic shock. Lancet 338: 507–508PubMedCrossRefGoogle Scholar
  35. 35.
    Schneider AJ, Voerman HJ (1991) Abrupt hemodynamic improvement in late septic shock with physiologic doses of glucocorticoids. Intensive Care Med 17: 436–437PubMedCrossRefGoogle Scholar
  36. 36.
    Bollaert PE, Charpentier C, Levy B et al (1998) Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med 26: 645–650PubMedCrossRefGoogle Scholar
  37. 37.
    Barnes PJ (1995) Beta-adrenergic receptors and their regulation. Am J Resp Crit Care Med 152: 838–860PubMedGoogle Scholar
  38. 38.
    Walker BR, Williams BC (1992) Corticosteroids and vascular tone: Mapping the messenger maze. Clin Sci 82: 597–605Google Scholar
  39. 39.
    Colucci WS, Wright RF, Braunwald E (1985) New positive inotropic agents in the treatment of congestive heart failure. N Eng J Med 314: 290–296CrossRefGoogle Scholar
  40. 40.
    Spitzer JA, Rodriguez de Turco EB, Deauciuc IV et al (1989) Receptor changes in endotoxemia. In: Passmore JC (ed) Perspectives in shock research. Liss, New York, pp 95–106Google Scholar
  41. 41.
    Sibley DR, Lefkovitz RJ (1985) Molecular mechanisms of receptor desensitization using the beta-adrenergic receptor-coupled adenylate cyclase system as a model. Nature 317: 124–129PubMedCrossRefGoogle Scholar
  42. 42.
    Colucci WS, Alexander RW, Williams GH, Braunwald E (1981) Decreased lymphocyte betaadrenergic-receptor density in patients with heart failure and tolerance to the beta-adrenergic agonist pirbuterol. N Eng J Med 305: 185–190CrossRefGoogle Scholar
  43. 43.
    Collins S, Caron MG, Lefkowits RJ (1988) Beta-adrenergic receptors in hamster smooth muscle cells are transcriptionally regulated by glucocorticoids. J Biol Chem 263: 9067–9070PubMedGoogle Scholar
  44. 44.
    Saito T, Takanashi M, Gallagher E et al (1995). Corticosteroid effect on early beta-adrenergic down-regulation during circulatory shock: hemodynamic study and beta-adrenergic receptor essay. Intensive Care Med 21: 204–210PubMedCrossRefGoogle Scholar
  45. 45.
    Asbaugh DG, Bigelow DB, Petty TL, Levine BE (1967) Acute respiratory distress in adults. Lancet 2: 319–323CrossRefGoogle Scholar
  46. 46.
    McConn R, Del Guercio LRM (1971) Respiratory function of blood in the acutely ill patient and the effect of steroids. Ann Surg 174: 436–450PubMedCrossRefGoogle Scholar
  47. 47.
    Lozman J, Dutton RE, English M, Powers SR (1975) Cardiopulmonary adjustments following single high dose administration of methylprednisolone in traumatized man. Ann Surg 181: 317PubMedCrossRefGoogle Scholar
  48. 48.
    Kusaijma K, Wax SD, Web WR (1974) Effects of methylprednisolone on pulmonary micro-circulation. Surg Gynecol & Obstet 139: 1Google Scholar
  49. 49.
    Bowers R, Brigham KL (1978) Methylprednisolone prevents endotoxin induced high lung vascular permeability in the awake sheep. Clin Res 444Google Scholar
  50. 50.
    Sladen A (1976) Methylprednisolone: pharmacologic dose in shock lung syndrome. J Thorac Cardiovasc Surg 71: 800–806PubMedGoogle Scholar
  51. 51.
    Lucas CE, Ledgerwood AM (1981) Pulmonary response of massive steroids in seriously injured patients. Ann Surg 194: 256–261PubMedCrossRefGoogle Scholar
  52. 52.
    Sibbald WJ, Anderson RR, Reid B et al (1981) Alveolo-capillary permeability in human septic ARDS: effect of high dose corticosteroid therapy. Chest 79: 133–142PubMedCrossRefGoogle Scholar
  53. 53.
    Weigelt JA, Norcross JF, Borman KR, Snyder WH (1985) Early steroid therapy for respiratory failure. Arch Surg 120: 536–540PubMedCrossRefGoogle Scholar
  54. 54.
    Bernard GR, Luce JM, Sprung CL et al (1987) High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Eng J Med 317: 1565–1570CrossRefGoogle Scholar
  55. 55.
    Elias JA, Freundlich B, Kern JA, Rosenbloom J (1990) Cytokine networks in the regulation of inflammation and fibrosis in the lung. Chest 97: 1439–1445PubMedCrossRefGoogle Scholar
  56. 56.
    Raponi GM, Antonelli M, Gaeta A et al (1992) Tumor necrosis factor in serum and bronchoalveolar lavage of patients at risk for ARDS. J Crit Care 7: 183–188CrossRefGoogle Scholar
  57. 57.
    Meduri GU, Headley S, Kohler G et al (1995) Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-lbeta and IL-6 levels are consistent and efficient predictors of outcome over time. Chest 107: 1062–1073PubMedCrossRefGoogle Scholar
  58. 58.
    Antonelli M, Raponi GM, Martino P et al (1995) High IL-6 serum levels are associated with septic shock and mortality in septic patients with severe leukopenia due to hematological malignancies. Scand J Infect Dis 27: 381–384PubMedCrossRefGoogle Scholar
  59. 59.
    Montgomery AB, Stager MA, Carrico CJ, Hudson LD (1985) Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 132: 485–489PubMedGoogle Scholar
  60. 60.
    Meduri GU, Belenchia JM, Estes RJ et al (1991) Fibroproliferative phase of ARDS. Clinical findings and effects of corticosteroids. Chest 100: 943–952Google Scholar
  61. 61.
    Meduri GU, Chinn AJ, Leeper KV et al (1994) Corticosteroid rescue treatment of progressive fibroproliferation in late ARDS. Patterns of response and predictors of outcome. Chest 105: 1516–1527Google Scholar
  62. 62.
    Meduri GU, Headley S, Tolley E et al (1995) Plasma and BAL cytokine response to corticosteroid rescue treatment in late ARDS. Chest 108: 1315–1325PubMedCrossRefGoogle Scholar
  63. 63.
    Meduri GU, Headley, Golden E, Carson SJ (1998) Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome. A randomized clinical trial. JA-MA; 280: 159–165Google Scholar

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© Springer-Verlag Italia 2000

Authors and Affiliations

  • M. Antonelli
  • M. Passariello

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