Abstract
For more than five decades, the use of corticosteroids as an adjunctive therapy to treat severe sepsis and septic shock has incited consistent debate. Negative results of the Corticosteroid Therapy of Septic Shock (CORTICUS) study evoked a revision of Surviving Sepsis Campaign guidelines suggesting a more restricted use of low-dose hydrocortisone only in patients with severe septic shock. Hemodynamic improvement by low-dose steroids was evident and independent from adrenal insufficiency, but did not improve survival. The roles of cortisol measurement and adrenal function tests for treatment decisions have been questioned. An international task force introduced the concept of critical illness-related corticosteroid insufficiency, which challenges the predominant role of adrenal dysfunction and underscores sustained inflammation due to tissue steroid resistance. Whether moderate steroid doses induce superinfections and muscle weakness is unclear. This article reviews recent publications, actual recommendations, ongoing discussions, and future perspectives.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References and Recommended Reading
Lefering R, Neugebauer EA: Steroid controversy in sepsis and septic shock: a meta-analysis. Crit Care Med 1995, 23:1294–1303.
Annane D, Bellissant E, Bollaert PE, et al.: Corticosteroids for treating severe sepsis and septic shock. Cochrane Database Syst Rev 2004, CD002243.
Minneci PC, Deans KJ, Banks SM, et al.: Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med 2004, 141:47–56.
Dellinger RP, Levy MM, Carlet JM, et al.: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 2008, 34:17–60.
Marik PE, Pastores SM, Annane D, et al.: Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med 2008, 36:1937–1949.
Dellinger RP, Carlet JM, Masur H, et al.: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med 2004, 30:536–555.
Annane D, Sebille V, Charpentier C, et al.: Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002, 288:862–871.
Cooper MS, Stewart PM: Adrenal insufficiency in critical illness. J Intensive Care Med 2007, 22:348–362.
Annane D, Sebille V, Troche G, et al.: A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 2000, 283:1038–1045.
Annane D, Maxime V, Ibrahim F, et al.: Diagnosis of adrenal insufficiency in severe sepsis and septic shock. AmJ Respir Crit Care Med 2006, 174:1319–1326.
Huh JW, Lim CM, Koh Y, Hong SB: Effect of low doses of hydrocortisone in patients with septic shock and relative adrenal insufficiency: 3 days versus 7 days treatment [abstract]. Crit Care Med 2006, 34:A101.
Sprung CL, Annane D, Keh D, et al.: Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008, 358:111–124.
Arafah BM: Hypothalamic pituitary adrenal function during critical illness: limitations of current assessment methods. J Clin Endocrinol Metab 2006, 91:3725–3745.
Eichacker PQ, Parent C, Kalil A, et al.: Risk and the efficacy of antiinflammatory agents: retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med 2002, 166:1197–1205.
Li Y, Cui X, Li X, et al.: Risk of death does not alter the efficacy of hydrocortisone therapy in a mouse E. coli pneumonia model: risk and corticosteroids in sepsis. Intensive Care Med 2008, 34:568–577.
Cicarelli DD, Vieira JE, Bensenor FE: Early dexamethasone treatment for septic shock patients: a prospective randomized clinical trial. Sao Paulo Med J 2007, 125:237–241.
Mikami K, Suzuki M, Kitagawa H, et al.: Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization. Lung 2007, 185:249–255.
Meduri GU, Yates CR: Systemic inflammation-associated glucocorticoid resistance and outcome of ARDS. Ann N Y Acad Sci 2004, 1024:24–53.
Meduri GU, Muthiah MP, Carratu P, et al.: Nuclear factor-kappaB-and glucocorticoid receptor alpha-mediated mechanisms in the regulation of systemic and pulmonary inflammation during sepsis and acute respiratory distress syndrome. Evidence for inflammation-induced target tissue resistance to glucocorticoids. Neuroimmunomodulation 2005, 12:321–338.
Bornstein SR, Chrousos GP: Clinical review 104: adrenocorticotropin (ACTH)-and non-ACTH-mediated regulation of the adrenal cortex: neural and immune inputs. J Clin Endocrinol Metab 1999, 84:1729–1736.
Confalonieri M, Urbino R, Potena A, et al.: Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit Care Med 2005, 171:242–248.
Meduri GU, Golden E, Freire AX, et al.: Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest 2007, 131:954–963.
Steinberg KP, Hudson LD, Goodman RB, et al.: Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006, 354:1671–1684.
Meduri GU, Headley AS, Golden E, et al.: Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA 1998, 280:159–165.
Annane D, Sebille V, Bellissant E: Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome. Crit Care Med 2006, 34:22–30.
Meduri GU, Marik PE, Chrousos GP, et al.: Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature. Intensive Care Med 2008, 34:61–69.
Agarwal R, Nath A, Aggarwal AN, Gupta D: Do glucocorticoids decrease mortality in acute respiratory distress syndrome? A meta-analysis. Respirology 2007, 12:585–590.
Peter JV, John P, Graham PL, et al.: Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis. BMJ 2008, 336:1006–1009.
Oppert M, Schindler R, Husung C, et al.: Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock. Crit Care Med 2005, 33:2457–2464.
Hermans G, Wilmer A, Meersseman W, et al.: Impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive care unit. AmJ RespirCrit Care Med 2007, 175:480–489.
Kellum JA, Kong L, Fink MP, et al.: Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med 2007, 167:1655–1663.
Yende S, D’Angelo G, Kellum JA, et al.: Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis. Am J Respir Crit Care Med 2008, 177:1242–1247.
Keh D, Boehnke T, Weber-Carstens S, et al.: Immunologic and hemodynamic effects of “low-dose” hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med 2003, 167:512–520.
Briegel J, Kellermann W, Forst H, et al.: Low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome. The Phospholipase A2 Study Group. Clin Investig 1994, 72:782–787.
Van den Berghe G, Wouters P, Weekers F, et al.: Intensive insulin therapy in the critically ill patients. N Engl J Med 2001, 345:1359–1367.
Van den Berghe G, Wilmer A, Hermans G, et al.: Intensive insulin therapy in the medical ICU. N Engl J Med 2006, 354:449–461.
Brunkhorst FM, Engel C, Bloos F, et al.: Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008, 358:125–139.
Krinsley JS: Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc 2004, 79:992–1000.
Krinsley JS: Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. Mayo Clin Proc 2003, 78:1471–1478.
Finney SJ, Zekveld C, Elia A, Evans TW: Glucose control and mortality in critically ill patients. JAMA 2003, 290:2041–2047.
Egi M, Bellomo R, Stachowski E, et al.: Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology 2006, 105:244–252.
Annane D, Bellissant E, Bollaert PE, et al.: Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ 2004, 329:480.
Loisa P, Parviainen I, Tenhunen J, et al.: Effect of mode of hydrocortisone administration on glycemic control in patients with septic shock: a prospective randomized trial. Crit Care 2007, 11:R21.
Weber-Carstens S, Deja M, Bercker S, et al.: Impact of bolus application of low-dose hydrocortisone on glycemic control in septic shock patients. Intensive Care Med 2007, 33:730–733.
Ahlers O, Sprung CL, Briegel J, et al.: Immune effects of hydrocortisone in septic shock: results from the CORTICUS Berlin Study Group. Intensive Care Med 2007, 33:S5.
De Jonghe B, Sharshar T, Lefaucheur JP, et al.: Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA 2002, 288:2859–2867.
Bolton CF: Neuromuscular manifestations of critical illness. Muscle Nerve 2005, 32:140–163.
Huang CJ, Lin HC: Association between adrenal insufficiency and ventilator weaning. Am J Respir Crit Care Med 2006, 173:276–280.
Alberti C, Brun-Buisson C, Goodman SV, et al.: Influence of systemic inflammatory response syndrome and sepsis on outcome of critically ill infected patients. Am J Respir Crit Care Med 2003, 168:77–84.
Bone RC, Fisher CJJ, Clemmer TP, et al.: A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 1987, 317:653–658.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Keh, D., Weber-Carstens, S. & Ahlers, O. Adjunctive therapies in severe sepsis and septic shock: Current place of steroids. Curr Infect Dis Rep 10, 354–361 (2008). https://doi.org/10.1007/s11908-008-0058-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11908-008-0058-z