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Glucocorticoids in sepsis: dissecting facts from fiction

Dr Marik's recent commentary [1] states that " a result of an overwhelming selection bias, only approximately 5% of eligible patients were enrolled in the CORTICUS study [2]." As its authors, we are unaware as to what constitutes this overwhelming bias and from where he has plucked a figure of 5%. CORTICUS enrolled patients with clinical evidence of infection, systemic inflammatory response syndrome, shock within 72 hours (defined by a systolic blood pressure <90 mmHg despite adequate fluid replacement OR need for vasopressors for ≥1 hour), and hypoperfusion or organ dysfunction attributable to sepsis [2]. The placebo group received a maximum norepinephrine dose of 0.4 ± 0.5 mcg/kg/minute and their 28-day mortality was 31.5%. We openly acknowledged that slow recruitment was partly related to loss of equipoise; however, the above data not only appear representative of real life practice but are comparable to other contemporary septic shock studies, for example, VASST [3]. His contention that 7 to 10 days of low-dose hydrocortisone should be considered in patients receiving norepinephrine or equivalent at doses >0.1 mcg/kg/minute within 12 hours of shock onset is not supported by any evidence base, contradicts presently accepted international recommendations [4] and portrays a far more striking example of bias.


  1. Marik PE: Glucocorticoids in sepsis: dissecting facts from fiction. Crit Care 2011, 15: 158. 10.1186/cc10101

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  2. Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J: Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008, 358: 111-124. 10.1056/NEJMoa071366

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  3. Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper J, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D, for the VASST Investigators: Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008, 358: 877-887. 10.1056/NEJMoa067373

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  4. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL, International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases, et al.: Surviving Sepsis Campaign: International guidelines for the management of severe sepsis and septic shock: 2008. Crit Care Med 2008, 36: 296-327. 10.1097/01.CCM.0000298158.12101.41

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Correspondence to Charles L Sprung.

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Sprung, C.L., Annane, D., Singer, M. et al. Glucocorticoids in sepsis: dissecting facts from fiction. Crit Care 15, 446 (2011).

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