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Corticosteroids in Septic Shock — No Benefit

Hydrocortisone did not lead to better outcomes in adults with septic shock.

Many experts recommend low-to-moderate-dose corticosteroid therapy in patients with septic shock who respond poorly to stimulation with adrenocorticotropic hormone (ACTH; e.g., cosyntropin). This recommendation is based largely on results of a single placebo-controlled trial published in 2002 (Journal Watch Aug 30 2002), in which steroid therapy lowered short-term mortality from 63% to 53% (P=0.04) in cosyntropin nonresponders. Now, investigators have conducted another multicenter trial — the CORTICUS study.

Researchers randomized 499 adults with septic shock (onset within 72 hours) to receive 11-day courses of either hydrocortisone (50 mg intravenously every 6 hours for 5 days, followed by tapering dose) or placebo. All patients underwent 60-minute cosyntropin testing; 47% were considered to be cosyntropin nonresponders (i.e., cortisol increased by 9 µg/dL).

No significant differences were found in 28-day mortality between the steroid and placebo groups in the overall study population (34% vs. 32%), among cosyntropin nonresponders (39% vs. 36%), and among cosyntropin responders (both 29%). Blood pressure improved more quickly with hydrocortisone than with placebo, but hydrocortisone recipients were more likely to develop superinfections (including new episodes of sepsis).

Comment: In this trial — the largest thus far — hydrocortisone therapy did not lead to better outcomes in adults with septic shock. Differences between this trial and the 2002 trial might explain the divergent results (e.g., the 2002 study had a narrower window for enrollment [8 hours] and included only patients whose blood pressure was unresponsive to vasopressors). The authors of the current study conclude that "hydrocortisone cannot be recommended as general adjuvant therapy for septic shock," although they speculate that hydrocortisone could have a role in patients who begin steroid therapy very early after onset of septic shock.

New guidelines on management of sepsis and septic shock have just been published by the "Surviving Sepsis Campaign," an international effort to improve outcomes in patients with severe sepsis (Crit Care Med 2008 Jan; 36:296). After discussion of both the CORTICUS trial and the 2002 trial, the guidelines make a grade 2C recommendation (a weak recommendation based on "low-quality" evidence) that steroids be considered for adult septic shock patients with blood pressure that responds poorly to fluid resuscitation and vasopressor therapy. The guidelines also recommend against use of ACTH-stimulation testing to guide steroid-treatment decisions.

— Allan S. Brett, MD

Published in Journal Watch General Medicine January 9, 2008

Citation(s):

Sprung CL et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008 Jan 10; 358:111.

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