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Are Corticosteroids Beneficial in Severe Sepsis?

Meta-analysis suggests that low-dose, long-duration therapy benefits septic patients with relative adrenal insufficiency.

The role of corticosteroid therapy for septic patients has been debated for decades. Older studies, in which patients tended to receive high-dose therapy of short duration, generally showed no benefit. In more recent studies, researchers have tended to examine low-dose therapy of long duration. In this meta-analysis, investigators identified 16 randomized trials in which corticosteroids were compared with placebo (or supportive therapy alone) and which involved 2063 severely septic patients. Study populations were heterogeneous.

Overall, corticosteroids did not significantly lower mortality rates at 28 days (relative risk, 0.92) compared with placebo. However, subgroup analyses showed that long courses (5 days) of low-dose corticosteroids (300 mg of hydrocortisone equivalents) significantly lowered mortality rates at 28 days (RR, 0.80). Low-dose corticosteroids also reversed shock by day 7 in 50% of treated patients (vs. 31% of controls). Corticosteroids did not confer risk for gastroduodenal bleeding, superinfections, or hyperglycemia.

Comment: Recent research suggests that some septic patients have relative adrenal insufficiency; thus, it is plausible that long courses of physiologic "stress-dose" steroids -- as opposed to brief "mega-dose" therapy -- would improve outcomes. The authors recommend that patients with septic shock receive 200 to 300 mg of hydrocortisone daily after undergoing rapid adrenocorticotropic-hormone (ACTH) testing and that those with relative adrenal insufficiency be treated for 5 to 11 days. However, interpretation of ACTH testing is complicated by a recent finding that total serum cortisol levels don't necessarily reflect adrenal status accurately in critically ill patients (Journal Watch Apr 23 2004). A large ongoing European trial called CORTICUS is anticipated to provide definitive guidance on the use of steroids in septic patients. At the time of publication, the full text of the original article was available free of charge.

— Keith I. Marton, MD, and Allan S. Brett, MD

Published in Journal Watch General Medicine September 28, 2004

Citation(s):

Annane D et al. Corticosteroids for severe sepsis and septic shock: A systematic review and meta-analysis. BMJ 2004 Aug 28; 329:480-4.

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