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Low-Dose Steroid Therapy Reduces Mortality from Septic Shock

In patients with septic shock and relative adrenal insufficiency, low-dose corticosteroid therapy reduced mortality without increasing adverse events.

Because septic shock may be associated with relative adrenal insufficiency, corticosteroid replacement has been advocated. Trials of short-course, high-dose corticosteroid therapy have not been successful, however. These authors evaluated treatment with low-dose corticosteroids in a controlled, randomized, double-blind study conducted at 19 intensive care units in France.

Three hundred adults who met each of 6 clinical or laboratory criteria for septic shock (including systolic arterial blood pressure <90 mm Hg for at least 1 hour despite adequate fluid replacement and treatment with dopamine, epinephrine, or norepinephrine) received placebo or hydrocortisone (50-mg IV bolus every 6 hours) and fludrocortisone (50-µg oral dose once daily) for 7 days. Patients were classified as nonresponders (i.e., having adrenal insufficiency) or responders (i.e., having normal adrenal function) according to corticotropin stimulation test (CST) results. Among the 229 patients in the nonresponder cohort, the placebo recipients had a higher incidence of death at 28 days (the primary outcome) than did corticosteroid recipients (63% vs. 53%; P=0.02) and a lower incidence of withdrawal from vasopressor support (40% vs. 57%; P=0.001). Among patients in the responder cohort, there were no significant differences in these measures between the groups. The incidence of adverse events was similar in the corticosteroid and placebo groups.

Comment: Severe sepsis accounts for nearly 10% of all deaths in the U.S. The dramatic results of this study indicate that for every 7 patients with septic shock and relative adrenal insufficiency, 1 life would be saved at day 28 by using this corticosteroid regimen. The authors advocate instituting this regimen empirically for patients who present with septic shock but continuing the regimen only in patients whose CST results demonstrate nonresponsiveness (i.e., adrenal insufficiency).

— John A. Marx, MD, FACEP

Published in Journal Watch Emergency Medicine November 13, 2002

Citation(s):

Annane D et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002 Aug 21; 288:862-71.

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