Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.

CONTEXT: Septic shock may be associated with relative adrenal insufficiency. Thus, a replacement therapy of low doses of corticosteroids has been proposed to treat septic shock.

OBJECTIVE: To assess whether low doses of corticosteroids improve 28-day survival in patients with septic shock and relative adrenal insufficiency.

DESIGN AND SETTING: Placebo-controlled, randomized, double-blind, parallel-group trial performed in 19 intensive care units in France from October 9, 1995, to February 23, 1999.

PATIENTS: Three hundred adult patients who fulfilled usual criteria for septic shock were enrolled after undergoing a short corticotropin test.

INTERVENTION: Patients were randomly assigned to receive either hydrocortisone (50-mg intravenous bolus every 6 hours) and fludrocortisone (50- micro g tablet once daily) (n = 151) or matching placebos (n = 149) for 7 days.

MAIN OUTCOME MEASURE: Twenty-eight-day survival distribution in patients with relative adrenal insufficiency (nonresponders to the corticotropin test).

RESULTS: One patient from the corticosteroid group was excluded from analyses because of consent withdrawal. There were 229 nonresponders to the corticotropin test (placebo, 115; corticosteroids, 114) and 70 responders to the corticotropin test (placebo, 34; corticosteroids, 36). In nonresponders, there were 73 deaths (63%) in the placebo group and 60 deaths (53%) in the corticosteroid group (hazard ratio, 0.67; 95% confidence interval, 0.47-0.95; P =.02). Vasopressor therapy was withdrawn within 28 days in 46 patients (40%) in the placebo group and in 65 patients (57%) in the corticosteroid group (hazard ratio, 1.91; 95% confidence interval, 1.29-2.84; P =.001). There was no significant difference between groups in responders. Adverse events rates were similar in the 2 groups.

CONCLUSION: In our trial, a 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly reduced the risk of death in patients with septic shock and relative adrenal insufficiency without increasing adverse events.