Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock

JAMA. 2002 Aug 21;288(7):862-71. doi: 10.1001/jama.288.7.862.

Abstract

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 Vasopressor therapy was withdrawn within 28 days in 46 patients (40%) in the placebo group and in 65 patients (57%) in the corticosteroid group (hazard ratio, 1.91; 95% confidence interval,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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Insufficiency / complications*
  • Adrenal Insufficiency / diagnosis
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use*
  • Double-Blind Method
  • Female
  • Fludrocortisone / administration & dosage
  • Fludrocortisone / therapeutic use*
  • Humans
  • Hydrocortisone / administration & dosage
  • Hydrocortisone / therapeutic use*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Severity of Illness Index
  • Shock, Septic / complications*
  • Shock, Septic / drug therapy*
  • Shock, Septic / mortality
  • Survival Analysis
  • Vasoconstrictor Agents / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Vasoconstrictor Agents
  • Fludrocortisone
  • Hydrocortisone