The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock

Intensive Care Med. 2009 Nov;35(11):1868-76. doi: 10.1007/s00134-009-1603-4. Epub 2009 Aug 4.


Rationale: Use of etomidate in the critically ill is controversial due to its links with an inadequate response to corticotropin and potential for excess mortality. In a septic shock population, we tested the hypotheses that etomidate administration induces more non-responders to corticotropin and increases mortality and that hydrocortisone treatment decreases mortality in patients receiving etomidate.

Methods: An a-priori sub-study of the CORTICUS multi-centre, randomised, double-blind, placebo-controlled trial of hydrocortisone in septic shock. Use and timing of etomidate administration were collected. Endpoints were corticotropin response and all-cause 28-day mortality in patients receiving etomidate.

Measurements and main results: Five hundred patients were recruited, of whom 499 were analysable; 96 (19.2%) were administered etomidate within the 72 h prior to inclusion. The proportion of non-responders to corticotropin was significantly higher in patients who were given etomidate in the 72 h before trial inclusion than in other patients (61.0 vs. 44.6%, P = 0.004). Etomidate therapy was associated with a higher 28-day mortality in univariate analysis (P = 0.02) and after correction for severity of illness (42.7 vs. 30.5%; P = 0.06 and P = 0.03) in our two multi-variant models. Hydrocortisone administration did not change the mortality of patients receiving etomidate (45 vs. 40%).

Conclusions: The use of bolus dose etomidate in the 72 h before study inclusion is associated with an increased incidence of inadequate response to corticotropin, but is also likely to be associated with an increase in mortality. We recommend clinicians demonstrate extreme caution in the use of etomidate in critically ill patients with septic shock.

Publication types

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

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenocorticotropic Hormone* / blood
  • Adrenocorticotropic Hormone* / drug effects
  • Aged
  • Analysis of Variance
  • Anti-Inflammatory Agents / therapeutic use
  • Cause of Death
  • Critical Care / methods
  • Double-Blind Method
  • Drug Antagonism
  • Etomidate / adverse effects*
  • Europe / epidemiology
  • Female
  • Humans
  • Hydrocortisone / analogs & derivatives
  • Hydrocortisone / therapeutic use
  • Hypnotics and Sedatives / adverse effects*
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Patient Selection
  • Prospective Studies
  • Severity of Illness Index
  • Shock, Septic / blood
  • Shock, Septic / drug therapy*
  • Shock, Septic / mortality*
  • Statistics, Nonparametric
  • Treatment Failure


  • Anti-Inflammatory Agents
  • Hypnotics and Sedatives
  • Adrenocorticotropic Hormone
  • hydrocortisone hemisuccinate
  • Hydrocortisone
  • Etomidate