title: The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock.
abstract: BACKGROUND
  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.
  
  
  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.
authors: Health Services Research Unit, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK. b.h.cuthbertson@abdn.ac.uk
authors: Brian H
authors: BH
authors: Cuthbertson
authors: Charles L
authors: CL
authors: Sprung
authors: Djillali
authors: D
authors: Annane
authors: Sylvie
authors: S
authors: Chevret
authors: Mark
authors: M
authors: Garfield
authors: Serge
authors: S
authors: Goodman
authors: Pierre-Francois
authors: PF
authors: Laterre
authors: Jean Louis
authors: JL
authors: Vincent
authors: Klaus
authors: K
authors: Freivogel
authors: Konrad
authors: K
authors: Reinhart
authors: Mervyn
authors: M
authors: Singer
authors: Didier
authors: D
authors: Payen
authors: Yoram G
authors: YG
authors: Weiss
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects; D000368:Aged; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002423:Cause of Death; D003422:Critical Care / Q000379:methods; D004311:Double-Blind Method; D004336:Drug Antagonism; D005045:Etomidate / Q000009:adverse effects*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000627:therapeutic use; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018579:Patient Selection; D011446:Prospective Studies; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D018709:Statistics, Nonparametric; D017211:Treatment Failure
chemical_list: D000893:Anti-Inflammatory Agents; D006993:Hypnotics and Sedatives; D000324:Adrenocorticotropic Hormone; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone; D005045:Etomidate