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

Intensive Care Medicine (Impact Factor: 7.21). 11/2009; 35(11):1868-1876. DOI: 10.1007/s00134-009-1603-4
Source: PubMed


RationaleUse 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.

MethodsAn 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 resultsFive hundred patients were recruited, of whom 499 were analysable; 96 (19.2%) were administered etomidate within the 72h
prior to inclusion. The proportion of non-responders to corticotropin was significantly higher in patients who were given
etomidate in the 72h 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%).

ConclusionsThe use of bolus dose etomidate in the 72h 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.

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Available from: Didier Payen
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    • "Fig. 3. Mean arterial pressure before induction agent and up to 72 hours postinduction agent administration. transient period of etomidate-associated adrenal insufficiency [8] [9] [10] [11]. A retrospective cohort study including patients with severe sepsis and septic shock investigated the association between adrenal dysfunction and mortality and found that etomidate was associated with an increased mortality risk (OR, 1.53; 95% CI, 1.1-2.3), "
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    • "Etomidate is also a short-acting drug, which is commonly used for induction and maintenance of anesthesia.[13] The most important side-effects of Etomidate are nausea and vomiting that may lead to aspiration in patients.[141516] "
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    • "The systemic inflammatory response causes tissue damage in the lung, which is the most insidious component in sepsis due to compromised gas exchange. Despite modern treatment modalities, the mortality of these patients remains high in intensive care units (Cuthbertson et al., 2009; Schramm et al., 2011; Yano et al., 2006). Thus, there is an urgent need to develop more specific and effective therapies for patients with sepsis. "
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