The Effects of Etomidate Anesthesia on Adrenal Insufficiency and Relative Risk of Mortality Associated with Severity of Critical Illness. A Meta-Analysis
32 Pages Posted: 24 Jun 2019More...
Background: Etomidate, a preferred anesthetic agent, causes partial adrenal insufficiency [PAI] by inhibiting cortisol synthesis. It is controversial whether it increases mortality. The relative risks [rr] of PAI and mortality of etomidate was evaluated regarding e severity of illness (Simplified Acute Physiology II, [SAPSII]).
Methods: Literature searches were performed within Cochrane Reviews (search terms "etomidate" and "adrenal"), and then on PubMed and SCOPUS (search terms" etomidate", "critical care", "adrenal insufficiency", "glucocorticoid" or "corticosteroid"). Primary outcome was 28-day survival. Secondary outcome was PAI. PRISMA guidelines were implemented.
Findings: There were 28 trials of etomidate vs comparator anesthetics (4 randomized controlled, 15 retrospective and 9 post hoc) of 8429 patients. PAI, pre-defined in 13 trials, occurred at a rr =1·57 (95%confidence interval (CI):1·43; 1·71, p<0·0001). Excess mortality was associated with etomidate ( rr= 1·10, CI: 10·4; 1·16, p=0·001) , especially with a pre-specified SAPS >50 (rr= 1·2, CI: 1·11; 1·30, p<0·001) compared to SAPS <50 (rr=1·02, CI: 0·94; 1·11, p=0·69), p(interaction)= 0·01. There was a trend (p(interaction)= 0·07) for a progressive increase in mortality with increasing quartiles of SAPS < 44 (rr=1·08), 45-50 (rr=1·01), 51-57 (rr=1·19), and >57 (rr=1·22). No overall clinical benefit was found when corticosteroids were added to etomidate, although a post-hoc evaluation showed survival benefit for SAPS >55.
Interpretation: Etomidate causes PAI which lasts for 24 hours. In critically ill patients with SAPS >50 there is a 20% increase in mortality. There is limited evidence that early institution of corticosteroids in those with SAPS >50 may be protective.
Funding Statement: The authors declared: "None."
Declaration of Interests: The authors stated: "None."
Ethics Approval Statement: PRISMA guidelines were implemented.
Keywords: etomidate, critical illness, adrenal insufficiency
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