Etomidate (E): a potent inhibitor of adrenocortical 11 β-hydroxylase activity

Abstract

Increased mortality with long-term E infusions in intensive care patients has been reported and evidence is accumulating that E causes reversible adrenocortical suppression with decreased serum cortisol levels. A direct inhibition of adrenal steroidogenesis has been suggested, but so far data on the mechanism of this action are lacking. A 6 1/2 year old boy with convulsions due to encephalitis was treated with constant E infusions (1 - 2 mg/kg/h). Prior to E administration, adrenocortical function was normal as tested by an ACTH-test. 5 days after institution of therapy and 14 days after discontinuation, plasma levels of 11-deoxycorticosterone (DOC), corticosterone (B), 11-deoxycortisol (S) and cortisol (F) were measured by RIAs after Sephadex LH-20 chromatography. During E therapy DOC and S levels were highly elevated, while B was in the lower normal range and F was markedly decreased. Likewise the ratios of B/DOC and F/S, which reflect adrenocortical 11 β-hydroxylase activity, were extremely decreased (B/DOC:0.06 vs 27 in controls; F/S:0.009 vs 230 in controls). After discontinuation of therapy, the absolute values as well as the ratios returned to normal. These results show, that E is a potent inhibitor of adrenal 11 β-hydroxylation.Increased precaution seems to be necessary when this drug is used in patients who are under considerable amount of stress.