Dual effect of etomidate on mineralocorticoid biosynthesis.
The effects of the intravenous anesthetic agent etomidate on adrenal steroidogenesis were studied in 14 pre-menopausal women undergoing abdominal hysterectomy. Anesthesia was induced with either thiopentone (group A) or etomidate (groups B and C) and maintained with nitrous oxide-oxygen 0.5% halothane (groups A and B) or an infusion of etomidate to supplement nitrous oxide-oxygen (group C). Serum concentrations of cortisol, aldosterone and 11-deoxycorticosterone (DOC) were measured pre-induction, at the end of surgery, and at 4, 10 and 24 hours after induction. In group A, concentrations of all three hormones were significantly elevated in response to surgery. In group B, the increases in cortisol and aldosterone were obtunded, but there was a greater increase in DOC at 4 hours after induction. In group C, there were no increases in cortisol or aldosterone up to 4 hours after induction, and the increase in DOC was significantly lower than in group B. These results suggest that etomidate inhibits adrenal steroidogenesis at two separate sites. With low doses of the drug, as used for induction, 11 beta-hydroxylase is inhibited lowering both cortisol and aldosterone secretion. The reduction in aldosterone is, however, offset by a rise in DOC. With higher doses, there is an additional early pathway effect so that the compensatory rise in DOC is reduced.
Sear
J W
JW
Nuffield Department of Anesthetics, John Radcliffe Hospital, Headington, Oxford.
Edwards
C R
CR
Atherden
S M
SM
D000328:Adult; D000450:Aldosterone / Q000097:blood; D003900:Desoxycorticosterone / Q000097:blood; D005045:Etomidate / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007044:Hysterectomy; D008875:Middle Aged; D008901:Mineralocorticoids / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009609:Nitrous Oxide / Q000494:pharmacology; D013874:Thiopental / Q000494:pharmacology
D008901:Mineralocorticoids; D003900:Desoxycorticosterone; D000450:Aldosterone; D013874:Thiopental; D009609:Nitrous Oxide; D006854:Hydrocortisone; D005045:Etomidate