Endocrinology, Vol 115, 2266-2270, Copyright © 1984 by Endocrine Society

ARTICLES

The effect of etomidate on adrenocortical function in dogs before and during hemorrhagic shock

R Fraser, I Watt, CE Gray, IM Ledingham and AF Lever

The effects of the hypnotic agent ethyl phenylethyl imidazole carboxylate (etomidate), on corticosteroidogenesis were studied in greyhound dogs during a 2-h period of anesthetic followed by a further 2 h of anesthetic combined with hemorrhage. Three groups of dogs were studied. The first, a control, received thiopentone and pentobartitone for induction and maintenance of anesthesia. A second control group received the chemically unrelated hypnotic preparation, althesin, after induction with thiopentone and pentobarbitone. In the first control group and the althesin-treated control group, changes in plasma ACTH and in plasma renin and angiotensin II concentrations were followed closely by changes in the levels of their respective dependent corticosteroids. A third experimental group received etomidate after induction of anesthesia with thiopentone and pentobarbitone. In these, in contrast, plasma levels of progesterone, 17 alpha- hydroxyprogesterone, corticosterone, cortisol, and aldosterone decreased during the experiment even failing to respond to massive rises in plasma ACTH concentration, renin, and angiotensin II levels after hemorrhage. However, the ability of 11-deoxycortisol and 11- deoxycorticosterone to respond was retained. These results suggest that etomidate inhibits corticosteroidogenesis directly, probably acting at more than one point in the biosynthetic pathway. It is suggested that it inhibits mitochondrial steroid hydroxylation (e.g. side chain cleavage, 11 beta-hydroxylation), but not 21-hydroxylation which occurs outside the mitochondrion.