Inhibition of adrenal steroidogenesis by the anesthetic etomidate.
The use of the intravenous anesthetic etomidate for prolonged sedation has been associated with low levels of plasma cortisol and increased mortality. We measured the cortisol and aldosterone responses to ACTH stimulation in five patients receiving etomidate, and we also studied the direct effects of etomidate on enzymes in the rat steroidogenic pathway. One patient who was receiving a 20-hour infusion of etomidate (1.3 to 1.5 mg per kilogram of body weight per hour) had marked adrenocortical suppression that was still evident four days after etomidate was discontinued. Four surgical patients receiving etomidate during their operations were all found to have adrenal suppression four hours after the operation; mean (+/- S.D.) increases in cortisol and aldosterone after ACTH stimulation were only 1.8 +/- 0.5 micrograms per deciliter and 0.5 +/- 1.1 ng per deciliter, respectively. In rat adrenal cells, etomidate produced a concentration-dependent blockade of the two mitochondrial cytochrome P-450-dependent enzymes, cholesterol-side-chain cleavage enzyme, and 11 beta-hydroxylase, without evident inhibition of the microsomal enzymes in the glucocorticoid pathway. Physicians should be aware that etomidate inhibits adrenal steroidogenesis, and they should consider treating selected patients with corticosteroids if etomidate is used.
D000302:Adrenal Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000758:Anesthesia / Q000009:adverse effects; D000818:Animals; D003345:Corticosterone / Q000096:biosynthesis; D065607:Cytochrome P-450 Enzyme Inhibitors; D003864:Depression, Chemical; D005045:Etomidate / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006993:Hypnotics and Sedatives / Q000009:adverse effects; D007093:Imidazoles / Q000009:adverse effects*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology; D051381:Rats; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors
D000305:Adrenal Cortex Hormones; D065607:Cytochrome P-450 Enzyme Inhibitors; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D013252:Steroid 11-beta-Hydroxylase; D003345:Corticosterone; D006854:Hydrocortisone; D005045:Etomidate