Endocrinological changes following etomidate, midazolam, or methohexital for minor surgery

Abstract

Etomidate is known to inhibit adrenocorticosteroid synthesis. The extent and duration of the effects of etomidate (63 ± 6.4 mg) on spontaneous and stimulated corticosteroid levels, as well as on plasma concentrations of ACTH, β-endorphin, and catecholamines were examined and compared to those following administration of the new benzodiazepine, midazolam, or of methohexital. Twenty-nine healthy, young, male orthopedic patients were randomized into three groups receiving either etomidate/fentanyl (n = 12), midazolam/fentanyl (n = 8), or methohexital/fentanyl (n = 9). Etomidate caused cortisol levels to decrease from 12.5 ± 1.2 μg/dl preoperatively to 5.9 ± 0.8 μg/dl after operation (P < 0.001), compared to an increase from 12.0 ± 1.9 μg/dl to 18.5 ± 2.9 μg/dl in the group receiving methohexital. At 6 and 20 h postoperatively, all cortisol levels were normal. The cortisol decrease from 12.5 ± 1.7 to 7.6 ± 1.5 caused by midazolam was similar to that following etomidate, but the response to exogenous ACTH was significantly impaired in patients receiving etomidate as compared to those receiving midazolam. ACTH and β-endorphin levels increased in patients receiving etomidate, presumably as a result of the interruption of negative feedback due to cortisol synthesis inhibition. Midazolam on the other hand prevented the increase of ACTH and β-endorphin levels. Etomidate completely suppressed spontaneous aldosterone levels (from 33 ± 6.7 to 7 ± 2.1 pg/ml), as well as the response to stimulation with exogenous ACTH without affecting serum electrolytes. Etomidate had no influence on plasma catecholamines, but midazolam attenuated the stress-related epinephrine increase.