Effect of a single bolus of etomidate upon eight major corticosteroid hormones and plasma ACTH.
In a prospective controlled trial we investigated the effect of an induction dose of etomidate (0.26 mg/kg i.v.) on plasma ACTH, progesterone, 17 alpha OH-progesterone, 11-deoxycortisol, cortisol, cortisone, corticosterone, 11-deoxycorticosterone, and aldosterone in seven males undergoing general anaesthesia. Seven other male patients receiving thiopentone at induction (5.0 mg/kg i.v.) served as controls. Plasma ACTH concentrations rose higher in the etomidate group (346 +/- 124 vs. 117 +/- 74 pg/ml, mean +/- SEM), but the difference was not significant. After etomidate we found a clear suppression of plasma cortisol (P less than 0.01), cortisone (P less than 0.01), corticosterone (P less than 0.01), and aldosterone (P less than 0.05) compared to corticosteroid levels after induction with thiopentone. Plasma 11-deoxycortisol and 11-deoxycorticosterone concentrations were grossly elevated 210 min after etomidate (91 +/- 28 nmol/l and 7.04 +/- 0.47 nmol/l, respectively, P less than 0.01) demonstrating inhibition of 11 beta-hydroxylation of both glucocorticoid and mineralocorticoid intermediates. In contrast, no significant difference in plasma progesterone and 17 alpha-OH-progesterone levels was found between the two groups indicating that the cholesterol-side-chain cleavage enzyme is less sensitive to etomidate than 11 beta-hydroxylase. Our results suggest that after induction of anaesthesia with a single bolus of etomidate, inhibition of other enzymes in the corticosteroid-synthetic pathway (e.g. cholesterol-side-chain cleavage enzyme) is of little clinical relevance.
Allolio
B
B
Dörr
H
H
Stuttmann
R
R
Knorr
D
D
Engelhardt
D
D
Winkelmann
W
W
D019326:17-alpha-Hydroxyprogesterone; D000293:Adolescent; D000302:Adrenal Cortex / Q000187:drug effects; D000305:Adrenal Cortex Hormones / Q000097:blood*; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D002986:Clinical Trials as Topic; D003345:Corticosterone / Q000097:blood; D003348:Cortisone / Q000097:blood; D003350:Cortodoxone / Q000097:blood; D003900:Desoxycorticosterone / Q000097:blood; D005045:Etomidate / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006908:Hydroxyprogesterones / Q000097:blood; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011374:Progesterone / Q000097:blood; D013874:Thiopental; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D006908:Hydroxyprogesterones; D007093:Imidazoles; D003900:Desoxycorticosterone; D000450:Aldosterone; D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D013874:Thiopental; D003348:Cortisone; D003345:Corticosterone; D003350:Cortodoxone; D006854:Hydrocortisone; D005045:Etomidate