Effect of a Single Bolus of Etomidate Upon Eight Major Corticosteroid Hormones and Plasma Acth

Abstract

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.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

“…Cortisol immunoassays may overor underestimate the actual cortisol level, affecting the assignment of patients to responders or nonresponders [307]. Although the clinical significance is not clear, it is now recognized that etomidate, when used for induction for intubation, will suppress the hypothalamic-pituitary-adrenal axis [308,309]. Moreover, a subanalysis of the CORTICUS trial revealed that the use of etomidate before application of low-dose steroids was associated with an increased 28-day mortality rate [302].…”

THERAPY OF ENDOCRINE DISEASE: Steroidogenesis enzyme inhibitors in Cushing's syndrome

“…Etomidate is a potent inhibitor of 11b-hydroxylation and to a lesser degree 20,22-desmolase (26,91,92) (Fig. 1).…”

Safety of etomidate bolus administration in patients with septic shock

“…[1][2][3] However, critical illness-related corticosteroid insufficiency has been associated with etomidate after the administration of a single dose. 4,5 Critical illness-related corticosteroid insufficiency, commonly referred to as adrenal insufficiency, is defined as inadequate cellular corticosteroid activity for the severity of the patient's illness. It is best diagnosed by a delta serum cortisol of less than 248 nmol/L after administration of cosyntropin 250 mg or a random total serum cortisol of less than 276 nmol/L.…”