Journal ArticleDOI
Inhibition of Adrenal Steroidogenesis by the Anesthetic Etomidate
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TLDR
Physicians should be aware that etomidate inhibits adrenal steroidogenesis, and they should consider treating selected patients with corticosteroids if etamidate is used.Abstract:
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.read more
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References
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Influence of sedation on mortality in critically ill multiple trauma patients.
I. McA. Ledingham,Ian Watt +1 more
Journal ArticleDOI
Ketoconazole blocks adrenal steroidogenesis by inhibiting cytochrome P450-dependent enzymes.
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Journal ArticleDOI
Ketoconazole Blocks Adrenal Steroid Synthesis
Allan Pont,Paul L. Williams,David S. Loose,David Feldman,Richard E. Reitz,Charlotte Bochra,David A. Stevens +6 more
TL;DR: In healthy humans, the cortisol response to adrenocorticotropic hormone was significantly blunted 4 hours after a 400-mg or 600-mg dose, and this finding indicated that adrenal androgen response was reduced.
Journal ArticleDOI
Ketoconazole Blocks Testosterone Synthesis
Allan Pont,Paul L. Williams,Salman Azhar,Richard E. Reitz,Charlotte Bochra,Erla R. Smith,David A. Stevens +6 more
TL;DR: The diminution of testosterone synthesis could be significant as further therapeutic trials may use larger doses or more than once-daily administration, and the paucity of reports of endocrinologic toxicity may relate to the "escape from the block demonstrated in vivo.
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