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
Citations
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Effects of 3-MeSO2-DDE and some CYP inhibitors on glucocorticoid steroidogenesis in the H295R human adrenocortical carcinoma cell line.
TL;DR: The inhibition of cortisol formation by 3-MeSO2-DDE supports an interaction with the active site of CYP11B1, as previously reported in mouse adrenocortical Y1 cells, and studies on the adrenotoxicity of 3- MeSO2 -DDE in humans are needed.
Journal ArticleDOI
Etomidate-®Lipuro is associated with considerably less injection pain in children compared with propofol with added lidocaine
TL;DR: The use of a new lipid formulation of etomidate is associated with significantly less injection pain than propofol with added lidocaine in children, and may warrant a change in clinical practice in order to avoid unnecessary pain in children.
Journal ArticleDOI
Long-term post-operative cognitive decline in the elderly: the effects of anesthesia type, apolipoprotein E genotype, and clinical antecedents.
Marie-Laure Ancelin,Guilhem de Roquefeuil,Jacqueline Scali,François Bonnel,Jean-François Adam,Jean-Claude Cheminal,Jean-Paul Cristol,Anne-Marie Dupuy,Isabelle Carrière,Karen Ritchie +9 more
TL;DR: A clear dissociation effect was observed for several areas of visuospatial functioning which persisted up to the 13-month follow-up, suggesting that cognitive dysfunction may be attributable at least in part to peri-operative conditions, notably stress and glucocorticoid exposure.
Journal ArticleDOI
Adrenocortical suppression by a single induction dose of etomidate
TL;DR: It is concluded that a single i.v. bolus of etomidate leads to significant adrenal insufficiency in patients without preexisting endocrine abnormalities, indicating relative unresponsiveness of the adrenal cortex to stimulation by endogenous ACTH.
References
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TL;DR: In this paper, the authors described a simplified version of the method and reported the results of a study of its application to different tissues, including the efficiency of the washing procedure in terms of the removal from tissue lipides of some non-lipide substances of special biochemical interest.
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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.
TL;DR: It is concluded that ketoconazole may be a general inhibitor of mitochondrial P450 enzymes, and the possibility that this drug action may be beneficially exploited in situations where inhibition of steroidogenesis is a therapeutic goal is raised.
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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