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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Journal ArticleDOI
Etomidate enabled electroconvulsive therapy without suppressing adrenocortical function in a case with difficulties in inducing seizures by conventional methods.
Kristian H. R. Jensen,Martin Kryspin Sørensen,Ulla Knorr,Martin Balslev Jørgensen,Anders W Jørgensen +4 more
TL;DR: Quite remarkably, the patient achieved rapid and complete relief from lifethreatening catatonia with just three sessions of ECT, illustrating that with appropriate risk-mitigation measures, ECT may be delivered safely post-MI when its benefits are compelling.
Book ChapterDOI
Etomidat: Ein sicheres Narkoseeinleitungsmittel?
TL;DR: In dem Bemuhen, das ideale Einleitungsmittel zu finden, sind in den letzten Jahrzehnten eine ganze Reihe neuer Hypnotika entwickelt worden, die die Erwartungen in einzelnen Aspekten erfullten, jedoch auch gravierende Nachteile aufwiesen as discussed by the authors.
Book ChapterDOI
Endocrine Disruption of Adrenocortical Function
TL;DR: The endocrinology of the hypothalamo-pituitary-adrenocorticals (HPA) axis, physiological actions of adrenocortical steroids, common manifestations of adrenal toxicity, and a strategy for distinguishing the mechanisms of Adrenal functional disruption are outlined.
References
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Journal ArticleDOI
A simple method for the isolation and purification of total lipides from animal tissues.
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.
Journal ArticleDOI
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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