Closed-loop continuous infusions of etomidate and etomidate analogs in rats: a comparative study of dosing and the impact on adrenocortical function.

Anesthesiology
Joseph F CottenDouglas E Raines

Abstract

Etomidate is a sedative-hypnotic that is often given as a single intravenous bolus but rarely as an infusion because it suppresses adrenocortical function. Methoxycarbonyl etomidate and (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) are etomidate analogs that do not produce significant adrenocortical suppression when given as a single bolus. However, the effects of continuous infusions on adrenocortical function are unknown. In this study, we compared the effects of continuous infusions of etomidate, methoxycarbonyl etomidate, and carboetomidate on adrenocortical function in a rat model. A closed-loop system using the electroencephalographic burst suppression ratio as the feedback was used to administer continuous infusions of etomidate, methoxycarbonyl etomidate, or carboetomidate to Sprague-Dawley rats. Adrenocortical function was assessed during and after infusion by repetitively administering adrenocorticotropic hormone 1-24 and measuring serum corticosterone concentrations every 30 min. The sedative-hypnotic doses required to maintain a 40% burst suppression ratio in the presence of isoflurane, 1%, and the rate of burst suppression ratio recovery on infusion termination varied (methoxycarbonyl etomid...Continue Reading

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Citations

Sep 11, 2013·Journal of Neural Engineering·Jessica ChemaliEmery N Brown
Nov 5, 2011·Anesthesia and Analgesia·Ri Le GeDouglas E Raines
Mar 16, 2013·Anesthesia and Analgesia·Sivananthaperumal ShanmugasundararajDouglas E Raines
Nov 10, 2013·PLoS Computational Biology·Maryam M ShanechiEmery N Brown
Jun 3, 2014·Anesthesiology Clinics·M Stephen MeltonTong J Gan
Apr 16, 2016·Scientific Reports·Marija M PetrinovicThomas Mueggler
Mar 26, 2015·International Anesthesiology Clinics·Douglas E Raines
Jan 8, 2015·Frontiers in Systems Neuroscience·Jonathan D KennyKen Solt
Jul 16, 2016·Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology·Christos PapadelisTobias Loddenkemper
Oct 19, 2016·Anesthesiology·Ervin PejoDouglas E Raines
Oct 19, 2017·CNS Drugs·Janette Brohan, Basavana G Goudra
Mar 27, 2019·Expert Opinion on Drug Discovery·Bernd Antkowiak, Gerhard Rammes
Mar 12, 2019·Journal of Neural Engineering·Yuxiao YangMaryam M Shanechi
Jun 8, 2013·Journal of Neural Engineering·Max Y LibermanEmery N Brown
Jun 2, 2021·Clinical Pharmacokinetics·Beatrijs I Valk, Michel M R F Struys
Nov 22, 2017·British Journal of Anaesthesia·J R Sneyd

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