Plasma concentrations of etomidate during an intravenous infusion over 48 hours

Hebron, B. S.

doi:10.1111/j.1365-2044.1983.tb15175.x

Cited by 17 publications

(5 citation statements)

References 5 publications

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“…fluid administration that occurred during the PK sampling. While etomidate PK is linear in adults in the dose range 0.2–0.6 mg/kg, it is possible that at the upper range of adult etomidate dosing recommendations (0.6 mg/kg) infants may not exhibit linear PK, as this has not been studied and infants may be exposed to higher plasma concentrations and durations of effect than our simulations predict . Finally, the effect of etomidate on adrenal function, which remains an important topic of debate, was not elucidated in this study.…”

Section: Discussionmentioning

confidence: 78%

Population pharmacokinetics of etomidate in neonates and infants with congenital heart disease

Elkomy

Hammer

et al. 2015

Biopharm & Drug Disp

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Background Etomidate is a rapid-onset, short-acting hypnotic medication administered for induction of anesthesia. It is currently approved by the Food and Drug Administration for use in older children and adults. Pharmacokinetic data to help guide dosing in neonates and infants is lacking. Objective The aim of this study was to determine the pharmacokinetics of etomidate in neonates and infants with congenital heart disease undergoing cardiac surgery. Methods Four neonates and sixteen infants, postnatal age 0.3 – 11.7 months, requiring open-heart surgery received 0.3 mg/kg of etomidate administered as a single intravenous dose prior to surgery. Blood sampling for plasma etomidate concentration occurred immediately following etomidate administration until the initiation of cardiopulmonary bypass. A population pharmacokinetic approach using nonlinear mixed–effects modeling was applied to characterize etomidate pharmacokinetics. Results The pharmacokinetics of etomidate was described by a two-compartment model with first-order elimination. An allometric weight-based model was applied to scale results to a 70 kg adult. Covariates including age and cardiac physiology were not found to significantly impact etomidate pharmacokinetics. The study population was found to have a central and intercompartmental clearance of 0.624 L/min/70-kg and 0.44 L/min/70-kg, respectively; central and peripheral distribution volume of 9.47 and 22.8 L/70-kg, respectively. Inter-individual variability was between 94–142% for all parameters and residual variability was 29%. Conclusions The clearance of etomidate is lower in neonates and infants with congenital heart disease compared to published values for older children without congenital heart disease. In addition, etomidate pharmacokinetics is highly variable in this pediatric cardiac population.

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Section: Discussionmentioning

confidence: 78%

Population pharmacokinetics of etomidate in neonates and infants with congenital heart disease

Elkomy

Hammer

et al. 2015

Biopharm & Drug Disp

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“…The doses of etomidate used in the study are clinically relevant. It has been estimated that the peak plasma concentration of etomidate during induction of general anesthesia is approximately 10 –5 M [ 22 – 24 ]. The free plasma concentration is likely to be 2.5 × 10 –6 M. In addition, it has been reported that 5 × 10 –5 M concentration of etomidate is clinically relevant [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Endothelium-dependent relaxation induced by etomidate in the aortas of insulin-resistant rats

Xue

et al. 2018

aoms

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IntroductionFew reports have mentioned the effect of etomidate on the aortas of insulin-resistant (IR) rats. In this study, we investigated the effect of etomidate on isolated IR aortas of rats, and explored its underlying mechanism.Material and methodsThe IR rat model was established through feeding with a high-fructose diet. The systolic blood pressure (SBP) was measured by the tail-cuff method before grouping and at the end of the 8-week feeding; blood samples were also obtained for analysis. Thoracic aorta rings of IR rats were isolated and suspended in a tissue bath. The tensile force was recorded isometrically. The effect of etomidate on provoked contraction of the rings was assessed with or without a potassium channel blocker or NO synthase inhibitor.ResultsEtomidate-induced relaxation in IR rings was greater than normal control (NC) rings (all p < 0.001 with etomidate log M of –4 to –6). NG-nitro-L-arginine methyl ester (L-NAME, an NO synthase inhibitors) inhibited etomidate-induced relaxation in NC rings, but had no effect on the IR rings (all p < 0.001 with etomidate log M of –4 to –6). Pre-incubation with glibenclamide (Gli, a potassium channel blocker) significantly inhibited etomidate-induced relaxation in NC and IR rings (all p < 0.001 with etomidate log M of –4 to –6), and had no inhibited effect on endothelial denuded aortic rings.ConclusionsInsulin resistance increased etomidate-induced relaxation in rat aortas. Etomidate causes vasodilation in IR rat aortas via both endothelium-dependent and independent ways; impaired NO-mediated relaxation was disrupted and ATP-sensitive potassium (KATP) channel-mediated relaxation may be involved in the endothelium-dependent relaxation of etomidate in IR rats.

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“…The peak plasma concentration of etomidate during induction of general anaesthesia is approximately 10 -5 M 20,21 , whereas the free plasma concentration is likely to be less than 10 -5 M because about 76.5% of etomidate 22 is bound to plasma protein. Thus, the inhibitory effects of etomidate of endotheliumdependent vasorelaxation induced by acetylcholine in this study appear to be significant at clinically relevant concentrations.…”

Section: Discussionmentioning

confidence: 99%

Effect of Etomidate on Endothelium-dependent Relaxation Induced by Acetylcholine in Rat Aorta

Sohn

Kim

et al. 2004

Anaesth Intensive Care

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The goals of this in vitro study were to investigate effects of etomidate on endothelium-dependent relaxation induced by acetylcholine in rat aorta, and to elucidate the associated cellular mechanism. In endothelium-intact rings precontracted with phenylephrine 10−6 M, dose-response curves for acetylcholine (10−9 to 10−5 M) and calcium ionophore (10−9 to 10−6 M) were generated in the presence and absence of etomidate (5×10−6, 10−5 M). In endothelium-intact or -denuded rings precontracted with phenylephrine 10−6 M, sodium nitroprusside (10−9 to 10−6 M) dose-response curves were generated in the presence and absence of etomidate (10−5 M). Etomidate (5×10−6, 10−5 M) produced a significant rightward shift in the dose-response curves induced by acetylcholine (receptor-mediated endothelium-dependent agonist) and calcium ionophore A23187 (non receptor-mediated endothelium-dependent agonist). Etomidate (10−5 M) had no effect on sodium nitroprusside (endothelium-independent nitric oxide donor)-induced vasorelaxant response in both endothelium-intact and -denuded rings. These results indicate that etomidate at clinically relevant concentrations attenuates endothelium-dependent relaxation induced by acetylcholine by an acting at a site distal to the endothelial muscarinic receptor, but proximal to guanylate cyclase activation of vascular smooth muscle in rat aorta.

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Plasma concentrations of etomidate during an intravenous infusion over 48 hours

Abstract: Summary

Cited by 17 publications

References 5 publications

Population pharmacokinetics of etomidate in neonates and infants with congenital heart disease

Population pharmacokinetics of etomidate in neonates and infants with congenital heart disease

Endothelium-dependent relaxation induced by etomidate in the aortas of insulin-resistant rats

Effect of Etomidate on Endothelium-dependent Relaxation Induced by Acetylcholine in Rat Aorta

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