More than 45 years after its development, etomidate still sees widespread use as a hypnotic agent for single-dose sedation of critically ill and hemodynamically unstable patients. Potent and prolonged inhibition of cortisol synthesis by etomidate, even following single-dose administration, is controversial and a legitimate concern for clinicians. This article will briefly review etomidate pharmacology. It will also discuss some recent basic science and translational studies that have yielded several novel and clinically promising etomidate analogues designed to circumvent etomidate adrenal suppression.
StanleyTHEganTDVan AkenH. A tribute to Dr. Paul A. J. Janssen: entrepreneur extraordinaire, innovative scientist, and significant contributor to anesthesiology. Anesth Analg. 2008;106:451-462.
2.
GodefroiEFJanssenPAVandereyckenCAVanheertumAHNiemegeersCJ.Dl-1-(1-arylalkyl)imidazole-5-carboxylate esters. A novel type of hypnotic agents. J Med Chem. 1965;8:220-223.
3.
FormanSA.Clinical and molecular pharmacology of etomidate. Anesthesiology. 2011;114:695-707.
4.
LedinghamIMWattI.Influence of sedation on mortality in critically ill multiple trauma patients. Lancet. 1983;1(8336):1270.
5.
LiGDChiaraDCSawyerGWHusainSSOlsenRWCohenJB.Identification of a GABAA receptor anesthetic binding site at subunit interfaces by photolabeling with an etomidate analog. J Neurosci. 2006;26:11599-11605.
6.
ChiaraDCDostalovaZJayakarSSZhouXMillerKWCohenJB.Mapping general anesthetic binding site(s) in human α1β3 γ-aminobutyric acid type A receptors with [(3)H]TDBzl-etomidate, a photoreactive etomidate analogue. Biochemistry. 2012;51:836-847.
7.
StewartDSMillerKWFormanSA.MTS-etomidate selectively reacts within the GABAA receptor etomidate binding site. Meeting Abstract Biophysical Society;2009.
CottenJFHusainSSFormanSA. Methoxycarbonyl-etomidate: a novel rapidly metabolized and ultra-short-acting etomidate analogue that does not produce prolonged adrenocortical suppression. Anesthesiology. 2009;111:240-249.
12.
PejoEGeRBanacosNCottenJFHusainSSRainesDE.Electroencephalographic recovery, hypnotic emergence, and the effects of metabolite after continuous infusions of a rapidly metabolized etomidate analog in rats. Anesthesiology. 2012;116:1057-1065.
13.
HusainSSPejoEGeRRainesDE.Modifying methoxycarbonyl etomidate inter-ester spacer optimizes in vitro metabolic stability and in vivo hypnotic potency and duration of action. Anesthesiology. 2012;117:1027-1036.
14.
PejoECottenJFKellyEW. In vivo and in vitro pharmacological studies of methoxycarbonyl-carboetomidate. Anesth Analg. 2012;115:297-304.
15.
CottenJFLe GeRBanacosN. Closed-loop continuous infusions of etomidate and etomidate analogs in rats: a comparative study of dosing and the impact on adrenocortical function. Anesthesiology. 2011;115:764-773.
16.
GeRPejoEHusainSSCottenJFRainesDE.Electroencephalographic and hypnotic recoveries after brief and prolonged infusions of etomidate and optimized soft etomidate analogs. Anesthesiology. 2012;117:1037-1043.
17.
GeRPejoECottenJFRainesDE.Adrenocortical suppression and recovery after continuous hypnotic infusion: etomidate versus its soft analogue cyclopropyl-methoxycarbonyl metomidate. Crit Care. 2013;17:R20.
18.
CottenJFFormanSALahaJK. Carboetomidate: a pyrrole analog of etomidate designed not to suppress adrenocortical function. Anesthesiology. 2010;112:637-644.
19.
PejoEFengYChaoWCottenJFLe GeRRainesDE.Differential effects of etomidate and its pyrrole analogue carboetomidate on the adrenocortical and cytokine responses to endotoxemia. Crit Care Med. 2012;40:187-192.
