Etomidate is an imidazole derivative first synthesized in 1964 and introduced into clinical practice in 1972; its antifungal activity was noted early, but it was its hypnotic potency that carried it into anesthesia. Etomidate works by potentiating and directly activating both synaptic and extrasynaptic GABA receptors, making it an effective agent for sedation or induction of anesthesia. Unlike other anesthetics, etomidate is unique for its hemodynamic neutrality, meaning it does not cause significant blood pressure or cardiac output depression, which makes it particularly valuable for patients with unstable cardiovascular status. Its costs are dose-dependent adrenocortical suppression through 11-beta-hydroxylase inhibition (measurable for 24 hours or more after a single induction dose), myoclonus on induction, and activation of epileptiform foci, which is a liability in most patients and occasionally a tool during seizure-focus mapping.
In terms of cerebral perfusion, etomidate administration reduces cerebral blood flow (CBF), cerebral metabolic rate of oxygen consumption (CMRO₂), and intracranial pressure (ICP). These reductions in CBF are speculated to be secondary to the reduction of CMRO₂, as well as possible direct vasoconstrictive properties of etomidate, likely through the inhibition of nitric oxide signaling. This vasoconstriction helps explain the decreases in CBF observed during etomidate administration.
However, the assumption that etomidate's ability to reduce CBF and CMRO₂ results in neuroprotection has been challenged. Studies of cerebral aneurysm clipping and temporary vessel occlusion suggest that etomidate might induce tissue hypoxia, which is a significant concern for patients undergoing neurosurgical procedures. Retrospective analysis of data from the IHAST trial (International Hypothermia for Aneurysm Surgery Trial) did not find a clear association between etomidate use and improved neurological outcomes following temporary vessel clipping. Further studies have reported reduced cerebral oxygenation following induction doses of etomidate, even in patients with intact cerebral vasculature. These findings suggest that cerebral vasoconstriction induced by etomidate might not be fully balanced by a reduction in CMRO₂, casting doubt on its neuroprotective potential in ischemic conditions.
