Etomidate

Mechanisms of Action

Depression of reticular activating system and GABA mimetic inhibitory effects. Etomidate binds to GABA type A receptor. Unlike barbiturates, it may have disinhibitory effects on the parts of the nervous system that control extrapyramidal motor activity. This disinhibition is responsible for a 30–60% incidence of myoclonus.

Structure–Activity Relationships

Structurally it is a carboxylated imidazole compound. Etomidate is dissolved in propylene glycol. This solution often causes pain on injection that can be lessened by a prior injection of lidocaine.

Pharmacokinetics

Absorption

Etomidate is available only for intravenous administration and is used primarily for induction of general anesthesia (see Table 8–7).

Distribution

Although it is highly protein bound, etomidate is characterized by a very rapid onset of action due to its high lipid solubility and large nonionized fraction at physiological pH. Redistribution is responsible for decreasing the plasma concentration to awakening levels.

Biotransformation

Hepatic microsomal enzymes and plasma esterases rapidly hydrolyze etomidate to an inactive metabolite. The rate of biotransformation is five times greater for etomidate than for thiopental.

Excretion

The end product of hydrolysis is primarily excreted in the urine.

Effects on Organ Systems

Cardiovascular

Etomidate has minimal effects on the cardiovascular system. A mild reduction in peripheral vascular resistance is responsible for a slight decline in arterial blood pressure. Myocardial contractility and cardiac output are usually unchanged. Etomidate does not release histamine.

Respiratory

Ventilation is affected less with etomidate than with barbiturates or benzodiazepines. Even induction doses usually do not result in apnea unless opioids have also been administered.

Cerebral

Etomidate decreases the cerebral metabolic rate, cerebral blood flow, and intracranial pressure to the same extent as thiopental. Because of minimal cardiovascular effects, CPP is well maintained. Although changes on EEG resemble those associated with barbiturates, etomidate enhances somatosensory evoked potentials. Postoperative nausea and vomiting are more common than following barbiturate induction, but can be minimized by antiemetic medications. Etomidate is a sedative-hypnotic but lacks analgesic properties.

Endocrine

Induction doses of etomidate transiently inhibit enzymes involved in cortisol and aldosterone synthesis. Long-term infusions lead to adrenocortical suppression that may be associated with an increased mortality rate in critically ill patients.

Drug Interactions

Fentanyl increases the plasma level and prolongs the elimination half-life of etomidate.

Opioids decrease the myoclonus characteristic of an etomidate induction.