First introduced into clinical practice in 1972, etomidate has a long history of use as an intravenous anesthetic and sedative. Like propofol, etomidate has a hypnotic effect but does not provide any analgesia. It is preferred primarily for its stable effect on circulatory hemodynamics in patients with decreased myocardial contractility. Etomidate is also indicated for anesthetic induction in patients with severe neurologic disease, such as elevated intracranial hypertension, who require maintenance of cerebral perfusion pressure. Etomidate may also be particularly useful as an anesthetic for emergency intubation in ICU or trauma patients.
Etomidate has the chemical structure of a carboxylated imidazole (Figure 54-1). Its mechanism of action targets the major inhibitory ion channels in the brain: the gamma-aminobutyric acid (GABAA) receptors. Potentiation, or positive modulation, of GABAA receptors increases chloride ion conduction, leading to neuronal hyperpolarization and depression of the reticular activating system.
PHARMACOKINETICS AND METABOLISM
The standard induction dose is 0.2-0.3 mg/kg. Because of its high lipid solubility, etomidate has a rapid onset of action. Its elimination half-life is 2-4 minutes with a duration of 3-8 minutes. Every 0.1 mg/kg dose leads to about 100 seconds of unconsciousness. Redistribution is responsible for the recovery and emergence from etomidate. Although the drug has a short context-sensitive half-life, it is rarely given in repeated doses or by infusion due to concern over adrenocortical suppression. More than 75% of the drug will bind to plasma proteins but with decreased protein binding in severe liver disease and uremia. End-stage liver disease leads to increased volume of distribution and decreased clearance of etomidate.
Degradation into inactive metabolites occurs mostly due to ester hydrolysis, primarily in the liver but also in the plasma. Etomidate has a high rate of clearance. Metabolites are excreted in urine (80%) and bile (20%). Less than 3% of etomidate is excreted unchanged in urine.
Circulation—Most anesthetic induction agents are associated with cardiovascular instability. In contrast, etomidate decreases systemic vascular resistance to a much lesser degree. Mean arterial blood pressure usually is maintained or only slightly decreased. Etomidate does not cause significant alterations in heart rate, cardiac output, central venous pressure, pulmonary artery pressure, and pulmonary occlusion pressure. Decreases in myocardial contractility can occur but are negligible with common induction doses. Blood pressure is more likely to decrease in patients with hypovolemia. Of note, etomidate does not blunt the sympathetic responses to laryngoscopy and intubation, so opioids are usually coadministered at induction. Because of these properties, etomidate is the induction agent of choice in patients for whom cardiac stability is of upmost importance.
Respiration—Etomidate can cause respiratory depression but to a lesser degree than other induction agents. Apnea is more likely ...