Etomidate - Intravenous Anesthetics

ETOMIDATE

Etomidate (Figure 24–6) is an intravenous anesthetic with hypnotic but not analgesic effects and is often chosen for its minimal hemodynamic effects. Although its pharmacokinetics are favorable, endocrine side effects limit its use for continuous infusions. Etomidate is a carboxylated imidazole derivative that is poorly soluble in water and is therefore supplied as a 2 mg/mL solution in 35% propylene glycol. The solution has a pH of 6.9 and thus does not cause problems with precipitation as thiopen-tal does. Etomidate appears to have GABA-like effects and seems to act primarily through potentiation of GABA_A-mediated chloride currents, like most other intravenous anesthetics.

Pharmacokinetics

An induction dose of etomidate produces rapid onset of anesthesia, and recovery depends on redistribution to inactive tissue sites, comparable to thiopental and propofol. Metabolism is primarily by ester hydrolysis to inactive metabolites, which are then excreted in urine (78%) and bile (22%). Less than 3% of an administered dose of etomidate is excreted as unchanged drug in urine. Clearance of etomidate is about five times that of thiopental, as reflected by a shorter elimination half-time (Table 25–2). The duration of action is linearly related to the dose, with each 0.1 mg/kg providing about 100 seconds of unconsciousness. Because of etomidate’s minimal effects on hemodynamics and short context-sensitive half-time, larger doses, repeated boluses, or continuous infusions can safely be administered. Etomidate, like most other intravenous anesthetics, is highly protein bound (77%), primarily to albumin.

Organ System Effects

A. CNS Effects

Etomidate is a potent cerebral vasoconstrictor, as reflected by decreases in cerebral blood flow and ICP. These effects are similar to those produced by comparable doses of thiopental. Despite its reduction of CMRO₂, etomidate has failed to show neuroprotective properties in animal studies, and human studies are lacking. The frequency of excitatory spikes on the EEG after the administration of etomidate is greater than with thiopental. Similar to metho-hexital, etomidate may activate seizure foci, manifested as fast activity on the EEG. In addition, spontaneous movements charac-terized as myoclonus occur in more than 50% of patients receiving etomidate, and this myoclonic activity may be associated with seizure-like activity on the EEG.

B. Cardiovascular Effects

A characteristic and desired feature of induction of anesthesia with etomidate is cardiovascular stability after bolus injection. In this regard, decrease in systemic blood pressure is modest or absent and principally reflects a decrease in systemic vascular resistance. Therefore, the systemic blood pressure-lowering effects of etomidate are probably exaggerated in the presence of hypo-volemia, and optimization of the patient’s intravascular fluid volume status before induction of anesthesia should be achieved.

Etomidate produces minimal changes in heart rate and cardiac output. Its depressant effects on myocardial contractility are minimal at concentrations used for induction of anesthesia.

C. Respiratory Effects

The depressant effects of etomidate on ventilation are less pro-nounced than those of barbiturates, although apnea may occasion-ally follow rapid intravenous injection of the drug. Depression of ventilation may be exaggerated when etomidate is combined with inhaled anesthetics or opioids.

D. Endocrine Effects

Etomidate causes adrenocortical suppression by producing a dose-dependent inhibition of 11β-hydroxylase, an enzyme necessary for the conversion of cholesterol to cortisol. This suppression lasts 4–8 hours after an induction dose of the drug. Despite concerns regarding this finding, no outcome studies have demonstrated an adverse effect. However, because of its endocrine effects, etomi-date is not used as continuous infusion.

Clinical Uses & Dosage

Etomidate is an alternative to propofol and barbiturates for the rapid intravenous induction of anesthesia, especially in patients with compromised myocardial contractility. After a standard induction dose (0.2–0.3 mg/kg IV), the onset of unconsciousness is comparable to that achieved by thiopental and propofol. Similar to propofol, during intravenous injection of etomidate there is a high incidence of pain, which may be followed by venous irritation. Involuntary myoclonic movements are also common but may be masked by the concomitant administration of neuromuscular blocking drugs. Awakening after a single intra-venous dose of etomidate is rapid, with little evidence of any residual depressant effects. Etomidate does not produce analgesia, and postoperative nausea and vomiting may be more common than after the administration of thiopental or propofol.