Etomidate

Mechanism

Mechanism of action

Etomidate acts as a highly selective allosteric agonist of the GABA_A receptor that has the β₃ subunit. It does not alter peripheral sympathetic vascular tone or compromise intrinsic myocardial contractility, optimally preserving the cardiac sinus baroreflex.

Adrenocortical Suppression by Inhibition of 11-β-hydroxylase

Etomidate exerts a dose-dependent and reversible inhibition of the adrenal mitochondrial enzyme 11-β-hydroxylase, the limiting step for the synthesis of cortisol and aldosterone from cholesterol.

Cholesterol → Progesterone 11-β-hydroxylase blockade Cortisol

Even a single induction dose of etomidate (0.3 mg/kg) can measurably suppress the endogenous cortisol response to ACTH stimulation for a period of 12 to 24 hours. This suppression may limit its continued use in infusion in patients with severe septic shock where the adrenal reserve is compromised at baseline.

Pharmacokinetics

Pharmacokinetics

• Distribution: Rapid passage of the blood-brain barrier with induction of hypnosis in less than 45 seconds.
• Metabolism: Extensive hepatic through enzymatic hydrolysis of its carboxylic ester group by nonspecific microsomal and plasma esterases, yielding an inactive carboxylic acid metabolite.
• Excretion: Renal 85% in the form of inactive metabolites; minor fecal (13%).

Indicators and dose

Indications and Dosage

• Induction of General Anesthesia in Unstable Patients: 0.2 - 0.3 mg/kg slowly intravenously. It is of choice in severe aortic stenosis, cardiac tamponade, multivessel coronary disease or active hemorrhagic shock.
• Frequent Side Effects: Pain upon injection (classic formula with propylene glycol), transient myoclonus during induction (explained by the disinhibition of extrapyramidal cortical pathways, attenuated by co-administering low doses of previous opioids) and postoperative nausea and vomiting.