ETOMIDATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ETOMIDATE (ETOMIDATE).
Etomidate is a nonbarbiturate hypnotic agent that acts as a positive allosteric modulator of the gamma-aminobutyric acid (GABA) type A receptor, enhancing GABA-mediated inhibition in the central nervous system. It produces rapid anesthesia with minimal cardiovascular and respiratory depression.
| Metabolism | Etomidate is extensively metabolized in the liver via hydrolysis of the ester side chain by hepatic esterases to its principal metabolite, etomidate carboxylic acid. A minor metabolite is formed via N-demethylation. Metabolites are inactive. |
| Excretion | Renal: 75% as metabolite (carboxylic acid), 2% unchanged; fecal/biliary: minimal. |
| Half-life | Terminal elimination half-life: 2.9–5.3 hours (context: redistribution shortens clinical effect; hepatic impairment prolongs). |
| Protein binding | 76% bound to albumin. |
| Volume of Distribution | Vd: 2.5–4.5 L/kg (large, indicating extensive tissue uptake). |
| Bioavailability | IV: 100% (only route used clinically). |
| Onset of Action | IV: 30–60 seconds (one arm–brain circulation time). |
| Duration of Action | IV: 3–5 minutes for hypnosis (due to rapid redistribution); context: single induction dose. |
Induction: 0.2–0.6 mg/kg IV over 30–60 seconds. Maintenance: 10–20 mcg/kg/min IV continuous infusion.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment. Hemodialysis does not alter dosing. Use caution in severe renal failure due to propylene glycol vehicle if prolonged infusion. |
| Liver impairment | No specific adjustment for Child-Pugh class. However, prolonged effect may occur in severe hepatic impairment; reduce induction dose by 50% and titrate to effect. |
| Pediatric use | Induction: 0.2–0.6 mg/kg IV (max 40 mg). Age >10 years: use adult dosing. Neonates and infants: reduce dose to 0.3 mg/kg due to higher volume of distribution. |
| Geriatric use | Induction: 0.15–0.3 mg/kg IV (50% reduction of adult dose) due to decreased clearance and increased sensitivity. Use lower end of dosing range. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ETOMIDATE (ETOMIDATE).
| Breastfeeding | It is unknown whether etomidate is excreted in human breast milk. The molecular weight (244.3) suggests potential excretion into milk. The milk-to-plasma ratio (M/P) has not been determined. Due to the short half-life (2–5 hours) and use as a single induction dose, transfer to the infant is likely minimal. However, caution is advised. The American Academy of Pediatrics classifies etomidate as 'compatible' with breastfeeding after a single dose, but data are insufficient for repeated or prolonged use. Infants should be monitored for sedation and respiratory depression. |
| Teratogenic Risk | Etomidate is classified as FDA Pregnancy Category C. Animal studies have shown embryotoxicity and teratogenicity at doses higher than human doses. There are no adequate and well-controlled studies in pregnant women. First trimester exposure may be associated with a slightly increased risk of congenital malformations, but data are limited. Risks to the fetus should be weighed against the benefits of maternal anesthesia. The drug is not recommended during pregnancy unless clearly needed, especially during organogenesis. In the second and third trimesters, etomidate may cause fetal central nervous system depression and respiratory depression if used near term. |
■ FDA Black Box Warning
Etomidate has been associated with mortality in children. It should not be used in children younger than 6 months of age. (This warning is included in the prescribing information based on FDA labeling; specific text may vary.)
| Serious Effects |
["Hypersensitivity to etomidate","Patients with acute porphyria (may be porphyrinogenic)"]
| Precautions | ["Inhibition of adrenal steroidogenesis (adrenal suppression) due to blockade of 11-beta-hydroxylase, leading to decreased cortisol and aldosterone production; may persist for 12-24 hours after single dose","Myoclonic movements during induction (involuntary muscle contractions)","Hypotension and bradycardia (less common than with other induction agents)","Venous irritation and pain on injection (may be reduced by using larger veins)"] |
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| Fetal Monitoring | Maternal monitoring: continuous ECG, blood pressure, heart rate, oxygen saturation, and respiratory rate. Fetal monitoring: electronic fetal heart rate monitoring should be considered if the fetus is viable, as etomidate may reduce uterine blood flow and cause fetal bradycardia. Neonatal monitoring: Apgar scores, respiratory effort, heart rate, and muscle tone should be assessed following delivery if etomidate was used for cesarean section. Prolonged use or high doses may require neonatal resuscitation support. |
| Fertility Effects | No human data are available on the effect of etomidate on fertility. Animal studies have shown no significant impairment of fertility in rats at clinically relevant doses. Reversible adrenal suppression may occur with prolonged use, potentially affecting hormonal balance, but single doses for anesthesia are unlikely to impact fertility. |