ETOMIDATE
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 244.29 |
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 | Crosses placenta; fetal acidosis noted in animal studies; limited human data; use only if clearly needed. |
| 2nd trimester | Fetal acidosis reported; avoid if possible; consider alternative agents. |
| 3rd trimester | Neonatal acidosis and respiratory depression possible; use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for ETOMIDATE (ETOMIDATE).
| Placental transfer | Rapidly crosses placenta; fetal/maternal ratio ~0.5-0.8 in humans. |
| Breastfeeding | Excreted in breast milk in low concentrations; no adverse effects reported in infants; caution with repeated dosing. |
| Lactation Rating | L2 |
| 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. |
| 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. |
■ 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 etomidateAdrenal suppression (relative unless urgent)Patients with porphyria
| 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) |
| Food/Dietary | No specific food interactions are known. Etomidate is administered intravenously and does not have oral bioavailability. However, concurrent use of drugs that affect CYP3A4 (e.g., grapefruit juice) is not clinically significant due to IV route. |
| Clinical Pearls | Etomidate is an induction agent of choice in hemodynamically unstable patients due to minimal cardiovascular depression. Adrenal suppression occurs even after a single dose, manifesting as decreased cortisol and aldosterone synthesis via 11β-hydroxylase inhibition. Administer slowly over 30-60 seconds to reduce myoclonus and pain on injection. Use a lower dose (0.2-0.3 mg/kg IV) in elderly or debilitated patients. Etomidate is not recommended for rapid sequence intubation in septic shock due to risk of adrenal insufficiency; consider ketamine as alternative. Prolonged infusion is not advised due to propylene glycol vehicle and adrenal suppression. |
| Patient Advice | You may experience brief involuntary muscle movements during injection, which are usually harmless. · Tell your doctor if you have adrenal gland problems or are taking corticosteroids. · This drug may cause a temporary decrease in your body's ability to produce stress hormones. · Avoid driving or operating machinery until the effects of the medication have completely worn off. · Report any severe pain at the injection site or unusual weakness after the procedure. |
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