Etomidate Elimination Half-Time
The elimination half-life of etomidate in patients with normal liver function is approximately 3.9-5 hours (terminal elimination phase), though the clinically relevant distribution half-life that determines duration of anesthetic effect is much shorter at approximately 20 minutes. 1, 2, 3
Pharmacokinetic Profile
Etomidate follows a three-compartment pharmacokinetic model with distinct phases that are critical to understanding its clinical behavior 2, 4:
Initial distribution half-life (t½α): 2.6-2.8 minutes - this represents the ultra-rapid redistribution from plasma into highly perfused tissues like the brain 2, 3
Intermediate distribution half-life: approximately 20 minutes - this phase correlates with the hypnotic effect, as plasma concentrations above 0.23 mcg/mL (the minimum anesthetic level) are maintained during this period 1, 2
Terminal elimination half-life (t½β): 3.9-5 hours (approximately 75 minutes in some studies) - this represents the true elimination phase via hepatic metabolism 1, 2, 3
Clinical Implications of the Pharmacokinetics
The brief duration of anesthesia (3-5 minutes with standard 0.3 mg/kg dosing) is explained by rapid redistribution, not elimination. 1 The drug quickly leaves the central compartment and brain tissue during the intermediate distribution phase, terminating the hypnotic effect well before significant metabolism occurs 2.
Hypnotic plasma concentrations (>0.2 mcg/mL) are observed only during the intermediate distribution phase with t½ of approximately 20 minutes 2
The slow terminal elimination phase becomes clinically significant only with prolonged infusions exceeding 2 hours, where cumulative effects may occur 2
For continuous infusions, maintenance doses should be reduced by 50% (to approximately 0.005 mg/kg/min) after 2 hours to prevent drug accumulation 2
Metabolism and Clearance
Etomidate undergoes rapid hepatic metabolism that contributes to its pharmacokinetic profile 1, 2:
Metabolic pathway: Hydrolysis by hepatic esterases to R-(+)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid (inactive metabolite) 1, 5
Clearance: 954 ± 178 mL/min in healthy adults, which exceeds hepatic blood flow and indicates extrahepatic metabolism also occurs 3, 6
Urinary excretion: Approximately 75% of the administered dose is excreted in urine within the first 24 hours, with 80% as the inactive carboxylic acid metabolite 1
Special Populations Requiring Dose Adjustment
Elderly Patients
- Clearance decreases by approximately 2 mL/min/kg per decade of life 2
- Initial distribution volume is reduced 2
- Clinical consideration: Standard induction doses may produce prolonged effects; consider dose reduction in geriatric patients, particularly those with hypertension who may experience decreased heart rate and cardiac index 1
Cirrhotic Patients
- Terminal elimination half-life increases by 100% (doubles) 2
- Volume of distribution approximately doubles 1
- Clinical consideration: Significantly prolonged drug effect; use reduced doses and extend dosing intervals 1, 2
Patients with Severe Hepatic Dysfunction
- Impaired clearance due to reduced esterase activity 1
- Pharmacokinetic data in patients with cirrhosis and esophageal varices confirm doubled elimination half-life and volume of distribution 1
Common Pitfalls to Avoid
Do not confuse the brief clinical duration (3-5 minutes) with the elimination half-life (3.9-5 hours) - the short anesthetic effect is due to redistribution, not metabolism 1, 2
Avoid prolonged infusions without dose adjustment - after 2 hours of continuous infusion, reduce the maintenance rate by 50% to prevent accumulation related to the slow terminal elimination phase 2
Do not use standard dosing in cirrhotic patients - the doubled elimination half-life and volume of distribution necessitate significant dose reductions 1, 2
Remember that repeated bolus dosing does not cause tolerance - unlike some anesthetics, etomidate maintains consistent pharmacodynamic effects with repeated administration 3