[Comparison of the pharmacokinetics of etomidate in children and in adults]
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M Sfez1, Y Le Mapihan, J C Levron
1Département d'Anesthésie-Réanimation, Hôpital Saint-Vincent de Paul, Paris.
Insights
Children require a higher etomidate dose than adults due to differences in initial distribution volume. Higher clearance in children suggests increased maintenance dose needs for etomidate.
Area of Science:
- Anesthesiology
- Pharmacokinetics
- Pediatric Medicine
Background:
- Etomidate is a widely used anesthetic agent.
- Understanding etomidate pharmacokinetics is crucial for safe and effective anesthesia, particularly in pediatric populations.
- Limited data exists comparing etomidate pharmacokinetics between children and adults.
Purpose of the Study:
- To compare the pharmacokinetics of etomidate in children and adult women.
- To determine if age influences etomidate's pharmacokinetic parameters in children.
- To establish appropriate dosing guidelines for etomidate in pediatric anesthesia.
Main Methods:
- A pharmacokinetic study comparing 12 children (7-13 years) and 4 adult women.
- Patients received alfentanil and isoflurane anesthesia.
- Etomidate was administered as a bolus (0.4 mg/kg in children, 0.3 mg/kg in adults).
- Plasma samples were analyzed using High-Performance Liquid Chromatography (HPLC).
- Data were fitted to a three-compartment model.
Main Results:
- Children exhibited a significantly higher volume of distribution of the central compartment (Vdc) compared to adults (P: 0.66 ± 0.31 vs. A: 0.27 ± 0.15 L/kg; p < 0.01).
- The initial distribution half-life (t1/2 pi) was longer in children (P: 5.4 ± 2.9 vs. A: 2.7 ± 5.7 min; p < 0.05).
- Plasma clearance was significantly higher in children (P: 17.2 ± 4.6 vs. A: 10.9 ± 3.3 mL/kg/min; p < 0.05).
- No significant age-related differences in pharmacokinetics were observed within the pediatric group.
Conclusions:
- A 30% higher etomidate bolus dose is necessary in children compared to adults to achieve similar plasma concentrations.
- The increased Vdc in children accounts for the higher initial etomidate dosage requirement.
- Higher plasma clearance in children suggests a need for potentially higher maintenance doses of etomidate.
Abstract:
Etomidate pharmacokinetics were compared in 12 children (P group) (age 7 to 13 years, weight 22 to 48 kg) and in 4 adult women (A group) (age 28 to 52 years, weight 46 to 72 kg), A.S.A. 1, undergoing minor non abdominal surgery. They were unpremedicated and anaesthetized with alfentanil 100 micrograms.kg-1, and isoflurane 2 vol % in N2O/O2 (1/1). Etomidate was administered as a bolus: 0.3 mg.kg-1 in adults and 0.4 mg.kg-1 in children. Venous plasma samples were frozen until further etomidate assay with a HPLC technique. In all patients but two children, data were fitted to a three rather than a two compartment model. Differences between groups (mean +/- SD values) included Vdc (P: 0.66 +/- 0.31 l.kg-1; A: 0.27 +/- 0.15 l.kg-1; p less than 0.01), t1/2 pi (P: 5.4 +/- 2.9 min; A: 2.7 +/- 5.7 min; p less than 0.05) and plasma clearance (P: 17.2 +/- 4.6 ml.kg-1.min-1; A: 10.9 +/- 3.3 ml.kg-1.min-1; p less than 0.05). No statistical difference was found between A and P groups for the following parameters: t1/2 alpha (37.1 +/- 12.0 min vs 26.8 + 15.1 min), t1/2 beta (260 +/- 99 min vs 175 +/- 99 min), Vdss (2.5 +/- 1.11.kg-1 vs 2.8 +/- 1.61.kg-1), Vd beta (4.1 +/- 2.41.kg-1 vs 4.0 +/- 2.21.kg-1), and MRT (228 +/- 80 min vs 172 +/- 101 min). No age-related difference was found inside P group with regard to pharmacokinetic parameters. In conclusion, a 30% higher etomidate bolus dosage is required in children than in adults to achieve similar plasma concentrations, due to a higher volume of the initial compartment. In comparison to adults the higher clearance suggests higher maintenance dose requirements in children.