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Pharmacokinetics of bupivacaine following caudal anesthesia in infants
J X Mazoit1, D D Denson, K Samii
1Department of Anesthesiology, University Paris-Sud, Hôpital, Bicétre, France.
Insights
Bupivacaine pharmacokinetics in infants show similar peak concentrations to adults but a higher free drug fraction, especially in younger infants. This increased free fraction necessitates caution when using bupivacaine in pediatric patients.
Area of Science:
- Anesthesiology
- Pediatric Pharmacology
- Clinical Chemistry
Background:
- Bupivacaine is a commonly used local anesthetic in pediatric surgery.
- Understanding its pharmacokinetic profile and protein binding in infants is crucial for safe dosing.
Purpose of the Study:
- To investigate the pharmacokinetics and protein binding of bupivacaine following caudal injection in infants.
- To compare infant bupivacaine pharmacokinetics with adult data.
Main Methods:
- Caudal injection of bupivacaine (2.5 mg/kg) in 13 infants (1-6 months).
- Serial blood sampling for bupivacaine concentration measurement (gas chromatography).
- Ultrafiltration technique for protein binding assessment.
Main Results:
- Peak serum bupivacaine concentrations were comparable to adult values.
- Terminal half-life (T1/2 beta) was 7.7 ± 2.4h, volume of distribution (Vss) was 3.9 ± 2.0 L/kg, and clearance (CL) was 7.1 ± 3.2 mL/min/kg.
- The free fraction of bupivacaine was significantly higher in infants (0.16 ± 0.07) and inversely correlated with age.
Conclusions:
- Infant pharmacokinetics of caudal bupivacaine are characterized by Cmax similar to adults.
- Increased bupivacaine free fraction in infants up to 6 months requires careful consideration.
- Clinical significance of elevated free bupivacaine fraction in infants warrants further investigation.
Abstract:
Pharmacokinetics and protein binding of bupivacaine were studied after caudal injection of 2.5 mg/kg in 13 ASA PS 1 infants (1-6 months of age) scheduled for elective hernia repair. Blood was sampled at frequent intervals from 5 min to 600 min in all but one patients. Additional samples were taken at 720 and 840 min in five patients. Bupivacaine concentration was measured using gas chromatography. Protein binding was measured using ultrafiltration. Peak serum concentrations ranged between 0.55 and 1.93 micrograms/ml. The time to reach the peak ranged from 10 to 60 min. Terminal half-life (T1/2 beta) was 7.7 +/- 2.4h (mean +/- SD), the volume of distribution (Vss) was 3.9 +/- 2.01.kg, and the total body clearance (CL) was 7.1 +/- 3.2 ml.min.kg-1. The free fraction was markedly increased (0.16 +/- 0.07) when compared with published adult values, and showed a highly significant negative correlation with age. Alpha 1 acid glycoprotein measured in the same infants correlated significantly with age. In conclusion, pharmacokinetics of caudal bupivacaine in infants are characterized by Cmax of total drug similar to those observed in adults after epidural injection. The free fraction is increased at least until 6 months of life. This suggests caution in the use of bupivacaine in infants until we understand the clinical significance of this increased free fraction.