Pharmacokinetics of Bupivacaine following Caudal Anesthesia in Infants

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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 .mu.g/ml. This time to reach the peak ranged from 10 to 60 min. Terminal half-life (T 1/2.beta.) was 7.7 .+-. 2.4 h (mean .+-. SD), the volume of distribution (Vss) was 3.9 .+-. 2.0 l .cntdot. kg, and the total body clearance (CL) was 7.1 .+-. 3.2 ml .cntdot. min .cntdot. 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.