Pharmacokinetics of bupivacaine following intraoperative intercostal nerve block in neonates and in infants aged less than 6 months

Abstract

Pharmacokinetics and blood concentrations of bupivacaine were studied after intercostal nerve blocks were performed intraoperatively using 1.5 mg·kg-1 in 11 neonates (age 0-28 days) and 11 infants between age 1 and 6 months. The study aimed to provide pharmacokinetic data that are limited in these age groups, and to identify any adverse effects of intercostal nerve block in infancy. Arterial blood samples were taken at 0, 5, 10, 15, 20, 30, 60, 120, 240, and 360 min. Whole blood bupivacaine was assayed by high-performance liquid chromatography. Peak blood concentrations were attained within 10 min in 18 of 22 subjects, and were 0.82 ± 0.56 μg·ml-1 (mean and SD) and 0.91 ± 0.27 μg·ml-1 in neonates and infants, respectively. Pharmacokinetic variables in the two groups included elimination half-life (t 1/2 β): 132 ± 59 min and 102 ± 39 min; steady-state volume of distribution (V(d)ss): 2.56 ± 0.76 l·kg-1 and 2.17 ± 0.17 l·kg-1; and total body clearance (Clt): 16.93 ± 9.32 ml·min-1·kg-1 and 15.71 ± 6.99 ml·min-1·kg-1. There was no statistically significant difference between neonates and infants with regard to any of these parameters. Patients were further divided into those with acyanotic and cyanotic disease. Cyanotic infants were significantly heavier than acyanotic infants (P < 0.05), but no other differences were demonstrated. No adverse effects resulting from the technique were identified. Elimination half-lives were shorter and total body clearance greater than has been reported in some pediatric studies, and in comparison with published adult data, pharmacokinetics of bupivacaine in the neonates and infants in this study are characterized by larger volumes of distribution, greater clearance, and similar elimination half-lives.