Population pharmacokinetics of levobupivacaine during a transversus abdominis plane block in children

TL;DR

This study characterizes the pharmacokinetics of levobupivacaine in children during transversus abdominis plane blocks to optimize dosing and reduce toxicity risk, considering variability among patients.

Contribution

It provides the first detailed pharmacokinetic analysis of levobupivacaine in pediatric TAP blocks, informing safer and more effective dosing guidelines.

Findings

Median Cmax was 0.315 mg/L, with a tmax of 17 minutes.

Between-subject variability in clearance was mainly explained by weight.

No toxicity signs observed at 0.4 mg/kg dose, but some block failures occurred.

Abstract

BACKGROUND:Levobupivacaine is commonly used during transversus abdominis plane block in pediatric patients. However, the dosing regimen is still empirical, and the pharmacokinetic properties of levobupivacaine are not considered. Here, the pharmacokinetics of levobupivacaine during an ultrasound-guided transversus abdominis plane block were evaluated to optimize dosing regimen, with regard to the between-subject variability and the volume of levobupivacaine injected.METHOD:The clinical trial (prospective, randomized, double-blind study protocol) was conducted in 40 children aged 1 to 5 years, who were scheduled for inguinal surgery. Each patient received 0.4 mg/kg of levobupivacaine with a volume of local anesthesia solution adjusted to 0.2 mL/kg of 0.2% or 0.4 mL/kg of 0.1% levobupivacaine. Blood samples were collected at 5, 15, 20, 25, 30, 45, 60, and 75 min following the block injection. The population pharmacokinetic analysis was performed using the NONMEM software.RESULTS:From the pharmacokinetic parameters obtained, median Cmax, tmax, and area under the concentration versus time curve were 0.315 mg/L, 17 min, and 41 mg/L. min, respectively. Between-subject variability (BSV) of clearance was explained by weight. At the dose regimen of 0.4 mg/kg, none of the infants showed signs of toxicity, but in 13 patients, transversus abdominis plane block failed. After analysis, BSV for absorption rate constant, distribution volume, and clearance were 81%, 47%, and 41%, respectively. Residual unexplained variability was estimated to be 14%.CONCLUSION:For improved efficiency in the pediatric population, the dose of levobupivacaine should be greater than 0.4 mg/kg. Children's weight should be considered to anticipate any risk of toxicity.