  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.
