Prediction of levobupivacaine concentrations in neonates and infants following neuraxial rescue blocks.

Aim: Pharmacokinetic simulation was used to characterize levobupivacaine disposition after regional anesthetic rescue for failed spinal anesthesia in neonates and infants.

Methods: Population pharmacokinetics of levobupivacaine were estimated after spinal blockade in a cohort of neonates and infants (n = 25, postnatal age 5-18 weeks, gestation 21-41 weeks, weight 2.4-6 kg). Total levobupivacaine concentrations were assayed 3-4 times in the first hour after spinal levobupivacaine 1 mg kg administration. Parameters were estimated using nonlinear mixed-effects models and supported by priors. Covariates included postnatal age and total body weight. Parameter estimates were used to simulate total levobupivacaine concentrations after a primary spinal levobupivacaine 1 mg kg with rescue caudal levobupivacaine 1.5-2.5 mg kg .

Results: A one-compartment model with a mature clearance 21.5 L h  70 kg (CV 47.3%) and central volume 189 L 70 kg (CV 37%) adequately described time-concentration profiles. Clearance maturation was described using a maturation half-time of 11.5 weeks postnatal age. The absorption half-time for spinal levobupivacaine was 2.6 min (CV 56.8%). The upper (97.5% prediction) for peak concentrations after rescue caudal levobupivacaine were 1.5 mg kg , 2 mg kg , and 2.5 mg kg was 2.05 mg L , 2.5 mg L , and 2.9 mg L respectively.

Conclusion: Total bupivacaine concentrations greater than 2.5 mg L are associated with neurotoxicity in adults. Predicted concentrations after either a repeat spinal or a caudal rescue dose of levobupivacaine 1.5 mg kg 1 h after spinal levobupivacaine administration are below the neurotoxic concentration threshold.