Abstract

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−1 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−1 with rescue caudal levobupivacaine 1.5–2.5 mg kg−1. Results: A one-compartment model with a mature clearance 21.5 L h−1 70 kg−1 (CV 47.3%) and central volume 189 L 70 kg−1 (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−1, 2 mg kg−1, and 2.5 mg kg−1 was 2.05 mg L−1, 2.5 mg L−1, and 2.9 mg L−1 respectively. Conclusion: Total bupivacaine concentrations greater than 2.5 mg L−1 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 1 h after spinal levobupivacaine administration are below the neurotoxic concentration threshold.