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

Abstract

<h4>Aim</h4>Pharmacokinetic simulation was used to characterize levobupivacaine disposition after regional anesthetic rescue for failed spinal anesthesia in neonates and infants.<h4>Methods</h4>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 .<h4>Results</h4>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.<h4>Conclusion</h4>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.