Disposition of levobupivacaine during intraoperative continuous caudal epidural analgesia in a preterm neonate

Background. Continuous caudal epidural analgesia used intraoperatively in children is an effective and safe technique. However, in preterm neonates, developmental factors may significantly affect levobupivacaine disposition, leading to variable pharmacokinetics, pharmacodynamics, and potential large-variable systemic toxicity of local anesthetics. Objective. To our knowledge, this is the first case report describing the disposition of levobupivacaine used for intraoperative caudal epidural analgesia in a preterm neonate treated for the postoperative pain profile. Method. 4-days old neonate (postmenstrual age 35+5, weight 2140 g) with congenital anal atresia received continuous caudal epidural long-term analgesia (loading dose 1.694 mg/kg, initial infusion 0.34 mg/kg/hour) before correction surgery. The blood samples were obtained at 1.0, 1.5, 6.5, 12, and 36.5 h after the start of epidural infusion. The pharmacokinetic profile of levobupivacaine was determined by using the Stochastic Approximation Expectation Maximization algorithm. COMFORT and NIPS pain scores were used for the assessment of epidural analgesia. Results. The levobupivacaine absorption rate constant, apparent volume of distribution, apparent clearance, and elimination half-life were 10.8 h-1, 0.9 L, 0.086 L/h, and 7.3 h, respectively. Conclusion. The results confirm our hypothesis of altered pharmacokinetics in the preterm neonate. Therefore, levobupivacaine therapy in these patients should be carefully monitored. Since therapeutic drug monitoring of levobupivacaine is not established in clinical routines, we suggest monitoring the intraoperative pain profile using validated scores. Trial Registration: EudraCT number: 2020-000595-37