Pharmacokinetics of levobupivacaine following infant spinal anesthesia

Background: Infant spinal anesthesia with levobupivacaine has been promoted as a technique to reduce both the risk of postoperative apnea and exposure to volatile anesthesia. There is, however, no pharmacokinetic data to support the currently recommended doses. 

Aims: Our aim was to determine whether infant levobupivacaine spinal anesthesia is associated with plasma concentrations consistent with a low risk of local anesthetic systemic toxicity. 

Methods: This was an open-label pharmacokinetic safety and tolerability study of levobupivacaine spinal anesthesia in infants <55 weeks Post Menstrual Age undergoing lower abdominal surgery. Infants received a spinal anesthetic with levobupivacaine 1 mg·kg^-1 in the left lateral position. 

Results: Spinal anesthesia was successful in 25 (86.2%) of 29 infants (postmenstrual age 36-52 weeks; weight 2.2-4.7 kg). The median (IQR) total venous levobupivacaine plasma concentrations was 0.33 (0.25-0.42) μg·ml^-1 and unbound venous levobupivacaine was 19.5 (14.5-38) ng·ml^-1. Median protein binding was 93.5 (91.4-96%). Alpha-1 acid glycoprotein concentrations were 0.25 (0.17-0.37) g·l^-1 and albumin concentrations were 29 (24-32) g·l^-1. 

Conclusion: Total plasma concentrations and unbound (free) concentration of levobupivacaine were consistently lower than concentrations reported in cases of pediatric local anesthetic toxicity. In a small number of infants requiring a repeat spinal of 1 mg·kg^-1 was also associated with acceptable total and free concentrations. We conclude that levobupivacaine at 1 mg·kg^-1 is associated with no systemic side effects in infants receiving awake spinal anesthesia.