Pharmacokinetic profiles of epidural bupivacaine and ropivacaine following single-shot and continuous epidural use in young infants

Aims: The primary aim of this study was to describe the pharmacokinetics of total and unbound bupivacaine and ropivacaine following epidural bolus and infusion in neonates and young infants. Secondary aims were to investigate the influence of alpha-1-acid glycoprotein (AAG) on the concentration–time profiles and to determine the efficacy and adverse event profile of the epidural regimen. Methods/Materials: Thirty-one infants aged 40–63 weeks of postmenstrual age (PMA) undergoing hernia repair or abdominal surgery received an epidural injection of 1.5 mg·kg−1 bupivacaine (0.25%) or ropivacaine (0.2%) followed 2 h later by an infusion of 0.2 mg·kg−1·h−1 in those undergoing abdominal surgery. Total and unbound concentrations of bupivacaine and ropivacaine were analyzed using nonmem. Hourly pain scores and adverse effects were recorded. Results: Bupivacaine data were available from 11 infants (five had infusions) and ropivacaine from 13 infants (four had infusions). Alpha-1-acid glycoprotein and total bupivacaine and ropivacaine concentrations accumulated during infusions, but unbound concentrations did not. Maximum unbound concentrations for bupivacaine and ropivacaine were 0.12 mg·l−1 (bupivacaine) and 0.13 mg·l−1 (ropivacaine). Typical clearance/bioavailability estimates of total (unbound) bupivacaine were 0.215 (4.65) l·h−1·kg−1 and of total (unbound) ropivacaine were 0.288 (3.31) l·h−1·kg−1. Pain scores requiring pain team referral occurred once with bupivacaine and four times with ropivacaine. No toxicity was observed. Conclusions: Epidural infusions of 0.2 mg−1·kg−1·h−1 bupivacaine or ropivacaine appeared to be well tolerated and efficacious in this population. No accumulation of unbound drug concentrations occurred