A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17 years (PLAY).

Study Objective: To evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery.

Design: Multicenter, open-label, phase 3, randomized trial (PLAY; NCT03682302).

Setting: Operating room.

Patients: Two separate age groups were evaluated (age group 1: patients 12 to <17 years undergoing spine surgery; age group 2: patients 6 to <12 years undergoing spine or cardiac surgery).

Intervention: Randomized allocation of liposomal bupivacaine 4 mg/kg or bupivacaine hydrochloride (HCl) 2 mg/kg via local infiltration at the end of spine surgery (age group 1); liposomal bupivacaine 4 mg/kg via local infiltration at the end of spine or cardiac surgery (age group 2).

Measurements: The primary and secondary objectives were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine concentrations [C], time to C) and safety of liposomal bupivacaine, respectively.

Main Results: Baseline characteristics were comparable across groups. Mean C after liposomal bupivacaine administration was lower versus bupivacaine HCl in age group 1 (357 vs 564 ng/mL); mean C in age group 2 was 320 and 447 ng/mL for spine and cardiac surgery, respectively. Median time to C of liposomal bupivacaine occurred later with cardiac surgery versus spine surgery (22.7 vs 7.4 h). In age group 1, the incidence of adverse events (AEs) was comparable between liposomal bupivacaine (61% [19/31]) and bupivacaine HCl (73% [22/30]). In age group 2, 100% (5/5) and 31% (9/29) of patients undergoing spine and cardiac surgery experienced AEs, respectively. AEs were generally mild or moderate, with no discontinuations due to AEs or deaths.

Conclusions: Plasma bupivacaine levels following local infiltration with liposomal bupivacaine remained below the toxic threshold in adults (~2000-4000 ng/mL) across age groups and procedures. AEs were mild to moderate, supporting the safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. Clinical trial number and registry URL: ClinicalTrials.gov identifier: NCT03682302.