Incidence of adverse events attributable to bupivacaine liposome injectable suspension or plain bupivacaine for postoperative pain in pediatric surgical patients: A retrospective matched cohort analysis

Abstract Surgical wound infiltration with local anestheticsis common as part of multimodal analgesia and enhanced recovery pathways in pediatric surgical patients. Liposomal bupivacainecan provide up to 92 hours of pain relief, and was approved by the U.S Food and Drug Administration for local infiltration in adults. It is also commonly used by pediatric surgeons, but its safety profile in this age group has not been described. The aim of this study was to describe the incidence of local anestheticsystemic toxicity syndrome in pediatric surgical patients receiving liposomal bupivacainecompared to plain bupivacainefor surgical wound infiltration. We conducted a retrospective, single center, assessor blinded cohort study of pediatric surgical inpatients having open or laparoscopic surgery in the Cleveland Clinic between 2013 and 2017 and receiving wound infiltration with local anesthetics. We compared the incidence of local anestheticsystemic toxicity among those who received any dose of liposomal bupivacaineand those who received plain bupivacaine. Groups were matched 1:2 according to procedure type, age, and physical status score. Local anestheticsystemic toxicity was primarily defined as at least two signs or symptoms possibly related to anesthetictoxicity, as judged by two independent adjudicators blinded to the type of local anesthetic. A sensitivity analysis compared the incidence of a single sign/symptom possibly related to anesthetictoxicity. A total of 924 surgical cases were included in the final analysis (356 liposomal bupivacaineand 568 plain bupivacainecases). The primary outcome did not occur in any patient. The sensitivity analysis found three cases in the liposomal bupivacainegroup and two cases in the plain bupivacainegroup having a single sign/symptom possibly related to local anestheticadministration (relative risk 2.4, 95% CI 0.4-14.0, P = 0.38). In a cohort of pediatric surgical patients receiving wound infiltration with either plain or liposomal bupivacaine, we identified no cases of local anestheticsystemic toxicity syndrome, and only few patients with any sign or symptom that could potentially be related to local anesthetic toxicity.