Safety of Additional Local Anesthetics Soon After Liposomal Bupivacaine: A Retrospective Cohort Study

Introduction Liposomal bupivacaine (LB) produces a prolonged serum bupivacaine level. It carries a warning to avoid additional local anesthetics for 96 hours due to a theoretical additive risk of local anesthetic systemic toxicity (LAST). Whether patients exposed to additional local anesthetics soon after LB have a clinically detectable increased risk of LAST is unknown. Materials and methods Data from a single academic center were used in a cohort study of adults who received LB intraoperatively. The exposure was to additional local anesthetics within 96 hours of LB administration, and the outcome was a composite of electronic medical record data indicating possible LAST. The cumulative incidence and hazard of possible LAST (with weighted adjustment for propensity to exposure to additional local anesthetics) were calculated. A propensity score-matched sensitivity analysis was performed using an outcome based on a manual chart review. Results We identified 4306 patients who received LB, of whom 466 (12.1%) were exposed to additional local anesthetics within 96 hours of LB. There was no significant difference in the cumulative incidence of possible LAST between exposed and unexposed patients (0.9% vs. 1.5%, p = 0.28) as compared to unexposed and no significant increase in the unadjusted hazard (HR 0.51, 95% CI 0.18-1.42, p = 0.21) or the adjusted hazard (HR 0.25, 95% CI 0.07-0.89, p = 0.033) of possible LAST after exposure to additional local anesthetic. The sensitivity analysis had similar findings. Conclusions We found no evidence that exposure to additional local anesthetics within 96 hours of LB administration increases the hazard of possible LAST.