Impact of Local Administration of Liposome Bupivacaine for Postsurgical Analgesia on Wound Healing: A Review of Data From Ten Prospective, Controlled Clinical Studies

摘要

Background: Liposome bupivacaine is a liposomal formulation that allows delivery of bupivacaine for 96 hours with a single local administration. It is indicated for the management of postsurgical pain. Objective: This retrospective review of 10 clinical trials assessed the potential impact of local anesthetics on wound healing and chondrolysis. Various doses of liposome bupivacaine and bupivacaine hydrochloride (HCl) were evaluated. Methods: Primary inclusion criteria across the 10 Phase 2 and Phase 3 randomized, double-blind studies required that patients be ≥18 years of age at the screening visit and scheduled to undergo the specified surgical procedure in each study (inguinal hernia repair, total knee arthroplasty, hemorrhoidectomy, breast augmentation, or bunionectomy). Key exclusion criteria were: a history of clinically significant medical conditions (including cardiovascular, hepatic, renal, neurologic, psychiatric, or metabolic disease) or laboratory results that indicated an increased vulnerability to the study drugs and/or procedures; medical condition(s) or concurrent surgery that may have required analgesic treatment in the postoperative period for pain that was not strictly related to the study surgery; and/or any clinically significant event or condition discovered during surgery that could have complicated the patient's postsurgical course. Assessments included the clinician's overall satisfaction with the patient's wound healing, wound status (erythema, drainage, edema, and induration), and wound scarring. Adverse events (AEs) potentially manifesting as wound complications and local AEs were also assessed. Results: In total, 823 patients received liposome bupivacaine at doses ranging from 66 to 532 mg across the 5 different surgical settings; 446 patients received bupivacaine HCl (75-200 mg), and 190 patients received placebo. Few studies showed statistically significant differences between liposome bupivacaine and the comparator (bupivacaine HCl or placebo) with regard to the clinician's overall satisfaction with patient wound healing; the incidence of erythema, drainage, edema, and induration; and wound scarring. The incidences of local AEs were similar between treatments, ranging from 9% to 20% with liposome bupivacaine across the studies compared with 8% to 19% with bupivacaine HCl. Conclusions: Liposome bupivacaine given locally at the surgical wound site appeared to have no clinically evident impact on wound or bone healing at doses up to 532 mg across different surgical models. The wound-healing profile of liposome bupivacaine was similar to that of bupivacaine HCl.