RESUMO
STUDY OBJECTIVE: To investigate the efficacy, safety, pharmacodynamics, and pharmacokinetics of liposomal bupivacaine (LB) administered via ultrasound-guided sciatic nerve block in the popliteal fossa in participants undergoing bunionectomy. DESIGN: Two-part, randomized, double-blind, active-controlled trial (NCT05157841). SETTING: Operating room, postanesthesia care unit, and health care facility (6 sites). PATIENTS: Adults with American Society of Anesthesiologists physical status classification ≤3 and body mass index ≥18 to <40â¯kg/m2 undergoing elective distal metaphyseal osteotomy. INTERVENTIONS: Part A participants were randomized 1:1:1 to LB 266â¯mg, LB 133â¯mg, or bupivacaine hydrochloride 50â¯mg (BUPI). Part B participants were randomized 1:1 to LB (at the dose established by part A) or BUPI. MEASUREMENTS: The primary endpoint was area under the curve (AUC) of numerical rating scale (NRS) pain intensity scores 0-96â¯h after surgery. Secondary endpoints included total postsurgical opioid consumption, opioid-free status 0-96â¯h after surgery, and pharmacokinetic endpoints. MAIN RESULTS: Part A enrolled 22 participants per group. In part B, additional participants were randomized to LB 133â¯mg (nâ¯=â¯59) and BUPI (nâ¯=â¯60) (185 total). LB 133â¯mg had significant reductions versus BUPI in the AUC of NRS pain intensity score (least squares mean [LSM], 207.4 vs 371.4; Pâ¯<â¯0.00001) and total opioid consumption 0-96â¯h after surgery (LSM, 17.7 [95% confidence interval (CI), 13.7, 22.8] morphine milligram equivalents [MMEs] vs 45.3 [95% CI, 35.1, 58.5] MMEs; Pâ¯<â¯0.00001) and an increased proportion of opioid-free participants (24.4% vs 6%; odds ratio, 5.04 [95% CI, 2.01, 12.62]; Pâ¯=â¯0.0003) in parts Aâ¯+â¯B. Adverse events were similar across groups. CONCLUSIONS: LB 133â¯mg administered via sciatic nerve block in the popliteal fossa after bunionectomy demonstrated superior and long-lasting postsurgical pain control versus BUPI. The clinical relevance of these findings is supported by concurrent reductions in pain and opioid consumption over 4â¯days after surgery and a significantly greater percentage of participants remaining opioid-free.