Abstract：
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.
Two-part, randomized, double-blind, active-controlled trial (NCT05157841).
Operating room, postanesthesia care unit, and health care facility (6 sites).
Adults with American Society of Anesthesiologists physical status classification ≤3 and body mass index ≥18 to <40 kg/m2 undergoing elective distal metaphyseal osteotomy.
Part A participants were randomized 1:1:1 to LB 266 mg, LB 133 mg, or bupivacaine hydrochloride 50 mg (BUPI). Part B participants were randomized 1:1 to LB (at the dose established by part A) or BUPI.
The primary endpoint was area under the curve (AUC) of numerical rating scale (NRS) pain intensity scores 0-96 h after surgery. Secondary endpoints included total postsurgical opioid consumption, opioid-free status 0-96 h after surgery, and pharmacokinetic endpoints.
Part A enrolled 22 participants per group. In part B, additional participants were randomized to LB 133 mg (n = 59) and BUPI (n = 60) (185 total). LB 133 mg had significant reductions versus BUPI in the AUC of NRS pain intensity score (least squares mean [LSM], 207.4 vs 371.4; P < 0.00001) and total opioid consumption 0-96 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; P < 0.00001) and an increased proportion of opioid-free participants (24.4% vs 6%; odds ratio, 5.04 [95% CI, 2.01, 12.62]; P = 0.0003) in parts A + B. Adverse events were similar across groups.
LB 133 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 4 days after surgery and a significantly greater percentage of participants remaining opioid-free.
Two-part, randomized, double-blind, active-controlled trial (NCT05157841).
Operating room, postanesthesia care unit, and health care facility (6 sites).
Adults with American Society of Anesthesiologists physical status classification ≤3 and body mass index ≥18 to <40 kg/m2 undergoing elective distal metaphyseal osteotomy.
Part A participants were randomized 1:1:1 to LB 266 mg, LB 133 mg, or bupivacaine hydrochloride 50 mg (BUPI). Part B participants were randomized 1:1 to LB (at the dose established by part A) or BUPI.
The primary endpoint was area under the curve (AUC) of numerical rating scale (NRS) pain intensity scores 0-96 h after surgery. Secondary endpoints included total postsurgical opioid consumption, opioid-free status 0-96 h after surgery, and pharmacokinetic endpoints.
Part A enrolled 22 participants per group. In part B, additional participants were randomized to LB 133 mg (n = 59) and BUPI (n = 60) (185 total). LB 133 mg had significant reductions versus BUPI in the AUC of NRS pain intensity score (least squares mean [LSM], 207.4 vs 371.4; P < 0.00001) and total opioid consumption 0-96 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; P < 0.00001) and an increased proportion of opioid-free participants (24.4% vs 6%; odds ratio, 5.04 [95% CI, 2.01, 12.62]; P = 0.0003) in parts A + B. Adverse events were similar across groups.
LB 133 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 4 days after surgery and a significantly greater percentage of participants remaining opioid-free.
摘要：
目的：为了研究疗效，安全,药效学,和脂质体布比卡因（LB）的药代动力学，通过超声引导的坐骨神经阻滞在pop窝接受骨切除术的参与者中。
方法：两部分，随机化，双盲,主动对照试验（NCT05157841）。
方法：手术室，麻醉后护理部门，和医疗保健设施(6个地点)。
方法：美国麻醉医师协会身体状况分类≤3且体重指数≥18至<40kg/m2的成年人接受选择性远端干骨干端截骨术。
方法：A部分参与者以1：1：1随机分配至LB266mg，LB133毫克，或盐酸布比卡因50mg（BUPI）。B部分参与者以1:1随机分配至LB(以A部分确定的剂量)或BUPI。
方法：主要终点是手术后0-96小时的数字评定量表（NRS）疼痛强度评分的曲线下面积（AUC）。次要终点包括术后阿片类药物总消耗量，手术后0-96小时无阿片类药物状态，和药代动力学终点。
结果：A部分每组登记22名参与者。在B部分,其他参与者被随机分为LB133mg(n=59)和BUPI(n=60)(共185例).LB133mg与BUPI相比，NRS疼痛强度评分的AUC显着降低（最小二乘平均值[LSM]，207.4vs371.4；P<0.00001）和术后0-96小时的阿片类药物总消耗量（LSM，17.7[95%置信区间(CI)，13.7，22.8]吗啡毫克当量[MME]对45.3[95％CI，35.1，58.5]MME；P<0.00001），无阿片类药物参与者的比例增加（24.4％对6％；比值比，A+B部分为5.04[95%CI,2.01,12.62];P=0.0003)。
结论：经坐骨神经阻滞后在the窝给予LB133mg，与BUPI相比，手术后疼痛控制效果更好，持续时间更长。这些发现的临床相关性得到了术后4天内疼痛和阿片类药物消耗同时减少的支持，并且参与者中保持无阿片类药物的比例明显更高。
方法：两部分，随机化，双盲,主动对照试验（NCT05157841）。
方法：手术室，麻醉后护理部门，和医疗保健设施(6个地点)。
方法：美国麻醉医师协会身体状况分类≤3且体重指数≥18至<40kg/m2的成年人接受选择性远端干骨干端截骨术。
方法：A部分参与者以1：1：1随机分配至LB266mg，LB133毫克，或盐酸布比卡因50mg（BUPI）。B部分参与者以1:1随机分配至LB(以A部分确定的剂量)或BUPI。
方法：主要终点是手术后0-96小时的数字评定量表（NRS）疼痛强度评分的曲线下面积（AUC）。次要终点包括术后阿片类药物总消耗量，手术后0-96小时无阿片类药物状态，和药代动力学终点。
结果：A部分每组登记22名参与者。在B部分,其他参与者被随机分为LB133mg(n=59)和BUPI(n=60)(共185例).LB133mg与BUPI相比，NRS疼痛强度评分的AUC显着降低（最小二乘平均值[LSM]，207.4vs371.4；P<0.00001）和术后0-96小时的阿片类药物总消耗量（LSM，17.7[95%置信区间(CI)，13.7，22.8]吗啡毫克当量[MME]对45.3[95％CI，35.1，58.5]MME；P<0.00001），无阿片类药物参与者的比例增加（24.4％对6％；比值比，A+B部分为5.04[95%CI,2.01,12.62];P=0.0003)。
结论：经坐骨神经阻滞后在the窝给予LB133mg，与BUPI相比，手术后疼痛控制效果更好，持续时间更长。这些发现的临床相关性得到了术后4天内疼痛和阿片类药物消耗同时减少的支持，并且参与者中保持无阿片类药物的比例明显更高。
