Oxford Orthopaedic Engineering Centre, Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom.
Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom.
JAMA Surg. 2022 Jun 1;157(6):481-489. doi: 10.1001/jamasurg.2022.0713.
More than half of patients who undergo knee replacement surgery report substantial acute postoperative pain.
To evaluate the efficacy and cost-effectiveness of periarticular liposomal bupivacaine for recovery and pain management after knee replacement.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, patient-blinded, pragmatic, randomized clinical superiority trial involved 533 participants at 11 institutions within the National Health Service in England. Adults undergoing primary unilateral knee replacement for symptomatic end-stage osteoarthritis were enrolled between March 29, 2018, and February 29, 2020, and followed up for 1 year after surgery. Follow-up was completed March 1, 2021. A per-protocol analysis for each coprimary outcome was performed in addition to the main intention-to-treat analysis.
Two hundred sixty-six milligrams of liposomal bupivacaine admixed with 100 mg of bupivacaine hydrochloride compared with 100 mg of bupivacaine hydrochloride alone (control) administered by periarticular injection at the time of surgery.
The coprimary outcomes were Quality of Recovery 40 (QoR-40) score at 72 hours and pain visual analog scale (VAS) score area under the curve (AUC) from 6 to 72 hours. Secondary outcomes included QoR-40 and mean pain VAS at days 0 (evening of surgery), 1, 2, and 3; cumulative opioid consumption for 72 hours; functional outcomes and quality of life at 6 weeks, 6 months, and 1 year; and cost-effectiveness for 1 year. Adverse events and serious adverse events up to 12 months after randomization were also assessed.
Among the 533 participants included in the analysis, the mean (SD) age was 69.0 (9.7) years; 287 patients were women (53.8%) and 246 were men (46.2%). Baseline characteristics were balanced between study groups. There was no difference between the liposomal bupivacaine and control groups in QoR-40 score at 72 hours (adjusted mean difference, 0.54 [97.5% CI, -2.05 to 3.13]; P = .64) or the pain VAS score AUC at 6 to 72 hours (-21.5 [97.5% CI, -46.8 to 3.8]; P = .06). Analyses of pain VAS and QoR-40 scores demonstrated only 1 statistically significant difference, with the liposomal bupivacaine arm having lower pain scores the evening of surgery (adjusted difference -0.54 [97.5% CI, -1.07 to -0.02]; P = .02). No difference in cumulative opioid consumption and functional outcomes was detected. Liposomal bupivacaine was not cost-effective compared with the control treatment. No difference in adverse or serious adverse events was found between the liposomal bupivacaine and control groups.
This study found no difference in postoperative recovery or pain associated with the use of periarticular liposomal bupivacaine compared with bupivacaine hydrochloride alone in patients who underwent knee replacement surgery.
isrctn.com Identifier: ISRCTN54191675.
超过一半接受膝关节置换手术的患者报告术后存在明显的急性疼痛。
评估关节周围包埋型布比卡因在膝关节置换术后恢复和疼痛管理中的疗效和成本效益。
设计、地点和参与者：这是一项多中心、患者盲法、实用、随机临床优势试验，涉及英格兰国民保健服务系统内 11 个机构的 533 名参与者。招募了 533 名患有症状性终末期骨关节炎的成年人，接受单侧初次膝关节置换术，于 2018 年 3 月 29 日至 2020 年 2 月 29 日入组，并在手术后 1 年进行随访。2021 年 3 月 1 日完成随访。对每个主要复合结局进行了意向治疗分析和主要方案分析。
关节周围注射时，与单独 100mg 布比卡因盐酸盐（对照）相比，注射 266mg 包埋型布比卡因，混合 100mg 布比卡因盐酸盐。
主要复合结局是术后 72 小时 QoR-40 评分和术后 6 至 72 小时疼痛视觉模拟评分（VAS）曲线下面积（AUC）。次要结局包括术后 0（手术当晚）、1、2 和 3 天的 QoR-40 和平均疼痛 VAS、72 小时内累积阿片类药物消耗量、术后 6 周、6 个月和 1 年的功能结局和生活质量，以及术后 1 年的成本效益。还评估了随机分组后 12 个月内的不良事件和严重不良事件。
在纳入分析的 533 名参与者中，平均（SD）年龄为 69.0（9.7）岁；287 名患者为女性（53.8%），246 名患者为男性（46.2%）。两组的基线特征平衡。在术后 72 小时 QoR-40 评分（调整平均差异，0.54 [97.5%CI，-2.05 至 3.13]；P = .64）或术后 6 至 72 小时疼痛 VAS 评分 AUC（-21.5 [97.5%CI，-46.8 至 3.8]；P = .06）方面，包埋型布比卡因与对照组之间没有差异。疼痛 VAS 和 QoR-40 评分分析仅显示出 1 个有统计学意义的差异，包埋型布比卡因组在手术当晚疼痛评分较低（调整差异-0.54 [97.5%CI，-1.07 至 -0.02]；P = .02）。未发现累积阿片类药物消耗和功能结局的差异。与布比卡因盐酸盐对照治疗相比，包埋型布比卡因不具有成本效益。包埋型布比卡因组与对照组之间未发现不良或严重不良事件的差异。
本研究发现，在膝关节置换术后恢复或疼痛方面，与单独使用布比卡因盐酸盐相比，关节周围使用包埋型布比卡因没有差异。
isrctn.com 标识符：ISRCTN54191675。
