Postoperative pain treatment after total knee arthroplasty: A systematic review

IntroductionThe aim of this systematic review was to document efficacy, safety and quality of evidence of analgesic interventions after total knee arthroplasty (TKA).MethodsThis PRISMA-compliant and PROSPERO-registered review includes all-language randomized controlled trials of medication-based analgesic interventions after TKA. Bias was evaluated according to Cochrane methodology. Outcomes were opioid consumption (primary), pain scores at rest and during mobilization, adverse events, and length of stay. Interventions investigated in three or more trials were meta-analysed. Outcomes were evaluated using forest plots, Grading of Recommendations Assessment, Development and Evaluation (GRADE), L’Abbe Plots and trial sequential analysis.ResultsThe included 113 trials, investigating 37 different analgesic interventions, were characterized by unclear/high risk of bias, low assay sensitivity and considerable differences in pain assessment tools, basic analgesic regimens, and reporting of adverse events. In meta-analyses single and continuous femoral nerve block (FNB), intrathecal morphine, local infiltration analgesia, intraarticular injection of local anaesthetics, non-steroidal anti-inflammatory drugs, and gabapentinoids demonstrated significant analgesic effects. The 24-hour morphine-sparing effects ranged from 4.2 mg (CI: 1.3, 7.2; intraarticular local anaesthetics), to 16.6 mg (CI: 11.2, 22; single FNB). Pain relieving effects at rest at 6 hours ranged from 4 mm (CI: -10, 2; gabapentinoids), to 19 mm (CI: 8, 31; single FNB), and at 24 hours from 3 mm (CI: -2, 8; gabapentinoids), to 16 mm (CI: 8, 23; continuous FNB). GRADE-rated quality of evidence was generally low.ConclusionA low quality of evidence, small sample sizes and heterogeneity of trial designs prohibit designation of an optimal procedure-specific analgesic regimen after TKA.

引言
本系统综述旨在明确全膝关节置换术（total knee arthroplasty, TKA）后镇痛干预措施的疗效、安全性及证据质量。

方法
本符合PRISMA标准且已在PROSPERO注册的综述，纳入所有语言的全膝关节置换术后药物镇痛干预相关随机对照试验。偏倚评估采用Cochrane协作网方法。结局指标包括阿片类药物消耗量（主要结局）、静息及活动时疼痛评分、不良事件与住院时长。对在3项及以上试验中被研究的干预措施开展Meta分析。结局指标通过森林图、推荐意见分级、评估、发展与评价系统（Grading of Recommendations Assessment, Development and Evaluation, GRADE）、L'Abbe图以及试验序贯分析进行评价。

结果
纳入的113项试验共研究了37种不同的镇痛干预措施，其特点为偏倚风险不明确或偏高、检测敏感性较低，且疼痛评估工具、基础镇痛方案以及不良事件报告方式存在显著异质性。Meta分析结果显示，单次及持续股神经阻滞（femoral nerve block, FNB）、鞘内注射吗啡、局部浸润镇痛、关节腔内局部麻醉药注射、非甾体类抗炎药以及加巴喷丁类药物均展现出显著镇痛效果。24小时阿片类药物节约效应范围为4.2mg（置信区间（confidence interval, CI）：1.3, 7.2；关节腔内局部麻醉药）至16.6mg（CI: 11.2, 22；单次股神经阻滞）。静息状态下6小时的疼痛缓解效应差值范围为4mm（CI: -10, 2；加巴喷丁类）至19mm（CI: 8, 31；单次股神经阻滞）；24小时的疼痛缓解效应差值范围为3mm（CI: -2, 8；加巴喷丁类）至16mm（CI: 8, 23；持续股神经阻滞）。GRADE评级的证据质量整体偏低。

结论
证据质量偏低、样本量较小以及试验设计异质性较高，使得无法确定全膝关节置换术后最优的个体化镇痛方案。