Weinstein Erica J, Levene Jacob L, Cohen Marc S, Andreae Doerthe A, Chao Jerry Y, Johnson Matthew, Hall Charles B, Andreae Michael H
Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Ave, Bronx, NY, USA, 10461.
Cochrane Database Syst Rev. 2018 Jun 20;6(6):CD007105. doi: 10.1002/14651858.CD007105.pub4.
Regional anaesthesia may reduce the rate of persistent postoperative pain (PPP), a frequent and debilitating condition. This review was originally published in 2012 and updated in 2017.
To compare local anaesthetics and regional anaesthesia versus conventional analgesia for the prevention of PPP beyond three months in adults and children undergoing elective surgery.
We searched CENTRAL, MEDLINE, and Embase to December 2016 without any language restriction. We used a combination of free text search and controlled vocabulary search. We limited results to randomized controlled trials (RCTs). We updated this search in December 2017, but these results have not yet been incorporated in the review. We conducted a handsearch in reference lists of included studies, review articles and conference abstracts. We searched the PROSPERO systematic review registry for related systematic reviews.
We included RCTs comparing local or regional anaesthesia versus conventional analgesia with a pain outcome beyond three months after elective, non-orthopaedic surgery.
At least two review authors independently assessed trial quality and extracted data and adverse events. We contacted study authors for additional information. We presented outcomes as pooled odds ratios (OR) with 95% confidence intervals (95% CI), based on random-effects models (inverse variance method). We analysed studies separately by surgical intervention, but pooled outcomes reported at different follow-up intervals. We compared our results to Bayesian and classical (frequentist) models. We investigated heterogeneity. We assessed the quality of evidence with GRADE.
In this updated review, we identified 40 new RCTs and seven ongoing studies. In total, we included 63 RCTs in the review, but we were only able to synthesize data on regional anaesthesia for the prevention of PPP beyond three months after surgery from 39 studies, enrolling a total of 3027 participants in our inclusive analysis.Evidence synthesis of seven RCTs favoured epidural anaesthesia for thoracotomy, suggesting the odds of having PPP three to 18 months following an epidural for thoracotomy were 0.52 compared to not having an epidural (OR 0.52 (95% CI 0.32 to 0.84, 499 participants, moderate-quality evidence). Simlarly, evidence synthesis of 18 RCTs favoured regional anaesthesia for the prevention of persistent pain three to 12 months after breast cancer surgery with an OR of 0.43 (95% CI 0.28 to 0.68, 1297 participants, low-quality evidence). Pooling data at three to 8 months after surgery from four RCTs favoured regional anaesthesia after caesarean section with an OR of 0.46, (95% CI 0.28 to 0.78; 551 participants, moderate-quality evidence). Evidence synthesis of three RCTs investigating continuous infusion with local anaesthetic for the prevention of PPP three to 55 months after iliac crest bone graft harvesting (ICBG) was inconclusive (OR 0.20, 95% CI 0.04 to 1.09; 123 participants, low-quality evidence). However, evidence synthesis of two RCTs also favoured the infusion of intravenous local anaesthetics for the prevention of PPP three to six months after breast cancer surgery with an OR of 0.24 (95% CI 0.08 to 0.69, 97 participants, moderate-quality evidence).We did not synthesize evidence for the surgical subgroups of limb amputation, hernia repair, cardiac surgery and laparotomy. We could not pool evidence for adverse effects because the included studies did not examine them systematically, and reported them sparsely. Clinical heterogeneity, attrition and sparse outcome data hampered evidence synthesis. High risk of bias from missing data and lack of blinding across a number of included studies reduced our confidence in the findings. Thus results must be interpreted with caution.
AUTHORS' CONCLUSIONS: We conclude that there is moderate-quality evidence that regional anaesthesia may reduce the risk of developing PPP after three to 18 months after thoracotomy and three to 12 months after caesarean section. There is low-quality evidence that regional anaesthesia may reduce the risk of developing PPP three to 12 months after breast cancer surgery. There is moderate evidence that intravenous infusion of local anaesthetics may reduce the risk of developing PPP three to six months after breast cancer surgery.Our conclusions are considerably weakened by the small size and number of studies, by performance bias, null bias, attrition and missing data. Larger, high-quality studies, including children, are needed. We caution that except for breast surgery, our evidence synthesis is based on only a few small studies. On a cautionary note, we cannot extend our conclusions to other surgical interventions or regional anaesthesia techniques, for example we cannot conclude that paravertebral block reduces the risk of PPP after thoracotomy. There are seven ongoing studies and 12 studies awaiting classification that may change the conclusions of the current review once they are published and incorporated.
区域麻醉可能降低持续性术后疼痛（PPP）的发生率，这是一种常见且使人衰弱的病症。本综述最初发表于2012年，并于2017年更新。
比较局部麻醉药和区域麻醉与传统镇痛方法在接受择期手术的成人和儿童中预防三个月以上PPP的效果。
我们检索了截至2016年12月的CENTRAL、MEDLINE和Embase，无语言限制。我们使用了自由文本搜索和控制词汇搜索相结合的方法。我们将结果限制为随机对照试验（RCT）。我们在2017年12月更新了此搜索，但这些结果尚未纳入本综述。我们对纳入研究的参考文献列表、综述文章和会议摘要进行了手工检索。我们在PROSPERO系统评价注册库中搜索相关的系统评价。
我们纳入了比较局部或区域麻醉与传统镇痛方法的RCT，这些研究的疼痛结局是在择期非骨科手术后三个月以上。
至少两名综述作者独立评估试验质量，并提取数据和不良事件。我们联系研究作者获取更多信息。我们基于随机效应模型（逆方差法），将结局呈现为合并比值比（OR）及95%置信区间（95%CI）。我们按手术干预分别分析研究，但合并不同随访间隔报告的结局。我们将结果与贝叶斯模型和经典（频率学派）模型进行比较。我们调查了异质性。我们使用GRADE评估证据质量。
在本次更新的综述中，我们识别出40项新的RCT和7项正在进行的研究。我们总共纳入了63项RCT进行综述，但我们仅能综合39项研究中关于区域麻醉预防术后三个月以上PPP的数据，在我们的纳入分析中共有3027名参与者。七项RCT的证据综合表明，开胸手术采用硬膜外麻醉有优势，提示开胸手术后采用硬膜外麻醉，在3至18个月发生PPP的几率为0.52，而未采用硬膜外麻醉的几率为0.52（OR 0.52（95%CI 0.32至0.84，499名参与者，中等质量证据）。同样，18项RCT的证据综合表明，区域麻醉在预防乳腺癌手术后3至12个月持续性疼痛方面有优势，OR为0.43（95%CI 0.28至0.68，1297名参与者，低质量证据）。四项RCT在术后3至8个月的数据合并表明，剖宫产术后区域麻醉有优势，OR为0.46，（95%CI 0.28至0.78；551名参与者，中等质量证据）。三项研究连续输注局部麻醉药预防髂嵴取骨（ICBG）后3至55个月PPP的证据综合尚无定论（OR 0.20，95%CI 0.04至1.09；123名参与者，低质量证据）。然而，两项RCT的证据综合也表明，乳腺癌手术后3至6个月静脉输注局部麻醉药预防PPP有优势，OR为0.24（95%CI 0.08至0.69，97名参与者，中等质量证据）。我们未综合肢体截肢、疝气修补、心脏手术和剖腹手术等手术亚组的证据。我们无法汇总不良反应的证据，因为纳入研究未系统检查不良反应，且报告稀少。临床异质性、失访和稀疏的结局数据阻碍了证据综合。许多纳入研究中数据缺失和缺乏盲法导致的高偏倚风险降低了我们对研究结果的信心。因此，结果必须谨慎解释。
我们得出结论，有中等质量证据表明，区域麻醉可能降低开胸手术后3至18个月以及剖宫产术后3至12个月发生PPP的风险。有低质量证据表明，区域麻醉可能降低乳腺癌手术后3至12个月发生PPP的风险。有中等证据表明，静脉输注局部麻醉药可能降低乳腺癌手术后3至6个月发生PPP风险。我们的结论因研究规模小、数量少、执行偏倚、零效应偏倚、失访和数据缺失而大为削弱。需要开展更大规模、高质量的研究，包括儿童。我们提醒，除乳腺手术外，我们的证据综合仅基于少数小型研究。需注意的是，我们不能将结论推广到其他手术干预或区域麻醉技术，例如我们不能得出椎旁阻滞可降低开胸手术后PPP风险的结论。有7项正在进行的研究和12项待分类研究，一旦发表并纳入，可能会改变当前综述的结论。
