局麻药中加入肾上腺素在椎管内麻醉或局部麻醉中的益处及危害：meta分析
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Benefit and Harm of Adding Epinephrine to a Local Anesthetic for Neuraxial and Locoregional Anesthesia:A Meta-analysis of Randomized Controlled Trials With Trial Sequential Analyses
背景与目的：本研究主要探讨局麻药中加入肾上腺素在硬膜外麻醉、蛛网膜下腔麻醉及局部麻醉中的益处和危害。
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方法：检索相关数据库2017年10月前的随机对照试验：任何局部麻醉药联合肾上腺素的方案与同一局部麻醉药未加入肾上腺素进行比较，指标为镇痛持续时间，运动及感觉消退时间或任何不良反应。使用Cochrane偏倚风险工具评估各随机试验质量，并使用随机效应模型。应用试验序贯分析（TSA）来确定样本量大小，并根据所考虑的指标设定检验效能，对于多个结果指标的比较，检验水准调整为α=1％。
结果：本试验共纳入70项随机试验（从1970年至2017年3644例患者，17个国家）。每项试验的中位人数为44（9-174）。 37项随机试验（1781例患者）：硬膜外肾上腺素， 27项随机试验（1660例患者）：蛛网膜下腔麻醉，6项随机试验（203例）：局部麻醉（坐骨，股骨，腋窝）。在硬膜外局麻药中添加肾上腺素不能将术后疼痛强度降低30％，并且不影响术中动脉低血压的风险。差异不足以证实肾上腺素添加对分娩时运动阻滞，低血压（20％），尿潴留（23％）或静息时疼痛强度（27％）的影响是否有区别。蛛网膜下腔麻醉时局麻药中加入肾上腺素可增加运动阻滞持续时间（加权平均差[WMD]=64分钟; 99％CI：37-91），镇痛时间（WMD=34分钟; 99％CI=6-62）和到运动、感觉消退的时间差值（WMD= 20分钟; 99％CI=11-28）。在局部麻醉药中添加肾上腺素可以增加镇痛时间（WMD= 66分钟; 98％CI=32-100）。
结论：蛛网膜下腔麻醉或局部麻醉时局麻药中加入肾上腺素可延长镇痛和运动阻滞时间，且均不超过60分钟。但硬膜外醉或腰硬联合麻醉时这一影尚不明确。
Clément Tschopp；MSc,Martin R. Tramèr； DPhil,Alexis Schneider；
Benefit and Harm of Adding Epinephrine to a LocalAnesthetic for Neuraxial and Locoregional Anesthesia:A Meta-analysis of Randomized Controlled Trials With Trial Sequential Analyses；
Anesthesia and analgesia ,2018
BACKGROUND: This systematic review examines the benefit and harm of adding epinephrine to local anesthetics for epidural, intrathecal, or locoregional anesthesia.
METHODS:We searched electronic databases to October 2017 for randomized trials comparing any local anesthetic regimen combined with epinephrine, with the same local anesthetic regimen without epinephrine, reporting on duration of analgesia, time to 2 segments regression,or any adverse effects. Trial quality was assessed using the Cochrane risk of bias tool and a random-effects model was used. Trial sequential analyses (TSA) were applied to identify the information size (IS; number of patients needed to reach a definite conclusion) and were set to detect an increase or decrease of effect of 30%–50%, depending on the end point considered.Alpha levels were adjusted (1%) for multiple outcome testing.
RESULTS:We identified 70 trials (3644 patients, 17 countries, from 1970 to 2017). Median number of patients per trial was 44 (range, 9–174). Thirty-seven trials (1781 patients) tested epinephrine for epidural, 27 (1660) for intrathecal, and 6 (203) for locoregional anesthesia (sciatic,femoral, popliteal, axillary blocks). TSA enabled us to conclude that adding epinephrine to epidural local anesthetics could not decrease postoperative pain intensity by 30%, and did not impact the risk of intraoperative arterial hypotension. IS was insufficient to conclude on the impact of epinephrine on the risk of motor block (IS, 4%), arterial hypotension (20%), urinary retention (23%), or pain intensity at rest (27%) during labor. TSA confirmed that adding epinephrine to intrathecal local anesthetics increased the duration of motor block (weighted mean difference [WMD] 64 minutes;99% CI, 37–91), analgesia (WMD 34 minutes; 99% CI, 6–62), and the time to 2 segments regression(WMD 20 minutes; 99% CI, 11–28). IS was insufficient to conclude on its impact on arterial hypotension (IS, 15%), or when administrated in a combined spinal-epidural, on motor block (IS,11%) or arterial hypotension (IS, 11%). Adding epinephrine to local anesthetics for a locoregional block increased the duration of analgesia (WMD 66 minutes; 98% CI, 32–100]).
CONCLUSIONS:Adding epinephrine to intrathecal or locoregional local anesthetics prolongs analgesia and motor block by no more than 60 minutes. The impact of adding epinephrine to epidural local anesthetics or to a combined spinal-epidural remains uncertain.
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