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利多卡因与其他局部麻醉药用于成年外科手术患者脊髓麻醉后的短暂性神经症状(TNS):一项网状Meta分析

Transient neurological symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics in adult surgical patients: a network meta-analysis.

作者信息

Forget Patrice, Borovac Josip A, Thackeray Elizabeth M, Pace Nathan L

机构信息

University of Aberdeen, Institute of Applied Health Sciences, Epidemiology Group, School of Medicine, Medical Sciences and Nutrition, Aberdeen, UK.

NHS Grampian, Department of Anaesthesia, Aberdeen, UK.

出版信息

Cochrane Database Syst Rev. 2019 Dec 1;12(12):CD003006. doi: 10.1002/14651858.CD003006.pub4.

Abstract

BACKGROUND

Spinal anaesthesia has been implicated as one of the possible causes of neurological complications following surgical procedures. This painful condition, occurring during the immediate postoperative period, is termed transient neurological symptoms (TNS) and is typically observed after the use of spinal lidocaine. Alternatives to lidocaine that can provide high-quality anaesthesia without TNS development are needed. This review was originally published in 2005, and last updated in 2009.

OBJECTIVES

To determine the frequency of TNS after spinal anaesthesia with lidocaine and compare it with other types of local anaesthetics by performing a meta-analysis for all pair-wise comparisons, and conducting network meta-analysis (NMA) to rank interventions.

SEARCH METHODS

We searched CENTRAL, MEDLINE, Elsevier Embase, and LILACS on 25 November 2018. We searched clinical trial registries and handsearched the reference lists of trials and review articles.

SELECTION CRITERIA

We included randomized and quasi-randomized controlled trials comparing the frequency of TNS after spinal anaesthesia with lidocaine to other local anaesthetics. Studies had to have two or more arms that used distinct local anaesthetics (irrespective of the concentration and baricity of the solution) for spinal anaesthesia in preparation for surgery. We included adults who received spinal anaesthesia and considered all pregnant participants as a subgroup. The follow-up period for TNS was at least 24 hours.

DATA COLLECTION AND ANALYSIS

Four review authors independently assessed studies for inclusion. Three review authors independently evaluated the quality of the relevant studies and extracted the data from the included studies. We performed meta-analysis for all pair-wise comparisons of local anaesthetics, as well as NMA. We used an inverse variance weighting for summary statistics and a random-effects model as we expected methodological and clinical heterogeneity across the included studies resulting in varying effect sizes between studies of pair-wise comparisons. The NMA used all included studies based on a graph theoretical approach within a frequentist framework. Finally, we ranked the competing treatments by P scores.

MAIN RESULTS

The analysis included 24 trials reporting on 2226 participants of whom 239 developed TNS. Two studies are awaiting classification and one is ongoing. Included studies mostly had unclear to high risk of bias. The NMA included 24 studies and eight different local anaesthetics; the number of pair-wise comparisons was 32 and the number of different pair-wise comparisons was 11. This analysis showed that, compared to lidocaine, the risk ratio (RR) of TNS was lower for bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine with RRs in the range of 0.10 to 0.23 while 2-chloroprocaine and mepivacaine did not differ in terms of RR of TNS development compared to lidocaine. Pair-wise meta-analysis showed that compared with lidocaine, most local anaesthetics were associated with a reduced risk of TNS development (except 2-chloroprocaine and mepivacaine) (bupivacaine: RR 0.16, 95% confidence interval (CI) 0.09 to 0.28; 12 studies; moderate-quality evidence; 2-chloroprocaine: RR 0.09, 95% CI 0.01 to 1.51; 2 studies; low-quality evidence; levobupivacaine: RR 0.13, 95% CI 0.02 to 0.69; 2 studies; low-quality evidence; mepivacaine: RR 1.01, 95% CI 0.18 to 5.82; 4 studies; very low-quality evidence; prilocaine: RR 0.18, 95% CI 0.07 to 0.49; 4 studies; moderate-quality evidence; procaine: RR 0.14, 95% CI 0.04 to 0.52; 2 studies; moderate-quality evidence; ropivacaine: RR 0.10, 95% CI 0.01 to 0.78; 2 studies; low-quality evidence). We were unable to perform any of our planned subgroup analyses due to the low number of TNS events.

AUTHORS' CONCLUSIONS: Results from both NMA and pair-wise meta-analysis indicate that the risk of developing TNS after spinal anaesthesia is lower when bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine are used compared to lidocaine. The use of 2-chloroprocaine and mepivacaine had a similar risk to lidocaine in terms of TNS development after spinal anaesthesia. Patients should be informed of TNS as a possible adverse effect of local anaesthesia with lidocaine and the choice of anaesthetic agent should be based on the specific clinical context and parameters such as the expected duration of the procedure and the quality of anaesthesia. Due to the very low- to moderate-quality evidence (GRADE), future research efforts in this field are required to assess alternatives to lidocaine that would be able to provide high-quality anaesthesia without TNS development. The two studies awaiting classification and one ongoing study may alter the conclusions of the review once assessed.

摘要

背景

脊髓麻醉被认为是外科手术后神经并发症的可能原因之一。这种在术后即刻出现的疼痛状况被称为短暂性神经症状(TNS),通常在使用脊髓利多卡因后观察到。需要能够提供高质量麻醉且不发生TNS的利多卡因替代药物。本综述最初发表于2005年,最近一次更新于2009年。

目的

通过对所有成对比较进行荟萃分析,并进行网络荟萃分析(NMA)以对干预措施进行排序,确定利多卡因脊髓麻醉后TNS的发生率,并将其与其他类型的局部麻醉药进行比较。

检索方法

我们于2018年11月25日检索了CENTRAL、MEDLINE、爱思唯尔Embase和LILACS。我们检索了临床试验注册库,并手工检索了试验和综述文章的参考文献列表。

入选标准

我们纳入了比较利多卡因脊髓麻醉后TNS发生率与其他局部麻醉药的随机和半随机对照试验。研究必须有两个或更多使用不同局部麻醉药(无论溶液浓度和比重如何)进行脊髓麻醉以准备手术的组。我们纳入了接受脊髓麻醉的成年人,并将所有孕妇参与者视为一个亚组。TNS的随访期至少为24小时。

数据收集与分析

四位综述作者独立评估纳入研究。三位综述作者独立评估相关研究的质量,并从纳入研究中提取数据。我们对局部麻醉药的所有成对比较进行了荟萃分析以及NMA。我们使用逆方差加权进行汇总统计,并使用随机效应模型,因为我们预计纳入研究之间存在方法学和临床异质性,导致成对比较研究之间的效应大小不同。NMA在频率学派框架内基于图论方法使用所有纳入研究。最后,我们通过P值对竞争治疗进行排序。

主要结果

分析纳入了24项试验,涉及2226名参与者,其中239人发生了TNS。两项研究等待分类,一项研究正在进行中。纳入研究的偏倚风险大多为不明确至高风险。NMA纳入了24项研究和8种不同的局部麻醉药;成对比较的数量为32,不同成对比较的数量为11。该分析表明,与利多卡因相比,布比卡因、左旋布比卡因、丙胺卡因、普鲁卡因和罗哌卡因发生TNS的风险比(RR)较低,RR范围为0.10至0.23,而与利多卡因相比,2 - 氯普鲁卡因和甲哌卡因在TNS发生的RR方面没有差异。成对荟萃分析表明,与利多卡因相比,大多数局部麻醉药发生TNS的风险降低(2 - 氯普鲁卡因和甲哌卡因除外)(布比卡因:RR 0.16,95%置信区间(CI)0.09至0.28;12项研究;中等质量证据;2 - 氯普鲁卡因:RR 0.09,95% CI 0.01至1.51;2项研究;低质量证据;左旋布比卡因:RR 0.13,95% CI 0.02至0.69;2项研究;低质量证据;甲哌卡因:RR 1.01,95% CI 0.18至5.82;4项研究;极低质量证据;丙胺卡因:RR 0.18,95% CI 0.07至0.49;4项研究;中等质量证据;普鲁卡因:RR 0.14,95% CI 0.04至0.52;2项研究;中等质量证据;罗哌卡因:RR 0.10,95% CI 0.01至0.78;2项研究;低质量证据)。由于TNS事件数量较少,我们无法进行任何计划中的亚组分析。

作者结论

NMA和成对荟萃分析的结果均表明,与利多卡因相比,使用布比卡因、左旋布比卡因、丙胺卡因、普鲁卡因和罗哌卡因进行脊髓麻醉后发生TNS的风险较低。在脊髓麻醉后TNS发生方面,使用2 - 氯普鲁卡因和甲哌卡因与利多卡因的风险相似。应告知患者TNS是利多卡因局部麻醉可能的不良反应,麻醉剂的选择应基于具体临床情况和参数,如预期手术持续时间和麻醉质量。由于证据质量极低至中等(GRADE),该领域未来需要进行研究以评估能够提供高质量麻醉且不发生TNS的利多卡因替代药物。等待分类的两项研究和一项正在进行的研究一旦评估,可能会改变本综述的结论。

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