Canniesburn Plastic Surgery Unit & Scottish National Brachial Plexus Injury Service, Glasgow Royal Infirmary, Glasgow, UK.
School of Molecular Biosciences, University of Glasgow, Glasgow, UK.
Cochrane Database Syst Rev. 2022 Dec 7;12(12):CD012574. doi: 10.1002/14651858.CD012574.pub2.
BACKGROUND: Traumatic peripheral nerve injury is common and incurs significant cost to individuals and society. Healing following direct nerve repair or repair with autograft is slow and can be incomplete. Several bioengineered nerve wraps or devices have become available as an alternative to direct repair or autologous nerve graft. Nerve wraps attempt to reduce axonal escape across a direct repair site and nerve devices negate the need for a donor site defect, required by an autologous nerve graft. Comparative evidence to guide clinicians in their potential use is lacking. We collated existing evidence to guide the clinical application of currently available nerve wraps and conduits. OBJECTIVES: To assess and compare the effects and complication rates of licensed bioengineered nerve conduits or wraps for surgical repair of traumatic peripheral nerve injuries of the upper limb. To compare effects and complications against the current gold surgical standard (direct repair or nerve autograft). SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was 26 January 2022. We searched online and, where not accessible, contacted societies' secretariats to review abstracts from the British Surgical Society of the Hand, International Federation of Surgical Societies of the Hand, Federation of European Surgical Societies of the Hand, and the American Society for Peripheral Nerve from October 2007 to October 2018. SELECTION CRITERIA: We included parallel group randomised controlled trials (RCTs) and quasi-RCTs of nerve repair in the upper limb using a bioengineered wrap or conduit, with at least 12 months of follow-up. DATA COLLECTION AND ANALYSIS: We used standard Cochrane procedures. Our primary outcomes were 1. muscle strength and 2. sensory recovery at 24 months or more. Our secondary outcomes were 3. British Medical Research Council (BMRC) grading, 4. integrated functional outcome (Rosén Model Instrument (RMI)), 5. touch threshold, 6. two-point discrimination, 7. cold intolerance, 8. impact on daily living measured using the Disability of Arm Shoulder and Hand Patient-Reported Outcome Measure (DASH-PROM), 9. sensory nerve action potential, 10. cost of the device, and 11. adverse events (any and specific serious adverse events (further surgery)). We used GRADE to assess the certainty of the evidence. MAIN RESULTS: Five studies involving 213 participants and 257 nerve injuries reconstructed with wraps or conduits (129 participants) or standard repair (128 participants) met the inclusion criteria. Of those in the standard repair group, 119 nerve injuries were managed with direct epineurial repair, and nine autologous nerve grafts were performed. One study excluded the outcome data for the repair using an autologous nerve graft from their analysis, as it was the only autologous nerve graft in the study, so data were available for 127 standard repairs. There was variation in the functional outcome measures reported and the time postoperatively at which they were recorded. Mean sensory recovery, assessed with BMRC sensory grading (range S0 to S4, higher score considered better) was 0.03 points higher in the device group (range 0.43 lower to 0.49 higher; 1 RCT, 28 participants; very low-certainty evidence) than in the standard repair group (mean 2.75 points), which suggested little or no difference between the groups, but the evidence is very uncertain. There may be little or no difference at 24 months in mean touch thresholds between standard repair (0.81) and repair using devices, which was 0.01 higher but this evidence is also very uncertain (95% confidence interval (CI) 0.06 lower to 0.08 higher; 1 trial, 32 participants; very low-certainty evidence). Data were not available to assess BMRC motor grading at 24 months or more. Repair using bioengineered devices may not improve integrated functional outcome scores at 24 months more than standard techniques, as assessed by the Rosén Model Instrument (RMI; range 0 to 3, higher scores better); the CIs allow for both no important difference and a better outcome with standard repair (mean RMI 1.875), compared to the device group (0.17 lower, 95% CI 0.38 lower to 0.05 higher; P = 0.13; 2 trials, 60 participants; low-certainty evidence). Data from one study suggested that the five-year postoperative outcome of RMI may be slightly improved after repair using a device (mean difference (MD) 0.23, 95% CI 0.07 to 0.38; 1 trial, 28 participants; low-certainty evidence). No studies measured impact on daily living using DASH-PROM. The proportion of people with adverse events may be greater with nerve wraps or conduits than with standard techniques, but the evidence is very uncertain (risk ratio (RR) 7.15, 95% CI 1.74 to 29.42; 5 RCTs, 213 participants; very low-certainty evidence). This corresponds to 10 adverse events per 1000 people in the standard repair group and 68 per 1000 (95% CI 17 to 280) in the device group. The use of nerve repair devices may be associated with a greater need for revision surgery but this evidence is also very uncertain (12/129 device repairs required revision surgery (removal) versus 0/127 standard repairs; RR 7.61, 95% CI 1.48 to 39.02; 5 RCTs, 256 nerve repairs; very low-certainty evidence). AUTHORS' CONCLUSIONS: Based on the available evidence, this review does not support use of currently available nerve repair devices over standard repair. There is significant heterogeneity in participants, injury pattern, repair timing, and outcome measures and their timing across studies of nerve repair using bioengineered devices, which make comparisons unreliable. Studies were generally small and at high or unclear risk of bias. These factors render the overall certainty of evidence for any outcome low or very low. The data reviewed here provide some evidence that more people may experience adverse events with use of currently available bioengineered devices than with standard repair techniques, and the need for revision surgery may also be greater. The evidence for sensory recovery is very uncertain and there are no data for muscle strength at 24 months (our primary outcome measures). We need further trials, adhering to a minimum standard of outcome reporting (with at least 12 months' follow-up, including integrated sensorimotor evaluation and patient-reported outcomes) to provide high-certainty evidence and facilitate more detailed analysis of effectiveness of emerging, increasingly sophisticated, bioengineered repair devices.
背景:外伤性周围神经损伤很常见,会给个人和社会带来巨大的经济负担。直接神经修复或自体移植物修复后的愈合过程缓慢且可能不完全。几种生物工程神经套管或装置已经作为直接修复或自体神经移植物的替代方法出现。神经套管试图减少直接修复部位轴突逃逸,神经装置消除了自体神经移植物所需的供体部位缺陷。目前缺乏指导临床医生潜在使用的比较证据。我们整理了现有的证据,以指导目前可用的神经套管和导管的临床应用。
目的:评估和比较经许可的生物工程神经导管或套管用于修复上肢外伤性周围神经损伤的效果和并发症发生率。将效果和并发症与当前的金标准手术(直接修复或神经自体移植)进行比较。
检索方法:我们使用了标准的、广泛的 Cochrane 检索方法。最新检索日期为 2022 年 1 月 26 日。我们在线检索,并在无法在线获取的情况下,联系了英国手外科学会、国际手外科学会联合会、欧洲手外科学会联合会和美国周围神经学会的学会秘书,查阅了 2007 年 10 月至 2018 年 10 月的英国外科杂志、国际手外科学会联合会杂志、欧洲手外科学会联合会杂志和美国周围神经学会杂志的摘要。
选择标准:我们纳入了上肢使用生物工程套管或导管修复的平行组随机对照试验(RCT)和准 RCT,随访时间至少 12 个月。
数据收集和分析:我们使用了标准的 Cochrane 程序。我们的主要结局是 1. 肌肉力量和 2. 24 个月或更长时间的感觉恢复。我们的次要结局是 3. British Medical Research Council (BMRC) 分级、4. 综合功能结局(Rosen 模型仪器(RMI))、5. 触觉阈值、6. 两点辨别觉、7. 冷不耐受、8. 使用手臂肩和手患者报告结果测量表(DASH-PROM)评估日常生活的影响、9. 感觉神经动作电位、10. 设备成本和 11. 不良事件(任何和特定的严重不良事件(进一步手术))。我们使用 GRADE 评估证据的确定性。
主要结果:有 5 项研究共纳入 213 名参与者和 257 例神经损伤,这些损伤通过套管或导管(129 名参与者)或标准修复(128 名参与者)进行修复。在标准修复组中,119 例神经损伤采用直接神经外膜修复,9 例采用自体神经移植物修复。一项研究排除了自体神经移植物修复的结果数据,因为它是研究中唯一的自体神经移植物,因此 127 例标准修复有可用数据。报告的功能结局测量方法和术后记录时间存在差异。设备组的感觉恢复评分(范围 S0 至 S4,分数越高表示恢复越好)比标准修复组高 0.03 分(范围低 0.43 分至高 0.49 分;1 项 RCT,28 名参与者;极低确定性证据),这表明两组之间的差异可能很小或没有,但证据非常不确定。在 24 个月时,标准修复(0.81)和使用设备修复的触觉阈值均值可能差异较小或没有差异,设备修复的触觉阈值高 0.01,但该证据也非常不确定(95%置信区间(CI)0.06 至 0.08 低;1 项试验,32 名参与者;极低确定性证据)。没有数据评估 24 个月或更长时间的 BMRC 运动分级。与标准技术相比,生物工程设备修复可能不会改善 24 个月或更长时间的综合功能结局评分,评估方法为 Rosen 模型仪器(RMI;范围 0 至 3,分数越高表示结果越好);CIs 允许标准修复有更好的结果,也允许设备组有差异(RMI 平均差值 0.17,95%CI 0.38 至 0.05;P = 0.13;2 项试验,60 名参与者;低确定性证据)。一项研究表明,使用设备修复后,RMI 的五年术后结果可能略有改善(平均差值(MD)0.23,95%CI 0.07 至 0.38;1 项试验,28 名参与者;低确定性证据)。没有研究使用 DASH-PROM 评估对日常生活的影响。使用神经套管或导管的不良事件发生率可能高于标准技术,但证据非常不确定(风险比(RR)7.15,95%CI 1.74 至 29.42;5 项 RCT,213 名参与者;极低确定性证据)。这相当于标准修复组每 1000 人中有 10 例不良事件,而设备组每 1000 人中有 68 例(95%CI 17 至 280)。神经修复装置的使用可能与需要更多的修复手术有关,但这一证据也非常不确定(12/129 例设备修复需要(去除)修复,而 127/127 例标准修复不需要;RR 7.61,95%CI 1.48 至 39.02;5 项 RCT,256 例神经修复;极低确定性证据)。
作者结论:基于现有证据,本综述不支持目前使用神经修复装置替代标准修复。使用生物工程设备修复神经的研究中,参与者、损伤模式、修复时机和结局测量及其时间存在显著异质性,使得比较不可靠。研究通常规模较小,且高度或不确定偏倚风险。这些因素使得任何结局的总体证据确定性都很低或非常低。本综述中评估的数据提供了一些证据,表明与标准修复技术相比,目前可用的生物工程设备的使用可能会导致更多的不良事件,需要修复手术的可能性也更大。感觉恢复的证据非常不确定,24 个月(我们的主要结局指标)没有肌肉力量的数据。我们需要进一步的试验,遵循最低标准的结局报告(至少 12 个月的随访,包括综合感觉运动评估和患者报告的结局),以提供高确定性证据,并促进对新兴的、日益复杂的生物工程修复设备的更详细分析。
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