RESUMEN
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.
