Department of Neurosurgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Intensive Care Med. 2023 Jun;49(6):633-644. doi: 10.1007/s00134-023-07072-1. Epub 2023 May 13.
Severe traumatic brain injury (TBI) leads to acute coma and may result in prolonged disorder of consciousness (pDOC). We aimed to determine whether right median nerve electrical stimulation is a safe and effective treatment for accelerating emergence from coma after TBI.
This randomised controlled trial was performed in 22 centres in China. Participants with acute coma at 7-14 days after TBI were randomly assigned (1:1) to either routine therapy and right median nerve electrical stimulation (RMNS group) or routine treatment (control group). The RMNS group received 20 mA, 300 μs, 40 Hz stimulation pulses, lasting 20 s per minutes, 8 h per day, for 2 weeks. The primary outcome was the proportion of patients who regained consciousness 6 months post-injury. The secondary endpoints were Glasgow Coma Scale (GCS), Full Outline of Unresponsiveness scale (FOUR), Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS) and Glasgow Outcome Scale Extended (GOSE) scores reported as medians on day 28, 3 months and 6 months after injury, and GCS and FOUR scores on day 1 and day 7 during stimulation. Primary analyses were based on the intention-to-treat set.
Between March 26, 2016, and October 18, 2020, 329 participants were recruited, of whom 167 were randomised to the RMNS group and 162 to the control group. At 6 months post-injury, a higher proportion of patients in the RMNS group regained consciousness compared with the control group (72.5%, n = 121, 95% confidence interval (CI) 65.2-78.7% vs. 56.8%, n = 92, 95% CI 49.1-64.2%, p = 0.004). GOSE at 3 months and 6 months (5 [interquartile range (IQR) 3-7] vs. 4 [IQR 2-6], p = 0.002; 6 [IQR 3-7] vs. 4 [IQR 2-7], p = 0.0005) and FOUR at 28 days (15 [IQR 13-16] vs. 13 [interquartile range (IQR) 11-16], p = 0.002) were significantly increased in the RMNS group compared with the control group. Trajectory analysis showed that significantly more patients in the RMNS group had faster GCS, CRS-R and DRS improvement (p = 0.01, 0.004 and 0.04, respectively). Adverse events were similar in both groups. No serious adverse events were associated with the stimulation device.
Right median nerve electrical stimulation is a possible effective treatment for patients with acute traumatic coma, that will require validation in a confirmatory trial.
严重创伤性脑损伤（TBI）可导致急性昏迷，并可能导致意识障碍持续时间延长（pDOC）。我们旨在确定右正中神经电刺激是否是加速 TBI 后昏迷患者苏醒的安全有效治疗方法。
这是一项在中国 22 个中心进行的随机对照试验。TBI 后 7-14 天处于急性昏迷的患者被随机分配（1:1）至常规治疗和右正中神经电刺激（RMNS 组）或常规治疗（对照组）。RMNS 组接受 20 mA、300 μs、40 Hz 刺激脉冲，持续 20 秒/分钟，每天 8 小时，持续 2 周。主要结局是受伤后 6 个月恢复意识的患者比例。次要终点是格拉斯哥昏迷量表（GCS）、全面无反应量表（FOUR）、昏迷恢复量表修订版（CRS-R）、残疾评定量表（DRS）和格拉斯哥结局量表扩展版（GOSE）评分，分别在伤后 28 天、3 个月和 6 个月时以中位数报告，以及在刺激期间第 1 天和第 7 天的 GCS 和 FOUR 评分。主要分析基于意向治疗集。
2016 年 3 月 26 日至 2020 年 10 月 18 日，共招募 329 名参与者，其中 167 名被随机分配至 RMNS 组，162 名被分配至对照组。受伤后 6 个月时，RMNS 组恢复意识的患者比例高于对照组（72.5%，n=121，95%置信区间（CI）65.2-78.7%比 56.8%，n=92，95%CI 49.1-64.2%，p=0.004）。3 个月和 6 个月时的 GOSE（5 [四分位距（IQR）3-7]比 4 [IQR 2-6]，p=0.002；6 [IQR 3-7]比 4 [IQR 2-7]，p=0.0005）和 28 天时的 FOUR（15 [IQR 13-16]比 13 [IQR 11-16]，p=0.002）在 RMNS 组中均显著升高。轨迹分析显示，RMNS 组患者的 GCS、CRS-R 和 DRS 改善速度明显更快（p=0.01、0.004 和 0.04）。两组的不良事件相似。没有与刺激设备相关的严重不良事件。
右正中神经电刺激可能是一种治疗急性创伤性昏迷患者的有效方法，但需要在一项确证性试验中进行验证。
