Zhang Jun, Shen Qi-Hong, Lin Xinru, Liu Tieshuai, Yu Yunyun, Li Yu, Song Keqin, Yu Xin, Chen Gang
Department of Anesthesiology, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China.
Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China.
BMJ Open. 2025 Apr 5;15(4):e093647. doi: 10.1136/bmjopen-2024-093647.
Postoperative delirium (POD) is a frequent complication in elderly patients undergoing major surgery. Research has shown that neuroinflammation, postoperative pain and autonomic nervous system dysfunction play significant roles in its onset. Vagus nerve stimulation (VNS) has the potential to reduce inflammation, ease postoperative pain and aid in recovery by enhancing acetylcholine release and activating the cholinergic anti-inflammatory pathway. This study aims to assess the effectiveness and safety of transauricular VNS (ta-VNS) in preventing POD in elderly patients undergoing major surgery.
This multicentre, participant-blinded and assessor-blinded, randomised, parallel-group controlled trial will compare the incidence of POD in elderly patients undergoing major surgery who receive ta-VNS versus sham stimulation. A total of 300 eligible patients will be randomly assigned in a 1:1 ratio to either the active or sham stimulation group. The active stimulation group will receive electrical stimulation to the left cymba conchae at a frequency of 30 Hz and a pulse width of 250 µs, with a 30 s on/30 s off cycle. The intensity will start at 0.4V and be increased in 0.4V increments until a tingling sensation is felt, then adjusted to the highest tolerable level without pain. After obtaining informed consent and randomisation, the initial intervention will begin in the preoperative area and continue throughout the surgery. For the four postoperative days, the intervention will be administered twice daily in 2-hour sessions each morning and afternoon. The sham group will follow the same procedure, with electrodes placed on the left cymba conchae. After adjusting the stimulation intensity, the device will be switched off. The primary outcome is the incidence of POD from postoperative day 0 to day 7 or discharge. Secondary outcomes include the severity of POD, quality of recovery, sleep quality and adverse events.
The protocol was approved by Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine on 9 January 2024 (Approval number: 20240014), and the trial was registered on the Chinese Clinical Trial Registry on 21 February 2024, prior to recruitment. The study will be performed according to the guidelines of the Declaration of Helsinki. Written informed consent will be obtained from all participants. The results will be submitted for publication in a refereed journal.
ChiCTR2400081078.
术后谵妄（POD）是接受大手术的老年患者常见的并发症。研究表明，神经炎症、术后疼痛和自主神经系统功能障碍在其发病过程中起重要作用。迷走神经刺激（VNS）有可能通过增强乙酰胆碱释放和激活胆碱能抗炎途径来减轻炎症、缓解术后疼痛并促进恢复。本研究旨在评估经耳迷走神经刺激（ta-VNS）预防接受大手术的老年患者发生POD的有效性和安全性。
本多中心、参与者设盲和评估者设盲、随机、平行组对照试验将比较接受ta-VNS与假刺激的接受大手术的老年患者中POD的发生率。总共300名符合条件的患者将按1:1的比例随机分配到主动刺激组或假刺激组。主动刺激组将以30Hz的频率和250µs的脉冲宽度对左耳甲进行电刺激，开/关周期为30秒。强度将从0.4V开始，以0.4V的增量增加，直到有刺痛感，然后调整到最高可耐受水平且无疼痛。在获得知情同意并随机分组后，初始干预将在术前区域开始，并在整个手术过程中持续进行。在术后四天，干预将每天进行两次，每次2小时，分别在上午和下午。假刺激组将遵循相同的程序，电极置于左耳甲。在调整刺激强度后，设备将关闭。主要结局是术后第0天至第7天或出院时POD的发生率。次要结局包括POD的严重程度、恢复质量、睡眠质量和不良事件。
该方案于2024年1月9日获得浙江大学医学院附属邵逸夫医院批准（批准号：20240014），该试验于2024年2月21日在招募前在中国临床试验注册中心注册。本研究将按照《赫尔辛基宣言》的指导原则进行。将从所有参与者处获得书面知情同意。研究结果将提交至同行评审期刊发表。
ChiCTR2400081078。
