Effect of transcutaneous auricular vagus nerve stimulation on perioperative psychological symptoms in patients undergoing elective thoracoscopic lung resection: A randomized controlled trial

BACKGROUND: Perioperative anxiety is highly prevalent in patients undergoing thoracoscopic lung resection, adversely affecting postoperative recovery. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising noninvasive neuromodulatory intervention with demonstrated efficacy in various psychiatric and stress-related conditions. This study aimed to evaluate the efficacy and safety of taVNS in reducing perioperative anxiety in this population. METHODS: This single-center, parallel-group, randomized, double-blind, superiority trial was conducted at the Department of Anesthesiology and Thoracic Surgery, the Affiliated Hospital of Xuzhou Medical University between October 10, 2024, and April 30, 2025. A total of 176 eligible patients aged ≥18 years with ASA physical status I-III and scheduled for elective thoracoscopic lung resection were enrolled. Patients with neuropsychiatric disorders, auricular lesions, severe cardio-cerebrovascular diseases, implanted electronic devices, Mini-Mental State Examination (MMSE) score <15, long-term psychotropic medication use or postural tachycardia syndrome were excluded. All participants were randomly allocated to receive four sessions of either active taVNS or sham taVNS. Stimulation was delivered via the auricular branch of the vagus nerve at the cymba conchae of the left ear at four predefined perioperative time points: the afternoon before surgery, the morning of surgery, immediately after tracheal extubation, and the afternoon of the first postoperative day. The primary outcome was the incidence of perioperative anxiety, assessed from the initiation of the first taVNS session through 3 days postoperatively. All participants, healthcare providers, outcome assessors and data analysts were blinded to group assignment during the whole study. RESULTS: A total of 176 patients were randomly assigned, with 88 participants in the active taVNS group and 88 in the sham taVNS group. After excluding 2 patients (1 patient from each group) who were transferred to the ICU postoperatively, a total of 174 patients (median age, 58 years; 105 women [60.4%]) completed the study and were analysed for the primary outcome, including 87 patients in each group. The incidence of perioperative anxiety was significantly lower in the active taVNS group than in the sham taVNS group (50.6% vs. 73.6%; relative risk [RR], 0.59; 95% confidence interval [CI], 0.41-0.85; χ2 = 9.76; P = 0.002). Compared with sham stimulation, active taVNS was associated with reductions in anxiety and depression scores, postoperative pain intensity, and physiological stress indices and improvement in sleep quality and overall postoperative recovery. No severe adverse events were observed in either group. The main mild adverse reactions included nausea, vomiting, local tingling, dizziness and headache, and the incidence of adverse events was similar between the two groups. CONCLUSIONS: Four perioperative sessions of taVNS applied to the left cymba conchae significantly reduced the incidence of perioperative anxiety in patients undergoing thoracoscopic lung resection and were additionally associated with improvements in depressive symptoms, stress burden, sleep quality, and pain outcomes. TRIAL REGISTRATION: Chinese Clinical Trial Register Identifier: ChiCTR2400090542 (http://www.chictr.org.cn).