Auricular Vagus Nerve Stimulation Reduces Postoperative Delirium After Major Non-Cardiac Surgery in Elderly Patients

Jinyun Shi,1,2 Dapeng Gao,3 Xiaoyi Hu,4 Yue Zhang,1,2 Ting Guo,4 Qinghong Mao,1,2 Qingren Liu,5 Muhuo Ji4 1Department of Anesthesiology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China; 2Department of Anesthesiology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People’s Republic of China; 3Department of Anesthesiology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210018, People’s Republic of China; 4Department of Anesthesiology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, People’s Republic of China; 5Department of Anesthesiology, Xishan People’s Hospital of Wuxi City, Wuxi, 214105, People’s Republic of ChinaCorrespondence: Muhuo Ji, Department of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, People’s Republic of China, Email [email protected]: Postoperative delirium (POD) is a prevalent and devastating complication in elderly patients undergoing major surgery, marked by substantial increases in morbidity, mortality, and long-term cognitive decline. However, treatment and prevention methods are limited. Accumulating evidence suggests that vagus nerve stimulation effectively enhances cognitive function.Objective: To evaluate the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) on POD in elderly patients undergoing major non-cardiac surgery.Methods: Patients aged ≥ 65 years scheduled for major non-cardiac surgery were randomly assigned to either the active taVNS group or the sham taVNS group, with stimulation targeting the cymba conchae or earlobe, respectively. In both groups, stimulation was initiated 5 minutes prior to anesthesia induction and continued until the end of surgery. The only difference between the two groups was the stimulation site. The primary outcome was the incidence of POD during the first 3 postoperative days.Results: A total of 150 patients (median age, 73 years; 96 women [64%]) completed this trial. The incident POD risk was 12% (n = 9) vs 25.3% (n = 19) in active-taVNS and sham-taVNS groups, respectively (relative risk, 0.47; 95% CI, 0.23– 0.98; P = 0.036). The mediation analysis revealed that postoperative sleep quality played a significant mediating role in the effect of taVNS on POD (z = − 2.30, P = 0.02).Conclusion: In this study, taVNS reduces the incidence of POD in elderly patients undergoing major non-cardiac surgery, possibly by improving postoperative sleep quality. We suggest that this non-invasive neuromodulation technique could be considered as a potential preventive strategy for POD. Further validation in future large-scale randomized controlled trials is warranted.Keywords: taVNS, postoperative delirium, sleep quality, mediation effects