Transcutaneous Auricular Vagus Nerve Stimulation and Pectoral-Intercostal Fascial Block for the Prevention of Chronic Postsurgical Pain in Elderly Patients Undergoing Off-Pump Coronary Artery Bypass Grafting: A 2×2 Factorial, Double-Blinded

Sichen Cui,1,* Luguang Yan,1,* Peiying Huang,1 Haitao Yang,2– 4 Weimin Liang,1 Lining Huang1,5,6 1Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Division of Health Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 3Hebei Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 4Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 5Hebei Key Laboratory of Neurodegenerative Disease Mechanism, Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 6Key Laboratory of Clinical Neurology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lining Huang, Department of Anesthesiology, The Second Hospital of Hebei Medical University, No. 215, Heping West Road, Xinhua District, Shijiazhuang, 050000, People’s Republic of China, Tel +86 15803213730, Email [email protected]: Chronic postsurgical pain (CPSP) is common after off-pump coronary artery bypass grafting (OPCABG) in elderly patients. This trial investigated the efficacy of perioperative transcutaneous auricular vagus nerve stimulation (taVNS) and pectoral-intercostal fascial block (PIFB) for CPSP prevention.Methods: In this 2× 2 factorial trial, 260 elderly patients (≥ 60 years) undergoing OPCABG were randomized to taVNS + ropivacaine PIFB, taVNS + placebo PIFB, sham taVNS + ropivacaine PIFB, or sham taVNS + placebo PIFB groups. The primary outcome was CPSP incidence at 3 months postoperatively. Several secondary outcomes were evaluated. Logistic regression was employed to analyze risk factors associated with CPSP. Lastly, mediation analyses were performed to explore the mediating factors between interventions and CPSP.Results: The overall incidence of CPSP was 34.6%. No interaction was found between taVNS and PIFB. Compared with sham taVNS, taVNS significantly reduced CPSP incidence (28.6% vs 40.9%, P = 0.036), alleviated acute pain and improved recovery quality. PIFB did not reduce overall CPSP incidence (30.2% vs 38.8%, P = 0.143), though it alleviated acute pain on postoperative day 1 and reduced moderate-to-severe CPSP. Risk factors for CPSP included preoperative anxiety, pain catastrophizing, acute postoperative pain, and high IL-6 levels. Mediation analysis indicated taVNS’s benefits were partially mediated by reducing acute pain (19.3%) and IL-6 (20.4%).Conclusion: Perioperative taVNS significantly reduced CPSP incidence and enhanced postoperative recovery in elderly OPCABG patients, partly mediated by alleviating acute pain and inflammation. Single-shot PIFB showed limited preventive effect on overall CPSP.Keywords: postoperative pain, vagus nerve stimulation, nerve block, aged, randomized controlled trial