Transcutaneous Auricular Vagus Nerve Stimulation and Quality of Recovery After Major Noncardiac Surgery

NCT06957912 | Recruiting DMC

• 1 other identifier: 2025-066
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

Brief Summary

Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel non-invasive neuromodulation technique. Existing evidence suggested that taVNS improves pain management, sleep quality, inflammatory responses, and gastrointestinal recovery after surgery. This study is designed to test the hypothesis that perioperative use of taVNS may improve quality of recovery in patients after major noncardiac surgery.

Conditions

Vagus Nerve Stimulation; Transcutaneous Electric Nerve Stimulation; Noncardiac Surgery; Quality of Recovery

Keywords

Transcutaneous auricular vagus nerve stimulation; Noncardiac surgery; Quality of recovery

Outcome Measures

Primary Outcomes (1)

• Quality of recovery scores at 24 hours after surgery

  Quality of recovery is assessed using the 15-item Quality of Recovery (QoR-15) Scale. The QoR-15 is a valid, reliable, responsive, and simple-to-use measure that can be applied across a broad range of surgical settings. The scale contains 15 questions that measure five dimensions of patient's health, including: physical comfort, emotional state, physical independence, psychological support, and pain, with scores ranging from 0 (the poorest quality of recovery) to 150 (the best quality of recovery).

  At 24 hours after surgery

Secondary Outcomes (5)

• Quality of recovery scores at 48 and 72 hours after surgery

  At 48 and 72 hours after surgery

• Pain intensity both at rest and with movement after surgery

  Up to 3 days after surgery.

• Subjective sleep quality after surgery

  Up to 3 days after surgery.

• Opioid consumption within 3 days after surgery

  Up to 3 days after surgery.

• Pain intensity and opioid consumption (PIOC) index within 3 days after surgery.

  Up to 3 days after surgery.

Other Outcomes (9)

• Heart rate variability (HRV) before and after each intervention.

  Up to 3 days after surgery.

• Depression after surgery

  On the 5th day or before hospital discharge after surgery.

• Anxiety after surgery

  On the 5th day or before hospital discharge after surgery.

Study Arms (2)

Transcutaneous auricular vagus nerve stimulation group

EXPERIMENTAL

Transcutaneous auricular vagus nerve stimulation

Device: Transcutaneous auricular vagus nerve stimulation

Sham stimulation group

PLACEBO COMPARATOR

Sham stimulation

Device: Sham stimulation

Interventions

Transcutaneous auricular vagus nerve stimulation DEVICE

Transcutaneous auricular vagus nerve stimulation is performed using earphone-shaped stimulators (tVNS501, Ruishenan Medical Device, Inc. JiangSu, China) on the left tragus areas of the outer ear for a total of 30 min. Using parameters we have identified through systematic review, electrical stimulation (pulse width: 200-300 μs; frequency: 25 Hz; duty cycles: 50%) is initiated at 200% perceptual threshold (PT) which means the minimum amount of electricity required to perceive electrical stimulation on the skin described as a pricking or tingling sensation. All conscious patients will be told they may or may not feel any sensation from the stimulation. The stimulation will be performed between 15:00 and 17:00 on the first day before surgery, at least 30 minutes before the start of surgery and between 08:00 and 10:00 on the first to third day after surgery.

Also known as: taVNS

Transcutaneous auricular vagus nerve stimulation group

Sham stimulation DEVICE

Sham stimulation is performed using earphone-shaped stimulators (tVNS501, Ruishenan Medical Device, Inc. JiangSu, China) on the left tragus areas of the outer ear for a total of 30 min. Using parameters we have identified through systematic review, electrical stimulation (pulse width: 200-300 μs; frequency: 25 Hz; duty cycles: 50%) is initiated at 200% perceptual threshold (PT) which means the minimum amount of electricity required to perceive electrical stimulation on the skin described as a pricking or tingling sensation. And the current will be automatically switched off after 15 s. All conscious patients will be told they may or may not feel any sensation from the stimulation. The stimulation will be performed between 15:00 and 17:00 on the first day before surgery, at least 30 minutes before the start of surgery and between 08:00 and 10:00 on the first to third day after surgery.

Sham stimulation group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 years but \<85 years.
• Scheduled for elective or limited-time noncardiac surgery with expected duration ≥2 hours.

You may not qualify if:

• Lesions or infections of the auricle skin.
• Recent or long-term use of cholinergic or anticholinergic medications.
• Neurosurgery.
• Expected mechanical ventilation with intubation for ≥1 day after surgery.
• Diagnosed schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis before surgery.
• Preoperative left ventricular ejection fraction (LVEF) \<30%, or those with sick sinus syndrome, sinus bradycardia (heart rate \<50 beats per minute), atrioventricular block of grade II or above, or implanted pacemaker.
• Inability to communicate due to coma, severe dementia, or language barrier before surgery, or unable to cooperate with intervention.
• American Society of Anesthesiologists physical status grade \>IV, or estimated survival \<24 hours.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

RECRUITING

Related Publications (30)

• Ljungqvist O, de Boer HD, Balfour A, Fawcett WJ, Lobo DN, Nelson G, Scott MJ, Wainwright TW, Demartines N. Opportunities and Challenges for the Next Phase of Enhanced Recovery After Surgery: A Review. JAMA Surg. 2021 Aug 1;156(8):775-784. doi: 10.1001/jamasurg.2021.0586.

  PMID: 33881466 BACKGROUND

• Wessels E, Perrie H, Scribante J, Jooma Z. Quality of recovery in the perioperative setting: A narrative review. J Clin Anesth. 2022 Jun;78:110685. doi: 10.1016/j.jclinane.2022.110685. Epub 2022 Feb 18.

  PMID: 35190342 BACKGROUND

• Campfort M, Cayla C, Lasocki S, Rineau E, Leger M. Early quality of recovery according to QoR-15 score is associated with one-month postoperative complications after elective surgery. J Clin Anesth. 2022 Jun;78:110638. doi: 10.1016/j.jclinane.2021.110638. Epub 2022 Jan 13.

  PMID: 35033845 BACKGROUND

• Kleif J, Gogenur I. Severity classification of the quality of recovery-15 score-An observational study. J Surg Res. 2018 May;225:101-107. doi: 10.1016/j.jss.2017.12.040. Epub 2018 Feb 21.

  PMID: 29605019 BACKGROUND

• Leger M, Campfort M, Cayla C, Lasocki S, Rineau E. Postoperative quality of recovery measurements as endpoints in comparative anaesthesia studies: a systematic review. Br J Anaesth. 2021 Jun;126(6):e210-e212. doi: 10.1016/j.bja.2021.03.008. Epub 2021 Apr 21. No abstract available.

  PMID: 33892949 BACKGROUND

• Myles PS, Boney O, Botti M, Cyna AM, Gan TJ, Jensen MP, Kehlet H, Kurz A, De Oliveira GS Jr, Peyton P, Sessler DI, Tramer MR, Wu CL; StEP-COMPAC Group; Myles P, Grocott M, Biccard B, Blazeby J, Boney O, Chan M, Diouf E, Fleisher L, Kalkman C, Kurz A, Moonesinghe R, Wijeysundera D. Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: patient comfort. Br J Anaesth. 2018 Apr;120(4):705-711. doi: 10.1016/j.bja.2017.12.037. Epub 2018 Feb 2.

  PMID: 29576111 BACKGROUND

• Myles PS, Shulman MA, Reilly J, Kasza J, Romero L. Measurement of quality of recovery after surgery using the 15-item quality of recovery scale: a systematic review and meta-analysis. Br J Anaesth. 2022 Jun;128(6):1029-1039. doi: 10.1016/j.bja.2022.03.009. Epub 2022 Apr 14.

  PMID: 35430086 BACKGROUND

• Stark PA, Myles PS, Burke JA. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15. Anesthesiology. 2013 Jun;118(6):1332-40. doi: 10.1097/ALN.0b013e318289b84b.

  PMID: 23411725 BACKGROUND

• Decarie-Spain L, Hayes AMR, Lauer LT, Kanoski SE. The gut-brain axis and cognitive control: A role for the vagus nerve. Semin Cell Dev Biol. 2024 Mar 15;156:201-209. doi: 10.1016/j.semcdb.2023.02.004. Epub 2023 Feb 16.

  PMID: 36803834 BACKGROUND

• Zou N, Zhou Q, Zhang Y, Xin C, Wang Y, Claire-Marie R, Rong P, Gao G, Li S. Transcutaneous auricular vagus nerve stimulation as a novel therapy connecting the central and peripheral systems: a review. Int J Surg. 2024 Aug 1;110(8):4993-5006. doi: 10.1097/JS9.0000000000001592.

  PMID: 38729100 BACKGROUND

• Wang Y, Li SY, Wang D, Wu MZ, He JK, Zhang JL, Zhao B, Hou LW, Wang JY, Wang L, Wang YF, Zhang Y, Zhang ZX, Rong PJ. Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application. Neurosci Bull. 2021 Jun;37(6):853-862. doi: 10.1007/s12264-020-00619-y. Epub 2020 Dec 23.

  PMID: 33355897 BACKGROUND

• Farmer AD, Strzelczyk A, Finisguerra A, Gourine AV, Gharabaghi A, Hasan A, Burger AM, Jaramillo AM, Mertens A, Majid A, Verkuil B, Badran BW, Ventura-Bort C, Gaul C, Beste C, Warren CM, Quintana DS, Hammerer D, Freri E, Frangos E, Tobaldini E, Kaniusas E, Rosenow F, Capone F, Panetsos F, Ackland GL, Kaithwas G, O'Leary GH, Genheimer H, Jacobs HIL, Van Diest I, Schoenen J, Redgrave J, Fang J, Deuchars J, Szeles JC, Thayer JF, More K, Vonck K, Steenbergen L, Vianna LC, McTeague LM, Ludwig M, Veldhuizen MG, De Couck M, Casazza M, Keute M, Bikson M, Andreatta M, D'Agostini M, Weymar M, Betts M, Prigge M, Kaess M, Roden M, Thai M, Schuster NM, Montano N, Hansen N, Kroemer NB, Rong P, Fischer R, Howland RH, Sclocco R, Sellaro R, Garcia RG, Bauer S, Gancheva S, Stavrakis S, Kampusch S, Deuchars SA, Wehner S, Laborde S, Usichenko T, Polak T, Zaehle T, Borges U, Teckentrup V, Jandackova VK, Napadow V, Koenig J. International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020). Front Hum Neurosci. 2021 Mar 23;14:568051. doi: 10.3389/fnhum.2020.568051. eCollection 2020.

  PMID: 33854421 BACKGROUND

• Jin H, Li M, Jeong E, Castro-Martinez F, Zuker CS. A body-brain circuit that regulates body inflammatory responses. Nature. 2024 Jun;630(8017):695-703. doi: 10.1038/s41586-024-07469-y. Epub 2024 May 1.

  PMID: 38692285 BACKGROUND

• Wu Z, Zhang X, Cai T, Li Y, Guo X, Zhao X, Wu D, Li Z, Zhang L. Transcutaneous auricular vagus nerve stimulation reduces cytokine production in sepsis: An open double-blind, sham-controlled, pilot study. Brain Stimul. 2023 Mar-Apr;16(2):507-514. doi: 10.1016/j.brs.2023.02.008. Epub 2023 Feb 16.

  PMID: 36801260 BACKGROUND

• Patel ABU, Bibawy PPWM, Althonayan JIM, Majeed Z, Gan WL, Abbott TEF, Ackland GL. Effect of transauricular nerve stimulation on perioperative pain: a single-blind, analyser-masked, randomised controlled trial. Br J Anaesth. 2023 Apr;130(4):468-476. doi: 10.1016/j.bja.2022.12.025. Epub 2023 Feb 22.

  PMID: 36822987 BACKGROUND

• Kaniusas E, Kampusch S, Tittgemeyer M, Panetsos F, Gines RF, Papa M, Kiss A, Podesser B, Cassara AM, Tanghe E, Samoudi AM, Tarnaud T, Joseph W, Marozas V, Lukosevicius A, Istuk N, Sarolic A, Lechner S, Klonowski W, Varoneckas G, Szeles JC. Current Directions in the Auricular Vagus Nerve Stimulation I - A Physiological Perspective. Front Neurosci. 2019 Aug 9;13:854. doi: 10.3389/fnins.2019.00854. eCollection 2019.

  PMID: 31447643 BACKGROUND

• Patel ABU, Weber V, Gourine AV, Ackland GL. The potential for autonomic neuromodulation to reduce perioperative complications and pain: a systematic review and meta-analysis. Br J Anaesth. 2022 Jan;128(1):135-149. doi: 10.1016/j.bja.2021.08.037. Epub 2021 Nov 18.

  PMID: 34801224 BACKGROUND

• Hong GS, Pintea B, Lingohr P, Coch C, Randau T, Schaefer N, Wehner S, Kalff JC, Pantelis D. Effect of transcutaneous vagus nerve stimulation on muscle activity in the gastrointestinal tract (transVaGa): a prospective clinical trial. Int J Colorectal Dis. 2019 Mar;34(3):417-422. doi: 10.1007/s00384-018-3204-6. Epub 2018 Dec 5.

  PMID: 30519842 BACKGROUND

• Ru O, Jin X, Qu L, Long D, Liu M, Cheng L, Jiang Y. Low-intensity transcutaneous auricular vagus nerve stimulation reduces postoperative ileus after laparoscopic radical resection of colorectal cancer: a randomized controlled trial. Minerva Anestesiol. 2023 Mar;89(3):149-156. doi: 10.23736/S0375-9393.22.16735-0. Epub 2022 Nov 3.

  PMID: 36326770 BACKGROUND

• Wu Y, Song L, Wang X, Li N, Zhan S, Rong P, Wang Y, Liu A. Transcutaneous Vagus Nerve Stimulation Could Improve the Effective Rate on the Quality of Sleep in the Treatment of Primary Insomnia: A Randomized Control Trial. Brain Sci. 2022 Sep 26;12(10):1296. doi: 10.3390/brainsci12101296.

  PMID: 36291230 BACKGROUND

• Wang L, Zhang J, Guo C, He J, Zhang S, Wang Y, Zhao Y, Li L, Wang J, Hou L, Li S, Wang Y, Hao L, Zhao Y, Wu M, Fang J, Rong P. The efficacy and safety of transcutaneous auricular vagus nerve stimulation in patients with mild cognitive impairment: A double blinded randomized clinical trial. Brain Stimul. 2022 Nov-Dec;15(6):1405-1414. doi: 10.1016/j.brs.2022.09.003. Epub 2022 Sep 21.

  PMID: 36150665 BACKGROUND

• Hilz MJ. Transcutaneous vagus nerve stimulation - A brief introduction and overview. Auton Neurosci. 2022 Dec;243:103038. doi: 10.1016/j.autneu.2022.103038. Epub 2022 Sep 27.

  PMID: 36201901 BACKGROUND

• Myles PS, Myles DB. An Updated Minimal Clinically Important Difference for the QoR-15 Scale. Anesthesiology. 2021 Nov 1;135(5):934-935. doi: 10.1097/ALN.0000000000003977. No abstract available.

  PMID: 34543410 BACKGROUND

• Leger M, Perrault T, Pessiot-Royer S, Parot-Schinkel E, Costerousse F, Rineau E, Lasocki S. Opioid-free Anesthesia Protocol on the Early Quality of Recovery after Major Surgery (SOFA Trial): A Randomized Clinical Trial. Anesthesiology. 2024 Apr 1;140(4):679-689. doi: 10.1097/ALN.0000000000004840.

  PMID: 37976460 BACKGROUND

• Myles PS, Myles DB, Galagher W, Chew C, MacDonald N, Dennis A. Minimal Clinically Important Difference for Three Quality of Recovery Scales. Anesthesiology. 2016 Jul;125(1):39-45. doi: 10.1097/ALN.0000000000001158.

  PMID: 27159009 BACKGROUND

• Kim AY, Marduy A, de Melo PS, Gianlorenco AC, Kim CK, Choi H, Song JJ, Fregni F. Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Sci Rep. 2022 Dec 21;12(1):22055. doi: 10.1038/s41598-022-25864-1.

  PMID: 36543841 BACKGROUND

• Badran BW, Yu AB, Adair D, Mappin G, DeVries WH, Jenkins DD, George MS, Bikson M. Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. J Vis Exp. 2019 Jan 7;(143):10.3791/58984. doi: 10.3791/58984.

  PMID: 30663712 BACKGROUND

• Bu XS, Zhang J, Zuo YX. Validation of the Chinese Version of the Quality of Recovery-15 Score and Its Comparison with the Post-Operative Quality Recovery Scale. Patient. 2016 Jun;9(3):251-9. doi: 10.1007/s40271-015-0148-6.

  PMID: 26518201 BACKGROUND

• Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.

  PMID: 15273542 BACKGROUND

• Andersen LPK, Gogenur I, Torup H, Rosenberg J, Werner MU. Assessment of Postoperative Analgesic Drug Efficacy: Method of Data Analysis Is Critical. Anesth Analg. 2017 Sep;125(3):1008-1013. doi: 10.1213/ANE.0000000000002007.

  PMID: 28632527 BACKGROUND

Study Officials

• Dong-Xin Wang, MD, PhD

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dong-Xin Wang, MD, PhD

CONTACT

86(10) 83572784; wangdongxin@hotmail.com

Hong Hong, MD

CONTACT

+86 17810265121

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chairman, Department of Anesthesiology

Study Record Dates

• First Submitted: April 23, 2025
• First Posted: May 6, 2025
• Study Start: May 13, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: June 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)