Clinical trial NCT06957912: Transcutaneous Auricular Vagus Nerve Stimulation and Quality of Recovery After Major Noncardiac Surgery
Official title: Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Quality of Recovery After Major Noncardiac Surgery: A Randomized Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Vagus Nerve Stimulation
Transcutaneous Electric Nerve Stimulation
Noncardiac Surgery
Quality of Recovery
Keywords: Transcutaneous auricular vagus nerve stimulation
Noncardiac surgery
Quality of recovery
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2025-05-06
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: The evolution of quality improvement initiatives, such as Enhanced Recovery After Surgery (ERAS) protocols, has shifted perioperative management paradigms toward prioritizing patient-centered subjective experiences such as quality of recovery over traditional outcomes such as mortality, morbidity, or physiological parameter recovery. Poor quality of recovery after surgery not only diminishes patient satisfaction but also correlates with increased 30-day postoperative complications, prolonged hospital stays, and elevated medical expenses.

The vagus nerve is a major component of the parasympathetic nervous system and is a critical relay for neuro-metabolic signals between the abdominal viscera and the brain. The ear is the only area where the vagus nerve is distributed on the body surface, and the auricular branch of the vagus nerve can project to nerve centers such as nucleus of solitary tract in the brainstem and the nucleus coeruleus in the midbrain.

Transcutaneous auricular vagus nerve stimulation (taVNS) can stimulate the auricular branch of the vagus nerve through surface electrodes located in the cymba conchae, and thus activate the vagus nerve circuit, regulate the activity of the brainstem, thalamus, and other brain regions, and regulate the related peripheral organs. Available evidences showed that taVNS reduces inflammatory response to surgery through cholinergic anti-inflammatory pathways, improves analgesia by reducing inflammation and activating serotonin and endorphins analgesic pathways, and promotes gastrointestinal function by regulating peristalsis and secretion of the digestive system; it was also found effective in improving sleep quality and relieving anxiolytic and depressive symptoms. The use of taVNS is relative safe; the incidence of adverse event is low and mainly included transient earache, headache, and local tingling, with no causal association to serious adverse events.

The investigators hypothesize that the application of taVNS in patients undergoing major noncardiac surgery may improve early postoperative quality of recovery.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Lesions or infections of the auricle skin.
2. Recent or long-term use of cholinergic or anticholinergic medications.
3. Neurosurgery.
4. Expected mechanical ventilation with intubation for ≥1 day after surgery.
5. Diagnosed schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis before surgery.
6. 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.
7. Inability to communicate due to coma, severe dementia, or language barrier before surgery, or unable to cooperate with intervention.
8. American Society of Anesthesiologists physical status grade \>IV, or estimated survival \<24 hours.

Primary outcomes:
measure: Quality of recovery scores at 24 hours after surgery
timeFrame: At 24 hours after surgery
Secondary outcomes:
measure: Quality of recovery scores at 48 and 72 hours after surgery
timeFrame: At 48 and 72 hours after surgery
measure: Pain intensity both at rest and with movement after surgery
timeFrame: Up to 3 days after surgery.
measure: Subjective sleep quality after surgery
timeFrame: Up to 3 days after surgery.
measure: Opioid consumption within 3 days after surgery
timeFrame: Up to 3 days after surgery.
measure: Pain intensity and opioid consumption (PIOC) index within 3 days after surgery.
timeFrame: Up to 3 days after surgery.
Other outcomes:
measure: Heart rate variability (HRV) before and after each intervention.
timeFrame: Up to 3 days after surgery.
measure: Depression after surgery
timeFrame: On the 5th day or before hospital discharge after surgery.
measure: Anxiety after surgery
timeFrame: On the 5th day or before hospital discharge after surgery.
measure: Incidence of postoperative nausea and vomiting
timeFrame: Up to 3 days after surgery.
measure: Length of stay in postanesthesia care unit (PACU) after surgery.
timeFrame: Up to 2 hours after surgery.
measure: Length of stay in hospital after surgery
timeFrame: Up to 30 days after surgery.
measure: Time to first flatus and defecation after surgery
timeFrame: Up to 30 days after surgery.
measure: Incidence of postoperative complications
timeFrame: Up to 30 days after surgery.
measure: All-cause mortality after surgery
timeFrame: Up to 30 days after surgery.
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Dong-Xin Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.