Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Postoperative Delirium and Negative Emotions in Patients Undergoing Cardiac Surgery

Effect of Intraoperative Transcutaneous Auricular Vagus Nerve Stimulation on Postoperative Delirium and Negative Emotional States in Patients Undergoing Cardiac Surgery: A Multicenter, Randomized, Double-Blind, Sham-Controlled Trial

A multicenter, randomized, double-blind, sham-controlled trial to investigate the effects of intraoperative transcutaneous auricular vagus nerve stimulation (taVNS) on the incidence of postoperative delirium and negative emotional states (anxiety, depression) in patients undergoing elective cardiac surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression; Anxiety; Postoperative Delirium (POD); Cardiac Surgical Procedures; Postoperative
• Intervention / Treatment: Device: Active taVNS; Device: Sham taVNS Group

Detailed Description

Cardiac surgery is associated with a high risk of postoperative neurocognitive disorders, including delirium and negative emotional states such as anxiety and depression, which significantly impact patient recovery and long-term outcomes. This study aims to evaluate whether intraoperative taVNS, a non-invasive neuromodulation technique, can reduce the incidence and severity of these complications. Patients will be randomized to receive either active taVNS or sham stimulation during surgery. Outcomes including delirium, anxiety, depression, pain, sleep quality, recovery quality, and relevant biomarkers will be assessed postoperatively.

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • First Medical Center of Chinese PLA General Hospital, Beijing, China.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18 to 85 years. Scheduled for elective cardiac surgery (e.g., CABG, valve replacement/repair). NYHA cardiac function class I-III. Willing and able to provide informed consent. Expected surgery duration ≥ 2 hours.

Exclusion Criteria:

• Preoperative MMSE score < 24; severe communication barriers. History of diagnosed delirium, dementia, Parkinson's disease, schizophrenia, bipolar disorder, major depressive disorder, or long-term use of psychotropic drugs.

Skin lesions, infection, or deformity of bilateral ears; history of ear surgery or nerve injury; allergy to electrode materials.

Severe arrhythmia; implanted electronic devices (e.g., pacemaker, ICD). Participation in another interventional trial within 3 months. Other conditions deemed unsuitable by investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active taVNS Group; Patients receiving active transcutaneous auricular vagus nerve stimulation during surgery.	Device: Active taVNS; Stimulation parameters: Amplitude 20 (mA), Frequency 20Hz, Pulse width 200μs, asymmetric biphasic square wave. The current is gradually increased from 10mA to a level slightly below the individual's "prickling" sensation threshold (20-60mA). Stimulation is applied to the left auricular concha for 30 minutes after anesthesia induction and for another 30 minutes after cardiopulmonary bypass weaning.
Sham Comparator: Sham taVNS Group; Patients receiving sham (placebo) stimulation with an identical device during surgery.	Device: Sham taVNS Group; The sham device is identical in appearance, weight, indicator lights, and operation sounds to the active device but delivers no effective electrical current. It is applied to the left auricular concha at the same time points as the active group (30 minutes after induction and 30 minutes after CPB weaning).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Postoperative Delirium	Postoperative delirium will be assessed using the 3-Minute Diagnostic Interview for CAM (3D-CAM) for general ward patients and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) for ICU patients, from postoperative day 1 to day 7. Diagnosis requires the presence of acute onset/fluctuating course and inattention, plus either disorganized thinking or altered level of consciousness.	Within 7 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Postoperative Depression	Postoperative Anxiety Incidence and Severity: HADS-D (Hospital Anxiety and Depression Scale - Anxiety Subscale) Score.Higher score indicates greater depression severity. A score ≥ 8 is considered clinically significant for depression (per standard cutoff).	Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Incidence and Severity of Postoperative Anxiety	Postoperative Anxiety Incidence and Severity: HADS-A (Hospital Anxiety and Depression Scale - Anxiety Subscale) Score. Higher score indicates greater anxiety severity. A score ≥ 8 is considered clinically significant for anxiety (per standard cutoff).	Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Incidence and Severity of Postoperative Depression	Assessed using Hamilton Depression Rating Scale (HAMD-17). Scores above standard cut-offs indicate depressive states.	Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Incidence and Severity of Postoperative Anxiety (HADS-A)	Assessed using the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A) at specified time points. Scores above standard cut-offs indicate anxiety states.	Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Postoperative Agitation Score	Assessed using the Riker Sedation-Agitation Scale (SAS) at the time of extubation.	At the time of extubation (within 24 hours post-surgery)
Postoperative Nausea and Vomiting (PONV)	Assessed using a Visual Analogue Scale (VAS, 0-10) within 3 days after extubation.	Within 3 days after extubation
Postoperative Pain Score	Assessed using the Numerical Rating Scale (NRS, 0-10).	Postoperative day 1, 2, 3, 7, and 30
Postoperative Sleep Quality	Assessed using the Insomnia Severity Index (ISI, score 0-28).	Postoperative day 1, 2, 3, 7, and 30
Postoperative Recovery Quality	Assessed using the Quality of Recovery-15 or QoR-40 scale.	Postoperative day 7 and 30
Incidence and Severity of Postoperative Anxiety (GAD-7)	Assessed using the Generalized Anxiety Disorder-7 (GAD-7) at specified time points. Scores above standard cut-offs indicate anxiety states.	Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Incidence and Severity of Postoperative Anxiety (SAS)	Assessed using the Self-Rating Anxiety Scale (SAS) at specified time points. Scores above standard cut-offs indicate anxiety states.	Preoperative day, Postoperative day 1, 2, 3, 7, and 30

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Complications	Incidence of complications such as respiratory failure, stroke, acute kidney injury, etc.	From surgery completion to hospital discharge or up to 30 days postoperatively
CRP	Perioperative Serum Biomarker: C-Reactive Protein (CRP) Levels	Preoperative day, end of surgery, postoperative day 1
Arterial Blood Pressure	Perioperative Arterial Blood Pressure	Perioperative period
Perioperative Electroencephalogram (EEG) Data	Including Ai (0-100), EMG index, BSR, SEF95, α/β/γ band power.	Intraoperative period
Heart Rate	Perioperative Heart Rate	Perioperative period
Postoperative Quality of Life	Assessed using the EQ-5D-5L scale.	Postoperative day 7 and 30
Length of Hospital Stay	Length of Hospital Stay	The duration is calculated from the date of admission (Day 0) until the date of discharge. The assessment period was censored at 100 days, meaning if patients were not discharged by then, they were considered censored at that point.
Adverse Events Related to taVNS	Including skin reactions, dizziness, nausea, etc.	From stimulation start to postoperative day 3
IL-6	Interleukin-6 (IL-6) Levels	Preoperative day, end of surgery, postoperative day 1
S100β	S100β Protein Levels	Preoperative day, end of surgery, postoperative day 1
BDNF	Brain-Derived Neurotrophic Factor (BDNF) Levels	Preoperative day, end of surgery, postoperative day 1
IL-10	Interleukin-10 (IL-10) Levels	Preoperative day, end of surgery, postoperative day 1

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Collaborators: The Sixth Medical Center of Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 28, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Anxiety; Randomized Controlled Trial; Cardiac Surgery; Transcutaneous Vagus Nerve Stimulation; Postoperative Delirium
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Behavioral Symptoms; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Emergence Delirium; Anxiety Disorders; Depression
• Other Study ID Numbers: PLAGH-RCT-taVNS-Cardiac

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No