Transcutaneous Auricular Vagus Nerve Stimulation for Prevention of Emergence Agitation and Delirium in Children Undergoing Tonsillectomy and Adenoidectomy

February 1, 2026 updated by: The First Affiliated Hospital of Zhejiang Chinese Medical University

Transcutaneous Auricular Vagus Nerve Stimulation for Preventing Emergence Agitation and Delirium After Pediatric Tonsillectomy and Adenoidectomy: A Randomized, Double-Blind, Interventional Study

Brief Summary This study is designed to find out whether transcutaneous auricular vagus nerve stimulation (taVNS) can safely reduce restlessness and confusion when children wake up from anesthesia after tonsillectomy and adenoidectomy. These problems, called emergence agitation and delirium, are common after surgery and can cause distress for both children and their families.TaVNS is a non-invasive treatment that delivers mild electrical stimulation to a specific area of the ear connected to the vagus nerve. It does not involve needles or medication, and children usually feel only a gentle tingling sensation.In this randomized, double-blind study, children will be assigned by chance to receive either taVNS or a sham (placebo) stimulation during surgery. Neither the children, their families, nor the medical team providing care will know which treatment each child receives.Researchers will observe and record how calmly children wake up from anesthesia, whether they show signs of delirium, and any side effects. The goal of this study is to test whether taVNS is an effective and safe way to improve recovery and comfort for children after surgery.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Background and Rationale Emergence delirium (ED) in pediatric patients is a common postoperative complication linked to exposure to volatile anesthetics, particularly sevoflurane. The proposed mechanism involves dysregulation of the autonomic nervous system, characterized by reduced vagal tone and sympathetic hyperactivity. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique designed to increase vagal activity by delivering low-intensity electrical currents to the auricular branch of the vagus nerve in the ear. Preclinical and clinical evidence suggests taVNS can exert anti-inflammatory, analgesic, and anxiolytic effects via central and peripheral pathways. This trial is designed to investigate whether perioperative taVNS can mitigate ED by modulating autonomic balance.

Intervention and Blinding Methodology The study employs a double-blind, sham-controlled design. Active and sham stimulation devices are physically identical. The active device delivers electrical stimulation with parameters set at a frequency of 25 Hz, a pulse width of 300 μs, and a cyclic mode of 30 seconds on followed by 30 seconds off. Stimulation intensity is individually titrated to a perceptible but non-painful tingling sensation. The sham device follows an identical placement and titration procedure but ceases output after the initial adjustment phase. This methodology ensures participants, caregivers, and outcome assessors are blinded to group assignment. Stimulation is initiated in the preoperative holding area, continues intraoperatively, and concludes upon discharge from the post-anesthesia care unit (PACU). Supplemental stimulation sessions are administered on postoperative days 1 and 2.

Study Procedures Overview Following enrollment and randomization, the stimulation device is applied to the left auricular concha. Standardized general anesthesia is administered per protocol, utilizing sevoflurane for maintenance with titration guided by bispectral index (BIS) monitoring. Intraoperative vital signs and anesthetic depth are recorded. Upon cessation of anesthetics, continuous behavioral observation begins in the PACU.

Technical and Mechanistic Considerations The selection of the left auricle for stimulation is based on anatomical studies indicating a lower density of cardiac vagal fibers compared to the right side. The chosen stimulation parameters (25 Hz, 300 μs) are derived from prior neurophysiology studies suggesting efficacy in activating afferent vagal pathways. The cyclic on/off pattern is intended to prevent nerve accommodation. The perioperative timing of stimulation is designed to preemptively modulate autonomic tone prior to the emergence phase, a period of high neurophysiological lability.

Data Collection and Management Primary and secondary outcome data are collected at predetermined time points by trained, blinded assessors. Data pertaining to device adherence (session timing, wear status) are recorded by nursing staff. All data are entered into a secure, electronic data capture system. Source data verification is performed per the monitoring plan.

Statistical Considerations The primary analysis will utilize the intention-to-treat principle. The primary endpoint, incidence of emergence delirium, will be compared between groups using a chi-square test. A secondary logistic regression analysis will adjust for predefined covariates (e.g., age, surgery duration) to evaluate the independent effect of the intervention. Analysis of continuous secondary endpoints will employ t-tests or non-parametric equivalents based on data distribution. A two-sided p-value <0.05 will define statistical significance.

Safety Monitoring Adverse events are monitored from device application through the follow-up period. Specific attention is given to local skin reactions at the electrode site and any potential device-related incidents. All adverse events are documented and reported according to the protocol and regulatory requirements.

Significance and Implications This investigation aims to provide high-level evidence on the efficacy of a non-pharmacologic, neuromodulatory approach to preventing pediatric emergence delirium. Positive results could establish taVNS as a viable strategy to enhance postoperative recovery and safety, with potential implications for broadening the application of bioelectronic medicine in perioperative care.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310006
        • The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Children aged 3 to 8 years.
  • Patients receiving care at The First Affiliated Hospital of Zhejiang Chinese Medical University with a diagnosis of tonsil and/or adenoid hypertrophy, scheduled for tonsillectomy and/or adenoidectomy under sevoflurane inhalation general anesthesia.
  • American Society of Anesthesiologists (ASA) physical status I-II.
  • Ability to understand the study procedures and assessment scales, and to communicate effectively with study personnel.

Exclusion Criteria:

  • ASA physical status III-IV, or presence of hepatic or renal dysfunction, cardiovascular disease, or endocrine disorders.
  • Neuromuscular disorders or dermatitis of the left auricle.
  • Recent respiratory infection, developmental delay, or autism spectrum disorder.
  • Receipt of specialized care, residence in social welfare institutions, or any other condition that may interfere with study participation.
  • Current enrollment in another clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active taVNS Group

Participants in this group will receive active transcutaneous auricular vagus nerve stimulation (taVNS) during the perioperative period.

Stimulation will be applied to the left cymba conchae using an ear-clip electrode connected to a portable taVNS device.

Parameters: 25 Hz frequency, 300 µs pulse width, duty cycle 30 seconds ON / 30 seconds OFF.

The stimulation starts before anesthesia induction and continues during surgery and recovery in the PACU.

On postoperative days 1 and 2, stimulation will be administered twice daily for 30 minutes each session.

Intensity is adjusted until a mild tingling sensation is perceived without pain.
Device: Active taVNS Group
Active taVNS Group：The taVNS device delivers electrical stimulation via an ear-clip electrode placed on the left cymba conchae.Parameters: 25 Hz frequency, 300 µs pulse width, 30 s ON / 30 s OFF duty cycle.Applied from pre-induction through postoperative recovery, then twice daily for 30 min on POD 1-2.Intensity adjusted to induce mild tingling without discomfort.
Sham Comparator: Sham Stimulation Group
Participants receive sham stimulation applied to the left auricular concha. The device is applied in the same manner as the active group, but stimulation is inactive after initial titration. Stimulation schedule and duration are identical to the active group to maintain blinding
Device: Sham stimulation group
The sham stimulation device is visually identical to the active taVNS unit. Electrodes are placed on the same auricular site, and procedures mimic active stimulation, but no electrical current is delivered.Used to maintain blinding and control for placebo effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The incidence of emergence delirium (ED)
Time Frame: Every 10 min during after the patient removed the endotracheal tube ，in the first 30 min in the Post-Anesthesia Care Unit (PACU).

Measurement Tools: Diagnosis will be made using the Pediatric Anesthesia Emergence Delirium (PAED) Scale (score range: 0-20, higher scores indicate worse delirium) and the FLACC (Face, Legs, Activity, Cry, Consolability) Pain Scale (score range: 0-10, higher scores indicate worse pain).

Diagnostic Criteria:

  1. ED is defined as a PAED score ≥ 10 and a FLACC score < 4.
  2. If both PAED score ≥ 10 and FLACC score ≥ 4, the child will first receive intravenous fentanyl 0.5 μg·kg-¹ for analgesia.
  3. Five minutes after analgesia, both scales will be reassessed. If the PAED score remains ≥ 10, the diagnosis of ED will be confirmed regardless of the FLACC score.
Every 10 min during after the patient removed the endotracheal tube ，in the first 30 min in the Post-Anesthesia Care Unit (PACU).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The incidence of postoperative pain
Time Frame: Assessed at 0, 5, 10, 20, and 30 minutes after emergence from anesthesia.
Defined as a FLACC score (Face, Legs, Activity, Cry, Consolability scale; score range 0-10, where higher scores indicate worse pain outcomes) of ≥ 4.
Assessed at 0, 5, 10, 20, and 30 minutes after emergence from anesthesia.
Quality of Recovery in Children (PedS-QoR Score)
Time Frame: Assessed at 24 and 48 hours after surgery.

Postoperative recovery quality will be assessed using the Pediatric Quality of Recovery Scale (PedS-QoR, 20-item version).

This validated questionnaire evaluates children's physical comfort, emotional state, psychological well-being, and independence after surgery and anesthesia.

Proxy Report: For children aged 2-7 years, completed by parents or caregivers. Self-Report: For children aged 8-17 years, completed by the child. The total score ranging from 20 to 100, where higher scores indicate better recovery quality.
Assessed at 24 and 48 hours after surgery.
Recovery Time
Time Frame: Recovery parameters were assessed every 5 min in the first 30 min after anesthesia discontinuation and then every 10 min until discharge criteria were met or up to 120 min.
The time interval from the discontinuation of sevoflurane to the moment when the child is awakened and able to respond to their name spoken in a normal tone of voice, including cases where response is delayed due to emergence delirium (ED).
Recovery parameters were assessed every 5 min in the first 30 min after anesthesia discontinuation and then every 10 min until discharge criteria were met or up to 120 min.
Adverse Events
Time Frame: From initiation of the intervention through 3 days after surgery.
All adverse events occurring during hospitalization will be recorded, including nausea, vomiting, pneumonia, and ta-VNS-related complications such as skin irritation, dizziness, or bradycardia.
From initiation of the intervention through 3 days after surgery.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital of Zhejiang Chinese Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 24, 2026

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

December 30, 2026

Study Registration Dates

First Submitted

December 10, 2025

First Submitted That Met QC Criteria

February 1, 2026

First Posted (Actual)

February 6, 2026

Study Record Updates

Last Update Posted (Actual)

February 6, 2026

Last Update Submitted That Met QC Criteria

February 1, 2026

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MR-33-25-067114

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified IPD will be available beginning 6 months after publication of the primary results manuscript. Data will be shared with researchers who provide a methodologically sound proposal for use in non-commercial research. Proposals should be directed to the corresponding author. To gain access, requestors will need to sign a data access agreement.

IPD Sharing Time Frame

Supporting information (study protocol and statistical analysis plan) will be available beginning 6 months after study completion and for up to 3 years following publication of the primary results.

IPD Sharing Access Criteria

Access to the study protocol and statistical analysis plan will be granted to academic researchers affiliated with recognized institutions for non-commercial research purposes. Requests should be submitted to the principal investigator by email. Data sharing will require prior approval and signing of a data use agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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