An interventional study of Active taVNS Group and Sham stimulation group in Emergence Agitation and Emergence Delirium, sponsored by The First Affiliated Hospital of Zhejiang Chinese Medical University. Not yet recruiting at 1 site in China. Open to participants aged 3 Years to 8 Years. Per ClinicalTrials.gov, last updated 2026-02-06.
Sponsored by The First Affiliated Hospital of Zhejiang Chinese Medical University · Not applicable, Interventional, and Prevention
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.
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.
Exclusion Criteria:
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
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
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.
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.
The incidence of emergence delirium (ED)
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.
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).
The incidence of postoperative pain
Defined as a FLACC score (Face, Legs, Activity, Cry, Consolability scale; score range 0-10, where higher scores indicate worse pain outcomes) of ≥ 4.
Time frame: Assessed at 0, 5, 10, 20, and 30 minutes after emergence from anesthesia.
Quality of Recovery in Children (PedS-QoR Score)
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.
Time frame: Assessed at 24 and 48 hours after surgery.
Recovery Time
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).
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.
Adverse Events
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.
Time frame: From initiation of the intervention through 3 days after surgery.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — 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.
Supporting information: Study protocol, Sap
This study is not yet recruiting, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
The First Affiliated Hospital of Zhejiang Chinese Medical University