Emergence AgitationNCT07394647
Transcutaneous Auricular Vagus Nerve Stimulation for Prevention of Emergence Agitation and Delirium in Children Undergoing Tonsillectomy and Adenoidectomy
A study testing Active taVNS Group in people with Emergence Agitation and Emergence Delirium, run by The First Affiliated Hospital of Zhejiang Chinese Medical University at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 3 to 8 years
- Conditions the study is for
- Emergence Agitation, Emergence Delirium
- What is being tested?
- Active taVNS Group
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- 24 Feb 2026to 30 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 8 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)
Hangzhou, Zhejiang, 310006
Man Lu, +8618368021733, 18368021733@163.com
Lu, 18368021733@163.com
About this study
Official title: 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.
Read the 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.
- Conditions
- Emergence Agitation, Emergence Delirium
- Being tested
- Active taVNS Group, Sham stimulation group
- Keywords
- Pediatric, Emergence Agitation, Emergence Delirium, taVNS, Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)
- Medical subject headings
- Emergence Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active taVNS GroupDevice
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 stimulation groupDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Active taVNS Group | Experimental | 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. Receives: Device: Active taVNS Group |
| Sham Stimulation Group | Sham comparator | 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 Receives: Device: Sham stimulation group |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- ED is defined as a PAED score ≥ 10 and a FLACC score < 4.
- If both PAED score ≥ 10 and FLACC score ≥ 4, the child will first receive intravenous fentanyl 0.5 μg·kg-¹ for analgesia.
- 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.
Measured: Every 10 min during after the patient removed the endotracheal tube ，in the first 30 min in the Post-Anesthesia Care Unit (PACU).
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: From initiation of the intervention through 3 days after surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2026
- Study start24 Feb 2026 (estimated)
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (36)Papers the sponsor has linked to this study.
- Other trials for Emergence AgitationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomly assigned in a 1:1 ratio to either the active transcutaneous auricular vagus nerve stimulation (taVNS) group or the sham stimulation group. Both participants and study personnel involved in intervention delivery and outcome assessment are blinded to group allocation. The effects of taVNS on emergence agitation and emergence delirium after pediatric tonsillectomy and adenoidectomy will be compared between the two parallel groups.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The First Affiliated Hospital of Zhejiang Chinese Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07394647
- Sponsor's protocol ID
- MR-33-25-067114
- Status last verified
- Feb 2025
- First submitted
- 10 Dec 2025
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Publications
Graydon C, Stricker PA, Kelleher S, Cravero J, Karim N, Muhly WT, Lee-Archer P. Development of the Pediatric Scale for Quality of Recovery (PedSQoR). Anesthesiology. 2025 Aug 1;143(2):275-286. doi: 10.1097/ALN.0000000000005503. Epub 2025 Apr 14.
PubMed 40227959Cai YH, Zhong JW, Ma HY, Szmuk P, Wang CY, Wang Z, Zhang XL, Dong LQ, Liu HC. Effect of Remimazolam on Emergence Delirium in Children Undergoing Laparoscopic Surgery: A Double-blinded Randomized Trial. Anesthesiology. 2024 Sep 1;141(3):500-510. doi: 10.1097/ALN.0000000000005077.
PubMed 38758221Badran BW, Brown JC, Dowdle LT, Mithoefer OJ, LaBate NT, Coatsworth J, DeVries WH, Austelle CW, McTeague LM, Yu A, Bikson M, Jenkins DD, George MS. Tragus or cymba conchae? Investigating the anatomical foundation of transcutaneous auricular vagus nerve stimulation (taVNS). Brain Stimul. 2018 Jul-Aug;11(4):947-948. doi: 10.1016/j.brs.2018.06.003. Epub 2018 Jun 6. No abstract available.
PubMed 29895444May SM, Reyes A, Martir G, Reynolds J, Paredes LG, Karmali S, Stephens RCM, Brealey D, Ackland GL. Acquired loss of cardiac vagal activity is associated with myocardial injury in patients undergoing noncardiac surgery: prospective observational mechanistic cohort study. Br J Anaesth. 2019 Dec;123(6):758-767. doi: 10.1016/j.bja.2019.08.003. Epub 2019 Sep 3.
PubMed 31492527Abbott TEF, Pearse RM, Cuthbertson BH, Wijeysundera DN, Ackland GL; METS study investigators. Cardiac vagal dysfunction and myocardial injury after non-cardiac surgery: a planned secondary analysis of the measurement of Exercise Tolerance before surgery study. Br J Anaesth. 2019 Feb;122(2):188-197. doi: 10.1016/j.bja.2018.10.060. Epub 2018 Dec 17.
PubMed 30686304Wang X, Huang ZG, Gold A, Bouairi E, Evans C, Andresen MC, Mendelowitz D. Propofol modulates gamma-aminobutyric acid-mediated inhibitory neurotransmission to cardiac vagal neurons in the nucleus ambiguus. Anesthesiology. 2004 May;100(5):1198-205. doi: 10.1097/00000542-200405000-00023.
PubMed 15114218May SM, Chiang E, Reyes A, Martir G, Patel A, Karmali S, Patel S, West S, Del Arroyo AG, Gourine AV, Ackland GL. Neuromodulation of innate immunity by remote ischaemic conditioning in humans: Experimental cross-over study. Brain Behav Immun Health. 2021 Jul 15;16:100299. doi: 10.1016/j.bbih.2021.100299. eCollection 2021 Oct.
PubMed 34589791Ackland GL, Abbott TEF, Cain D, Edwards MR, Sultan P, Karmali SN, Fowler AJ, Whittle JR, MacDonald NJ, Reyes A, Paredes LG, Stephens RCM, Del Arroyo AG, Woldman S, Archbold RA, Wragg A, Kam E, Ahmad T, Khan AW, Niebrzegowska E, Pearse RM. Preoperative systemic inflammation and perioperative myocardial injury: prospective observational multicentre cohort study of patients undergoing non-cardiac surgery. Br J Anaesth. 2019 Feb;122(2):180-187. doi: 10.1016/j.bja.2018.09.002. Epub 2018 Oct 2.
PubMed 30686303Sullere S, Kunczt A, McGehee DS. A cholinergic circuit that relieves pain despite opioid tolerance. Neuron. 2023 Nov 1;111(21):3414-3434.e15. doi: 10.1016/j.neuron.2023.08.017. Epub 2023 Sep 20.
PubMed 37734381Fang J, Rong P, Hong Y, Fan Y, Liu J, Wang H, Zhang G, Chen X, Shi S, Wang L, Liu R, Hwang J, Li Z, Tao J, Wang Y, Zhu B, Kong J. Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder. Biol Psychiatry. 2016 Feb 15;79(4):266-73. doi: 10.1016/j.biopsych.2015.03.025. Epub 2015 Apr 2.
PubMed 25963932Han B, Li X, Hao J. The cholinergic anti-inflammatory pathway: An innovative treatment strategy for neurological diseases. Neurosci Biobehav Rev. 2017 Jun;77:358-368. doi: 10.1016/j.neubiorev.2017.04.002. Epub 2017 Apr 6.
PubMed 28392244Qi M, Huang Y, Mai R, Yan Z, Xu B, Liu B, Zhang Y. Baseline functional connectivity of the basal forebrain-cortical circuit predict taVNS treatment response in primary insomnia: a randomized controlled trial and fMRI study. BMC Med. 2025 Jul 9;23(1):412. doi: 10.1186/s12916-025-04126-7.
PubMed 40629377Austelle CW, Cox SS, Connolly DJ, Baker Vogel B, Peng X, Wills K, Sutton F, Tucker KB, Ashley E, Manett A, Cortese B, Short EB, Badran BW. Accelerated Transcutaneous Auricular Vagus Nerve Stimulation for Inpatient Depression and Anxiety: The iWAVE Open Label Pilot Trial. Neuromodulation. 2025 Jun;28(4):672-681. doi: 10.1016/j.neurom.2025.02.003. Epub 2025 Mar 19.
PubMed 40117415Zhang J, Chen Q, Shen Q, Yan C, Jiang T, Li J, Sayer S, Ai Z, Yu X, Zeng Q, Chen G. Effectiveness of Transcutaneous Auricular Vagal Nerve Stimulation on Alleviating Postoperative Pain Following Thoracoscopic Lobectomy: A Participant- and Assessor-blinded, Randomized Controlled Trial. Clin J Pain. 2025 Oct 1;41(10):e1315. doi: 10.1097/AJP.0000000000001315.
PubMed 40775700Ilfeld BM, Finneran JJ 4th, Alexander B, Abramson WB, Sztain JF, Ball ST, Gonzales FB, Abdullah B, Cha BJ, Said ET. Percutaneous auricular neuromodulation (nerve stimulation) for the treatment of pain following total knee arthroplasty: a randomized, double-masked, sham-controlled pilot study. Reg Anesth Pain Med. 2025 Jan 7;50(1):26-35. doi: 10.1136/rapm-2023-105028.
PubMed 38388019
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcutaneous Auricular Vagus Nerve Stimulation for Preventing Emergence Agitation and Delirium After Pediatric Tonsillectomy and Adenoidectomy: A Randomized, Double-Blind, Interventional Study
- ClinicalTrials.gov ID
- NCT07394647
- Acronym / sponsor ID
- MR-33-25-067114
- Conditions
- Emergence Agitation, Emergence Delirium
- Keywords
- Pediatric, Emergence Agitation, Emergence Delirium, taVNS, Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Zhejiang Chinese Medical UniversityUniversity, hospital or other
- Study start
- 24 Feb 2026 (estimated)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 6 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomly assigned in a 1:1 ratio to either the active transcutaneous auricular vagus nerve stimulation (taVNS) group or the sham stimulation group. Both participants and study personnel involved in intervention delivery and outcome assessment are blinded to group allocation. The effects of taVNS on emergence agitation and emergence delirium after pediatric tonsillectomy and adenoidectomy will be compared between the two parallel groups.
| Arm | Type | Receives |
|---|---|---|
| Active taVNS Group | Experimental | Device: Active taVNS GroupParticipants 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. |
| Sham Stimulation Group | Sham comparator | Device: Sham stimulation groupParticipants 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 |
Who may qualify
- Ages
- 3 to 8 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active taVNS GroupActive 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. | Device | Active taVNS Group |
| Sham stimulation groupThe 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. | Device | Sham Stimulation Group |
Primary outcome
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.
4 secondary outcomes
The incidence of postoperative pain
Time frame: 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.
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.
Adverse Events
Time frame: From initiation of the intervention through 3 days after surgery.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
- Background: PubMed 40227959Graydon C, Stricker PA, Kelleher S, Cravero J, Karim N, Muhly WT, Lee-Archer P. Development of the Pediatric Scale for Quality of Recovery (PedSQoR). Anesthesiology. 2025 Aug 1;143(2):275-286. doi: 10.1097/ALN.0000000000005503. Epub 2025 Apr 14.
- Background: PubMed 38758221Cai YH, Zhong JW, Ma HY, Szmuk P, Wang CY, Wang Z, Zhang XL, Dong LQ, Liu HC. Effect of Remimazolam on Emergence Delirium in Children Undergoing Laparoscopic Surgery: A Double-blinded Randomized Trial. Anesthesiology. 2024 Sep 1;141(3):500-510. doi: 10.1097/ALN.0000000000005077.
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- The First Affiliated Hospital of Zhejiang Chinese Medical University official siteLink provided by the sponsor.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active taVNS Group in people with Emergence Agitation and Emergence Delirium, run by The First Affiliated Hospital of Zhejiang Chinese Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Man Lu, M.Sc. (+8618368021733, 18368021733@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07394647, which also lists 36 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2026.