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| ID | Type | Description | Link |
|---|---|---|---|
| 96691226.0.0000.0049 | Registry Identifier | 8.416.413 |
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| Name | Class |
|---|---|
| Faculdade de Medicina de Botucatu, UNESP, Botucatu, Brasil | OTHER |
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The goal of this clinical trial is to learn whether different frequencies of transauricular vagus nerve stimulation (tVNS) can reduce postoperative pain and opioid consumption in adults undergoing abdominal or urologic surgery. It will also evaluate the effects of tVNS on recovery quality, autonomic function, and treatment safety. The main questions it aims to answer are:
Does transauricular vagus nerve stimulation reduce postoperative opioid consumption during the first 24 hours after surgery? Do different stimulation frequencies (high-frequency and low-frequency tVNS) produce different effects on postoperative pain and autonomic responses? Is transauricular vagus nerve stimulation safe and well tolerated in surgical patients?
Researchers will compare high-frequency tVNS, low-frequency tVNS, and sham stimulation (inactive stimulation) to determine their effects on postoperative pain and opioid requirements.
Participants will:
Be randomly assigned to receive high-frequency tVNS, low-frequency tVNS, or sham stimulation.
Receive two 30-minute stimulation sessions, one before anesthesia and one after surgery in the post-anesthesia care unit.
Undergo assessments of postoperative pain, opioid consumption, need for rescue analgesics, postoperative nausea and vomiting, heart rate changes, and quality of recovery.
Be monitored for adverse events related to the intervention during the study period.
A total of 174 participants will be enrolled in this single-center, randomized, double-blind, sham-controlled clinical trial.
Postoperative pain remains a major challenge in perioperative care and is associated with delayed recovery, increased healthcare utilization, and greater opioid consumption. Despite advances in multimodal analgesia, opioid medications continue to play a central role in postoperative pain management and may be associated with adverse effects such as nausea, vomiting, respiratory depression, and prolonged recovery. Therefore, the development of effective non-pharmacological adjunctive strategies is of considerable clinical interest.
Transauricular vagus nerve stimulation (tVNS) is a non-invasive neuromodulation technique that stimulates the auricular branch of the vagus nerve through the external ear. Experimental and clinical studies suggest that vagal stimulation may modulate pain perception through activation of central autonomic pathways, enhancement of descending inhibitory pain mechanisms, and regulation of inflammatory responses. Previous clinical trials have demonstrated promising effects of tVNS on acute and chronic pain conditions, including reductions in postoperative pain scores.
However, the optimal stimulation parameters for perioperative analgesia remain uncertain. In particular, the influence of stimulation frequency on clinical outcomes and autonomic responses has not been adequately investigated. Different stimulation frequencies may activate distinct neural pathways and produce different effects on pain modulation and autonomic regulation.
This study is designed to evaluate the effects of different frequencies of transauricular vagus nerve stimulation applied before and after surgery in adult patients undergoing elective surgical procedures. In addition to assessing postoperative opioid requirements, the study will explore the relationship between autonomic responses and postoperative recovery. The findings may contribute to the optimization of non-pharmacological analgesic strategies and support the incorporation of transauricular vagus nerve stimulation into multimodal perioperative pain management protocols.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High-Frequency tVNS | Experimental | Participants will receive active transauricular vagus nerve stimulation (tVNS) at a frequency of 60-120 Hz. Stimulation will be applied bilaterally to the auricular branch of the vagus nerve for 30 minutes before anesthesia and for 30 minutes after surgery. Current intensity will be adjusted between 2 and 6 mA according to participant tolerance. |
|
| Low-Frequency tVNS | Experimental | Participants will receive active transauricular vagus nerve stimulation (tVNS) at a frequency of 10-20 Hz. Stimulation will be applied bilaterally to the auricular branch of the vagus nerve for 30 minutes before anesthesia and for 30 minutes after surgery. Current intensity will be adjusted between 2 and 6 mA according to participant tolerance. |
|
| Sham tVNS | Sham Comparator | Participants will receive sham transauricular vagus nerve stimulation. The device will be positioned and activated to mimic active treatment, but stimulation will be discontinued shortly after initiation. Participants will undergo two 30-minute sessions, one before anesthesia and one after surgery, while maintaining blinding to treatment allocation. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transauricular Vagus Nerve Stimulation (tVNS) | Device | Non-invasive electrical stimulation of the auricular branch of the vagus nerve applied bilaterally through ear electrodes. Stimulation is delivered before anesthesia and after surgery using predefined frequency settings. |
| Measure | Description | Time Frame |
|---|---|---|
| Total postoperative opioid consumption during the first 24 hours after surgery | Total opioid consumption during the first 24 postoperative hours, recorded according to the institutional postoperative analgesia protocol. | 24 hours after surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Postoperative pain intensity (VAS) | Pain intensity measured using a 100-mm Visual Analog Scale (VAS). Pain scores will be assessed at predefined postoperative time points and compared among study groups. | Before stimulation in the post-anesthesia care unit, immediately after stimulation, 2 hours after surgery, and 24 hours after surgery |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rodrigo L Alves, MD, PhD | Contact | 71 99961-9818 | rlalves@ufba.br | |
| João Paulo A de Carvalho | Contact | 75 98295-3834 | joaoaureliano@ufba.br |
| Name | Affiliation | Role |
|---|---|---|
| Rodrigo M Vieira, MD | Botucatu Medical School, São Paulo State University (UNESP) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitário Professor Edgard Santos, Federal University of Bahia (HUPES-UFBA) | Recruiting | Salvador | Estado de Bahia | 40170-110 | Brazil |
De-identified individual participant data underlying the results reported in publications arising from this study will be made available, including demographic characteristics, intervention allocation, primary and secondary outcome measures, and adverse event data. Data will be shared only after removal of all direct identifiers to protect participant confidentiality.
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De-identified individual participant data and supporting study documents will be available beginning 3 months after publication of the primary study results and will remain available indefinitely, with no end date.
De-identified data will be available to qualified researchers who provide a methodologically sound research proposal. Requests should be submitted to the principal investigator. Access will be granted following review and approval of the proposed use and execution of a data-sharing agreement.
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Participants will be randomly assigned in a 1:1:1 ratio to receive high-frequency transauricular vagus nerve stimulation (60-120 Hz), low-frequency transauricular vagus nerve stimulation (10-20 Hz), or sham stimulation. Each participant will remain in the assigned group throughout the study and will receive two stimulation sessions, one before anesthesia and one after surgery. Outcomes will be compared across the three parallel groups.
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Participants, outcome assessors, and data analysts will remain blinded to treatment allocation throughout the study. The researcher responsible for administering the stimulation will not be blinded because intervention assignment is required for device setup and delivery.
| Sham Transauricular Vagus Nerve Stimulation (sham tVNS) | Device | Sham stimulation delivered using the same device and electrode placement as active stimulation. The device is activated to mimic treatment but does not deliver therapeutic electrical stimulation. |
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| Rescue analgesic use |
Number of participants requiring rescue analgesics and total rescue analgesic administration during the first 24 postoperative hours. |
| Within 24 hours after surgery |
| Postoperative nausea and vomiting (PONV) | Incidence of postoperative nausea and/or vomiting and use of rescue antiemetic medication during the postoperative period. | Within 24 hours after surgery |
| Heart rate changes | Changes in heart rate measured immediately before and immediately after transauricular vagus nerve stimulation sessions as an indicator of autonomic nervous system activity. | Immediately before and immediately after each stimulation session (preoperative and postoperative). |
| Quality of Recovery (QoR-15 Score) | Quality of postoperative recovery assessed using the 15-item Quality of Recovery questionnaire (QoR-15). Higher scores indicate better recovery. | Baseline (preoperative) and 24 hours after surgery. |
| Adverse events related to transauricular Vagus Nerve Stimulation | Incidence of adverse events potentially related to the intervention, including auricular discomfort, skin irritation, headache, bradycardia, hypotension, bronchospasm, or other treatment-related events. | From the first stimulation session until 24 hours after surgery. |
| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| D020250 | Postoperative Nausea and Vomiting |
| D000377 | Agnosia |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D009325 | Nausea |
| D012817 | Signs and Symptoms, Digestive |
| D014839 | Vomiting |
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009422 | Nervous System Diseases |
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