Transcutaneous Autonomic Modulation in Thoracic Surgery

Study Overview
=================
Brief Summary
-----------------
In this study, the investigators aim to determine whether non-invasive autonomic modulation decreases inflammation and complications after thoracic surgery. The investigators will test the hypothesis that low-level transcutaneous vagal nerve stimulation (LLVNS) during major thoracic surgery reduces inflammation and complications, particularly postoperative atrial fibrillation (POAF). This will be a prospective randomized pilot trial of 200 patients undergoing major thoracic surgery including lobectomy, bilobectomy, or pneumonectomy via either video-assisted thoracoscopic (VAT) or open thoracotomy. Patients will be randomized to receive ether a) LLVNS (n=100) or b) sham LLVNS (n=100) during their procedure. All patients will receive standardized anesthetic, surgical, and post-surgical care. The primary outcome in this study will be time to occurrence of in-hospital POAF, which will be compared between groups using Cox proportional hazards models. Secondary outcomes will be ICU and hospital length of stay, postoperative morbidity, postoperative mortality, and serologic markers of inflammation.

Official Title
-----------------
Transcutaneous Autonomic Modulation to Prevent Organ Injury After Thoracic Surgery

Conditions
-----------------
Atrial Fibrillation, Postoperative, Postoperative Complications, Inflammation

Intervention / Treatment
-----------------
* Device: Transcutaneous Low-Level Vagal Nerve Stimulation (LLVNS)
* Device: Sham LLVNS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Major thoracic surgery (lobectomy, bilobectomy, or pneumonectomy via either video-assisted thoracoscopic (VAT) or open thoracotomy) Exclusion Criteria: Patients >90 or <40 years of age Chronic atrial fibrillation Prior splenectomy Preoperative inotropic support Hepatic or renal failure Currently receiving vagal nerve stimulation therapy Taking centrally-acting cholinergic medications (tacrine, donepezil, rivastigmine) High-grade atrioventricular block (>2nd degree atrioventricular blockade)

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcutaneous low-level vagal nerve stimulation (LLVNS)<br>n=100 patients will be randomized to transcutaneous low-level vagal nerve stimulation (LLVNS), via a clip applied to the ear. Stimulation will be delivered throughout the procedure. | Device: Transcutaneous Low-Level Vagal Nerve Stimulation (LLVNS)<br>* Low-level vagal nerve stimulation will be delivered via a clip applied to the ear throughout the surgical procedure. The voltage used will be individualized to each patient, based upon the voltage necessary to slow the sinus rate during testing.<br>|
| Sham Comparator: Sham LLVNS<br>n=100 patients will be randomized to sham LLVNS, with the clip applied but no stimulation delivered. | Device: Sham LLVNS<br>* A clip will be applied to the ear, but no stimulation will be delivered throughout the procedure.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence/Burden of Postoperative Atrial Fibrillation |  | Inpatient hospitalization approximately 3 to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative morbidity | The incidence of complications during the index hospitalization and one year after surgery | Inpatient hospitalization approximately 3 to 7 days, and one year after surgery | 
| Postoperative mortality | The incidence of complications during the index hospitalization and one year after surgery | Inpatient hospitalization approximately 3 to 7 days, and one year after surgery | 
| Serologic Markers of Inflammation | Cytokine levels, measured in pg/mL | Inpatient hospitalization approximately 3 to 7 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Autonomic, Vagal nerve stimulation, Postoperative atrial fibrillation