Acute kidney injury (AKI) is a common complication after cardiac surgery using cardiopulmonary bypass, leading to longer hospital stays and worse outcomes. Effective preventive therapies are lacking.
This randomized controlled trial investigates whether transcutaneous auricular vagus nerve stimulation (taVNS)-a non-invasive ear stimulation technique-can reduce AKI after cardiac surgery. A total of 152 patients undergoing elective cardiac surgery with cardiopulmonary bypass will be randomly assigned to receive either taVNS or sham stimulation. The intervention begins before surgery and continues daily through postoperative day 5.
The primary outcome is the incidence of AKI within 7 days after surgery. Secondary outcomes include AKI severity, need for dialysis, kidney function recovery, complications, and inflammatory biomarkers.
This study is approved by the institutional ethics committee. All participants will provide written informed consent.
Age ≥18 years
Scheduled for elective cardiac surgery with cardiopulmonary bypass under general anesthesia
Baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m² (CKD-EPI formula)
American Society of Anesthesiologists (ASA) physical status classification I-III
Solitary kidney, history of kidney transplantation, pre-existing renal replacement therapy, or pre-existing acute kidney injury (KDIGO criteria)
Contraindications to transcutaneous auricular vagus nerve stimulation, including active infection, dermatitis, skin breakdown, or severe psoriasis in the bilateral auricular region; allergy to silicone, electrode gel, or device materials; uncontrolled arrhythmia, symptomatic bradycardia, sick sinus syndrome, second- or third-degree atrioventricular block, implanted pacemaker or defibrillator; carotid sinus hypersensitivity; uncontrolled epilepsy; or active peptic ulcer disease
Received vagus nerve stimulation, auricular acupuncture, or transcutaneous electrical nerve stimulation within 1 month prior to enrollment
Long-term use of medications that significantly affect autonomic nervous system tone or renal blood flow and cannot be safely paused before surgery
Parallel
Transcutaneous Auricular Vagus Nerve Stimulation
DeviceParticipants in this arm receive active transcutaneous auricular vagus nerve stimulation (ta-VNS) using the tVNS501 device. Stimulation is delivered to the left cymba conchae (auricular branch of the vagus nerve) with the following parameters: frequency 25 Hz, pulse width 250 µs, 30 seconds on / 30 seconds off cycling. Intensity is adjusted starting from 0.4 V and increased in 0.4 V increments until the participant perceives mild discomfort, then reduced to the highest tolerable non-painful level. The intervention begins on the day of surgery (from the preoperative holding area through 6 hours postoperatively in the ICU) and continues on postoperative days 1 through 5 with two 120-minute sessions per day (at 9:00 and 14:00). The device is applied by trained non-blinded operators.
Sham Stimulation
DeviceParticipants in this arm receive sham stimulation using the same tVNS501 device. Electrodes are placed on the left cymba conchae following the same procedure as the active group, but no electrical current is delivered. The stimulation settings are displayed on the device to maintain blinding, but the output is turned off. The schedule and duration of device application are identical to those in the active stimulation group.
Incidence of Acute Kidney Injury (AKI) Within 7 Days After Surgery
Severity of Acute Kidney Injury (AKI) by KDIGO Stage
The severity of AKI will be assessed using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patients are staged from Stage 1 to Stage 3 based on the maximal change in serum creatinine from baseline or the duration and intensity of oliguria (reduced urine output). Stage 1 is defined as a 1.5-1.9 fold increase in baseline creatinine; Stage 2 as a 2.0-2.9 fold increase; and Stage 3 as a ≥ 3.0 fold increase, a creatinine level ≥ 4.0 mg/dL, or the initiation of renal replacement therapy. Higher stages represent greater severity of kidney dysfunction and are associated with worse clinical outcomes.
Requirement of Renal Replacement Therapy (RRT)
Proportion of participants requiring acute RRT during index hospitalization.
Duration of RRT
Number of days of RRT received during index hospitalization (calculated only for participants who required RRT).
Persistent AKI at Postoperative Day 7
Percentage of participants who developed AKI within the first 7 postoperative days and still meet KDIGO criteria for AKI on postoperative day 7.
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