Inhaled Nitric Oxide for Prevention of Postoperative AKI in High-Risk Cardiac Surgery Patients

This is a single-center, prospective, randomized, double-blind, placebo-controlled superiority trial. It evaluates whether intraoperative inhaled nitric oxide (iNO) at 80 ppm reduces the incidence of acute kidney injury (AKI) within 7 days after cardiac surgery with cardiopulmonary bypass (CPB) in high-risk patients (Mayo Clinic renal risk score ≥2).

Intervention: Patients receive inhaled nitric oxide at 80 ppm via the ventilator circuit during CPB and until the end of surgery.

Control: The same device is connected but remains turned off (no iNO delivery). The device screen is covered in both groups to maintain blinding.

Randomization and blinding: Randomization (1:1) uses a blocked scheme with allocation concealment. Patients, surgeons, anesthesiologists, ICU staff, and outcome assessors are blinded. A dedicated gas therapist (not otherwise involved) manages the device.

Standardized management: All patients receive standardized anesthesia, CPB, and KDIGO-recommended AKI prevention bundle (MAP>55 mmHg, goal-directed perfusion).

Safety monitoring: Intraoperative methemoglobin (blood gas) and nitrogen dioxide (device readout) are monitored with predefined safety thresholds for dose adjustment.

Exploratory biomarker substudy (optional): Blood and urine samples are collected at perioperative time points to measure biomarkers of kidney injury and inflammation.

Follow-up: In-hospital outcomes (complications, ventilation duration, length of stay) and telephone follow-up at 30 and 90 days for major adverse kidney and cardiovascular events.

Sample size: Approximately 330 participants (1:1) are planned.

Statistical analysis: The primary analysis compares 7-day AKI incidence between groups with a two-sided α=0.05. Secondary outcomes will be analyzed using appropriate parametric or non-parametric methods.

Inclusion criteria

• Age ≥18 years
• Scheduled for elective cardiac surgery with cardiopulmonary bypass, including valve surgery and/or coronary artery bypass grafting (CABG)
• Mayo Clinic renal risk score ≥2

Exclusion criteria

• Emergency surgery
• Cardiac or major vascular surgery requiring deep hypothermic circulatory arrest
• Use of potentially nephrotoxic drugs (e.g., radiocontrast agents, aminoglycosides, amphotericin) within 24 hours before surgery
• Preoperative heart failure or low cardiac output syndrome requiring life support devices (ECMO, Impella or other left ventricular assist devices, mechanical ventilation), or left ventricular ejection fraction <30%, or other equivalent severe cardiac dysfunction
• Receipt of inhaled nitric oxide or inhaled prostacyclin within 7 days before randomization
• End-stage renal disease with eGFR <15 mL/min, or currently receiving renal replacement therapy, or prior kidney transplantation
• Hemophilia A or B
• Other end-stage chronic disease with estimated life expectancy <1 year (as assessed by the attending physician)
• Pregnancy
• Active endocarditis or other active infection