Nitric Oxide to Reduce Acute Kidney Injury in Patients with Pre-existing Endothelial Dysfunction Requiring Prolonged Cardiopulmonary Bypass: A Randomized Clinical Trial

Background: Prolonged cardiopulmonary bypass (CPB) causes hemolysis, reducing nitric oxide (NO) availability and increasing the risk of acute kidney injury (AKI) after cardiac surgery. While prior studies suggest inhaled NO may reduce AKI in certain populations, its effect in patients with pre-existing endothelial dysfunction, a condition marked by impaired NO production is unknown. This trial investigates whether perioperative NO administration reduces AKI in patients with pre-existing endothelial dysfunction undergoing prolonged CPB. Methods: We conducted a double-blind, single-center, placebo-controlled, randomized clinical trial involved 250 adult cardiac surgery patients with pre-existing endothelial dysfunction undergoing cardiopulmonary bypass lasting more than 90 minutes. Participants were randomized to either receive NO at 80 ppm via the oxygenator during cardiopulmonary bypass, continuing post-operatively via ventilator and facemask, or a placebo of nitrogen-oxygen gas mixture for 24 hours. The primary outcome was the incidence of post-operative AKI, defined by KDIGO criteria. Secondary outcomes included AKI severity, and the need for renal replacement therapy (RRT) during hospitalization and at 6 weeks, 90 days, and 1 year. Results: Of the 250 patients [median age: 66 (59, 73) years; 56 (22.4%) females], 125 were assigned to each group. AKI occurred in 55 (44.0%) patients in the NO group and 54 (43.2%) patients in the control group [OR adj : 1.00 (95%CI: 0.59-1.69)]. Secondary outcomes, including stage 1, 2, or 3 AKI and RRT at all time points, were also similar between groups. Conclusions: In cardiac surgery patients with pre-existing endothelial dysfunction undergoing prolonged cardiopulmonary bypass, peri-operative administration of 80 ppm NO for 24 hours did not significantly reduce post-operative AKI. These findings do not support the routine use of NO in this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT02836899