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

Abstract

Prolonged cardiopulmonary bypass (CPB) causes hemolysis, reducing nitric oxide availability and increasing the risk of acute kidney injury (AKI) after cardiac surgery. While previous studies suggest inhaled nitric oxide may reduce AKI in certain populations, its effect in patients with preexisting endothelial dysfunction, a condition marked by impaired nitric oxide production, is unknown. This trial investigates whether perioperative nitric oxide administration reduces AKI in patients with preexisting endothelial dysfunction undergoing prolonged CPB. The authors conducted a double-blind, single-center, placebo-controlled, randomized clinical trial involved 250 adult cardiac surgery patients with preexisting endothelial dysfunction undergoing CPB lasting more than 90 min. Participants were randomized to either receive nitric oxide at 80 ppm via the oxygenator during CPB, continuing postoperatively via ventilator and facemask, or a placebo of nitrogen-oxygen gas mixture for 24 h. The primary outcome was the incidence of postoperative AKI, defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary outcomes included AKI severity and the need for renal replacement therapy during hospitalization and at 6 weeks, 90 days, and 1 yr. Of the 250 patients (median age, 66 yr; interquartile range, 59, 73 yr; 56 [22.4%] women), 125 were assigned to each group. AKI occurred in 55 (44.0%) patients in the nitric oxide group and 54 (43.2%) patients in the control group (adjusted odds ratio, 1.00; 95% CI, 0.59 to 1.69). Secondary outcomes, including stage 1, 2, or 3 AKI and renal replacement therapy at all timepoints, were also similar between groups. In cardiac surgery patients with preexisting endothelial dysfunction undergoing prolonged CPB, perioperative administration of 80 ppm nitric oxide for 24 h did not significantly reduce postoperative AKI. These findings do not support the routine use of nitric oxide in this patient population.