Hemolysis-mediated Toxicity during Cardiopulmonary Bypass Ameliorated by Inhaled Nitric Oxide Gas

In a randomized clinical trial in China of 244 adults undergoing elective, multiple valve replacement surgery, Lei and colleagues administered 80 parts per million nitric oxide (NO) gas during and after prolonged cardiopulmonary bypass, mostly indicated for rheumatic disease valve replacement. They report in this issue of the Journal (pp. 1279–1287) that the treatment group demonstrated reduced incidence of acute kidney injury and improved renal function at follow-up 1 year after surgery (1). Clinical endpoints were coupled to assessment of intravascular hemolysis; cell-free plasma hemoglobin levels; the ability of plasma hemoglobin to scavenge NO; and biomarkers of kidney injury, including KIM-1 (kidney injury molecule 1), NGAL (neutrophil gelatinase-associated lipocalin), and creatinine. Of note, in this study, no patient exceeded 10% methemoglobin at any time, and no adverse events occurred, suggesting the safety of this treatment at these higher doses of NO gas.