Methemoglobin (metHb) is routinely monitored as a safety marker during inhaled nitric oxide (NO) therapy but may also reflect systemic NO uptake. This study aims to investigate how different NO delivery systems influence metHb formation rates and systemic NO uptake.

Retrospective analysis of a randomized controlled trial.

Single-center study at an academic institution.

Adults undergoing cardiac surgery with preoperative signs/symptoms suggestive of endothelial dysfunction.

Patients received 80 parts-per-million (ppm) of NO for 24 consecutive hours to prevent postoperative kidney injury. NO was subsequently administered via cardiopulmonary bypass (CPB), mechanical ventilation (MV), and nasal cannula (NC). Systemic metHb formation and NO uptake rates were assessed and compared across different NO delivery methods.

Data on metHb from 105 patients were analyzed. Median metHb levels were 0.6% during CPB, 2.1% during ICU MV, and 0.8% during NC administration. Duration of NO exposure significantly affected metHb levels (p < 0.001). The slope of metHb increase was higher during MV than during CPB (β = 8.354 * 10^–3v β = 3.738 * 10^–3, p < 0.001), whereas metHb levels declined during NC with a negative slope compared with CPB (β = –5.352 * 10^–3v β = 3.738 * 10^–3, p < 0.001). Estimated NO delivery rates were greater with MV than with CPB (median 25.1 v 8.2 μmol/min, p < 0.001).

NO delivery modalities significantly influence metHb formation and systemic NO uptake. Monitoring biomarkers of NO uptake, such as metHb, may help optimize NO therapy beyond delivered concentration, particularly when extrapulmonary effects are desired.