Methemoglobin Formation Reflects Systemic Nitric Oxide Uptake: The Critical Role of Delivery Method-Results from Secondary Analysis of a Randomized Controlled Trial.
Stefano Cenci, Mokshad Gaonkar, Regina Villalobos et al.
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In 30 seconds
This retrospective secondary analysis of a randomized controlled trial examined methemoglobin (metHb) formation as a marker of systemic nitric oxide (NO) uptake in adults undergoing cardiac surgery with signs or symptoms suggestive of endothelial dysfunction. Patients received 80 ppm NO through cardiopulmonary bypass (CPB), mechanical ventilation (MV), and nasal cannula (NC). Among 105 patients, metHb rose more steeply during MV than CPB, and estimated NO delivery was higher with MV than CPB (median 25.1 v 8.2 μmol/min, p < 0.001). MetHb declined during NC administration.
Key findings
- Median metHb levels were 0.6% during CPB, 2.1% during ICU MV, and 0.8% during NC administration.
- MetHb increased more steeply during MV than CPB (β = 8.354 * 10 -3 v β = 3.738 * 10 -3, p < 0.001).
- Estimated NO delivery rates were higher with MV than CPB (median 25.1 v 8.2 μmol/min, p < 0.001).
- MetHb declined during NC, with a negative slope compared with CPB (β = -5.352 * 10 -3 v β = 3.738 * 10 -3, p < 0.001).
Why it matters
The findings indicate that delivered NO concentration alone may not capture systemic uptake: metHb formation differed across delivery methods and exposure duration. This supports considering metHb as more than a safety measure when assessing NO exposure, while recognizing that the study evaluated biomarker patterns rather than clinical benefit from biomarker-guided treatment.
What to keep in mind
This was a retrospective analysis at a single academic centre, in adults undergoing cardiac surgery with signs or symptoms suggestive of endothelial dysfunction.