Medium-Term Effect of Inhaled Nitric Oxide in Mechanically Ventilated COVID-19 Patients

Background: Nitric oxide (NO) plays a key role in various physiological processes. Inhaled NO (iNO) has been studied for treating acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic, interest grew in its potential role for patients with COVID-19 ARDS, with studies showing improved oxygenation over 48 h. Methods: This is a retrospective study of adult patients with severe COVID-19 ARDS and refractory hypoxemia admitted to the medical ICU requiring mechanical ventilation and treated with iNO. The effect on oxygenation, respiratory, and ventilation parameters is measured. Significant improvement is defined as an increase in PaO₂/FiO₂ ≥ 20% from a baseline. Results: This study includes 87 patients (55 men, mean age 58.7 ± 15.2) with 164 iNO connections (mean 1.9 per patient). iNO is independently associated with a significant PaO₂/FiO₂ ratio improvement, with an OR of 1.26 (95% CI 1.09-1.46), even after accounting for these potential confounders. The time to maximal PaO₂/FiO₂ improvement is 14.5 ± 5.0 h for men and 78.5 ± 5.5 h for women, with respective ratio increases of 42.5 ± 8.1 and 52.5 ± 13.6 mmHg. Conclusions: Our study demonstrates that severe ARDS COVID-19 patients may benefit from inhaled nitric oxide, with delayed oxygenation improvements lasting up to 96 h and slower responses observed in women, raising the possibility that current guidelines against its use could be reconsidered.