A retrospective evaluation of clinical outcomes in the use of inhaled nitric oxide in acute respiratory distress syndrome caused by COVID-19: The NITRICOVID study

Background: Acute respiratory distress syndrome (ARDS) remains a leading cause of mortality among critically ill patients with COVID-19. Inhaled nitric oxide (iNO), a selective pulmonary vasodilator, is often used as rescue therapy to improve oxygenation; however, its impact on survival remains uncertain.

Objective: To evaluate the clinical outcomes of iNO therapy in patients with COVID-19-related ARDS and to stratify patients into Early, Delayed, and Non-Responder groups based on the timing of their oxygenation response.

Methods: A retrospective cohort study of 99 patients with COVID-19-related ARDS who received iNO was conducted. Patients were categorized as:

Early Responders: ≥20% improvement in the PaO2/FiO2 ratio within 8 h;

Delayed Responders: ≥20% improvement in the PaO2/FiO2 ratio between 8 and 24 h;

Non-Responders: <20% improvement in the PaO2/FiO2 ratio within 24 h, including those who showed no improvement in their PaO2/FiO2 ratio within 24 h of iNO initiation.

Baseline demographics, comorbidities, and outcomes, including duration of mechanical ventilation, ICU and hospital length of stay, and mortality, were compared.

Results: Early and Delayed Responders showed significant improvement in oxygenation (mean PaO2/FiO2: 137.3 vs. 126.9 vs. 106.4; p = 0.004), with mean percentage increases of 65.3%, 56.6%, and 8.2%, respectively (p < 0.001). However, this did not translate into differences in ICU mortality (64.8%, 62.5%, and 71.4%, respectively; p = 0.81) or other hospital outcomes. Rates of acute kidney injury (AKI), methemoglobinemia, and other complications were comparable among the groups.

Conclusion: iNO improved oxygenation in a subset of patients with COVID-19-related ARDS but did not reduce mortality. Stratification by timing of response highlights patient heterogeneity and supports response-guided, time-limited use of iNO in critical care.