# 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

## TL;DR

This study evaluated inhaled nitric oxide in patients with severe lung disease from COVID-19 and found it improved oxygen levels but did not reduce deaths.

## Contribution

The study introduces a method to classify patients based on their timing of response to inhaled nitric oxide in ARDS due to COVID-19.

## Key findings

- iNO improved oxygenation in Early and Delayed Responders but not in Non-Responders.
- There was no significant difference in ICU mortality across the three groups.
- Complication rates were similar among all groups receiving iNO.

## Abstract

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.

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.

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

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

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

<20% improvement in the PaO2/FiO2 ratio within 24 h, including those who showed 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.

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.

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.