Real-world use of inhaled nitric oxide therapy in patients with COVID-19 and mild-to-moderate acute respiratory distress syndrome

Steven H Abman, Nicholas R Fox, M Ibrahim Malik, Sneha S Kelkar, Shelby L Corman, Sanika Rege, Jenna Bhaloo, Rachel Shah, Ren-Jay Shei, Dana Saporito, Nisreen Shamseddine, Erik DeBoer, George J Wan, on behalf of the NOTICE Study Investigators


Background: Inhaled nitric oxide (iNO) has been studied in patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 when it may be too late to impact disease course. This article aims to describe real-world iNO use and outcomes in patients with COVID-19 with mild-to-moderate ARDS in the United States.

Methods: This was a retrospective medical chart review study that included patients who were ≥18 years old, hospitalized for COVID-19, met the Berlin ARDS definition, received iNO for ≥24 hours continuously during hospitalization, and had a partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (P/F ratio) of >100 to ≤300 mmHg at iNO initiation. Outcomes included oxygenation parameters, physician-rated Clinical Global Impression–Improvement (CGI-I) scale scores, and adverse events. Response to iNO was defined as >20% improvement in P/F ratio.

Results: Thirty-seven patients at six sites were included. A P/F ratio of ≤100 was the most common reason for exclusion (n=146; 83% of excluded patients). The mean P/F ratio (SD) increased from 136.7 (34.4) at baseline to 140.3 (53.2) at 48 hours and 151.8 (50.0) at 72 hours after iNO initiation. The response rate was 62% (n=23). During hospitalization, no patient experienced adverse events, including methemoglobinaemia, airway injury, or worsening pulmonary oedema associated with iNO. At discharge, 54.0% (n=20) of patients improved or remained stable according to the CGI-I.

Conclusion: In patients hospitalized with COVID-19 and mild-to- moderate ARDS, iNO was associated with improvement in the P/F ratio with no reported toxicity. This study provides additional evidence supporting a favourable benefit–risk profile for iNO in the treatment of mild-to-moderate ARDS in patients with COVID-19 infection.

Article Details

Article Type

Original Research



Publication Dates

Accepted: ; Published: .


Abman SH, Fox NR, Malik MI, Kelkar SS, Corman SL, Rege S, Bhaloo J, Shah R, Shei R-J, Saporito D, Shamseddine N, DeBoer E, Wan GJ, on behalf of the NOTICE Study Investigators. Real-world use of inhaled nitric oxide therapy in patients with COVID-19 and mild-to-moderate acute respiratory distress syndrome. Drugs Context. 2022;11:2022-1-4.

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