Efficacy and safety of inhaled nitric oxide in the treatment of severe/critical COVID-19 patients: A systematic review

Indian J Pharmacol. May-Jun 2021;53(3):236-243. doi: 10.4103/ijp.ijp_382_21.


Objective: Present systematic review aimed to analyze the effect of inhaled nitric oxide (iNO) in the treatment of severe COVID-19 and to compare it to standard of care (SOC), antiviral medications, and other medicines.

Materials and methods: Medline (PubMed), Scopus, Embase, Ovid, Web of Science, Science Direct, Wiley Online Library, BioRxiv and MedRxiv, and Cochrane (up to April 20, 2021) were the search databases. Two reviewers (SK and CK) independently selected the electronic published literature that studied the effect of nitric oxide with SOC or control. The clinical and physiological outcomes such as prevention of progressive systemic de-oxygenation/clinical improvement, mortality, duration of mechanical ventilation, improvement in pulmonary arterial pressure, and adverse events were assessed.

Results: The 14 retrospective/protective studies randomly assigning 423 patients met the inclusion criteria. Cumulative study of the selected articles showed that iNO has a mild impact on ventilation time or ventilator-free days. iNO has increased the partial pressure of oxygen/fraction of inspired oxygen ratio of fraction of inspired oxygen in a few patients as compared to baseline. However, in most of the studies, it does not have better outcome when compared to the baseline improvement.

Conclusions: In patients with COVID-19 with acute respiratory distress syndrome, nitric oxide is linked to a slight increase in oxygenation but has no effect on mortality.

Keywords: COVID-19; Coronavirus; inhaled nitric oxide; nitric oxide; oxygenation; ventilation.

Publication types

  • Systematic Review

MeSH terms

  • Administration, Inhalation
  • Bronchodilator Agents / administration & dosage*
  • COVID-19 / diagnosis
  • COVID-19 / drug therapy*
  • COVID-19 / mortality
  • Critical Illness / therapy*
  • Humans
  • Nitric Oxide / administration & dosage*
  • Respiration, Artificial / trends
  • Retrospective Studies
  • Severity of Illness Index*
  • Treatment Outcome


  • Bronchodilator Agents
  • Nitric Oxide