Inhaled Nitric Oxide for Clinical Management of COVID-19: A Systematic Review and Meta-Analysis

Jaber S. Alqahtani, Abdulelah M. Aldhahir, Shouq S. Al Ghamdi, Salma AlBahrani, Ibrahim A. AlDraiwiesh, Abdullah A. Alqarni, Kamaluddin Latief, Reynie Purnama Raya and Tope Oyelade ()
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Jaber S. Alqahtani: Department of Respiratory Care, Prince Sultan Military College of Health Sciences, Dammam 34313, Saudi Arabia
Abdulelah M. Aldhahir: Respiratory Therapy Department, Faculty of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia
Shouq S. Al Ghamdi: Anesthesia Technology Department, Prince Sultan Military College of Health Sciences, Dammam 34313, Saudi Arabia
Salma AlBahrani: Department of Internal Medicine, King Fahad Military Medical Complex, Dhahran 31932, Saudi Arabia
Ibrahim A. AlDraiwiesh: Department of Respiratory Care, Prince Sultan Military College of Health Sciences, Dammam 34313, Saudi Arabia
Abdullah A. Alqarni: Department of Respiratory Therapy, Faculty of Medical Rehabilitation Sciences, King Abdulaziz University, Jeddah 22254, Saudi Arabia
Kamaluddin Latief: Global Health and Health Security Department, College of Public Health, Taipei Medical University, Taipei 11031, Taiwan
Reynie Purnama Raya: Institute for Global Health, Faculty of Population Health Sciences, University College London, London NW3 2PF, UK
Tope Oyelade: Institute for Liver and Digestive Health, Division of Medicine, University College London, London NW3 2PF, UK

IJERPH, 2022, vol. 19, issue 19, 1-16

Abstract: Background: Severe COVID-19 is associated with hypoxemia and acute respiratory distress syndrome (ARDS), which may predispose multiorgan failure and death. Inhaled nitric oxide (iNO) is a clinical vasodilator used in the management of acute respiratory distress syndrome (ARDS). This study evaluated the response rate to iNO in patients with COVID-19-ARDS. Method: We searched Medline and Embase databases in May 2022, and data on the use of iNO in the treatment of ARDS in COVID-19 patients were synthesized from studies that satisfied predefined inclusion criteria. A systematic synthesis of data was performed followed by meta-analysis. We performed the funnel plot and leave-one-out sensitivity test on the included studies to assess publication bias and possible exaggerated effect size. We compared the effect size of the studies from the Unites States with those from other countries and performed meta-regression to assess the effect of age, year of publication, and concomitant vasodilator use on the effect size. Results: A total of 17 studies (including 712 COVID-19 patients) were included in this systematic review of which 8 studies (involving 265 COVID-19 patients) were subjected to meta-analysis. The overall response rate was 66% (95% CI, 47–84%) with significantly high between-studies heterogeneity (I2 = 94%, p < 0.001). The funnel plot showed publication bias, although the sensitivity test using leave-one-out analysis showed that removing any of the study does not remove the significance of the result. The response rate was higher in the Unites States, and meta-regression showed that age, year of publication, and use of concomitant vasodilators did not influence the response rate to iNO. Conclusion: iNO therapy is valuable in the treatment of hypoxemia in COVID-19 patients and may improve systemic oxygenation in patients with COVID-19-ARDS. Future studies should investigate the mechanism of the activity of iNO in COVID-19 patients to provide insight into the unexplored potential of iNO in general ARDS.

Keywords: inhaled nitric oxide (iNO); acute respiratory distress syndrome (ARDS); COVID-19; hypoxemia; meta-analysis (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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