Inhaled High Dose Nitric Oxide is a Safe and Effective Respiratory Treatment in Spontaneous Breathing Hospitalized Patients with COVID-19 pneumonia

Fakhr, Bijan Safaee; Di Fenza, Raffaele; Gianni, Stefano; Wiegand, Steffen B.; Miyazaki, Yusuke; Araujo Morais, Caio C.; Gibson, Lauren E.; Chang, Marvin G.; Mueller, Ariel L.; Rodriguez-Lopez, Josanna M.; Ackman, Jeanne B.; Arora, Pankaj; Scott, Louie K.; Bloch, Donald B.; Zapol, Warren M.; Carroll, Ryan W.; Ichinose, Fumito; Berra, Lorenzo

BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. In-vitro studies report that NO donors can inhibit replication of SARS-CoV-2. This multicenter study evaluated the feasibility and effects of high-dose inhaled NO in non-intubated spontaneously breathing patients with Coronavirus disease-2019 (COVID-19). METHODS: This is an interventional study to determine whether NO at 160 parts-per-million (ppm) inhaled for thirty minutes twice daily might be beneficial and safe in non-intubated COVID-19 patients. RESULTS: Twenty-nine COVID-19 patients received a total of 217 intermittent inhaled NO treatments for 30 minutes at 160 ppm between March and June 2020. Breathing NO acutely decreased the respiratory rate of tachypneic patients and improved oxygenation in hypoxemic patients. The maximum level of nitrogen dioxide delivered was 1.5 ppm. The maximum level of methemoglobin (MetHb) during the treatments was 4.7%. MetHb decreased in all patients 5 minutes after discontinuing NO administration. No adverse events during treatment, such as hypoxemia, hypotension, or acute kidney injury during hospitalization occurred. In our NO treated patients, one patient of 29 underwent intubation and mechanical ventilation, and none died. The median hospital length of stay was 6 days [interquartile range 4-8]. No discharged patients required hospital readmission nor developed COVID-19 related long-term sequelae within 28 days of follow-up. CONCLUSIONS: In spontaneous breathing patients with COVID-19, the administration of inhaled NO at 160 ppm for thirty minutes twice daily promptly improved the respiratory rate of tachypneic patients and systemic oxygenation of hypoxemic patients. No adverse events were observed. None of the subjects was readmitted or had long-term COVID-19 sequelae.