A comparison between high dose nitric oxide delivered from pressurized cylinders and nitric oxide produced by an electric generator from air. A safety pilot study.

Gianni, Stefano; Di Fenza, Raffaele; Araujo Morais, Caio C; Fakhr, Bijan Safaee; Mueller, Ariel L; Yu, Binglan; Carroll, Ryan W; Ichinose, Fumito; Zapol, Warren M; Berra, Lorenzo

Background: High dose (≥80 parts-per-million[ppm]) inhaled nitric oxide (NO) has antimicrobial effects. We designed a trial to test the preventive effects of high dose NO on coronavirus disease (COVID-19) in healthcare providers working with COVID-19 patients. The study was interrupted prematurely due to the introduction of COVID-19 vaccines for healthcare professionals. We thereby present data on safety and feasibility of breathing 160 ppm NO using two different NO sources, namely pressurized nitrogen/NO cylinders (iNO) and electric NO generators (eNO).Methods: Nitric oxide gas was inhaled at 160 ppm in air for 15 minutes twice a day, before and after each work shift, over 14 days to healthcare providers (NCT04312243). During NO administration vital signs were continuously monitored. Safety was assessed by measuring transcutaneous methemoglobinemia (SpMet) and the inhaled nitrogen dioxide (NO2) concentration.Results: 12 healthy healthcare professionals received a collective total of 185 administrations of high dose NO (160 ppm) for 15 minutes twice daily. 171 doses were delivered by iNO and 14 doses by eNO. During NO administration SpMet increased similarly in both groups (p=.82). Methemoglobin decreased in all subjects at five minutes after discontinuing NO administration. Inhaled NO2 concentrations remained between 0.70 [0.63-0.79] and 0.75 [0.67-0.83] ppm in the iNO group and between 0.74 [0.68-0.78] and 0.88 [0.70-0.93] ppm in eNO group. During NO administration peripheral oxygen saturation and heart rate did not change. No adverse events occurred.Conclusion: This pilot study testing high dose inhaled NO (160 ppm) for 15 minutes twice a day using eNO seem feasible and similarly safe when compared with iNO.