Ideation and assessment of a nitric oxide delivery system for spontaneously breathing subjects

Background: There is an increasing interest in safely delivering high dose of inhaled nitric oxide (NO) as an antimicrobial and antiviral therapeutics for spontaneously breathing patients. A novel NO delivery system is described. Methods: We developed a gas delivery system that utilizes standard respiratory circuit connectors, a reservoir bag, and a scavenging chamber containing calcium hydroxide. The performance of the system was tested using a mechanical lung, assessing the NO concentration delivered at varying inspiratory flows. Safety was assessed in vitro and in vivo by measuring nitrogen dioxide (NO2) levels in the delivered NO gas. Lastly, we measured the inspired and expired NO and NO2 of this system in 5 healthy subjects during a 15-min administration of high dose NO (160 parts-per-million, ppm) using our delivery system. Results: The system demonstrated stable delivery of prescribed NO levels at various inspiratory flow rates (0-50 L/min). The reservoir bag and a high flow of entering air minimized the oscillation of NO concentrations during inspiration on average 4.6 ppm for each 10 L/min increment in lung inspiratory flow. The calcium hydroxide scavenger reduced the inhaled NO2 concentration on average 0.9 ppm (95% CI -1.58, 0.22; p = .01). We performed 49 NO administrations of 160 ppm in 5 subjects. The average concentration of inspired NO was 164.8 +/- 10.74 ppm, with inspired NO2 levels of 0.7 +/- 0.13 ppm. The subjects did not experience any adverse events; transcutaneous methemoglobin concentrations increased from 1.05 +/- 0.58 to 2.26 +/- 0.47%. Conclusions: The system we developed to administer high-dose NO for inhalation is easy to build, reliable, was well tolerated in healthy subjects.