Ideation and Assessment of a Novel Nitric Oxide Delivery System for Spontaneously Breathing Subjects S. Gianni1

ABSTRACT

Rationale High dose nitric oxide (NO) produces broad antimicrobial activity and several clinical trials are now testing the efficacy of NO inhalation on patients infected by SARS CoV-2. Nitrogen dioxide (NO2) is formed by the reaction between NO and oxygen, and when combined with water in the airways, NO2, forms nitric acid, leading to a caustic burn of the airways. In this study, we designed and developed a breathing system capable of safely delivering high concentrations of NO. Methods We developed a gas delivery system that utilizes standard respiratory circuit connectors, a reservoir bag, and a scavenging chamber containing calcium hydroxide (Ca(OH)2) (Fig. 1). The system was tested using a bench testing lung and a mechanical ventilator. The NO concentration was measured by a NO analyzer connected to the inspiratory limb via a sampling line. NO2 levels were simultaneously evaluated by the Cavity Attenuated Phase Shift (CAPS) NO2 monitor using the same sampling port. To assess the efficacy of the Ca(OH)2 scavenger in reducing the inspiratory levels of NO2, we used a range of target NO concentrations (50, 150, and 250 ppm), two different levels of FiO2 (0.21 and 0.40) and measured NO2 levels with and without the scavenger. We administered high-dose NO with our system to healthy adult volunteers as part of a trial conducted at MGH. Each administration lasted for 15 minutes. Peripheral oxygen saturation (SpO2) and methemoglobin (MetHb) were continuously monitored with a pulse co-oximeter. Results Using our delivery system, we were able to reach NO concentration up 250 ppm with an Inspired oxygen fraction (FiO2) between 0.21 and 0.4. The scavenger reduced the inhaled NO2 concentration to an average of 0.9 ppm (CI -1.58, -0.22;p=0.01). At 150 ppm of inhaled NO, the NO2 concentration was maintained below 1.2 ppm with FiO2 from 0.21 to 0.40. Our data suggest that the scavenger can efficiently reduce NO2 in the circuit for NO delivery. We administered NO to 4 adult volunteers. The total number of NO administrations was 30. The average concentration of inspired NO was 163.9±10.1 ppm with NO2 levels of 0.75±0.08 ppm. During the administration methemoglobin levels increased from a baseline value of 0.97±0.6% to 2.17±0.43%. The subjects did not experience any adverse events. Conclusions We built a NO delivery system that provides a safe alternative to a ventilator-based system to give high dose NO to spontaneously breathing patients.