Evaluation of Inhaled Nitric Oxide Generation Systems at Altitude

Inhaled nitric oxide (INO) is a selective pulmonary vasodilator delivered from compressed gas cylinders filled to 2,200 psig (137.8 bar) with 800 ppm of NO in a balance of nitrogen. NO is currently FDA-approved for use in term or near-term infants with hypoxemia and signs of pulmonary hypertension in the absence of cardiac disease. INO has also been shown to improve oxygenation in adults with refractory hypoxemia. Current doctrine precludes the use of NO during military aeromedical transport owing to the requirement for large compressed gas cylinders. We performed a bench evaluation of 2 delivery systems that create NO from room air without the need for pressurized cylinders.

We evaluated 2 portable nitric oxide INO generation systems (LungFit PH, Beyond Air Inc, Garden City, NJ and a prototype NO generator, Odic Inc, Littleton, MA) at ground level, 8,000, and 14,000 feet (2,437 and 4,267 meter) simulated altitude in an altitude chamber. The output from each device was injected into the inspiratory limb of the ventilator circuit that was attached to a test lung. A 731 ventilator (Zoll Medical, Chelmsford, MA) and T1 (Hamilton Medical, Reno, NV) were used employing 24 combinations of ventilator settings each repeated in duplicate. An INOmax DS IR was used to measure delivered INO and NO2 via a sampling line attached in the ventilator circuit inspiratory limb. A fast response oxygen analyzer (O2CAP, Oxigraf Inc, Sunnyvale, CA) was used to measure inspired FiO2. Target INO concentration was 20 ppm.

Across all ventilator settings, the LungFit device delivered INO was 19.8 ± 1.6 ppm, 16.1 ± 1.9 ppm, and 11.6 ± 1.7 ppm at ground level, 8,000 ft (2,437 meter), and 14,000 ft (4,267 meter), respectively. The Odic device delivered INO dose was 20.6 ± 1.4 ppm, 21.3 ± 5.5 ppm, and 20.4 ± 9.1 ppm at ground level, 8,000 ft (2,437 meter), and 14,000 ft (4,267 meter), respectively.

Both devices delivered a reliable INO dose at ground level. Altitude significantly affected INO delivery accuracy at 14,000 ft (4,267 meter) (P < 0.01) with both devices and at 8,000 ft (2,437 meter) (P < 0.01) with LungFit. Differences in INO dosage were not statistically significant with the Odic device at 8,000 ft (2,437 meter)(P > 0.05) although there were large variations with selected ventilator settings. With careful monitoring, devices creating INO from room air without cylinders could be used during aeromedical transport without the need for pressurized cylinders.