In vitro study of the formation of NO2 in inhalation of nitrogen monoxide

Abstract

Nitric oxide (NO), an endogenous endothelium-derived relaxing factor, produces profound relaxation of vascular smooth muscle. Thus, inhaled NO is a potent and selective pulmonary vasodilator that may be useful for treatment of pulmonary hypertension of different aetiologies. However, the main danger of NO inhalation is spontaneous formation of toxic nitrogen dioxide (NO2) if NO is added to an oxygen-containing gas mixture. This chemical reaction depends on the time available for the oxidation and the concentration of NO and oxygen. The aim of this study was to assess in vitro the spontaneous formation of NO2 during administration of various NO concentrations with a ventilator. A modified ventilator system is described which can deliver NO within clinically relevant concentrations avoiding excessive formation of toxic NO2. The system was evaluated using an artificial lung. NO and NO2 concentrations were measured by chemiluminescence at the proximal and distal end of the inspiratory limb. In-vitro NO2 formation was assessed during administration of 10, 20, 40, 80 ppm NO while ventilating with an FiO2 of 0.25, 0.5 and 0.75, an inspiratory minute volume of 5, 7.5 and 10 l/min (IMV) and a respiratory rate of 12/min. NO2 concentration correlated with increasing FiO2 and NO concentration and was inversely correlated to IMV. While ventilating with 5-40 ppm NO, an FiO2 of 0.25-0.75 and an IMV of 10 l per minute, the NO2 formation was measured to be less than 0.2 ppm and thus not clinically relevant. During administration of 80 ppm NO the NO2 formation increased to 0.3-0.6 ppm. We conclude that for patients safety concentrations less than 80 ppm of inhaled NO should be used with this ventilator system. In addition, online monitoring of the NO2 concentration in the inspiratory limb should always be performed.