Motsch J, Weimann J, Fresenius M, Gagel K, Martin E
Klinik für Anästhesiologie, Ruprecht-Karls-Universität Heidelberg.
Anasthesiol Intensivmed Notfallmed Schmerzther. 1994 May;29(3):157-62. doi: 10.1055/s-2007-996706.
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.
一氧化氮（NO）作为一种内源性内皮衍生舒张因子，可使血管平滑肌产生显著舒张。因此，吸入性NO是一种强效且具选择性的肺血管扩张剂，可能对不同病因的肺动脉高压治疗有用。然而，吸入NO的主要风险在于，若将NO添加到含氧气的气体混合物中，会自发形成有毒的二氧化氮（NO₂）。此化学反应取决于氧化所需时间以及NO和氧气的浓度。本研究旨在通过体外实验评估使用呼吸机给予不同浓度NO时NO₂的自发形成情况。本文描述了一种改良的呼吸机系统，该系统能在临床相关浓度范围内输送NO，避免过量形成有毒的NO₂。
使用人工肺对该系统进行评估。通过化学发光法在吸气支近端和远端测量NO和NO₂浓度。在给予10、20、40、80 ppm NO的过程中，以0.25、0.5和0.75的吸入氧分数（FiO₂）、5、7.5和10升/分钟的吸气分钟量（IMV）以及12次/分钟的呼吸频率进行通气，评估体外NO₂的形成情况。
NO₂浓度与FiO₂和NO浓度的增加相关，与IMV呈负相关。在使用5 - 40 ppm NO、0.25 - 0.75的FiO₂以及每分钟10升的IMV进行通气时，测得NO₂形成量小于0.2 ppm，因此与临床无关。在给予80 ppm NO时，NO₂形成量增加至0.3 - 0.6 ppm。
我们得出结论，对于使用该呼吸机系统的患者，应使用浓度低于80 ppm的吸入性NO以确保安全。此外，应始终对吸气支中的NO₂浓度进行在线监测。
