Nishimura M, Hess D, Kacmarek R M, Ritz R, Hurford W E
Department of Anesthesia, Harvard Medical School, Boston, Massachusetts, USA.
Anesthesiology. 1995 May;82(5):1246-54. doi: 10.1097/00000542-199505000-00020.
Inhaled nitric oxide (NO) may be useful in the treatment of adult respiratory distress syndrome and other diseases characterized by pulmonary hypertension and hypoxemia. NO is rapidly converted to nitrogen dioxide (NO2) in oxygen (O2) environments. We hypothesized that in patients whose lungs are mechanically ventilated and in those with a long residence time for NO in the lungs, a clinically important [NO2] may be present. We therefore determined the rate constants for NO conversion in adult mechanical ventilators and in a test lung simulating prolonged intrapulmonary residence of NO.
NO (800 ppm) was blended with nitrogen (N2), delivered to the high-pressure air inlet of a Puritan-Bennett 7200ae or Siemens Servo 900C ventilator, and used to ventilate a test lung. The ventilator settings were varied: minute ventilation (VE) from 5 to 25 l/min, inspired O2 fraction (FIO2) from 0.24 to 0.87, and [NO] from 10 to 80 ppm. The experiment was then repeated with air instead of N2 as the dilution gas. The effect of pulmonary residence time on NO2 production was examined at test lung volumes of 0.5-4.0 l, VE of 5-25 l/min, FIO2 of 0.24-0.87, and [NO] of 10-80 ppm. The inspiratory gas mixture was sampled 20 cm from the Y-piece and from within the test lung. NO and NO2 were measured by chemiluminescence. The rate constant (k) for the conversion of NO to NO2 was determined from the relation 1/[NO]t-1/[NO]o = k x [O2] x t, where t = residence time.
No NO2 was detected during any trial with VE 20 or 25 l/min. With N2 dilution and the Puritan-Bennett 7200ae, NO2 (< or = 1 ppm) was detected only at a VE of 5 l/min with an FIO2 of 0.87 and [NO] > or = 70 ppm. In contrast, [NO2] values were greater with the Servo 900C ventilator than with the Puritan-Bennett 7200ae at similar settings. When NO was diluted with air, clinically important [NO2] values were measured with both ventilators at high [NO] and FIO2. Rate constants were 1.46 x 10(-9) ppm-2.min-1 when NO was mixed with N2, 1.17 x 10(-8) ppm-2.min-1 when NO was blended with air, and 1.44 x 10(-9) ppm-2.min-1 in the test lung.
[NO2] increased with increased FIO2 and [NO], decreased VE, blending with air, and increased lung volumes. Higher [NO2] was produced with the Servo 900C ventilator than the Puritan-Bennett 7200ae because of the greater residence time. With long intrapulmonary residence times for NO, there is a potential for NO2 production within the lungs. The rate constants determined can be used to estimate [NO2] in adult mechanical ventilation systems.
吸入一氧化氮（NO）可能有助于治疗成人呼吸窘迫综合征及其他以肺动脉高压和低氧血症为特征的疾病。在氧气（O₂）环境中，NO会迅速转化为二氧化氮（NO₂）。我们推测，在接受机械通气的患者以及肺部中NO停留时间较长的患者中，可能会出现具有临床意义的[NO₂]。因此，我们测定了成人机械通气设备以及模拟NO在肺内长时间停留的测试肺中NO转化的速率常数。
将NO（800 ppm）与氮气（N₂）混合，输送至伟康7200ae型或西门子Servo 900C型呼吸机的高压空气入口，用于给测试肺通气。改变呼吸机设置：分钟通气量（VE）从5至25升/分钟，吸入氧分数（FIO₂）从0.24至0.87，[NO]从10至80 ppm。然后用空气代替N₂作为稀释气体重复该实验。在测试肺容积为0.5 - 4.0升、VE为5 - 25升/分钟、FIO₂为0.24 - 0.87以及[NO]为10 - 80 ppm的条件下，研究肺内停留时间对NO₂生成的影响。在距Y形管20厘米处以及测试肺内部采集吸气气体混合物样本。通过化学发光法测量NO和NO₂。根据关系式1/[NO]t - 1/[NO]o = k×[O₂]×t（其中t = 停留时间）确定NO转化为NO₂的速率常数（k）。
在任何VE为20或25升/分钟的试验中均未检测到NO₂。使用N₂稀释且采用伟康7200ae型呼吸机时，仅在VE为5升/分钟、FIO₂为0.87且[NO]≥70 ppm时检测到NO₂（≤1 ppm）。相比之下，在类似设置下，Servo 900C型呼吸机的[NO₂]值高于伟康7200ae型呼吸机。当用空气稀释NO时，在高[NO]和FIO₂条件下，两种呼吸机均检测到具有临床意义的[NO₂]值。当NO与N₂混合时，速率常数为1.46×10⁻⁹ ppm⁻²·分钟⁻¹；当NO与空气混合时，速率常数为1.17×10⁻⁸ ppm⁻²·分钟⁻¹；在测试肺中的速率常数为1.44×10⁻⁹ ppm⁻²·分钟⁻¹。
[NO₂]随FIO₂和[NO]的增加、VE的降低、与空气混合以及肺容积的增加而升高。由于停留时间更长，Servo 900C型呼吸机产生的[NO₂]高于伟康7200ae型呼吸机。当肺内NO停留时间较长时，肺内有产生NO₂的可能性。所测定的速率常数可用于估计成人机械通气系统中的[NO₂]。
