Background

There is an increasing interest in safely delivering high dose of inhaled nitric oxide (NO) as an antimicrobial and antiviral therapeutics for spontaneously breathing patients. A novel NO delivery system is described.

Methods

We developed a gas delivery system that utilizes standard respiratory circuit connectors, a reservoir bag, and a scavenging chamber containing calcium hydroxide. The performance of the system was tested using a mechanical lung, assessing the NO concentration delivered at varying inspiratory flows. Safety was assessed in vitro and in vivo by measuring nitrogen dioxide (NO₂) levels in the delivered NO gas. Lastly, we measured the inspired and expired NO and NO₂ of this system in 5 healthy subjects during a 15-min administration of high dose NO (160 parts-per-million, ppm) using our delivery system.

Results

The system demonstrated stable delivery of prescribed NO levels at various inspiratory flow rates (0–50 L/min). The reservoir bag and a high flow of entering air minimized the oscillation of NO concentrations during inspiration on average 4.6 ppm for each 10 L/min increment in lung inspiratory flow.

The calcium hydroxide scavenger reduced the inhaled NO₂ concentration on average 0.9 ppm (95% CI -1.58, −0.22; p = .01). We performed 49 NO administrations of 160 ppm in 5 subjects. The average concentration of inspired NO was 164.8$\pm$10.74 ppm, with inspired NO₂ levels of 0.7$\pm$0.13 ppm. The subjects did not experience any adverse events; transcutaneous methemoglobin concentrations increased from 1.05$\pm$0.58 to 2.26$\pm$0.47%.

Conclusions

The system we developed to administer high-dose NO for inhalation is easy to build, reliable, was well tolerated in healthy subjects.

中文翻译：

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自发呼吸对象的一氧化氮输送系统的构想和评估。

背景

安全地释放高剂量吸入一氧化氮（NO）作为自发呼吸患者的抗微生物和抗病毒治疗剂的兴趣日益浓厚。描述了一种新颖的NO输送系统。

方法

我们开发了一种气体输送系统，该系统利用标准的呼吸回路连接器，储气袋和装有氢氧化钙的扫气室。使用机械肺对系统的性能进行测试，评估在不同吸气流量下输送的NO浓度。通过测量输送的NO气体中的二氧化氮（NO ₂）水平，在体内和体外评估安全性。最后，我们在15分钟内使用我们的输送系统对高剂量NO（百万分之160，ppm）进行了15分钟的测量，在5名健康受试者中测量了该系统的灵感和呼出的NO和NO ₂。

结果

系统显示了在各种吸气流速（0–50升/分钟）下稳定递送规定的一氧化氮水平。储气袋和高流量的进气使吸气过程中每10 L / min的肺吸气流量增加平均4.6 ppm时NO浓度的波动最小。

氢氧化钙清除剂将吸入的NO ₂浓度平均降低了0.9 ppm（95％CI -1.58，-0.22；p  = 0.01）。我们对5位受试者进行了49次NO给药，每分钟160 ppm。吸入NO的平均浓度为164.8$\pm$10.74 ppm，NO ₂激发水平为0.7$\pm$0.13 ppm。受试者没有经历任何不良事件。经皮高铁血红蛋白浓度从1.05增加$\pm$0.58至2.26$\pm$0.47％。

结论

我们开发的用于吸入高剂量NO的系统易于构建，可靠，并且在健康受试者中耐受性良好。