Novartis Pharmaceuticals , San Carlos, California.
J Aerosol Med Pulm Drug Deliv. 2018 Apr;31(2):94-102. doi: 10.1089/jamp.2017.1372. Epub 2017 Aug 16.
In an in vitro model of mechanical ventilation with gravity-dependent filter position we observed artificially high delivered doses resulting from liquid droplet collection and precipitation of aerosolized drug. We sequentially modified the model to obtain accurate reproducible measurements of delivered dose and particle size at endotracheal tube exit.
Stepwise changes in the model included (1) altering the endotracheal tube position to a gravity-independent position, (2) adding fluid traps, (3) humidifying air near the test lung, and (4) simplifying test lung and filters. Delivered dose of aerosolized vancomycin and losses in different compartments were assessed under low-flow and high-flow conditions, with or without circuit humidification. Droplet size distribution (DSD) of aerosolized Amikacin Inhalation Solution at endotracheal tube exit was measured by laser diffraction.
Changing endotracheal tube position and adding traps allowed separation of liquid droplets and aerosolized drug, providing a delivered vancomycin dose of 35.1% (high flow). Active heated humidification of exhaled air significantly reduced delivered dose (21.0%) and dose variability. Simplification of the model to improve usability had no further effect on delivered dose, which was higher under low-flow than high-flow conditions, although there was no difference between humidified (high flow, 20.3%; low flow, 45.8%) and nonhumidified (high flow, 22.8%; low flow, 47.3%) conditions. With circuit humidification, drug loss decreased in endotracheal tube and nebulizer T-piece, whereas more drug was captured in traps. Lower inspiratory flow and humidity in the circuit were associated with higher Dv50 of aerosolized Amikacin Inhalation Solution at endotracheal tube exit.
We successfully modified our in vitro model of mechanical ventilation to allow more accurate measurement of the delivered dose of aerosolized vancomycin and DSD profile of aerosolized Amikacin Inhalation Solution at the endotracheal tube exit.
在一项依赖重力的过滤位置的机械通气体外模型中,我们观察到由于液滴收集和雾化药物沉淀,导致输送剂量人为升高。我们逐步修改模型,以获得在气管内导管出口处输送剂量和颗粒大小的准确可重复测量。
模型的逐步改变包括:(1)将气管内导管位置改为不依赖重力的位置;(2)添加液体阱;(3)在测试肺附近加湿空气;(4)简化测试肺和过滤器。在低流量和高流量条件下,评估有无回路加湿,雾化万古霉素的输送剂量和不同部位的损失。通过激光衍射测量气管内导管出口处雾化阿米卡星吸入溶液的雾滴大小分布(DSD)。
改变气管内导管位置和添加阱可以分离液滴和雾化药物,提供 35.1%(高流量)的输送万古霉素剂量。呼出空气的主动加热加湿显著降低输送剂量(21.0%)和剂量变异性。模型的简化以提高可用性没有进一步影响输送剂量,低流量条件下的输送剂量高于高流量条件,尽管加湿(高流量,20.3%;低流量,45.8%)和非加湿(高流量,22.8%;低流量,47.3%)条件之间没有差异。有回路加湿时,药物在气管内导管和雾化器 T 型件中的损失减少,而阱中捕获的药物更多。较低的吸气流量和回路中的湿度与气管内导管出口处雾化阿米卡星吸入溶液的 Dv50 较高有关。
我们成功地修改了我们的机械通气体外模型,以更准确地测量雾化万古霉素的输送剂量和气管内导管出口处雾化阿米卡星吸入溶液的 DSD 谱。