1 Department of Respiratory Care, Texas State University , San Marcos, TX.
2 iPharma Limited , Brisbane, California.
J Aerosol Med Pulm Drug Deliv. 2018 Feb;31(1):42-48. doi: 10.1089/jamp.2016.1347. Epub 2017 Aug 22.
Placement of a heat moisture exchanger (HME) between aerosol generator and patient has been associated with greatly reduced drug delivery. The purpose of this study was to evaluate the effect of filtered and nonfiltered HMEs placed between nebulizer and patient on aerosol deposition and airway resistance (Raw) in simulated ventilator-dependent adults.
An in vitro lung model was developed to simulate a mechanically ventilated adult (Vt 500 mL, RR 15/min, and PEEP 5 cmHO, using two inspiratory flow rates 40 and 50 L/min) using an intubated adult manikin with an endotracheal tube (8 mmID). The bronchi of the manikin were connected to a Y-adapter through a collecting filter (Respirgard II) attached to a test lung through a heated humidifier (37°C producing 100% relative humidity) to simulate exhaled humidity. For treatment conditions, a nonfiltered HME (ThermoFlo™ 6070; ARC Medical) and filtered HMEs (ThermoFlo™ Filter; ARC Medical and PALL Ultipor; Pall Medical) were placed between the ventilator circuit at the endotracheal tube and allowed to acclimate to the exhaled heat and humidity for 30 minutes before aerosol administration. Airway resistance (cmHO/L/s) was taken at 0, 10, 20, and 30 minutes after HME placement and after each of four aerosol treatments. Albuterol sulfate (2.5 mg/3 mL) was administered with jet (Misty Max 10; Airlife) and mesh (Aerogen Solo; Aerogen) nebulizers positioned in the inspiratory limb proximal to the Y-adapter. Control consisted of nebulization with no HME. Drug was eluted from filter at the end of the trachea and measured using spectrophotometry (276 nm).
Greater than 60% of the control dose was delivered through the ThermoFlo. No significant difference was found between the first four treatments given by the jet (p = 0.825) and the mesh (p = 0.753) nebulizers. There is a small increase in Raw between pre- and post-four treatments with the jet (p = 0.001) and mesh (p = 0.015) nebulizers. Aerosol delivery through filtered HMEs was similar (<0.5%) across the four treatments. Airway resistance was similar using the ThermoFlo Filter. With the PALL Ultipor, changes in Raw increased with mesh nebulizer after treatment (p = 0.005). Changes in resistance pre- and post-treatment were similar with both filtered HMEs.
The ThermoFlo™ nonfilter HME allowed the majority of the control dose to be delivered to the airway. Increases in Raw would likely not be outside of a tolerable range in ventilated patients. In contrast, filtered HMEs should not be placed between nebulizers and patient airways. Further research with other HMEs and materials is warranted.
在雾化器和患者之间放置热湿交换器(HME)会大大降低药物输送。本研究的目的是评估在模拟依赖呼吸机的成人中,在雾化器和患者之间放置过滤和未过滤的 HME 对气溶胶沉积和气道阻力(Raw)的影响。
开发了一种体外肺模型,以模拟机械通气的成人(Vt 500 mL,RR 15/min,PEEP 5 cmHO,使用两种吸气流量 40 和 50 L/min),使用带有气管内管的插管成人人体模型(8 mmID)。人工呼吸器的支气管通过带有收集过滤器(Respirgard II)的 Y 型适配器连接到测试肺,通过加热加湿器(产生 100%相对湿度的 37°C)模拟呼出的湿度。对于治疗条件,在气管内管和允许适应呼出热和湿度的呼吸机回路之间放置非过滤 HME(ThermoFlo™ 6070;ARC Medical)和过滤 HME(ThermoFlo™ Filter;ARC Medical 和 Pall Ultipor;Pall Medical),然后在放置 HME 后 0、10、20 和 30 分钟以及每次四个气溶胶治疗后测量气道阻力(cmHO/L/s)。用射流(Misty Max 10;Airlife)和网孔(Aerogen Solo;Aerogen)雾化器将硫酸沙丁胺醇(2.5 mg/3 mL)施用于近端在 Y 型适配器的吸气侧。对照包括没有 HME 的雾化。在气管末端从过滤器洗脱药物,并使用分光光度法(276nm)测量。
超过 60%的对照剂量通过 ThermoFlo 输送。射流(p=0.825)和网孔(p=0.753)雾化器的前四个治疗之间没有发现显著差异。使用射流(p=0.001)和网孔(p=0.015)雾化器进行四次治疗后,Raw 略有增加。过滤 HME 之间的气溶胶输送相似(<0.5%)。ThermoFlo Filter 中的气道阻力相似。对于 Pall Ultipor,在用网孔雾化器治疗后,Raw 的变化增加(p=0.005)。治疗前后的阻力变化与两种过滤 HME 相似。
ThermoFlo™ 非过滤 HME 允许将大部分对照剂量输送到气道。Raw 的增加可能不会超出通气患者可耐受的范围。相比之下,不应该在雾化器和患者气道之间放置过滤 HME。需要对其他 HME 和材料进行进一步研究。