Clinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Chest Diseases Department, Kasr Al Einy Faculty of Medicine, Cairo University, Cairo, Egypt.
Eur J Pharm Sci. 2021 Dec 1;167:105988. doi: 10.1016/j.ejps.2021.105988. Epub 2021 Sep 4.
Aerosol delivery to mechanically ventilated patients requires add-on connections to place the inhalation device within the ventilation circuit. The study aimed to evaluate the performance of Combihaler in dual limb invasive mechanical ventilation (IMV). A ventilator with a humidified dual limb circuit was adjusted to volume-controlled mode to imitate the adult breathing parameters. 24 (12 females) intubated chronic obstructive pulmonary disease (COPD) subjects had undergone the study. All patients were prescribed inhaled salbutamol dose delivered by either a metered-dose inhaler (pMDI) or vibrating mesh nebulizer (VMN). Each subject received salbutamol in four different inhalation device/connection conditions; pMDI+VMN+Combihaler, VMN+Combihaler, VMN+T-piece, and pMDI+T-piece. They were individually placed in the inspiratory limb at Y-piece. 5mg salbutamol was delivered by VMN with and without 2 pMDI puffs of salbutamol (100 µg), and 500µg was delivered by pMDI+T-piece. After aerosol delivery, two urine samples were collected from the patient; 30 min post-inhalation (USAL0.5) and cumulatively 24 h post-inhalation (USAL24) as indexes of lung deposition and systemic absorption, respectively. For the ex-vivo study, a collecting filter was placed before an endotracheal tube (ETT) to collect the delivered inhalable dose. In-vitro aerodynamic characteristics were also investigated. pMDI+VMN+Combihaler delivered more salbutamol to the lung and the ex-vivo filter than VMN+T-piece (p˂0.05, p≤0.01, respectively). VMN delivered a higher salbutamol amount to the lung, systemically, and the ex-vivo filter than pMDI+T-piece (p˂0.001). pMDI+VMN+Combihaler and VMN+Combihaler delivered aerosols with a less mass median aerodynamic diameter (MMAD) and higher fine particle fraction (FPF) compared to VMN+T-piece (p≤0.01 for MMAD, p˂0.01 for FPF) and pMDI+T-piece (p˂0.01 for both MMAD and FPF). Results of the study showed that pMDI+VMN+ Combihaler delivered more salbutamol than VMN+T-piece in IMV and demonstrate that 5 puffs (500-µg) of salbutamol with pMDI+T-piece has a lower aerosol delivering power at the level of USAL0.5, USAL24, and the ex-vivo inhalable dose than 5 mg nebulized salbutamol by VMNs in IMV.
在机械通气患者中进行气溶胶输送需要附加连接，以便将吸入装置放置在通气回路中。本研究旨在评估 Combihaler 在双肢机械通气（IMV）中的性能。带有加湿双肢回路的通气机被调整为容量控制模式，以模拟成人呼吸参数。24 名（12 名女性）插管慢性阻塞性肺疾病（COPD）患者接受了这项研究。所有患者均接受沙丁胺醇吸入治疗，吸入装置分别为定量吸入器（pMDI）或振动网孔雾化器（VMN）。每个患者在四种不同的吸入装置/连接条件下接受沙丁胺醇治疗：pMDI+VMN+Combihaler、VMN+Combihaler、VMN+T 型管和 pMDI+T 型管。它们分别放置在 Y 型管的吸气肢上。5mg 沙丁胺醇通过 VMN 输送，并与 2 个 pMDI 沙丁胺醇喷（100μg）一起输送，500μg 通过 pMDI+T 型管输送。气溶胶输送后，从患者身上采集 2 个尿样；吸入后 30 分钟（USAL0.5）和累积 24 小时（USAL24）作为肺沉积和全身吸收的指标。对于离体研究，在气管内导管（ETT）前放置一个收集过滤器，以收集输送的可吸入剂量。还研究了体外空气动力学特性。与 VMN+T 型管相比，pMDI+VMN+Combihaler 向肺和离体过滤器输送的沙丁胺醇更多（p<0.05，p≤0.01）。VMN 向肺、全身和离体过滤器输送的沙丁胺醇量高于 pMDI+T 型管（p<0.001）。与 VMN+T 型管相比，pMDI+VMN+Combihaler 和 VMN+Combihaler 输送的气雾剂的质量中值空气动力学直径（MMAD）更小，细颗粒分数（FPF）更高（p≤0.01 为 MMAD，p<0.01 为 FPF）和 pMDI+T 型管（p<0.01 为 MMAD 和 FPF）。研究结果表明，在 IMV 中，pMDI+VMN+Combihaler 比 VMN+T 型管输送更多的沙丁胺醇，并且在 USAL0.5、USAL24 和离体可吸入剂量方面，5 次（500μg）pMDI+T 型管的沙丁胺醇输送能力低于 IMV 中 5mg 雾化沙丁胺醇。
