Aerosol delivery of inhalation devices with different add-on connections to invasively ventilated COPD subjects: An in-vivo study

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.