Aerosol deposition in a mechanically ventilated ex vivo porcine lung using a vibrating mesh nebuliser and a pressurized metered dose inhaler  

Ronan MacLoughlin¹, C Champigny², J Montharu², L Vecellio², & E Dalloneau³

¹Research and Development, Science and Emerging Technologies, Aerogen Limited, IDA Business Park, H91 HE94 Galway, Ireland
² Université de Tours, Plateforme Scientifique et Technique Animaleries (PST-A), 37032, Tours, France
³Inhalation solutions, 37510, Tours, France

Summary

Introduction: Despite its frequency of use aerosol delivery during mechanical ventilation of the anesthetised patient is not yet well described in humans. Porcine lungs are known to approximate the airway diameters, branching geometries and volumes of the human lung and ex-vivo lung models have shown utility across several studies. Here, we applied scintigraphic imaging in an ex vivo porcine lung model in the characterisation of aerosol delivery performance of the vibrating mesh nebuliser (VMN)  and pMDI during simulated adult mechanical ventilation. Methods: Two groups of three lungs from Large White pigs were used (body weight 102-126 kg). Ventilation parameters were fixed using volume control ventilation. V_t 800, I:E 1:2, BPM 15, PEEP 5cmH₂0. 5 mg/5 mL of salbutamol with 0.1mL of ^99mTc-DTPA (37mBq) was loaded into the VMN (Aeroneb Solo, Aerogen, Ireland). 10 puffs of ^99mTc-DTPA labelled salbutamol were delivered by the pMDI (Ventolin®, GSK, UK). Ventilator Circuit resistance was measured pre, during and post dosing to quantify any change. Results: For both VMN and pMDI no change in ventilator circuit resistance was noted. Aerosol deposition obtained in the porcine lung was higher with VMN than pMDI (11.59 ± 1.25% vs 1.31 ± 0.46%). Conclusion: The choice of aerosol drug delivery device has a significant bearing on the amount of drug delivered to the ventilated lung. These findings may be of use in the design and optimisation of clinical interventions but may also inform device selection criteria during pharmaceutical development of therapeutics indicated for use in mechanically ventilated patients.

 Key Message

During mechanical ventilation in an ex vivo model of adult lung a vibrating mesh nebuliser delivered significantly more aerosolised drug than a pMDI. Neither device was shown to adversely affect ventilation parameters. These findings are of use in the optimisation of clinical interventions and development of therapeutics indicated for ventilated patients.