Introduction: Many devices (e.g., nebulizers and spacers) are used to deliver aerosol in a non-invasive ventilation circuit (NIV) without any special recommendation. The aim of the present work was to compare the doses delivered from seven different aerosol delivery systems when placed in the NIV using automatic continuous positive airway pressure (Auto-CPAP). Methods: Three spacers and three vibrating mesh nebulizers were compared to a Sidestream jet nebulizer (SIDE). Each device was placed proximal to a breathing simulator in a standard NIV circuit with a 500 ml tidal volume, 15 breaths/min and a 1:3 inspiratory-expiratory ratio. Two ml of salbutamol solution containing 10,000 lg was nebulized using Aerogen Pro (PRO), Aerogen Solo (SOLO), NIVO and SIDE. Twelve metered dose inhaler doses, containing 100 lg salbutamol each, were delivered using AeroChamber MV (AC), AeroChamber Vent (VC) and AeroChamber Mini (MC). Total emitted dose (TED) and its percentage were determined. Aerodynamic droplet characteristics were measured using cooled Andersen Cascade Impactor. Results: The vibrating mesh nebulizers used had significantly more (p\0.001) TED compared to the jet nebulizer. The spacers used had higher TED % (p\0.001) compared to the nebulizers. The fine particle fraction of SIDE was the highest (p = 0.021) and mass median aerodynamic diameter of the spacers was the smallest (p = 0.001). The fine particle dose from vibrating mesh nebulizers was the greatest (p = 0.02).

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Substituting spacer by another in noninvasive ventilation (NIV) involves many variables, e.g. total emitted dose (TED), mass median aerodynamic diameter (MMAD), type of spacer, total lung deposition and total systemic absorption, which must be adjusted to ensure patient optimum therapy. Data mining based on artificial neural networks and genetic algorithms were used to model in vitro inhalation process, predict and optimize bioavailability from inhaled doses delivered by metered dose inhaler (MDI) using different spacers in NIV. Modeling of data indicated that in vitro performance of MDI-spacer systems was dependent mainly on fine particle dose (FPD), fine particle fraction (FPF), MMAD and to lesser extent on spacer type. Ex vivo model indicated that amount of salbutamol collected on facemask filter was directly affected by FPF. In vivo model (24hQ) depended directly on spacer type, FPF and TED. Female patients showed higher 0.5hQ and 24hQ values than males. AeroChamber VC spacer demonstrated higher TED and 24hQ in vivo values. Results indicated suitability of MDI-spacer systems in achieving appropriate in vitro inhalation performance. The possibility of modeling and predicting both ex vivo and in vivo capabilities of MDI-spacer systems from knowledge of in vitro attributes enabled detailed focus on important variables required to deliver safe and accurate doses of salbutamol to ventilated patients.

Aerodynamic characteristics of aerosol delivery during invasive mechanical ventilation (IMV) are mostly determined by inserting cascade impactor in the circuit. Impactor might have some effect on airflow within IMV. Hence, the aim of the present study was to develop and evaluate new in vitro aerodynamic characterization methodology without affecting airflow in IMV. Breathing simulator was set in standard adult IMV circuit with inspiratory and expiratory pressures of 20 and 5 cm HO, 1:3 inspiratory-expiratory ratio, 15 breaths min, and tidal volume of 500 ml. Two ml of salbutamol solution containing 10,000 μg was nebulized using three different vibrating mesh nebulizers (VMNs) and Sidestream jet nebulizer (JET). Sixteen-metered doses, containing 100 μg salbutamol each, were delivered using three different spacers. Each device was placed in inspiration limb of Y-piece of ventilator tubing. Aerodynamic characteristics of aerosol delivered were measured using cooled Andersen cascade impactor, with mixing inlet connected to it. VMNs used had significantly more total mass in the impactor (p < .001) and fine particle dose (p < .001) compared to JET. Spacers used had higher total mass in the impactor percent (p < .001) and fine particle fraction compared to nebulizers. The in vitro IMV methodology setting suggested here showed encouraging results in comparison of different aerosol delivery systems in intubated patient.

These similarities and differences between the three aerosol generators tested suggest that aerosol delivery methods should be carefully chosen or substituted in non-invasive ventilated patients.

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