Abstract
Background: The objective of this study was to characterize aerosol droplet size and distribution with laser diffraction for nebulized 3% NaCl, albuterol, and epoprostenol sodium. Methods: A series of flow tests were run on each of 8 Aerogen Solo nebulizer heads prior to the study to verify accuracy of flows in mL/minute. Aerosolized droplets exiting the nebulizer heads were then measured using a phase Doppler particle analyzer. Data collected during delivery of 3% NaCl, albuterol, and epoprostenol sodium included aerosol droplet size distribution, mass median aerodynamic diameter (MMAD), and geometric standard deviation. For each nebulizer head, droplet size measurements were taken at the following locations: 2 cm away from the nebulizer head and 2 cm away from the Y-piece of a heated, humidified adult ventilator circuit. For measurements taken at the Y-piece, 4 distinct, continuous flows (2, 10, 20, and 40 L/min) were generated by an air pump to simulate inspiratory flows delivered with mechanical ventilation. The expiratory limb was capped, and the nebulizer head was inserted into the breathing circuit upstream of the humidifier. Results: Each Solo nebulizer met Aerogen’s recommended minimum flow of 0.2 mL/min, ranging from 0.23 to 0.31 mL/min. The MMAD of the 3 tested aerosols was several times larger when measured directly at the cup outlet (MMAD, 4.6-7.3 µm) than at the outlet of the heated/humidified breathing circuit (MMAD, 0.85-2.73 µm). See Figure displaying MMAD and geometric standard deviations. The lower limit of detection for droplet size of the phase Doppler particle analyzer is 0.5 µm. Conclusions: Aerosol size was smaller than expected with the simulation. Previous studies using cascade impactors to evaluate MMAD indicate that vibrating mesh nebulizers should be expected to generate droplets <3.3 µm in diameter. Evaluation of Solo nebulizers in high-flow nasal cannulas shows that over 80% of the inhalable mass is fine particles between 0.4-4.4 µm. In the current simulation study, most particles ≥3 µm in diameter appeared to be trapped in the inspiratory circuit before they could have had a chance to be delivered to the patient. Droplets up to 1 µm may be exhaled before diffusion takes place. This may result in less drug being delivered to the patient than previously realized.
Footnotes
Commercial Relationships: Kelly McDermott and Jason G. Oakley: Paid participants in 2017 for Mallinckrodt instruction validation testing.
Support: Mallinckrodt Pharmaceuticals
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