In Vitro Model for Analysis of High-Flow Aerosol Delivery During Continuous Nebulization

BACKGROUND: To understand the fate of aerosols delivered by high-flow nasal cannula using continuous nebulization, an open-source anatomical model was developed and vali-dated with a modified real-time gamma ratemeter technique. Mass balance defined circuit losses. Responsiveness to infusion rate and device technology were tested. METHODS: A nasal airway cast derived from a computed tomography scan was converted to a 3-dimen-sional–printed head and face structure connected to a piston ventilator (breathing frequency 30 breaths/min, tidal volume 750 mL, duty cycle 0.50). For mass balance experiments, saline mixed with Technetium-99m was infused for 1 h. Aerosol delivery was measured using a gamma ratemeter oriented to an inhaled mass filter at the hypopharynx of the model. Background and dead-space effects were minimized. All components were imaged by scin-tigraphy. Continuous nebulization was tested at infusion rates of 10–40 mL/h with gas flow of 60 L/min using a breath-enhanced jet nebulizer (BEJN), and a vibrating mesh nebulizer. Drug delivery rates were defined by the slope of ratemeter counts/min (CPM/min) versus time (min). RESULTS: The major source of aerosol loss was at the nasal interface (25%). Significant differences in deposition on circuit components were seen between nebulizers. The nebulizer residual was higher for BEJN (P 5.006), and circuit losses, including the humidifier, were higher for vibrating mesh nebulizer (P 5.006). There were no differences in delivery to the filter and head model. For 60 L/min gas flow, as infusion pump flow was increased, the rate of aerosol delivery (CPM/min) increased, for BEJN from 338 to 8,111; for vibrating mesh nebulizer, maximum delivery was 2,828. CONCLUSIONS: The model defined sites of aerosol losses during continuous nebulization and provided a realistic in vitro system for testing aerosol delivery during continuous nebulization. Real-time analysis can quantify effects of multiple changes in variables (nebulizer technology, infusion rate, gas flow, and ventilation) during a given experiment.