High-Efficiency Generation and Delivery of Aerosols Through Nasal Cannula During Noninvasive Ventilation

Abstract

Background: Previous studies have demonstrated the delivery of pharmaceutical aerosols through nasal cannula and the feasibility of enhanced condensational growth (ECG) with a nasal interface. The objectives of this study were to develop a device for generating submicrometer aerosols with minimal depositional loss in the formation process and to improve aerosol delivery efficiencies through nasal cannulas. Methods: A combination of in vitro experiments and computational fluid dynamics (CFD) simulations that used the strengths of each method was applied. Aerosols were formed using a conventional mesh nebulizer, mixed with ventilation gas, and heated to produce submicrometer sizes. An improved version of the mixer and heater unit was developed based on CFD simulations, and performance was verified with experiments. Aerosol delivery was considered through a commercial large-bore adult cannula, a divided (D) design for use with ECG, and a divided and streamlined (DS) design. Results: The improved mixer design reduced the total deposition fraction (DF) of drug within the mixer by a factor of 3 compared with an initial version, had a total DF of approximately 10%, and produced submicrometer aerosols at flow rates of 10 and 15 L/min. Compared with the commercial and D designs for submicrometer aerosols, the DS cannula reduced depositional losses by a factor of 2-3 and retained only approximately 5% or less of the nebulized dose at all flow rates considered. For conventional-sized aerosols (3.9 and 4.7 lm), the DS device provided delivery efficiencies of approximately 80% and above at flow rates of 2-15 L/min. Conclusions: Submicrometer aerosols can be formed using a conventional mesh nebulizer and delivered through a nasal cannula with total delivery efficiencies of 80-90%. Streamlining the nasal cannula significantly improved the delivery efficiency of both submicrometer and micrometer aerosols; however, use of submicrometer particles with ECG delivery resulted in overall lower depositional losses.

Optimal Delivery of Aerosols to Infants During Mechanical Ventilation

“…(30) A range of realistic aerosol particle sizes was then generated by connecting the nebulizer with either a custom mixer-heater device or a CM neonatal T-connector (Aerogen Limited). The mixer-heater was previously developed and optimized by Longest et al (31) to modify aerosol particle size with controlled heat and humidity conditions along with low (<10%) depositional loss of the drug. As described by Longest et al, (31) the mixer-heater operates with air flow rates in the range of 5-30 L/min and aerosol nebulization rates of approximately 0.2-0.4 mL/min, but can be extended to other flow rates by adjusting the heating controls.…”

Intermittent Aerosol Delivery to the Lungs During High-Flow Nasal Cannula Therapy

“…This method may allow simultaneous aerosol delivery without significant interruption of HFNC therapy. The technique employs a conventional mesh nebulizer, coupled with a simple mixer-heater, 14 to produce submicrometer aerosols. This base technology would be readily applicable to other nebulized drugs required for patients with asthma exacerbations, pneumonia with severe hypoxemia, sickle cell disease (acute chest syndrome), pulmonary hypertension, cystic fibrosis, and other chronic lung infections like Mycobacterium avium complex.…”

“…Steadystate studies were performed using a constant inhalation flow to assess device deposition, NMT model deposition, and aerosol growth. The aerosol delivery setup consisted of a low-volume vibrating mesh nebulizer (Aeroneb Lab) and a mixer-heater 14 to produce the submicrometer aerosol. The mixer-heater uses heated compressed gas (37-43°C) to evaporate the aerosol droplet output of the commercial nebulizer, reducing its mass median aerodynamic diameter from 4 -6 m to Ͻ 1 m. The development of the mixer-heater was described previously by Longest et al 14 and characterized as having a high emitted dose (Ͼ 90%) and aerosol mass median aerodynamic diameter of 0.91 (0.08) m when tested under steady-state flow conditions.…”

“…The remainder of the setup consisted of the aerosol mixer-heater, 14 which was used to generate the submicrometer aerosol by mixing the droplets emitted from a vibrating mesh nebulizer (Aeroneb Lab) with the heated compressed air stream. The nebulizer formulation contained 0.2% albuterol sulfate and 0.2% sodium chloride in deionized water.…”

“…1B) to the NMT model at a flow of 20 L/min. For ECG delivery, a divided ECG cannula, 14 with separate inlets for the aerosol and heated humidified high-flow air, was employed. The aerosol was delivered at 20 L/min from the mixer-heater to the aerosol side of the cannula, and the additional humidified high-flow air at a flow of 15 L/min and a temperature of 43°C was delivered to the humidity side (see Fig.…”