Under-Dosing of Inhaled Medication Delivered by Continuous Nebulizers Is Possible as the Result of Changes to Inspiratory/Expiratory (I/E) Ratio Brought About by Obstructive Lung Disease.

SESSION TITLE: Outcomes/Quality Control Posters IISESSION TYPE: Original Investigation PosterPRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PMPURPOSE: To demonstrate the likely variability of medication delivery from continuously operating pneumatic nebulizers at different I/E ratios as adult patient I/E ratios are known to vary widely in advanced obstructive disease (Nikander, K, Denyer,J. Eur.Respir.Rev. 2000;10(76):576-579).METHODS: Two continuously operating jet nebulizers (n=5/group; AirLife® Misty Fast™, CareFusion, San Diego, CA, and NebuTech® HDN®, Salter Labs, Arvin, CA) operated with compressed air at 50 psig were evaluated with an adult tidal breathing waveform (tidal volume-500 mL) with I:E ratios = 1:1, 1:2, 1:3 and 1:4 with 15, 10, 7 and 6 breaths/min respectively, delivered by breathing simulator (ASL5000, IngMar Medical, Pittsburgh, PA). These I:E ratios were chosen to represent the various patient disease states. An electret filter at the mouthpiece of the nebulizer captured emitted aerosol containing 2.5 mg albuterol sulfate (ALB) in a 3-mL fill (Hi Tech Pharmacal, Amityville NY) at minute intervals until onset of sputter. Total mass (TM) was calculated after assaying for ALB by a validated HPLC-based procedure. In parallel experiments fine droplet fraction < 4.7 µm (FDF<4.7µm) were determined by laser diffractometry.RESULTS: Fine droplet mass (FDM<4.7µm, mean ± SD) values (μg) obtained as the product of TM and FDF<4.7µm were as follows: Misty Fast™: I:E = 1:1, 183 ± 28; I:E = 1:2, 139 ± 11; I:E = 1:3, 102 ± 4; I:E = 1:4, 107 ± 2 NebuTech® HDN®: I=E = 1:1, 206 ± 21; I:E = 1:2, 151 ± 21; I:E = 1:3, 140 ± 9; I:E = 1:4, 112 ± 15 The percentage decreases in mean FDM<4.7µm from the reference condition (I:E =1:1), Δ FDM<4.7µm, were: Misty Fast™: I:E = 1:2, 75.9%; I:E = 1:3, 55.7%; I:E = 1:4, 58.4% NebuTech® HDN®: I:E = 1:2, 73.3%; I:E = 1:3, 68.0%; I:E = 1:4, 54.3%FDM<4.7µm decreased with increasing I:E ratio for both nebulizer groups (1-way RMANOVA, p < 0.001), the decline across the range studied taking I:E = 1:1 as reference (100-Δ FDM<4.7µm) was -42%, Misty Fast™ and -46%, HDN™.

CONCLUSIONS: Significantly less medication was delivered per treatment by either nebulizer with increasing I:E ratio, due to wastage during each exhalation.CLINICAL IMPLICATIONS: This is a likely clinical scenario as disease state worsens or in patients with a compromised respiratory condition, and could result in potential under-dosing. One potential solution to this clinical challenge would be the use of a breath-actuated nebulizer (Schneider, J et al., Abstract 52461, ATS Annual Meeting, San Diego May 2014).DISCLOSURE: Jolyon Mitchell: Employee: Trudell Medical International Dominic Coppolo: Employee: Monagfhan Medical Corporation Mark Nagel: Employee: Trudell Medical International Heather Schneider: Employee: Trudell Medical International Jason Suggett: Employee: Trudell Medical InternationalNo Product/Research Disclosure Information.