Inhaled Treprostinil Drug Delivery During Mechanical Ventilation and Spontaneous Breathing Using Two Different Nebulizers :

Abstract

<div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d9229381e166">Objective</h5> <p id="P1">To determine the feasibility of delivering inhaled treprostinil during mechanical ventilation and spontaneous unassisted ventilation using the Tyvaso Inhalation System (TIS), and t Vibrating Mesh Nebulizer (VMN). We sought to compare differences in fine particle fraction (FPF), and absolute inhaled treprostinil mass delivered to neonatal, pediatric, and adult models affixed with a facemask, conventional, and high frequency ventilation between TIS and with different nebulizer locations between TIS and VMN. </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <h5 class="section-title" id="d9229381e171">Design</h5> <p id="P2">FPF was first determined via cascade impaction with both the TIS and VMN. Next, a test lung, configured with neonatal, pediatric, and adult mechanics and a filter to capture medication was attached to a realistic face model during spontaneous breathing or an ETT during conventional ventilation and HFOV. Inhaled treprostinil was then nebulized with both the TIS, and VMN, and the filter was analyzed via HPLC. Testing was done in triplicate. Independent two-sample t-tests were used to compare mean FPF, and inhaled mass between devices. ANOVA with Tukey post-hoc tests were used to compare within device differences. </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <h5 class="section-title" id="d9229381e176">Setting</h5> <p id="P3">Academic children’s hospital aerosol research laboratory.</p> </div><div class="section"> <a class="named-anchor" id="S4"> <!-- named anchor --> </a> <h5 class="section-title" id="d9229381e181">Measurements and Main Results</h5> <p id="P4">FPF was not different between the TIS and VMN (0.78 ± 0.04 vs 0.77 ± 0.08, respectively, P = 0.79). The VMN delivered the same or greater inhaled treprostinil than the TIS in every simulated model and condition. When using the VMN, delivery was highest when using HFOV in the neonatal and pediatric models, and with the nebulizer in the distal position in the adult model. </p> </div><div class="section"> <a class="named-anchor" id="S5"> <!-- named anchor --> </a> <h5 class="section-title" id="d9229381e186">Conclusion</h5> <p id="P5">The VMN is a suitable alternative to the TIS for inhaled treprostinil delivery. FPF is similar between devices, and VMN delivery meets or exceeds delivery of the TIS. Delivery for infants and children during HFOV with the VMN may result in higher than expected dosages. </p> </div>