Iloprost is a selective pulmonary vasodilator approved for inhalation by the Food and Drug Administration. Iloprost has been increasingly used in the management of critically ill neonates with hypoxic lung disease. This in vitro study was designed to test the hypothesis that aerosol drug delivery could be effectively administered to infants with both conventional ventilation and high-frequency oscillatory ventilation (HFOV). A neonatal test lung model configured with newborn lung mechanics was ventilated with a conventional ventilator and an HFOV with standard settings. A vibrating-mesh nebulizer was placed (1) proximal to the patient airway in the inspiratory limb between the humidifier probe and patient wye (conventional) as well as between the vent circuit and the endotracheal tube (ETT) for HFOV and (2) between the ventilator and humidifier (distal). Iloprost was nebulized in three separate runs using three new nebulizers in each of the circuit locations. A collecting filter was placed at the distal end of the ETT for each trial. Iloprost was quantified using highperformance liquid chromatography. The percentage of nominal dose delivered was greater with the nebulizer placed proximal to the airway for conventional ventilation (10.74% ± 2%) and HFOV (29% ± 2%) than with it placed in the distal position (2.96% ± 0.2% vs. 0.96% ± 0.8%, respectively; P < 0.05). Drug delivery in proximal position was nearly threefold greater during HFOV than during conventional ventilation. In conclusion, iloprost drug delivery was best achieved when the nebulizer was placed proximal to the patient airway during neonatal mechanical ventilation. Drug delivery appears to be more efficient during HFOV than during conventional ventilation.Keywords: neonatal ventilation, pediatric aerosol delivery, high-frequency ventilation, inhaled pulmonary vasodilation, infant hypoxic lung disease. Iloprost (Ventavis; Actelion Pharmaceuticals US) is a stable prostacyclin analog used in the treatment of pulmonary hypertension. It is pharmacologically similar to epoprostenol, with vasodilatory, vascular remodeling, and platelet inhibitory properties, but it is a more stable compound, with an elimination half-life of 20-30 minutes. 1The longer half-life than that of other prostacyclin formulations allows the drug to be delivered with less frequency. Iloprost was the first prostacyclin designed specifically for aerosolization and approved for inhalation in ambulatory adults with primary pulmonary hypertension using the I-neb AAD system (Philips Respironics, Netherlands), a vibrating-mesh smart nebulizer. The design of the I-neb precludes its use in a closed ventilator circuit. While researchers have described a strategy for aerosol delivery during adult mechanical ventilation, none have applied such strategies for use with iloprost in infants. 2 Iloprost inhalation has been reported to be of some benefit in the management of critically ill neonates and infants with hypoxic lung disease and pulmonary hypertension.3-17 Many neonates with sever...

BACKGROUND: Noninvasive ventilation (NIV) is usually applied using bi-level positive airway pressure devices, and many of these devices use a single-limb patient circuit with an integrated leak port to purge the circuit of exhaled carbon dioxide. Sometimes bronchodilator therapy is indicated in pediatric patients, but there have been no studies of the optimal nebulizer position, with respect to leak, during pediatric NIV. We hypothesized that there would be no differences in albuterol delivery with a vibrating-mesh nebulizer between 3 different positions/exhalation leak valve combinations in the patient circuit during simulated pediatric NIV. METHODS: A simulated upper airway model was attached to a lung model that simulated spontaneous breathing. A noninvasive ventilator equipped with heated wire circuit and heated humidifier was attached to the lung model via a pediatric oronasal mask. Albuterol (5 mg) was delivered with a vibrating-mesh nebulizer, at 3 different circuit position/leak condition combinations: prior to the humidifier and leak valve; between the humidifier and leak valve; and integrated within the mask and after the leak. Albuterol was captured on a filter and quantified with chromatography. RESULTS: Greater albuterol mass was delivered to the filter with the nebulizer integrated into the mask than at any other testing condition (P < .001). In the conditions where the nebulizer was placed prior to the exhalation leak valve, greater drug delivery was observed when the nebulizer was placed proximal to the mask (position 2) than when placed prior to the humidifier (position 3, P ‫؍‬ .002). CONCLUSIONS: Albuterol delivery during simulated pediatric NIV was affected by the position of the nebulizer in relation to the expiratory leak valve and the nebulizer's distance from the filter. A vibrating-mesh nebulizer placed intra-mask may provide a better alternative for medication delivery than those previously used during pediatric NIV.

Using the MIE via tracheostomy tube in an infant lung model, we found that an insufflation time of >1 sec is required for equilibration of insufflation pressure and alveolar pressure. Longer exsufflation time does not significantly alter MEF. Higher insufflation and exsufflation pressures both increased MEF, but greater exsufflation pressure had more substantial impact.

Objective 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. Design 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. Setting Academic children’s hospital aerosol research laboratory. Measurements and Main Results 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. Conclusion 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.