Description and Evaluation of a Delivery System for Aerosolized Prostacyclin

INTRODUCTION: Inhaled vasodilators such as nitric oxide and aerosolized prostacyclin (PGI₂) are used to treat severe hypoxemia in acute respiratory distress syndrome. Preferential distribution of nitric oxide and PGI₂ to ventilated areas of the lung causes selective pulmonary vasodilation, improved ventilation/perfusion matching, and decreased hypoxemia. Because of the technical limitations of previously described methods, we developed a PGI₂ delivery technique that allows the aerosolized drug dose to be easily calculated, set, and adjusted.

METHODS: A 50 mL solution of PGI₂ (3.0×10⁴ ng/mL) and a 500 mL normal saline solution were infused by a dual-channel volumetric infusion pump into a MiniHEART jet nebulizer that has a manufacturer-specified output of 8 mL/h at a set flow of 2 L/min. By adjusting the pump infusion rate to achieve a total output of 8 mL/h, the PGI₂ concentration was altered to deliver a calculated aerosolized dose of 10-50 ng/kg/min. The effectiveness of the delivery system was retrospectively evaluated by way of the responses of 11 severely hypoxemic acute respiratory distress syndrome patients who received PGI₂ via the system we describe. The MiniHEART nebulizer output, particle size, and dose delivery were evaluated in a laboratory bench study, using a set flow of 2 L/min.

RESULTS: Aerosolized PGI₂ therapy (mean dose 28 ± 17 ng/kg/min, range 10–50 ng/kg/min) significantly increased the ratio of P_aO2 to fraction of inspired oxygen (P_aO2/F_IO2) (60 ± 11 mm Hg vs 80 ± 17 mm Hg, p = 0.003) and arterial oxygen saturation measured via pulse oximetry (86 ± 8% vs 94 ± 3%, p = 0.005) (differences evaluated with the Wilcoxon signed rank test). There was no difference in positive end-expiratory pressure, mean airway pressure, or F_IO2, before and after aerosolized PGI₂ (p > 0.05). Nebulizer output was 6.8 ± 0.9 mL/h, range 6.0–7.8 mL/h. The inhaled aerosol particles had a mass median diameter of 3.1 μm. Emitted dose was 67 ± 13% (range 57–81%) of the calculated dose.

CONCLUSION: Our system is effective in delivering aerosolized PGI₂ to the alveolar-capillary interface, as indicated by significant oxygenation improvements soon after therapy commenced. The performance of the MiniHEART nebulizer varies from the manufacturer's specifications, which may alter the delivered dose.