Aerosolized Iloprost Customized for the Critically Ill

BACKGROUND: Aerosolized iloprost, an inhaled synthetic analogue of prostacyclin, is an approved therapy for stage III and IV pulmonary hypertension. However, currently iloprost is delivered via a device that requires a clinically stable patient who can use a hand-held nebulizer. We designed separate aerosol delivery systems to nebulize iloprost to critically ill patients during (1) mechanical ventilation and (2) spontaneous breathing that requires a high fraction of inspired oxygen. The goal was to deliver doses similar to the currently approved high-efficiency I-neb nebulizer system.

METHODS: For the intubated patient we used the high-efficiency AeroTech II jet nebulizer and a breath-actuated ventilator circuit, without humidification. For spontaneous breathing, our delivery system consisted of a Pulmanex Hi-Ox disposable oxygen mask and an AeroTech II nebulizer. With a nebulizer charge of 20 μg, the drug presented to the patient (inhaled mass) was captured on a filter and analyzed using radioactivity (technetium-99m). The accuracy of the radiolabel was quantified by directly measuring iloprost with high-performance liquid chromatography and comparing the results. A cascade impactor measured particle distribution.

RESULTS: A line of identity confirmed that the radiolabel accurately represented the drug. The mean ± SD inhaled mass was 6.02 ± 0.87 μg (n = 5) on the ventilator and 3.77 ± 0.46 μg (n = 5) during spontaneous ventilation. The mass median aerodynamic diameter and fine-particle fraction were 0.7 μm, 0.99, and 0.7 μm, 0.99, respectively.

CONCLUSIONS: Clinically effective doses of iloprost can be delivered to patients who require high-flow oxygen or mechanical ventilation.