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 microg, 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 microg (n = 5) on the ventilator and 3.77 +/- 0.46 microg (n = 5) during spontaneous ventilation. The mass median aerodynamic diameter and fine-particle fraction were 0.7 microm, 0.99, and 0.7 microm, 0.99, respectively.


CONCLUSIONS
Clinically effective doses of iloprost can be delivered to patients who require high-flow oxygen or mechanical ventilation.
Harris
Keith W
KW
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-8172, USA. kharris@notes.cc.sunysb.edu
O'Riordan
Thomas G
TG
Smaldone
Gerald C
GC
D000280:Administration, Inhalation; D000336:Aerosols; D002851:Chromatography, High Pressure Liquid; D016638:Critical Illness / Q000628:therapy*; D004867:Equipment Design; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D016285:Iloprost / Q000008:administration & dosage* / Q000737:chemistry; D008397:Masks; D009330:Nebulizers and Vaporizers / Q000592:standards*; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000737:chemistry
D000336:Aerosols; D014665:Vasodilator Agents; D016285:Iloprost