title: Aerosolized iloprost customized for the critically ill.
abstract: 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.
authors.affiliation: 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
authors.forename: Keith W
authors.initials: KW
authors.lastname: Harris
authors.forename: Thomas G
authors.initials: TG
authors.lastname: O'Riordan
authors.forename: Gerald C
authors.initials: GC
authors.lastname: Smaldone
mesh_terms: 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
chemical_list: D000336:Aerosols; D014665:Vasodilator Agents; D016285:Iloprost