Description and evaluation of a delivery system for aerosolized prostacyclin.
BACKGROUND
Inhaled vasodilators such as nitric oxide and aerosolized prostacyclin (PGI(2)) are used to treat severe hypoxemia in acute respiratory distress syndrome. Preferential distribution of nitric oxide and PGI(2) 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 PGI(2) delivery technique that allows the aerosolized drug dose to be easily calculated, set, and adjusted.


METHODS
A 50 mL solution of PGI(2) (3.0x10(4) 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 PGI(2) 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 PGI(2) 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 PGI(2) therapy (mean dose 28 +/- 17 ng/kg/min, range 10-50 ng/kg/min) significantly increased the ratio of P(aO)(2) to fraction of inspired oxygen (P(aO)(2)/F(IO)(2)) (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(IO)(2), before and after aerosolized PGI(2) (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 micro m. Emitted dose was 67 +/- 13% (range 57-81%) of the calculated dose.


CONCLUSIONS
Our system is effective in delivering aerosolized PGI(2) 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.
Siobal
Mark S
MS
Respiratory Care Services, San Francisco General Hospital, NH:GA-2, 1001 Potrero Avenue, San Francisco CA 94110, USA. msiobal@sfghsom.ucsf.edu
Kallet
Richard H
RH
Pittet
Jean-François
JF
Warnecke
Edna L
EL
Kraemer
Roger W
RW
Venkayya
Rajeev V
RV
Tang
Julin F
JF
D000280:Administration, Inhalation; D000328:Adult; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D011464:Epoprostenol / Q000008:administration & dosage* / Q000627:therapeutic use*; D004867:Equipment Design; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D009330:Nebulizers and Vaporizers; D017063:Outcome Assessment, Health Care; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000188:drug therapy*; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D012720:Severity of Illness Index
D010975:Platelet Aggregation Inhibitors; D011464:Epoprostenol