Dose-response to inhaled aerosolized prostacyclin for hypoxemia due to ARDS.
OBJECTIVE
This study was carried out to determine the efficacy of and dose-response relationships to inhaled aerosolized prostacyclin (IAP), when used as a selective pulmonary vasodilator (SPV) in patients with severe hypoxemia due to ARDS.


METHODS
Unblinded, interventional, prospective clinical study.


METHODS
A general ICU in a university-affiliated, tertiary referral center.


METHODS
Nine adult patients with severe ARDS (lung injury score, > or = 2.5).


METHODS
All patients received IAP over the dose range 0 to 50 ng/kg/min. The IAP was delivered via a jet nebulizer placed in the ventilator circuit. Dose increments were 10 ng/kg/min every 30 min.


RESULTS
Cardiovascular parameters (cardiac index and mean pulmonary and systemic pressures), indexes of oxygenation (PaO(2)/fraction of inspired oxygen [FIO(2)] ratio and alveolar-arterial oxygen partial pressure difference [P(A-a)O(2)]) and shunt fraction were measured or calculated at each dose interval, as were platelet aggregation and systemic levels of prostacyclin metabolite (6-keto prostaglandin F1(alpha)). A generalized linear regression model was used to determine a dose effect of IAP on these parameters. The Wilcoxon rank sum test for related measures was used to compare the effects of various doses of IAP. IAP acted as an SPV, with a statistically significant dose-related improvement in PaO(2)/FIO(2) ratio (p = 0.003) and P(A-a)O(2) (p = 0.01). Systemic prostacyclin metabolite levels increased significantly in response to delivered IAP (p = 0.001). There was no significant dose effect on systemic or pulmonary arterial pressures, or on platelet function, as determined by platelet aggregation in response to challenge with adenosine diphosphate.


CONCLUSIONS
IAP is an efficacious SPV, with marked dose-related improvement in oxygenation and with no demonstrable effect on systemic arterial pressures over the dose range 0 to 50 ng/kg/min. Despite significant systemic levels of prostacyclin metabolite, there was no demonstrable platelet function defect.
van Heerden
P V
PV
Department of Pharmacology, University of Western Australia, Nedlands. vernon@iinet.net.au
Barden
A
A
Michalopoulos
N
N
Bulsara
M K
MK
Roberts
B L
BL
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D011464:Epoprostenol / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
D000336:Aerosols; D014665:Vasodilator Agents; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D010100:Oxygen