Study objectives: This study was carried out to determine the efficacy of a
nd dose-response relationships to inhaled aerosolized prostacyclin (LAP), w
hen used as a selective pulmonary vasodilator (SPV) in patients with severe
hypoxemia due to ARDS.
Design: Unblinded, interventional, prospective clinical study.
Setting: A general ICU in a university-affiliated, tertiary referral center
.
Patients: Nine adult patients with severe ARDS (lung injury score, greater
than or equal to 2.5).
Interventions: 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 cir
cuit. Dose increments were 10 ng/kg/min every 30 min.
Measurements and results: Cardiovascular parameters (cardiac index and mean
pulmonary and systemic pressures), indexes of oxygenation (Pao(2)/fraction
of inspired oxygen [FIO2] ratio and alveolar-arterial oxygen partial press
ure difference [P(A-a)O-2] and shunt fraction were measured or calculated a
t each dose interval, as were platelet aggregation and systemic levels of p
rostacyclin metabolite (6-keto prostaglandin F1 alpha). A generalized linea
r regression model was used to determine a dose effect of MP on these param
eters, The Wilcoxon rank sum test for related measures was used to compare
the effects of various doses of LAP, IAP acted as an SPV, with a statistica
lly significant dose-related improvement in Pao(2)/FIO2 ratio (p = 0.003) a
nd P(A-a)O-2 (p = 0.01). Systemic prostacyclin metabolite levels increased
significantly in response to delivered LAP (p = 0.001). There was no signif
icant dose effect on systemic or pulmonary arterial pressures, or on platel
et function, as determined by platelet aggregation in response to challenge
with adenosine diphosphate.
Conclusions: LAP is an efficacious SPV, with marked dose-related improvemen
t in oxygenation and with no demonstrable effect on systemic arterial press
ures over die dose range 0 to 50 ng/kg/min. Despite significant systemic le
vels of prostacyclin metabolite, there was no demonstrable platelet functio
n defect.