Nebulized prostacyclin (PGI(2)) in acute respiratory distress syndrome: Impact of primary (pulmonary injury) and secondary (extrapulmonary injury) disease on gas exchange response

Objectives: To examine the hypothesis that the response to inhaled prostacy clin (PGI(2)) on oxygenation and pulmonary hemodynamics may be related to d ifferent morphologic features that are supposed to be present in acute resp iratory distress syndrome (ARDS) originating from pulmonary (primary ARDS [ ARDS(PR)]) and from extrapulmonary disease (secondary ARDS [ARD(SEC)]). Design: Prospective, nonrandomized interventional study. Setting: Multidisciplinary intensive care unit, secondary care center. Patients: Fifteen consecutive, mechanically ventilated patients with ARDS a nd severe hypoxemia, defined as PaO2/FIO2 of <150 torr at the time of admis sion. Interventions: After an initial stable period of at least 60 mins, patients received nebulized PGI(2) in 15-min steps; the drug was titrated to find t he dose with the best improvement of PaO2, starting with 2 ng/kg/min up to an allowed maximum dose of 40 ng/kg/min. Measurements and Main Results: Blood gas, gas exchange, and hemodynamic mea surements were performed at the following time points: a) baseline; b) duri ng the optimal or maximum dose of PGI(2); and c) 1 hr after withdrawal of t he drug. Patients underwent a computed tomographic (CT) scan using a basal CT section to compute the mean CT numbers and the density histogram. Patien ts were considered responders to PGI(2) if an increase in PaO2 of <greater than or equal to>7.5 torr or an increase in PaO2/FIO2 ratio of greater than or equal to 10% occurred. For the group as a whole, mean pulmonary artery pressure decreased from 32 +/- 1 to 29 +/- 1 mm Hg during PGI(2) nebulizati on, whereas pulmonary vascular resistance decreased 1 hr after withdrawal o f nebulization from 177 +/- 18 to 153 +/- 16 dyne.sec/cm(5); oxygenation di d not change significantly. Eight patients responded to PGI(2) nebulization on oxygenation (all were in the ARDSSEC subgroup), whereas seven did not t all but one were in the ARDSPR subgroup). Among the physiologic variables e xamined to assess any difference between the two ARDS groups at time of PGI (2) nebulization, there was a significant difference concerning the mean CT density number, which was -445 +/- 22 Hounsfield Units in the ARDS(SEC) gr oup and -258 +/- 16 Hounsfield Units in the ARDS(PR) group. In patients pre senting with an ARDS(PR), PGI(2) induced a reduction in PaO2/FIO2 and a red uction in PaO2 from 87 +/- 2 to 79 +/- 2 torr, whereas in patients with an ARDS(SEC) there was an increase in PaO2/FIO2 and in PaO2 from 76 +/- 4 to 8 4 +/- 4 torr with a decrease in mean pulmonary artery pressure. Conclusions: Based on the data from this study, the clinical recognition of the two types of the syndrome together with the CT number frequency distri bution analysis may be associated with a prediction of the PGI(2) nebulizat ion response on oxygenation.