Severity of Hypoxemia and Other Factors That Influence the Response to Aerosolized Prostacyclin in ARDS.

BACKGROUND: ARDS is characterized by decreased functional residual capacity (FRC), heterogeneous lung injury, and severe hypoxemia. Tidal ventilation is preferentially distributed to ventilated alveoli. Aerosolized prostaglandin I2 exploits this pathophysiology by inducing local vasodilation, thereby increasing ventilation-perfusion matching and reducing hypoxemia. Therefore, aerosolized prostaglandin I2 efficacy may depend upon FRC. Both PaO2 /FIO2 and compliance of the respiratory system (CRS ) are indirect signifiers of FRC and thus may partly determine the response to aerosolized prostaglandin I2 .

METHODS: We reviewed the records of 208 ARDS subjects who received aerosolized prostaglandin I2 and had arterial blood gases done before and after the initiation of therapy, without other ventilator manipulations. Subjects were grouped according to baseline PaO2 /FIO2 (lowest: < 60, intermediate: 60-90, highest: > 90 mm Hg) and CRS (< 20, 20-29, 30-39, and ≥ 40 mL/cm H2 O) and by other factors, such as sepsis. Comparisons were analyzed by paired t tests, or Kruskal-Wallis and Dunn post-tests. Multivariate logistic regression modeling was done to determine which of 18 clinically relevant factors were most predictive for responding to aerosolized prostaglandin I2 . α was set at .05.

RESULTS: Mean PaO2 /FIO2 increased by 33 mm Hg (42%) upon initiation of prostaglandin I2 , with a responder rate of 62%. PaO2 /FIO2 increased significantly in all oxygenation groups. The highest baseline PaO2 /FIO2 group had the greatest improvement and responder rate (51 ± 63 mm Hg, and 82%). In addition, those with sepsis had a smaller improvement in PaO2 /FIO2 compared with those without sepsis (18 ± 35 vs 40 ± 55 mm Hg, P = .002). Both PaO2 /FIO2 and responder rate increased as CRS improved, but between-group improvements were not as consistent. In the final model, the only factors that predicted a positive response to aerosolized prostaglandin I2 were baseline PaO2 /FIO2 (odds ratio 1.10 [1.004-1.205], P = .042) and CRS (odds ratio 1.04 [1.01-1.08], P = .02).

CONCLUSIONS: Aerosolized prostaglandin I2 improves oxygenation in approximately 60% of ARDS cases. A favorable response was most strongly associated with baseline PaO2 /FIO2 and CRS .