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

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 P_aO /F_IO and compliance of the respiratory system (C_RS) are indirect signifiers of FRC and thus may partly determine the response to aerosolized prostaglandin I₂.

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 P_aO /F_IO (lowest: < 60, intermediate: 60-90, highest: > 90 mm Hg) and C_RS (< 20, 20-29, 30-39, and ≥ 40 mL/cm H₂O) 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.

Mean P_aO /F_IO increased by 33 mm Hg (42%) upon initiation of prostaglandin I₂, with a responder rate of 62%. P_aO /F_IO increased significantly in all oxygenation groups. The highest baseline P_aO /F_IO group had the greatest improvement and responder rate (51 ± 63 mm Hg, and 82%). In addition, those with sepsis had a smaller improvement in P_aO /F_IO compared with those without sepsis (18 ± 35 vs 40 ± 55 mm Hg, P = .002). Both P_aO /F_IO and responder rate increased as C_RS 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 P_aO /F_IO (odds ratio 1.10 [1.004-1.205], P = .042) and C_RS (odds ratio 1.04 [1.01-1.08], P = .02).

Aerosolized prostaglandin I₂ improves oxygenation in approximately 60% of ARDS cases. A favorable response was most strongly associated with baseline P_aO /F_IO and C_RS.