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 P_aO2/F_IO2 and compliance of the respiratory system (C_RS) 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 P_aO2/F_IO2 (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.

RESULTS: Mean P_aO2/F_IO2 increased by 33 mm Hg (42%) upon initiation of prostaglandin I₂, with a responder rate of 62%. P_aO2/F_IO2 increased significantly in all oxygenation groups. The highest baseline P_aO2/F_IO2 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_aO2/F_IO2 compared with those without sepsis (18 ± 35 vs 40 ± 55 mm Hg, P = .002). Both P_aO2/F_IO2 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_aO2/F_IO2 (odds ratio 1.10 [1.004–1.205], P = .042) and C_RS (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 P_aO2/F_IO2 and C_RS.