Inhaled Prostacyclins for Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis

OBJECTIVES: Studies evaluating inhaled prostacyclins for the management of acute respiratory distress syndrome (ARDS) have produced inconsistent results regarding their effect on oxygenation. The purpose of this systematic review and meta-analysis was to evaluate the change in the Pao(2)/Fio(2) ratio after administration of an inhaled prostacyclin in patients with ARDS. DATA SOURCES: We searched Ovid Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane, Scopus, and Web of Science. STUDY SELECTION: We included abstracts and trials evaluating administration of inhaled prostacyclins in patients with ARDS. DATA EXTRACTION: Change in the Pao(2)/Fio(2) ratio, Pao(2), and mean pulmonary artery pressure (mPAP) were extracted from included studies. Evidence certainty and risk of bias were evaluated using Grading of Recommendations Assessment, Development, and Evaluation and the Cochrane Risk of Bias tool. DATA SYNTHESIS: We included 23 studies (1,658 patients) from 6,339 abstracts identified by our search strategy. The use of inhaled prostacyclins improved oxygenation by increasing the Pao(2)/Fio(2) ratio from baseline (mean difference [MD], 40.35; 95% CI, 26.14-54.56; p < 0.00001; I-2 = 95%; very low quality evidence). Of the eight studies to evaluate change in Pao(2), inhaled prostacyclins also increased Pao(2) from baseline (MD, 12.68; 95% CI, 2.89-22.48 mm Hg; p = 0.01; I-2 = 96%; very low quality evidence). Only three studies evaluated change in mPAP, but inhaled prostacyclins were found to improve mPAP from baseline (MD, -3.67; 95% CI, -5.04 to -2.31 mm Hg; p < 0.00001; I-2 = 68%; very low quality evidence). CONCLUSIONS: In patients with ARDS, use of inhaled prostacyclins improves oxygenation and reduces pulmonary artery pressures. Overall data are limited and there was high risk of bias and heterogeneity among included studies. Future studies evaluating inhaled prostacyclins for ARDS should evaluate their role in ARDS subphenotypes, including cardiopulmonary ARDS.