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Original Research: Critical Care |

The Use of Inhaled Prostaglandins in Patients With ARDSInhaled Prostaglandins for ARDS: A Systematic Review and Meta-analysis

Brian M. Fuller, MD, MSCI; Nicholas M. Mohr, MD; Lee Skrupky, PharmD, BCPS; Susan Fowler, MLIS; Marin H. Kollef, MD, FCCP; Christopher R. Carpenter, MD
Author and Funding Information

From the Department of Anesthesiology (Dr Fuller), Division of Critical Care, Department of Emergency Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO; Departments of Emergency Medicine and Anesthesiology (Dr Mohr), Division of Critical Care, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA; Department of Pharmacy (Dr Skrupky), Aurora BayCare Medical Center, Green Bay, WI; and Bernard Becker Medical Library (Ms Fowler), the Department of Medicine, Division of Pulmonary and Critical Care Medicine (Dr Kollef), and the Department of Emergency Medicine (Dr Carpenter), Washington University School of Medicine in St. Louis, St. Louis, MO.

CORRESPONDENCE TO: Brian M. Fuller, MD, MSCI, Department of Anesthesiology, Division of Critical Care, Department of Emergency Medicine, Washington University in St. Louis School of Medicine, 660 South Euclid Ave, St. Louis, MO 63110; e-mail: fullerb@wusm.wustl.edu


FUNDING/SUPPORT: Dr Fuller was supported by the Emergency Medicine Grant-in-Aid from the Department of Emergency Medicine, Washington University School of Medicine in St. Louis and the KL2 Career Development Award. Dr Mohr was supported by the Emergency Medicine Foundation Research Fellowship. Dr Kollef was supported by the Barnes-Jewish Hospital Foundation. This research was supported by the Washington University Emergency Care Research Core, which receives funding from the Barnes-Jewish Hospital Foundation, as well as the Washington University Institute of Clinical and Translational Sciences [Grants UL1 TR000448 and KL2 TR000450] from the National Institutes of Health National Center for Advancing Translational Sciences.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(6):1510-1522. doi:10.1378/chest.14-3161
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OBJECTIVE:  This study aimed to determine whether inhaled prostaglandins are associated with improvement in pulmonary physiology or mortality in patients with ARDS and assess adverse effects.

METHODS:  The following data sources were used: PubMed, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, reference lists, conference proceedings, and ClinicalTrials.gov. Studies selected included randomized controlled trials and nonrandomized studies. For data extraction, two reviewers independently screened titles and abstracts for eligibility. With regard to data synthesis, 25 studies (two RCTs) published over 21 years (1993-2014) were included. The PROSPERO registration number was CRD42014013180.

RESULTS:  One randomized controlled trial showed no difference in the change in mean Pao2 to Fio2 ratio when comparing inhaled alprostadil to placebo: 141.2 (95% CI, 120.8-161.5) to 161.5 (95% CI, 134.6-188.3) vs 163.4 (95% CI, 140.8-186.0) to 186.8 (95% CI, 162.9-210.7), P = .21. Meta-analysis of the remaining studies demonstrated that inhaled prostaglandins were associated with improvement in Pao2 to Fio2 ratio (16 studies; 39.0% higher; 95% CI, 26.7%-51.3%), and Pao2 (eight studies; 21.4% higher; 95% CI, 12.2%-30.6%), and a decrease in pulmonary artery pressure (−4.8 mm Hg; 95% CI, −6.8 mm Hg to −2.8 mm Hg). Risk of bias and heterogeneity were high. Meta-regression found no association with publication year (P = .862), baseline oxygenation (P = .106), and ARDS etiology (P = .816) with the treatment effect. Hypotension occurred in 17.4% of patients in observational studies.

CONCLUSIONS:  In ARDS, inhaled prostaglandins improve oxygenation and decrease pulmonary artery pressures and may be associated with harm. Data are limited both in terms of methodologic quality and demonstration of clinical benefit. The use of inhaled prostaglandins in ARDS needs further study.

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