The use of inhaled prostaglandins in patients with ARDS: a systematic review and meta-analysis.
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.
Department of Anesthesiology, Division of Critical Care, Department of Emergency Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO. Electronic address: fullerb@wusm.wustl.edu.
Brian M
BM
Fuller
Departments of Emergency Medicine and Anesthesiology, Division of Critical Care, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA.
Nicholas M
NM
Mohr
Department of Pharmacy, Aurora BayCare Medical Center, Green Bay, WI.
Lee
L
Skrupky
Bernard Becker Medical Library, Washington University School of Medicine in St. Louis, St. Louis, MO.
Susan
S
Fowler
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO.
Marin H
MH
Kollef
Department of Emergency Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO.
Christopher R
CR
Carpenter
D000280:Administration, Inhalation; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism; D011453:Prostaglandins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000503:physiopathology; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016896:Treatment Outcome
D011453:Prostaglandins; D010100:Oxygen