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PurposeThe soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury.MethodsWe conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume.ResultsHigher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01-1.38; P = 0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02-1.07; P = 0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07-3.64; P = 0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher VT.ConclusionsHigher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241).

Original publication

DOI

10.1007/s00134-018-5327-1

Type

Journal

Intensive care medicine

Publication Date

09/2018

Volume

44

Pages

1388 - 1399

Addresses

Department of Perioperative Medicine, CHU Clermont-Ferrand, 1 Place Lucie Aubrac, 63003, Clermont-Ferrand Cedex 1, France. mjabaudon@chu-clermontferrand.fr.

Keywords

Humans, Respiratory Distress Syndrome, Adult, Tidal Volume, Work of Breathing, APACHE, Risk Factors, Middle Aged, Female, Male, Randomized Controlled Trials as Topic, Biomarkers, Observational Studies as Topic, Receptor for Advanced Glycation End Products