• Matthieu Jabaudon, Raiko Blondonnet, Bruno Pereira, Rodrigo Cartin-Ceba, Christoph Lichtenstern, Tommaso Mauri, Rogier M Determann, Tomas Drabek, Rolf D Hubmayr, Ognjen Gajic, Florian Uhle, Andrea Coppadoro, Antonio Pesenti, Marcus J Schultz, Marco V Ranieri, Helena Brodska, Ségolène Mrozek, Vincent Sapin, Michael A Matthay, Jean-Michel Constantin, and Carolyn S Calfee.
• Department of Perioperative Medicine, CHU Clermont-Ferrand, 1 Place Lucie Aubrac, 63003, Clermont-Ferrand Cedex 1, France. mjabaudon@chu-clermontferrand.fr.
• Intensive Care Med. 2018 Sep 1; 44 (9): 138813991388-1399.

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).

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