Department of Perioperative Medicine, CHU Clermont-Ferrand, 1 Place Lucie Aubrac, 63003, Clermont-Ferrand Cedex 1, France.
CNRS, UMR 6293, INSERM U1103, GReD, Université Clermont Auvergne, Clermont-Ferrand, France.
Intensive Care Med. 2018 Sep;44(9):1388-1399. doi: 10.1007/s00134-018-5327-1. Epub 2018 Jul 26.
The 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.
We 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.
Higher 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 V.
Higher 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).
晚期糖基化终产物的可溶性受体（sRAGE）是肺上皮损伤和肺泡液清除（AFC）的标志物，其对急性呼吸窘迫综合征（ARDS）的预后和肺损伤严重程度评估具有良好的应用价值。由于 AFC 在大多数 ARDS 患者中受损，且与更高的死亡率相关，我们假设基线血浆 sRAGE 可预测死亡率，且与呼吸机所致肺损伤的两个关键介质无关。
我们对 2016 年 3 月前发表的 8 项前瞻性随机对照和观察性研究的 746 名患者的个体数据进行了荟萃分析，这些研究均检测了 ARDS 患者的血浆 sRAGE。主要终点为 90 天死亡率。我们采用多变量和中介分析，检测了基线血浆 sRAGE 与死亡率之间的关联，且这种关联与驱动压和潮气量无关。
较高的基线血浆 sRAGE [每个对数增加单位的比值比（OR）为 1.18；95%置信区间（CI）为 1.01-1.38；P=0.04]、驱动压（每个增加 1 个点的 OR 为 1.04；95%CI 为 1.02-1.07；P=0.002）和潮气量（每个对数增加单位的 OR 为 1.98；95%CI 为 1.07-3.64；P=0.03）在多变量分析中与较高的 90 天死亡率独立相关。基线血浆 sRAGE 部分介导了较高的ΔP 对死亡率的影响，但不能介导较高的 V 对死亡率的影响。
在 ARDS 患者中，较高的基线血浆 sRAGE 与较高的 90 天死亡率相关，且与驱动压和潮气量无关，因此强化了肺泡上皮损伤作为 ARDS 中一个重要预后因素的可能性。注册：PROSPERO（ID：CRD42018100241）。
