Data_Sheet_1_ARDS Patients Exhibiting a “Hyperinflammatory Anasarca” Phenotype Could Benefit From a Conservative Fluid Management Strategy.pdf

Object: The fluid management strategy in ARDS is not very clear. A secondary analysis of RCT data was conducted to identify patients with ARDS benefitting from a conservative strategy of fluid management.
Methods: The data of this study were downloaded from the ARDS network series of randomized controlled trials (Conservative Strategy vs. Liberal Strategy in 2006). Based on the clinical feature of patients, within the first 24 h after admission, clustering was performed using the k-means clustering algorithm to identify the phenotypes of ARDS. Survival was analyzed using the Kaplan-Meier survival analysis to assess the effect of the two fluid management strategies on the 90-day cumulative mortality. Categorical/dichotomic variables were analyzed by the chi-square test. Continuous variables were expressed as the mean and standard deviation and evaluated through a one-way ANOVA. A P-value < 0.05 was defined as the statistically significant cut-off value.
Results: A total of 1,000 ARDS patients were enrolled in this unsupervised clustering research study, of which 503 patients were treated with a conservative fluid-management strategy, and 497 patients were treated with a liberal fluid-management strategy. The first 7-day cumulative fluid balance in patients with the conservative strategy and liberal strategy were −136 ± 491 ml and 6,992 ± 502 ml, respectively (P < 0.001). Four phenotypes were found, and the conservative fluid-management strategy significantly improved the 90-day cumulative mortality compared with the liberal fluid-management strategy (HR = 0.532, P = 0.024) in patients classified as “hyperinflammatory anasarca” phenotype (phenotype II). The characteristics of this phenotype exhibited a higher WBC count (20487.51 ± 7223.86/mm3) with a higher incidence of anasarca (8.3%) and incidence of shock (26.6%) at baseline. The furthermore analysis found that the conservative fluid management strategy was superior to the liberal fluid management strategy in avoiding superinfection (10.10 vs. 14.40%, P = 0.037) and returned to assisted breathing (4.60 vs. 16.20%, P = 0.030) in patients classified as “hyperinflammatory anasarca” phenotype. In addition, patients with other phenotypes given the different fluid management strategies did not show significant differences in clinical outcomes.
Conclusion: Patients exhibiting a “hyperinflammatory anasarca” phenotype could benefit from a conservative fluid management strategy.

研究背景与目的：急性呼吸窘迫综合征（Acute Respiratory Distress Syndrome, ARDS）的液体管理策略目前尚未明确。本研究通过对随机对照试验（Randomized Controlled Trial, RCT）数据进行二次分析，旨在筛选出可从保守液体管理策略中获益的ARDS患者。
研究方法：本研究数据来源于2006年ARDS网络系列随机对照试验（保守策略vs. 自由液体策略）。基于患者临床特征，于入院后24小时内采用k-means聚类算法对患者进行聚类分析，以明确ARDS的临床表型。采用Kaplan-Meier生存分析评估两种液体管理策略对患者90天累积死亡率的影响。分类变量/二分类变量采用卡方检验进行分析；连续性变量以均数±标准差表示，采用单因素方差分析（One-way Analysis of Variance, ANOVA）进行组间比较。以P值<0.05作为统计学显著性界值。
研究结果：本无监督聚类研究共纳入1000例ARDS患者，其中503例接受保守液体管理策略，497例接受自由液体管理策略。保守策略组与自由策略组患者的前7天累积液体平衡分别为-136±491 ml与6992±502 ml（P<0.001）。共筛选出4种ARDS临床表型，其中在被归类为"高炎症性全身性水肿"表型（表型II）的患者中，与自由液体管理策略相比，保守液体管理策略可显著改善其90天累积死亡率（风险比HR=0.532，P=0.024）。该表型患者的基线特征表现为白细胞计数（White Blood Cell, WBC）更高（20487.51±7223.86/mm³），全身性水肿发生率（8.3%）与休克发生率（26.6%）均更高。进一步分析显示，在"高炎症性全身性水肿"表型患者中，保守液体管理策略在降低继发感染发生率（10.10% vs. 14.40%，P=0.037）及恢复辅助通气比例（4.60% vs. 16.20%，P=0.030）方面均优于自由液体管理策略。此外，其余表型患者在接受不同液体管理策略后，临床结局未表现出显著差异。
研究结论：表现为"高炎症性全身性水肿"表型的ARDS患者可从保守液体管理策略中获益。