Lu Zongqing, Fang Pu, Xia Dunling, Li Mengdie, Li Seruo, Wang Yu, Fu Lin, Sun Gengyun, You Qinghai
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Front Pharmacol. 2023 Mar 1;14:1125611. doi: 10.3389/fphar.2023.1125611. eCollection 2023.
This present study aimed to infer the association between aspirin exposure prior to ICU admission and the clinical outcomes of patients with Sepsis-associated acute respiratory failure (S-ARF). We obtained data from the Medical Information Mart for Intensive Care IV 2.0. Patients were divided into pre-ICU aspirin exposure group and Non-aspirin exposure group based on whether they took aspirin before ICU admission. The primary outcome is 28-day mortality. Augmented inverse propensity weighted was used to explore the average treatment effect (ATE) of the pre-ICU aspirin exposure. A generalized additive mixed model was used to analyze the longitudinal data of neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), oxygenation index (P/F), dynamic lung compliance (Cdyn), mechanical power (MP), and mechanical power normalized to predicted body weight (WMP) in the two groups. A multiple mediation model was constructed to explore the possible mediators between pre-ICU aspirin exposure and outcomes of patients with S-ARF. A total of 2090 S-ARF patients were included in this study. Pre-ICU aspirin exposure decreased 28-day mortality (ATE, -0.1945, 95% confidence interval [CI], -0.2786 to -0.1103, < 0.001), 60-day mortality (ATE, -0.1781, 95% Cl, -0.2647 to -0.0915, < 0.001), and hospital mortality (ATE, -0.1502, 95%CI, -0.2340 to -0.0664, < 0.001). In subgroup analysis, the ATE for 28-day mortality, 60-day mortality, and hospital mortality were not statistically significant in the coronary care unit group, high-dose group (over 100 mg/d), and no invasive mechanical ventilation (IMV) group. After excluding these non-beneficiaries, Cdyn and P/F ratio of the pre-ICU aspirin exposure group increased by 0.31mL/cmHO (SE, 0.21, = 0.016), and 0.43 mmHg (SE, 0.24, = 0.041) every hour compared to that of non-aspirin exposure group after initialing IMV. The time-weighted average of NLR, Cdyn, WMP played a mediating role of 8.6%, 24.7%, and 13% of the total effects of pre-ICU aspirin exposure and 28-day mortality, respectively. Pre-ICU aspirin exposure was associated with decreased 28-day mortality, 60-day mortality, and hospital mortality in S-ARF patients except those admitted to CCU, and those took a high-dose aspirin or did not receive IMV. The protective effect of aspirin may be mediated by a low dynamic level of NLR and a high dynamic level of Cdyn and WMP. The findings should be interpreted cautiously, given the sample size and potential for residual confounding.
本研究旨在推断重症监护病房(ICU)入院前阿司匹林暴露与脓毒症相关性急性呼吸衰竭(S-ARF)患者临床结局之间的关联。我们从重症监护医学信息数据库IV 2.0获取数据。根据患者在ICU入院前是否服用阿司匹林,将其分为ICU入院前阿司匹林暴露组和非阿司匹林暴露组。主要结局为28天死亡率。采用增强逆概率加权法探讨ICU入院前阿司匹林暴露的平均治疗效果(ATE)。使用广义相加混合模型分析两组中性粒细胞与淋巴细胞比值(NLR)、红细胞分布宽度(RDW)、氧合指数(P/F)、动态肺顺应性(Cdyn)、机械功率(MP)以及按预测体重标准化的机械功率(WMP)的纵向数据。构建多重中介模型以探讨ICU入院前阿司匹林暴露与S-ARF患者结局之间可能的中介因素。本研究共纳入2090例S-ARF患者。ICU入院前阿司匹林暴露降低了28天死亡率(ATE,-0.1945,95%置信区间[CI],-0.2786至-0.1103,<0.001)、60天死亡率(ATE,-0.1781,95%CI,-0.2647至-0.0915,<0.001)和医院死亡率(ATE,-0.1502,95%CI,-0.2340至-0.0664,<0.001)。在亚组分析中,冠心病监护病房组、高剂量组(超过100mg/d)和无创机械通气(IMV)组中,28天死亡率、60天死亡率和医院死亡率的ATE无统计学意义。排除这些无获益患者后,与非阿司匹林暴露组相比,ICU入院前阿司匹林暴露组在开始IMV后每小时Cdyn和P/F比值分别增加0.31mL/cmH₂O(标准误,0.21,P = 0.016)和0.43mmHg(标准误,0.24,P = 0. —— 原文此处有误,推测为P = 0.041)。NLR、Cdyn、WMP的时间加权平均值分别在ICU入院前阿司匹林暴露与28天死亡率总效应中起8.6%、24.7%和13%的中介作用。ICU入院前阿司匹林暴露与S-ARF患者28天死亡率、60天死亡率和医院死亡率降低相关,但入住冠心病监护病房、服用高剂量阿司匹林或未接受IMV的患者除外。阿司匹林的保护作用可能由低动态水平的NLR以及高动态水平的Cdyn和WMP介导。鉴于样本量和潜在的残余混杂因素,这些研究结果应谨慎解读。