AUTHOR=Lu Zongqing , Fang Pu , Xia Dunling , Li Mengdie , Li Seruo , Wang Yu , Fu Lin , Sun Gengyun , You Qinghai 

TITLE=The impact of aspirin exposure prior to intensive care unit admission on the outcomes for patients with sepsis-associated acute respiratory failure

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1125611

DOI=10.3389/fphar.2023.1125611

ISSN=1663-9812

ABSTRACT=<p><bold>Objectives:</bold> 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).</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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, <italic>p</italic> &lt; 0.001), 60-day mortality (ATE, −0.1781, 95% Cl, −0.2647 to −0.0915, <italic>p</italic> &lt; 0.001), and hospital mortality (ATE, −0.1502, 95%CI, −0.2340 to −0.0664, <italic>p</italic> &lt; 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/cmH<sub>2</sub>O (SE, 0.21, <italic>p</italic> = 0.016), and 0.43 mmHg (SE, 0.24, <italic>p</italic> = 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.</p><p><bold>Conclusion:</bold> 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.</p>