Investigating the role of aspirin on the mortality risk of sepsis-associated encephalopathy: A retrospective study

Fengzhen Huang^1,2Jiping Yi^3,4Qiuli Li^1,3Tieqiao Zhou⁵Dongyou Yue⁶Xiaoxiang Gong⁷Heng Meng^1*

• ¹Department of Neurology and Stroke Center, The first affiliated hospital of Jinan University, Guangzhou, China
• ²Department of Neurology, The First People's Hospital of Chenzhou affiliated to the University of South China, Chenzhou, Hunan Province, China
• ³The First People's Hospital of Chenzhou affiliated to the University of South China, Chenzhou, Hunan Province, China
• ⁴Department of Neurology, The First Affiliated Hospital of Xiangnan University, Chenzhou, Hunan Province, China
• ⁵Department of Laboratory Medicine, The First People's Hospital of Chenzhou affiliated to the University of South China, Chenzhou, Hunan Province, China
• ⁶Department of Emergency, The First People's Hospital of Chenzhou affiliated to the University of South China, Chenzhou, Hunan Province, China
• ⁷Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China

Background: Sepsis-associated encephalopathy (SAE) is one of the most common complications of sepsis. Aspirin can serve as a promising therapeutic candidate and help improve patient outcomes in sepsis and its complications. However, the efficacy and safety of aspirin on SAE remains largely unexplored.Patients for this retrospective study were collected from MIMIC-IV (version 3.0). Propensity score matching (PSM) was used to balance the baseline characteristics between the no aspirin group and aspirin group. The association between aspirin therapy and mortality risk of in-hospital, 30-day, 60-day, 90-day, and 180-day was analyzed by Cox proportional hazards model and Kaplan-Meier method. E-value analysis was used to evaluate the potential influence of unmeasured or unkown confounding factors. Subgroup analysis was applied to explore potential differences in the effects of aspirin therapy on clinical outcomes across these various groups.Results: Our study recruited 4707 SAE patients in total, and 2518 patients were enrolled after PSM. The mortality rate for in-hospital, 30-day, 60-day, 90-day, and 180-day in the aspirin group was consistently significant lower than that in the no aspirin group. Kaplan-Meier curves revealed that the SAE patients received aspirin therapy exhibited a notably higher survival rate compared to those who did not. The risk of gastrointestinal hemorrhagere had no significant difference between the two groups. Additionally, the mortality rate of SAE patients in aspirin pre-ICU group, aspirin in-ICU group, and aspirin pre-ICU and in-ICU group decreased significantly compared to the no aspirin group. The high-dose aspirin group experienced a significantly higher mortality rate compared to those in the low-dose group.Aspirin could reduce the mortality risk of SAE patients for in-hospital, 30-day, 60-day, 90-day, and 180-day, without increasing the risk of gastrointestinal hemorrhage. The benefits observed persisted regardless of aspirin exposure timing. Patients received high-dose aspirin exhibited a higher mortality risk compared to those in the low-dose group.