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. 2025 Jun 23;30(1):512.
doi: 10.1186/s40001-025-02786-y.

Early acetaminophen use is associated with the reduced mortality risk in patients with sepsis-associated encephalopathy: a retrospective study

Fengzhen Huang  1   2 , Jiping Yi  1   2 , Tieqiao Zhou  3 , Xiaoxiang Gong  4
Affiliations

Early acetaminophen use is associated with the reduced mortality risk in patients with sepsis-associated encephalopathy: a retrospective study

Fengzhen Huang et al. Eur J Med Res. .

Abstract

Background: Sepsis-associated encephalopathy (SAE), a severe neurological complication of systemic infection, carries substantial morbidity and mortality risks. This study aims to examine the relationship between early acetaminophen use and survival rates in critically ill SAE patients.

Methods: Using data from the MIMIC-IV database, we conducted a retrospective cohort study on patients with SAE, stratified by acetaminophen exposure within 48 h of ICU admission. Among the 4111 eligible patients (1689 acetaminophen recipients versus 2422 non-recipients), propensity score matching resulted in 3124 matched subjects (1562 per cohort). The primary outcome was 90-day mortality, while secondary outcomes included mortality rates at 30, 60, 180, and 365 days. Survival analyses utilized Cox proportional hazards regression and Kaplan-Meier curves, supplemented by subgroup analyses for 90-day mortality.

Results: Acetaminophen exposure was correlated with reduced 30-day mortality rate (HR = 0.78, 95%CI [0.65-0.94], p < 0.05), as well as decreased 60-day (HR = 0.71, 95%CI [0.60-0.83], p < 0.001), 90-day (HR = 0.70, 95%CI [0.60-0.81], p < 0.001), 180-day (HR = 0.70, 95%CI [0.60-0.80], p < 0.001) and 365-day (HR = 0.69, 95%CI [0.61-0.79], p < 0.001) mortality rate after PSM. The Kaplan-Meier analysis demonstrated significantly higher survival rates in the acetaminophen group compared to the non-acetaminophen group, with a persistent trend at 30, 90, 180, and 365 days (log-rank p < 0.05). The protective effect was consistent across subgroups except acetaminophen dosage ≥ 650 mg.

Conclusion: Early administration of acetaminophen is associated with reduced short- and long-term mortality in SAE patients. These findings support a potential therapeutic role for acetaminophen in SAE and warrant further mechanistic and prospective validation.

Keywords: Acetaminophen; MIMIC IV database; Mortality; Sepsis; Sepsis-associated encephalopathy.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study utilized the MIMIC database, which has been approved for research use by the Institutional Review Boards of both Beth Israel Deaconess Medical Center and the Massachusetts Institute of Technology. Because the database is HIPAA compliant and in compliance with the Declaration of Helsinki, the need for ethics approval was waived. A waiver of informed consent was granted due to the retrospective nature of the study and the use of de-identified data. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The flowchart for the selection of SAE patients. GCS: Glasgow Coma Scale, SAE: sepsis-associated encephalopathy, ICU: intensive care unit
Fig. 2
Fig. 2
Standardized mean difference (SMD) of variables before and after propensity score matching (PSM)
Fig. 3
Fig. 3
Kaplan–Meier survival curves between the acetaminophen group and non-acetaminophen group before PSM. A 30-day survival curves before PSM; B 90-day survival curves before PSM; C 180-day survival curves before PSM; D 365-day survival curves before PSM
Fig. 4
Fig. 4
Kaplan–Meier survival curves between the acetaminophen group and non-acetaminophen group after PSM. A 30-day survival curves after PSM; B 90-day survival curves after PSM; C 180-day survival curves after PSM; D 365-day survival curves after PSM
Fig. 5
Fig. 5
Subgroup analysis of the 90-day mortality in SAE patients. HR: hazard ratio, CI: confidence interval, SOFA: Sepsis-related Organ Failure Assessment, GCS: Glasgow Coma Scale
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