Early acetaminophen Use and 90-day mortality in ICU patients with ischemic stroke

Abstract

Introduction: The impact of acetaminophen on the prognosis of ischemic stroke patients admitted to intensive care units remains unclear. Although acetaminophen is commonly used for fever and pain management, its potential benefits beyond temperature control require further investigation.

Methods: Using the MIMIC-IV database, we retrospectively identified 494 ICU-admitted ischemic stroke patients, of whom 362 (73.28%) received early acetaminophen treatment within 48 h after ICU admission. Patients were stratified based on acetaminophen exposure. Weighted Cox regression was applied after inverse probability of treatment weighting (IPTW) adjustment. Subgroup and sensitivity analyses were performed to assess the consistency of associations.

Results: After IPTW adjustment, early acetaminophen use was associated with reduced 30-day mortality (HR 0.54, 95% CI 0.31-0.94, p = 0.030), and reduced 90-day mortality (HR 0.53, 95% CI 0.32-0.87, p = 0.013). There were no significant differences in in-hospital mortality or hospital length of stay. Subgroup analyses revealed no significant interaction effects, suggesting a consistent association across different clinical strata.

Discussion: Early acetaminophen use may be associated with improved survival outcomes in critically ill ischemic stroke patients. These findings highlight the potential therapeutic value of acetaminophen beyond symptomatic treatment, warranting confirmation through prospective, multicenter randomized controlled trials.

Keywords: acetaminophen; intensive care units; inverse probability of treatment weighting; ischemic stroke; mortality.

FIGURE 1

Flowchart of patient selection. A total of 3,799 patients diagnosed with ischemic stroke were initially screened from the MIMIC-IV v3.1 database. Patients were excluded if they had an ICU stay of less than 2 days, were younger than 18 years, used acetaminophen combination products during hospitalization, received acetaminophen prior to ICU admission, initiated acetaminophen use only after 48 h of ICU admission, had a non-first ICU admission, or had a documented malignancy. After applying these criteria, 494 patients were included in the final cohort. Patients were then categorized into two groups based on acetaminophen exposure within the first 48 h of ICU admission.

FIGURE 2

Kaplan–Meier Survival Curves Comparing acetaminophen Users and Non-Users. (A) 30-day survival before IPTW adjustment; (B) 90-day survival before IPTW adjustment; (C) 30-day survival after IPTW adjustment; (D) 90-day survival after IPTW adjustment. In all analyses, patients who received acetaminophen had significantly higher survival rates compared to non-users (log-rank test, P < 0.0001 for all comparisons). IPTW = inverse probability of treatment weighting.

FIGURE 3

Subgroup Analyses of the Association Between acetaminophen Use and 90-Day Mortality Before IPTW Adjustment. Forest plot showing hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between acetaminophen use and 90-day mortality across various patient subgroups before inverse probability of treatment weighting (IPTW) adjustment. No significant interaction effects were observed across subgroups (all P for interaction >0.05), indicating consistent benefits of acetaminophen use. Notably, the protective effect of acetaminophen was consistent across different inflammatory statuses, including CRP levels, WBC counts, and body temperature groups. Abbreviations: HR, hazard ratio; CI, confidence interval; CRP, C-reactive protein; WBC, white blood cell; IPTW, inverse probability of treatment weighting.

FIGURE 4

Subgroup Analyses of the Association Between acetaminophen Use and 90-Day Mortality After IPTW Adjustment. Forest plot illustrating hazard ratios (HRs) and 95% confidence intervals (CIs) for 90-day mortality associated with acetaminophen use in various subgroups following inverse probability of treatment weighting (IPTW). No significant interaction was observed between treatment effect and any subgroup (all P for interaction >0.05), indicating a consistent survival benefit across populations. The effect remained stable in patients with differing levels of inflammation, including CRP, WBC, and body temperature subgroups. Abbreviations: HR, hazard ratio; CI, confidence interval; CRP, C-reactive protein; WBC, white blood cell; IPTW, inverse probability of treatment weighting.