Abstract
Background: Acetaminophen is widely used in intensive care units, yet its impact on mortality among critically ill patients with primary lung cancer remains unclear. Given the high disease burden and potential immunomodulatory effects of acetaminophen, robust evidence is needed to clarify its prognostic relevance in this population. Methods: We conducted a retrospective cohort study using the MIMIC-IV v2.2 database, including 1,127 critically ill patients with primary lung cancer. Baseline variables comprised demographics, comorbidities, illness severity scores (SOFA, APSIII, SAPSII, OASIS), and laboratory parameters. To minimize confounding, propensity score matching was applied. Results: A total of 1,127 critically ill patients with primary lung cancer were included, of whom 403 received acetaminophen. The 28-day mortality rate was 22.0% in the acetaminophen group compared to 37.5% in the non-acetaminophen group. After adjusting for baseline differences using inverse probability of treatment weighting (IPTW), acetaminophen exposure was associated with a significantly lower risk of 28-day mortality (HR=0.75, 95% CI: 0.60-0.93, p=0.015). In addition to 28-day mortality, acetaminophen use was consistently associated with reduced risks of ICU mortality, in-hospital mortality, 30-day mortality, 90-day mortality, and 365-day mortality. Subgroup analyses identified patients aged ≥65 years and those with a SOFA score ≥3 as particularly noteworthy subgroups. Conclusion: Acetaminophen use was associated with significantly reduced short- and long-term mortality in critically ill patients with primary lung cancer. These findings suggest a potential survival benefit beyond its conventional symptomatic use and underscore the need for prospective studies to validate its therapeutic role in this high-risk population.