Abstract
OBJECTIVE: Sepsis remains a leading cause of intensive care unit (ICU) mortality worldwide, characterized by dysregulated inflammation and immune dysfunction mechanisms also central to many neglected tropical diseases. Omega-3 fatty acids (Ω-3 FAs) possess potent anti-inflammatory and immunomodulatory properties that may improve survival outcomes in such conditions. This retrospective real-world study evaluated the impact of Ω-3 FA supplementation on ICU mortality among patients with sepsis and identified prognostic factors influencing therapeutic efficacy. METHODS: Patients admitted with sepsis to the ICU of Shenzhen People's Hospital between December 2016 and July 2019 were retrospectively analyzed. Propensity score matching (PSM) was applied at a 1:2 ratio between Ω-3 FA-treated and control groups using covariates including age, sex, diagnosis, norepinephrine (NE) requirement, hemofiltration (HF), C-reactive protein (CRP), and lymphocyte count. Logistic regression and inverse probability of treatment weighting (IPTW) were performed to determine the independent effect of Ω-3 FAs on mortality. RESULTS: A total of 633 patients were included (Ω-3 FA group, n = 211; control, n = 422). The unadjusted mortality rate was 32.7% in the Ω-3 FA group and 24.6% in controls (p = 0.032). Univariate analysis showed a weak protective effect of Ω-3 FAs (HR = 0.74, 95% CI: 0.54-1.02, p = 0.062). After adjusting for age, HF and NE requirements, CRP, lymphocyte count, Sequential Organ Failure Assessment (SOFA) score, and abdominal infection, Ω-3 FAs demonstrated a significant protective effect (HR = 0.60, 95% CI: 0.43-0.83, p = 0.003). Kaplan-Meier analysis confirmed improved survival in the Ω-3 FA group (p = 0.038). Advanced age, elevated CRP, and higher NE dependence were identified as factors that negatively modulated Ω-3 FA efficacy. CONCLUSION: Omega-3 fatty acid supplementation was associated with significantly reduced adjusted ICU mortality in sepsis, underscoring its host-directed immunomodulatory properties. These findings highlight the translational potential of Ω-3 FAs as adjunct therapeutic agents in sepsis and other infection-associated inflammatory disorders, supporting further drug development toward host-directed treatments for neglected tropical diseases.