Abstract
BACKGROUND: Septic shock is a life-threatening syndrome often triggered by respiratory infections, frequently accompanied by coagulation dysfunction, leading to high mortality rates. Heparin, as an anticoagulant, exhibits multiple effects, but its specific prognostic value in such patients remains unclear. OBJECTIVE: To investigate association between early prophylactic heparin therapy and mortality in patients with septic shock secondary to respiratory infections. METHODS: Patient data were extracted from MIMIC-IV database. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding variables. Kaplan-Meier (K-M) curves were utilized to assess survival rates. Cox proportional hazards model was employed to evaluate relationship between early prophylactic heparin therapy and 28-day mortality. Subgroup analyses were performed, along with time-effect (timing of the initial dose) and dose-effect (cumulative dose) association analyses. RESULTS: 882 eligible patients were included, of whom 191 received early prophylactic heparin therapy. K-M survival curves demonstrated that 28-day mortality was significantly lower in heparin-treated group compared to non-heparin group (P = 0.006). After IPTW adjustment, prophylactic heparin use was associated with a reduced risk of 28-day mortality (HR: 0.626, 95% CI: 0.425-0.922, P = 0.018). The sensitivity analysis (propensity score matching) demonstrated a consistent negative correlation trend (HR: 0.754, 95% CI: 0.472-1.203, P = 0.236). Subgroup analyses revealed that both before and after IPTW adjustment, heparin use was significantly associated with reduced 28-day mortality in patients aged ≥ 60 years and those receiving antibiotics (all HR < 1, all P < 0.05). The time-effect analysis demonstrated that patients who received the first dose within 0-6 h showed significant survival benefits compared to the non-heparin group (HR: 0.308, 95% CI: 0.137-0.694, P = 0.005). The dose-effect relationship revealed that patients with a cumulative dose of ≥ 5 doses exhibited significant survival benefits (HR: 0.264, 95% CI: 0.095-0.737, P = 0.011), with a dose-dependent trend observed (P for trend = 0.007). CONCLUSION: Early prophylactic heparin therapy significantly reduced mortality in patients with septic shock secondary to respiratory infections, showing enhanced efficacy when administered within the first 6 hospital hours or reaching cumulative doses of ≥ 5 doses. This finding provides critical evidence for optimizing treatment strategies for septic shock. CLINICAL TRIAL NUMBER: Not applicable.