Time-dependent association between colchicine administration and 28-day mortality in critically ill patients with sepsis: A propensity score-matched cohort study.

OBJECTIVE: To evaluate the association between colchicine administration and 28-day mortality in septic patients while assessing its real-world safety profile. METHODS: This retrospective study utilized the MIMIC-IV (v3.1) database to identify adults meeting Sepsis-3.0 criteria. We employed 1:2 propensity score matching (PSM) and a time-dependent Cox proportional hazards model to mitigate immortal time bias. Exposure was stratified into new users (therapy initiated >24 hours after ICU admission) and pre-ICU users (maintenance therapy). RESULTS: Among 25,119 patients, 434 received colchicine. After PSM (423 users, 835 controls), colchicine was associated with a significantly lower risk of 28-day mortality (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.26 - 0.87; P = 0.016). This observed survival association was concentrated among new users (HR, 0.26; 95% CI, 0.13 - 0.51; P < 0.001), whereas no significant advantage was observed for pre-ICU users (P = 0.168). While risks for acute kidney injury and hepatotoxicity were comparable, colchicine recipients had a higher incidence of thrombocytopenia (17.3% vs. 12.9%; P = 0.016). Hospital length of stay was significantly longer in the colchicine group compared to controls (median, 10.75 vs. 8.43 days; P < 0.001). CONCLUSIONS: Colchicine administration exhibits a significant survival association in patients with sepsis, with lower 28-day mortality risks observed primarily when initiated during the acute phase. However, these retrospective findings are purely hypothesis-generating, and prospective randomized controlled trials are essential to validate these clinical implications.