Uncovering the Untapped Potential of Furosemide in Sepsis: Real-World Evidence on Coagulopathy and Organ Outcomes

BACKGROUND: Sepsis-related coagulopathy is a major driver of organ failure and mortality, yet effective adjuncts remain limited. We therefore examined whether early furosemide use is associated with reduced coagulopathy and improved organ outcomes in real-world practice. METHODS: Using Taiwan's National Health Insurance Research Database (2000-2013), we assembled a population-based matched cohort of 9,934 adults with incident sepsis. Exposure was receipt of furosemide during the index hospitalization; comparators were other diuretics (e.g., acetazolamide, hydrochlorothiazide, and spironolactone). The primary outcome was disseminated intravascular coagulation; secondary outcomes included transfusion, organ failures (cardiac, respiratory, renal, and hepatic), and all-cause mortality. Multivariable Cox models estimated adjusted hazard ratios. RESULTS: In the primary analysis (3-month follow-up), furosemide use was associated with a lower risk of disseminated intravascular coagulation (adjusted hazard ratio 0.196, 95% confidence interval 0.067-0.516, P < 0.001) and transfusion. These associations remained durable in the exploratory 12-month analysis. Significant protective associations were also observed for cardiac, respiratory, and acute renal failure, alongside lower all-cause mortality. Crucially, active comparator analysis revealed that while associations with lower mortality were shared across diuretic classes, the protective associations with organ failure were specific to furosemide and not observed with other diuretics, supporting a distinct pharmacological effect beyond general diuresis. CONCLUSIONS: Real-world evidence suggests that furosemide use is associated with reduced sepsis-related coagulopathy and favorable organ outcomes. These findings generate a biologically plausible hypothesis consistent with Na + -K + -2Cl - cotransporter 1-related antioxidant and anti-inflammatory pathways observed in preclinical models, warranting confirmation in prospective trials.