Early fluid resuscitation and 28-day mortality in burns: A mediation analysis via coagulation biomarkers.

BACKGROUND: Fluid resuscitation is a critical treatment in the shock phase for burn patients, but excessive fluid infusion has adverse effects. METHODS: We conducted a multicenter retrospective cohort study involving 12 burn centers across mainland China. Adult patients (age >18 years) with severe burns were included. The primary exposure was the 24-hour fluid volume (ml/kg/%TBSA). The primary outcome was 28-day mortality. Cox proportional hazards models were used to evaluate the association between fluid volume and mortality. Secondary outcomes included changes in coagulation parameters (prothrombin time, activated partial thromboplastin time [APTT], INR, D-dimer, fibrinogen, thrombin time, and platelet count) and incidence of coagulopathy. Mediation analysis was performed to assess whether the effect of fluid rate on mortality was mediated through alterations in coagulation markers. RESULTS: A total of 475 patients were included in the initial cohort for mortality analysis, and 278 patients with complete coagulation data were analyzed in the secondary cohort for mediation. After adjusting for multiple confounders, higher fluid volume was significantly associated with increased 28-day mortality (adjusted HR = 1.74, 95% CI: 1.30-2.32, P < 0.001). Elevated fluid volume was also associated with prolonged APTT, reduced platelet count, and higher incidence of coagulopathy. Mediation analysis revealed that the effect of fluid rate on mortality was partially mediated by decline in platelet count (P = 0.002), whereas other coagulation parameters did not show significant mediating effects. CONCLUSIONS: Higher initial fluid volume not only has a direct effect on coagulation but also leads to an increased risk of 28-day mortality. The difference in platelet count statistically mediates the effect of fluid volume on mortality outcomes.