Association between Cumulative Fluid Overload and Clinical Outcomes in Intensive Care Unit Patients with Sepsis: A Retrospective Cohort Study

Abstract Background: Fluid resuscitation is essential in early sepsis management, but excessive fluid administration may be harmful. This study aimed to investigate the association between cumulative fluid balance and key clinical outcomes in critically ill patients with sepsis. Materials and Methods: We conducted a retrospective cohort study of adult intensive care unit (ICU) patients with sepsis admitted to a tertiary referral hospital between January 2022 and December 2024. Patients aged 18–65 years meeting sepsis-3 criteria were included. The primary exposure was cumulative fluid balance; the primary outcome was in-hospital mortality. Secondary outcomes included acute kidney injury (AKI), duration of mechanical ventilation, and ICU length of stay. Multivariable regression analyses were performed to identify independent predictors of mortality. Receiver operating characteristic (ROC) curve analysis evaluated the discriminatory ability of fluid balance. Results: Of 295 patients included, 144 (48.8%) developed fluid overload (FO). Non-survivors had significantly higher cumulative fluid balance than survivors (−724.5 mL vs. −1924 mL; P < 0.001). FO was associated with higher mortality (Risk Ratio RR: 21.8), increased incidence of AKI (RR: 12.9), prolonged ICU stay, and ventilator duration (all P < 0.001). ROC analysis revealed good predictive value of fluid balance for mortality (area under the curve AUC: 0.874). In multivariate analysis, FO (RR: 11.26; 95% CI: 5.41–23.43) and AKI were independently associated with mortality. Conclusion: FO is an independent predictor of mortality and organ dysfunction in septic ICU patients. These findings support the need for early, individualized fluid management strategies and further prospective studies to define optimal thresholds and timing of fluid interventions.