Combination Therapy of Albumin and Loop Diuretics May Improve Survival in Patients with Sepsis Receiving Mechanical Ventilation: A Propensity Score Matched Analysis

Background: Fluid overload and hypoalbuminemia are typical and associated with poor outcomes in patients with sepsis receiving mechanical ventilation. While loop diuretics are used for fluid management, their efficacy can be limited by intravascular volume depletion and hypoalbuminemia. This study examines whether the combined administration of albumin and loop diuretics enhances clinical outcomes in this high-risk population. Methods: In this retrospective cohort study utilizing the MIMIC-IV database, adult patients with sepsis who required mechanical ventilation were categorized into two groups: those receiving albumin alone and those receiving albumin in combination with loop diuretics. Propensity score matching was employed to ensure balance in baseline characteristics between the groups. The primary outcome of the study was in-hospital mortality, while secondary outcomes included mortality rates at 30 and 90 days, length of hospital stay, and fluid balance. Results: After matching, a total of 1,032 patients were included in each group. The in-hospital mortality rate was significantly lower in the combination therapy group compared to the albumin-alone group (21.2% vs. 33.0%, p < 0.001). Similarly, the 30-day (22.4% vs. 32.8%) and 90-day (28.3% vs. 40.0%) mortality rates were also reduced, with both differences being statistically significant (p < 0.001). The combination therapy group exhibited a significantly lower 7-day fluid balance (1,462 mL vs. 4,304 mL, p < 0.001), despite longer durations of ICU and hospital stays. Subgroup analyses indicated a consistent benefit across most subgroups. A dose-response relationship was observed, with low-to-moderate furosemide-equivalent doses (<40 mg/day) associated with reduced mortality (HR 0.37–0.58). In contrast, higher doses (>80 mg/day) did not demonstrate any survival advantage. Conclusion: In patients with sepsis receiving mechanical ventilation, the combination of albumin and loop diuretics may be associated with reduced 30-day and 90-day mortality, as well as improved fluid balance compared to the use of albumin alone. The benefits appear to be dose-dependent, favoring low to moderate diuretic intensity. These findings suggest a potential therapeutic role for the combined use of albumin and loop diuretic therapy in this patient population.