Association between fluid administration and 28-day mortality in sepsis: a retrospective cohort study

The optimal volume of early fluid resuscitation in sepsis remains controversial. We investigated the association between intravenous (IV) fluid volume and the 28-day mortality in sepsis. We conducted a retrospective cohort study using the MIMIC-IV database. Cumulative IV fluid administration during the first three days in the ICU was evaluated. Risk-adjusted restricted cubic splines were used to model the non-linear relationship between total IV fluid volume and mortality. Inflection points were used to stratify patients into lower and higher fluid volume groups. Propensity score matching (PSM) and multivariate Cox regression were conducted to assess robustness. Among 14,435 patients with sepsis (mean [standard deviation] age, 64.58 [15.68] years; 59.19% male), the 28-day mortality rate was 15.19% (n = 2,192). After adjustment, 28-day mortality risk increased when IV fluid volume exceeded 5,000 mL. In PSM analysis (n = 2,089 vs. 4,178), patients receiving IV fluid volume ≥ 5,000 mL had a higher 28-day mortality risk (347 [16.6%] vs. 564 [13.5%]); hazard ratio (HR): 1.20, 95% confidence interval [CI]: 1.02-1.41, P = 0.0248. In the multivariate analysis, the 28-day, 90-day, and 180-day mortality in patients receiving higher fluid volume than patients receiving lower fluid volume increased by 22%, 24%, and 19%, respectively. Adjusted HR (95% CI) was 1.22 (1.04, 1.44), 1.22 (1.04, 1.44), and 1.19 (1.04, 1.36), respectively. Overall, excessive IV fluid administration is associated with increased all-cause mortality in the early treatment of sepsis, underscoring the need for cautious fluid management.