Fluid balance and mortality in adult ICU patients with sepsis or septic shock: a systematic review and meta-analysis of observational studies

Background: Fluid therapy is a cornerstone of sepsis management; however, excessive fluid accumulation might be associated with adverse outcomes. The association between fluid balance (FB) and mortality in critically ill patients with sepsis or septic shock remains uncertain. Methods: We conducted a systematic review and meta-analysis of observational studies assessing the association between FB and mortality in adult ICU patients with sepsis or septic shock (PubMed, Scopus, CINAHL; through May 2024). Random-effects models estimated pooled odds ratios (ORs) for all-cause mortality; meta-regression explored dose–response patterns and heterogeneity. Risk of bias was assessed with ROBINS-E; certainty of evidence with GRADE. Results: Twenty-six studies(64,755 patients) were included, most of which were retrospective with moderate-to-high risk of bias. Higher cumulative FB was associated with higher odds of mortality (OR 2.11, 95% CI 1.65–2.69). This association was consistent across different FB time windows and definitions; subgroup analyses did not identify study-level factors explaining heterogeneity. Meta-regression supported a linear dose–response relationship. No statistically significant association was observed between FB and the need for renal replacement therapy (OR 1.34, 95% CI 0.76–2.36). According to GRADE, the certainty of evidence was very low. Conclusions: Among critically ill adults with sepsis or septic shock, higher fluid balance was associated with higher mortality. These observational associations are vulnerable to confounding by illness severity, precluding causal inference. Given the very low certainty of evidence, standardised definitions of fluid balance and randomised trials are needed. Potential differences between sepsis and septic shock warrant shock-status stratification. Trial registration: PROSPERO CRD42024538393.