Association of Fluid Balance Trajectories and Daily Change in Fluid Balance with Mortality in Critically Ill Children

Background: Despite well-documented links between fluid accumulation and AKI and mortality, critical knowledge gaps remain in understanding of the full continuum of fluid balance (FB). This study aimed to identify FB trajectory patterns, examine their relationships with clinical characteristics and outcomes, and evaluate the association between daily changes in cumulative FB (CFB) and mortality risk. Methods: The multicenter prospective study employed a derivation-validation design. The derivation cohort comprised 897 critically ill children admitted to four PICUs. Validations were conducted in an external cohort of 684 children and a composite cohort of 868 children with complete CFB data from both cohorts.Fluid intake and output were recorded during the first four days post-PICU admission to calculate daily CBF. Primary outcome was 30-day PICU mortality including deaths resulting from treatment withdrawal. Group-based trajectory modeling identified trajectory clusters; causal mediation analysis quantified confounder mediation; Cox models using restricted cubic splines captured non-linear risk relationship. Results: In derivation cohort, patients were categorized into three FB trajectories with unique clinical characteristics: stable (79.4%), inverted U-shaped (7.3%), and declining (13.4%). The inverted U-shaped and declining trajectories were associated with lower survival probabilities, even after adjusting for confounders. AKI mediated 18.1% of the effect of FB trajectory on mortality, whereas age exhibited an inverse mediating effect of -16.1%. Additionally, daily CFB changes of less than -2.0% or greater than 6.5% were correlated with increased mortality risk, whereas maintaining changes within 0% to 2% conferred lower risk. Specifically, a -2.0% change was associated with a 19.5% increase in risk (95%CI 1.020-1.402), while a 6.5% change was linked to a 25.6% increase (95%CI 1.003-1.573). These findings were reproducible in both validation and composite cohorts. Conclusion: The study delineated three distinct FB trajectories with unique clinical characteristics and varying mortality rates in critically ill children. Daily CFB changes of less than -2.0% or greater than +6.5% were linked to higher mortality, while changes between 0% to 2% conferred lower risk. These findings underscore the importance of precise FB monitoring and suggest actionable intervention thresholds.