Supplementary file 1_Cumulative intravenous fluid volume in the first 24 hours and risk of respiratory deterioration in children hospitalized with community acquired pneumonia.docx

BackgroundIntravenous (IV) fluids are frequently administered to children hospitalized with community-acquired pneumonia (CAP), yet excessive early IV volume may worsen gas exchange in inflamed lungs. We evaluated whether cumulative IV fluid exposure during the first 24 h was associated with subsequent respiratory deterioration.
MethodsWe conducted a single-center observational study using electronic health record data and a prespecified 24-hour landmark design. Early IV fluid exposure was quantified as the fluid-to-maintenance ratio (FMR), defined as total IV volume in 0–24 h divided by predicted 24-hour maintenance volume using Holliday-Segar and categorized into quartiles. The primary outcome was respiratory deterioration between 24 and 72 h, defined as escalation to high-flow nasal cannula, noninvasive ventilation, or invasive mechanical ventilation and/or ICU transfer for respiratory support. Associations were assessed using multivariable logistic regression, restricted cubic splines, overlap weighting for Q4 vs. Q1–Q3, and prespecified sensitivity/subgroup analyses.
ResultsOverall, 243 developed respiratory deterioration. Event rates increased across FMR quartiles (3.1%, 6.1%, 9.6%, 21.2%). Each 0.5-unit increase in FMR was associated with higher adjusted odds of deterioration (adjusted OR 1.45, 95% CI 1.28–1.65; p < 0.001). Compared with Q1, Q4 had higher adjusted odds (adjusted OR 3.56, 95% CI 2.08–6.10; p < 0.001), supported by overlap-weighted analysis (Q4 vs. Q1-Q3, OR 2.01, 95% CI 1.29–3.13). Spline modeling showed progressively increasing risk at higher FMR. Results were robust in most sensitivity analyses. In an early-response sensitivity analysis incorporating first 0–6 h fluid front-loading and age-standardized physiological response, the association attenuated but remained significant (adjusted OR 1.27, 95% CI 1.10–1.47; p = 0.001). A complementary repeated-measures 0–6 h time-slope analysis using all available vital-sign recordings yielded similar results (adjusted OR 1.29, 95% CI 1.12–1.49; p = 0.001) (adjusted OR 1.31, 95% CI 1.14–1.50; p < 0.001). In the complete-case procalcitonin (PCT) subset, the estimate attenuated after additional adjustment for log(PCT) (adjusted OR 1.18, 95% CI 0.98–1.43).
ConclusionsHigher IV fluid exposure relative to maintenance during the first 24 h was associated with increased risk of subsequent respiratory deterioration in children hospitalized with CAP. These findings support prospective validation and evaluation of maintenance-aware IV fluid approaches.