Abstract
BACKGROUND: Intravenous (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. METHODS: We 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. RESULTS: Overall, 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). CONCLUSIONS: Higher 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.