565 - Route of Furosemide Administration is Not Associated with a Differential Diuretic Response in Infants with Bronchopulmonary Dysplasia

Poster Number: 565
Publication Number: 565.2948

Background: Furosemide exposure occurs in 75% of infants with high-grade bronchopulmonary dysplasia (BPD). Although intravenous (IV), gastric, and post-pyloric administrations are routine in clinical practice, the impact of route on diuretic response is unknown.

Objective: To compare the association between route of furosemide administration and diuretic response in very preterm infants with BPD. A secondary objective identified drug and clinical characteristics independently associated with diuresis.

Design/Methods: In a single-center cohort study, we compared diuresis after IV, gastric, and post-pyloric furosemide exposures occuring between 36-60 weeks postmenstrual age (PMA) in hospitalized infants with grade 2-3 BPD. Eligible exposures required 7 preceding days without furosemide to control for diuretic tolerance, and could be given once, every 24h, or every 8 or 12h if the dose and route were consistent for a 24h period. We measured the within-subject change in total net fluid balance (ml/kg/day) in the 24 hours before and after furosemide exposure as a surrogate measure of diuretic response. We standardized doses assuming a bioavailability of 50% relative to IV for both enteral routes. The comparative effect of administration route on diuresis was evaluated through multivariable linear regression using robust variance estimates. We adjusted for potential confounding by including diuretic dose and frequency a priori, in addition to covariates associated with diuresis at p < 0.10 in bivariable regression.

Results: Characteristics of the 165 eligible infants are displayed in Table 1. The mean decrease in net fluid balance following furosemide exposure was -25.1 ml/kg/day. There were no differences in response between routes of administration in either unadjusted (Table 2) or adjusted multivariable analyses, with a similar decrease in fluid balance for gastric (-24.2 ml/kg/d), IV (-26.6 ml/kd/d), and post-pyloric (-24.7 ml/kg/d) furosemide (Table 3). Only blood urea nitrogen (BUN) was independently associated with diuretic response. For every mg/dL increase in BUN, the mean change in fluid balance following furosemide exposure was 1.0 ml/kg/d less negative; p = 0.01.

Conclusion(s): The diuretic response to furosemide was similar across IV, gastric, and post-pyloric administrations in infants with BPD. Research on the bioavailability of gastric and duodenal furosemide is needed to fully characterize the dose-exposure-response relationship. The role of BUN as a mediator of diuretic response in infants with BPD, potentially as a biomarker of volume status, deserves dedicated study.