533 - Short-term respiratory response to furosemide among infants with grade 3 bronchopulmonary dysplasia (BPD)

Publication Number: 3514.533

Timothy Nelin, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Matthew Huber, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; David M. Rub, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Nicolas P. Goldstein Novick, Children's Hospital of Philadelphia, Rose Valley, PA, United States; Heidi Morris, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Kathleen Gibbs, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Erik Jensen, Stanford University School of Medicine, Palo Alto, CA, United States; Sara DeMauro, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Nicolas A. Bamat, Children's Hospital of Philadelphia, Swarthmore, PA, United States

Background: Furosemide is frequently used in infants with grade 3 BPD. We previously demonstrated that furosemide tolerance, with respect to total fluid balance, occurs after 24h of sustained use. Physiologic effects on respiratory mechanics in the first 24h after administration remain understudied.

Objective: To evaluate within-infant changes in respiratory mechanics and oxygenation following furosemide administration in invasively ventilated infants with grade 3 BPD.

Design/Methods: We conducted a retrospective cohort study of infants with grade 3 BPD who received 1 dose of furosemide. Qualifying exposures occurred between 36-60 weeks' post-menstrual age (PMA) following >7 days without furosemide. We analyzed longitudinal repeated physiologic measures from the electronic health record from 24h pre- to 24h post-furosemide exposure. Outcomes were the respiratory severity score (RSS) - MAPxFiO2, oxygen saturation index (OSI) - (MAPxFiO2)/SpO2, SpO2/FiO2 (S/F) ratio, compliance, and resistance. Primary analyses compared adjusted means within 4 distinct time windows post-furosemide exposure (0-6h, 6-12h, 12-18h, 18-24h) with the mean in the 6h before exposure. Within-subject fixed-effects regression models estimated adjusted means with robust standard errors clustered by infant. Covariates were selected based on clinical relevance and included in final models if associated with each outcome at P < 0.1 in bivariable models.

Results: We identified 247 infants contributing 427 qualifying furosemide exposures (Table 1). Most exposures were intravenous (62.3%) and equivalent to a 1 mg/kg IV dose (85.2%). Figure 1 displays unadjusted mean outcome values 24h pre- and post-furosemide exposure. S/F ratio appeared to decrease pre-furosemide exposure with subsequent increase in the 24h post-exposure. Compared to 6h pre-exposure, RSS decreased modestly from 5.97 to 5.75 (-0.22, p=0.003) and OSI from 6.45 to 6.19 (-0.27, p=0.005) at 6-12h post-exposure, returning toward baseline by 18-24h. Compliance similarly increased modestly in the 6-12h (+0.09, p=0.024) and 12-18h (+0.10, p=0.045) windows. The S/F ratio rose steadily to 271 at 6-12h (+9.6, p< 0.001) with a sustained increase through 18-24h (+12.2, p< 0.001) (Table 2).

Conclusion(s): Among infants with grade 3 BPD, furosemide administration was associated with transient improvements in respiratory mechanics and a modest, sustained rise in oxygenation. Furosemide may be initiated during clinical worsening, with short-term physiologic change thereafter. Prospective studies are needed to determine whether observed changes reflect therapeutic response or the natural course of illness.

Table 1. Cohort characteristics of 247 infants with grade 3 BPD and 427 qualifying furosemide exposures
Abbreviations: SD, standard deviation; IV, intravenous
Missing Data: Albumin, n = 70


Figure 1. Mean respiratory severity score, oxygen saturation index, SpO2/FiO2 ratio, compliance, and resistance in the 24 hours before and after furosemide administration among infants with grade 3 BPD.
Plots display mean and 95% CI for RSS, OSI, SpO2/FiO2 (S/F) ratio, compliance, and resistance centered at the time of furosemide administration (t = 0).

Table 2. Adjusted^ associations of change in respiratory severity score, SpO2/FiO2 ratio, Oxygen Saturation Index, Compliance, and Resistance before and after furosemide administration among preterm infants with Grade 3 BPD.
^ All models utilized robust standard errors clustered by infant to account for within-subject correlation
a RSS: model adjusted for route of administration, dexamethasone co-administration, chloride value
b SpO2/FiO2 ratio: model adjusted for PMA at exposure, route, chlorothiazide, dopamine, albumin, calcium, creatinine, potassium, sodium, eGFR
c OSI: model adjusted for route, dexamethasone co-administration
d Compliance: model adjusted for PMA, route, chlorothiazide, dexamethasone, vecuronium, albumin, creatinine, eGFR
e Resistance: model adjusted for PMA, route, chlorothiazide, albumin, calcium, creatinine, eGFR