75 - Evaluation Of Acetaminophen Vs. High-Dose Ibuprofen In Late Patent Ductus Arteriosus Closure In Preterm Infants At Sunnybrook Health Sciences Centre: A Retrospective Study

Poster Number: 75
Publication Number: 75.1760

Background: Initial management of patent ductus arteriosus (PDA) remains challenging as standard-dose ibuprofen (SD-IBU) and acetaminophen (APAP) have been shown to have comparable success. The emergence of high-dose ibuprofen (HD-IBU) has overshadowed SD-IBU, but the only literature currently available to guide the choice between HD-IBU or APAP is in infants born at a gestational age (GA) >30 weeks and for PDA in the first seven days of life.

Objective: As HD-IBU use at our centre has been extrapolated to extremely preterm and very low birth weight (BW) infants for late PDA, the objectives of this study were to compare the effectiveness and safety of HD-IBU and APAP in managing PDA in a subpopulation and timeframe lacking robust data.

Design/Methods: We conducted a retrospective cohort study on neonates born at < 28 weeks GA or BW < 1500 g and treated with HD-IBU or APAP for PDA at a postnatal age of at least seven days. Infants were excluded if they received either agent at postnatal age of one to six days, but could have used SD-IBU. Efficacy outcomes include the incidence of constriction to a non-hemodynamically significant PDA (non-hsPDA), need for surgical closure, and time to PDA constriction. Safety outcomes include incidence of new or worsened bleeding, acute kidney injury (AKI), hepatotoxicity, necrotizing enterocolitis, bronchopulmonary dysplasia and death. Descriptive statistics, linear and logistic regression analyses were used, adjusted for PDA diameter, GA at birth, and postnatal age during treatment.

Results: Ninety-four neonates with median GA 25 (interquartile range [IQR] 24-27) weeks and BW 711 (IQR 604-880) g were included. HD-IBU infants had higher odds of achieving non-hsPDA (adjusted odds ratio [aOR]=2.5; 95% confidence interval [CI] 0.9-6.4; p=0.06) with marginal significance (Table 1). Significantly less infants among the HD-IBU group required surgical closure (aOR=0.3; 95% CI 0.1-0.9; p=0.03) indicated in Table 1, but at an increased risk of AKI (aOR=14.6; 95% CI 0.8-281.3; p=0.08) regardless of baseline renal impairment. No other considerable differences in efficacy or safety were observed.

Conclusion(s): In extremely preterm or very low BW infants with late PDA, HD-IBU is associated with a lower chance of surgical closure, but not in achieving non-hsPDA, consistent with how it compares to SD-IBU in previous studies. With higher rates of AKI, HD-IBU should be used judiciously in this subpopulation, such as when PDA ligation risk is high. Rates of PDA constriction are low with monotherapy, and future studies should explore a combination pharmacotherapy regimen to reduce morbidity with PDA.