Evidence-based use of acetaminophen for hemodynamically significant ductus arteriosus in preterm infants

Abstract

While cyclooxygenase inhibitors have been the most common medications used to facilitate earlier closure of patent ductus arteriosus in preterm infants, adverse effects and variable efficacy have highlighted a need for alternative options. Acetaminophen facilitates ductal closure via an alternate pathway of prostaglandin inhibition. Despite treatment with high doses, toxicity is uncommon in preterm infants, possibly due to immature hepatic metabolism. Pooled data from randomized clinical trials of early treatment demonstrate that acetaminophen has similar efficacy as cyclooxygenase inhibitors for PDA closure with a favorable side effect profile and without any apparent increase in adverse neonatal outcomes. Acetaminophen may therefore be an ideal first-line agent among moderately and extremely preterm infants, though there is a paucity of data from controlled trials regarding its use in infants at the border of viability (gestation age ≤25 weeks). Evidence from clinical studies of limited quality supports acetaminophen treatment as rescue therapy for infants with persistent PDA after unsuccessful cyclooxygenase inhibitor treatment, including those being considered for surgical ligation.