Pharmacotherapy for patent ductus arteriosus closure

Abstract

Even though up to 60% of premature infants less than 28 weeks gestation develop persistent patent ductus arteriosus (PDA), there remains controversy regarding if, when, and how to close the PDA. Failure to close the PDA has been associated with significant morbidity but no cause-and-effect has been proven for short-term or long-term outcomes in modern times. Surgical closure has the advantage of eliminating the PDA, but short-term complications and long-term adverse outcomes are worrisome. Intravenous indomethacin has been the "gold standard" for pharmacologic treatment over the past 40 years with high closure rates and decreased incidence of severe intraventricular hemorrhage (IVH) and pulmonary hemorrhage with early treatment but without improvement in long-term outcomes and with risk of renal toxicity. Intravenous ibuprofen has less vasoconstrictive toxicity than indomethacin with comparable closure rates but without improvement in IVH and with hyperbilirubinemia risks. Earlier this decade, acetaminophen (paracetamol) was discovered to effectively close the PDA with good short-term safety profile. Although promising, acetaminophen treatment requires further studies regarding long-term safety as well as ideal dosing and route of administration.

Keywords: acetaminophen (paracetamol); cyclooxygenase (COX) inhibitors; ibuprofen; indomethacin; patent ductus arteriosus; peroxidase (POX) inhibitor.