To treat or not to treat beyond three days: Acetaminophen for treatment of the patent ductus arteriosus in premature infants

Premature infants often experience a delay in the physiologic closure of the patent ductus arteriosus (PDA). Lack of spontaneous closure may be associated with significant morbidity and mortality in infants.1–3 Historically, the standard pharmacologic treatment for a hemodynamically significant PDA has been the administration of either ibuprofen or indomethacin.4 The use of these medications has been limited by potential side effects and, therefore, may not be safe therapeutic options for some premature infants, including those with renal impairment, severe intraventricular hemorrhage, and necrotizing enterocolitis. In recent years, there has been increasing evidence to support the use of acetaminophen for facilitating PDA closure in preterm infants.5 Intravenous acetaminophen has a wide therapeutic index, and its safety for use is well established. However, as with all medications, acetaminophen is not entirely without risk and has the potential adverse effect of hepatotoxicity.6 It is, therefore, important to identify the optimal duration of treatment and to avoid prolonged exposure to acetaminophen when it is not indicated. Treatment regimens for the use of acetaminophen for PDA closure vary with neonatal reference guides, recommending treatment for a three to seven- day course.2 There is a lack of information in the literature to support the optimal duration of treatment, three versus seven days, or how to identify those infants in which a longer course may be beneficial. In this study, we attempted to identify the optimal duration of treatment. The results of our study show that the beneficial effect of intravenous acetaminophen on PDA closure is established by three days. It is less likely to be effective if, by three days of treatment, there has been no change in the PDA size on the echocardiogram. We concluded that the optimal duration of treatment for a PDA with IV acetaminophen is three days. Although acetaminophen has a narrow spectrum of side effects, preterm babies should not have prolonged exposure to it when it is unnecessary.