Ductal Closure With Paracetamol: A Surprising New Approach to Patent Ductus Arteriosus Treatment

Abstract

Standard pharmacologic closure of the patent ductus arteriosus currently involves the administration of 1 of 2 cyclooxygenase inhibitors: either indomethacin or ibuprofen. However, both of these drugs can be associated with potentially significant adverse effects. We present here the cases of 5 preterm infants (gestational age: 26-32 weeks; postnatal age: 3-35 days) with large, hemodynamically significant patent ductus arteriosus who had either failed or had contraindications to ibuprofen therapy. Each of these infants was treated with off-label oral paracetamol (15 mg/kg per dose every 6 hours). Ductal closure was achieved within 48 hours in all the treated infants. No toxicity was observed.

Eficacia del paracetamol intravenoso para el cierre del conducto arterioso en recién nacidos prematuros

“…Esto permite que la inhibición de la peroxidasa sea efectiva en condiciones en que la inhibición de la ciclooxigenasa es menos activa. 16,17 Estas observaciones estimularon en los autores el interés por responder a la siguiente interrogante: ¿cuál es la eficacia y seguridad del paracetamol intravenoso para el cierre del conducto arterioso hemodinámicamente significativo?, planteándonos como objetivo evaluar estos parámetros. Nuestra intención fue confirmar que el paracetamol es eficaz y seguro para el cierre del conducto arterioso.…”

“…3,9,16,17 En nueve (75%) de éstos se identificó por ecocardiografía persistencia del conducto arterioso hemodinámicamente significativo. De éstos 44% pesaban menos de 1 500 gramos.…”

“…La literatura recomienda que en general se solicite ecocardiografía a los recién nacidos prematuros entre las 48 y 72 horas de vida, cuando teóricamente se ha producido el cierre funcional del conducto arterioso. 16,17,19 El diagnóstico ecocardiográfico, y por ende el inicio de tratamiento en estos pacientes se retrasó por circunstancias ajenas a los autores, ya que en todos fue solicitado al tercer día de vida.…”

IV Paracetamol for closure of patent ductus arteriosus in preterm neonates admitted to a tertiary care centre

“…Hammerman et al reported the first case series of preterm infants and observed that oral paracetamol for a period of 3 days at a dose of 60 mg/kg/qid was effective in closing PDA. 25 Oncel et al reported the results of ramdomised contolled trial in preterm infants treated with oral paracetamol in whom closue of PDA was acheieved with no side effects. 29 According to Terrin et al a case series of neonates with hs-PDA treated with paracetamol because of contraindication to ibuprofen or indomethacin, ductal closure was noted in 70% of neonates with no adverse reactions likewise in our study ductal closure was noted in 75% neonates with IV paracetamol.…”

“…23,24 Recent studies have shown that paracetamol, a common antipyretic and analgesic drug can be used as an alternative to treat PDA in preterm with good efficacy and less side effects. 25 The prostaglandin-H2 synthetase (PGHS) enzyme system has two active sites: the cyclo-oxygenase (COX) and peroxidase (POX) sites. PGHS produces circulating prostaglandins (PG) that help to regulate the ductal patency.…”