Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure

Abstract

Finding the optimal pharmacological treatment of a patent ductus arteriosus (PDA) in preterm neonates remains challenging. There is a growing interest in paracetamol as a new drug for PDA closure. In this prospective observational cohort study, we evaluated the effectiveness of intravenous paracetamol in closing a PDA in very low birth weight infants with a hemodynamically significant PDA who either did not respond to ibuprofen or had a contraindication for ibuprofen. They received high-dose paracetamol therapy (15 mg/kg/6 h intravenous) for 3–7 days. Cardiac ultrasounds were performed before and 3 and 7 days after treatment. Thirty-three patients were included with a median gestational age of 251/7 weeks (IQR 1.66), a median birth weight of 750 g (IQR 327), and a median postnatal age of 14 days (IQR 12). Paracetamol was ineffective in 27/33 patients (82 %). Even more, after previous exposure to ibuprofen, this was even 100 %.Conclusion: In this study, paracetamol after ibuprofen treatment failure was not effective for PDA closure in VLBW infants. From the findings of this study, paracetamol treatment for PDA closure cannot be recommended for infants with a postnatal age >2 weeks. Earlier treatment with paracetamol for PDA might be more effective. What is known: • The ductus arteriosus fails to close after birth in 30 to 60 % of prematurely born neonates and is a significant cause of morbidity and mortality in these infants. • Paracetamol gained importance as an alternative drug in PDA closure. What is new: • Paracetamol for PDA closure after ibuprofen treatment failure was not effective in VLBW infants. • Effect of paracetamol on PDA closure was observed when given as primary treatment.

Acetaminophen for Patent Ductus Arteriosus in Extremely Low-Birth-Weight Neonates

“…Notable exceptions include recent reports of acetaminophen use in extremely premature neonates treated at a late postnatal age. 17,18,21,23 Findings in these reports correlate well with our study, demonstrating a low rate of complete ductal closure, but a high rate of clinical constriction requiring no further intervention. These findings highlight the utility of a composite endpoint representing clinical efficacy (absence of the need for further PDA therapy) as opposed to the disease-oriented outcome of PDA closure on echocardiogram.…”

“…The use of acetaminophen to facilitate ductal closure in this population is supported by numerous observational studies. 9,[17][18][19][20][21][22] Similarly to the randomized controlled trials, most neonates in these reports were more mature than our study population and most acetaminophen courses were initiated within the first week of life. Notable exceptions include recent reports of acetaminophen use in extremely premature neonates treated at a late postnatal age.…”

The strategy of paracetamol (acetaminophen) use in closing patent ductus arteriosus in premature neonates.

“…The lowest success rate of PDA closure with paracetamol of 18.18 % was reported by. Roofthooft DW et al (25) with the studied infants had the lowest gestational age (23-26 weeks) as compared to the other series and very close success rates of 20% and 27.77 % were reported by Roofthooft DW et al (26) and EL-Khuffash A et al (24) with very similar range of gestational age for the studied sample ranging between 23-27.9 weeks . Nearly all of those infants were given I.V paracetamol in a dose of 15 mg/kg/6 h for 3-8 days depending on the results of their echocardiographic evaluation during the treatment course.…”

“…A total number of 13 case series have been evaluated (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). The lowest success rate of PDA closure with paracetamol of 18.18 % was reported by.…”

Efficacy and Safety of Paracetamol for Patent Ductus Arteriosus Closure in Preterm Infants: An Updated Systematic Review and Meta-Analysis

“…The overall closure rate of our study was slightly higher than that reported by El-Mashad et al (24), probably because of the higher weights of the infants with a higher mean gestational age after the merger. Higher prostaglandin receptor expression in the PDA wall demonstrated a lesser response to COX inhibition in young premature infants (45). In addition, a longer average treatment time after the merger may have led to a higher closure rate.…”