Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure.
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 25(1/7) 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 %.


CONCLUSIONS
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.
Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia Children's Hospital, Room Sp2463, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. d.roofthooft@erasmusmc.nl.
Daniëlla W E
DW
Roofthooft
Department of Pediatric Cardiology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. i.vanbeynum@erasmusmc.nl.
Ingrid M
IM
van Beynum
Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia Children's Hospital, Room Sp2463, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. j.deklerk@erasmusmc.nl.
Johan C A
JC
de Klerk
Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia Children's Hospital, Room Sp2463, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. m.vandijk.3@erasmusmc.nl.|Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. m.vandijk.3@erasmusmc.nl.
Monique
M
van Dijk
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. jvandena@cnmc.org.|Department of Pediatric Pharmacology, University Children's Hospital, Basel, Switzerland. jvandena@cnmc.org.
John N
JN
van den Anker
Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia Children's Hospital, Room Sp2463, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. i.reiss@erasmusmc.nl.
Irwin K M
IK
Reiss
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. d.tibboel@erasmusmc.nl.
Dick
D
Tibboel
Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia Children's Hospital, Room Sp2463, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. s.simons@erasmusmc.nl.
Sinno H P
SH
Simons
D000082:Acetaminophen / Q000008:administration & dosage / Q000627:therapeutic use*; D061605:Administration, Intravenous; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015331:Cohort Studies; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use*; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D008297:Male; D011446:Prospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; D007052:Ibuprofen
Ibuprofen contraindication; Ibuprofen treatment failure; Paracetamol; Patent ductus arteriosus; VLBW infants