A Comparison between the Safety and Efficacy of IV Paracetamol (Acetaminophen) and IV Ibuprofen in Treating Premature Neonates with Patent Ductus Arteriosus

Document Type: Original article


1 Department of Pediatric disease, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

2 Department of Public Health, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran


Background: Patent Ductus Arteriosus (PDA) is a common congenital heart disease (CHD) that can lead to infant mortality. This study compared the impact of two treatment approaches (i.e. intravenous acetaminophen and ibuprofen) on the closure rate of PDA.
Methods: In this randomized controlled trial, 30 infants with PDA were divided into two groups based on the applied treatment approaches (IV acetaminophen and IV ibuprofen). The two groups were compared with each other in terms of primary outcomes including post-intervention PDA grades, length of stay, duration of mechanical ventilation, and patient outcomes (i.e. death or discharge).
Results: Based on the results, none of the participants had a moderate or large-sized PDA after the intervention. The post-intervention PDA closure rates in the acetaminophen and ibuprofen groups were 87.5% and 92.1%, respectively (p = 0.626). The mortality rate in the acetaminophen and ibuprofen groups were 12.5% and 14.3%, respectively (p = 0.886). In addition, no significant difference was found between the two groups in terms of the length of stay and duration of mechanical ventilation (P-value > 0.05).
Conclusion: The results showed that the efficacy of IV acetaminophen was similar to that of IV ibuprofen in the treatment of PDA. However, authors recommend conducting randomized multicenter clinical trials with larger sample sizes to confirm the replacement of IV ibuprofen by acetaminophen.


1. Bernstein D. The cardiovascular system. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF. Nelson Textbook of Pediatrics. 20th ed. Volume 2. Philadelphia: Elsevier, Saunders; 2016. p. 2197-202.
2. Katzung BG, Anthony J, editors. Basic & Clinical Pharmacology, A Lange Medical Book. 13th ed. New York, USA: McGraw-Hill Education; 2015. p. 618-34.
3. Clyman RI. Patent ductus arteriosus in the preterm infant. In: Avery’s Diseases of the Newborn. Gleason CA and Devaskar S (eds.). 9th edition. Philadelphia, PA: Saunders; 2012. p.751-61. 
4. Huang X, Wang F, Wang K. Paracetamol versus ibuprofen for the treatment of patent ductus arteriosus in preterm neonates:a meta analysis of randomized controlled trials. J Matern Fetal Neonatal Med 2018 Aug;31(16):2216-22.
5. Clyman RI. Mechanisms regulating the ductus arteriosus. Biol Neonate 2006;89(4):330-5. https://www.ncbi.nlm.nih.gov/pubmed/16770073
6. Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev 2010;(4):CD003481. https://www.ncbi.nlm.nih.gov/pubmed/23633310
7. Aikio O, Härkin P, Saarela T, Hallman M. Early paracetamol treatment associated with lowered risk persistent ductus arteriosus in very preterm infants. J Matern Fetal Neonatal Med 2014;27(12):1252-6. https://www.ncbi.nlm.nih.gov/pubmed/24111688
8. Benitz WE. The Cardiovascular System. Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff & Martin’s Neonatal Medicine-Diseases of the Fetus and Infant. 10th edition. Volume 2. Philadelphia: Elsevier Saunders; 2015. p. 1223-9. 
9. Allegaert K, Anderson B, Simons S, van Overmeire B. Paracetamol to induce ductus arteriosus closure: is it valid? Arch Dis Child 2013;98(6):462-6. https://www.ncbi.nlm.nih.gov/pubmed/23606713
10. Dani C, Poggi C, Mosca F, Schena F, Lista G, Ramenghi L,et al. Efficacy and safety of intravenous paracetamol in comparison to ibuprofen for the treatment of patent ductus arteriosus in preterm infants: study protocol for a randomized control trial. Trials 2016 Apr 2;17:182. https://www.ncbi.nlm.nih.gov/pubmed/27038924
11. Hammerman C, Bin-Nun A, Markovitch E, Schimmel MS, Kaplan Fink D. Ductal closure with paracetamol: a surprising new approach to patent ductus arteriosus treatment. Pediatrics 2011;128(6):1618-21. https://www.ncbi.nlm.nih.gov/pubmed/22065264
12. Oncel MY, Yurttutan S, Uras N, Altug N, Ozdemir R, Ekmen S, et al. An alternative drug (paracetamol) in the management of patent ductus arteriosus in ibuprofen-resistant or contraindicated preterm infants, Arch Dis Child Fetal Neonatal Ed 2013;98(1):F94. https://www.ncbi.nlm.nih.gov/pubmed/22611117
13. Dang D, Wang D, Zhang C, Zhou W, Zhou Q, Wu H. Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: A randomized controlled trial. PLoS One 2013 Nov 4;8(11):e77888. https://www.ncbi.nlm.nih.gov/pubmed/24223740
14. Sinha R, Negi V, Dalal SS. An interesting observation of PDA closure with oral paracetamol in preterm neonates. J ClinNeonatol 2013 Jan;2(1):30-2. https://www.ncbi.nlm.nih.gov/pubmed/24027742
15. Huang X, Wang F, Wang K. Paracetamol versus ibuprofen for the treatment of patent ductus arteriosus in preterm neonates: a meta-analysis of randomized controlled trials. J Matern Fetal Neonatal Med 2018 Aug;31(16):2216-22. https://www.ncbi.nlm.nih.gov/pubmed/28720053
16. Ratcliffe SJ, Sherlock LG, Wright CJ. Oral paracetamol or oral ibuprofen to close the ductus arteriosus: both ‘work’, but do we know when to use them? Acta Paediatrica, 2017 Sep;106(9):1539.  https://www.ncbi.nlm.nih.gov/pubmed/28370568
17. Rolland A, Shankar-Aguilera S, Diomande D, Zupan-Simunek V, Boileau P. Natural evolution of patent ductus arteriosus in the extremely preterm infant. Arch Dis Child Fetal Neonatal Ed 2015;100(1):F55-8. https://www.ncbi.nlm.nih.gov/pubmed/25169243
18. Yang B, Gao X, Ren Y, Wang Y, Zhang Q. Oral paracetamol vs. oral ibuprofen in the treatment of symptomatic patent ductus arteriosus in premature infants: A randomized controlled trial. Exp Ther Med 2016 Oct;12(4):2531-6.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038853/
19. Hamrick SE, Hansmann G. Patent ductus arteriosus of the preterm infant. Pediatrics 2010 May;125(5):1020-30.  https://www.ncbi.nlm.nih.gov/pubmed/20421261
20. Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci USA 2002 Oct 15;99(21):13926-31. https://www.ncbi.nlm.nih.gov/pubmed/12242329
21. Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF. The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings. Inflammopharmacology 2013 Jun;21(3):201-32.  https://www.ncbi.nlm.nih.gov/pubmed/23719833