Use of paracetamol for the treatment of patent ductus arteriosus in premature Newborns: A systematic review

Authors

DOI:

https://doi.org/10.33448/rsd-v11i14.36002

Keywords:

Patent ductus arteriosus; Premature infant; Drug therapy; Acetaminophen.

Abstract

Objective: Patent ductus arteriosus is associated with multiple complications and high neonatal mortality. This study aimed to evaluate the efficacy and benefits of paracetamol compared to ibuprofen and indomethacin, non-steroidal anti-inflammatory drugs usually used to close the ductus arteriosus in premature newborns. Data source: We searched the PubMed, SciELO, Lilacs, Bireme, ClinicalTrials.gov and Embase databases for articles published between January 2005 and December 2020. The descriptors used were: premature newborn, patent ductus arteriosus, pharmacotherapy, closure and paracetamol / acetaminophen. The quality of the articles was evaluated by the classification of the Oxford Centre for Evidence based Medicine. Data synthesis: The efficacy of paracetamol is comparable to that of ibuprofen and indomethacin, and it is associated with lower rates of gastrointestinal and intracerebral hemorrhage, spontaneous intestinal perforation, thrombocytopenia, hepatic and renal intolerance, and lower serum values of urea, creatinine, and bilirubin. Furthermore, it is more advantageous than placebo or nonintervention and may be the best option in cases with contraindications for other drugs. Gestational age and birth weight were factors that influenced the efficacy of paracetamol and showed reduced efficacy in extremely premature newborns with extremely low and very low birth weights. Conclusions: Other clinical and prospective studies are needed to support the indication of paracetamol in patent ductus arteriosus. However, this drug proves to be a promising pharmacological alternative, having similar efficacy to classic non-steroidal anti-inflammatory drugs, with fewer adverse effects.

References

Aikio, O., Juujärvi, S., Saarela, T., & Hallman, M. (2020). Simultaneous paracetamol may promote ibuprofen-induced closure of ductus arteriosus. European journal of clinical pharmacology, 76(8), 1193–1195. https://doi.org/10.1007/s00228-020-02884-2

Al-lawama, M., Alammori, I., Abdelghani, T. & Badran, E. (2017). Oral paracetamol versus oral ibuprofen for treatment of patent ductus arteriosus. Journal of International Medical Research, 46(2), 811-818. doi:10.1177/0300060517722698

Asadpour, N., Harandi P., Hamidi, M., Malek, M.A. & Malekpour-Tehrani, A. (2018). Comparison of the effect of oral acetaminophen and ibuprofen on patent ductus arteriosus closure in premature infants referred to hajar hospital in Shahrekord in 2016-2017. Journal of Clinical Neonatology, 4(24), 224-230. doi: 10.4103/jcn.JCN_47_18

Azevedo, L.F. & Sousa-Pinto, B. (2019). Avaliação Crítica de uma Revisão Sistemática e Meta- Análise: Da Definição da Questão de Investigação à Pesquisa de Estudos Primários. Revista Da Sociedade Portuguesa De Anestesiologia, 28(1), 53–56.

Babaei, H., Nemati, R. & Daryoshi, H. (2018). Closure of patent ductus arteriosus with oral acetaminophen in preterm neonates: A randomized trial. Biomedical Research and Therapy. (2), 2034–44. doi: 10.15419/bmrat.v5i02.418

Bagheri, M.M., Niknafs P., Sabsevari, F., Torabi, M.H., Bijari, B.B., Noroozi, E. & Mossavi H. (2016). Comparison of oral acetaminophen versus ibuprofen in premature infants with patent ductus arteriosus. Iranian Journal of Pediatrics. 26(4), e3975. doi: 10.5812/ijp.3975.

Balachander, B., Mondal, N., Bhat, V., Adhisivam, B., Kumar, M., Satheesh S. & Thulasingam M. (2020). Comparison of efficacy of oral paracetamol versus ibuprofen for PDA closure in preterms–a prospective randomized clinical trial. Journal of Maternal-Fetal and Neonatal Medicine, 33(9), 1587–92. doi: 10.1080/14767058.2018.1525354.

Benitz, W. E., & Bhombal, S. (2017). The use of non-steroidal anti-inflammatory drugs for patent ductus arteriosus closure in preterm infants. Seminars in fetal & neonatal medicine, 22(5), 302–307. https://doi.org/10.1016/j.siny.2017.07.004

Buck, M.L. (2018). Update on the use of Acetaminophen for Patent Ductus Arteriosus Closure. Pediatric Pharmacotherapy, 24(5). https://www.semanticscholar.org/paper/Number-5-May-2018-Update-on-the-Use-of-for-Patent-Buck/84cd2e601ab65fd0c1af34cfcfff4e0c2dcfde76

Cakir, U., Tayman, C., Karacaglar, N.B., Beser, E., Ceran, B. & Unsal, H. (2021). Comparison of the effect of continuous and standard intermittent bolus paracetamol infusion on patent ductus arteriosus. European Journal of Pediatrics, 180(2), 433–40. doi: 10.1007/s00431-020-03822-1

Capuruçu, C. & Mota, C. (2014). Patent Ductus Arteriosus in Preterm Infant: review of diagnosis and management. Nascer e Crescer. 23(4), 201-206. http://www.scielo.mec.pt/scielo.php?script=sci_arttext&pid=S0872-07542014000700005&lng=pt

Dang, D., Wang D., Zhang, C., Zhou, W., Zhou, Q. & Wu, H. (2013). Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: a randomized controlled trial. PloS one, 8(11). doi: 10.1371/journal.pone.0077888

Dani, C., Lista, G., Bianchi, S., Mosca, F., Schena, F., Ramenghi, L., Zecca, E., Vento, G., Poggi, C., Leonardi, V., Minghetti, D., Rosignoli, M.T., Calisti, F., Comandini, A., Cattaneo, A. & Lipone, P. (2021). Intravenous paracetamol in comparison with ibuprofen for the treatment of patent ductus arteriosus in preterm infants: a randomized controlled trial. European Journal of Pediatrics, 180(3), 807–16. doi: 10.1007/s00431-020-03780-8

Dash, S.K., Kabra, N.S., Avasthi, B.S., Sharma, S.R., Padhi, P. & Ahmed, J. (2015). Enteral paracetamol or intravenous indomethacin for closure of patent ductus arteriosus in preterm neonates: A randomized controlled trial. Indian Journal of Pediatrics, 52(7), 573-578. doi: 10.1007/s13312-015-0677-z

Davidson, J. M., Ferguson, J., Ivey, E., Philip, R., Weems, M. F., & Talati, A. J. (2021). A randomized trial of intravenous acetaminophen versus indomethacin for treatment of hemodynamically significant PDAs in VLBW infants. Journal of perinatology: official journal of the California Perinatal Association, 41(1), 93–99. https://doi.org/10.1038/s41372-020-0694-1

Donato, H., & Donato, M. (2019). Etapas na Condução de uma Revisão Sistemática. Acta Médica Portuguesa, 32(3), 227-35. doi: 10.20344/amp.11923

Echtler, K., Stark, K., Lorenz, M., Kerstan, S., Walch, A., Jennen, L., Rudelius, M., Seidl, S., Kremmer, E., Emambokus, N. R., von Bruehl, M. L., Frampton, J., Isermann, B., Genzel-Boroviczény, O., Schreiber, C., Mehilli, J., Kastrati, A., Schwaiger, M., Shivdasani, R. A., & Massberg, S. (2010). Platelets contribute to postnatal occlusion of the ductus arteriosus. Nature medicine, 16(1), 75–82. https://doi.org/10.1038/nm.2060

El-Farrash, R.A., El Shimy, M.S., El-Sakka, A.S., Ahmed, M.G. & Abdel-Moez, D.G. (2018). Efficacy and safety of oral paracetamol versus oral ibuprofen for closure of patent ductus arteriosus in preterm infants: a randomized controlled trial. The Journal of Maternal-Fetal & Neonatal Medicine, 32(21), 3647-3654. doi: 10.1080/14767058.2018.1470235

El-Khuffash A., James A.T., Cleary A., Semberova J., Franklin O. & Miletin J. Late medical therapy of patent ductus arteriosus using intravenous paracetamol. Arch Dis Child-Fetal. 100(3), 253-256. doi: 10.1136/archdischild-2014-307930

El-Mashad, A.E.R., El-Mahdy, H., El Amrousy, D. & Elgendy, M. (2016). Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates. European Journal of Pediatrics, 176(2), 233-240. doi: 10.1007/s00431-016-2830-7

El-Khuffash, A., Jain A., Corcoran, D., Shah, P.S., Hooper, C.W., Brown, N., Poole, S.D., Shelton, E.L., Milne, G.L., Reese, J. & McNamara P.J. (2014). Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies. Pediatric Research, 76(3), 238-244. doi: 10.1038/pr.2014.82

Ercole, F.F., Melo, L.S.D., & Alcoforado, C.L.G.C. (2014). Revisão integrativa versus revisão sistemática. Revista Mineira de Enfermagem, 18(1), 9-12. doi: 10.5935/1415-2762.20140001

Ferguson, J.M. Pharmacotherapy for patent ductus arteriosus closure (2018). Congenital Heart Disease, 14(1), 52-56. doi: 10.1111/chd.12715

Ghaderian, M., Barekatain, B. & Dardashty, A.B. (2019). Comparison of oral acetaminophen with oral ibuprofen on closure of symptomatic patent ductus arteriosus in preterm neonates. Journal of Research in Medical Sciences, 24(96). doi: 10.4103/jrms.JRMS_197_19

Guimarães, A.F.M., Araújo, F.D.R., Meira, Z.M.A., Tonelli, H.A.F., Duarte, G.G., Ribeiro, L.C., Rezende, G.Q.M. & Castilho, S.R.T. (2019). Acetaminophen in low doses for closure of the ductus arteriosus of the premature. Annals of Pediatric Cardiology, 12(2), 97-102. doi: 10.4103/apc.APC_42_18

Hammerman, C., Bin-Nun, A., Markovitch, E., Schimmel, M.S., Kaplan, M. & Fink, D. (2011). Ductal closure with paracetamol: a surprising new approach to patent ductus arteriosus treatment. Pediatrics, 128(6), 1618-1621. doi: 10.1542/peds.2011-0359

Hamrick, S.E.G. & Hansmann, G. (2010). Patent ductus arteriosus of the preterm infant. Pediatrics, 125(5), 1020-1030. doi: 10.1542/peds.2009-3506

Härkin, P., Härmä A., Aikio O., Valkama M., Leskinen M., Saarela T. & Hallman M. (2016). Paracetamol accelerates closure of the ductus arteriosus after premature birth: a randomized trial. Pediatrics, 177, 72-77. doi: 10.1016/j.jpeds.2016.04.066

Hochwald, O., Mainzer, G., Borenstein-Levin, L., Jubran, H., Dinur, G., Zucker, M., Mor, M., Khoury, A., & Kugelman, A. (2018). Adding Paracetamol to Ibuprofen for the Treatment of Patent Ductus Arteriosus in Preterm Infants: A Double-Blind, Randomized, Placebo-Controlled Pilot Study. American journal of perinatology, 35(13), 1319–1325. https://doi.org/10.1055/s-0038-1653946

Higgins, J.P.T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M.J., & Welch, V.A (2021). Cochrane Handbook for Systematic Reviews of Interventions version 6.2. Cochrane. www.training.cochrane.org/handbook.

Higgins, J.P., Thomas, J. & Chandler, J. (2019). Cochrane Database Systematic Review (2a ed.) Nova Jersey: Editora Jonn Wiley & Sons.

Iacobelli, S., Lorrain, S., Gouyon, B., Gambacorta, S., Laforgia, N., Gouyon, J. B., & Bonsante, F. (2020). Drug exposure for PDA closure in France: a prospective, cohort-based, analysis. European journal of clinical pharmacology, 76(12), 1765–1772. https://doi.org/10.1007/s00228-020-02974-1

Juujärvi, S., Saarela, T., Hallman, M., & Aikio, O. (2018). Intravenous paracetamol was associated with closure of the ductus arteriosus in extremely premature infants. Acta paediatrica: nurturing the child, 107(4), 605–610. https://doi.org/10.1111/apa.14137

Karabulut, B. & Paytoncu, S. Efficacy and Safety of Oral Paracetamol vs (2019). Oral Ibuprofen in the Treatment of Symptomatic Patent Ductus Arteriosus in Premature Infants. Pediatric Drugs, 21(2), 113-121. doi: 10.1007/s40272-019-00331-z

Keller, R. L., Tacy, T. A., Fields, S., Ofenstein, J. P., Aranda, J. V., & Clyman, R. I. (2005). Combined treatment with a nonselective nitric oxide synthase inhibitor (l-NMMA) and indomethacin increases ductus constriction in extremely premature newborns. Pediatric research, 58(6), 1216–1221. https://doi.org/10.1203/01.pdr.0000183659.20335.12

Kimani, S., Surak, A., Miller, M., & Bhattacharya, S. (2020). Use of combination therapy with acetaminophen and ibuprofen for closure of the patent ductus arteriosus in preterm neonates. Pediatrics & Child Health, 26(4), 177-183. https://doi.org/10.1093/pch/pxaa057

King, R., Colon, M., Stanfel, L., & Tauber, K. A. (2020). Late Acetaminophen Therapy for Patent Ductus Arteriosus in the Preterm Neonate. The journal of pediatric pharmacology and therapeutics, 25(6), 507–513. https://doi.org/10.5863/1551-6776-25.6.507

Kumar, A., Gosavi, R.S., Sundaram, V., Oleti, T.P., Krishnan, A., Kiran, S., Kumar, J., Murki, S., SundRm, M., Saini, S.S. & Dutta, S. (2020). Oral Paracetamol vs Oral Ibuprofen in Patent Ductus Arteriosus: A Randomized, Controlled, Noninferiority Trial. Journal of Pediatrics. 222, 79-84. doi: 10.1016/j.jpeds.2020.01.058

Luecke, C.M., Liviskie, C.J., Zeller, B.N., Vesoulis, Z.A. & McPherson, C. (2017). Acetaminophen for patent ductus arteriosus in extremely low-birth-weight neonates. The Journal of Pediatric Pharmacology and Therapeutics, 22(6), 461-466. doi: 10.5863/1551-6776-22.6.461

Lu, J., Li, Q., Zhu, L., Chen, C. & Li, Z. (2019) Oral ibuprofen is superior to oral paracetamol for patent ductus arteriosus in very low and extremely low birth weight infants. Medicine (Baltimore), 98(31), 16689. doi: 10.1097/MD.0000000000016689

Locali, R.F., Matsuoka, P.K., Gabriel, E.A., Bertini Júnior, A., La Rotta, C.A., Catani, R., Carvalho, A.C.C. & Buffolo, E. (2008). Patent Ductus Arteriosus Treatment in the Premature Newborn: Clinical and Surgical Analisys. Arquivos Brasileiros de Cardiologia, 90(5), 345-349. doi: 10.1590/S0066-782X2008000500007

Meena, V., Meena, D., Rathore, P., Chaudhary, S. & Soni, J. (2020). Comparison of the efficacy and safety of indomethacin, ibuprofen, and paracetamol in the closure of patent ductus arteriosus in preterm neonates – A randomized controlled trial. Annals Pediatric Cardiology, 13(2), 130-135. doi: 10.4103/apc.APC_115_19

Morandi, M.I.W.M. & Camargo, L.F.R. (2015). Revisão sistemática da literatura. In: Dresch, A., Lacerda, D.P., & Antunes, J.R., JAV. Design sciencie research: método e pesquisa para avanço da ciência e da tecnologia. Porto Alegre: Bookman.

Mukherjee, A., Jadhav, V., & Gupta, A. (2020). Off-label use of paracetamol in managing patent ductus arteriosus across neonatal intensive care units in the UK. Archives of Disease in Childhood - Fetal and Neonatal Edition, 106(1), 113–114. https://doi.org/10.1136/archdischild-2020-320207

Oboodi, R., Najib, K. S., Amoozgar, H., Pourarian, S., Moghtaderi, M., Mehdizadegan, N., & Sabzevari, F. (2020). Positive tendency toward synchronous use of acetaminophen and ibuprofen in treating patients with patent ductus arteriosus. Patent duktus arteriyozuslu hastaların tedavisinde eş zamanlı asetaminofen ve ibuprofen kullanımına yönelik artmış eğilim. Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir, 48(6), 605–612. https://doi.org/10.5543/tkda.2020.03902

Ohlsson, A., Shah, P.S. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database Syst. Rev [internet], [S.I.] n. 1, 27 de Jan, 2020 [acesso em: 20 de maio, 2020]. doi: 10.1002/14651858.CD010061.pub3

Okulu, E., Erdeve, O., Arslan, Z., Demirel, N., Kaya, H., Gokce, I. K., Ertugrul, S., Cetinkaya, M., Buyukkale, G., Ozlu, F., Simsek, H., Celik, Y., Ozkan, H., Köksal, N., Akcan, B., Turkmen, M., Celik, K., Armangil, D., Bulbul, A., Tekgunduz, K. S., Turkish Neonatal Society INTERPDA Study Group (2020). An Observational, Prospective, Multicenter, Registry-Based Cohort Study Comparing Conservative and Medical Management for Patent Ductus Arteriosus. Frontiers in pediatrics, 8, 434. https://doi.org/10.3389/fped.2020.00434

Oncel, M.Y., Yurttutan, S., Erdeve, O., Uras, N., Altug, N., Oguz, S.S. & Canpolat, F.E. (2014). Oral paracetamol versus oral ibuprofen in the management of patent ductus arteriosus in preterm infants: a randomized controlled trial. The Journal of Pediatrics, 164(3), 510-514. doi: 10.1016/j.jpeds.2013.11.008

Oncel, M. Y., & Erdeve, O. (2016). Oral medications regarding their safety and efficacy in the management of patent ductus arteriosus. World journal of clinical pediatrics, 5(1), 75–81. https://doi.org/10.5409/wjcp.v5.i1.75

Oshima, A., Matsumura, S., Iwatani, A., Morita, M., Fujinuma, S., Motojima, Y., Tanaka, K., Masutani, S., Kabe, K., Ueda, K. & Namba, F. (2020). Safety and Feasibility of Intravenous Paracetamol for Patent Ductus Arteriosus in Indomethacin-/Ibuprofen-Resistant or -Contraindicated Preterm Infants: A Case Series. American Journal of Perinatology Reports, 10(1), 49-53. doi: 10.1055/s-0040-1702945

Pharande, P., Watson, H., Tan, K. & Sehgal, A. (2018). Oral paracetamol for patent ductus arteriosus rescue closure. Pediatric. Cardiology, 39(1), 183-190. doi: 10.1007/s00246-017-1745-z

Prado, R., Camacho, J.C.A., Paredes, R.A.M., Coutinho, F.M., Ribeiro, M.A.L. & Riera, A.R.P. (2019). Preterm newborns undergoing selective correction surgery of the patent ductus arteriosus: is there still space for these procedures?. Journal of Human Growth and Development, 29(3), 325-337. doi: 10.7322/jhgd.v29.9528

Roofthooft, D. W., Van Beynum, I. M., de Klerk, J. C., van Dijk, M., van den Anker, J. N., Reiss, I. K., Tibboel, D., & Simons, S. H. (2015). Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure. European journal of pediatrics, 174(11), 1433–1440. https://doi.org/10.1007/s00431-015-2541-5

Sallmon, H., Koehne, P. & Hansmann, G. (2016). Recent advances in the treatment of preterm newborn infants with patent ductus arteriosus. Clinics Perinatology, 43(1), 113-129. doi: 10.1016/j.clp.2015.11.008

Staunton, D., & El-Khuffash, A. (2020). The unintended consequences of acetaminophen use for ductal closure in premature infants. Pediatric research, 87(7), 1153–1154. https://doi.org/10.1038/s41390-020-0864-z

Terrin, G., Conte, F., Oncel, M.Y., Scipione, A., McNamara, P.J., Simons, S., Sinha, R., Erdeve, O., Tekgunduz, K.S., Dogan, M., Kessel, I., Hammerman, C. & Nadir, E. (2015). Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis. Archives of Disease in Childhood, 101(2), 127-136. doi: 10.1136/archdischild-2014-307312

Terrin, G., Conte, F., Scipione, A., Bacchio, E., Conti, M. G., Ferro, R., Ventriglia, F., & De Curtis, M. (2014). Efficacy of paracetamol for the treatment of patent ductus arteriosus in preterm neonates. Italian journal of pediatrics, 40(1), 21. https://doi.org/10.1186/1824-7288-40-21

Tauber, K.A., King, R. & Colon, M. (2020). Intravenous acetaminophen vs intravenous ibuprofen to close a patent ductus arteriosus closure: A pilot randomized controlled trial. Health Science Reports, 3(3), 1-5. doi: 10.1002/hsr2.183

Tekgündüz, K.Ş., Ceviz, N., Caner, I,, Olgun, H., Demirelli, Y., Yolcu, C., Sahin, I.O. & Kara, M. (2014). Intravenous paracetamol with a lower dose is also effective for the treatment of patent ductus arteriosus in pre-term infants. Cardiology in the Young, 25(6), 1060-1064. doi: 10.1017/S1047951114001577

Vaidya, R., Knee, A., Paris, Y., & Singh, R. (2021). Predictors of successful patent ductus arteriosus closure with acetaminophen in preterm infants. Journal of perinatology : official journal of the California Perinatal Association, 41(5), 998–1006. https://doi.org/10.1038/s41372-020-00803-y

Valerio, E., Valente, M.R., Salvadori, S., Frigo, A.C., Baraldi, E. & Lago, P. (2016). Intravenous paracetamol for PDA closure in the preterm: a single-center experience. European Journal of Pediatrics, 175(7), 953-966. doi: 10.1007/s00431-016-2731-9

Yang, B., Gao, X., Ren, Y., Wang, Y. & Zhang, Q. (2016). Oral paracetamol vs. oral ibuprofen in the treatment of symptomatic patent ductus arteriosus in premature infants: A randomized controlled trial. Experimental and Therapeutic Medicine, 12(4), 2531–36. doi: 10.3892/etm.2016.3676

Yurttutan, S., Oncel, M. Y., Arayicı, S., Uras, N., Altug, N., Erdeve, O., & Dilmen, U. (2013). A different first-choice drug in the medical management of patent ductus arteriosus: oral paracetamol. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 26(8), 825–827. https://doi.org/10.3109/14767058.2012.755162

Published

21/10/2022

How to Cite

RESENDE, M. D. C. de .; REIS, S. M. dos .; MINUCCI, G. S.; HERNANDES, B. L. T.; VASCONCELLOS, R. C.; LAMOUNIER, J. A. . Use of paracetamol for the treatment of patent ductus arteriosus in premature Newborns: A systematic review. Research, Society and Development, [S. l.], v. 11, n. 14, p. e128111436002, 2022. DOI: 10.33448/rsd-v11i14.36002. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/36002. Acesso em: 25 apr. 2024.

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Review Article