Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
Users Online: 380
About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Advertise Login 

 Table of Contents  
Year : 2013  |  Volume : 2  |  Issue : 1  |  Page : 30-32

An interesting observation of PDA closure with oral paracetamol in preterm neonates

1 Department of Pediatrics, 167 Military Hospital, Pathankot, Punjab, India
2 Department of Pediatrics, Army Hospital (R and R), New Delhi, India
3 Department of Pediatrics, Command Hospital Air Force, Bangalore, Karnataka, India

Date of Web Publication20-Mar-2013

Correspondence Address:
Rahul Sinha
167 Military Hospital, Pathankot, Punjab
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2249-4847.109245

Rights and Permissions

Patent ductus arteriosus (PDA), in which there is a persistent communication between the descending thoracic aorta and the pulmonary artery that results from failure of normal physiologic closure of the fetal ductus, is one of the more common congenital heart defects in preterm neonates. The closure of PDA can be done with either Indomethacin or Brufen which are cyclooxygenase 1, 2 inhibitor; however these drugs are associated with side effects. We report an interesting findings of ductal closure in 10 preterm neonates (gestational age 27-33 wks) presenting with significant large PDA who had failed or had absolute contraindication with Brufen. These preterm neonates were treated with oral paracetamol in the dose of 15 mg/kg 8 hourly. The PDA closure was achieved within 48 h and there was no complication.

Keywords: Ductus, paracetamol, brufen, preterm

How to cite this article:
Sinha R, Negi V, Dalal S S. An interesting observation of PDA closure with oral paracetamol in preterm neonates. J Clin Neonatol 2013;2:30-2

How to cite this URL:
Sinha R, Negi V, Dalal S S. An interesting observation of PDA closure with oral paracetamol in preterm neonates. J Clin Neonatol [serial online] 2013 [cited 2022 Jul 6];2:30-2. Available from: https://www.jcnonweb.com/text.asp?2013/2/1/30/109245

  Introduction Top

It was observational study for six months from November 2011 to April 2012. There were total of 96 NICU admissions. An ethical committee consent was taken to use oral paracetamol for patent ductus closure in preterm neonates with significant PDA who had contraindication for Brufen/Indomethacin use. [1] Also the parental consent was taken before the study. There were total of 18 preterm neonates who had significant PDA, out of these oral Brufen was given to eight preterm neonates and 10 were given oral Paracetamol as Brufen was contraindicated. We report 10 preterm neonates born at gestational age 27-33 weeks with birth weight range 800 grams to 1,400 grams admitted to our NICU. All these preterm neonates were diagnosed to have hemodynamically significant (features of congestive cardiac failure) PDA at 4-7 days of life. All these neonates had contraindication to Brufen/Indomethacin for ductal closure. Each of these neonates were given oral paracetamol in the dosage of 15 mg/kg 8 hourly for 48 h. These neonates were monitored for temperature changes before and 30 min after giving oral paracetamol and no significant temperature difference was noted. The ductal closure was achieved in all neonates by 48 h of administration. The ductal closure was confirmed with repeat echocardiography after 72 h of administration of oral paracetamol. These neonates did not suffer any complication related to paracetamol.

  Results Top

The results are referred in [Table 1].
Table 1: Gestational age, weight, paracetamol dosage and echocardiographic findings

Click here to view

  Discussion Top

Approximately, 70-80% of preterm neonates require pharmacologic and/or surgical intervention to close a hemodynamically significant patent ductus arteriosus (PDA). Indomethacin has been the pharmacologic treatment of choice and has also been used prophylactically in very premature neonates to prevent PDA. [2],[3] The drug, however, is associated with renal and gastrointestinal adverse effects. In July 2006, intravenous ibuprofen became available in the United States for treatment of hemodynamically significant PDA. The mechanism of action for both indomethacin and ibuprofen is through inhibition of prostaglandin synthesis, resulting in ductal constriction. Both drugs appear to be equally efficacious in closing echocardiographically confirmed PDA. Ibuprofen has demonstrated significantly less effects on cerebral, renal, and mesenteric blood flow in premature neonates when compared with indomethacin. [4],[5] A transient but significant increase in serum creatinine concentration, decrease in urine output, and increase in frequency of oliguria were observed with indomethacin when compared with ibuprofen. However, the rate of reopening of the ductus after pharmacologic closure and the need for rescue therapy were not different between the two drugs. In addition, no differences were noted in other outcomes such as frequency of intraventricular hemorrhage, necrotizing enterocolitis, or chronic lung disease, as well as in duration of mechanical ventilation and length of hospital stay. [4],[5]

The paracetamol also inhibits prostaglandin synthetase activity. Although its precise mechanism of action remains controversial, Paracetamol seems to act at the peroxidase segment of the enzyme. Peroxidase is activated at 10-fold-lower peroxide concentrations than is cyclooxygenase. [6],[7] Therefore, paracetamol-mediated inhibition is facilitated at reduced local peroxide concentrations (e.g., hypoxia). Theoretically, these differences would permit peroxidase inhibition to be optimally effective under conditions in which cyclooxygenase inhibition is less active or hypothetically, render it ideally suited for treatment in the PDA environment. The exact mechanism use of oral paracetamol in ductal closure has not been studied on large scale; however with this study it is evident that oral paracetamol is equally effective in ductal closure with no side effects which was there with Brufen/Indomethacin. However, a large randomized study is needed to validate this interesting observation.

  References Top

1.Hammerman C, Bin-Nun A, Markovitch E, Schimmel MS, Kaplan M, Fink D. Ductal closure with paracetamol: A surprising new approach to patent ductus arteriosus treatment. Pediatrics 2011;128:e1618-21.  Back to cited text no. 1
2.Vanhaesebrouck S, Zonnenberg I, Vandervoort P, Bruneel E, Van Hoestenberghe MR, Theyskens C. Conservative treatment for patent ductus arteriosus in the preterm. Arch Dis Child Fetal Neonatal Ed 2007;92:F244-7.  Back to cited text no. 2
3.Sekar KC, Corff KE. Treatment of patent ductus arteriosus: Indomethacin or ibuprofen? J Perinatol 2008;28:S60-2.  Back to cited text no. 3
4.Shah SS, Ohlsson A. Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev 2006;1:CD004213.  Back to cited text no. 4
5.Jones LJ, Craven PD, Attia J, Thakkinstian A, Wright I. Network meta-analysis of indomethacin versus ibuprofen versus placebo for PDA in preterm infants. Arch Dis Child Fetal Neonatal Ed 2011;96:F45-52.  Back to cited text no. 5
6.Grèen K, Drvota V, Vesterqvist O. Pronounced reduction of in vivo prostacyclin synthesis in humans by paracetamol. Prostaglandins 1989;37:311-5.  Back to cited text no. 6
7.Lucas R, Warner TD, Vojnovic I, Mitchell JA. Cellular mechanisms of acetaminophen: Role of cyclo-oxygenase. FASEB J 2005;19:635-7.  Back to cited text no. 7


  [Table 1]

This article has been cited by
1 Different approaches for patent ductus arteriosus in premature infants using acetaminophen
Aimann Surak, Amish Jain, Abbas Hyderi
World Journal of Pediatrics. 2022;
[Pubmed] | [DOI]
Clyde J. Wright
The Journal of Pediatrics. 2021;
[Pubmed] | [DOI]
3 Qual Deve Ser o Tratamento de Primeira Linha para o Fechamento de Persistência de Canal Arterial Hemodinamicamente Significativo em Bebês Prematuros?
Ufuk Cakir, Cuneyt Tayman
Arquivos Brasileiros de Cardiologia. 2021;
[Pubmed] | [DOI]
4 Paracetamol for closure of patent ductus arteriosus in preterm babies born before 32-week gestational age: academic unit experience
NagwaSabry Mahmoud,Hany Asklany
Journal of Clinical Neonatology. 2021; 10(2): 79
[Pubmed] | [DOI]
5 Oral Versus Intravenous Medications for Treatment of Patent Ductus Arteriosus in Preterm Neonates: A Cost-Saving Initiative
Robert Godin,Juan Carlos Rodriguez,Doron J. Kahn
The Journal of Pediatric Pharmacology and Therapeutics. 2021; 26(3): 291
[Pubmed] | [DOI]
6 Differences in Outcomes According to the Time of Patent Ductus Arteriosus Closure in Preterm Infants
Changhun Han,Ga Won Jeon
Neonatal Medicine. 2020; 27(3): 111
[Pubmed] | [DOI]
7 Paracetamol vs. Ibuprofen in Preterm Infants With Hemodynamically Significant Patent Ductus Arteriosus: A Non-inferiority Randomized Clinical Trial Protocol
Ana García-Robles,Ana Gimeno Navarro,María del Mar Serrano Martín,María José Párraga Quiles,Anna Parra Llorca,José Luis Poveda-Andrés,Máximo Vento Torres,Marta Aguar Carrascosa
Frontiers in Pediatrics. 2020; 8
[Pubmed] | [DOI]
8 Oral Paracetamol vs Oral Ibuprofen in Patent Ductus Arteriosus: A Randomized, Controlled, Noninferiority Trial
Ashutosh Kumar,Rahul Subhash Gosavi,Venkataseshan Sundaram,Tejo Pratap Oleti,Arun Krishnan,Sai Kiran,Jogender Kumar,Srinivas Murki,Mangalabharathi Sundaram,Shiv Sajan Saini,Sourabh Dutta
The Journal of Pediatrics. 2020;
[Pubmed] | [DOI]
9 Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants
Arne Ohlsson,Prakeshkumar S Shah
Cochrane Database of Systematic Reviews. 2020;
[Pubmed] | [DOI]
10 Efficacy and Safety of Oral Paracetamol vs. Oral Ibuprofen in the Treatment of Symptomatic Patent Ductus Arteriosus in Premature Infants
Birol Karabulut,Sebnem Paytoncu
Pediatric Drugs. 2019;
[Pubmed] | [DOI]
11 Tratamiento farmacológico del conducto arterioso permeable en recién nacidos prematuros
Hellmann Adrián Escobar,Gyhill Meneses-Gaviria,Nataly Revelo-Jurado,Julián Felipe Villa-Rosero,Jhon Edison Ijají Piamba,Alexander Burbano-Imbachí,Anuar Alonso Cedeño-Burbano
Revista de la Facultad de Medicina. 2019; 67(2): 333
[Pubmed] | [DOI]
12 Early PARacetamol (EPAR) trial: a study protocol for a randomised controlled trial of early paracetamol to promote closure of the ductus arteriosus in preterm infants
Tim Schindler,John Smyth,Srinivas Bolisetty,Joanna Michalowski,Kei Lui
BMJ Open. 2019; 9(10): e031428
[Pubmed] | [DOI]
13 Comparison of oral acetaminophen with oral ibuprofen on closure of symptomatic patent ductus arteriosus in preterm neonates
Mehdi Ghaderian,Behzad Barekatain,AmirBanazade Dardashty
Journal of Research in Medical Sciences. 2019; 24(1): 96
[Pubmed] | [DOI]
14 Paracetamol treatment for patent ductus arteriosus: practice and attitudes in Australia and New Zealand
L. A. Dowd,B. J. Wheeler,H. S. Al-Sallami,R. S. Broadbent,L. K. Edmonds,N. J. Medlicott
The Journal of Maternal-Fetal & Neonatal Medicine. 2018; : 1
[Pubmed] | [DOI]
15 Efficacy and safety of oral paracetamol versus oral ibuprofen for closure of patent ductus arteriosus in preterm infants: a randomized controlled trial
Rania A. El-Farrash,Mohammed S. El Shimy,Abeer S. El-Sakka,Manal G. Ahmed,Dina G. Abdel-Moez
The Journal of Maternal-Fetal & Neonatal Medicine. 2018; : 1
[Pubmed] | [DOI]
16 The dark side of ibuprofen in the treatment of patent ductus arteriosus: could paracetamol be the solution?
Laura Cuzzolin,Flamina Bardanzellu,Vassilios Fanos
Expert Opinion on Drug Metabolism & Toxicology. 2018; : 1
[Pubmed] | [DOI]
17 Early treatment versus expectative management of patent ductus arteriosus in preterm infants: a multicentre, randomised, non-inferiority trial in Europe (BeNeDuctus trial)
Tim Hundscheid,Wes Onland,Bart van Overmeire,Peter Dijk,Anton H. L. C. van Kaam,Koen P. Dijkman,Elisabeth M. W. Kooi,Eduardo Villamor,André A. Kroon,Remco Visser,Daniel C. Vijlbrief,Susanne M. de Tollenaer,Filip Cools,David van Laere,Anne-Britt Johansson,Catheline Hocq,Alexandra Zecic,Eddy Adang,Rogier Donders,Willem de Vries,Arno F. J. van Heijst,Willem P. de Boode
BMC Pediatrics. 2018; 18(1)
[Pubmed] | [DOI]
18 Efficacy of Paracetamol in Closure of Ductus Arteriosus in Infants under 32?Weeks of Gestation
Ines Tofe,Maria Dolores Ruiz-González,Maria Dolores Cañete,Asuncion Pino,Rosa Lorena Rueda,Maria Jose Parraga,Juan Luis Perez-Navero
Frontiers in Pediatrics. 2018; 6
[Pubmed] | [DOI]
19 Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants
Arne Ohlsson,Prakeshkumar S Shah
Cochrane Database of Systematic Reviews. 2018;
[Pubmed] | [DOI]
20 Effect on cerebral oxygenation of paracetamol for patent ductus arteriosus in preterm infants
Carlo Dani,Chiara Poggi,Ilaria Cianchi,Iuri Corsini,Venturella Vangi,Simone Pratesi
European Journal of Pediatrics. 2018;
[Pubmed] | [DOI]
21 Oral Paracetamol for Patent Ductus Arteriosus Rescue Closure
Pramod Pharande,Hadley Watson,Kenneth Tan,Arvind Sehgal
Pediatric Cardiology. 2017;
[Pubmed] | [DOI]
22 Oral pharmacological treatment for patent ductus arteriosus in premature neonates with hemodynamic repercussions
Clarissa de Albuquerque Botura,Bruno Ambrósio da Rocha,Thiely Balensiefer,Franciele Queiroz Ames,Ciomar Aparecida Bersani-Amado,Roberto Kenji Nakamura Cuman
Asian Pacific Journal of Tropical Medicine. 2017;
[Pubmed] | [DOI]
23 Dysfunction of the foetal arterial duct results in a wide spectrum of cardiovascular pathology
Marc Gewillig,Stephen C. Brown,Mieke Roggen,Benedicte Eyskens,Ruth Heying,Patrice Givron,Bjorn Cools,Luc de Catte
Acta Cardiologica. 2017; : 1
[Pubmed] | [DOI]
24 Paracetamol jako alternatywna metoda leczenia hemodynamicznie istotnego PDA u noworodków urodzonych przedwczesnie – wstepne wyniki badan
Agata Jankowska,Beata Loniewska,Agnieszka Szpiek,Agnieszka Kordek,Barbara Michalczyk
Pediatria Polska. 2017;
[Pubmed] | [DOI]
25 Oral paracetamol versus oral ibuprofen for closure of haemodynamically significant patent ductus arteriosus in preterm neonates (<32 weeks): a blinded, randomised, active-controlled, non-inferiority trial
Ashutosh Kumar,Venkataseshan Sundaram,Rahul Yadav,Tejo Pratap Oleti,Srinivas Murki,Arun Krishna,Mangalabharathi Sundaram,Shiv Sajan Saini,Sourabh Dutta
BMJ Paediatrics Open. 2017; 1(1): e000143
[Pubmed] | [DOI]
26 Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis
Gianluca Terrin,Francesca Conte,Mehmet Yekta Oncel,Antonella Scipione,Patrick J McNamara,Sinno Simons,Rahul Sinha,Omer Erdeve,Kadir S Tekgunduz,Mustafa Dogan,Irena Kessel,Cathy Hammerman,E Nadir,Sadik Yurttutan,Bonny Jasani,Serdar Alan,Francesco Manguso,Mario De Curtis
Archives of Disease in Childhood - Fetal and Neonatal Edition. 2016; 101(2): F127
[Pubmed] | [DOI]
27 Oral paracetamol vs. oral ibuprofen in the treatment of symptomatic patent ductus arteriosus in premature infants: A randomized controlled trial
Bo Yang,Xiangyu Gao,Yi Ren,Yun Wang,Qinglin Zhang
Experimental and Therapeutic Medicine. 2016; 12(4): 2531
[Pubmed] | [DOI]
28 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
Carlo Dani,Chiara Poggi,Fabio Mosca,Federico Schena,Gianluca Lista,Luca Ramenghi,Costantino Romagnoli,Enrica Salvatori,Maria Teresa Rosignoli,Paola Lipone,Alessandro Comandini
Trials. 2016; 17(1)
[Pubmed] | [DOI]
29 Recent Advances in the Treatment of Preterm Newborn Infants with Patent Ductus Arteriosus
Hannes Sallmon,Petra Koehne,Georg Hansmann
Clinics in Perinatology. 2016; 43(1): 113
[Pubmed] | [DOI]
30 Intravenous paracetamol for PDA closure in the preterm: a single-center experience
Enrico Valerio,Marta Rossella Valente,Sabrina Salvadori,Anna Chiara Frigo,Eugenio Baraldi,Paola Lago
European Journal of Pediatrics. 2016;
[Pubmed] | [DOI]
31 Pharmacological Closure of Patent Ductus Arteriosus: Selecting the Agent and Route of Administration
Sindhu Sivanandan,Ramesh Agarwal
Pediatric Drugs. 2016; 18(2): 123
[Pubmed] | [DOI]
32 Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure
Daniëlla W. E. Roofthooft,Ingrid M. van Beynum,Johan C. A. de Klerk,Monique van Dijk,John N. van den Anker,Irwin K. M. Reiss,Dick Tibboel,Sinno H. P. Simons
European Journal of Pediatrics. 2015; 174(11): 1433
[Pubmed] | [DOI]
33 Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low-birth-weight infants
Arne Ohlsson,Prakeshkumar S Shah
Cochrane Database of Systematic Reviews. 2015;
[Pubmed] | [DOI]
34 Ductal Closure With Intravenous Paracetamol: A New Approach To Patent Ductus Arteriosus Treatment
Asli Memisoglu,Zeynep Alp Ünkar,Nilufer Cetiner,Figen Akalin,Hulya Ozdemir,Hülya Selva Bilgen,Eren Ozek
The Journal of Maternal-Fetal & Neonatal Medicine. 2015; : 1
[Pubmed] | [DOI]
35 Acetaminophen for Patent Ductus Arteriosus
Jennifer Le,Mark A. Gales,Barry J. Gales
Annals of Pharmacotherapy. 2015; 49(2): 241
[Pubmed] | [DOI]
36 Efficacy of paracetamol for the treatment of patent ductus arteriosus in preterm neonates
Gianluca Terrin,Francesca Conte,Antonella Scipione,Erica Bacchio,Maria Conti,Rosalia Ferro,Flavia Ventriglia,Mario De Curtis
Italian Journal of Pediatrics. 2014; 40(1): 21
[Pubmed] | [DOI]
37 Intravenous paracetamol with a lower dose is also effective for the treatment of patent ductus arteriosus in pre-term infants
Kadir Serafettin Tekgündüz,Naci Ceviz,Ibrahim Caner,Hasim Olgun,Yasar Demirelli,Canan Yolcu,Irfan Oguz Sahin,Mustafa Kara
Cardiology in the Young. 2014; : 1
[Pubmed] | [DOI]
38 Paracetamol treatment of patent ductus arteriosus in preterm infants
E Nadir,E Kassem,S Foldi,A Hochberg,M Feldman
Journal of Perinatology. 2014;
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Article Tables

 Article Access Statistics
    PDF Downloaded968    
    Comments [Add]    
    Cited by others 38    

Recommend this journal