Prophylactic intravenous paracetamol use in extremely premature infants for patent ductus arteriosus

Musa Silahli; Zeynel Gokmen; Mehmet Tekin

doi:10.1515/jbcpp-2020-0006

Article

Prophylactic intravenous paracetamol use in extremely premature infants for patent ductus arteriosus

Musa Silahli , Zeynel Gokmen and Mehmet Tekin

Published/Copyright: December 14, 2020

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 32 Issue 5

Abstract

Objectives

Patency of ductus arteriosus (PDA) is a very common problem among extremely low birth weight infants (ELBW). Hemodynamic instability caused by PDA is associated with important morbidities. This study aims to evaluate the effects of prophylactic intravenous paracetamol on the hemodynamically significant patent ductus arteriosus (hsPDA).

Methods

A total of 75 infants of <28 week-gestational age were enrolled into the study which was retrospective. Prophylactic paracetamol as the experimental group and none-prophylaxis group as the control group were compared in the study.

Results

There were 35 subjects in the prophylactic paracetamol group (PPG), and 40 in the control group. Primary outcome measures were ductal closure, ductal diameter, grade 3–4 IVH, and repeated ibuprofen need for the treatment of hsPDA. At the time of the evaluation by echo, hsPDA, and the diameter of the ductus higher than 1 mm were found significantly lower in the PPG (p=0.004 and p=0.013). Additionally, the repeated course of ibuprofen was significantly lower in the PPG (p=0.025). Secondary outcomes were the other perinatal morbidities. According to the results of the study, the male gender is 6.6, and the paracetamol use is 5.5 times more likely to suffer from ROP.

Conclusions

The results of the study indicated that prophylactic paracetamol use in ELBW infants decreases the likelihood of hsPDA. The repeated course of ibuprofen for the treatment of hsPDA can be reduced. Furthermore, it can be understood that while prophylactic use of paracetamol is preventive for intraventricular hemorrhage, it does not function in the same way for retinopathy of prematurity or bronchopulmonary dysplasia. It might even worse the retinopathy of prematurity. Further prospective randomized controlled and larger sample-sized studies are needed.

Keywords: extremely low birth weight infants; paracetamol; patency of ductus arteriosus

Corresponding author: Mehmet Tekin, Department of Pediatrics, Baskent University Konya Practice and Research Center, Saray Street, 42080 Selcuklu, Konya, Turkey, E-mail: dr.mehmettekin@gmail.com

Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was not obtained since it was a retrospective study.
Ethical approval: This study has been approved by Baskent University Institutional Review and Ethical Board (project no: KA19/70).

References

1. Reller, MD, Rice, MJ, McDonald, RW. Review of studies evaluating ductal patency in the premature infant. J Pediatr 1993;122:S59–62. https://doi.org/10.1016/S0022-3476(09)90044-0.Search in Google Scholar

2. Reese, J, Shelton, EL, Slaughter, JC, McNamara, PJ. Prophylactic indomethacin revisited. J Pediatr 2017;186:11–14.e1. https://doi.org/10.1016/j.jpeds.2017.03.036.Search in Google Scholar

3. EL-Khuffash, AF, Jain, A, McNamara, PJ. Ligation of the patent ductus arteriosus in preterm infants: understanding the physiology. J Pediatr 2013;6:1100–6. https://doi.org/10.1016/j.jpeds.2012.12.094.Search in Google Scholar

4. Knight, DB. The treatment of patent ductus arteriosus in preterm infants. A review and overview of randomized trials. Semin Neonatol 2001;6:63–73. https://doi.org/10.1053/siny.2000.0036.Search in Google Scholar

5. Fanos, V, Pusceddu, M, Dessì, A, Marcialis, MA. Should we definitively abandon prophylaxis for patent ductus arteriosus in preterm new-borns? Clinics 2011;66:2141–9. https://doi.org/10.1590/s1807-59322011001200022.Search in Google Scholar

6. Clyman, RI, Couto, J, Murphy, GM. Patent ductus arteriosus: are current neonatal treatment options better or worse than no treatment at all? Semin Perinatol 2012;36:123–9. https://doi.org/10.1053/j.semperi.2011.09.022.Search in Google Scholar

7. Ment, LR, Stewart, WB, Scott, DT, Duncan, CC. Beagle puppy model of intraventricular hemorrhage: randomized indomethacin prevention trial. Neurology 1983;33:179–84. https://doi.org/10.1212/wnl.33.2.179.Search in Google Scholar

8. Mahony, L, Carnero, V, Brett, C, Heymann, MA, Clyman, RI. Prophylactic indomethacin therapy for patent ductus arteriosus in very-low-birth-weight infants. N Engl J Med 1982;306:506–10. https://doi.org/10.1056/nejm198203043060903.Search in Google Scholar

9. Mahony, L, Caldwell, RL, Girod, DA, Hurwitz, RA, Jansen, RD, Lemons, JA, et al.. Indomethacin therapy on the first day of life in infants with very low birth weight. J Pediatr 1985;106:801–5. https://doi.org/10.1016/s0022-3476(85)80361-9.Search in Google Scholar

10. Ment, LR, Oh, W, Ehrenkranz, RA, Phillip, AG, Vohr, B, Allan, W, et al.. Low-dose indomethacin therapy and extension of intraventricular hemorrhage: a multicenter randomized trial. J Pediatr 1994;124:951–5. https://doi.org/10.1016/s0022-3476(05)83191-9.Search in Google Scholar

11. Schmidt, B, Davis, P, Moddemann, D, Ohlsson, A, Roberts, RS, Saigal, S, et al.. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med 2001;344:1966–72. https://doi.org/10.1056/nejm200106283442602.Search in Google Scholar

12. Gersony, WM, Peckham, GJ, Ellison, RC, Miettinen, OS, Nadas, AS. Effects of indomethacin in premature infants with patent ductus arteriosus: results of a national collaborative study. J Pediatr 1983;102:895–906. https://doi.org/10.1016/s0022-3476(83)80022-5.Search in Google Scholar

13. Ment, LR, Oh, W, Ehrenkranz, RA, Philip, AG, Vohr, B, Allan, W, et al.. Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial. Pediatrics 1994;93:543–50.10.1097/00006254-199409000-00011Search in Google Scholar

14. Schena, F, Francescato, G, Cappelleri, A, Picciolli, I, Mayer, A, Mosca, F, et al.. Association between hemodynamically significant patent ductus arteriosus and bronchopulmonary dysplasia. J Pediatr 2015;166:1488–92. https://doi.org/10.1016/j.jpeds.2015.03.012.Search in Google Scholar PubMed

15. Nelin, TD, Pena, E, Giacomazzi, T, Lee, S, Logan, JW, Moallem, M, et al.. Outcomes following indomethacin prophylaxis in extremely preterm infants in an all-referral NICU. J Perinatol 2017;37:932–7. https://doi.org/10.1038/jp.2017.71.Search in Google Scholar PubMed

16. Liebowitz, M, Clyman, RI. Prophylactic indomethacin compared with delayed conservative management of the patent ductus arteriosus in extremely preterm infants: effects on neonatal outcomes. J Pediatr 2017;187:119–26.e1. https://doi.org/10.1016/j.jpeds.2017.03.021.Search in Google Scholar PubMed PubMed Central

17. Kanmaz, G, Erdeve, O, Canpolat, FE, Oğuz, SS, Uras, N, Altug, N, et al.. Serum ibuprofen levels of extremely preterm infants treated prophylactically with oral ibuprofen to prevent patent ductus arteriosus. Eur J Clin Pharmacol 2013;69:1075–81. https://doi.org/10.1007/s00228-012-1438-8.Search in Google Scholar PubMed

18. Aikio, O, Härkin, P, Saarela, T, Hallman, M. Early paracetamol treatment associated with lowered risk of persistent ductus arteriosus in very preterm infants. J Matern Fetal Neonatal Med 2014;27:1252–6. https://doi.org/10.3109/14767058.2013.854327.Search in Google Scholar PubMed

19. Asbagh, PA, Zarkesh, MR, Nili, F, Sadat Nayeri, FS, Naeem, AT. Prophylactic treatment with oral paracetamol for patent ductus arteriosus in preterm infants: a randomized clinical trial. Tehran Univ Med J 2015;73:86–92.Search in Google Scholar

20. Härkin, P, Härmä, A, Aikio, O, Valkama, M, Leskinen, M, Saarela, T, et al.. Paracetamol accelerates closure of the ductus arteriosus after premature birth: a randomized trial. J Pediatr 2016;177:72–7.e2. https://doi.org/10.1016/j.jpeds.2016.04.066.Search in Google Scholar PubMed

21. Ohlsson, A, Shah, PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database Syst Rev 2018;4:CD010061. https://doi.org/10.1002/14651858.cd010061.pub3.Search in Google Scholar PubMed PubMed Central

22. Mirza, H, Laptook, AR, Oh, W, Vohr, BR, Stoll, BJ, Kandefer, S, et al.. Effects of indomethacin prophylaxis timing on intraventricular haemorrhage and patent ductus arteriosus in extremely low birth weight infants. Arch Dis Child Fetal Neonatal Ed 2016;101:F418–22.10.1136/archdischild-2015-309112Search in Google Scholar PubMed PubMed Central

23. Benitz, WE, Committee on Fetus and Newborn, American Academy of Pediatrics. Patent ductus arteriosus in preterm infants. Pediatrics 2016;137:e20153730. https://doi.org/10.1542/peds.2015-3730.Search in Google Scholar PubMed

24. Fanos, V, Marcialis, MA, Bassareo, PP, Antonucci, R, Zaffanello, M, Dessì, A, et al.. Renal safety of non steroidal anti inflammatory drugs (NSAIDs) in the pharmacologic treatment of patent ductus arteriosus. J Matern Fetal Neonatal Med 2011;24(1 Suppl):50–2. https://doi.org/10.3109/14767058.2011.607593.Search in Google Scholar PubMed

25. Sallmon, H, Koehne, P, Hansmann, G. Recent advances in the treatment of preterm newborn infants with patent ductus arteriosus. Clin Perinatol 2016;43:113–29. https://doi.org/10.1016/j.clp.2015.11.008.Search in Google Scholar PubMed

26. 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. https://doi.org/10.1542/peds.2011-0359.Search in Google Scholar PubMed

27. Kane, SP. Sample size calculator. ClinCalc; 2019. Available from: https://clincalc.com/stats/SampleSize.aspx [Updated July 24, 2019] [Accessed 15 Nov 2019].Search in Google Scholar

28. Oncel, MY, Yurttutan, S, Degirmencioglu, H, Uras, N, Altug, N, Erdeve, O, et al.. Intravenous paracetamol treatment in the management of patent ductus arteriosus in extremely low birth weight infants. Neonatology 2013;103:166–9. https://doi.org/10.1159/000345337.Search in Google Scholar PubMed

29. El-Khuffash, A, Jain, A, Corcoran, D, Shah, PS, Hooper, CW, Brown, N, et al.. Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies. Pediatr Res 2014;76:238–44. https://doi.org/10.1038/pr.2014.82.Search in Google Scholar PubMed PubMed Central

30. El-Mashad, AE, El-Mahdy, H, El Amrousy, D, Elgendy, M. Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates. Eur J Pediatr 2017;176:233–40. https://doi.org/10.1007/s00431-016-2830-7.Search in Google Scholar PubMed

31. 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;8:e77888. https://doi.org/10.1371/journal.pone.0077888.Search in Google Scholar PubMed PubMed Central

32. Dani, C, Poggi, C, Cianchi, I, Corsini, I, Vangi, V, Pratesi, S. Effect on cerebral oxygenation of paracetamol for patent ductus arteriosus in preterm infants. Eur J Pediatr 2018;177:533–9. https://doi.org/10.1007/s00431-018-3086-1.Search in Google Scholar PubMed

33. Tekgündüz, KŞ, Ceviz, N, Caner, İ, Olgun, H, Demirelli, Y, Yolcu, C, et al.. Intravenous paracetamol with a lower dose is also effective for the treatment of patent ductus arteriosus in pre-term infants. Cardiol Young 2015;25:1060–4.10.1017/S1047951114001577Search in Google Scholar PubMed

34. Oncel, MY, Yurttutan, S, Erdeve, O, Uras, N, Altug, N, Oguz, SS, et al.. Oral paracetamol versus oral ibuprofen in the management of patent ductus arteriosus in preterm infants: a randomized controlled trial. J Pediatr 2014;164:510–14.e1. https://doi.org/10.1016/j.jpeds.2013.11.008.Search in Google Scholar PubMed

35. Ding, Y, Wang, X, Wu, Y, Li, H, Xu, J, Wang, X. Effects of prophylactic oral ibuprofen on the closure rate of patent ductus arteriosus in premature infants. Medicine (Baltim) 2018;97:e12206.10.1097/MD.0000000000012206Search in Google Scholar PubMed PubMed Central

36. Höck, M, Brunner, B, Rier, V, Thöni, S, Trawöger, R, Geiger, R, et al.. Prophylactic low-dose paracetamol administration associated with lowered rate of patent ductus arteriosus in preterm infants e impact on outcome and pain perception. Pediatr Neonatol 2020;61:84–91. https://doi.org/10.1016/j.pedneo.2019.06.011.Search in Google Scholar PubMed

Received: 2020-01-09

Accepted: 2020-08-21

Published Online: 2020-12-14

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2020-0006

Keywords for this article

extremely low birth weight infants; paracetamol; patency of ductus arteriosus