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Treatment of patent ductus arteriosus: indomethacin or ibuprofen?

Journal of Perinatology volume 28, pages S60–S62 (2008)Cite this article

Abstract

Persistent patent ductus arteriosus (PDA) in preterm infants can result in serious hemodynamic changes causing respiratory, gastrointestinal and renal morbidities if not treated within the first week of life. The treatment options available are a conservative approach, pharmacological treatment with cyclo-oxygenase (COX) inhibitors and surgical ligation. The COX inhibitors approved for use in the United States are indomethacin and ibuprofen lysine. Both of these drugs are equally effective in closing the PDA. Subtle differences exist between these two preparations. Indomethacin has a protective effect on the incidence of intraventricular hemorrhage (IVH) but reduces the blood flow to the kidneys and the brain. Ibuprofen is less toxic but has no effect on IVH. Efficacy of pharmacological treatment is influenced by timing of initiation of therapy. Surgical treatment is the only option when pharmacological treatment fails to close the PDA in symptomatic infants. Long-term neurological and respiratory morbidities are associated with surgical ligation. This paper reviews these medical considerations in the treatment options for PDA in premature infants.

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References

  1. Clyman RI . Mechanisms regulating the ductus arteriosus. Biol Neonate 2006; 89: 330–335.

    Article  Google Scholar 

  2. Cardiac abnormalities. In: Gomella TL, Cunningham MD, Eyal FG (eds). Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugs. 4th edn. Appleton & Lange: Stamford, CT, 1999 pp 335–352.

    Google Scholar 

  3. Bancalari E, Claure N, Ganzalez A . Patent ductus arteriosus and respiratory outcome in premature infants. Biol Neonate 2005; 88: 192–201.

    Article  Google Scholar 

  4. Cotton RB, Stahlman MT, Dovar I, Catterton WZ . Medical management of small preterm infants with symptomatic patent ductus arteriosus. J Pediatr 1979; 2: 467–473.

    Google Scholar 

  5. Corff KE, Sekar KC . Clinical considerations for the pharmacological management of patent ductus arteriosus with cyclooxygenase inhibitors in premature infants. J Pediatr Pharmacol Ther 2007; 12: 147–157.

    PubMed  PubMed Central  Google Scholar 

  6. Evans N, Malcolm G, Osborn D, Kluckow M . Diagnosis of patent ductus arteriosus in preterm infants. Neonatal Rev 2004; 5: e86–e97.

    Google Scholar 

  7. Van Overmeire B, Smets K, Lecoutere D, Van de Broek H, Weyler J, Degroote K et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med 2000; 343: 674–681.

    Article  CAS  Google Scholar 

  8. Hermes-DeSantis ER, Clyman RI . Patent ductus arteriosus: pathophysiology and management. J Perinatol 2006; 26: S14–S18.

    Article  Google Scholar 

  9. Clyman RI, Chorne N . Patent ductus arteriosus: evidence for and against treatment. J Pediatr 2007; 150: 216–219.

    Article  Google Scholar 

  10. Clyman RI . Ibuprofen and patent ductus arteriosus. N Engl J Med 2000; 343: 728–729.

    Article  CAS  Google Scholar 

  11. Kabra NS, Schmidt B, Roberts S, Doyle LW, Papile L, Fanaroof A et al. Neurosensory impairment after surgical closure of patent ductus arteriosus in extremely low birth weight infants: results from the trial of indomethacin prophylaxis in preterms. J Pediatr 2007; 150: 229–234.

    Article  CAS  Google Scholar 

  12. Van Overmeire B, Follens I, Hartmann S, Creten WL, Van Acker KJ . Treatment of patent ductus arteriosus with ibuprofen. Arch Dis Child Fetal Neonatal Ed 1997; 76: F179–F184.

    Article  CAS  Google Scholar 

  13. In: Yaffe, Aranda eds. Neonatal and Pediatric Pharmacology, 3rd edn. 2005 p670.

  14. Grosfeld JL, Kamman K, Gross K, Cikrit D, Ross D, Wolfe M et al. Comparative effects of indomethacin, prostaglandin E1, and ibuprofen on bowel ischemia. J Pediatr Surg 1983; 18: 738–742.

    Article  CAS  Google Scholar 

  15. In: Yaffe, Aranda eds. Neonatal and Pediatric Pharmacology, 3rd edn. 2005; pp 671–675.

  16. Mosca F, Bray M, Lattanzio M, Fumagalli M, Tosetto C . Comparative evaluation of the effects of indomethacin and ibuprofen on cerebral perfusion and oxygenation in preterm infants with patent ductus arteriosus. J Pediatr 1997; 131: 549–554.

    Article  CAS  Google Scholar 

  17. McCormick DC, Edwards AD, Brown GC, Wyatt JS, Potter A, Cope M et al. Effect of indomethacin on cerebral oxidized cytochrome oxidase in preterm infants. Pediatr Res 1993; 33: 603–608.

    Article  CAS  Google Scholar 

  18. Fowlie PW, Davis PG . Cochrane Database of Systematic Reviews 2002, Issue 3. Art. No.: CD000174.

  19. Shah SS, Ohlsson A . Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD004213.

  20. Pezzati M, Vangi V, Biagiotti R, Bertini G, Cianciulli D, Rubaltelli FF . Effects of indomethacin and ibuprofen on mesenteric and renal blood flow in preterm infants with patent ductus arteriosus. J Pediatr 1999; 135: 733–738.

    Article  CAS  Google Scholar 

  21. Van Overmeire B, Smets K, Lecoutere D, Van de Broek H, Weyler J, Degroote K et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med 2000; 343: 674–681.

    Article  CAS  Google Scholar 

  22. Ohlsson A, Walia R, Shah S . The Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.:CD003481.

  23. Shah SS, Ohlsson A . The Cochrane Database of Systematic Reviews 2006, Issue 1.Art. No.: CD004213.

  24. Koehne PS, Helfenstein D, Pees C, Walch E, Obladen M . Neurodevelopmental outcome of very low birth weight infants after intervention for patent ductus arteriosus with cyclooxygenase inhibitors. EPAS 2007; 615911: 14.

    Google Scholar 

  25. Ahlfors CE . Effect of ibuprofen on bilirubin–albumin binding. J Pediatr 2004; 144 (3): 386–388.

    Article  CAS  Google Scholar 

  26. Cooper-Peel C, Brodersen R, Robertson A . Does ibuprofen affect bilirubin–albumin binding in the newborn infant serum? Pharmacol Toxicol 1996; 79 (6): 297–299.

    Article  CAS  Google Scholar 

  27. Gourney V, Roze JC, Kuster A, Daoud P, Cambonie G, Hascoet JM et al. Prophylactic ibuprofen versus placebo in very premature infants: a randomized, double-blind, placebo-controlled trial. Lancet 2004; 364: 1939–1944.

    Article  Google Scholar 

  28. 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: 1966–1972.

    Article  CAS  Google Scholar 

  29. Clyman R, Saha S, Jobe A, Oh W . Indomethacin prophylaxis for pre term infants: The impact of 2 multi-center randomized controlled trials on clinical practice. J Pediatr 2007; 150: 46–50.

    Article  CAS  Google Scholar 

  30. Van Overmeire B, Allegaert K, Casaer A, Debauche C, Decaluwé W, Jespers A et al. Prophylactic ibuprofen in premature infants: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2004; 364: 1945–1949.

    Article  CAS  Google Scholar 

  31. Thomas RL, Parker GC, Van Overmeire B, Aranda JV . A meta-analysis of ibuprofen versus indomethacin for closure of patent ductus arteriosus. Eur J Pediatr 2005; 164: 135–140.

    Article  CAS  Google Scholar 

  32. Ment LR, Vohr B, Allen W, Westerveld M, Sparrow SS, Schneider KC et al. Outcome of children in the indomethacin intraventricular hemorrhage prevention trial. Pediatrics 2000; 105: 485–491.

    Article  CAS  Google Scholar 

  33. Ment LR, Vohr BR, Makuch RW, Westerveld M, Katz KH, Schneider KC et al. Prevention of intraventricular hemorrhage by indomethacin in male preterm infants. J Pediatr 2004; 145: 832–834.

    Article  CAS  Google Scholar 

  34. Aranda JV, Thomas R . Systematic review: intravenous ibuprofen in preterm newborns. Semin Perinatol 2006; 30: 114–120.

    Article  CAS  Google Scholar 

  35. Koch J, Hensley G, Roy L, Brown S, Ramaciotti C, Rosenfield CR . Prevalence of spontaneous closure of the ductus arteriosus in the neonates at a birth weight of 1000 grams or less. Pediatrics 2006; 4: 1113–1121.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Neonatal-Perinatal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    K C Sekar & K E Corff

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  1. K C Sekar
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  2. K E Corff
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Correspondence to K C Sekar.

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Dr. Corff is in the speaker's bureau of Ovation Pharmaceuticals and both authors have received honoraria for speaking engagements.

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Sekar, K., Corff, K. Treatment of patent ductus arteriosus: indomethacin or ibuprofen?. J Perinatol 28 (Suppl 1), S60–S62 (2008). https://doi.org/10.1038/jp.2008.52

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