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Enteral paracetamol or intravenous indomethacin for closure of patent ductus arteriosus in preterm neonates: A randomized controlled trial

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Abstract

Objective

To compare the efficacy of enteral paracetamol and intravenous indomethacin for closure of patent ductus arteriosus (PDA) in preterm neonates.

Design

Randomized controlled trial.

Setting

Level III neonatal intensive care unit.

Participants

77 preterm neonates with birth weight ≤1500 g and PDA size ≥1.5 mm, with left to right ductal flow with left atrium to aortic root ratio >1.5:1; diagnosed by 2D-Echo within first 48 hours of life.

Intervention

Paracetamol drops through the infant feeding tube (15mg/kg/dose 6 hourly for 7 days) or intravenous indomethacin (0.2 mg/kg/dose once daily for 3 days).

Outcome measures

Primary: PDA closure rate assessed by echocardiography. Secondary: need for surgical closure of PDA, renal impairment, gastrointestinal bleed, necrotising enterocolitis, hepatotoxicity, pulmonary hemorrhage, sepsis, hypothermia, retinopathy of prematurity, intraventricular hemorrhage, bronchopulmonary dysplasia and mortality.

Results

PDA closure rate was 100% (36/36) in enteral paracetamol group as compared to 94.6% (35/37) in intravenous indomethacin group (P=0.13). The secondary outcomes were also similar between the two groups. There was no occurrence of hepatotoxicity.

Conclusions

Enteral paracetamol is safe but not superior to intravenous indomethacin in the treatment of PDA in preterm neonates.

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References

  1. Nemerofsky SL, Parravicini E, Bateman D, Kleinman C, Polin RA, Lorenz JM. The Ductus arteriosus rarely requires treatment in infants >1000 grams. Am J Perinatol. 2008; 25:661–6.

    Article  PubMed  Google Scholar 

  2. Koch J, Hensley G, Roy L, Brown S, Ramaciotti C, Rosenfeld CR. Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less. Pediatrics. 2006;117:1113–21.

    Article  PubMed  Google Scholar 

  3. Herrman K, Bose C, Lewis K, Laughon M. Spontaneous closure of the patent ductus arteriosus in very low birth weight infants following discharge from the neonatal unit. Arch Dis Child Fetal Neonatal Ed. 2009;94:48–50.

    Article  Google Scholar 

  4. Jhaveri N, Moon-Grady A, Clyman RI. Early surgical ligation versus a conservative approach for management of patent ductus arteriosus that fails to close after indomethacin treatment. J Pediatr. 2010;157:381–7.

    Article  PubMed Central  PubMed  Google Scholar 

  5. 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;343:674–81.

    Article  PubMed  Google Scholar 

  6. Sankaran K, Puckett B, Lee DS, Seshia M, Boulton J, Qiu Z, et al. Variations in incidence of necrotizing enterocolitis in Canadian neonatal intensive care units. J Pediatr Gastroenterol Nutr. 2004;39:366–72.

    Article  PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. Lago P, Bettiol T, Salvadori S, Pitassi I, Vianello A, Chiandetti L, et al. Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial. Eur J Pediatr. 2002;161:202–7.

    Article  CAS  PubMed  Google Scholar 

  9. Vieux R, Desandes R, Boubred F, Semama D, Guillemin F, Buchweiller MC, et al. Ibuprofen in very preterm infants impairs renal function for the first month of life. Pediatr Nephrol. 2010;25:267–74.

    Article  PubMed  Google Scholar 

  10. Ahlfors CE. Effect of ibuprofen on bilirubin-albumin binding. J Pediatr. 2004;144:386–8.

    Article  CAS  PubMed  Google Scholar 

  11. Rheinlaender C, Helfenstein D, Walch E, Berns M, Obladen M, Koehne P. Total serum bilirubin levels during cyclooxygenase inhibitor treatment for patent ductus arteriosus in preterm infants. Acta Paediatr. 2009;98:36–42.

    Article  CAS  PubMed  Google Scholar 

  12. 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;128:1618–21.

    Article  Google Scholar 

  13. Yurttutan S, Oncel MY, Arayicý S, Uras N, Altug N, Erdeve O, et al. A different first-choice drug in the medical management of patent ductus arteriosus: Oral paracetamol. J Matern Fetal Neonatal Med. 2013;26:825–7.

    Article  CAS  PubMed  Google Scholar 

  14. 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 ibuprofenresistant or contraindicated preterm infants. Arch Dis Child Fetal Neonatal Ed. 2013;98:94.

    Article  Google Scholar 

  15. Evans N. Diagnosis of patent ductus arteriosus in the preterm newborn. Arch Dis Child. 1993;68:58–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Kluckow M, Evans N. Early echocardiographic prediction of symptomatic patent ductus arteriosus in preterm infants undergoing mechanical ventilation. J Pediatr. 1995;127:774–9.

    Article  CAS  PubMed  Google Scholar 

  17. Young TE, Mangum B. Neofax ® 2010, 23rd edition, Montavale NJ, Thomson Reuters; 2010;180–1.

  18. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187:1–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. International Committee for the Classification of Retinopathy of Prematurity. The International classification of retinopathy of prematurity revisited. Arch Ophthalmol. 2005;123:991–9.

    Article  Google Scholar 

  20. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: A study of infants with birth weights less than 1,500 gm. J Pediatr. 1978;92:529–34.

    Article  CAS  PubMed  Google Scholar 

  21. Shennan AT, Dunn MS, Ohlsson A, Lennox K, Hoskins EM. Abnormal pulmonary outcomes in premature infants: Prediction from oxygen requirement in the neonatal period. Pediatrics. 1988;82:527–32.

    CAS  PubMed  Google Scholar 

  22. Knight DB. The treatment of patent ductus arteriosus in preterm infants. A review and overview of randomized trials. Semin Neonatol. 2001;6:63–73.

    CAS  PubMed  Google Scholar 

  23. Jasani B, Kabra N, Nanavati RN. Oral paracetamol in treatment of closure of patent ductus arteriosus in preterm neonates. J Postgrad Med. 2013;59:312–4.

    Article  CAS  PubMed  Google Scholar 

  24. 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;8:77888.

    Article  Google Scholar 

  25. 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;164:510–4.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. From Department of Neonatology, Surya Children’s Hospital, Mangal Ashirwad, Santacruz West, Mumbai, India

    Swarup Kumar Dash, Nandkishor S Kabra, Bhupendra S Avasthi, Shobha R Sharma, Phalguni Padhi & Javed Ahmed

Authors
  1. Swarup Kumar Dash
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  2. Nandkishor S Kabra
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  3. Bhupendra S Avasthi
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  4. Shobha R Sharma
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  5. Phalguni Padhi
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  6. Javed Ahmed
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Corresponding author

Correspondence to Nandkishor S Kabra.

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Dash, S.K., Kabra, N.S., Avasthi, B.S. et al. Enteral paracetamol or intravenous indomethacin for closure of patent ductus arteriosus in preterm neonates: A randomized controlled trial . Indian Pediatr 52, 573–578 (2015). https://doi.org/10.1007/s13312-015-0677-z

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  • DOI: https://doi.org/10.1007/s13312-015-0677-z

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