Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Acetaminophen to avoid surgical ligation in extremely low gestational age neonates with persistent hemodynamically significant patent ductus arteriosus

Abstract

Objective:

The objective of this study was to evaluate the effectiveness of rescue oral acetaminophen in improving echocardiography (echo) indices of patent ductus arteriosus (PDA) shunt volume and avoiding surgical ligation in extremely low gestational age (GA) neonates (ELGANs, <28 weeks) with persistent PDA.

Study Design:

Retrospective cohort study of ELGANs with moderate or severe PDA at risk for ligation after a practice change introducing oral acetaminophen (60 mg kg−1 day−1 for 3 to 7 days) to facilitate ductal constriction after indomethacin failure.

Results:

Twenty-six infants (median GA 24.4 weeks at birth) with persistent PDA under consideration for surgical ligation were treated with oral acetaminophen at a mean of 27 days of life. Echo indices of shunt volume improved in 12 (46%) infants (3 closed and 9 reduced to mild shunt), all of whom avoided ligation. There was no echo improvement in 14 (54%) infants, of which 8/14 underwent ligation, and ligation was deferred in 6/14 infants, mostly owing to improvement in respiratory stability. Fewer responders than non-responders underwent ligation (0% vs 57%, P<0.01), though there were no differences in other neonatal outcomes.

Conclusions:

In ELGANs with persistent significant PDA, rescue therapy with oral acetaminophen was associated with improvement in echo indices of shunt volume and avoidance of ligation in nearly half of infants.

This is a preview of subscription content, access via your institution

Access options

Buy this article

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Kabra NS, Schmidt B, Roberts RS, Doyle LW, Papile L, Fanaroff 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 (3): 229–234, e221.

    Article  CAS  Google Scholar 

  2. Madan JC, Kendrick D, Hagadorn JI, Frantz IID . Patent ductus arteriosus therapy: Impact on neonatal and 18-month outcome. Pediatrics 2009; 123 (2): 674–681.

    Article  Google Scholar 

  3. Weisz DE, More K, McNamara PJ, Shah PS . PDA ligation and health outcomes: a meta-analysis. Pediatrics 2014; 133 (4): e1024–e1046.

    Article  Google Scholar 

  4. Morriss FH Jr, Saha S, Bell EF, Colaizy TT, Stoll BJ, Hintz SR et al. Surgery and neurodevelopmental outcome of very low-birth-weight infants. JAMA Pediatr 2014; 168 (8): 746–754.

    Article  Google Scholar 

  5. Wickremasinghe AC, Rogers EE, Piecuch RE, Johnson BC, Golden S, Moon-Grady AJ et al. Neurodevelopmental outcomes following two different treatment approaches (early ligation and selective ligation) for patent ductus arteriosus. J Pediatr 2012; 161 (6): 1065–1072.

    Article  Google Scholar 

  6. Shah P, Mirea L, Weisz D, Barrington K, Lee K, Sorokan T et al. Trends in patent ductus arteriosus management and association with neonatal mortality and morbidities among very preterm infants in Canada. E-PAS 2014; 2850: 8.

    Google Scholar 

  7. Bose CL, Laughon MM . Patent ductus arteriosus: lack of evidence for common treatments. Arch Dis Child Fetal Neonatal Ed 2007; 92 (6): F498–F502.

    Article  Google Scholar 

  8. Noori S, McCoy M, Friedlich P, Bright B, Gottipati V, Seri I et al. Failure of ductus arteriosus closure is associated with increased mortality in preterm infants. Pediatrics 2009; 123 (1): e138–e144.

    Article  Google Scholar 

  9. Kaempf JW, Wu YX, Kaempf AJ, Kaempf AM, Wang L, Grunkemeier G . What happens when the patent ductus arteriosus is treated less aggressively in very low birth weight infants? J Perinatol 2012; 32 (5): 344–348.

    Article  CAS  Google Scholar 

  10. 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 (6): 1488–1492.

    Article  Google Scholar 

  11. 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 (11): e77888.

    Article  CAS  Google Scholar 

  12. 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 (3): 510–514 e511.

    Article  CAS  Google Scholar 

  13. Roofthooft DW, van Beynum IM, Helbing WA, Reiss IK, Simons SH . Paracetamol for ductus arteriosus closure: not always a success story. Neonatology 2013; 104 (3): 170.

    Article  CAS  Google Scholar 

  14. Ozdemir OM, Dogan M, Kucuktasci K, Ergin H, Sahin O . Paracetamol therapy for patent ductus arteriosus in premature infants: a chance before surgical ligation. Pediatr Cardiol 2014; 35 (2): 276–279.

    Article  Google Scholar 

  15. 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 (3): 238–244.

    Article  CAS  Google Scholar 

  16. Fajardo MF, Claure N, Swaminathan S, Sattar S, Vasquez A, D'Ugard C et al. Effect of positive end-expiratory pressure on ductal shunting and systemic blood flow in preterm infants with patent ductus arteriosus. Neonatology 2014; 105 (1): 9–13.

    Article  Google Scholar 

  17. De Buyst J, Rakza T, Pennaforte T, Johansson AB, Storme L . Hemodynamic effects of fluid restriction in preterm infants with significant patent ductus arteriosus. J Pediatr 2012; 161 (3): 404–408.

    Article  Google Scholar 

  18. El-Khuffash AF, Jain A, McNamara PJ . Ligation of the patent ductus arteriosus in preterm infants: Understanding the physiology. J Pediatr 2013; 162 (6): 1100–1106.

    Article  Google Scholar 

  19. 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 (6): e1618–e1621.

    Article  Google Scholar 

  20. 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 ibuprofen-resistant or contraindicated preterm infants. Arch Dis Child Fetal Neonatal Ed 2013; 98 (1): F94.

    Article  Google Scholar 

  21. Kessel I, Waisman D, Lavie-Nevo K, Golzman M, Lorber A, Rotschild A . Paracetamol effectiveness, safety and blood level monitoring during patent ductus arteriosus closure: a case series. J Matern Fetal Neonatal Med 2014; 27 (16): 1719–1721.

    Article  CAS  Google Scholar 

  22. 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): 1–7.

    Article  CAS  Google Scholar 

  23. Smith A, Maguire M, Livingstone V, Dempsey EM . Peak systolic to end diastolic flow velocity ratio is associated with ductal patency in infants below 32 weeks of gestation. Arch Dis Child Fetal Neonatal Ed 2015; 100 (2): F132–F136.

    Article  CAS  Google Scholar 

  24. Jasani B, Kabra N, Nanavati RN . Oral paracetamol in treatment of closure of patent ductus arteriosus in preterm neonates. J Postgrad Med 2013; 59 (4): 312–314.

    Article  CAS  Google Scholar 

  25. El-Khuffash A, James AT, Cleary A, Semberova J, Franklin O, Miletin J . Late medical therapy of patent ductus arteriosus using intravenous paracetamol. Arch Dis Child Fetal Neonatal Ed 2015; 100 (3): F253–F256.

    Article  Google Scholar 

  26. Allegaert K, Anderson B, Simons S, van Overmeire B . Paracetamol to induce ductus arteriosus closure: is it valid? Arch Dis Child 2013; 98 (6): 462–466.

    Article  Google Scholar 

  27. Anderson BJ . Paracetamol (Acetaminophen): mechanisms of action. Paediatr Anaesth 2008; 18 (10): 915–921.

    Article  Google Scholar 

  28. Rolland A, Shankar-Aguilera S, Diomande D, Zupan-Simunek V, Boileau P . Natural evolution of patent ductus arteriosus in the extremely preterm infant. Arch Dis Child Fetal Neonatal Ed 2015; 100 (1): F55–F58.

    Article  Google Scholar 

  29. El-Khuffash A, James AT, Corcoran JD, Dicker P, Franklin O, Elsayed YN et al. A patent ductus arteriosus severity score predicts chronic lung disease or death before discharge. J Pediatr 2015; 167: 1354–1361.e2.

    Article  Google Scholar 

  30. Sehgal A, Paul E, Menahem S . Functional echocardiography in staging for ductal disease severity: role in predicting outcomes. Eur J Pediatr 2013; 172 (2): 179–184.

    Article  Google Scholar 

  31. El-Khuffash AF, Slevin M, McNamara PJ, Molloy EJ . Troponin T, N-terminal pro natriuretic peptide and a patent ductus arteriosus scoring system predict death before discharge or neurodevelopmental outcome at 2 years in preterm infants. Arch Dis Child Fetal Neonatal Ed 2011; 96 (2): F133–F137.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D E Weisz.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Weisz, D., Martins, F., Nield, L. et al. Acetaminophen to avoid surgical ligation in extremely low gestational age neonates with persistent hemodynamically significant patent ductus arteriosus. J Perinatol 36, 649–653 (2016). https://doi.org/10.1038/jp.2016.60

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/jp.2016.60

This article is cited by

Search

Quick links