Hostname: page-component-848d4c4894-nr4z6 Total loading time: 0 Render date: 2024-05-14T08:32:17.505Z Has data issue: false hasContentIssue false

Combined (dual) drug therapy for the treatment of patent ductus arteriosus: last approach prior to ligation

Published online by Cambridge University Press:  06 December 2022

Mehmet F. Deveci*
Affiliation:
Division of Neonatology, Department of Pediatrics, Inonu University School of Medicine, Malatya, Turkey
Huseyin Kaya
Affiliation:
Division of Neonatology, Department of Pediatrics, Inonu University School of Medicine, Malatya, Turkey
Sadik Yurttutan
Affiliation:
Division of Neonatology, Department of Pediatrics, KSU University School of Medicine, Kahramanmaras, Turkey
Meral Alagoz
Affiliation:
Division of Neonatology, Department of Pediatrics, Inonu University School of Medicine, Malatya, Turkey
Ismail K. Gokce
Affiliation:
Division of Neonatology, Department of Pediatrics, Inonu University School of Medicine, Malatya, Turkey
Cemsit Karakurt
Affiliation:
Division of Cardiology, Department of Pediatrics, Inonu University School of Medicine, Malatya, Turkey
Ufuk U. Gullu
Affiliation:
Division of Cardiology, Department of Pediatrics, KSU University School of Medicine, Kahramanmaras, Turkey
Mehmet Oncul
Affiliation:
Division of Cardiology, Department of Pediatrics, Inonu University School of Medicine, Malatya, Turkey
Ramazan Ozdemir
Affiliation:
Division of Neonatology, Department of Pediatrics, Inonu University School of Medicine, Malatya, Turkey
*
Author for correspondence: M. F. Deveci, MD, Division of Neonatology, Department of Pediatrics, Inonu University School of Medicine, Turgut Ozal Medical Center, 44280, Malatya, Turkey. Tel: +90 422 3410660; Fax: +90 422 3410736. E-mail: dr-mfd@hotmail.com

Abstract

Objective:

We aimed to evaluate the efficacy of combined (ibuprofen+paracetamol) medical therapy in cases of persistent haemodynamically significant patent ductus arteriosus that are resistant to standard medical monotherapy (ibuprofen and/or paracetamol) in this retrospective multi-centre study.

Methods:

The combined therapy included the administration of 15mg/kg/dose of paracetamol every 6 h for 3 days and ibuprofen at an initial dose of 10mg/kg/dose followed by 5 mg/kg/dose every 24 h. After 2 days following the administration of the last dose, the researchers evaluated the efficacy of combined treatment by conducting an echocardiographic examination.

Results:

Of all 42 patients who received combined therapy, 37 (88.1%) patients exhibited closure of the haemodynamically significant patent ductus arteriosus without requiring surgical ligation. Patients who did not respond to combined therapy had a higher mean birth weight and gestational age compared to those who responded (p < 0.05).

Conclusion:

The researchers believe the success of ibuprofen and paracetamol in haemodynamically significant patent ductus arteriosus treatment may be due to their synergistic efficacy and inhibition of the prostaglandin synthesis pathway through different enzymes. The results of our retrospective trial suggest that combination therapy with paracetamol and ibuprofen can be attempted when monotherapy is unsuccessful in treating haemodynamically significant patent ductus arteriosus, especially in centres without a surgical department.

Type
Original Article
Copyright
© The Author(s), 2022. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Arcilla, RA, Thilenius, OG, Ranniger, K. Congestive heart failure from suspected ductal closure in utero. J Pediatr 1969; 75: 7478.CrossRefGoogle ScholarPubMed
Ellison, RC, Peckham, GJ, Lang, P, et al. Evaluation of the preterm infant for patent ductus arteriosus. Pediatrics 1983; 71: 364372.CrossRefGoogle ScholarPubMed
Moore, P, Brook, MM. Patent Ductus Arteriosus and aorticopulmonary window. In: Allen, HD, Driscoll, DJ, Shaddy, RE, et al. (eds). Heart Disease. Wolters Kluwer Lipincott Williams & Wilkins, ABD, Philadelphia, 2013.722-45.Google ScholarPubMed
Jim, WT, Chiu, NC, Chen, MR, et al. Cerebral hemodynamic change and intraventricular hemorrhage in very low birth weight infants with patent ductus arteriosus. Ultrasound Med Biol 2005; 31: 197202.CrossRefGoogle ScholarPubMed
Todd, DA, Jana, A, John, E. Chronic oxygen dependency in infants born at 24-32 weeks' gestation: the role of antenatal and neonatal factors. J Paediatr Child Health 1997; 33: 402407.CrossRefGoogle ScholarPubMed
Cassady, G, Crouse, DT, Kirklin, JW, et al. A randomized, controlled trial of very early prophylactic ligation of the ductus arteriosus in babies who weighed 1000 g or less at birth. N Engl J Med 1989; 320: 15111516.CrossRefGoogle ScholarPubMed
Sash, SD, Makker, K, Nandula, P, Smotherman, C, Kropf, A, Hudak, ML. Effectiveness of dual medication (oral asitaminofen+ıbuprofen) for the management of patent duktus arteriozus in extremely prematüre infants. a feasibility. Am J Perinatol 2022; 39: 1326–1333.Google Scholar
Chiruvolu, A, Jaleel, M. Therapeutic management of patent ductusarteriosus. Early Hum Dev 2009; 85: 151155.CrossRefGoogle Scholar
Weisz, DE, More, K, McNamara, PJ, Shah, PS. PDA ligation and health outcomes: a meta-analysis. Pediatrics 2014; 133: 10241046.CrossRefGoogle ScholarPubMed
Gokmen, T, Erdeve, O, Altug, N, Oguz, SS, Uras, N, Dilmen, U. Efficacy and safety of oral versus intravenous ibuprofen in very low birth weight preterm infants with patent ductus arteriosus. J Pediatr 2011; 158: 549554.CrossRefGoogle ScholarPubMed
Oncel, MY, Yurttutan, S, Erdeve, O, 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: 510514.CrossRefGoogle ScholarPubMed
Andreoli, SP. Acute renal failure in the newborn. Semin Perinatol 2004; 28: 112123.CrossRefGoogle ScholarPubMed
Clyman, RI. Mechanisms regulating the ductus arteriosus. Biol Neonate 2006; 89: 330335.CrossRefGoogle ScholarPubMed
Hamrick, SE, Hansmann, G. Patent ductus arteriosus of the preterm infant. Pediatrics 2010; 125: 10201030.CrossRefGoogle ScholarPubMed
El-Khuffash, A, Jain, A, Corcoran, D, et al. Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies. Pediatr Res 2014; 76: 238244.CrossRefGoogle ScholarPubMed
Van Overmeire, B, Chemtob, S. The pharmacologic closure of the patent ductus arteriosus. Semin Fetal Neonatal Med 2005; 10: 177184.CrossRefGoogle ScholarPubMed
Mitra, S, Florez, ID, Tamayo, ME, et al. Association of placebo, indomethacin, ibuprofen, and acetaminophen with closure of hemodynamically significant patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. JAMA 2018; 319: 12211238.CrossRefGoogle ScholarPubMed
Yurttutan, S, Bozkaya, A, Hüdayioğlu, F, Oncel, MY. The effect of combined therapy for treatment of monotherapy-resistant PDA in preterm infants. J Matern Fetal Neonatal Med 2019; 32: 36623665.CrossRefGoogle ScholarPubMed
Sahin, IO, Dinlen Fettah, N, Kara, M, et al. May we use ibuprofen as doses against courses in thetreatment of patent ductus arteriosus in premature infants? J Matern Fetal Neonatal Med 2016; 29: 18571860.Google Scholar
Terrin, G, Conte, F, Scipione, A, et al. Efficacy of paracetamol for the treatment of patent ductus arteriosus in preterm neonates. Ital J Pediatr 2014; 40: 21.CrossRefGoogle ScholarPubMed
Sjoukes, A, Venekamp, RP, van de Pol, AC, et al. Paracetamol (acetaminophen) or non-steroidal antiinflammatory drugs, alone or combined, for pain relief in acute otitis media in children. Cochrane Database Syst Rev 2016; 12: 11534.Google ScholarPubMed
Mattos, JL, Robison, JG, Yellon, RF. Acetaminophen plus ibuprofen for treatment of Post-tonsillectomy pain in children. Otolaryngol Head Neck Surg 2013; 149: 113114.CrossRefGoogle Scholar
Wong, T, Stang, AS, Ganshorn, H, et al. Combined and alternating paracetamol and ibuprofen therapy for febrile children. Cochrane Database Syst Rev 2013; 10: 9572.Google Scholar