Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates
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In this prospective study, we compared the efficacy and side effects of indomethacin, ibuprofen, and paracetamol in patent ductus arteriosus (PDA) closure in preterm neonates. Three hundred preterm neonates with hemodynamically significant PDA (hs-PDA) admitted at our neonatal intensive care unit were enrolled in the study. They were randomized into three groups. Group I (paracetamol group) received 15 mg/kg/6 h IV paracetamol infusion for 3 days. Group II (ibuprofen group) received 10 mg/kg IV ibuprofen infusion followed by 5 mg/kg/day for 2 days. Group III (indomethacin group) received 0.2 mg/kg/12 h indomethacin IV infusion for three doses. Laboratory investigations such as renal function test, liver function test, complete blood count, and blood gases were conducted in addition to echocardiographic examinations. All investigations were done before and 3 days after treatment. There was no significant difference between all groups regarding efficacy of PDA closure (P = 0.868). There was a significant increase in serum creatinine levels and serum blood urea nitrogen (BUN) in the ibuprofen and indomethacin groups (P < 0.001). There was a significant reduction in platelet count and urine output (UOP) in both ibuprofen and indomethacin groups (P < 0.001). There was a significant increase in bilirubin levels in only the ibuprofen group (P = 0.003). No significant difference of hemoglobin (HB) level or liver enzymes in all groups (P > 0.05). Ventilatory settings improved significantly in patients with successful closure of PDA than those with failed PDA closure (P < 0.001).
What is Known:
• Hemodynamically significant patent ductus arteriosus has many complications for preterm and low birth weight neonates and better to be closed. Many drugs were used for medical closure of PDA e.g. indomethacin, ibuprofen and recently paracetamol. Many studies compare safety and efficacy of paracetamol with either indomethacin or ibuprofen.
What is New:
• It is the first large study that compares the efficacy and side effects of the three drugs in one study.
KeywordsPDA closure Preterm neonate Paracetamol Ibuprofen Indomethacin
Blood urea nitrogen
Hemodynamically significant patent ductus arteriosus
Neonatal intensive care unit
Nonsteroidal anti-inflammatory drugs
Patent ductus arteriosus
Positive intermittent pressure
Retinopathy of prematurity
Serum glutamate-oxaloacetic transaminase
Serum glutamate-pyruvate transaminase
Abd El-Rahman El-Mashad: the idea of the research, supervising the work of research, and revising and approving the manuscript.
Heba El-Mahdy: selecting patients and dividing them into groups, supervising and following up patients, and revising the manuscript.
Doaa El-Amrousy: performing the echocardiography, writing the manuscript, doing the statistical analysis, and following up the patients.
Marwa Elgendy: following up the patients, gathering the data, and helping in writing the manuscript.
Compliance with ethical standards
None to declare.
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants
The study was approved by the local Ethics Committee of Faculty of Medicine of our University and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from all parents of the participants included in the study.
- 5.Dang D, Wang D, Zhang C, Zhou W, Zhou Q, Wu H (2013) Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: a randomized controlled trial. PLoS One 8:e778–e788Google Scholar
- 6.Dani C (2014) Ibuprofen and paracetamol for patent ductus arteriosus. J Pediatr Neonat Individual Med 3(2):1–4Google Scholar
- 12.Jones LJ, Craven PD, Attia J, Thakkinstian A, Wright I (2010) Network meta-analyses of indomethacin versus ibuprofen versus placebo for PDA in preterm infants. Arch Dis Child Fetal Neonatal 164(3):135–140Google Scholar
- 26.Roofthooft DW, van Beynum IM, de Klerk JC, van Dijk M, van den Anker JN, Reiss IK, Tibboel D, Simons SH (2015) Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure. Eur J Pediatr 174(11):1433–1440CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Vane JR, Botting RM (1997) Mechanism of action of anti-inflammatory drugs. In: Sinzinger H, Samuelsson B, Vane JR, Paoletti R, Ramwell P, Wong PY-K (eds) Recent advances in prostaglandin, thromboxane, and leukotriene research. Advances in experimental medicine and biology. Plenum Press, New York, pp. 131–138CrossRefGoogle Scholar