Oral Paracetamol for Closure of Patent Ductus Arteriosus in Selected Preterm Neonates

research letter

Indian Pediatr 2016;53: 171-172

	Oral Paracetamol for Closure of Patent Ductus Arteriosus in Selected Preterm Neonates
*Pankaj kumar Mohanty, Karthik Nagesh N and Abdul Razak** Department of Neonatology, Manipal Hospital, Bangalore, India. Email: [email protected]
We prospectively studied the effect of oral paracetamol in closing hemodynamically significant Patent ductus arteriosus in preterm infants (gestational age <32 weeks) where Ibuprofen was contraindicated. 29 of 40 neonates (72.5%) showed successful response while 11 (29.5%) failed to show any response. No major complications were seen. Keywords: Paracetamol, Patent Ductus arteriosus, Prematurity.
A hemodynamically-significant Patent ductus arteriosus (PDA) may cause cardiovascular instability, exacerbate respiratory distress syndrome and also prolong the requirement for assisted ventilation in preterm neonates. The options available to close the duct are pharmacological (Ibuprofen or indomethacin) and surgical. Recently, paracetamol has been shown to be an alternative treatment for closure of PDA [1-4]. We aimed to analyze the efficacy of paracetamol in closing PDA in preterm neonates where ibuprofen was contra-indicated. This observational study was performed at a tertiary Level IIIB Neonatal Intensive Care Unit in Southern India. The study was approved by Institutional ethics committee. Preterm neonates with hemodynamically-significant PDA where ibuprofen was contraindicated-platelet count < 60,000/mm3, serum creatinine >1.5 mg/dL, necrotizing enterocolitis and bleeding diathesis [4,5], were included. Hemodynamically significant PDA was defined as transductal size >1.5 mm with Left atrium to Aortic root diameter >1.4 mm or reversal of diastolic flow in descending aorta causing increased fraction inspired oxygen (FiO2_of >40% or oxygenation index of >10 on invasive ventilation). Neonates with major congenital abnormality, elevated liver enzymes (AST >55 U/L or ALT >23 U/L) [6], and those with perinatal asphyxia were excluded. An informed consent was obtained from the parents. Echocardiography was performed by the same Pediatric Cardiologist. Oral paracetamol (Crocin drops 100 mg/mL, GlaxoSmithKline Asia), 15 mg/kg/dose every 6 hourly (gestational age >30 weeks) or 8 hourly (gestational age <30 weeks), was administered. There were 192 preterm neonates (gestational age <32 weeks) admitted in the unit during study period, of which forty were given paracetamol. Mean (SD) birth weight and gestation were 1186 (289) grams and 29 (1.9) weeks, respectively. All the neonates had PDA size of more than 1.5 mm and Left-atrium to aortic ratio of more than 1.4 mm; five had reversal of blood flow in descending aorta. The contraindications for ibuprofen were coagulopathy (n=25), suspected necrotizing enterocolitis (n=12), thrombocytopenia (n=7), Intraventricular hemorrhage (n=5), and oliguria (n=3). Of 40 neonates, 29 (72.5%) showed successful response while 11 neonates (29.5%) failed to show the response. PDA was found to be closed on day 3 in 10 cases (25%), day 4 in 17 cases (42.5%) and day 5 in 1 case. There was mild elevation of liver enzymes in 22 cases (55%) which returned to baseline spontaneously. No major complication pertaining to treatment was observed. Eleven neonates (28.5%) failed to show response; of which, two underwent ligation, four responded to repeat oral ibuprofen, one was lost to follow-up, and the remaining four responded to repeat doses of oral paracetamol. Earlier observational studies [7,8] and randomized controlled trials [1,9,10] have also documented successful closure of hemodynamically significant PDA in preterm neonates. Our study adds to the evidence that oral paracetamol may be used as an alternative for PDA closure in preterm infants where ibuprofen is contra-indicated. The limitations of our study were lack of pharmacokinetic data (i.e., optimal dosage, time to start therapy and route of administration), no control arm and lack of external validity. Spontaneous closure of PDA could also have confounded the results. We conclude that oral paracetamol is an alternative treatment for PDA closure where oral ibuprofen is contraindicated. 　 Contributors: KN: conceptualized and designed the study; PK: collected the data; AR, PK: written the manuscript and analyzed the data; KN: reviewed and approved the final manuscript. Funding: None; Competing interests: None stated. References 1. 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