Paracetamol in Ductal closure

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Paracetamol in Patent Ductus Arteriosus closure:

Paracetamol in Patent Ductus Arteriosus closure Dr.Ravi Sahota Fellow in NICU


Epidemiology Incidence and prevalence PDA is the most common congenital heart defect in preterm infants. Incidence: Approximately 8 per 1000 live births. Prevalence : Up to 60% infants <28 weeks' gestation have PDA. Frequency : PDA represents 5% to 10% of all congenital heart defects. Age : PDA is inversely correlated with gestational age, so that it is a common problem in premature infants and less prevalent in full-term neonates. Gender : PDA is more common in female than male neonates; ratio is 3:1 Elsevier

PowerPoint Presentation:

Echocardiography and Cerebral Doppler Sonography A left atrium–to–aortic root diameter ratio of 1.4 in the parasternal long-axis view, A DA diameter of 1.4 mm/kg body weight, Left ventricular enlargement, Holodiastolic flow reversal ,in the descending aorta indicate a significant PDA shunt. A resistance index of 0.9 ,on cerebral Doppler examination of the anterior cerebral artery, is a sign of significant ductal shunting with adverse cerebral steal effect. Diameter of the PDA =/ > the main pulmonary artery on the second day of life (DOL), then early pharmacologic or surgical treatment should be strongly considered. Ohlsson A, Shah PS

Pharmacotherapy of PDA:

Pharmacotherapy of PDA Indomethacin . Ibuprufen Use of paracetamol in ductal closure-which may be breakthrough event.

PowerPoint Presentation:

Mehmet Yekta Oncel , Sadik Yurttutan,Nurdan Uras , Nahide Altug,Ramazan Ozdemir,Sadrettin Ekmen,Omer Erdeve , Ugur Dilmen Department of Neonatology, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey Department of Pediatric Cardiology, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey Arch Dis Child Fetal Neonatal Ed January 2013

Methodology of study:

Methodology of study Observational study Efficacy of Paracetamol in Hemodynamically significant PDA Eligibility- Non responder or/and Contraindication for Ibuprofen. Contraindications for Ibuprofen- Renal failure, GI perforation , Hyperbilirubinemia , SevereThrombocytopenia . Dose : Paracetamol 15mg/kg Q6H and ECHO on day 3,and extension to day 7,if needed. Premedication and Post medication Liver Enzymes were checked.


Results Mean No. of subjects 8 Birth weight 630 – 2970 g 995 g Gestation age 23 -36 Wk 28.5 wk Non - responders to Ibuprofen 5 (62.5%) Subjects with C/I to Ibuprofen 2 (25%) ARF after 1 course of Ibuprofen 1 (12.5%) Ist dose Paracetamol 5 – 27d 9.5 d Duration of treatment 3 – 7 d 5d Success rate 7 (87.5%)



Discussion :

Discussion Mehmet et. al. (2012) Hammerman et. Al. (2011) No. of subjects 8 5 Birth weight 630 – 2970 g 720 – 1210 gm Gestation age 23 -36 Wk 26 – 29 wk Non - responders 5 (62.5%) 2 Subjects with C/I to nsaids 2 (25%) 3 ARF after 1 course of Ibuprufen 1 (12.5%) Ist dose Paracetamol 5 – 27d 3-17 d Duration of treatment 3 – 7 d Success rate 7 (87.5%) 5 (100%)


Discussion Precise MOA of Paracetamol is controversial. Paracetamol seems to act on peroxidase segment of prostaglandin synthetase , indicating reduction in local peroxidase concentration. Peroxidase is activated at 10-fold-lower peroxide concentrations than is cyclooxygenase . Therefore , paracetamol -mediated inhibition is facilitated at reduced local peroxide concentrations( eg , hypoxia). Theoretically , these differences would permit peroxidase inhibition to be optimally effective under conditions in which cyclooxygenase inhibition is less active. Grèen K, Drvota V, Vesterqvist O 1989;37:311–15. F94

Discussion -contd-:

Discussion - contd - There have been reports of paracetamol promoting ductal constriction , mostly in pregnant animal models, and there has been 1 case report of human in utero ductal closure after maternal self-medication with a combination of nimesulide and acetaminophen.

What is already known?:

What is already known? Ibuprofen and Indomethacin are efficacious in treating PDA and where ever one drug fails it is resistant to the other drug as well. Paracetamol has been used for Pain relief. Paracetamol seems to be quite free of the adverse effects preterm neonates, including Peripheral vasoconstriction, Gastrointestinal perforations, Oliguria , Impaired platelet aggregation, Hyperbilirubinemia .

PowerPoint Presentation:

Paracetamol can be used in three routes-Oral, Intravenous, Per rectal . All 3 forms are available in India.

What this study adds? :

What this study adds? Currently Paracetamol is Suggested as alternative to surgical ligation ,wherever NSAIDS are contraindicated or in resistant cases. Favourable side-effect profile v/s NSAIDS.

What is yet to know?:

What is yet to know? Paracetamol as 1 st line of drug treatment for PDA. Dose related closure of PDA by Paracetamol .

CloudNine Study:

CloudNine Study Objective: To compare the efficacy of ibuprofen & indomethacin for preterm ductal closure. Methods: This retrospective study was conducted from August 2007 to July 2012. A total 35 cases of PDA were identified. PDA was suspected clinically based on signs & symptoms. Echocardiographic confirmation was done in all cases. Of 35 newborn newborns 19 (54.28%)were male and 16 (45.72%) were female. Birth weight varied from 710 gm -3860 gm (mean 2000 gm) & gestation age varied from 27wks - 36 wks. Age at presentation varied from 1 to 6 days. Ibuprofen was administered to 22 (62.85%) babies IV Indomethacin was administered to 13 (37.14%) babies, of which 8 (61.58%) received at the rate of 0.2 mg/kg/dose for 3 days & remaining 5 ( 38.46%)received at the rate of 0.1 mg/kg/dose for 6 days. Results: Ductal closure was observed in 21 (95.45%) with ibuprofen and 12 (92.30%) with indomethacin . Babies who failed to respond to one mode of medical treatment was switched to other modality but no closure occurred & failure babies required surgical ligation. Side effect profile was comparable in both the groups. Conclusion: Treatment with ibuprofen & indomethacin is equally effective and the babies do not respond to one mode is unlikely to respond to other & requires surgical ligation.

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