An alternative drug (paracetamol) in the management of patent ductus arteriosus in ibuprofen-resistant or contraindicated preterm infants
- Mehmet Yekta Oncel1,
- Sadik Yurttutan1,
- Nurdan Uras1,
- Nahide Altug2,
- Ramazan Ozdemir1,
- Sadrettin Ekmen1,
- Omer Erdeve1,
- Ugur Dilmen1
- 1Department of Neonatology, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey
- 2Department of Pediatric Cardiology, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey
- Correspondence to Mehmet Yekta Oncel, Department of Neonatology, Zekai Tahir Burak Maternity Teaching Hospital, Hamaönü, Altındagğ, Ankara 06110, Turkey;
Contributors Oncel M Y and Uras N designed research; Oncel M Y, Yurttutan S, Ozdemir R and Ekmen S conducted research and followed by patients; Altug N made echocardiography. Oncel M Y and Erdeve O wrote the paper. Dilmen U had primary responsibility for final content. All authors read and approved the final manuscript.
- Received 14 March 2012
- Accepted 4 April 2012
- Published Online First 18 May 2012
The most commonly used drugs for closure of a haemodynamically significant patent ductus arteriosus (hsPDA) are cyclooxygenase inhibitors, mainly indomethacin and intravenous/oral ibuprofen. In contrast to high closure rates, several adverse effects have been reported with such medications, including gastrointestinal bleeding and perforation, weakened platelet aggregation, hyperbilirubinaemia and renal failure.1 ,2 The role of paracetamol as an alternative treatment for the closure of hsPDA has gained importance in recent years due to these potential side effects.3
We performed an observational study to evaluate the efficacy of paracetamol in preterm infants with hsPDA who did not respond to ibuprofen treatment in two sequential repeated courses and/or for whom treatment with ibuprofen was contraindicated. Contraindications for ibuprofen treatment included renal failure, gastrointestinal perforation, hyperbilirubinaemia and severe thrombocytopaenia. Treatment with oral paracetamol (Calpol, GlaxoSmithKline, Istanbul, Turkey) was started at a dose of 15 mg/kg every 6 h, with echocardiographic evaluation performed on the third day of treatment. In the event of evidence of a persistent hsPDA, treatment duration was extended up to 7 days in accordance to daily-performed echocardiography.
A total of eight preterm infants with a median gestational age of 28.5 weeks (234/7–365/7) and a median birth weight of 995 g (630–2970) were included in the study. Five (62.5%) of the infants were ibuprofen-resistant, while in two patients (25%) the drug was deemed contraindicated (renal failure, hyperbilirubinaemia-thrombocytopaenia). The other patient received paracetamol because of developed renal failure after the first cycle of ibuprofen treatment. The first dose of paracetamol was given after a median of 9.5 days (5–27), for a median duration of 5 days (3–7). Overall, paracetamol resulted in successful closure of hsPDA in seven (87.5%) patients, while one patient (12.5%) did not respond to treatment. Pre and post-treatment levels of liver enzymes were normal in all patients.
In a recent case series by Hammerman et al,3 paracetamol was given to two patients who did not respond to ibuprofen and to three patients with contraindications to treatment (hyperbilirubinaemia, thrombocytopaenia). Successful hsPDA closure was observed in all five patients whose gestational ages ranged from 26 to 296/7 weeks with birth weights between 720 and 1210 g without any side effect. Although its precise mechanism of action remains controversial, evidence suggests that paracetamol seems to act at the peroxidase segment of the enzyme, which indicates that paracetamol-mediated inhibition is facilitated by a reduction in the concentration of local peroxide.4
To date, our case series is the largest to evaluate the efficacy of paracetamol for the management of hsPDA. Based on our results, we suggest that paracetamol seems to be a valid alternative to surgical ligation in patients who are either ibuprofen resistant or for whom cyclooxygenase inhibitors are contraindicated. If paracetamol is proven to be effective in future randomised-controlled trials, it may become the treatment of choice for the management of hsPDA mainly due to its more favourable side-effect profile.
Competing interests None.
Patient Consent Obtained.
Ethics approval Zekai Tahir Burak Local Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.