Paracetamol for Ductus Arteriosus Closure: Not Always a Success Story

Roofthooft, Daniella; Beynum, Ingrid van; Helbing, Willem A.; Simons, Sinno

doi:10.1159/000353451

Cited by 30 publications

(25 citation statements)

References 10 publications

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“…Paracetamol, however, also possessed a significant but milder constrictive effect. The results of the clinical observation by Roofthooft (9) highlighted above support the finding of our animal study. The difference in response between the human and mouse preterm ductus may represent different expression of the peroxidase moiety of prostaglandin H 2 Synthetase enzyme responsible for metabolizing arachidonic acid (7).…”

Section: Discussionsupporting

confidence: 90%

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Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies

et al. 2014

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BACKGROUND We evaluated the clinical effectiveness of variable courses of paracetamol on patent ductus arteriosus (PDA) closure and examined its effect on the in vitro term and preterm murine ductus arteriosus (DA). METHODS Neonates received one of the following three paracetamol regimens: short course of oral paracetamol (SCOP), long course of oral paracetamol (LCOP), and intravenous paracetamol (IVP) for 2–6 d. Pressure myography was used to examine changes in vasomotor tone of the preterm and term mouse DA in response to paracetamol or indomethacin. Their effect on prostaglandin synthesis by DA explants was measured by mass spectroscopy. RESULTS Twenty-one preterm infants were included. No changes in PDA hemodynamics were seen in SCOP infants (n = 5). The PDA became less significant and eventually closed in six LCOP infants (n = 7). PDA closure was achieved in eight IVP infants (n = 9). On pressure myograph, paracetamol induced a concentration-dependent constriction of the term mouse DA, up to 30% of baseline (P < 0.01), but required >1 μmol/l. Indomethacin induced greater DA constriction and suppression of prostaglandin synthesis (P < 0.05). CONCLUSION The clinical efficacy of paracetamol on PDA closure may depend on the duration of treatment and the mode of administration. Paracetamol is less potent than indomethacin for constriction of the mouse DA in vitro.

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Section: Discussionsupporting

confidence: 90%

“…Roofthooft et al . (9) reported giving paracetamol at a dose of 60 mg/kg/d to 10 infants (9 with i.v. and 1 with oral paracetamol) with a median (range) gestation of 25 1/7 (23 6/7 –26 6/7 ) at a median age of 22 d. PDA failed to close in seven of those infants with all needing ligation.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies

et al. 2014

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Section: Discussionmentioning

confidence: 99%

“…Nine case series involving a total number of 67 neonates treated with paracetamol for PDA, have been previously reported [12-20]. The larger series evaluating efficacy of paracetamol in a similar setting, included a maximum number of 10 patients [13,16,20]. Six studies verified the efficacy of paracetamol in very low birth weight neonates [12,13,16,17,19,20]; four of them reported a rate of ductal closure of 71-100% [12,13,16,17], while 2 series observed a very low efficacy rate (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Six studies verified the efficacy of paracetamol in very low birth weight neonates [12,13,16,17,19,20]; four of them reported a rate of ductal closure of 71-100% [12,13,16,17], while 2 series observed a very low efficacy rate (i.e. 0-20%) [19,20]. In particular, Alan S. et al reported the failure of paracetamol in 3 neonates treated with this drug after one or more unsuccessful courses of ibuprofen [19].…”

Section: Discussionmentioning

confidence: 99%

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Efficacy of paracetamol for the treatment of patent ductus arteriosus in preterm neonates

et al. 2014

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Inhibitors of the cyclo-oxygenase component of prostaglandin-H2 synthetase, namely indomethacin and ibuprofen, are commonly used in the treatment of hemodynamically significant patent ductus arteriosus. These drugs are associated with serious adverse events, including gastrointestinal perforation, renal failure and bleeding. The role of paracetamol, an inhibitor of the peroxidase component of prostaglandin-H2 synthetase, has been proposed for the treatment of patent ductus arteriosus. We report a series of 8 neonates (birth weight: 724 ± 173 g; gestational age: 26 ± 2 weeks) treated with paracetamol for a hemodynamically significant patent ductus arteriosus, because of contraindications to ibuprofen or indomethacin. Successful closure was achieved in 6 out of 8 babies (75%). Median ductal diameter was significantly reduced after treatment (from 1.2 mm, range 1.0-2.5 mm to 0.6 mm, range 0.0-2.5 mm, p = 0.038). No adverse or side effects were observed during treatment. On the basis of these results, paracetamol could be considered a promising and safe therapy for the treatment of patent ductus arteriosus in neonates.

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Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure

et al. 2015

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Finding the optimal pharmacological treatment of a patent ductus arteriosus (PDA) in preterm neonates remains challenging. There is a growing interest in paracetamol as a new drug for PDA closure. In this prospective observational cohort study, we evaluated the effectiveness of intravenous paracetamol in closing a PDA in very low birth weight infants with a hemodynamically significant PDA who either did not respond to ibuprofen or had a contraindication for ibuprofen. They received high-dose paracetamol therapy (15 mg/kg/6 h intravenous) for 3–7 days. Cardiac ultrasounds were performed before and 3 and 7 days after treatment. Thirty-three patients were included with a median gestational age of 251/7 weeks (IQR 1.66), a median birth weight of 750 g (IQR 327), and a median postnatal age of 14 days (IQR 12). Paracetamol was ineffective in 27/33 patients (82 %). Even more, after previous exposure to ibuprofen, this was even 100 %.Conclusion: In this study, paracetamol after ibuprofen treatment failure was not effective for PDA closure in VLBW infants. From the findings of this study, paracetamol treatment for PDA closure cannot be recommended for infants with a postnatal age >2 weeks. Earlier treatment with paracetamol for PDA might be more effective. What is known: • The ductus arteriosus fails to close after birth in 30 to 60 % of prematurely born neonates and is a significant cause of morbidity and mortality in these infants. • Paracetamol gained importance as an alternative drug in PDA closure. What is new: • Paracetamol for PDA closure after ibuprofen treatment failure was not effective in VLBW infants. • Effect of paracetamol on PDA closure was observed when given as primary treatment.

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Paracetamol for Ductus Arteriosus Closure: Not Always a Success Story

Cited by 30 publications

References 10 publications

Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies

Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies

Efficacy of paracetamol for the treatment of patent ductus arteriosus in preterm neonates

Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure

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