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Intravenous paracetamol for PDA closure in the preterm: a single-center experience

Abstract

Increasing recent evidence favors paracetamol use for patent ductus arteriosus (PDA) closure in preterms. Our study aims were (1) to assess efficacy and safety of intravenous (i.v.) paracetamol for PDA closure in a 23–32-week preterm population, as “first-line” (when traditional ibuprofen treatment was contraindicated) or “rescue” treatment (after ibuprofen failed), and (2) to identify predictors of PDA closure. The cumulative efficacy of consecutive cycles of i.v. paracetamol on PDA closure was confirmed after both “first-line” and “rescue” treatment, the overall PDA closure rates being, respectively, 56.7 and 61.1 % (p = 0.7624) after two cycles and 63.3 and 77.8 % (p = 0.2959) after three cycles. No toxicity was apparent after either “first-line” or “rescue” i.v. paracetamol treatment. On multivariate analysis, gestational age (GA) emerged as an independent predictor of PDA closure in the “first-line” i.v. paracetamol treatment group, while clinical risk index for babies (CRIB) score (a patient risk index based on birth weight, GA at birth, sex, patient’s temperature on admission, and maximum base excess in first 12 h of life) was an independent predictor of PDA closure failure in the “rescue” group.

Conclusion: I.V. paracetamol proved effective in our study population. Randomized control trials (RCTs) are warranted to further investigate the efficacy and safety of i.v. paracetamol for PDA closure in preterms.

What is Known:
Oral paracetamol has been judged as effective as oral ibuprofen for PDA closure in the preterm.
To date, only a handful of non-randomized studies exist to support the effectiveness of i.v. paracetamol in PDA closure.
What is New:
Our observations confirm the clinical efficacy of i.v. paracetamol for PDA closure in a very low birth weight (VLBW)/extremely low birth weight (ELBW) preterm population.
• Gestational age and CRIB score emerge as independent predictors of PDA closure.

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Abbreviations

BUN:

Blood urea nitrogen

CI:

Confidence interval

ELBW:

Extremely low birth weight

GA:

Gestational age

HsPDA:

Hemodynamically significant patent ductus arteriosus

i.v.:

Intravenous

NEC:

Necrotizing enterocolitis

OR:

Odds ratio

PDA:

Patent ductus arteriosus

RCT:

Randomized control trial

VLBW:

Very low birth weight

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Author contributions

Enrico Valerio was involved in data analysis and wrote the first draft of the manuscript. Marta Rossella Valente was involved in patient enrolling, data analysis, and contributed to the critical review of the manuscript. Sabrina Salvadori performed cardiac ultrasounds and contributed to the critical review of the manuscript. Anna Chiara Frigo performed statistical analysis and contributed to the critical review of the manuscript. Eugenio Baraldi contributed to the critical review of the manuscript. Paola Lago acted as a team coordinator, was involved in patient enrolling and data analysis, and contributed to the critical review of the manuscript.

Author information

Correspondence to Enrico Valerio.

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Ethical approval

All procedures performed involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors do not have financial disclosures or conflicts of interest.

Additional information

Communicated by Patrick Van Reempts

Appendix 1

Appendix 1

Table 7 Published studies on paracetamol for PDA treatment

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Valerio, E., Valente, M.R., Salvadori, S. et al. Intravenous paracetamol for PDA closure in the preterm: a single-center experience. Eur J Pediatr 175, 953–966 (2016). https://doi.org/10.1007/s00431-016-2731-9

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Keywords

  • Patent ductus arteriosus
  • Preterm
  • Paracetamol
  • Acetaminophen
  • Ibuprofen