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Comparison of the effect of continuous and standard intermittent bolus paracetamol infusion on patent ductus arteriosus

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Abstract

The aim of this study was to evaluate the effect of paracetamol on patent ductus arteriosus (PDA) closure and clinical outcomes in preterm infants when used as standard intermittent bolus and continuous intravenous (IV) infusion. Preterm neonates with birth weight (BW) ≤ 1500 g and gestational age (GA) ≤ 30 weeks were included in this study. During the study period, IV paracetamol therapy was given to all infants with hemodynamically significant patent ductus arteriosus (hsPDA). The patients were divided into the standard IV intermittent bolus infusion group and the continuous IV infusion group. Standard IV intermittent bolus paracetamol therapy was administered in the form of 15-mg/kg doses as 1-h infusions every 6 h for 5 days, while continuous IV paracetamol infusion therapy was administered as a 60-mg/kg/day dose continuously for 5 days. During the study period, 247 patients were evaluated, of which a total of 137 patients with hsPDA were included. There were no significant differences between the intermittent bolus and continuous infusion groups in terms of mean GA or BW. The continuous paracetamol infusion group had significantly higher rates of PDA-related morbidities, multiple paracetamol courses, and PDA ligation procedure compared with the standard intermittent bolus group.

Conclusion: Our results were the first in the literature to compare IV paracetamol infusion regimens for PDA. Our results indicate that standard intermittent bolus infusion is still the most appropriate IV paracetamol regimen for the treatment of PDA.

Trial registration: ClinicalTrials.gov Identifier: NCT04469413

What is Known:

• Paracetamol has been proposed for the treatment of patent ductus arteriosus in preterm neonates.

• There is no consensus on the duration and form of administration of paracetamol in hsPDA, and the information on this issue is insufficient.

What is New:

• Our study was the first in the literature to compare IV paracetamol infusion regimens for PDA.

• Standard intravenous intermittent bolus paracetamol infusion was more effective in pharmacologic PDA closure compared with continuous intravenous paracetamol infusion and was associated with lower rates of PDA-related BPD, NEC, and need for ligation.

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Abbreviations

ALT:

Aminotransferase

AST:

Aspartate aminotransferase

BPD:

Bronchopulmonary dysplasia

BW:

Birth weight

COX:

Cyclo-oxygenase

CYP:

Cytochrome P450

ECHO:

Echocardiography

GA:

Gestational age

hsPDA:

Hemodynamically significant patent ductus arteriosus

IV:

Intravenous

IVH:

Intraventricular hemorrhage

MV:

Mechanical ventilation

NEC:

Necrotizing enterocolitis

NICU:

Neonatal intensive care unit

NIV:

Non-invasive ventilation

NSAID:

Non-steroidal anti-inflammatory drug

O2 :

Oxygen

PG:

Prostaglandin

PGHS:

Prostaglandin-H2 synthetase

POX:

Peroxidase

RDS:

Respiratory distress syndrome

ROP:

Retinopathy of prematurity

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Acknowledgments

The authors would like to thank all the nursing staff of neonatal intensive care unit in Zekai Tahir Burak Maternity Education and Research Hospital.

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Authors and Affiliations

  1. Division of Neonatology, Zekai Tahir Burak Maternity, Education, and Research Hospital, Health Sciences University, Ankara, Turkey

    Ufuk Cakir, Cuneyt Tayman, Nazmiye Bengu Karacaglar, Esra Beser & Burak Ceran

  2. Department of Pediatric Cardiology, Zekai Tahir Burak Maternity, Education, and Research Hospital, Health Sciences University, Ankara, Turkey

    Handan Unsal

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  1. Ufuk Cakir
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Contributions

Dr Cakir conceptualized and designed the study, interpreted the data, drafted the initial manuscript, and reviewed. Prof Tayman coordinated and supervised data collection, critically reviewed the manuscript for important intellectual content, and approved the final version. Dr Karacaglar, Dr Ozmen, and Dr Ceran collected data and carried out the initial analyses. Dr Unsal performed echocardiographic examination. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Ufuk Cakir.

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The authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved by the local ethics committees prior to the study.

Informed consent

Written informed consent was obtained from the parents.

Additional information

Communicated by Daniele De Luca

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Cakir, U., Tayman, C., Karacaglar, N.B. et al. Comparison of the effect of continuous and standard intermittent bolus paracetamol infusion on patent ductus arteriosus. Eur J Pediatr 180, 433–440 (2021). https://doi.org/10.1007/s00431-020-03822-1

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