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

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.