Paracetamol Dosing for PDA Closure in Preterm Infants
For preterm infants with hemodynamically significant patent ductus arteriosus, intravenous paracetamol should be administered at 15 mg/kg every 6 hours for 3 days, which achieves ductal closure in approximately 78-90% of cases. 1, 2, 3
Standard Dosing Regimen
The established protocol consists of:
- Initial and maintenance dose: 15 mg/kg intravenously every 6 hours 2, 4, 3
- Duration: 3 days (total of 12 doses) 2, 5
- Route: Intravenous administration is preferred in critically ill preterm neonates 2, 3
This dosing achieves therapeutic serum concentrations in 97-98% of patients at steady state, though extreme preterm neonates may be less likely to reach therapeutic levels after the first dose. 3
Alternative Lower-Dose Regimen
A reduced-dose alternative of 10 mg/kg every 8 hours can be considered if hepatotoxicity concerns arise, with an 83% closure rate. 6 This lower dose was developed after one patient experienced significant transaminase elevation with the standard regimen, though this approach provides less frequent dosing and may have slightly lower efficacy. 6
Clinical Context and Indications
Paracetamol should be used when:
- Contraindications exist to NSAIDs (ibuprofen/indomethacin) 2, 4, 5
- Previous NSAID therapy has failed 4, 5
- Risk factors for NSAID complications are present (renal dysfunction, active bleeding, thrombocytopenia) 1, 2
The diagnosis of hemodynamically significant PDA must be confirmed by echocardiography showing ductal diameter ≥1.4 mm/kg, LA:Ao ratio >1.4, unrestrictive pulsatile flow, or reversed diastolic flow in the descending aorta. 2
Monitoring Requirements
Serial echocardiograms should be performed daily during treatment, with repeat imaging 48 hours after completion to confirm closure. 2, 6, 5 Monitor for:
- Liver function tests (ALT/AST) to detect hepatotoxicity 6, 3
- Renal function (creatinine, urine output) to identify acute kidney injury 3
- Clinical signs of bleeding or perfusion changes 1
Approximately 10-18% of patients may develop elevated transaminases, though severe hepatotoxicity is uncommon with the standard regimen. 6, 3
Efficacy and Safety Profile
Paracetamol demonstrates:
- Closure rates: 78-100% across studies, with most achieving closure within 48 hours 2, 4, 3, 5
- Lower adverse event profile compared to NSAIDs: no gastrointestinal perforation, minimal renal toxicity, and no bleeding complications 2, 4, 5
- Effectiveness across gestational ages: 23-33 weeks and birth weights 415-1650g 2, 3, 5
Important Caveats
If ductal closure is not achieved after the first 3-day course, consider a second course of paracetamol or proceed to surgical ligation rather than continuing indefinitely. 7 Very low birth weight infants require particularly careful fluid management during treatment, as rapid volume administration can worsen left-to-right shunting and cause pulmonary edema. 8, 7
The standard ibuprofen regimen (10 mg/kg initial dose, then 5 mg/kg at 24-hour intervals) remains the guideline-recommended first-line pharmacologic therapy, but paracetamol represents a valuable alternative when NSAIDs cannot be used. 9, 1