## Patent Ductus Arteriosus (PDA) — Pharmacological Management **Key Point:** Indomethacin is the first-line NSAIDs for medical closure of hemodynamically significant PDA in neonates and preterm infants. ### Mechanism of Action Indomethacin inhibits prostaglandin E₁ (PGE₁) synthesis, which maintains ductal patency. By reducing PGE₁ levels, it promotes ductal smooth muscle contraction and closure. ### Efficacy & Dosing - **Success rate:** 70–80% closure in preterm infants when given within first 7–14 days of life - **Dosing:** 0.1 mg/kg IV every 12–24 hours for 3 doses - **Best window:** Most effective in infants <7 days old ### Alternative: Ibuprofen - Equally effective as indomethacin with fewer renal and GI side effects - Preferred in some centers, especially when renal function is a concern - Dosing: 10 mg/kg loading dose, then 5 mg/kg at 24 and 48 hours ### Contraindications to NSAIDs | Condition | Reason | |-----------|--------| | Active necrotizing enterocolitis (NEC) | Risk of perforation | | Thrombocytopenia (<50,000/μL) | Bleeding risk | | Active sepsis | Hemodynamic instability | | Renal impairment (Cr >1.8 mg/dL) | Nephrotoxicity | | Intraventricular hemorrhage (Grade III–IV) | Worsening hemorrhage | **High-Yield:** If medical management fails or is contraindicated, **acetaminophen** (15 mg/kg every 6 hours × 3–7 days) is emerging as an alternative. Surgical ligation is reserved for failed medical management or contraindications to NSAIDs. **Clinical Pearl:** PDA closure is most successful when initiated early (within first 2 weeks of life) in preterm infants. Term infants often require surgical closure. ### Why Other Agents Are Not First-Line - **Sildenafil:** Pulmonary vasodilator; used for pulmonary hypertension, not PDA closure - **Milrinone:** Inotrope/vasodilator; used for hemodynamic support, not ductal closure - **Enalapril:** ACE inhibitor; used for heart failure management, not PDA closure
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