Chapter 130: Persistent Pulmonary Hypertension of the Newborn (PPHN)

Persistent fetal circulation · Pathophysiology (maladaptation, maldevelopment, hypoplasia) · Clinical diagnosis · iNO · HFOV · ECMO · Prognosis
🫁 Key therapy: Inhaled nitric oxide (iNO) reduces need for ECMO by 40%. Survival >90% with optimal management.

🫁 Persistent Pulmonary Hypertension of the Newborn: Core Concepts

📊 Incidence
1 in 500-1,500 live births. Term/postterm infants. Associated with MAS, pneumonia, asphyxia, CDH, idiopathic.
🧬 Pathophysiology
Failure of postnatal drop in PVR → right-to-left shunting (ductus, foramen ovale) → severe hypoxemia. Etiologies: maladaptation (reactive), maldevelopment (idiopathic), hypoplasia (CDH).
🩺 Clinical signs
Cyanosis out of proportion to CXR, pre-ductal/post-ductal SpO2 gradient, labile hypoxemia, ± murmur of tricuspid regurgitation.
📷 Diagnosis
Echocardiogram: flattening of interventricular septum, right-to-left or bidirectional shunting, elevated RV pressure.
💊 Treatment
iNO (20 ppm), optimize lung inflation, gentle ventilation (avoid hyperoxia/hypocarbia), inotropes (dobutamine, milrinone), sedation, HFOV rescue, ECMO if refractory.
📈 Prognosis
Survival ~90%. Neurodevelopmental impairment and hearing loss occur in ~25% of survivors.
⚠️ Differential diagnosis: Cyanotic CHD (TGA, TAPVR, truncus, HLHS), alveolar capillary dysplasia (FOXF1 mutation – lethal), surfactant deficiency.

🔍 Approach to term newborn with severe hypoxemia: suspect PPHN

1
Recognize risk factors – MAS, pneumonia/sepsis, asphyxia, CDH, maternal SSRI use, meconium staining.
2
Clinical assessment – Cyanosis, labile SpO2, pre-ductal (right hand) > post-ductal (foot) gradient >5-10%. Respiratory distress may be minimal despite severe hypoxemia.
3
Hyperoxia test – Term infant: PaO2 <100 mmHg on 100% O2 suggests right-to-left shunt (PPHN or CHD).
4
Echocardiography (gold standard) – Assess direction of shunt, RV pressure, rule out structural CHD, evaluate function.
5
Exclude alveolar capillary dysplasia – Suspect if refractory to iNO/ECMO, associated with FOXF1 mutations, lethal.

📋 Stepwise management of PPHN

1
General supportive care – Correct acidosis (pH >7.25), maintain normothermia, treat hypoglycemia, consider volume/transfusion.
2
Optimize lung inflation – Recruit atelectasis with adequate PEEP (5-8 cmH2O). Avoid hyperinflation (volutrauma). Permissive hypercapnia (PaCO2 45-60) acceptable.
3
Inhaled nitric oxide (iNO) – Start at 20 ppm. Monitor methemoglobin and NO2. Wean after 6-24h as tolerated. Do not abruptly discontinue (rebound PH).
4
Inotropic support – Dobutamine or epinephrine to support cardiac output. Milrinone for lusitropy and pulmonary vasodilation. Avoid dopamine (may increase PVR).
5
High-frequency ventilation (HFOV) – Rescue for refractory hypoxemia or air leak. Improves lung recruitment and reduces volutrauma.
6
ECMO (extracorporeal membrane oxygenation) – Indicated when OI >40 despite optimal medical therapy (iNO, HFOV, inotropes). Survival >80-90%.
📌 Oxygenation index (OI) = (FiO2 × mean airway pressure) / PaO2 × 100. OI >40 predicts high mortality and need for ECMO.

🧠 Rapid reflex prompts – PPHN

📌 First-line pulmonary vasodilator?
Inhaled nitric oxide (iNO) 20 ppm.
📌 How to clinically suspect PPHN?
Pre-ductal SpO2 > post-ductal SpO2 (gradient >5-10%).
📌 Hyperoxia test: PaO2 >100 mm Hg on 100% O2?
Suggests pulmonary cause; PaO2 <100 suggests PPHN/CHD.
📌 Which inotrope is preferred in PPHN?
Dobutamine or epinephrine; avoid dopamine (may increase PVR).
📌 Indication for ECMO in PPHN?
OI >40 refractory to iNO and HFOV, or pH <7.15 with severe hypoxemia.
📌 Most lethal mimic of PPHN?
Alveolar capillary dysplasia (ACD) with FOXF1 mutation – uniformly fatal.
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