FCPS Paediatrics TOACS · Interactive Station RESPIRATORY EMERGENCY

✅ Candidate's answer:
• Diagnosis: Persistent pulmonary hypertension of the newborn (PPHN), also known as persistent fetal circulation.
• Supporting features:
1️⃣ Term infant with meconium aspiration syndrome (MAS) – a common predisposing condition.
2️⃣ Severe hypoxemia (PaO2 45-50 mmHg) on 100% oxygen – disproportionate to chest X-ray findings (clear lungs).
3️⃣ Preductal-postductal saturation gradient (85% right hand vs 60% foot) – indicates right-to-left shunting across the ductus arteriosus.
4️⃣ No evidence of parenchymal lung disease on chest X-ray.
5️⃣ Normal PaCO2 (not hypercapnic) – rules out primary hypoventilation.
6️⃣ Susceptible history: meconium aspiration, birth asphyxia.

✅ Candidate's answer:
• Normal transition at birth: Pulmonary vascular resistance (PVR) falls rapidly due to lung expansion, increased PaO2, and release of vasodilators (nitric oxide, prostacyclin). Systemic vascular resistance (SVR) rises. Ductus arteriosus constricts and foramen ovale closes.
• In PPHN: PVR remains elevated (maladaptation, maldevelopment, or underdevelopment of pulmonary vasculature).
- Right-to-left shunting occurs across the foramen ovale and ductus arteriosus → deoxygenated blood bypasses the lungs → profound hypoxemia.
• Preductal-postductal gradient:
- Preductal (right hand/right arm): Receives blood from left ventricle (oxygenated blood from lungs + some right-to-left shunt across foramen ovale). Less desaturated.
- Postductal (lower body): Blood from ductus arteriosus (right-to-left shunt from pulmonary artery to aorta) → deoxygenated blood → lower saturation.
- Gradient >5-10% (or absolute difference >10-15 mmHg PaO2) indicates right-to-left ductal shunting.

✅ Candidate's answer:
• Categories:
1️⃣ Maladaptation (acute/reactive vasoconstriction): Most common. Due to hypoxia, acidosis, sepsis, meconium aspiration, RDS, pneumonia. The pulmonary vasculature is normal but constricted.
2️⃣ Maldevelopment (remodeling): Chronic in utero hypoxia (e.g., oligohydramnios, IUGR, maternal NSAID use causing premature ductal constriction, post-term). Thickened pulmonary arterioles (increased muscularization).
3️⃣ Underdevelopment (hypoplastic): Decreased cross-sectional area of the pulmonary vascular bed (congenital diaphragmatic hernia, pulmonary hypoplasia, Potter syndrome).
• Predisposing conditions: Meconium aspiration syndrome, birth asphyxia, sepsis/pneumonia (especially GBS), RDS, congenital diaphragmatic hernia, oligohydramnios, maternal NSAIDs/SSRI use, polycythemia, hypoglycemia, hypothermia.

✅ Candidate's answer:
• Most important differential: Cyanotic congenital heart disease (CHD) – especially ductal-dependent lesions (e.g., transposition of great arteries, tricuspid atresia, pulmonary atresia, total anomalous pulmonary venous return, hypoplastic left heart syndrome).
• Differentiation (echocardiography is gold standard):
- PPHN: Structurally normal heart; right-to-left shunting at foramen ovale and/or PDA; elevated pulmonary artery pressure; right ventricular hypertrophy/dilation; no structural anomalies.
- Cyanotic CHD: Structural abnormality; may have abnormal chamber sizes; abnormal great vessel connections.
• Clinical clues to PPHN:
- Preductal-postductal saturation gradient (suggests PPHN, but can occur in some CHD).
- Hyperoxia test: In PPHN, PaO2 <100 mmHg on 100% oxygen (similar to CHD). Not discriminatory.
- Chest X-ray: Normal or clear lungs in PPHN; may show cardiomegaly or abnormal situs in CHD.
- ECG: May show right ventricular strain in both.
- Response to iNO (improvement in PPHN; no effect in CHD).
• Perform emergent echocardiography in all suspected PPHN cases to exclude CHD before starting iNO or other vasodilators.

✅ Candidate's answer:
• Echocardiogram (with Doppler) – the gold standard:
- Demonstrates right-to-left or bidirectional shunting across PDA and/or foramen ovale.
- Estimates pulmonary artery pressure (using tricuspid regurgitation jet velocity).
- Assesses septal flattening (systemic right ventricular pressure).
- Rules out structural congenital heart disease.
• Preductal and postductal pulse oximetry: Demonstrates saturation gradient.
• Arterial blood gas (from preductal and postductal sites): Shows PaO2 gradient.
• Chest X-ray: May be normal (maladaptation PPHN) or show underlying lung disease (MAS, RDS, pneumonia).
• Complete blood count, blood culture, CRP: To rule out sepsis.
• Hyperoxia test (using 100% oxygen for 10-15 minutes): Both PPHN and cyanotic CHD show minimal response (PaO2 <100 mmHg). Not reliable alone.

✅ Candidate's answer:
• Preductal saturation: Place the probe on the right hand or right arm (supplied by the brachiocephalic artery, which receives blood before the ductus arteriosus).
• Postductal saturation: Place the probe on either foot (supplied by descending aorta, distal to ductal insertion).
• Significant gradient: A difference of >5-10% in SpO2 between preductal and postductal sites, or an absolute difference in PaO2 >10-15 mmHg, suggests right-to-left shunting through the ductus arteriosus, indicating PPHN.
• In severe PPHN, postductal saturation may be as low as 40-60% while preductal saturation is 70-90%.
• Note: A gradient is NOT always present (e.g., if shunting is only at the atrial level or if there is bidirectional shunting).
• Always document preductal and postductal saturations in any cyanotic neonate.

✅ Candidate's answer:
• 1. Secure airway and optimize ventilation: Intubate if not already done. Use gentle ventilation strategies – avoid hyperventilation (which may worsen cerebral vasoconstriction) but aim for normocarbia or permissive hypercapnia (PaCO2 45-55 mmHg). Hypocarbia (PaCO2 <35 mmHg) should be avoided (reduces cerebral blood flow).
• 2. Optimize oxygenation: Target preductal SpO2 90-95%. Avoid hyperoxia (PaO2 >90 mmHg) – free radical injury.
• 3. Correct acidosis: Maintain pH >7.25. Use sodium bicarbonate if severe metabolic acidosis (controversial).
• 4. Maintain normothermia and euglycemia.
• 5. Minimize stimulation: Sedation (fentanyl, midazolam) to reduce agitation and oxygen consumption; may use muscle relaxants (pancuronium) if infant fights the ventilator.
• 6. Treat underlying conditions: Antibiotics if sepsis suspected; surfactant if MAS/RDS.
• 7. Inhaled nitric oxide (iNO): First-line pulmonary vasodilator. Start at 20 ppm (range 5-20 ppm).
• 8. Inotropes/vasopressors: To maintain systemic blood pressure (and avoid hypotension which worsens right-to-left shunting). Dopamine, dobutamine, milrinone, or epinephrine.
• 9. Consider high-frequency oscillatory ventilation (HFOV) if conventional ventilation fails to maintain oxygenation.
• 10. Prepare for possible ECMO if refractory.

✅ Candidate's answer:
• Role: iNO is a selective pulmonary vasodilator. It is the first-line treatment for PPHN. It reduces the need for ECMO by approximately 40%.
• Mechanism: iNO diffuses across the alveolar-capillary membrane, activates guanylyl cyclase in vascular smooth muscle, increases cGMP, and causes pulmonary vasodilation. It does not affect systemic vascular resistance (selective).
• Starting dose: 20 ppm (range 5-20 ppm). Some centers start at 10-20 ppm. Higher doses (40-80 ppm) are not more effective and increase toxicity risk.
• Weaning: Reduce to 5-10 ppm after 6-24 hours if improvement. Discontinue when FiO2 <0.6 and dose is 1-2 ppm. Do not stop abruptly (risk of rebound pulmonary hypertension).
• Side effects:
- Methemoglobinemia (rare at doses <20 ppm).
- Increased nitrogen dioxide (NO2) – a pulmonary irritant.
- Bleeding risk (inhibits platelet aggregation – theoretical).
- Rebound pulmonary hypertension if stopped abruptly.
• iNO is only effective if the infant has functional pulmonary vasculature (not effective in underdevelopment categories like CDH? – some benefit).

✅ Candidate's answer:
• Avoid hypocarbia (PaCO2 <35 mmHg): Hypocarbia causes cerebral vasoconstriction and may worsen neurologic outcomes. It is NOT recommended for routine management.
• Avoid hyperventilation (inducing respiratory alkalosis): While alkalosis (pH >7.45) theoretically reduces PVR, the risk of cerebral ischemia from hypocarbia outweighs benefits. No longer recommended.
• Permissive hypercapnia (PaCO2 45-55 mmHg) is safe and acceptable. Some centers target PaCO2 up to 60 mmHg.
• Goals: Maintain pH >7.25 (avoid acidosis), PaCO2 45-55 mmHg, preductal SpO2 90-95%.
• Use lung-protective ventilation: Low tidal volumes (4-6 mL/kg), moderate PEEP (5-8 cm H2O) to recruit atelectatic lungs.
• High-frequency oscillatory ventilation (HFOV): Considered if conventional ventilation fails to maintain oxygenation (OI >25), especially in parenchymal lung disease (MAS, RDS). HFOV improves lung recruitment and reduces volutrauma.

✅ Candidate's answer:
• Why systemic blood pressure is critical: Right-to-left shunting through the ductus arteriosus worsens when systemic vascular resistance (SVR) falls. Maintaining SVR reduces the shunting and improves oxygenation.
• Inotropes/vasopressors used:
- Dobutamine: Inotrope, increases cardiac output, mild vasodilator – good for myocardial dysfunction.
- Milrinone: Inotrope + pulmonary vasodilator (phosphodiesterase-3 inhibitor) – beneficial in PPHN with ventricular dysfunction.
- Epinephrine: Potent inotrope + vasopressor – used in severe shock.
- Vasopressin: May be used for refractory hypotension.
• Controversy with dopamine: Dopamine increases systemic blood pressure but may also increase PVR (via alpha-adrenergic effects). Some studies suggest dopamine worsens oxygenation. Dopamine is often avoided as a first-line agent in PPHN; dobutamine or milrinone are preferred.
• Hydrocortisone: Used in refractory shock with suspected adrenal insufficiency (common in severe PPHN).

✅ Candidate's answer:
• ECMO (extracorporeal membrane oxygenation) is used when maximal medical therapy (including iNO, HFOV, and inotropes) fails.
• Oxygenation index (OI) = (MAP × FiO2 × 100) ÷ PaO2
- OI >40 on two consecutive blood gases 30-60 minutes apart is a strong indication for ECMO.
- OI >40 predicts >80% mortality without ECMO.
• Other indications:
- PaO2 <50 mmHg on 100% oxygen for 4-12 hours.
- Acute deterioration with refractory hypoxemia.
- Contraindications to ECMO: <34 weeks gestation, weight <2 kg (some centers <1.8 kg), severe intraventricular hemorrhage, lethal congenital anomalies, irreversible brain damage, prolonged mechanical ventilation >10-14 days (due to risk of irreversible lung disease).
• With ECMO, survival in PPHN is >80-90%.

✅ Candidate's answer:
• Survival: Overall survival is ~90% with modern management (including iNO and ECMO). Survival is lower for severe maldevelopment/underdevelopment categories (e.g., CDH 50-70%).
• Neurodevelopmental outcome: Up to 25% of survivors may have neurodevelopmental impairment (cognitive delays, cerebral palsy, hearing loss, visual impairment). Risk factors: severe hypoxemia, need for ECMO, birth asphyxia, intraventricular hemorrhage.
• Sensorineural hearing loss: Occurs in ~10-20% of PPHN survivors, especially those requiring ECMO. All survivors need formal audiology testing.
• Pulmonary outcomes: Most children have normal lung function, but some develop reactive airway disease (wheezing) or persistent pulmonary hypertension in infancy.
• Recurrence: PPHN does not recur after the neonatal period. However, if there is an underlying condition (e.g., pulmonary hypoplasia), long-term pulmonary hypertension may persist.
• Follow-up: All PPHN survivors should have neurodevelopmental follow-up, hearing screening, and cardiology follow-up (echocardiogram to ensure resolution of pulmonary hypertension).

✅ Candidate's answer:
• Not routinely. PGE1 is NOT used to treat PPHN.
• Indications for PGE1 in a cyanotic neonate: To maintain ductal patency in ductal-dependent congenital heart disease (e.g., transposition of great arteries, pulmonary atresia, tricuspid atresia, hypoplastic left heart syndrome).
• Why not use PGE1 in PPHN? PGE1 is a non-selective vasodilator that may also cause systemic hypotension, worsening right-to-left shunting. It does NOT selectively lower PVR.
• However, if echocardiography cannot be performed urgently and the differential between PPHN and ductal-dependent CHD cannot be determined, some experts may start PGE1 while arranging definitive imaging, because missing CHD is more dangerous than giving unnecessary PGE1. But this is controversial.
• Best practice: Obtain an urgent echocardiogram to differentiate. If PPHN is confirmed, do NOT use PGE1.

✅ Candidate's answer:
• Alveolar capillary dysplasia (ACD) with misalignment of pulmonary veins is a rare, lethal developmental disorder of the lung. It is an important cause of refractory PPHN that fails to respond to iNO and ECMO.
• Presentation: Profound hypoxemia within hours to days of birth, unresponsive to maximal therapy (100% oxygen, iNO, HFOV, ECMO). Often associated with other congenital anomalies (gastrointestinal, genitourinary, cardiac).
• Diagnosis: Made on lung biopsy or autopsy (shows thickened alveolar septa, reduced capillaries, misaligned pulmonary veins that run with arteries). Genetic mutations in FOXF1 gene.
• Prognosis: Uniformly fatal (no effective treatment). Lung transplantation is experimental.
• Indication to suspect ACD: Persistent severe PPHN in a term infant without other risk factors, with no improvement on iNO and ECMO, and with associated extrapulmonary anomalies. Lung biopsy is rarely performed due to poor prognosis.