Persistent pulmonary hypertension of the newborn

Branch 1: Recognition and Initial Assessment

A 39-week infant born via planned Caesarean section develops grunting, tachypnoea, and central cyanosis at 3 hours of age. Pre-ductal SpO₂ reads 85% and post-ductal reads 68% on 60% FiO₂. The 17% pre–post ductal SpO₂ gradient in a term infant with respiratory distress and cyanosis is the key finding — it confirms right-to-left ductal shunting and points toward persistent pulmonary hypertension of the newborn. The planned Caesarean delivery without labour is a recognised risk factor for PPHN. [1]

I would assess ABC immediately: ensure the airway is patent, evaluate the work of breathing, and measure heart rate, blood pressure, perfusion, and capillary refill. I would place pre- and post-ductal pulse oximetry probes on all four limbs to map the shunt, and establish intravenous access for blood gas, glucose, calcium, and cultures. [1]

Branch 2: Differential Diagnosis

Cyanotic congenital heart disease is the most urgent differential — transposition of the great arteries, total anomalous pulmonary venous return, and truncus arteriosus can all present this way. Primary lung disease (respiratory distress syndrome, meconium aspiration, pneumonia, congenital diaphragmatic hernia) is the next consideration, though the clear chest X-ray in idiopathic PPHN helps distinguish it. Sepsis can cause inflammatory pulmonary vasoconstriction and must always be considered. [4]

Branch 3: Investigation

An echocardiogram is the single most important investigation. It estimates pulmonary artery pressure from tricuspid regurgitation velocity and septal bowing, demonstrates the direction and size of shunting across the foramen ovale and ductus arteriosus, assesses biventricular function, and — critically — excludes structural congenital heart disease. No infant should receive iNO before the echocardiogram confirms the cardiac anatomy. [4]

I would also send simultaneous pre- and post-ductal blood gases to quantify the shunt, calculate the Oxygenation Index from the ventilator settings, and check glucose, ionised calcium, lactate, and a septic screen. [1]

Branch 4: Management

With an OI of 22, I would follow a stepwise approach. First, optimise ventilation with adequate PEEP and FiO₂, targeting permissive hypercapnia with pH 7.35–7.50 — aggressive hyperventilation is outdated. Second, correct hypoglycaemia, hypocalcaemia, and hypothermia. Third, support systemic blood pressure with inotropes to keep mean BP above 39 (the gestational age in weeks). [7]

Fourth, I would start inhaled nitric oxide at 20 ppm as the first-line selective pulmonary vasodilator. The Cochrane review confirms iNO improves oxygenation and reduces ECMO use by approximately 40% in term and near-term infants. [5]

Branch 5: Escalation

Despite iNO at 20 ppm for 4 hours, the OI rises to 35. This infant has refractory PPHN. I would add adjunctive vasodilators — sildenafil (a PDE-5 inhibitor) and milrinone (a PDE-3 inhibitor with inotropic effects) — and simultaneously contact the nearest ECMO centre for urgent referral. An OI above 25–40 despite maximal medical therapy is an indication for ECMO, and the decision must be made before the infant is in extremis. Veno-arterial ECMO is preferred given the haemodynamic instability. [3]