Persistent pulmonary hypertension of the newborn is the persistence of or reversion to pulmonary arteriolar constriction, causing a severe reduction in pulmonary blood flow and right-to-left shunting. Symptoms and signs include tachypnea, retractions, and severe cyanosis or desaturation unresponsive to O₂. Diagnosis is by history, examination, chest x-ray, and response to O₂. Treatment is with O₂; alkalinization; high-frequency ventilation; nitric oxide; pressors, inotropes, or both; and extracorporeal membrane oxygenation if other therapies fail.

Persistent pulmonary hypertension of the newborn is a disorder of pulmonary vasculature that affects term or postterm infants.

Etiology

The most common causes involve

• Perinatal asphyxia or hypoxia

A history of meconium staining of amniotic fluid or meconium in the trachea is common. Hypoxia triggers reversion to or persistence of intense pulmonary arteriolar constriction, a normal state in the fetus.

Additional causes include

• Premature ductus arteriosus or foramen ovale closure, which increases fetal pulmonary blood flow and may be triggered by maternal NSAID use
• Polycythemia, which obstructs blood flow
• Congenital diaphragmatic hernia, in which one lung is severely hypoplastic, forcing most of the pulmonary blood flow through the other lung
• Neonatal sepsis presumably because vasoconstrictive prostaglandins are produced by activation of the cyclooxygenase pathway by bacterial phospholipids

Pathophysiology

Whatever the cause, elevated pressure in the pulmonary arteries causes abnormal smooth muscle development and hypertrophy in the walls of the small pulmonary arteries and arterioles and right-to-left shunting via the ductus arteriosus or a foramen ovale, resulting in intractable systemic hypoxemia. Both pulmonary and systemic resistances are high, which leads to an increased load on the heart. This load increase may result in right heart dilation, tricuspid insufficiency, and right heart failure.

Symptoms and Signs

Symptoms and signs include tachypnea, retractions, and severe cyanosis or desaturation unresponsive to supplemental O₂. In infants with a right-to-left shunt via a patent ductus arteriosus, oxygenation is higher in the right brachial artery than in the descending aorta; thus cyanosis may be differential (ie, O₂ saturation in the lower extremities is ≥ 5% lower than in the right upper extremity).

Diagnosis

• Cyanosis unresponsive to O₂ therapy
• Echocardiogram
• X-ray to identify underlying disorders

Diagnosis should be suspected in any near-term infant with arterial hypoxemia, cyanosis, or both, especially one with a suggestive history whose O₂ saturation does not improve with administration of 100% O₂. Diagnosis is confirmed by echocardiography, which can confirm the presence of elevated pressures in the pulmonary artery and simultaneously can exclude congenital heart disease. On x-ray, lung fields may be normal or may show changes due to the underlying disorder (eg, meconium aspiration syndrome, neonatal pneumonia, congenital diaphragmatic hernia).

Prognosis

An oxygenation index (mean airway pressure [cm H₂O] × fraction of inspired O₂ [Fio₂] × 100/Pao₂) > 40 predicts mortality of > 50%. Overall mortality ranges from 10 to 80% and is directly related to the oxygenation index but also varies with the underlying disorder. However, many survivors (perhaps one third) exhibit developmental delay, hearing deficits, functional disabilities, or a combination. This rate of disability may be no different from that of other infants with severe illness.

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Treatment

• O₂ to dilate pulmonary vasculature and improve oxygenation
• Mechanical ventilation support
• Use of nitric oxide considered
• Extracorporeal membrane oxygenation as needed
• Circulatory support

Treatment with O₂, which is a potent pulmonary vasodilator, is begun immediately to prevent disease progression. O₂ is delivered via bag and mask or mechanical ventilation; mechanical distention of alveoli aids vasodilation. Fio₂ should initially be 1 but can be titrated downward to maintain Pao₂ between 50 and 90 mm Hg to minimize lung injury. Once Pao₂ is stabilized, weaning can be attempted by reducing Fio₂ in decrements of 2 to 3%, then reducing ventilator pressures; changes should be gradual, because a large drop in Pao₂ can cause recurrent pulmonary artery vasoconstriction. High-frequency oscillatory ventilation expands and ventilates the lungs while minimizing barotrauma and should be considered for infants with underlying lung disease in whom atelectasis and ventilation/perfusion (V/Q) mismatch may exacerbate the hypoxemia of persistent pulmonary hypertension of the newborn.

Inhaled nitric oxide relaxes endothelial smooth muscle, dilating pulmonary arterioles, which increases pulmonary blood flow and rapidly improves oxygenation in as many as half of patients. Initial dose is 20 ppm, titrated downward by effect.

Extracorporeal membrane oxygenation (see Respiratory Disorders in Neonates, Infants, and Young Children: Extracorporeal membrane oxygenation (ECMO)) may be used in newborns with severe hypoxic respiratory failure defined by an oxygenation index > 35 to 40 despite maximum respiratory support.

Normal fluid, electrolyte, glucose, and Ca levels must be maintained. Infants should be kept in a neutral thermal environment and treated with antibiotics for possible sepsis until culture results are known. Inotropes and pressors may be required as part of circulatory support.

Last full review/revision March 2009 by Anand D. Kantak, MD; John T. McBride, MD