Persistent pulmonary hypertension of newborns

Persistent pulmonary hypertension of the newborn is the persistence or return of pulmonary arteriolar constriction, causing a significant reduction in pulmonary blood flow and a right-to-left shunt. Symptoms and signs include tachypnea, chest wall retractions, and marked cyanosis or decreased oxygen saturation that is unresponsive to oxygen therapy. Diagnosis is based on history, examination, chest radiography, and response to oxygen supplementation. Treatment includes oxygen therapy to counteract acidosis, nitric oxide, or, if drug therapy is ineffective, extracorporeal membrane oxygenation.

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What causes persistent pulmonary hypertension of the newborn?

Persistent pulmonary hypertension of the newborn (PPHN) is a disorder of pulmonary vascularization that occurs in full-term and post-term infants. The most common causes are perinatal asphyxia or hypoxia (often with a history of meconium staining of the amniotic fluid or meconium in the trachea); hypoxia provokes return or persistence of severe constriction of the pulmonary arterioles, which is normal in the fetus. Additional causes include premature closure of the ductus arteriosus or foramen ovale, which increases pulmonary blood flow in the fetus and may be provoked by maternal use of NSAIDs; polycythemia, which disrupts blood flow; congenital diaphragmatic hernia, in which the left lung is significantly hypoplastic, causing most of the blood to be directed to the right lung; neonatal sepsis, apparently due to the production of vasoconstrictor prostaglandins by bacterial phospholipids via activation of the cyclooxygenase pathway. Whatever the cause, elevated pulmonary artery pressure causes abnormal development and hypertrophy of the smooth muscle of the small pulmonary arteries and arterioles, as well as right-to-left shunting of blood through the arterial duct or foramen ovale, leading to persistent systemic hypoxemia.

Symptoms of persistent pulmonary hypertension of the newborn

Symptoms and signs include tachypnea, chest wall retractions, and marked cyanosis or decreased oxygen saturation that does not respond to oxygen therapy. In infants with a right-to-left patent duct shunt, oxygenation in the right brachial artery is higher than in the descending aorta; therefore, cyanosis may be variable, with oxygen saturation in the lower extremities being approximately 5% lower than in the upper right extremity.

Diagnosis of persistent pulmonary hypertension of the newborn

The diagnosis should be suspected in any infant born at or near term who has arterial hypoxemia and/or cyanosis, particularly with a consistent history, and who does not show an increase in oxygen saturation on 100% oxygen. The diagnosis is confirmed by echocardiography with Doppler, which can confirm elevated pulmonary artery pressures while simultaneously ruling out congenital heart disease. Chest radiography may show normal lung fields or abnormalities consistent with the cause (meconium aspiration syndrome, neonatal pneumonia, congenital diaphragmatic hernia).

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Treatment of persistent pulmonary hypertension of the newborn

An oxygenation index [mean airway pressure (cm H2O), fraction of inspired oxygen 100/PaO2] greater than 40 is associated with a mortality rate greater than 50%. Overall mortality varies from 10 to 80% and is directly related to the oxygenation index and also depends on the cause. Many patients (about 1/3) with persistent pulmonary hypertension of the newborn experience developmental delay, hearing impairment, and/or functional impairment. The incidence of these impairments may not differ from that seen in other severe diseases.

Oxygen therapy, a potent pulmonary vasodilator, is started immediately to prevent progression of the disease. Oxygen is given by bag and mask or mechanical ventilation; mechanical stretch of the alveoli promotes vasodilation. FiO2 should initially be 1 but should be gradually reduced to maintain Pa between 50 and 90 mmHg to minimize lung injury. When PaO2 has stabilized, an attempt can be made to wean the child off the ventilator by reducing FiO2 by 2 to 3% at a time and then decreasing inspiratory pressure; changes should be gradual as a large reduction in PaO2 may re-constrict the pulmonary artery. High frequency oscillatory ventilation expands and ventilates the lungs while minimizing barotrauma and should be considered for children with lung disease as a cause of persistent pulmonary hypertension of the newborn, in whom atelectasis and ventilation/perfusion (V/P) mismatch may exacerbate hypoxemia.

Nitric oxide, when inhaled, relaxes the smooth muscles of the vessels, dilating the pulmonary arterioles, thereby increasing blood flow in the lungs and rapidly improving oxygenation in 1/2 of patients. The initial dose is 20 ppm, which is then reduced to that required to maintain the desired effect.

Extracorporeal membrane oxygenation can be used in patients with severe hypoxic respiratory failure, which is defined as an oxygenation index greater than 35-40 despite maximal respiratory support.

Fluid, electrolyte, glucose, calcium levels should be maintained. Children should be kept in an optimal temperature environment and given antibiotics until culture results are available due to the possibility of sepsis.