Chapter 27: Inhaled Nitric Oxide

SCOPE

Use of inhaled nitric oxide in persistent pulmonary hypertension and hypoxemic respiratory failure in newborn infants.

DISEASE/CONDITION(S)

Persistent pulmonary hypertension of the newborn (PPHN) and hypoxemic respiratory failure (HRF) are common conditions in the neonatal intensive care unit (NICU) and affect both term and preterm infants. In term infants, pulmonary hypertension can be idiopathic, but is more commonly secondary to lung pathologies such as meconium aspiration syndrome (MAS), pneumonia, respiratory distress syndrome (RDS), perinatal asphyxia, congenital diaphragmatic hernia (CDH), and as a complication of congenital heart disease (CHD), usually in the postoperative period. Pulmonary hypertension is also observed in preterm infants either as a complication of RDS or bronchopulmonary dysplasia (BPD). The severity of HRF is commonly assessed by oxygenation index (OI). Oxygenation index (OI = mean airway pressure [MAP] in cm H₂O × FIO₂/PaO₂ in mmHg) is commonly used to assess severity and response to therapy in HRF. HRF is classified as mild (OI ≤15), moderate (OI >15 to ≤25), severe (OI >25 to ≤40), and very severe (OI >40).

BRIEF BACKGROUND

Infants with PPHN and HRF are commonly managed with mechanical ventilation, surfactant (in the presence of parenchymal lung disease), and supplemental oxygen to correct hypoxemia. If this conventional therapy is not effective, patients are treated with inhaled nitric oxide (iNO). Patients who fail to demonstrate sustained improvement in oxygenation with iNO and/or have persistent hypoxemia or evidence of cardiorespiratory compromise may need extracorporeal membrane oxygenation (ECMO). This chapter provides a framework for the indications, dosing, monitoring, contraindications, and side effects of iNO, the only FDA-approved pulmonary vasodilator in the newborn period.

RECOMMENDATIONS

The goal of therapy in HRF and PPHN is to improve oxygenation and reduce the stress on the right ventricle by reducing pulmonary vascular resistance. Specific pulmonary vasodilators such as iNO and oxygen reduce pulmonary vascular resistance and reduce right ventricular afterload.

INDICATIONS FOR INO

Severe HRF with PPHN

Inhaled nitric oxide is a pulmonary vasodilator approved for use in post-term, term, and late preterm infants (>34 weeks’ gestation at birth) for management of severe HRF (OI >25) associated with clinical or echocardiographic evidence of pulmonary hypertension in conjunction with ventilator support and other appropriate agents and reduces the need for ECMO (Class I; level of evidence A).

Moderate HRF with PPHN

Inhaled NO is indicated in term and late preterm infants with moderate HRF (OI >15 to ≤25) associated with evidence of PPHN to prevent further progression of disease (OI >30) (Class I; level of evidence B).

Non-Approved Uses of iNO

Preterm Infants

Rare instances of HRF associated with PPHN pathophysiology and ...