What is the supportive management of Persistent Pulmonary Hypertension of the Newborn (PPHN) in newborns?

Supportive Management of Persistent Pulmonary Hypertension of the Newborn (PPHN)

The cornerstone of supportive management for PPHN includes inhaled nitric oxide (iNO) therapy, lung recruitment strategies, and extracorporeal membrane oxygenation (ECMO) for severe cases refractory to initial management. 1

First-Line Management

• Inhaled nitric oxide (iNO) is indicated as first-line therapy for term and near-term infants with PPHN who have an oxygenation index exceeding 25 1, 2
• Lung recruitment strategies should be performed in patients with PPHN associated with parenchymal lung disease to improve the efficacy of iNO therapy 1, 3
• Optimal ventilation management is crucial, with careful attention to maintaining adequate lung inflation without causing volutrauma 2, 3
• Weaning iNO should be done gradually to 1 ppm before discontinuation to prevent rebound pulmonary hypertension, which can cause life-threatening elevations in pulmonary vascular resistance 1, 2

Escalation of Care for Refractory Cases

• ECMO support is indicated for term and near-term neonates with severe PH or hypoxemia that is refractory to iNO and optimization of respiratory and cardiac function 1
• ECMO should be considered when the oxygenation index exceeds 25 despite maximal medical therapy 1, 4
• Evaluation for underlying disorders such as alveolar capillary dysplasia and genetic surfactant protein diseases is reasonable for infants with severe PPHN who fail to improve after vasodilator, lung recruitment, or ECMO therapy 1

Adjunctive Pharmacological Therapies

• Sildenafil is a reasonable adjunctive therapy for infants with PPHN who are refractory to iNO, especially with an oxygenation index exceeding 25 1, 5
• Inhaled prostacyclin analogs may be considered as adjunctive therapy for infants with PPHN who are refractory to iNO and have an oxygenation index exceeding 25 1, 5
• Intravenous milrinone is reasonable in infants with PPHN and signs of left ventricular dysfunction 1, 5

Special Considerations for Different Etiologies

• Response to iNO is disease-specific - infants with idiopathic PPHN, acute respiratory distress syndrome, and sepsis (without refractory shock) typically show better responses compared to those with meconium aspiration syndrome or congenital diaphragmatic hernia 6
• For congenital diaphragmatic hernia (CDH), minimize peak inspiratory pressure and avoid large tidal volumes to reduce ventilator-associated lung injury 1
• High-frequency oscillatory ventilation is a reasonable alternative mode of ventilation for subjects with CDH when poor lung compliance, low volumes, and poor gas exchange complicate the clinical course 1, 3
• Use iNO cautiously in CDH patients with suspected left ventricular dysfunction, as it may worsen pulmonary edema due to increased preload to an abnormal left ventricle 1, 2

Monitoring and Follow-up

• Monitor methemoglobin levels during iNO therapy, as methemoglobin concentrations can increase during the first 8 hours of nitric oxide exposure 7
• Avoid abrupt discontinuation of iNO as it can cause rebound pulmonary hypertension even if no improvement in oxygenation was observed at the onset of therapy 1
• Serial echocardiograms are recommended to monitor response to therapy 1

Important Pitfalls to Avoid

• Failure to optimize lung inflation before or during iNO administration significantly reduces its efficacy 2, 3
• Inadequate ventilation strategies can compromise the effectiveness of iNO therapy 3
• Delayed referral to ECMO centers can increase mortality in severe cases 4
• Abrupt discontinuation of iNO can lead to life-threatening rebound pulmonary hypertension 1, 2

By following this comprehensive approach to the supportive management of PPHN, clinicians can optimize outcomes and reduce mortality in affected newborns.