From the Guidelines
Management of pulmonary hypertension in neonates should prioritize the use of inhaled nitric oxide (iNO) as the first-line pulmonary vasodilator, with ECMO support considered for term and near-term infants with severe PH or hypoxemia that is refractory to iNO and optimization of respiratory and cardiac function 1.
Initial Management
Initial management includes maintaining adequate oxygenation with a target SpO2 of 91-95%, ensuring normal pH (7.35-7.45), avoiding hypercapnia, and treating underlying conditions like sepsis or pneumonia.
- Maintaining adequate oxygenation is crucial to prevent further damage to the pulmonary vasculature.
- Ensuring normal pH and avoiding hypercapnia can help reduce pulmonary vascular resistance.
Use of iNO and Other Vasodilators
Inhaled nitric oxide (iNO) is typically started at 20 ppm and weaned gradually based on response.
- Sildenafil is commonly used as an oral agent, starting at 0.5-1 mg/kg every 8 hours and titrating up to 2 mg/kg every 6-8 hours as needed 1.
- For severe cases, intravenous prostacyclin analogs like epoprostenol (starting at 1-2 ng/kg/min and titrating up) may be necessary.
- Milrinone (loading dose 50 μg/kg over 30-60 minutes, followed by 0.33-1.0 μg/kg/min) can provide both pulmonary vasodilation and inotropic support.
Supportive Care
Supportive care includes maintaining normal blood pressure with vasopressors if needed (dopamine 5-20 μg/kg/min or norepinephrine 0.05-1 μg/kg/min), minimizing handling to reduce stress, providing adequate sedation with fentanyl (1-5 μg/kg/hour) or morphine (10-40 μg/kg/hour), and considering high-frequency oscillatory ventilation for severe cases.
- These interventions work by enhancing nitric oxide pathways, inhibiting phosphodiesterase enzymes, or directly relaxing vascular smooth muscle to reduce pulmonary vascular resistance and improve right ventricular function.
- Lung recruitment strategies can improve the efficacy of iNO therapy and should be performed in patients with PPHN associated with parenchymal lung disease 1.
From the FDA Drug Label
INOmax® is indicated to improve oxygenation and reduce the need for extracorporeal membrane oxygenation in term and near-term (>34 weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension in conjunction with ventilatory support and other appropriate agents. The recommended dose of INOmax is 20 ppm. Maintain treatment up to 14 days or until the underlying oxygen desaturation has resolved and the neonate is ready to be weaned from INOmax therapy.
The management of pulmonary hypertension in neonates involves the use of nitric oxide (INOmax) at a recommended dose of 20 ppm in conjunction with ventilatory support and other appropriate agents. Treatment should be maintained for up to 14 days or until the underlying oxygen desaturation has resolved and the neonate is ready to be weaned from INOmax therapy 2.
- Key considerations:
- Monitor methemoglobin levels within 4-8 hours after initiation of treatment and periodically throughout treatment.
- Monitor PaO2 and inspired NO2 during INOmax administration.
- Avoid abrupt discontinuation of INOmax to prevent Rebound Pulmonary Hypertension Syndrome.
- Wean INOmax in several steps, pausing several hours at each step to monitor for hypoxemia.
From the Research
Management of Pulmonary Hypertension in Neonates
The management of pulmonary hypertension in neonates is a complex and challenging process, requiring a comprehensive approach to address the underlying pathophysiology and hemodynamic abnormalities.
- Key management goals include adequate tissue oxygen delivery and avoiding harm 3.
- The condition is associated with several unique diagnoses, each with different pathophysiology, and optimal care requires frequent reassessment 3.
- Cyanotic congenital heart disease must be actively ruled out as part of the differential diagnosis of persistent pulmonary hypertension of the newborn (PPHN) 4.
Treatment Strategies
Various treatment strategies are available for the management of pulmonary hypertension in neonates, including:
- Modern ventilatory strategies 4
- Inhaled nitric oxide 4, 5
- Sildenafil 4
- Prostacyclin 4
- Extracorporeal membrane oxygenation 4
- Inhibition of cyclic guanosine monophosphate-specific phosphodiesterases and scavengers of reactive oxygen species 5
Diagnostic Approaches
Diagnostic approaches play a crucial role in the management of pulmonary hypertension in neonates, including:
- Echocardiographic measures to evaluate pulmonary blood flow, pulmonary vascular resistance, pulmonary capillary wedge pressure, and myocardial contractility 6
- Bedside echocardiography to establish early definitive diagnosis, understand the pathophysiology and hemodynamic abnormalities, monitor the disease process, and response to therapeutic intervention 7
Pathophysiology and Biochemical Pathways
There has been significant advancement in the understanding of the pathophysiology and biochemical pathways responsible for abnormal vasoconstriction of pulmonary vasculature in PPHN 7.