What medications can be used to treat pulmonary hypertension in the pediatric age group?

Medications for Pediatric Pulmonary Hypertension

For lower-risk pediatric PAH, initiate oral therapy with either sildenafil (a PDE5 inhibitor) or an endothelin receptor antagonist, while higher-risk children require immediate intravenous or subcutaneous prostacyclin therapy. 1

Risk-Stratified Initial Drug Selection

Lower-Risk PAH (WHO Functional Class I-II)

• Start with oral monotherapy using either a phosphodiesterase type 5 (PDE5) inhibitor OR an endothelin receptor antagonist (ERA) 1
• This approach is supported by Class I evidence from the American Heart Association and American Thoracic Society 1

Higher-Risk PAH (WHO Functional Class III-IV)

• Initiate intravenous or subcutaneous prostacyclin therapy immediately without attempting oral therapy first 1
• Do not delay prostacyclin in severely symptomatic children 1

Specific Drug Classes and Agents

PDE5 Inhibitors (Sildenafil)

Weight-based dosing algorithm: 2

• Infants <1 year: 0.5-1 mg/kg orally three times daily (delay in extremely preterm infants until retinal vascularization complete) 2
• Children <20 kg: 10 mg orally three times daily 2
• Children >20 kg: 20 mg orally three times daily 2

Critical safety warning: Avoid high-dose sildenafil (>20 mg TID in children >20 kg) due to 3.5-fold increased mortality risk demonstrated in the STARTS-2 study 2

Sildenafil improves exercise capacity, functional class, and hemodynamics at medium doses 3, 4

Endothelin Receptor Antagonists

• Bosentan is the most studied ERA in pediatric PAH 5
• Can be used as first-line oral therapy for lower-risk patients 1

Prostacyclin Analogs

Epoprostenol, treprostinil, and iloprost are available prostanoid options 5

• Intravenous or subcutaneous routes for severe disease 1
• Inhaled prostacyclin analogs may be considered as adjunctive therapy in refractory cases 5

Inhaled Nitric Oxide (iNO)

• Persistent pulmonary hypertension of the newborn (PPHN): iNO is indicated to reduce need for ECMO 5
• Bronchopulmonary dysplasia with PH: iNO can be effective for established BPD with symptomatic PH 5
• Congenital diaphragmatic hernia: iNO can improve oxygenation but use cautiously with LV dysfunction 5

Calcium Channel Blockers

Only use in children >1 year who demonstrate acute vasoreactivity during cardiac catheterization 1

• This represents a small minority of pediatric PAH patients 5
• Do not use empirically without documented vasoreactivity 1

Combination Therapy Strategy

Adopt a progressive treatment escalation approach where PAH-specific drugs are added sequentially to achieve therapeutic targets 1

Escalate therapy when patients demonstrate: 1

• Persistent WHO functional class III-IV symptoms despite initial therapy
• Worsening hemodynamics on serial echocardiograms
• Elevated NT-proBNP levels
• Declining six-minute walk distance (in children >8 years)

Combination therapy with bosentan, sildenafil, and inhaled iloprost may improve survival in severe PAH 5

Supportive Medications

Diuretics

• Loop diuretics, thiazides, or spironolactone for signs of right heart failure 5, 1
• Use cautiously as overdiuresis can reduce RV preload 5
• Class IIa recommendation 5

Oxygen Therapy

• Supplemental oxygen for saturations <92%, especially with associated respiratory disease 5, 1
• Target O2 saturations 92-95% in BPD with PH 5
• Class IIa recommendation 1

Digoxin

• Rarely used currently in pediatric PH 5
• Dose: 5 μg/kg orally twice daily up to 10 years, then once daily 5
• Class IIb recommendation with limited data 5

Anticoagulation (Warfarin)

• May be considered in IPAH/HPAH, low cardiac output states, long-term indwelling catheters, or hypercoagulable states 5
• Target INR 1.5-2.0 in young children 5
• Do NOT use in very young children due to hemorrhagic complication risks 5
• Class IIb recommendation 5

Special Population Considerations

Bronchopulmonary Dysplasia

• Optimize lung disease treatment before initiating PAH-targeted therapy 5
• iNO effective for established BPD with symptomatic PH 5, 1
• PAH-targeted therapy useful after optimizing respiratory and cardiac disease 5

Congenital Heart Disease-Associated PAH

• Cardiac catheterization mandatory to measure PVRI and determine operability before repair 1
• Same drug classes apply but careful monitoring required 2

Critical Monitoring Parameters

Serial assessments should include: 1

• Echocardiograms to assess RV function and estimate PA pressures
• NT-proBNP or BNP levels as biomarkers of disease severity
• Six-minute walk distance in children >8 years

Transplant Referral Threshold

Refer children in WHO functional class III-IV on optimized medical therapy or with rapidly progressive disease to lung transplantation centers 1

• This is a Class I recommendation with Level of Evidence A 1