Pediatric Pulmonary Hypertension

Pediatric Pulmonary Hypertension

• Definition: Pulmonary Hypertension (PH) is defined as a mean pulmonary artery pressure (mPAP) of >25mmHg at rest via catheterization.
• PAH (Pulmonary Arterial Hypertension) is a type of PH with mPAP of >25mmHg at rest via catheterization, pulmonary capillary wedge pressure ≤ 15 mm Hg, and increased pulmonary vascular resistance (PVR) > 3 wu x m2.

WHO Classification

• New classification system for Pediatrics established in 2011 in Panama Consensus.

Epidemiology

• Most common causes of PH in children: Transient disease processes (82%) such as PPHN, systemic-to-pulmonary shunts.
• Chronic PAH is rare in children (3 cases/million children), compared to PPHN, which is about 30 cases/million children.

Pathophysiology

• Abnormal function of the pulmonary vasculature leading to:
  • Excessive vasoconstriction
  • Smooth muscle hypertrophy and extension of smooth muscle cells onto arterioles
  • Pulmonary blood vessels obstruction due to monoclonal expansion of endothelial cells and plexiform lesions
  • Chronic thrombosis
  • Ongoing inflammation
• RV hypertension increases RV afterload, leading to:
  • Decreased stroke volume
  • RV hypertrophy
  • Tricuspid regurgitation
  • Diastolic dysfunction
  • RAS system activation
  • Atrial dilation
  • Septal flattening

Genetics

• Bone morphogenetic factor receptor type-II (BMPR-II) gene mutations are the most common identified genetic cause of PAH, found in 50%–90% of adults with HPAH.
• Presence of a BMPR-II mutation is associated with a 10%–20% lifetime risk of developing PAH.

Pulmonary Hypertension in Acute Lung Disease

• PH can occur as a consequence of increased PVR in severe lung disease, such as:
  • Acute lung injury/ARDS
  • Bronchiolitis
  • Pertussis

Clinical Presentation of PH

• Acute Pulmonary Hypertensive Crisis:
  • Hypotension is a common early sign
  • Late signs include bradycardia with hypotension and signal impending cardiac arrest

PH Diagnostic Evaluation

• Imaging:
  • X-ray: Enlarged cardiac silhouette due to RVH and enlarged central pulmonary arteries
  • CT: Helpful for excluding pulmonary causes of PH, such as interstitial lung disease or emphysema
  • MRI: May be superior to echocardiography for determining right ventricular volume and contraction
• Lung Biopsy: May be used for PH diagnosis

Treatment

• Oxygen and General Supportive Measures:
  • Oxygen
  • NIPPV
  • Inotropic medications (Adrenalin and/or milrinone)
  • Diuretics (for congestive symptoms, avoiding excessive reduction in intravascular volume)
  • Intubation and initiation of invasive mechanical ventilation
  • Hyperventilation (for severe, acute PH crisis)
• Pharmacotherapy:
  • Inhaled Nitric Oxide:
    • Vasodilatation by increasing cGMP within the vascular smooth muscle cells
    • Accumulation of nitrogen dioxide (NO2) and methemoglobin are potential toxicities
  • Calcium-Channel Blockers:
    • Nifedipine, diltiazem, and amlodipine
    • Only a small number of patients with IPAH will respond
  • Phosphodiesterase Type-5 Inhibitors:
    • Sildenafil
    • Increase intracellular cGMP and pulmonary vasodilatation
    • Reduce PAP and vascular resistance, effect is additive to that of NO
  • Prostacyclins:
    • Epoprostenol (Flolan)
    • Treprostinil (Remodulin)
    • Iloprost
  • Endothelin Receptor Antagonists:
    • Bosentan
    • Ambrisentan

Atrial Septostomy and Transplantation

• Atrial septostomy: for severe heart failure, refractory PH
• Transplantation: single lung, double lung, or heart–lung

Acute Pulmonary Hypertensive Crisis/RV Failure

• Adaptation of the RV to an increased afterload is critical
• Triggers:
  • Pain
  • Anxiety
  • Tracheal suctioning
  • Hypoxia
  • Acidosis
• Commonly described after:
  • Cardiac surgery
  • Rapid withdrawal of PH-specific therapy
  • Intercurrent illness or noncardiac interventions