Sildenafil exposure and hemodynamic effect after Fontan surgery.

Area of Science:

• Pediatric Cardiology
• Cardiovascular Surgery
• Pharmacology

Background:

• The Fontan procedure is a palliative surgery for single-ventricle defects, often leading to altered hemodynamics.
• Children post-Fontan surgery may experience elevated pulmonary vascular resistance and reduced cardiac output.

Purpose of the Study:

• To evaluate the hemodynamic effects and safety of sildenafil in children following Fontan surgery.
• To determine sildenafil exposure levels in this pediatric population.

Main Methods:

• A prospective, dose-escalation trial was conducted in a single-center pediatric catheterization laboratory.
• Nine children (median age 5.2 years) post-Fontan surgery received single-dose intravenous sildenafil (0.25-0.45 mg/kg).
• Hemodynamic parameters were assessed via cardiac catheterization and echocardiography before and after sildenafil administration.

Main Results:

• Sildenafil significantly increased stroke volume (+22%) and cardiac output (+10%), while decreasing systemic and pulmonary vascular resistance (-16% and -10%, respectively).
• Pulmonary arterial pressures decreased and pulmonary blood flow increased post-sildenafil.
• Peak sildenafil concentrations were within the range associated with significant phosphodiesterase type-5 inhibition, and no adverse events were reported.

Conclusions:

• Intravenous sildenafil acutely improves cardiopulmonary hemodynamics in children after Fontan surgery.
• The observed sildenafil exposure and hemodynamic improvements suggest a potential therapeutic role for sildenafil in this population.
• Sildenafil administration was safe within the studied dose range.