Effects of escalating doses of sildenafil on hemodynamics and gas exchange in children with pulmonary hypertension and congenital cardiac defects.

摘要

OBJECTIVE: Sildenafil (Viagra, Pfizer) is being increasingly used to treat pulmonary hypertension in children. However, there are limited data available to suggest dosage regimens. The purpose of this study was to determine the effects of escalating doses of sildenafil on hemodynamics and gas exchange in children with pulmonary hypertension because of congenital cardiac defects. DESIGN: Prospective, observational study. SETTING: Pediatric intensive care unit in a tertiary care children's hospital. PARTICIPANTS: Ten children with pulmonary hypertension because of congenital cardiac defects who were in the intensive care unit and on nitric oxide after cardiac surgery. INTERVENTION: Patients received sildenafil every 4 hours via a gastric tube in incremental doses of 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, and 2.0 mg/kg along with nitric oxide during their stay in the intensive care unit until they were extubated. Hemodynamic and arterial blood gas measurements were taken before (baseline) and 60 minutes after theadministration of sildenafil. MEASUREMENTS AND MAIN RESULTS: All doses of sildenafil caused significant reduction in pulmonary artery pressure with no significant effect on systemic arterial and central venous pressures. Arterial partial pressure of oxygen was decreased after a 2.0 mg/kg dose of sildenafil but not significantly. No significant differences were found among the 4 doses. CONCLUSION: For the treatment of pulmonary hypertension in children with congenital cardiac defects, a 0.5 mg/kg dose of sildenafil every 4 hours is therapeutically as effective as a 2.0 mg/kg dose every 4 hours. However, a large dose-ranging and pharmacokinetic study of sildenafil in children with pulmonary hypertension because of congenital cardiac defects is needed to validate the safety and efficacy of the dose-range and dosing interval suggested by this study.