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


METHODS
Prospective, observational study.


METHODS
Pediatric intensive care unit in a tertiary care children's hospital.


METHODS
Ten children with pulmonary hypertension because of congenital cardiac defects who were in the intensive care unit and on nitric oxide after cardiac surgery.


METHODS
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 the administration of sildenafil.


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.


CONCLUSIONS
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.
Raja
Shahzad G
SG
Department of Cardiac Surgery, Royal Hospital for Sick Children, Glasgow, UK. drrajashahzad@hotmail.com
Danton
Mark D
MD
MacArthur
Kenneth J
KJ
Pollock
James C
JC
D000704:Analysis of Variance; D001784:Blood Gas Analysis; D001993:Bronchodilator Agents / Q000627:therapeutic use; D006348:Cardiac Surgical Procedures; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood / Q000150:complications / Q000503:physiopathology* / Q000601:surgery; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage* / Q000494:pharmacology; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects*; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology; D012107:Research Design; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome; D006113:United Kingdom; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology
D001993:Bronchodilator Agents; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000068677:Sildenafil Citrate