Intravenous sildenafil for postoperative pulmonary hypertension in children with congenital heart disease

Abstract

PurposeTo evaluate the efficacy and safety of intravenous sildenafil for immediate postoperative pulmonary hypertension (PH) in pediatric patients undergoing congenital heart surgery.MethodsA double-blind, multicenter, placebo-controlled, dose-ranging, parallel-group trial was conducted. Patients were randomized to one of three doses of intravenous sildenafil, or placebo, for a minimum of 24 h.ResultsThe study was heavily underpowered. Whereas enrollment of 228 patients (57 per treatment arm) was required to achieve the sample size estimate to detect difference between arms, the sponsor terminated the study after 15 months owing to slow patient accrual. Seventeen patients (median age 5 months) experiencing postoperative PH were randomized and treated, five with placebo and four each with low-, medium-, and high-dose sildenafil. In the first 24 h, 40% of placebo and 17% of sildenafil patients required additional therapy (p = 0.330). Median time to extubation (3 versus 8 days, p = 0.023) and intensive care unit stay (6 versus 15 days, p = 0.008) were shorter for sildenafil patients. Mean ± standard deviation systolic pulmonary artery pressure was reduced with sildenafil (46 ± 11 to 35 ± 6 mmHg, p = 0.027 versus placebo). No adverse events or systemic hypotension were attributed to sildenafil.ConclusionIntravenous sildenafil reduced pulmonary artery pressure and shortened time to extubation and intensive care unit stay in children with postoperative PH.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-010-2065-4) contains supplementary material, which is available to authorized users.

Coronary Artery Bypass Surgery in Left Main Disease with Idiopathic Artery Pulmonary Hypertension. Role of PGE Therapy

“…Documented neuro-hormonal effects have been reported by Hulsmann, through a reduction of atrial natriuretic factor and norepinephrine on the one hand and increased renal blood flow, with increased diuresis [6][7][8][9][10].…”

The Pharmacological Treatment of Pulmonary Arterial Hypertension

“…In 36 neonates with a mean age of 34 h and persistent PH (29 receiving concomitant inhaled NO), intravenous sildenafil by continuous infusion for at least 48 h and up to 7 days resulted in acute and sustained improvement in oxygenation (Steinhorn et al, 2009), with survival of 35 neonates at day 28. Intravenous sildenafil given for a minimum of 24 h, compared with placebo, also reduced mPAP and shortened time to extubation for immediate postoperative PH in a study of 17 children (median age, 5 months) with congenital heart disease (Fraisse et al, 2011). Another study showed that intravenous sildenafil augmented the pulmonary vasodilator effect of inhaled NO in 15 infants after cardiac surgery, but produced systemic hypotension and impaired oxygenation (Stocker et al, 2003).…”

Stability of sildenafil (Revatio®) dilutions in dextrose 5%

“…As described by Fraisse et al [1], maintenance infusions of sildenafil may have clear advantages. However, in order to correctly administer continuous i.v.…”

“…Dear Editor, With great interest we read the paper of Fraisse et al [1] in which the authors document the intravenous (i.v.) use of sildenafil in paediatric patients with congenital heart disease and pulmonary hypertension.…”

“…administration should be prepared and stored. Also Fraisse et al [1] did not explicitly state how the maintenance infusion should be prepared and stored.…”