0936 Sildenafil for pulmonary hypertension (PulHT) in paediatrics

Given that PDE-5 (isoform 5 of phosphodiesterase) is located largely in pulmonary vascular smooth muscle and responsible for the breakdown of pulmonary vasodilating cyclicGMP, sildenafil as a PDE-5 inhibitor is a natural choice for the treatment of PulHT as it will increase levels of the vasodilator. This potential was recognised by the American FDA and the drug was approved in 2005 for use in adults. While relatively few studies have been done in children, sildenafil has nevertheless been incorporated into the management of paediatric PulHT. A recent review in Pediatric Cardiology covers the results for 193 children reported in 16 studies and 28 case series. Unlike adults, children usually present with secondary PulHT, and idiopathic disease is far less common. Associated/causative conditions are congenital cardiac and vascular disease, chronic lung disease and persistent PulHT of the newborn (PPHN). Pathophysiology has been identified as a combination of vasoconstriction, vascular remodelling and thrombus formation within the pulmonary vasculature. Twenty years ago median survival for children was only 10 months, however this has changed with treatment options that include nitric oxide, eprostenol, bosentan and sildenafil. Typical situations in which sildenafil has been studied include pre- and post-operative PulHT associated with congenital heart disease, first line use in PPHN, and in weaning off nitric oxide when the latter drug has resulted in a down-regulation of endogenous vasodilator. The drug is usually administered as a suspension of the adult tablets in a dose that ranges from 0.3 to 8mg/kg/day but usually 0.5 – 2mg/kg three times daily. Sildenafil has also been used for longer term outpatient therapy e.g. for children with congenital heart problems including Eisenmenger syndrome. In these cases exercise tolerance and haemodynamic parameters have improved. Intravenous sildenafil is available but adverse effects include systemic hypotension and impaired oxygenation. In terms of cost, the drug is considerably less expensive than the others mentioned above, and cost savings are also achieved through reductions in duration of ventilation and length of hospital stay.

Read more:
Pediatr Cardiol 2009; 15 June epub ahead of publication
Circulation 2005; 222: 3274-80
J Resp Crit Care Med 2006; 174: 1042-7