Abstract 2033: Sildenafil Prevents Rebound Pulmonary Hypertension After Discontinuation of Inhaled Nitric Oxide: A Randomized, Double-Blind Placebo-Controlled Study in Children
INTRODUCTION:Post operative pulmonary hypertension(PHT) is common after surgery for congenital heart disease and nitric oxide(NO) is a widely accepted treatment in this group of sick infants.Rebound PHT can complicate the weaning of inhaled NO, and is in part related to transient depletion of intrinsic cyclic-GMP during NO therapy.We hypothesised that prevention of breakdown of pulmonary vascular cyclic-GMP, using sildenafil, a phosphodiesterase-5 inhibitor, may prevent rebound PHT.
METHODS: Thirty patients (median weight 4.2Kg) were enrolled and 29 completed study. Patients were randomized to receive 0.4mg/kg of sildenafil or placebo, 1 hour before NO was stopped.PA pressures and blood gases were measured before giving the study drug, and one and 4 hours after stopping NO.Data are given as mean(SD) or median (IQR) as appropriate. RESULTS:Rebound PHT occurred in 10/14 placebo patients, and 0/15 sildenafil patients (P< 0.001). In the sildenafil group, PA pressure was 35.1(13.3)mmHg at baseline, 35.8 (14.8)mmHg 1 hour after stopping NO, and 33.8 (11.8)mmHg at 4 hours (P = 0.22). In the placebo group, PA pressure was 31.0 (9.0)mmHg at baseline, 45.2(20.4) mmHg at 1 hour after stopping NO and 36.6 (9.9)mmHg at 4 hours (P < 0.001). PA pressure increased by 25% (14,67) in placebo and by 1% (−9,5) in sildenafil patients (P<0.001). NO was restarted in 4/14 of placebo and 0/15 sildenafil patients (P=0.042). Ventilation duration after study was 98.0 (47.0,223.5) hrs for placebo and 28.2 (15.7,54.6) hrs for sildenafil group (P=0.024).
CONCLUSION: A single dose of enteral sildenafil prevented the development of rebound PHT and also reduced the duration of mechanical ventilation in children.