Abstract 1671: Randomized Controlled Trial of IV Sildenafil for Postoperative Pulmonary Hypertension in Children with Congenital Heart Disease
INTRODUCTION: Pulmonary hypertension (PH) may complicate the postoperative course of patients with congenital heart disease. Inhibition of the cGMP-specific phosphodiesterase is a potential therapeutic modality.
OBJECTIVE: To evaluate efficacy, safety and resource utilization of intravenous (IV) sildenafil at three doses (low, medium, high) for postoperative patients with PH.
METHODS: This was an early terminated, randomized, multicenter, double blind, placebo controlled, dose ranging trial of IV sildenafil among children in the immediate postoperative period with confirmed PH greater than half systemic pressure following surgical repair. The primary endpoint was the need for additional therapy for treatment of PH within 24 hours of starting drug infusion. Secondary endpoints were time to extubation and length of stay.
RESULTS: The study was terminated by the sponsor due to slow enrollment. There were 87 subjects screened who provided informed consent; 18 patients (21%) had postoperative PH (confirmed by direct measurement) and were randomized; one patient was withdrawn prior to treatment. The median age was 5 months(range 3 months–14 years); 5 received placebo and 4 were in each low, medium, and high dose sildenafil groups. Two of 5(40%) in the placebo group required additional therapy in the first 24 hours compared with 2/12(17%) sildenafil patients (all doses combined, p=NS). Reduction in pulmonary artery (PA) pressure during the first four hours of treatment was greater in sildenafil patients (47±11 to 35± 6 mmHg vs. 49±12 to 49±17mmHg, p=.026). The median time to extubation (3 days vs. 8 days, p=.022 log rank) and length of ICU stay (6 days vs. 15 days, p=.008) were shorter for sildenafil patients. Four patients died during hospitalization; two prior to randomization and two who had received placebo. No adverse events or systemic hypotension were attributable to IV sildenafil.
CONCLUSIONS: The difficulty predicting which preoperative patients will demonstrate important postoperative PH challenges new drug trials for this increasingly rare problem. Morbidity and mortality for those who demonstrate postoperative PH remain high. Use of IV sildenafil is associated with lower PA pressure, shorter time to extubation and shorter ICU length of stay.