Effects of Long-Term Sildenafil Treatment for Pulmonary Hypertension in Infants with Chronic Lung Disease

Objective

To determine the clinical course and outcomes of infants with chronic lung disease (CLD) and pulmonary hypertension (PH) who received prolonged sildenafil therapy.

Study design

We conducted a retrospective review of 25 patients <2 years of age with CLD in whom sildenafil was initiated for the treatment of PH while they were hospitalized from January 2004 to October 2007. Hemodynamic improvement was defined by a 20% decrease in the ratio of pulmonary to systemic systolic arterial pressure or improvement in the degree of ventricular septal flattening with serial echocardiograms.

Results

Chronic sildenafil therapy (dose range, 1.5-8.0 mg/kg/d) was initiated at a median of 171 days of age (range, 14-673 days of age) for a median duration of 241 days (range, 28-950 days). Twenty-two patients (88%) achieved hemodynamic improvement after a median treatment duration of 40 days (range, 6-600 days). Eleven of the 13 patients with interval estimates of systolic pulmonary artery pressure with echocardiogram showed clinically significant reductions in PH. Five patients (20%) died during the follow-up period. Adverse events leading to cessation or interruption of therapy occurred in 2 patients, 1 for recurrent erections, and the other had the medication held briefly because of intestinal pneumatosis.

Conclusion

These data suggest that chronic sildenafil therapy is well-tolerated, safe, and effective for infants with PH and CLD.

Abbreviations: ASD, Atrial septal, BPD, Bronchopulmonary dysplasia, CDH, Congenital diaphragmatic hernia, CLD, Chronic lung disease, iNO, Inhaled nitric oxide, mBP, Mean systemic blood pressure, mPAP, Mean pulmonary artery pressure, NO-cGMP, Nitric oxide/cyclic guanosine monophosphate, PCWP, Pulmonary capillary wedge pressure, PDA, Patent ductus arteriosus, PDE-5, Type 5 phosphodiesterase, PH, Pulmonary hypertension, PPHN, Persistent pulmonary hypertension of the newborn, PVR, Pulmonary vascular resistance, Qp, Pulmonary blood flow, Qs, Systemic blood flow, RA, Right atrial, RAP, Right atrial pressure, RV, Right ventricular, RVH, Right ventricular hypertrophy, sPAP, Systolic pulmonary artery pressure, ssBP, Systemic systolic blood pressure, SVR, Systemic vascular resistance, TRJV, Tricuspid regurgitant jet velocity