Sildenafil for Chronic Lung Disease

Mourani PM, Sontag MK, Ivy DD, and Abman SH. Effects of Long-Term Sildenafil Treatment for Pulmonary Hypertension in Infants with Chronic Lung Disease. J Pediatr (March 2009); 154: 379-384. Full Text | Full-Text PDF (197 KB)

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.

Comments. Sildenafil (aka Viagra®) treats pulmonary hypertension by selective inhibition of the PDE-5 enzyme thus increasing intracellular levels of cGMP. The effectiveness of this medication to treat pulmonary hypertension in the immediate neonatal period had been demonstrated in at least 1 small randomized, controlled trial (see Baquero Pediatrics 2006; 117:1077). We now see another potential use for sildenafil – the treatment of PH in older infants with chronic lung disease. Sildenafil treatment offers several advantages over treatment with inhaled nitric oxide in this setting:

4) Apparently well tolerated, even for very long courses of treatment (up to 600 days in this series).

As the authors point out, this retrospective series does not prove either the long-term efficacy or safety of Sildenafil for use in this setting. A large multicenter randomized, controlled trial is needed for that. In the meantime, caution is urged. ABK