IV Sildenafil

Intravenous sildenafil safely improves oxygenation in critically ill neonates with persistent pulmonary hypertension of the newborn.

These findings, the results of an open-label, dose-escalation trial, are reported in the December issue of the Journal of Pediatrics.

Despite a recent report that enteral sildenafil improves oxygenation and survival in babies with PPHN, little is known about the drug’s safety or efficacy in these tiny patients, in part because it has only been available for enteral administration, according to lead author Dr. Robin H. Steinhorn, of Northwestern University in Chicago, and her colleagues.

In the study they report this month, the researchers were able to use intravenous sildenafil to treat 36 near-term and term newborns with PPHN. Infants with PPHN and an oxygenation index (OI) of >15 were included in the study.

Infants were enrolled at a mean age of 34 hours. Twenty-nine were already receiving inhaled nitric oxide.

The study included eight sequential step-up dosing groups. Sildenafil was administered by continuous intravenous infusion for a minimum of 48 hours and a maximum of 7 days. The median duration of sildenafil infusion was 4 days. Three infants received sildenafil for 7 days.

In the higher-dose cohorts, who had a mean initial sildenafil concentration (after a loading dose) of 58.4 ng/mL, the mean OI significantly improved after 4 hours of sildenafil infusion (from 29 to 19; p = 0.0002). One infant required extracorporeal membrane oxygenation support.

In the seven infants who were not using inhaled nitric oxide at enrollment, the mean OI significantly improved within 4 hours after sildenafil was started (25 to 15; p = 0.0088). Six of these seven infants completed treatment without the need for inhaled nitric oxide or extracorporeal membrane oxygenation.

One infant died of a cause deemed unrelated to sildenafil. Four infants had serious adverse events, none of which was considered treatment-related. Six treatment-related adverse events, all mild to moderate in severity, were reported in five patients. Sildenafil was discontinued in four babies due to adverse events.