PAS: Sildenafil (Viagra) Eases Newborns' Pulmonary Hypertension

By Emily P. Walker, Washington Correspondent, MedPage Today
Published: May 06, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.

BALTIMORE, May 6 -- Using sildenafil (Viagra) to treat severe, persistent pulmonary hypertension of the newborn can help them adapt to breathing outside the womb, according to a researcher here.

The finding is particularly pertinent in developing countries, where the nitric oxide gas commonly used to treat U.S. infants is usually unavailable or prohibitively expensive, according to Amed Soliz, M.D., director of the Neonatal Intensive Care Unit at Miami Children's Hospital.

Dr. Soliz described his study during a poster session here at the Pediatric Academic Societies' annual meeting.

In a randomized trial of 49 infants with failure in both the systemic and pulmonary circulation, those who received sildenafil showed a significant improvement in oxygenation and had a 92% survival rate, compared with a 50% survival rate of neonates who received placebo, he said.

More than 90% of the half-million babies afflicted with the condition are in Third-World countries, and 40% to 80% of them die because there is no treatment available Dr. Soliz said.

In the U.S. and other developed countries, inhaled nitric oxide effectively treats infants with persistent pulmonary hypertension. But the gas is either unavailable or prohibitively expensive at most treatment centers in developing countries.

On the other hand, sildenafil -- a type V phosphodiesterase inhibitor primarily used for erectile dysfunction in adults -- is widely available for $5 to $10 per adult dose in developing areas, Dr. Soliz said.

The drug, originally developed to treat hypertension and angina, works in persistent pulmonary hypertension patients by selectively reducing pulmonary vascular resistance. It is not FDA approved for newborns.

Although smaller studies have shown the drug's utility in treating persistent pulmonary hypertension, the current study is the largest to date.

For the study, Dr. Soliz and colleagues randomized 49 neonates at three centers in Mexico and El Salvador to either sildenafil or placebo.

After crushing and diluting a 2 mg/kg dose of the normally adults-only pill, doctors administered the medication to the test group by orogastric tube every six hours from birth to three days.

Within the first hour, changes in the oxygenation index in the sildenafil group were significant through 72 hours (P<0.01).

The PaO₂ mean airway pressure and the number of days spent on a ventilator were both significantly lower in the sildenafil group compared with the placebo (P<0.01 for all).

There were two deaths out of the 29 infants given sildenafil, while eight babies out of 20 died in the placebo group (P<0.05).

No significant differences were observed between the two groups in blood pressure or PaCO₂ levels.

While the study confirms previous smaller studies, Dr. Soliz acknowledged that a large study pitting the drug against nitric oxide is needed, as is a safety study on sildenafil.

"We'd be very naive to think that sildenafil will fix all the problems," he said.

But it is a good starting point for what could become a treatment alternative in developing countries, said Herber Nielsen, M.D., a neonatologist at Tufts University who was not involved in the study.

Sildenafil is already being used worldwide to help wean babies off nitric oxide, but some researchers believe the drug itself holds the biggest promise in developing countries with no other options.

"This offers the opportunity of having a much less expensive, much less invasive therapy," Dr. Nielsen said.

He said there's a chance sildenafil might prove more effective than inhaled nitric oxide because it enhances the body's own ability to produce nitric oxide.

He said the physiologic mechanism of sildenafil that causes a release of nitric oxide is also what enables the drug to help cause erections during sexual stimulation.