Sildenafil prevents rebound pulmonary hypertension in infants

This research appears in the first issue for November 2006 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Lara Shekerdemian, M.D., of the Pediatric Intensive Care Unit at the Royal Children's Hospital in Melbourne, Australia, and five associates gave a single dose of sildenafil to 15 infants undergoing withdrawal from inhaled nitric oxide therapy. None experienced rebound pulmonary hypertension, a common therapeutic complication.

Fourteen children in the study cohort received a placebo. Ten of the 14 had an acute elevation of pulmonary artery pressure by 20 percent or more during the latter part of the weaning process.

Inhaled nitric oxide was first introduced in the early 1990s as a therapeutic agent to widen pulmonary blood vessels in ventilated lung regions by relaxing pulmonary vascular smooth muscle.

Although there have been no definitive studies of clinical benefit to date, the investigators believe that inhaled nitric oxide therapy warrants use as an adjunctive treatment in some of the sickest patients in the ICU. They call it “unrivaled” in its efficacy as a selective pulmonary vasodilator.

“An important complication that is associated with the use of inhaled nitric oxide is the development of rebound pulmonary hypertension on its withdrawal,” said Dr. Shekerdemian.

All infants who failed to respond were given sildenafil during a subsequent weaning attempt more than 24 hours later and were weaned successfully from nitric oxide treatment.

The total duration of ventilation for patients given sildenafil was slightly over 28 hours, as compared with 98 hours for those taking a placebo.

“The total ICU stay after the study was completed was 47.8 hours for the sildenafil group and 189 hours for the placebo group,” added Dr. Shekerdemian.

“This study is unique in a number of ways,” she continued. “It is the first study to investigate the pharmacologic prophylaxis of rebound pulmonary hypertension during the primary attempt to wean from inhaled nitric oxide. This is also the first prospective trial of sildenafil in the prevention of rebound pulmonary hypertension. Moreover, this study is the first that defines the extent of the problem of rebound pulmonary hypertension in infants and children weaning from inhaled nitric oxide in the pediatric ICU.”