Sildenafil prevents rebound pulmonary hypertension after inhaled NO withdrawal
Last Updated: 2006-11-01 14:47:21 -0400 (Reuters Health)
By Megan Rauscher
NEW YORK (Reuters Health) - Rebound pulmonary hypertension can be safely and effectively prevented in infants being withdrawn from inhaled nitric oxide (NO) therapy by administration of a single dose of enteral sildenafil at the final stage of the weaning process, new study results indicate.
The development of rebound pulmonary hypertension is an important and common problem during withdrawal of inhaled NO in the pediatric ICU, note study investigators in the November issue of the American Journal of Respiratory and Critical Care Medicine.
There is anecdotal evidence that sildenafil may prevent the sudden increase in the pulmonary artery pressure upon NO withdrawal, Dr. Lara Shekerdemian from the Royal Children's Hospital in Melbourne, Australia and colleagues report.
"Sildenafil acts by replenishing the body's levels of cyclic GMP -- the body's own nitric oxide," Dr. Shekerdemian noted in comments to Reuters Health. "The lungs usually produce plenty of cyclic GMP, which helps to control the pulmonary artery pressures, but the levels of this naturally fall during treatment with nitric oxide. We hoped that a dose of sildenafil would serve to replenish the levels of cyclic GMP, and so prevent rebound."
To test this, the research team randomly assigned 30 ventilated infants and children receiving 10 ppm or greater inhaled NO, to 0.4 mg/kg of sildenafil or placebo, given 1 hour before stopping NO. All but one subject completed the study.
"Our results demonstrated very convincingly that rebound, which occurred in over two-thirds of children who received placebo, was completely prevented with a single dose of sildenafil," Dr. Shekerdemian stated.
All patients who failed to wean were electively given sildenafil during a subsequent weaning attempt more than 24 hours later and were weaned successfully from NO treatment.
"Also, and of great importance, we found that children who were given sildenafil, subsequently spent less time on the ventilator, and in intensive care," Dr. Shekerdemian said.
"We would recommend that, unless there are any contra-indications to giving sildenafil, that this should be considered in all children weaning from nitric oxide in the pediatric ICU," Dr. Shekerdemian concluded.
Am J Respir Crit Care Med 2006;174:1042-1047.
