Inhaled nitric oxide for premature infants with severe respiratory failure.

Abstract

BACKGROUND:

Inhaled nitric oxide is a controversial treatment for premature infants with severe respiratory failure. We conducted a multicenter, randomized, blinded, controlled trial to determine whether inhaled nitric oxide reduced the rate of death or bronchopulmonary dysplasia in such infants.

METHODS:

We randomly assigned 420 neonates, born at less than 34 weeks of gestation, with a birth weight of 401 to 1500 g, and with respiratory failure more than four hours after treatment with surfactant to receive placebo (simulated flow) or inhaled nitric oxide (5 to 10 ppm). Infants with a response (an increase in the partial pressure of arterial oxygen of more than 10 mm Hg) were weaned according to protocol. Treatment with study gas was discontinued in infants who did not have a response.

RESULTS:

The rate of death or bronchopulmonary dysplasia was 80 percent in the nitric oxide group, as compared with 82 percent in the placebo group (relative risk, 0.97; 95 percent confidence interval, 0.86 to 1.06; P=0.52), and the rate of bronchopulmonary dysplasia was 60 percent versus 68 percent (relative risk, 0.90; 95 percent confidence interval, 0.75 to 1.08; P=0.26). There were no significant differences in the rates of severe intracranial hemorrhage or periventricular leukomalacia. Post hoc analyses suggest that rates of death and bronchopulmonary dysplasia are reduced for infants with a birth weight greater than 1000 g, whereas infants weighing 1000 g or less who are treated with inhaled nitric oxide have higher mortality and increased rates of severe intracranial hemorrhage.

CONCLUSIONS:

The use of inhaled nitric oxide in critically ill premature infants weighing less than 1500 g does not decrease the rates of death or bronchopulmonary dysplasia. Further trials are required to determine whether inhaled nitric oxide benefits infants with a birth weight of 1000 g or more.

• Authors: Krisa P Van Meurs, Linda L Wright, Richard A Ehrenkranz, James A Lemons, M Bethany Ball, W Kenneth Poole, Rebecca Perritt, Rosemary D Higgins, William Oh, Mark L Hudak, Abbot R Laptook, Seetha Shankaran, Neil N Finer, Waldemar A Carlo, Kathleen A Kennedy, Jon H Fridriksson, Robin H Steinhorn, Gregory M Sokol, G Ganesh Konduri, Judy L Aschner, Barbara J Stoll, Carl T D'Angio, David K Stevenson, Preemie Inhaled Nitric Oxide Study
• Journal: The New England journal of medicine (N Engl J Med) Vol. 353 Issue 1 Pg. 13-22 (Jul 07 2005) ISSN: 1533-4406 [Electronic] United States
• PMID: 16000352 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2005 Massachusetts Medical Society.

Chemical References

• Nitric Oxide
• Oxygen

Topics

• Administration, Inhalation
• Bronchopulmonary Dysplasia (prevention & control)
• Cerebral Hemorrhage (etiology)
• Combined Modality Therapy
• Female
• Humans
• Infant, Newborn
• Infant, Premature
• Infant, Premature, Diseases (drug therapy, mortality, therapy)
• Infant, Very Low Birth Weight
• Leukomalacia, Periventricular (etiology)
• Male
• Nitric Oxide (adverse effects, therapeutic use)
• Oxygen (blood)
• Respiration, Artificial
• Respiratory Distress Syndrome, Newborn (complications)
• Respiratory Insufficiency (complications, drug therapy, mortality)
• Single-Blind Method
• Treatment Outcome