Inhaled nitric oxide for premature infants with severe respiratory failure

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 & 3 others Barbara J. Stoll, Carl T. D'Angio, David K. Stevenson

Research output: Contribution to journalArticle

206 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)13-22
Number of pages10
JournalNew England Journal of Medicine
Volume353
Issue number1
DOIs
StatePublished - Jul 7 2005
Externally publishedYes

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Premature Infants
Respiratory Insufficiency
Bronchopulmonary Dysplasia
Nitric Oxide
Birth Weight
Mortality
Intracranial Hemorrhages
Placebos
Confidence Intervals
Periventricular Leukomalacia
Partial Pressure
Critical Illness
Surface-Active Agents
Therapeutics
Randomized Controlled Trials
Gases
Newborn Infant
Oxygen
Pregnancy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Van Meurs, K. P., Wright, L. L., Ehrenkranz, R. A., Lemons, J. A., Bethany Ball, M., Kenneth Poole, W., ... Stevenson, D. K. (2005). Inhaled nitric oxide for premature infants with severe respiratory failure. New England Journal of Medicine, 353(1), 13-22. https://doi.org/10.1056/NEJMoa043927

Inhaled nitric oxide for premature infants with severe respiratory failure. / Van Meurs, Krisa P.; Wright, Linda L.; Ehrenkranz, Richard A.; Lemons, James A.; Bethany Ball, M.; Kenneth Poole, W.; Perritt, Rebecca; Higgins, Rosemary D.; Oh, William; Hudak, Mark L.; Laptook, Abbot R.; Shankaran, Seetha; Finer, Neil N.; Carlo, Waldemar A.; Kennedy, Kathleen A.; Fridriksson, Jon H.; Steinhorn, Robin H.; Sokol, Gregory M.; Ganesh Konduri, G.; Aschner, Judy L.; Stoll, Barbara J.; D'Angio, Carl T.; Stevenson, David K.

In: New England Journal of Medicine, Vol. 353, No. 1, 07.07.2005, p. 13-22.

Research output: Contribution to journalArticle

Van Meurs, KP, Wright, LL, Ehrenkranz, RA, Lemons, JA, Bethany Ball, M, Kenneth Poole, W, Perritt, R, Higgins, RD, Oh, W, Hudak, ML, Laptook, AR, Shankaran, S, Finer, NN, Carlo, WA, Kennedy, KA, Fridriksson, JH, Steinhorn, RH, Sokol, GM, Ganesh Konduri, G, Aschner, JL, Stoll, BJ, D'Angio, CT & Stevenson, DK 2005, 'Inhaled nitric oxide for premature infants with severe respiratory failure', New England Journal of Medicine, vol. 353, no. 1, pp. 13-22. https://doi.org/10.1056/NEJMoa043927
Van Meurs KP, Wright LL, Ehrenkranz RA, Lemons JA, Bethany Ball M, Kenneth Poole W et al. Inhaled nitric oxide for premature infants with severe respiratory failure. New England Journal of Medicine. 2005 Jul 7;353(1):13-22. https://doi.org/10.1056/NEJMoa043927
Van Meurs, Krisa P. ; Wright, Linda L. ; Ehrenkranz, Richard A. ; Lemons, James A. ; Bethany Ball, M. ; Kenneth Poole, W. ; Perritt, Rebecca ; Higgins, Rosemary D. ; Oh, William ; Hudak, Mark L. ; Laptook, Abbot R. ; Shankaran, Seetha ; Finer, Neil N. ; Carlo, Waldemar A. ; Kennedy, Kathleen A. ; Fridriksson, Jon H. ; Steinhorn, Robin H. ; Sokol, Gregory M. ; Ganesh Konduri, G. ; Aschner, Judy L. ; Stoll, Barbara J. ; D'Angio, Carl T. ; Stevenson, David K. / Inhaled nitric oxide for premature infants with severe respiratory failure. In: New England Journal of Medicine. 2005 ; Vol. 353, No. 1. pp. 13-22.
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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.",
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AU - Van Meurs, Krisa P.

AU - Wright, Linda L.

AU - Ehrenkranz, Richard A.

AU - Lemons, James A.

AU - Bethany Ball, M.

AU - Kenneth Poole, W.

AU - Perritt, Rebecca

AU - Higgins, Rosemary D.

AU - Oh, William

AU - Hudak, Mark L.

AU - Laptook, Abbot R.

AU - Shankaran, Seetha

AU - Finer, Neil N.

AU - Carlo, Waldemar A.

AU - Kennedy, Kathleen A.

AU - Fridriksson, Jon H.

AU - Steinhorn, Robin H.

AU - Sokol, Gregory M.

AU - Ganesh Konduri, G.

AU - Aschner, Judy L.

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AU - D'Angio, Carl T.

AU - Stevenson, David K.

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N2 - 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.

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