Inhaled Nitric Oxide for Premature Infants with Severe Respiratory Failure
Krisa P. Van Meurs, M.D., Linda L. Wright, M.D., Richard A. Ehrenkranz, M.D., James A. Lemons, M.D., M. Bethany Ball, B.S., W. Kenneth Poole, Ph.D., Rebecca Perritt, M.S., Rosemary D. Higgins, M.D., William Oh, M.D., Mark L. Hudak, M.D., Abbot R. Laptook, M.D., Seetha Shankaran, M.D., Neil N. Finer, M.D., Waldemar A. Carlo, M.D., Kathleen A. Kennedy, M.D., M.P.H., Jon H. Fridriksson, M.D., Robin H. Steinhorn, M.D., Gregory M. Sokol, M.D., G. Ganesh Konduri, M.D., Judy L. Aschner, M.D., Barbara J. Stoll, M.D., Carl T. D'Angio, M.D., David K. Stevenson, M.D., for the Preemie Inhaled Nitric Oxide Study
Background Inhaled nitric oxide is a controversial treatmentfor premature infants with severe respiratory failure. We conducteda multicenter, randomized, blinded, controlled trial to determinewhether inhaled nitric oxide reduced the rate of death or bronchopulmonarydysplasia in such infants.
Methods We randomly assigned 420 neonates, born at less than34 weeks of gestation, with a birth weight of 401 to 1500 g,and with respiratory failure more than four hours after treatmentwith surfactant to receive placebo (simulated flow) or inhalednitric oxide (5 to 10 ppm). Infants with a response (an increasein the partial pressure of arterial oxygen of more than 10 mmHg) were weaned according to protocol. Treatment with studygas was discontinued in infants who did not have a response.
Results The rate of death or bronchopulmonary dysplasia was80 percent in the nitric oxide group, as compared with 82 percentin the placebo group (relative risk, 0.97; 95 percent confidenceinterval, 0.86 to 1.06; P=0.52), and the rate of bronchopulmonarydysplasia was 60 percent versus 68 percent (relative risk, 0.90;95 percent confidence interval, 0.75 to 1.08; P=0.26). Therewere no significant differences in the rates of severe intracranialhemorrhage or periventricular leukomalacia. Post hoc analysessuggest that rates of death and bronchopulmonary dysplasia arereduced for infants with a birth weight greater than 1000 g,whereas infants weighing 1000 g or less who are treated withinhaled nitric oxide have higher mortality and increased ratesof severe intracranial hemorrhage.
Conclusions The use of inhaled nitric oxide in critically illpremature infants weighing less than 1500 g does not decreasethe rates of death or bronchopulmonary dysplasia. Further trialsare required to determine whether inhaled nitric oxide benefitsinfants with a birth weight of 1000 g or more.
Source Information
From Stanford University School of Medicine, Palo Alto, Calif. (K.P.V.M., M.B.B., D.K.S.); the National Institute of Child Health and Human Development (NICHD), Bethesda, Md. (L.L.W., R.D.H.); Yale University School of Medicine, New Haven, Conn. (R.A.E.); Indiana University School of Medicine, Indianapolis (J.A.L., G.M.S.); Research Triangle Institute, Research Triangle Park, N.C. (W.K.P., R.P.); Women's and Infant's Hospital, Providence, R.I. (W.O., A.R.L.); University of Florida, Jacksonville (M.L.H.); Wayne State University, Detroit (S.S.); University of California at San Diego, San Diego (N.N.F.); University of Alabama, Birmingham (W.A.C.); University of Texas at Houston, Houston (K.A.K.); College of Medicine, University of Cincinnati, Cincinnati (J.H.F.); Northwestern University, Chicago (R.H.S.); Medical College of Wisconsin, Milwaukee (G.G.K.); Wake Forest University School of Medicine, Winston-Salem, N.C. (J.L.A.); Emory University School of Medicine, Atlanta (B.J.S.); and University of Rochester, Rochester, N.Y. (C.T.D.).
Address reprint requests to Dr. Van Meurs at the Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, 750 Welch Rd., Suite 315, Palo Alto, CA 94304, or at vanmeurs{at}stanford.edu.
Inhaled Nitric Oxide
Dani C., Bertini G., Rubaltelli F. F., Hasan S. U., Lasser E. C., Van Meurs K., Stevenson D., Schreiber M. D., Marks J. D., Mestan K. K.L., Martin R. J., Walsh M. C.
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N Engl J Med 2005;
353:1626-1628, Oct 13, 2005.
Correspondence
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