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Original Article
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Volume 342:469-474 February 17, 2000 Number 7
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Low-Dose Nitric Oxide Therapy for Persistent Pulmonary Hypertension of the Newborn
Reese H. Clark, M.D., Thomas J. Kueser, M.D., Marshall W. Walker, M.D., W. Michael Southgate, M.D., Jeryl L. Huckaby, R.R.T., Jose A. Perez, M.D., Beverly J. Roy, M.D., Martin Keszler, M.D., John P. Kinsella, M.D., for The Clinical Inhaled Nitric Oxide Research Group

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ABSTRACT

Background Inhaled nitric oxide improves gas exchange in neonates, but the efficacy of low-dose inhaled nitric oxide in reducing the need for extracorporeal membrane oxygenation has not been established.

Methods We conducted a clinical trial to determine whether low-dose inhaled nitric oxide would reduce the use of extracorporeal membrane oxygenation in neonates with pulmonary hypertension who were born after 34 weeks' gestation, were 4 days old or younger, required assisted ventilation, and had hypoxemic respiratory failure as defined by an oxygenation index of 25 or higher. The neonates who received nitric oxide were treated with 20 ppm for a maximum of 24 hours, followed by 5 ppm for no more than 96 hours. The primary end point of the study was the use of extracorporeal membrane oxygenation.

Results Of 248 neonates enrolled, 126 were randomly assigned to the nitric oxide group and 122 to the control group. Extracorporeal membrane oxygenation was used in 78 neonates in the control group (64 percent) and in 48 neonates in the nitric oxide group (38 percent) (P=0.001). The 30-day mortality rate in the two groups was similar (8 percent in the control group and 7 percent in the nitric oxide group). Chronic lung disease developed less often in neonates treated with nitric oxide than in those in the control group (7 percent vs. 20 percent, P=0.02). The efficacy of nitric oxide was independent of the base-line oxygenation index and the primary pulmonary diagnosis.

Conclusions Inhaled nitric oxide reduces the extent to which extracorporeal membrane oxygenation is needed in neonates with hypoxemic respiratory failure and pulmonary hypertension.


Source Information

From the Department of Pediatrics, Duke University, Durham, N.C. (R.H.C.); the Division of Neonatology, Carolinas Medical Center, Charlotte, N.C. (T.J.K.); the Department of Neonatology, Greenville Hospital System, Greenville, S.C. (M.W.W.); Medical University of South Carolina, Charleston (W.M.S.); Egleston Children's Hospital, Atlanta (J.L.H.); Arnold Palmer Hospital, Orlando, Fla. (J.A.P.); the Department of Pediatrics, Emory University, Atlanta (B.J.R.); the Division of Neonatology, Georgetown University Hospital, Washington, D.C. (M.K.); and the University of Colorado School of Medicine, Denver (J.P.K.).

Address reprint requests to Dr. Clark at Pediatrix Medical Group, 1301 Concord Terr., Sunrise, FL 33323, or at reese_clark{at}mail.pediatrix.com.

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