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
Background Inhaled nitric oxide improves gas exchange in neonates,but the efficacy of low-dose inhaled nitric oxide in reducingthe need for extracorporeal membrane oxygenation has not beenestablished.
Methods We conducted a clinical trial to determine whether low-doseinhaled nitric oxide would reduce the use of extracorporealmembrane oxygenation in neonates with pulmonary hypertensionwho were born after 34 weeks' gestation, were 4 days old oryounger, required assisted ventilation, and had hypoxemic respiratoryfailure as defined by an oxygenation index of 25 or higher.The neonates who received nitric oxide were treated with 20ppm for a maximum of 24 hours, followed by 5 ppm for no morethan 96 hours. The primary end point of the study was the useof extracorporeal membrane oxygenation.
Results Of 248 neonates enrolled, 126 were randomly assignedto the nitric oxide group and 122 to the control group. Extracorporealmembrane oxygenation was used in 78 neonates in the controlgroup (64 percent) and in 48 neonates in the nitric oxide group(38 percent) (P=0.001). The 30-day mortality rate in the twogroups was similar (8 percent in the control group and 7 percentin the nitric oxide group). Chronic lung disease developed lessoften in neonates treated with nitric oxide than in those inthe control group (7 percent vs. 20 percent, P=0.02). The efficacyof nitric oxide was independent of the base-line oxygenationindex and the primary pulmonary diagnosis.
Conclusions Inhaled nitric oxide reduces the extent to whichextracorporeal membrane oxygenation is needed in neonates withhypoxemic 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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