{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T01:33:03Z","timestamp":1773365583631,"version":"3.50.1"},"reference-count":26,"publisher":"American Academy of Pediatrics (AAP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,11,1]]},"abstract":"<jats:p>Recent reports indicate that inhaled nitric oxide (iNO) causes selective pulmonary vasodilation, increases arterial oxygen tension, and may decrease the use of extracorporeal membrane oxygenation (ECMO) in infants with persistent pulmonary hypertension of the newborn (PPHN). Despite these reports, the optimal dose and timing of iNO administration in PPHN remains unclear.<\/jats:p>\n               <jats:p>Objectives.\u2003To test the hypotheses that in PPHN 1) iNO at 2 parts per million (ppm) is effective at acutely increasing oxygenation as measured by oxygenation index (OI); 2) early use of 2 ppm of iNO is more effective than control (0 ppm) in preventing clinical deterioration and need for iNO at 20 ppm; and 3) for those infants who fail the initial treatment protocol (0 or 2 ppm) iNO at 20 ppm is effective at acutely decreasing OI.<\/jats:p>\n               <jats:p>Study Design.\u2003A randomized, controlled trial of iNO in 3 nurseries in a single metropolitan area. Thirty-eight children, average gestational age of 37.3 weeks and average age &amp;lt;1 day were enrolled. Thirty-five of 38 infants had echocardiographic evidence of pulmonary hypertension. On enrollment, median OI in the control group, iNO at 0 ppm, (n = 23) was 33.1, compared with 36.9 in the 2-ppm iNO group (n = 15).<\/jats:p>\n               <jats:p>Results.\u2003Initial treatment with iNO at 2 ppm for an average of 1 hour was not associated with a significant decrease in OI. Twenty of 23 (87%) control patients and 14 of 15 (92%) of the low-dose iNO group demonstrated clinical deterioration and were treated with iNO at 20 ppm. In the control group, treatment with iNO at 20 ppm decreased the median OI from 42.6 to 23.8, whereas in the 2-ppm iNO group with a change in iNO from 2 to 20 ppm, the median OI did not change (42.6 to 42.0). Five of 15 patients in the low-dose nitric oxide group required ECMO and 2 died, compared with 7 of 23 requiring ECMO and 5 deaths in the control group.<\/jats:p>\n               <jats:p>Conclusion.\u2003In infants with PPHN, iNO 1): at 2 ppm does not acutely improve oxygenation or prevent clinical deterioration, but does attenuate the rate of clinical deterioration; and 2) at 20 ppm acutely improves oxygenation in infants initially treated with 0 ppm, but not in infants previously treated with iNO at 2 ppm. Initial treatment with a subtherapeutic dose of iNO may diminish the clinical response to 20 ppm of iNO and have adverse clinical sequelae.<\/jats:p>","DOI":"10.1542\/peds.104.5.1089","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T23:45:45Z","timestamp":1092440745000},"page":"1089-1094","source":"Crossref","is-referenced-by-count":69,"title":["Randomized, Controlled Trial of Low-dose Inhaled Nitric Oxide in the Treatment of Term and Near-term Infants With Respiratory Failure and Pulmonary Hypertension"],"prefix":"10.1542","volume":"104","author":[{"given":"David N.","family":"Cornfield","sequence":"first","affiliation":[{"name":"From the Divisions of Pulmonary and Critical Care Medicine and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy C.","family":"Maynard","sequence":"additional","affiliation":[{"name":"Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; and"},{"name":"Children's Hospitals and Clinics, Minneapolis, Minnesota."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raye-Ann O.","family":"deRegnier","sequence":"additional","affiliation":[{"name":"Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; and"},{"name":"Children's Hospitals and Clinics, Minneapolis, Minnesota."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"Sixto F.","family":"Guiang","sequence":"additional","affiliation":[{"name":"Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel E.","family":"Barbato","sequence":"additional","affiliation":[{"name":"From the Divisions of Pulmonary and Critical Care Medicine and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos E.","family":"Milla","sequence":"additional","affiliation":[{"name":"From the Divisions of Pulmonary and Critical Care Medicine and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[1999,11,1]]},"reference":[{"key":"2021121003055934600_B1","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1161\/01.RES.57.6.811","article-title":"Distribution and regulation of blood flow in the fetal and neonatal lamb.","volume":"57","author":"Rudolph","year":"1985","journal-title":"Circ Res"},{"key":"2021121003055934600_B2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1113\/jphysiol.1964.sp007361","article-title":"The vascular resistance of the fetal and newly ventilated lung of the lamb.","volume":"171","author":"Cassin","year":"1964","journal-title":"J Physiol."},{"key":"2021121003055934600_B3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1113\/jphysiol.1953.sp004936","article-title":"Changes in the lungs of the newborn lamb.","volume":"121","author":"Dawes","year":"1953","journal-title":"J Physiol Lond."},{"key":"2021121003055934600_B4","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1203\/00006450-198410000-00006","article-title":"The onset of breathing at birth stimulates pulmonary vascular prostacyclin synthesis.","volume":"18","author":"Leffler","year":"1984","journal-title":"Pediatr Res."},{"key":"2021121003055934600_B5","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0022-3476(97)70245-2","article-title":"Effect of inhaled nitric oxide on endothelin-1 and cyclic guanosine 5\u2032-monophosphate plasma concentrations in newborn infants with persistent pulmonary hypertension.","volume":"130","author":"Christou","year":"1997","journal-title":"J Pediatr."},{"key":"2021121003055934600_B6","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1055\/s-2007-994352","article-title":"Plasma immunoreactive endothelin-1 concentrations in infants with persistent pulmonary hypertension of the newborn.","volume":"13","author":"Kumar","year":"1996","journal-title":"Am J Perinatol."},{"key":"2021121003055934600_B7","first-page":"H1921","article-title":"Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth.","volume":"259","author":"Abman","year":"1990","journal-title":"Am J Physiol."},{"key":"2021121003055934600_B8","first-page":"H1474","article-title":"Effects of birth-related stimuli on L-arginine-dependent pulmonary vasodilation in ovine fetus.","volume":"262","author":"Cornfield","year":"1992","journal-title":"Am J Physiol."},{"key":"2021121003055934600_B9"},{"key":"2021121003055934600_B10","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1097\/00000542-198904000-00008","article-title":"Prostaglandin E1 and nitroglycerin reduce pulmonary capillary wedge pressure but worsen V\/Q distribution in patients with adult respiratory distress syndrome.","volume":"70","author":"Radermacher","year":"1989","journal-title":"Anesthesiology."},{"key":"2021121003055934600_B11","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/0140-6736(92)92687-B","article-title":"Low-dose inhalational nitric oxide in persistent pulmonary hypertension of the newborn.","volume":"340","author":"Kinsella","year":"1992","journal-title":"Lancet."},{"key":"2021121003055934600_B12","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/0140-6736(92)92686-A","article-title":"Inhaled nitric oxide in persistent pulmonary hypertension of the newborn.","volume":"340","author":"Roberts","year":"1992","journal-title":"Lancet."},{"key":"2021121003055934600_B13","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1056\/NEJM199702273360902","article-title":"Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. 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