{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T01:38:23Z","timestamp":1774921103525,"version":"3.50.1"},"reference-count":30,"publisher":"American Academy of Pediatrics (AAP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,11,1]]},"abstract":"<jats:p>Objective.\u2003To determine the effect of inhaled nitric oxide (NO) on clinical outcome in newborns with persistent pulmonary hypertension (PPHN).<\/jats:p><jats:p>Design.\u2003A prospective, randomized trial of patients referred to a level 3 nursery in a single large center. Clinicians were not masked to group assignment. Crossover of patients from control to NO treatment was not permitted.<\/jats:p><jats:p>Methods.\u2003We randomized 49 mechanically ventilated newborns, transferred to our center with clinical and echocardiographic evidence of severe PPHN (arterial oxygen tension [Pao2] &amp;lt;100; fractional inspired oxygen = 1) to treatment with or without NO. Patients with gestational age &amp;lt;34 weeks or with congenital heart disease or diaphragmatic hernia were excluded. High-frequency oscillatory ventilation was used but not allowed concomitantly with NO. Primary outcome variables were oxygenation, mortality, and use of extracorporeal membrane oxygenation (ECMO).<\/jats:p><jats:p>Results.\u2003Meconium aspiration syndrome and isolated PPHN were the most common diagnoses (32\/49) and were distributed equally between groups. The median age at the time of entry into the study was similar between groups, 25 hours for control patients and 18 hours for NO patients. Median baseline oxygenation index (OI) was similar in 23 control (OI = 29) and 26 NO (OI = 30) patients. Mortality (8%), use of ECMO (33%), median days on mechanical ventilation (9 days), and duration of supplemental oxygen (13 days) were not different between treatment groups. Pao2, oxygen saturation, and OI improved in the NO group compared with baseline and to control patients at 15 minutes. The median percent change in OI (\u221231%) in the NO group was significantly different from baseline and from the control group. The difference in oxygenation between treatment groups was still apparent 12 hours after baseline. Before cannulation for ECMO, oxygenation was better in the NO group compared with control patients. Among patients who were placed on ECMO, the median time from baseline to ECMO cannulation was 2.4 hours (range, 1 to 12 hours) among control patients and 3.3 hours (range, 2 to 68 hours) for those randomized to receive NO. There was a tendency to observe fewer adverse neurologic events (seizure and intracranial hemorrhage) in the NO group (4\/26 vs 8\/23). One child with alveolar capillary dysplasia confirmed by postmortem examination could not be weaned from 80 parts per million of NO and transiently developed methemoglobinemia (peak methemoglobin level = 17%). No other side effects were observed.<\/jats:p><jats:p>Conclusions.\u2003Although mortality and ECMO use were similar for both treatment groups using this study size and design, sustained improvement in oxygenation with NO and better oxygenation at initiation of ECMO may have important clinical benefits. We speculate that modification of treatment to include specific lung expansion strategies with NO treatment and recognition that early improvement of oxygenation may be sustained with NO may lead to reduced use of ECMO in NO treated patients compared with controls.<\/jats:p>","DOI":"10.1542\/peds.100.5.e7","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T23:40:17Z","timestamp":1092440417000},"page":"e7-e7","source":"Crossref","is-referenced-by-count":122,"title":["Improved Oxygenation in a Randomized Trial of Inhaled Nitric Oxide for Persistent Pulmonary Hypertension of the Newborn"],"prefix":"10.1542","volume":"100","author":[{"given":"David L.","family":"Wessel","sequence":"first","affiliation":[{"name":"From the Departments of Cardiology,"},{"name":"Anesthesia,"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Adatia","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiology,"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda J.","family":"Van Marter","sequence":"additional","affiliation":[{"name":"Medicine,"},{"name":"Joint Program in Neonatology, Children's Hospital, and the"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John E.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Respiratory Care, and the"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janie W.","family":"Kane","sequence":"additional","affiliation":[{"name":"Joint Program in Neonatology, Children's Hospital, and the"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann R.","family":"Stark","sequence":"additional","affiliation":[{"name":"Medicine,"},{"name":"Joint Program in Neonatology, Children's Hospital, and the"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stella","family":"Kourembanas","sequence":"additional","affiliation":[{"name":"Medicine,"},{"name":"Joint Program in Neonatology, Children's Hospital, and the"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[1997,11,1]]},"reference":[{"key":"2021121006462173700_B1"},{"key":"2021121006462173700_B2","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/S0022-3476(71)80462-6","article-title":"Persistent pulmonary vascular obstruction in newborn infants.","volume":"78","author":"Siassi","year":"1971","journal-title":"J Pediatr"},{"key":"2021121006462173700_B3","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S0022-3476(76)80405-2","article-title":"Persistent pulmonary hypertension of the newborn infant.","volume":"89","author":"Levin","year":"1976","journal-title":"J Pediatr"},{"key":"2021121006462173700_B4","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/S0031-3955(16)38619-9","article-title":"Advances in the treatment of persistent pulmonary hypertension of the newborn.","volume":"40","author":"Roberts","year":"1993","journal-title":"Pediatr Clin North Am"},{"key":"2021121006462173700_B5","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1542\/peds.76.4.479","article-title":"Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study.","volume":"76","author":"Bartlett","year":"1985","journal-title":"Pediatrics"},{"key":"2021121006462173700_B6","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1542\/peds.84.6.957","article-title":"Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: a prospective randomized study.","volume":"84","author":"O'Rourke","year":"1989","journal-title":"Pediatrics"},{"key":"2021121006462173700_B7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0140-6736(96)04100-1","article-title":"UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation.","volume":"348","author":"UK Collaborative ECMO Trial Group","year":"1996","journal-title":"Lancet"},{"key":"2021121006462173700_B8","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1161\/01.CIR.83.6.2038","article-title":"Inhaled nitric oxide: a selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction.","volume":"83","author":"Frostell","year":"1991","journal-title":"Circulation"},{"key":"2021121006462173700_B9","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/0140-6736(91)92033-X","article-title":"Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension.","volume":"338","author":"Pepke-Zaba","year":"1991","journal-title":"Lancet"},{"key":"2021121006462173700_B10","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":"2021121006462173700_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":"2021121006462173700_B12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0022-3476(05)81551-3","article-title":"Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn with low doses of inhaled nitric oxide.","volume":"123","author":"Kinsella","year":"1993","journal-title":"J Pediatr"},{"key":"2021121006462173700_B13","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0022-3476(96)70255-X","article-title":"Inhaled nitric oxide in term infants with hypoxemic respiratory failure.","volume":"129","author":"Barefield","year":"1996","journal-title":"J Pediatr"},{"key":"2021121006462173700_B14","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/S0022-3476(94)70324-8","article-title":"Inhaled nitric oxide in infants referred for extracorporeal membrane oxygenation: dose response.","volume":"124","author":"Finer","year":"1994","journal-title":"J Pediatr"},{"key":"2021121006462173700_B15","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1542\/peds.98.4.698","article-title":"Acute response to inhaled nitric oxide in newborns with respiratory failure and pulmonary hypertension.","volume":"98","author":"Day","year":"1996","journal-title":"Pediatrics"},{"key":"2021121006462173700_B16","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1542\/peds.98.4.706","article-title":"Four patterns of response to inhaled nitric oxide for persistent pulmonary hypertension of the newborn.","volume":"98","author":"Goldman","year":"1996","journal-title":"Pediatrics"},{"key":"2021121006462173700_B17","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1111\/j.1651-2227.1995.tb13554.x","article-title":"Variable oxygenation response to inhaled nitric oxide in severe persistent pulmonary hypertension of the newborn.","volume":"84","author":"Turbow","year":"1995","journal-title":"Acta Paediatr"},{"key":"2021121006462173700_B18","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1056\/NEJM199702273360901","article-title":"Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure.","volume":"336","author":"The Neonatal Inhaled Nitric Oxide Study Group","year":"1997","journal-title":"N Engl J Med"},{"key":"2021121006462173700_B19","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1056\/NEJM199702273360902","article-title":"Inhaled nitric oxide and persistent pulmonary hypertension of the newborn.","volume":"336","author":"Roberts","year":"1997","journal-title":"N Engl J Med"},{"key":"2021121006462173700_B20","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/S0025-7125(16)32001-6","article-title":"Randomization of the first patient.","volume":"59","author":"Chalmers","year":"1975","journal-title":"Med Clin North Am"},{"key":"2021121006462173700_B21","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1097\/00003246-199406000-00009","article-title":"Delivery and monitoring of inhaled nitric oxide in patients with pulmonary hypertension.","volume":"22","author":"Wessel","year":"1994","journal-title":"Crit Care Med"},{"key":"2021121006462173700_B22","first-page":"706","article-title":"Inhaled nitric oxide: evaluation of a continuous titration delivery technique developed for infant mechanical ventilation and manual ventilation.","volume":"40","author":"Betit","year":"1995","journal-title":"Respir Care"},{"key":"2021121006462173700_B23","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0022-3476(97)70203-8","article-title":"Inhaled nitric oxide enhances oxygenation but not survival in infants with alveolar capillary dysplasia.","volume":"130","author":"Steinhorn","year":"1997","journal-title":"J Pediatr"},{"key":"2021121006462173700_B24","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0022-3476(96)70230-5","article-title":"Inhaled nitric oxide can cause severe systemic hypotension.","volume":"129","author":"Henrichsen","year":"1996","journal-title":"J Pediatr"},{"key":"2021121006462173700_B25","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/S0022-3468(96)90099-8","article-title":"ECMO in evolution: the impact of changing patient demographics and alternative therapies on ECMO.","volume":"31","author":"Wilson","year":"1996","journal-title":"J Pediatr Surg"},{"key":"2021121006462173700_B26","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1542\/peds.96.6.1153","article-title":"Inhaled nitric oxide for persistent pulmonary hypertension of the newborn. The physiology matters!","volume":"26","author":"Abman","year":"1995","journal-title":"Pediatrics"},{"key":"2021121006462173700_B27","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1161\/01.CIR.87.2.447","article-title":"Inhaled nitric oxide in congenital heart disease.","volume":"87","author":"Roberts","year":"1993","journal-title":"Circulation"},{"key":"2021121006462173700_B28"},{"key":"2021121006462173700_B29","first-page":"817","article-title":"Evaluation of four analyzers used to monitor nitric oxide and nitrogen dioxide concentrations during inhaled nitric oxide administration.","volume":"41","author":"Betit","year":"1996","journal-title":"Respir Care"},{"key":"2021121006462173700_B30","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/S0003-4975(96)00542-5","article-title":"Rebound pulmonary hypertension after inhalation of nitric oxide.","volume":"62","author":"Atz","year":"1996","journal-title":"Ann Thorac Surg"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/100\/5\/e7\/890704\/e7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/100\/5\/e7\/890704\/e7.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,14]],"date-time":"2024-01-14T05:04:44Z","timestamp":1705208684000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/100\/5\/e7\/64678\/Improved-Oxygenation-in-a-Randomized-Trial-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,11,1]]},"references-count":30,"journal-issue":{"issue":"5","published-online":{"date-parts":[[1997,11,1]]},"published-print":{"date-parts":[[1997,11,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.100.5.e7","relation":{},"ISSN":["1098-4275","0031-4005"],"issn-type":[{"value":"1098-4275","type":"electronic"},{"value":"0031-4005","type":"print"}],"subject":[],"published":{"date-parts":[[1997,11,1]]}}}