{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T01:33:04Z","timestamp":1773365584624,"version":"3.50.1"},"reference-count":24,"publisher":"American Academy of Pediatrics (AAP)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,10,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objective.<\/jats:title>\n                  <jats:p>There is little information on the response to very low doses of inhaled nitric oxide (iNO) in hypoxic near-term infants. The potential toxicities of iNO are dose related; thus, the ability to use lower doses safely and effectively may be advantageous. We hypothesized that there is no difference in the acute improvement in oxygenation between treatment with inhaled nitric oxide at 1 to 2 parts per million (ppm) or 10 to 20 ppm.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods.<\/jats:title>\n                  <jats:p>We randomized near-term and term infants with hypoxic respiratory failure with oxygenation indices (OIs) of \u226510 and Pao2 &amp;lt;100 on 2 separate blood gases taken at least 30 minutes apart. Infants with congenital diaphragmatic hernia were excluded. After parental consent was obtained, patients were randomized to receive a starting nitric oxide (iNO) dose of either 1 to 2 ppm (low-dose group, n = 15) or 10 to 20 ppm (high-dose group, n = 21). The response to iNO was assessed according to the increase in arterial Pao2 and decrease in OI 30 to 60 minutes after exposure to the initial starting concentration. A response of &amp;lt;10% increase on Pao2 and a &amp;lt;10% decrease in OI resulted in a doubling of iNO within the dose range protocol (1, 2, 4, and 8 ppm for the low-dose group; 10, 20, 40, and 80 ppm for the high-dose group).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results.<\/jats:title>\n                  <jats:p>Thirty minutes after the study gas was initiated, Pao2 increased significantly overall in the low-dose (90.7 \u00b1 41 torr to 166.8 \u00b1 95.6 torr) and high-dose (76.2 \u00b1 32.7 torr to 198.7 \u00b1 142.8 torr) groups; the maximal increase was seen in the infants who initially were treated with 10 ppm. The OI also decreased significantly overall and also was significant in the high-dose group (21.0 \u00b1 13.7 to 11.4 \u00b1 10.4; low-dose: 18.3 \u00b1 7.1 to 13.2 \u00b1 12.3). There was a nonsignificant fall of Paco2 with iNO treatment (low dose 35 \u00b1 7.3 to 30 \u00b1 8.5 torr vs high dose 35.2 \u00b1 9.9 to 32.4 \u00b1 10.7 torr). A sustained response (ie, maintaining a Pao2 and OI gain greater than 20% for the duration of the study gas administration) was greater in the high-dose group (53.3% vs 30.0%). In addition, dose increases were required more often in the low-dose group than in the high-dose group (80.0% vs 57.1%). Among patients who did not respond to the initial iNO dose, 100.0% and 83.3% responded at higher doses of iNO for the low- and high-dose groups, respectively. There were no differences for death, need for extracorporeal membrane oxygenation, or other outcomes between the groups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions.<\/jats:title>\n                  <jats:p>We did not find any significant difference in response to low- versus high-dose iNO. An initial exposure to low-dose iNO does not compromise the response to higher doses if required and may result in less toxicity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1542\/peds.108.4.949","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T23:55:51Z","timestamp":1092441351000},"page":"949-955","source":"Crossref","is-referenced-by-count":28,"title":["Randomized, Prospective Study of Low-Dose Versus High-Dose Inhaled Nitric Oxide in the Neonate With Hypoxic Respiratory Failure"],"prefix":"10.1542","volume":"108","author":[{"given":"Neil N.","family":"Finer","sequence":"first","affiliation":[{"name":"From the University of California, San Diego Medical Center, San Diego, California; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johnny W.","family":"Sun","sequence":"additional","affiliation":[{"name":"From the University of California, San Diego Medical Center, San Diego, California; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wade","family":"Rich","sequence":"additional","affiliation":[{"name":"From the University of California, San Diego Medical Center, San Diego, California; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen","family":"Knodel","sequence":"additional","affiliation":[{"name":"From the University of California, San Diego Medical Center, San Diego, California; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith J.","family":"Barrington","sequence":"additional","affiliation":[{"name":"Royal Victoria Hospital, Montreal, Quebec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[2001,10,1]]},"reference":[{"key":"2021121021575364000_B1"},{"key":"2021121021575364000_B2","first-page":"303","article-title":"Treatment of persistent pulmonary hypertension of the newborn without hyperventilation: an assessment of diffusion of innovation.","volume":"94","author":"Walsh-Sukys","year":"1994","journal-title":"Pediatrics"},{"key":"2021121021575364000_B3","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1542\/peds.105.1.14","article-title":"Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes.","volume":"105","author":"Walsh-Sukys","year":"2000","journal-title":"Pediatrics"},{"key":"2021121021575364000_B4","first-page":"602","article-title":"Inhaled nitric oxide for near-term infants with respiratory failure.","volume":"336","author":"The NINOS Study Group","year":"1997","journal-title":"N Engl J Med"},{"key":"2021121021575364000_B5","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":"2021121021575364000_B6","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0022-3476(97)70124-0","article-title":"Randomized, multicenter trial of inhaled nitric oxide and high frequency ventilation in severe persistent pulmonary hypertension of the newborn.","volume":"131","author":"Kinsella","year":"1997","journal-title":"J Pediatr"},{"key":"2021121021575364000_B7","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1542\/peds.101.3.325","article-title":", and the INO\/PPHN Study Group. 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Clinical Inhaled Nitric Oxide Research Group.","volume":"342","author":"Clark","year":"2000","journal-title":"N Engl J Med"},{"key":"2021121021575364000_B9","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":"2021121021575364000_B10","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1542\/peds.104.2.231","article-title":"Safety of withdrawing inhaled nitric oxide therapy in persistent pulmonary hypertension of the newborn.","volume":"104","author":"Davidson","year":"1999","journal-title":"Pediatrics"},{"key":"2021121021575364000_B11","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0146-0005(97)80006-7","article-title":"Nitric oxide and platelet function: implications for 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nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia.","volume":"99","author":"The Neonatal Inhaled Nitric Oxide Study Group","year":"1997","journal-title":"Pediatrics"},{"key":"2021121021575364000_B15","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1111\/j.1651-2227.1997.tb14852.x","article-title":"Endogenous nitric oxide in the upper airways of premature and term infants.","volume":"86","author":"Schedin","year":"1997","journal-title":"Acta Pediatr"},{"key":"2021121021575364000_B16","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1378\/chest.114.3.827","article-title":"Efficacy of inhaled nitric oxide in children with ARDS.","volume":"114","author":"Okamoto","year":"1998","journal-title":"Chest"},{"key":"2021121021575364000_B17","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0022-5223(12)70258-1","article-title":"Very-low-dose inhaled nitric oxide: a selective pulmonary vasodilator after operations for 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