{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:15:17Z","timestamp":1790381717126,"version":"4.1.0"},"reference-count":21,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Children\u2019s Miracle Network at the University of California, Davis","award":["NICHD 5R01 HD072929"],"award-info":[{"award-number":["NICHD 5R01 HD072929"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>The combination of perinatal acidemia with postnatal hyperoxia is associated with a higher incidence of hypoxic-ischemic encephalopathy (HIE) in newborn infants. In neonatal cardiac arrest, current International Liaison Committee on Resuscitation (ILCOR) and Neonatal Resuscitation Program (NRP) guidelines recommend increasing inspired O2 to 100% during chest compressions (CC). Following the return of spontaneous circulation (ROSC), gradual weaning from 100% O2 based on pulse oximetry (SpO2) can be associated with hyperoxia and risk for cerebral tissue injury owing to oxidative stress. We hypothesize that compared to gradual weaning from 100% O2 with titration based on preductal SpO2, abrupt or rapid weaning of inspired O2 to 21% after ROSC or use of 21% O2 during CC followed by upward titration of inspired O2 to achieve target SpO2 after ROSC will limit hyperoxia after ROSC. Nineteen lambs were randomized before delivery and asphyxial arrest was induced by umbilical cord occlusion. There was no difference in oxygenation during chest compressions between the three groups. Gradual weaning of inspired O2 from 100% O2 after ROSC resulted in supraphysiological PaO2 and higher cerebral oxygen delivery compared to 21% O2 during CC or 100% O2 during CC followed by abrupt weaning to 21% O2 after ROSC. The use of 21% O2 during CC was associated with very low PaO2 after ROSC and higher brain tissue lactic acid compared to other groups. Our findings support the current recommendations to use 100% O2 during CC and additionally suggest the benefit of abrupt decrease in inspired oxygen to 21% O2 after ROSC. Clinical studies are warranted to investigate optimal oxygen titration after chest compressions and ROSC during neonatal resuscitation.<\/jats:p>","DOI":"10.3390\/children10030575","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T05:06:01Z","timestamp":1679029561000},"page":"575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Randomized Trial of 21% versus 100% Oxygen during Chest Compressions Followed by Gradual versus Abrupt Oxygen Titration after Return of Spontaneous Circulation in Neonatal Lambs"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6704-6949","authenticated-orcid":false,"given":"Deepika","family":"Sankaran","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of California, Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0364-0057","authenticated-orcid":false,"given":"Evan M.","family":"Giusto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L.","family":"Lesneski","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Research, University of California, Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan E.","family":"Hardie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houssam M.","family":"Joudi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily C. A.","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria L.","family":"Hammitt","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Research, University of California, Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstie C.","family":"Tully","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Research, University of California, Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payam","family":"Vali","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-2155","authenticated-orcid":false,"given":"Satyan","family":"Lakshminrusimha","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, Davis, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1203\/PDR.0b013e3181bf587f","article-title":"Exposure to Supplemental Oxygen and Its Effects on Oxidative Stress and Antioxidant Enzyme Activity in Term Newborn Lambs","volume":"67","author":"Kumar","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Weiner, G.M., and Zaichkin, J. (2021). Textbook of Neonatal Resuscitation, American Heart Association. [8th ed.]. American Heart Association.","DOI":"10.1542\/9781610025256"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S524","DOI":"10.1161\/CIR.0000000000000902","article-title":"Part 5: Neonatal Resuscitation: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care","volume":"142","author":"Aziz","year":"2020","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1203\/00006450-199211000-00008","article-title":"Response of the cerebral circulation to hypocarbia in postasphyxia newborn lambs","volume":"32","author":"Rosenberg","year":"1992","journal-title":"Pediatr. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0022-3476(05)72459-8","article-title":"Vasoparalysis associated with brain damage in asphyxiated term infants","volume":"117","author":"Pryds","year":"1990","journal-title":"J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rawat, M., Chandrasekharan, P., Gugino, S., Koenigsknecht, C., Helman, J., Alsaleem, M., Mathew, B., Nair, J., Berkelhamer, S., and Vali, P. (2019). Oxygenation and Hemodynamics during Chest Compressions in a Lamb Model of Perinatal Asphyxia Induced Cardiac Arrest. Children, 6.","DOI":"10.3390\/children6040052"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.freeradbiomed.2019.03.035","article-title":"Oxygen radical disease in the newborn, revisited: Oxidative stress and disease in the newborn period","volume":"142","author":"Perez","year":"2019","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/s41390-021-01551-1","article-title":"Randomized trial of oxygen weaning strategies following chest compressions during neonatal resuscitation","volume":"90","author":"Sankaran","year":"2021","journal-title":"Pediatr. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1136\/archdischild-2020-321034","article-title":"Randomised trial of epinephrine dose and flush volume in term newborn lambs","volume":"106","author":"Sankaran","year":"2021","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"du Sert, N.P., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. 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Children, 6.","DOI":"10.3390\/children6040051"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.earlhumdev.2012.10.011","article-title":"Correlation between echocardiographic superior vena cava flow and short-term outcome in infants with asphyxia","volume":"89","author":"Kumagai","year":"2013","journal-title":"Early Hum. Dev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1203\/PDR.0b013e3181b3b110","article-title":"Circulatory Recovery Is as Fast with Air Ventilation as with 100% Oxygen After Asphyxia-Induced Cardiac Arrest in Piglets","volume":"66","author":"Linner","year":"2009","journal-title":"Pediatr. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sankaran, D., Rawat, M., and Lakshminrusimha, S. (2022). Optimal oxygen use in neonatal advanced cardiopulmonary resuscitation\u2014A literature review. Pediatr. Med., 1\u201317.","DOI":"10.21037\/pm-21-74"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.resuscitation.2016.06.014","article-title":"Myocardial perfusion and oxidative stress after 21% vs. 100% oxygen ventilation and uninterrupted chest compressions in severely asphyxiated piglets","volume":"106","author":"Lu","year":"2016","journal-title":"Resuscitation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"400","DOI":"10.3389\/fped.2018.00400","article-title":"A Review of Oxygen Use During Chest Compressions in Newborns\u2014A Meta-Analysis of Animal Data","volume":"6","author":"Cheung","year":"2018","journal-title":"Front. Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1159\/000143397","article-title":"Resuscitation of Newborn Infants with 21% or 100% Oxygen: An Updated Systematic Review and Meta-Analysis","volume":"94","author":"Saugstad","year":"2008","journal-title":"Neonatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1203\/PDR.0b013e31818a01a4","article-title":"High brain tissue oxygen tension during ventilation with 100% oxygen after fetal asphyxia in newborn sheep","volume":"65","author":"Nordh","year":"2009","journal-title":"Pediatr. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1038\/jcbfm.2008.15","article-title":"brief exposure to hyperoxia depletes the glial progenitor pool and impairs functional recovery after hypoxic-ischemic brain injury","volume":"28","author":"Koch","year":"2008","journal-title":"J. Cereb. 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