{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T11:43:18Z","timestamp":1776685398780,"version":"3.51.2"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022183","name":"Dansk Selskab for An\u00e6stesiologi og Intensiv Medicin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022183","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Anaesthesiol Scand"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Perioperative hyperoxia may be associated with increased long\u2010term mortality, whereas perioperative antioxidants may be associated with reduced long\u2010term mortality. This study aimed to determine if high perioperative inspiratory oxygen fraction (FiO\n                      <jats:sub>2<\/jats:sub>\n                      ) (0.80) compared with normal FiO\n                      <jats:sub>2<\/jats:sub>\n                      (0.30) would increase mortality, hospital admissions, and myocardial infarction (MI) within 1 year after surgery, and whether antioxidants compared with placebo would reduce this.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This was the preplanned 1\u2010year follow\u2010up of 600 patients with cardiovascular risk factors, scheduled for noncardiac surgery. They were randomized in a 2\u2009\u00d7\u20092 factorial design to perioperative FiO\n                      <jats:sub>2<\/jats:sub>\n                      of 0.80 or 0.30 and to receive antioxidants (vitamin C and N\u2010acetylcysteine) or matching placebo. The primary 1\u2010year outcome was all\u2010cause mortality, and secondary 1\u2010year outcomes were one or more hospital admissions and MIs, respectively. All outcomes were assessed using medical records and analyzed with the Cox proportional hazards model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Follow\u2010up was completed for 594 patients (99%). Twenty\u2010five of 298 patients (8.4%) allocated to FiO\n                      <jats:sub>2<\/jats:sub>\n                      of 0.80 died within 1 year as compared with 17 out of 296 (5.7%) allocated to FiO\n                      <jats:sub>2<\/jats:sub>\n                      of 0.30, HR 1.46 (95% CI, 0.79\u20132.70),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.23. A total of 260 patients had one or more hospital admissions (44%), and seven patients had MI (1.2%) with no significant difference when comparing FiO\n                      <jats:sub>2<\/jats:sub>\n                      of 0.80 with 0.30. Antioxidants had a HR of 0.98 (95% CI, 0.54\u20131.80),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.96 for all\u2010cause mortality vs. placebo. The interaction between the FiO\n                      <jats:sub>2<\/jats:sub>\n                      and antioxidant administration was statistically significant (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04) with fatalities overrepresented in patients given 80% oxygen and placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Differences in all\u2010cause mortality, hospital admission, or MI were not statistically significant at 1\u2010year follow\u2010up for either oxygen fractions or antioxidant administration in patients undergoing major noncardiac surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Editorial Comment<\/jats:title>\n                    <jats:p>In this preplanned long\u2010term study of the VIXIE trial, no differences in total mortality, hospitalization, or myocardial infarction were found for oxygen fractions of 0.80 compared to 0.30 or antioxidant administration compared to placebo. Interestingly, the study showed a higher rate of fatalities with 80% oxygen which appeared only to be present in patients not given the antioxidant intervention, but this is hypothesis\u2010generating and needs to be further investigated in new clinical trials.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">Clinicaltrials.gov<\/jats:ext-link>\n                      identifier: NCT03494387\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aas.70118","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T22:35:02Z","timestamp":1759876502000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Hyperoxia and Antioxidants on Mortality, Hospital Admissions, and Myocardial Infarction After Noncardiac Surgery: 1\u2010Year Follow\u2010Up of a Randomized Controlled Trial"],"prefix":"10.1111","volume":"69","author":[{"given":"Frederik C.","family":"Loft","sequence":"first","affiliation":[{"name":"Department of Anaesthesia and Intensive Care Copenhagen University Hospital \u2010 Bispebjerg and Frederiksberg Hospital  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilie","family":"Holse","sequence":"additional","affiliation":[{"name":"Novo Nordisk  S\u00f8borg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eske K.","family":"Aasvang","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia Center of Cancer and Organ Dysfunction, Copenhagen University Hospital \u2010 Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten","family":"Vester\u2010Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"},{"name":"Herlev Anaesthesia Critical and Emergency Care Science Unit, Department of Anaesthesiology Copenhagen University Hospital \u2013 Herlev and Gentofte Hospital  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7480-3004","authenticated-orcid":false,"given":"Lars S.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Personnel Agency Danish Ministry of Defence  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars N.","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"},{"name":"Digestive Disease Center Copenhagen University 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