{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:50:23Z","timestamp":1793163023162,"version":"4.5.0"},"reference-count":47,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"unspecified","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U01 NS099046"],"award-info":[{"award-number":["U01 NS099046"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2022,2,2]]},"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Management of traumatic brain injury (TBI) includes invasive monitoring to prevent secondary brain injuries. Intracranial pressure (ICP) monitor is the main measurement used to that intent but cerebral hypoxia can occur despite normal ICP. This study will assess whether the addition of a brain tissue oxygenation (PbtO\n                      <jats:sub>2<\/jats:sub>\n                      ) monitor prevents more secondary injuries that will translate into improved functional outcome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      Multicentre, randomised, blinded-endpoint comparative effectiveness study enrolling 1094 patients with severe TBI monitored with both ICP and PbtO\n                      <jats:sub>2<\/jats:sub>\n                      . Patients will be randomised to medical management guided by ICP alone (treating team blinded to PbtO\n                      <jats:sub>2<\/jats:sub>\n                      values) or both ICP and PbtO\n                      <jats:sub>2<\/jats:sub>\n                      . Management is protocolised according to international guidelines in a tiered approach fashion to maintain ICP &lt;22 mm Hg and PbtO\n                      <jats:sub>2<\/jats:sub>\n                      &gt;20 mm Hg. ICP and PbtO\n                      <jats:sub>2<\/jats:sub>\n                      will be continuously recorded for a minimum of 5 days. The primary outcome measure is the Glasgow Outcome Scale-Extended performed at 180 (\u00b130) days by a blinded central examiner. Favourable outcome is defined according to a sliding dichotomy where the definition of favourable outcome varies according to baseline severity. Severity will be defined according to the probability of poor outcome predicted by the IMPACT core model. A large battery of secondary outcomes including granular neuropsychological and quality of life measures will be performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This has been approved by Advarra Ethics Committee (Pro00030585). Results will be presented at scientific meetings and published in peer-reviewed publications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Registry (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03754114\">NCT03754114<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-060188","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T11:57:20Z","timestamp":1646913440000},"page":"e060188","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":138,"title":["Brain Oxygen Optimization in Severe Traumatic Brain Injury (BOOST-3): a multicentre, randomised, blinded-endpoint, comparative effectiveness study of brain tissue oxygen and intracranial pressure monitoring versus intracranial pressure alone"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct03754114","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9121-2882","authenticated-orcid":false,"given":"Francis","family":"Bernard","sequence":"first","affiliation":[{"name":"Critical Care, H\u00f4pital du Sacr\u00e9-Coeur de Montr\u00e9al, Montreal, Quebec, Canada"},{"name":"Department of Medicine, Universit\u00e9 de Montreal, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Barsan","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Diaz-Arrastia","sequence":"additional","affiliation":[{"name":"Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa H","family":"Merck","sequence":"additional","affiliation":[{"name":"Emergency Medicine and Neurology, Neurocritical Care, University of Florida College of Medicine, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Yeatts","sequence":"additional","affiliation":[{"name":"Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1390-0628","authenticated-orcid":false,"given":"Lori A","family":"Shutter","sequence":"additional","affiliation":[{"name":"Critical Care Medicine, Neurology, & Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"2025121221173683000_12.3.e060188.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30371-X"},{"key":"2025121221173683000_12.3.e060188.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsr.2012.08.011"},{"key":"2025121221173683000_12.3.e060188.3","doi-asserted-by":"publisher","DOI":"10.1097\/01.HTR.0000314531.30401.39"},{"key":"2025121221173683000_12.3.e060188.4","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2006.0209"},{"key":"2025121221173683000_12.3.e060188.5","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0000000000001432"},{"key":"2025121221173683000_12.3.e060188.6","unstructured":"Cryer H , Manley G , Adelson D . Acs TQIP best practices in the management of traumatic brain injury, 2015."},{"key":"2025121221173683000_12.3.e060188.7","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1056\/NEJMoa1207363","article-title":"A trial of intracranial-pressure monitoring in traumatic brain injury","volume":"367","author":"Chesnut","year":"2012","journal-title":"N Engl J Med Overseas Ed"},{"key":"2025121221173683000_12.3.e060188.8","first-page":"1751","article-title":"Intracranial-Pressure monitoring in traumatic brain injury","volume":"368","author":"Chesnut","year":"2013","journal-title":"N Engl J Med"},{"key":"2025121221173683000_12.3.e060188.9","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0000000000000078"},{"key":"2025121221173683000_12.3.e060188.10","first-page":"1","article-title":"Minimal PaO2 threshold after traumatic brain injury and clinical utility of a novel brain oxygenation ratio","author":"Dellazizzo","year":"2018","journal-title":"J Neurosurg"},{"key":"2025121221173683000_12.3.e060188.11","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e318192fbd7"},{"key":"2025121221173683000_12.3.e060188.12","doi-asserted-by":"publisher","DOI":"10.3171\/2020.1.JNS192732"},{"key":"2025121221173683000_12.3.e060188.13","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000127777.16609.08"},{"key":"2025121221173683000_12.3.e060188.14","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1001\/jamaneurol.2016.0091","article-title":"Pathophysiologic mechanisms of cerebral ischemia and diffusion hypoxia in traumatic brain injury","volume":"73","author":"Veenith","year":"2016","journal-title":"JAMA Neurol"},{"key":"2025121221173683000_12.3.e060188.15","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181a009f8"},{"key":"2025121221173683000_12.3.e060188.16","doi-asserted-by":"publisher","DOI":"10.3171\/2010.1.JNS09506"},{"key":"2025121221173683000_12.3.e060188.17","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000369607.71913.3E"},{"key":"2025121221173683000_12.3.e060188.18","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1227\/NEU.0b013e3182287ca7","article-title":"Brain hypoxia is associated with short-term outcome after severe traumatic brain injury independently of intracranial hypertension and low cerebral perfusion pressure","volume":"69","author":"Oddo","year":"2011","journal-title":"Neurosurgery"},{"key":"2025121221173683000_12.3.e060188.19","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1007\/s00134-019-05900-x","article-title":"A management algorithm for adult patients with both brain oxygen and intracranial pressure monitoring: the Seattle international severe traumatic brain injury consensus conference (SIBICC)","volume":"46","author":"Chesnut","year":"2020","journal-title":"Intensive Care Med"},{"key":"2025121221173683000_12.3.e060188.20","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1097\/CCM.0000000000002619","article-title":"Brain oxygen optimization in severe traumatic brain injury phase-II: a phase II randomized trial","volume":"45","author":"Okonkwo","year":"2017","journal-title":"Crit Care Med"},{"key":"2025121221173683000_12.3.e060188.21","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1097\/CCM.0000000000002575","article-title":"Individualizing thresholds of cerebral perfusion pressure using estimated limits of autoregulation","volume":"45","author":"Donnelly","year":"2017","journal-title":"Crit Care Med"},{"key":"2025121221173683000_12.3.e060188.22","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199910000-00002"},{"key":"2025121221173683000_12.3.e060188.23","doi-asserted-by":"crossref","first-page":"083","DOI":"10.1385\/NCC:2:1:083","article-title":"Physiological and biochemical principles underlying volume-targeted therapy--the \"Lund concept\"","volume":"2","author":"Nordstr\u00f6m","year":"2005","journal-title":"Neurocrit Care"},{"key":"2025121221173683000_12.3.e060188.24","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.482810"},{"key":"2025121221173683000_12.3.e060188.25","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.547950"},{"key":"2025121221173683000_12.3.e060188.26","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.972000"},{"key":"2025121221173683000_12.3.e060188.27","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70234-5"},{"key":"2025121221173683000_12.3.e060188.28","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2006.0035"},{"key":"2025121221173683000_12.3.e060188.29","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1207363"},{"key":"2025121221173683000_12.3.e060188.30","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1007\/s00134-018-5251-4","article-title":"Intracranial pressure thresholds in severe traumatic brain injury: we are not sure : Prudent clinical practice despite dogma or nihilism","volume":"44","author":"Stocchetti","year":"2018","journal-title":"Intensive Care Med"},{"key":"2025121221173683000_12.3.e060188.31","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181743d77"},{"key":"2025121221173683000_12.3.e060188.32","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-040550"},{"key":"2025121221173683000_12.3.e060188.33","doi-asserted-by":"publisher","DOI":"10.3171\/2014.3.JNS131500"},{"key":"2025121221173683000_12.3.e060188.34","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2005.102.2.0311"},{"key":"2025121221173683000_12.3.e060188.35","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1227\/NEU.0000000000001192","article-title":"Association of severe traumatic brain injury patient outcomes with duration of cerebrovascular autoregulation impairment events","volume":"79","author":"Preiksaitis","year":"2016","journal-title":"Neurosurgery"},{"key":"2025121221173683000_12.3.e060188.36","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1097\/CCM.0b013e3181d45530","article-title":"Effects of cerebrovascular pressure reactivity-guided optimization of cerebral perfusion pressure on brain tissue oxygenation after traumatic brain injury","volume":"38","author":"Jaeger","year":"2010","journal-title":"Crit Care Med"},{"key":"2025121221173683000_12.3.e060188.37","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200301000-00042"},{"key":"2025121221173683000_12.3.e060188.38","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000218413.51546.9E"},{"key":"2025121221173683000_12.3.e060188.39","doi-asserted-by":"publisher","DOI":"10.3171\/JNS\/2008\/108\/01\/0053"},{"key":"2025121221173683000_12.3.e060188.40","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00303.2003"},{"key":"2025121221173683000_12.3.e060188.41","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2004.101.2.0323"},{"key":"2025121221173683000_12.3.e060188.42","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-014-3555-6"},{"key":"2025121221173683000_12.3.e060188.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.resuscitation.2014.05.021"},{"key":"2025121221173683000_12.3.e060188.44","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.001016"},{"key":"2025121221173683000_12.3.e060188.45","doi-asserted-by":"crossref","first-page":"e279","DOI":"10.1097\/CCM.0000000000002935","article-title":"The cumulative partial pressure of arterial oxygen is associated with neurological outcomes after cardiac arrest treated with targeted temperature management","volume":"46","author":"Youn","year":"2018","journal-title":"Crit Care Med"},{"key":"2025121221173683000_12.3.e060188.46","doi-asserted-by":"publisher","DOI":"10.1136\/ip.2005.010983"},{"key":"2025121221173683000_12.3.e060188.47","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2013.3019"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2021-060188","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T05:17:45Z","timestamp":1765603065000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2021-060188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":47,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3,10]]},"published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1136\/bmjopen-2021-060188"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2021-060188","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3]]}}}