{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:50:22Z","timestamp":1793163022700,"version":"4.5.0"},"reference-count":34,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: The benefits of liberal transfusion strategies for neurological outcomes in critically ill patients with acute brain injuries (ABIs) remain uncertain due to conflicting evidence and potential risks. This study aimed to evaluate the efficacy and safety of a liberal transfusion strategy in adults with ABI. Methods: A systematic review of PubMed, Scopus, and the Cochrane Library was conducted from inception until 18 December 2024. Randomized clinical trials (RCTs) comparing liberal and restrictive transfusion strategies in adult patients admitted to intensive care units with ABI were included. The primary outcome was unfavorable neurological function at the last follow-up, defined as Glasgow Outcome Scale (GOS) score &lt;4, Extended GOS score &lt;5, or modified Rankin Scale score &gt;3. Results: Among 5859 screened records, five RCTs (2385 patients) met the inclusion criteria. Liberal transfusion significantly reduced unfavorable neurological outcomes (RR, 0.88; 95% CI, 0.82\u20130.95; p = 0.0009) without affecting mortality (RR, 0.97; 95% CI, 0.84\u20131.11; p = 0.66). A meta-analysis of two studies (n = 1465 patients) showed improved functional independence with liberal strategies (MD, 6.70; 95% CI, 2.07\u201311.33; p = 0.005) but no difference in quality of life (p = 0.30). Sepsis or septic shock occurred less frequently in the liberal group (RR, 0.68; 95% CI, 0.50\u20130.92; p = 0.01). Subgroup analysis indicated that liberal strategies improved neurological outcome in traumatic brain injury (TBI) patients (RR, 0.89; 95% CI, 0.82\u20130.97; p = 0.01) but did not yield significant differences in spontaneous subarachnoid hemorrhage (p = 0.09). Conclusions: Liberal transfusion strategies safely improve neurological outcomes in adults with ABI, specifically in the subgroup of TBI, whereas further studies are needed in patients with SAH.<\/jats:p>","DOI":"10.3390\/jcm14103487","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T06:57:28Z","timestamp":1747378648000},"page":"3487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transfusion Thresholds and Neurological Functional Outcome After Acute Brain Injury: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7683-5310","authenticated-orcid":false,"given":"Pierludovico","family":"Moro","sequence":"first","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2426-2075","authenticated-orcid":false,"given":"Marco","family":"Andrighetti","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Siconolfi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Catholic University of the Sacred Heart, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Sole","family":"Borioni","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Di Bonaventura","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danilo","family":"Toni","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3906-555X","authenticated-orcid":false,"given":"Emanuele","family":"Cerulli Irelli","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s13054-016-1321-6","article-title":"Anemia management after acute brain injury","volume":"20","author":"Lelubre","year":"2016","journal-title":"Crit. Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s12028-023-01815-0","article-title":"Anemia and Red Blood Cell Transfusion in Aneurysmal Subarachnoid Hemorrhage","volume":"39","author":"Terrett","year":"2023","journal-title":"Neurocrit. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.cnc.2017.04.012","article-title":"The Risks Associated with Red Blood Cell Transfusion: Implications for Critical Care Practice","volume":"29","author":"Sutton","year":"2017","journal-title":"Crit. Care Nurs. Clin. N. Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1089\/neur.2022.0056","article-title":"Transfusion Guidelines in Traumatic Brain Injury: A Systematic Review and Meta-Analysis of the Currently Available Evidence","volume":"3","author":"Montgomery","year":"2022","journal-title":"Neurotrauma Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1001\/jama.2014.6490","article-title":"Effect of Erythropoietin and Transfusion Threshold on Neurological Recovery After Traumatic Brain Injury: A randomized clinical trial","volume":"312","author":"Robertson","year":"2014","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13054-018-2273-9","article-title":"Transfusion requirements after head trauma: A randomized feasibility controlled trial","volume":"23","author":"Gobatto","year":"2019","journal-title":"Crit. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1001\/jama.2024.20424","article-title":"Restrictive vs Liberal Transfusion Strategy in Patients with Acute Brain Injury: The TRAIN Randomized Clinical Trial","volume":"332","author":"Taccone","year":"2024","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1056\/NEJMoa2404360","article-title":"Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury","volume":"391","author":"Turgeon","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1056\/NEJMoa2410962","article-title":"Liberal or Restrictive Transfusion Strategy in Aneurysmal Subarachnoid Hemorrhage","volume":"392","author":"English","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.tmrv.2015.08.004","article-title":"Red Blood Cell Transfusion in Patients with Traumatic Brain Injury: A Systematic Review and Meta-Analysis","volume":"30","author":"Boutin","year":"2016","journal-title":"Transfus. Med. Rev."},{"key":"ref_11","first-page":"1473","article-title":"Hemoglobin levels as a transfusion criterion in moderate to severe traumatic brain injury: A systematic review and meta-analysis","volume":"37","author":"Agrawal","year":"2021","journal-title":"Br. J. Neurosurg."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yu, Y., Fu, Y., Li, W., Sun, T., Cheng, C., Chong, Y., Han, R., and Cui, W. (2024). Red blood cell transfusion in neurocritical patients: A systematic review and meta-analysis. BMC Anesthesiol., 24.","DOI":"10.1186\/s12871-024-02487-9"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s13613-024-01411-1","article-title":"Efficacy of restrictive versus liberal transfusion strategies in patients with traumatic brain injury: A systematic review and meta-analysis of randomized controlled trials","volume":"14","author":"Yuan","year":"2024","journal-title":"Ann. Intensiv. Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1177\/0962280216669183","article-title":"Optimally estimating the sample mean from the sample size, median, mid-range, and\/or mid-quartile range","volume":"27","author":"Luo","year":"2018","journal-title":"Stat. Methods Med. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/jrsm.1429","article-title":"Optimally estimating the sample standard deviation from the five-number summary","volume":"11","author":"Shi","year":"2020","journal-title":"Res. Synth. Methods"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan\u2014A web and mobile app for systematic reviews","volume":"5","author":"Ouzzani","year":"2016","journal-title":"Syst. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"109981","DOI":"10.1016\/j.yebeh.2024.109981","article-title":"Cognitive behavioral therapy in adults with functional seizures: A systematic review and meta-analysis of randomized controlled trials","volume":"159","author":"Moro","year":"2024","journal-title":"Epilepsy Behav."},{"key":"ref_19","unstructured":"(2025, May 08). Review Manager (RevMan) [Computer Program], Available online: https:\/\/revman.cochrane.org\/info\/trial."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","article-title":"GRADE: An emerging consensus on rating quality of evidence and strength of recommendations","volume":"336","author":"Guyatt","year":"2008","journal-title":"BMJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1385\/NCC:5:1:4","article-title":"Effect of a Liberal Versus Restrictive Transfusion Strategy on Mortality in Patients with Moderate to Severe Head Injury","volume":"5","author":"McIntyre","year":"2006","journal-title":"Neurocrit. Care"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1056\/NEJM199902113400601","article-title":"A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group","volume":"340","author":"Wells","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/MCC.0000000000000485","article-title":"Is hemoglobin good for cerebral oxygenation and clinical outcome in acute brain injury?","volume":"24","author":"English","year":"2018","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_24","first-page":"131","article-title":"Early predictive factors on mortality in head injured patients: A retrospective analysis of 112 traumatic brain injured patients","volume":"56","author":"Prisco","year":"2012","journal-title":"J. Neurosurg. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s11136-023-03511-0","article-title":"Biopsychosocial factors of quality of life in individuals with moderate to severe traumatic brain injury: A scoping review","volume":"33","author":"Mamman","year":"2024","journal-title":"Qual. Life Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3171\/2016.11.JNS16805","article-title":"Long-term reintegration and quality of life in patients with subarachnoid hemorrhage and a good neurological outcome: Findings after more than 20 years","volume":"128","author":"Sonesson","year":"2018","journal-title":"J. Neurosurg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1089\/neu.2014.3652","article-title":"Neurologic Functional and Quality of Life Outcomes after TBI: Clinic Attendees versus Non-Attendees","volume":"32","author":"Patel","year":"2015","journal-title":"J. Neurotrauma"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1136\/jnnp-2021-326615","article-title":"Discrepancy between disability and reported well-being after traumatic brain injury","volume":"93","author":"Helmrich","year":"2022","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.hrtlng.2023.12.001","article-title":"Prognostic value of hemoglobin in patients with sepsis: A systematic review and meta-analysis","volume":"64","author":"Zhu","year":"2023","journal-title":"Heart Lung"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Peng, H., Su, Y., Luo, J., and Ding, N. (2024). Association between admission hemoglobin level and prognosis in sepsis patients based on a critical care database. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-55954-1"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/SHK.0000000000001612","article-title":"Early Hemoglobin Status as a Predictor of Long-Term Mortality for Sepsis Patients in Intensive Care Units","volume":"55","author":"Qi","year":"2021","journal-title":"Shock"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kristof, K., B\u00fcttner, B., Grimm, A., Mewes, C., Schmack, B., Popov, A.F., Ghadimi, M., Beissbarth, T., Hinz, J., and Bergmann, I. (2018). Anaemia requiring red blood cell transfusion is associated with unfavourable 90-day survival in surgical patients with sepsis. BMC Res. Notes, 11.","DOI":"10.1186\/s13104-018-3988-z"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"106845","DOI":"10.1016\/j.jstrokecerebrovasdis.2022.106845","article-title":"Evidence-based interconversion of the Glasgow Outcome a.nd modified Rankin scales: Pitfalls and best practices","volume":"31","author":"Gaastra","year":"2022","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/10\/3487\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:33:52Z","timestamp":1760031232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/10\/3487"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,16]]},"references-count":34,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["jcm14103487"],"URL":"https:\/\/doi.org\/10.3390\/jcm14103487","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,16]]}}}