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BackgroundErythropoietin (EPO) may reduce mortality after traumatic brain injury (TBI). Secondary brain injury is exacerbated by multiple trauma, and possibly modifiable by EPO. We hypothesized that EPO decreases mortality more in TBI patients with multiple trauma, than in patients with TBI alone.MethodsA post hoc analysis of the EPO-TBI randomized controlled trial conducted in 2009 to 2014. To evaluate the impact of injuries outside the brain, we calculated an extracranial Injury Severity Score (ISS) that included the same components of the ISS, excluding head and face components. We defined multiple trauma as two injured body regions with an Abbreviated Injury Scale (AIS) score of 3 or higher. Cox regression analyses, allowing for potential differential responses per the presence or absence of extracranial injury defined by these injury scores, were used to assess the effect of EPO on time to mortality.ResultsOf 603 included patients, the median extracranial ISS was 6 (interquartile range, 1-13) and 258 (43%) had an AIS score of 3 or higher in at least two body regions. On Cox regression, EPO was associated with decreased mortality in patients with greater extracranial ISS (interaction p = 0.048) and weakly associated with differential mortality with multiple trauma (AIS score > 3 or in two regions, interaction p = 0.17). At 6 months in patients with extracranial ISS higher than 6, 10 (6.8%) of 147 EPO-treated patients compared with 26 (17%) of 154 placebo-treated patients died (risk reduction, 10%; 95% confidence interval, 2.9-17%; p = 0.007).ConclusionIn this post hoc analysis, EPO administration was associated with a potential differential improvement in 6-month mortality in TBI patients with more severe extracranial injury. These findings need confirmation in future clinical and experimental studies.Level of evidenceTherapeutic study, level III.

Original publication





The journal of trauma and acute care surgery

Publication Date





449 - 456


From the Australian and New Zealand Intensive Care Research Centre (M.B.S., M.B., C.F., J.P., A.N., L.L., D.J.C., R.B.), School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Division of Intensive Care, Department of Anaesthesiology, Intensive Care and Pain Medicine (M.B.S.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Intensive Care Helsinki, Finland; Department of Intensive Care (C.F.), Western Health; University of Melbourne (C.F.); Department of Intensive Care (J.P.), Royal Melbourne Hospital, Melbourne, Victoria, Australia; School of Medicine and Medical Sciences (A.N.), University College Dublin, Dublin, Ireland; Department of Intensive Care and Hyperbaric Medicine (A.N., D.J.C.), The Alfred, Melbourne, Victoria, Australia; Département d'Anesthésie-Réanimation (J.D.), Hôpital de Bicêtre, Assistance Publique des Hopitaux de Paris, Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, Paris; Department of Anaesthesiology and Intensive Care Medicine (O.H.), CHU La Cavale Blanche, Brest, France; King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center (S.H., Y.A.), Riyadh, Saudi Arabia; Auckland City Hospital (C.M.), Auckland, New Zealand; and Department of Intensive Care (R.B.), Austin Health, Melbourne, Victoria, Australia.


EPO-TBI investigators and the ANZICS Clinical Trials Group, Humans, Multiple Trauma, Erythropoietin, Treatment Outcome, Abbreviated Injury Scale, Injury Severity Score, Adult, Middle Aged, Female, Male, Brain Injuries, Traumatic