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Title: Cause and Timing of Death and Subgroup Differential Effects of Erythropoietin in the EPO-TBI Study.
Austin Authors: Skrifvars, Markus B;French, Craig;Bailey, Michael;Presneill, Jeffrey;Nichol, Alistair;Little, Lorraine;Durantea, Jacques;Huet, Olivier;Haddad, Samir;Arabi, Yaseen;McArthur, Colin;Cooper, D James;Bellomo, Rinaldo 
Affiliation: Division of Intensive Care, Department of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University and Helsinki University Hospital, Helsinki, Finland
Department of Intensive Care, Austin Health, Heidelberg, Victoria, Australia
Department of Intensive Care and Hyperbaric Medicine, The Alfred, Melbourne, Victoria, Australia
School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland
St Vincent's University Hospital, Dublin, Ireland
Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia
Department of Intensive Care, Western Health, Melbourne, Victoria, Australia
North West Academic Centre, University of Melbourne, Melbourne, Victoria, Australia
Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
Département d'Anesthésie-Réanimation, Hôpital de Bicêtre, Assistance Publique des Hopitaux de Paris, Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, Paris, France
Department of Anaesthesiology and Intensive Care Medicine, CHU La Cavale Blanche, Brest, France
King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
Auckland City Hospital, Auckland, New Zealand
Issue Date: 2018
Publication information: Journal of neurotrauma 2018; 35(2): 333-340
Abstract: The EPO-TBI study randomized 606 patients with moderate or severe traumatic brain injury (TBI) to be treated with weekly epoetin alfa (EPO) or placebo. Six month mortality was lower in EPO treated patients in an analysis adjusting for TBI severity. Knowledge of possible differential effects by TBI injury subtype and acute neurosurgical treatment as well as timing and cause of death (COD) will facilitate the design of future interventional TBI trials. We defined COD as cerebral (brain death, cerebral death with withdrawal, or death during maximal care) and non-cerebral (death following withdrawal or during maximal care, which had a non-cerebral cause). The study included 305 patients treated with EPO and 297 treated with placebo, with COD recorded in 77 (99%) out of 78 non-survivors. Median time to death in patients dying of cerebral COD was 8 days (interquartile range [IQR] 5-16) compared with 29 days (IQR 7-56) (p = 0.01) for non-cerebral COD. When assessing subgroups by admission CT scan injury findings, we found no significant differential effects of EPO compared with placebo. However, EPO appeared more effective in patients with an injury type not requiring a neurosurgical operation prior to intensive care unit (ICU) admission (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.14-0.61, p = 0.001, p for interaction = 0.003) and in this subgroup, fewer patients died of cerebral causes in the EPO than in the placebo group (5% compared with 14%, p = 0.03). In conclusion, most TBI deaths were from cerebral causes that occurred during the first 2 weeks, and were related to withdrawal of care. EPO appeared to specifically reduce cerebral deaths in the important subgroup of patients with a diffuse type of injury not requiring a neurosurgical intervention prior to randomization.
DOI: 10.1089/neu.2017.5135
ORCID: 0000-0002-1650-8939
Journal: Journal of neurotrauma
PubMed URL: 29020866
Type: Journal Article
Subjects: adult brain injury
clinical management of central nervous system injury
head trauma
human studies
traumatic brain injury (TBI)
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