Cause and timing of death and sub-group differential effects of erythropoietin in the EPO-TBI study.
Identifieur interne : 000270 ( PubMed/Corpus ); précédent : 000269; suivant : 000271Cause and timing of death and sub-group differential effects of erythropoietin in the EPO-TBI study.
Auteurs : Markus Benedict Skrifvars ; Craig French ; Michael Bailey ; Jeffrey Presneill ; Alistair Nichol ; Lorraine Little ; Jacques Duranteau ; Olivier Huet ; Samir Haddad ; Yaseen Arabi ; Colin Mcarthur ; D James Cooper ; Rinaldo BellomoSource :
- Journal of neurotrauma [ 1557-9042 ] ; 2017.
Abstract
The EPO-TBI study randomised 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 due to a non-cerebral cause). The study included 305 patients treated with EPO and 297 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 (IQR 5-16) compared to 29 days (IQR 7-56) (p=0.01) with non-cerebral COD. When assessing subgroups by admission computed tomography scan injury findings, we found no significant differential effects of EPO compared to placebo. However, EPO appeared more effective in patients with an injury type not requiring a neurosurgical operation prior to ICU admission (OR 0.29, 95% confidence interval 0.14-0.61, p=0.001, p for interaction = 0.003) and in this sub-group, fewer patients died of cerebral causes in in the EPO compared to placebo group (5% compared to 14%, p=0.03). In conclusion, most TBI deaths were due to cerebral causesthat occurred during the first two 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 randomisation.
DOI: 10.1089/neu.2017.5135
PubMed: 29020866
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pubmed:29020866Le document en format XML
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<author><name sortKey="Arabi, Yaseen" sort="Arabi, Yaseen" uniqKey="Arabi Y" first="Yaseen" last="Arabi">Yaseen Arabi</name>
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<author><name sortKey="Bellomo, Rinaldo" sort="Bellomo, Rinaldo" uniqKey="Bellomo R" first="Rinaldo" last="Bellomo">Rinaldo Bellomo</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Cause and timing of death and sub-group differential effects of erythropoietin in the EPO-TBI study.</title>
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<author><name sortKey="French, Craig" sort="French, Craig" uniqKey="French C" first="Craig" last="French">Craig French</name>
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<author><name sortKey="Bailey, Michael" sort="Bailey, Michael" uniqKey="Bailey M" first="Michael" last="Bailey">Michael Bailey</name>
<affiliation><nlm:affiliation>Monash University, School of Public Health and Preventive Medicine, Melbourne, Victoria, Australia ; Michael.Bailey@monash.edu.</nlm:affiliation>
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<author><name sortKey="Presneill, Jeffrey" sort="Presneill, Jeffrey" uniqKey="Presneill J" first="Jeffrey" last="Presneill">Jeffrey Presneill</name>
<affiliation><nlm:affiliation>Royal Melbourne Hospital, 90134, Department of Intensive Care, Melbourne, Victoria, Australia ; intensive@fastmail.com.au.</nlm:affiliation>
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<author><name sortKey="Nichol, Alistair" sort="Nichol, Alistair" uniqKey="Nichol A" first="Alistair" last="Nichol">Alistair Nichol</name>
<affiliation><nlm:affiliation>Monash University School of Public Health and Preventive Medicine, 161667, ANZIC-RC, Melbourne, Victoria, Australia ; Alistair.Nichol@monash.edu.</nlm:affiliation>
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<author><name sortKey="Little, Lorraine" sort="Little, Lorraine" uniqKey="Little L" first="Lorraine" last="Little">Lorraine Little</name>
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<author><name sortKey="Duranteau, Jacques" sort="Duranteau, Jacques" uniqKey="Duranteau J" first="Jacques" last="Duranteau">Jacques Duranteau</name>
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</affiliation>
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<author><name sortKey="Huet, Olivier" sort="Huet, Olivier" uniqKey="Huet O" first="Olivier" last="Huet">Olivier Huet</name>
<affiliation><nlm:affiliation>Hopital de la Cavale-Blanche, 55359, Departement d'anesthésie-réanimation, Brest, Bretagne, France ; olivier.huet@chu-brest.fr.</nlm:affiliation>
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<author><name sortKey="Haddad, Samir" sort="Haddad, Samir" uniqKey="Haddad S" first="Samir" last="Haddad">Samir Haddad</name>
<affiliation><nlm:affiliation>King Abdullah International Medical Research Center, 309817, Intensive Care Department, Riyadh, Saudi Arabia ; samir.haddads55@yahoo.com.</nlm:affiliation>
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<author><name sortKey="Arabi, Yaseen" sort="Arabi, Yaseen" uniqKey="Arabi Y" first="Yaseen" last="Arabi">Yaseen Arabi</name>
<affiliation><nlm:affiliation>King Saud bin Abdulaziz University for Health Sciences, 48149, Intensive Care Department, Riyadh, Saudi Arabia ; yaseenarabi@yahoo.com.</nlm:affiliation>
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<author><name sortKey="Mcarthur, Colin" sort="Mcarthur, Colin" uniqKey="Mcarthur C" first="Colin" last="Mcarthur">Colin Mcarthur</name>
<affiliation><nlm:affiliation>Auckland City Hospital, 58991, Department of Critical Care Medicine, Auckland, New Zealand ; colinm@adhb.govt.nz.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Cooper, D James" sort="Cooper, D James" uniqKey="Cooper D" first="D James" last="Cooper">D James Cooper</name>
<affiliation><nlm:affiliation>The Alfred, Intensive Care , Commercial Road , Melbourne, Victoria, Australia , 3004.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Bellomo, Rinaldo" sort="Bellomo, Rinaldo" uniqKey="Bellomo R" first="Rinaldo" last="Bellomo">Rinaldo Bellomo</name>
<affiliation><nlm:affiliation>Monash University, ANZIC-RC , Level 6 , The Alfred Centre , 99 Commercial Road , Melbourne, Victoria, Australia , 3004 ; rinaldo.bellomo@austin.org.au.</nlm:affiliation>
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<front><div type="abstract" xml:lang="en">The EPO-TBI study randomised 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 due to a non-cerebral cause). The study included 305 patients treated with EPO and 297 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 (IQR 5-16) compared to 29 days (IQR 7-56) (p=0.01) with non-cerebral COD. When assessing subgroups by admission computed tomography scan injury findings, we found no significant differential effects of EPO compared to placebo. However, EPO appeared more effective in patients with an injury type not requiring a neurosurgical operation prior to ICU admission (OR 0.29, 95% confidence interval 0.14-0.61, p=0.001, p for interaction = 0.003) and in this sub-group, fewer patients died of cerebral causes in in the EPO compared to placebo group (5% compared to 14%, p=0.03). In conclusion, most TBI deaths were due to cerebral causesthat occurred during the first two 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 randomisation.</div>
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<ArticleTitle>Cause and timing of death and sub-group differential effects of erythropoietin in the EPO-TBI study.</ArticleTitle>
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<Abstract><AbstractText>The EPO-TBI study randomised 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 due to a non-cerebral cause). The study included 305 patients treated with EPO and 297 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 (IQR 5-16) compared to 29 days (IQR 7-56) (p=0.01) with non-cerebral COD. When assessing subgroups by admission computed tomography scan injury findings, we found no significant differential effects of EPO compared to placebo. However, EPO appeared more effective in patients with an injury type not requiring a neurosurgical operation prior to ICU admission (OR 0.29, 95% confidence interval 0.14-0.61, p=0.001, p for interaction = 0.003) and in this sub-group, fewer patients died of cerebral causes in in the EPO compared to placebo group (5% compared to 14%, p=0.03). In conclusion, most TBI deaths were due to cerebral causesthat occurred during the first two 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 randomisation.</AbstractText>
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<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Skrifvars</LastName>
<ForeName>Markus Benedict</ForeName>
<Initials>MB</Initials>
<AffiliationInfo><Affiliation>Helsinki University Hospital, Department of Anesthesia, Intensive Care and Pain Medicine , Haartmaninkatu 9 , 00029 HUS , HUS, Finland , 00029 ; markus.skrifvars@hus.fi.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>French</LastName>
<ForeName>Craig</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Intensive Care, Western Health, Melbourne, Victoria, Australia, Melbourne, Victoria, Australia ; Craig.French@wh.org.au.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Bailey</LastName>
<ForeName>Michael</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Monash University, School of Public Health and Preventive Medicine, Melbourne, Victoria, Australia ; Michael.Bailey@monash.edu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Presneill</LastName>
<ForeName>Jeffrey</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Royal Melbourne Hospital, 90134, Department of Intensive Care, Melbourne, Victoria, Australia ; intensive@fastmail.com.au.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Nichol</LastName>
<ForeName>Alistair</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Monash University School of Public Health and Preventive Medicine, 161667, ANZIC-RC, Melbourne, Victoria, Australia ; Alistair.Nichol@monash.edu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Little</LastName>
<ForeName>Lorraine</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Monash University School of Public Health and Preventive Medicine, 161667, ANZIC-RC, Melbourne, Victoria, Australia ; lorraine.little@monash.edu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Duranteau</LastName>
<ForeName>Jacques</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Hopitaux Universitaires Paris-Sud, 378965, Department of Anesthesia and Intensive Care, Le Kremlin-Bicetre, Île-de-France, France ; jacques.duranteau@aphp.fr.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Huet</LastName>
<ForeName>Olivier</ForeName>
<Initials>O</Initials>
<AffiliationInfo><Affiliation>Hopital de la Cavale-Blanche, 55359, Departement d'anesthésie-réanimation, Brest, Bretagne, France ; olivier.huet@chu-brest.fr.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Haddad</LastName>
<ForeName>Samir</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>King Abdullah International Medical Research Center, 309817, Intensive Care Department, Riyadh, Saudi Arabia ; samir.haddads55@yahoo.com.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Arabi</LastName>
<ForeName>Yaseen</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>King Saud bin Abdulaziz University for Health Sciences, 48149, Intensive Care Department, Riyadh, Saudi Arabia ; yaseenarabi@yahoo.com.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>McArthur</LastName>
<ForeName>Colin</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Auckland City Hospital, 58991, Department of Critical Care Medicine, Auckland, New Zealand ; colinm@adhb.govt.nz.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cooper</LastName>
<ForeName>D James</ForeName>
<Initials>DJ</Initials>
<AffiliationInfo><Affiliation>The Alfred, Intensive Care , Commercial Road , Melbourne, Victoria, Australia , 3004.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Monash University, ANZIC-RC , Level 6 , The Alfred Centre , 99 Commercial Road , Melbourne, Victoria, Australia , 3004 ; jamie.cooper@monash.edu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bellomo</LastName>
<ForeName>Rinaldo</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Monash University, ANZIC-RC , Level 6 , The Alfred Centre , 99 Commercial Road , Melbourne, Victoria, Australia , 3004 ; rinaldo.bellomo@austin.org.au.</Affiliation>
</AffiliationInfo>
</Author>
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<Month>10</Month>
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<MedlineTA>J Neurotrauma</MedlineTA>
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<ISSNLinking>0897-7151</ISSNLinking>
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<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">ADULT BRAIN INJURY</Keyword>
<Keyword MajorTopicYN="N">CLINICAL MANAGEMENT OF CNS INJURY</Keyword>
<Keyword MajorTopicYN="N">HEAD TRAUMA</Keyword>
<Keyword MajorTopicYN="N">HUMAN STUDIES</Keyword>
<Keyword MajorTopicYN="N">TRAUMATIC BRAIN INJURY</Keyword>
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