The effect of recombinant erythropoietin on long-term outcome after moderate-to-severe traumatic brain injury.

Skrifvars, Markus B; Luethi, Nora; Bailey, Michael; French, Craig; Nichol, Alistair; Trapani, Tony; McArthur, Colin; Arabi, Yaseen M; Bendel, Stepani; Cooper, David J; Bellomo, Rinaldo (2023). The effect of recombinant erythropoietin on long-term outcome after moderate-to-severe traumatic brain injury. Intensive care medicine, 49(7), pp. 831-839. Springer 10.1007/s00134-023-07141-5

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Recombinant erythropoietin (EPO) administered for traumatic brain injury (TBI) may increase short-term survival, but the long-term effect is unknown.


We conducted a pre-planned long-term follow-up of patients in the multicentre erythropoietin in TBI trial (2010-2015). We invited survivors to follow-up and evaluated survival and functional outcome with the Glasgow Outcome Scale-Extended (GOSE) (categories 5-8 = good outcome), and secondly, with good outcome determined relative to baseline function (sliding scale). We used survival analysis to assess time to death and absolute risk differences (ARD) to assess favorable outcomes. We categorized TBI severity with the International Mission for Prognosis and Analysis of Clinical Trials in TBI model. Heterogeneity of treatment effects were assessed with interaction p-values based on the following a priori defined subgroups, the severity of TBI, and the presence of an intracranial mass lesion and multi-trauma in addition to TBI.


Of 603 patients in the original trial, 487 patients had survival data; 356 were included in the follow-up at a median of 6 years from injury. There was no difference between treatment groups for patient survival [EPO vs placebo hazard ratio (HR) (95% confidence interval (CI) 0.73 (0.47-1.14) p = 0.17]. Good outcome rates were 110/175 (63%) in the EPO group vs 100/181 (55%) in the placebo group (ARD 8%, 95% CI [Formula: see text] 3 to 18%, p = 0.14). When good outcome was determined relative to baseline risk, the EPO groups had better GOSE (sliding scale ARD 12%, 95% CI 2-22%, p = 0.02). When considering long-term patient survival, there was no evidence for heterogeneity of treatment effect (HTE) according to severity of TBI (p = 0.85), presence of an intracranial mass lesion (p = 0.48), or whether the patient had multi-trauma in addition to TBI (p = 0.08). Similarly, no evidence of treatment heterogeneity was seen for the effect of EPO on functional outcome.


EPO neither decreased overall long-term mortality nor improved functional outcome in moderate or severe TBI patients treated in the intensive care unit (ICU). The limited sample size makes it difficult to make final conclusions about the use of EPO in TBI.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > University Emergency Center

UniBE Contributor:

Lüthi, Nora


600 Technology > 610 Medicine & health








Pubmed Import

Date Deposited:

06 Jul 2023 14:11

Last Modified:

19 Jul 2023 00:16

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Uncontrolled Keywords:

Erythropoietin Neurological outcome Traumatic brain injury




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