Therapeutic effect of erythropoietin in patients with traumatic brain injury: a meta-analysis of randomized controlled trials

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Erythropoietin (EPO) exerts a neuroprotective effect in animal models of traumatic brain injury (TBI). However, its effectiveness in human patients with TBI is unclear. In this study, the authors conducted the first meta-analysis to assess the effectiveness and safety of EPO in patients with TBI.


In December 2015, a systematic search was performed of PubMed, Web of Science, MEDLINE, Embase, the Cochrane Library databases, and Google Scholar. Only English-language publications of randomized controlled trials (RCTs) using EPO in patients with TBI were selected for analysis. The assessed outcomes included mortality, favorable neurological outcome, hospital stay, and associated adverse effects. Continuous variables were presented as mean difference (MD) with a 95% confidence interval (CI). Dichotomous variables were presented as risk ratio (RR) or risk difference (RD) with a 95% CI. Statistical heterogeneity was examined using both I2 and chi-square tests.


Of the 346 studies identified in the search, 5 RCTs involving 915 patients met the inclusion criteria. The overall results demonstrated that EPO significantly reduced mortality (RR 0.69, 95% CI 0.49–0.96, p = 0.03) and shortened the hospitalization time (MD −7.59, 95% CI −9.71 to −5.46, p < 0.0001) for patients with TBI. Pooled results of favorable outcome (RR 1.00, 95% CI 0.88–1.15, p = 0.97) and deep vein thrombosis (DVT; RD 0.00, 95% CI −0.05 to 0.05, p = 1.00) did not show a significant difference.


The authors suggested that EPO is beneficial for patients with TBI in terms of reducing mortality and shortening hospitalization time without increasing the risk of DVT. However, its effect on improving favorable neurological outcomes did not reach statistical significance. Therefore, more well-designed RCTs are necessary to ascertain the optimum dosage and time window of EPO treatment for patients with TBI.

ABBREVIATIONS CI = confidence interval; DVT = deep vein thrombosis; EPO = erythropoietin; GOS = Glasgow Outcome Scale; MD = mean difference; RCT = randomized controlled trial; RD = risk difference; RR = risk ratio; TBI = traumatic brain injury.

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Contributor Notes

Correspondence Xiao-Feng Yang, Department of Neurosurgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Rd., Hangzhou City, Zhejiang Province 310000, China. email: WHEN CITING Published online July 1, 2016; DOI: 10.3171/2016.4.JNS152909.

Drs. Liu and Wen contributed equally to this work.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.



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