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

Abstract

OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Keywords: 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; deep vein thrombosis; erythropoietin; favorable neurological outcome; meta-analysis; mortality; traumatic brain injury.