Efficacy and safety of erythropoietin for traumatic brain injury

Abstract

Background Recent studies regarding the effects of erythropoietin (EPO) for treating traumatic brain injury (TBI) have been inconsistent. This study conducts a meta-analysis of randomized controlled trials (RCTs) to assess the safety and efficacy of EPO for TBI patients at various follow-up time points. Methods A literature search was performed using PubMed, Web of Science, MEDLINE, Embase, Google Scholar and the Cochrane Library for RCTs studying EPO in TBI patients published through March 2019. Non-English manuscripts and non-human studies were excluded. The assessed outcomes include mortality, neurological recovery and associated adverse effects. Dichotomous variables are presented as risk ratios (RR) with a 95% confidence interval (CI). Results A total of seven RCTs involving 1197 TBI patients (611 treated with EPO, 586 treated with placebo) were included in this study. Compared to the placebo arm, treatment with EPO did not improve acute hospital mortality or short-term mortality. However, there was a significant improvement in mid-term (6 months) follow-up survival rates. EPO administration was not associated with neurological function improvement. Regarding adverse effects, EPO treatment did not increase the incidence of thromboembolic events or other associated adverse events. Conclusions This meta-analysis indicates a slight mortality benefit for TBI patients treated with EPO at mid-term follow-up. EPO does not improve in-hospital mortality, nor does it increase adverse events including thrombotic, cardiovascular and other associated complications. Our analysis did not demonstrate a significant beneficial effect of EPO intervention on the recovery of neurological function. Future RCTs are required to further characterize the use of EPO in TBI.

Comparative Safety of Multiple Doses of Erythropoietin for the Treatment of Traumatic Brain Injury: A Systematic Review and Network Meta-Analysis

“…Regarding the Incidence of pulmonary embolism events. Since the number of studies is small and the relationship is not prominent, we believe that the use of EPO did not increase the possibility of its occurrence temporarily, which is similar to the results of previous traditional meta-analyses [19], too. It's worth noting that EPO has been proved to be associated with increased blood viscosity, elevated hemoglobin concentration, and vasoconstriction, which may contribute to the incidence of thromboembolism and the risk of cardiovascular events, including death [7].…”

“…The results of our network meta-analysis displayed that erythropoietin did not show a statistically signi cant in reducing in mortality among TBI patients, which differs from previous studies [19][20][21][22]. The probable reason is that we excluded relevant RCT studies that did not accurately report drug doses and did not distinguish when mortality occurred, as well as the algorithm mechanism differences between traditional pairwise meta-analysis and network metaanalysis produced by Addis software.…”

“…Although erythropoietin has been found to improve the prognosis of neurological function after the treatment of TBI in most animal experiments, the improvement of neurological function has not been statistically signi cant in human studies in the recent meta-studies [19,20,22] based on RCT studies, which may be related to insu cient sample size and number of studies or the failure to adopt the most appropriate clinical observation indicators. But it's worth noting that erythropoietin plays an important role in reducing mortality in patients with TBI.…”

“…A network meta-analysis (NMA) enables a coherent ranking of multiple interventions, which can thus assist decision-makers who must choose among variable treatment options [18]. In the existing meta-analysis and related original studies [19][20][21][22], the dosage of erythropoietin in the treatment of TBI varies widely. Dose optimization studies were not clear, and no dose-response studies of erythropoietin in TBI treatment had been well established.…”

Effect of erythropoietin administration on the expression of brain-derived neurotrophic factor, stromal cell-derived Factor-1, and neuron-specific enolase in traumatic brain injury: A literature review

“…The administration of erythropoietin (EPO) can positively impact the clinical outcome of patients with severe traumatic brain injury (TBI) [ 1 , 2 ]. This review discusses the possibility that the therapeutic effects of EPO may affect neurological function, neurological performance, and neurological recovery through the expression mechanisms of brain-derived neurotrophic factor (BDNF), stromal cell-derived factor-1 (SDF-1), and neuron-specific enolase (NSE).…”