Meta-Analysis with Trial Sequential Analysis on the Efficacy and Safety of Erythropoietin in Traumatic Brain Injury: A New Paradigm.

Abstract

Erythropoietin (EPO) has been shown to be beneficial in traumatic brain injury (TBI). We have attempted to quantitatively synthesize the findings of current randomized controlled trials (RCTs) in this meta-analysis and analyzed the need for further trials using trial sequential analysis (TSA). A systematic search was performed in PubMed, the Cochrane Library databases, and Google Scholar for RCTs until December 2019 evaluating the role of EPO in patients with TBI. Seven RCTs were finally included in the quantitative analysis. TSA was done to evaluate the need for further studies. The pooled estimate demonstrated that EPO significantly reduced mortality at 6 months (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.43-0.97; P = 0.04) but not in hospital mortality (OR, 0.84; 95% CI, 0.31-2.32; P = 0.74). There was no significant difference in the rate of favorable outcomes with EPO (OR, 1.58; 95% CI, 0.84-2.99; P = 0.16). The rate of deep vein thrombosis (RD, -0.02; 95% CI, -0.06 to 0.02; P =0.41) was also not found to be significantly different in the 2 groups. TSA showed that the accrued information is insufficient to make any definitive conclusions. EPO seems to be beneficial in terms of reducing 6-month mortality, however, its effect on in-hospital mortality, neurologic outcomes, and risk of deep vein thrombosis fails to reach statistical significance. TSA suggests a need for large trials to evaluate the role of EPO in patients with TBI in a more systematic way.