AUTHOR=Zheng Qingyong , Duan Dan , Xu Jianguo , Wang Xing , Ge Yonggui , Xiong Lu , Yang Jingjing , Wulayin Saimire , Luo Xiaofeng 

TITLE=Comparative safety of multiple doses of erythropoietin for the treatment of traumatic brain injury: A systematic review and network meta-analysis

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.998320

DOI=10.3389/fneur.2022.998320

ISSN=1664-2295

ABSTRACT=Introduction: Over the past few decades, advances in traumatic brain injury (TBI) pathology research updated our understanding dynamically. We aimed to systematically elucidate the safety and efficacy of erythropoietin (EPO) administration regimens in patients with TBI.
Methods: Data search included PubMed, the Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov for articles published before December 2020, updated to July 2022. The network meta-analysis was conducted using ADDIS 1.16.8, and the CINeMA tool was used to assess the quality level of evidence.
Results: A total of six RCTs involving 981 patients were included in the network meta-analysis. EPO did not significantly reduce mortality in patients with TBI, but its risk of death decreased with increasing dosage (odd ratio (OR) of 12,000u vs Placebo=0.98, 95%CI, 0.03-40.34; OR of group 30,000u vs Placebo=0.56, 95%CI, 0.06-5.88; OR of 40,000u vs Placebo=0.35, 95%CI, 0.01-9.43; OR of 70,000u vs Placebo=0.29, 95%CI, 0.01-9.26; OR of group 80,000u vs Placebo=0.22, 95%CI, 0.00-7.45). Three studies involving 739 patients showed that EPO did not increase the incidence of deep vein thrombosis in patients with TBI. However, the risk tended to rise as the dosage increased. Two studies demonstrated that EPO did not increase the incidence of pulmonary embolism. The quality of evidence for all outcomes was low to moderate.
Conclusions: Although the efficacy of EPO was not statistically demonstrated, we found a trend towards an association between EPO dosage and reduced mortality and increased embolic events in patients with TBI. More high-quality original studies should be conducted to obtain strong evidence on the optimal dosage of EPO.
Systematic Review registration: The study protocol was registered with PROSPERO (CRD42021272500).