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Background:Significant blood loss is still one of the most frequent complications in spinal surgery,which often necessitates blood transfusion.Massive perioperative blood loss and blood transfusion can create additional risks.Aprotinin,tranexamic acid (TXA),and epsilon-aminocaproic acid (EACA) are antifibrinolytics currently offered as prophylactic agents to reduce surgery-associated blood loss.The aim of this study was to evaluate the efficacy and safety of aprotinin,EACA,and low/high doses of TXA in spinal surgery,and assess the use of which agent is the most optimal intervention using the network meta-analysis (NMA) method.Methods:Five electronic databases were searched,including PubMed,Cochrane Library,ScienceDirect,Embase,and Web of Science,from the inception to March 1,2018.Trials that were randomized and compared results between TXA,EACA,and placebo were identified.The NMA was conducted with software R 3.3.2 and STATA 14.0.Results:Thirty randomized controlled trial (RCT) studies were analyzed.Aprotinin (standardized mean difference [SMD]=-0.65,95％ credibility intervals [CrI;-1.25,-0.06]),low-dose TXA (SMD=-0.58,95％ CrI [-0.92,-0.25]),and high-dose TXA (SMD=-0.70,95％ CrI [-1.04,-0.36]) were more effective than the respective placebos in reducing intraoperative blood loss.Low-dose TXA (SMD =-1.90,95％ CrI [-3.32,-0.48]) and high-dose TXA (SMD=-2.31,95％ CrI [-3.75,-0.87]) had less postoperative blood loss.Low-dose TXA (SMD=-1.07,95％ CrI [-1.82,-0.31]) and high-dose TXA (SMD=-1.07,95％ CrI [-1.82,-0.31]) significantly reduced total blood loss.However,only high-dose TXA (SMD =-2.07,95％ CrI [-3.26,-0.87]) was more effective in reducing the amount of transfusion,and was significantly superior to low-dose TXA in this regard (SMD =-1.67,95％ CrI [-3.20,-0.13]).Furthermore,aprotinin (odds ratio [OR]=0.16,95％ CrI [0.05,0.54]),EACA (OR=0.46,95％ CrI [0.22,0.97]) and high dose of TXA (OR=0.34,95％ CrI [0.19,0.58]) had a significant reduction in transfusion rates.Antifibrinolytics did not show a significantly increased risk of postoperative thrombosis.Results of ranking probabilities indicated that high-dose TXA had the greatest efficacy and a relatively high safety level.Conclusions:The antifibrinolytic agents are able to reduce perioperative blood loss and transfusion requirement during spine surgery.And the high-dose TXA administration might be used as the optimal treatment to reduce blood loss and transfusion.