Efficacy and Safety of Using Antifibrinolytic Agents in Spine Surgery: a Meta-Analysis

Citation: Yuan C, Zhang H, He S ( Efficacy and Safety of Using Antifibrinolytic Agents in Spine Surgery: a Meta-Analysis Chaoqun Yuan 0 Hailong Zhang 0 Shisheng He 0 Toshiyuki Miyata, National Cerebral and Cardiovascular Center, Japan 0 Department of Orthopaedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine , Shanghai , China Purpose: Spine surgery, particularly reconstructive surgery, can be associated with significant blood loss, and blood transfusion. Antifibrinolytic agents are used routinely to reduce bleeding in cardiac, orthopaedic, and hepatic surgery. The purpose of this study was to assess the efficacy and safety of using antifibrinolytic agents in reducing blood loss and blood transfusions in spine surgery. Methods: A systematic search of all related studies written in English published by October 2012 was conducted using the MEDLINE, EMBASE and the Cochrane Library databases. Randomized controlled trials that reported the drug dosage, total blood loss, blood transfusion and incidence of deep vein thrombosis as the primary outcome were included. Results: Nine studies involving 482 patients were identified. Patients receiving antifibrinolytic agents had reduced blood loss (WMD =-288.8, 95 % CI - 46.49, - 110.19; P = 0.002), reduced blood transfusion (WMD =-242.7, 95 % CI - 422.57, - 62.95; P = 0.008), reduced blood transfusion rate (RR 0.73, 95% CI 0.58, 0.93; p = 0.010) and no increase (RR 0.25, 95 % CI 0.03, 2.22; P = 0.21) in the risk of deep vein thrombosis. Conclusions: We conclude that antifibrinolytic agents significantly decrease blood loss, blood transfusion, and there is no increase in the risk of deep vein thrombosisfor transfusion requirements in spine surgery. - These authors contributed equally to this work. Spine surgery has typically been associated with significant blood loss and transfusion requirements. It is particularly common for multilevel spinal fusion [1], deformity correction [2] and anterior-posterior spinal fusion [3]. Although blood transfusions may effectively replace perioperative blood loss, there is a potential for transfusion reactions/complications and disease transmission [4]. Data further suggests that both bleeding and resultant transfusions are associated with an increased risk of adverse outcomes [5]. Measures to decrease transfusion-related complications such as preoperative autologous blood donation, application of cell saver-systems or the use of erythropoietin are often associated with higher costs and logistic challenges [6-8]. Since the 1990s, intraoperative administration of antifibrinolytics has gained popularity as a means to control blood loss [9].There are various reports on the use of antifibrinolytic drugs, like tranexamic acid (TXA), epsilonaminocaproic acid (EACA), and aprotinin to reduce the blood loss and transfusion requirements in spine surgery. In 2008, Gill JB et al. [10] had performed a meta-analysis of prospective clinical trials to assess whether antifibrinolytic agents (TXA, EACA, Aprotinin) reduce bleeding and transfusion requirements in patients undergoing spine surgery. But the main limitation of that meta-analysis is the quality of the studies included. As more high quality Randomized controlled trials were published, we therefore performed this meta-analysis of RCTs to check if antifibrinolytic agents reduced blood loss and blood transfusions in patients undergoing spine surgery, as well as their effect on the incidence of DVT. Materials and Methods Computerised search of the electronic databases MEDLINE, EMBASE and the Cochrane Library databases were performed for all studies written in English published by October 2012 that compared antifibrinolytic agents with placebo for sipne surgery. The following search terms were used to maximize the search specificity and sensitivity: spine surgery, spinal surgery, antifibrinolytic agents, tranexamic acid, and epsilonaminocaproic acid. Secondary searches of the unpublished literature were conducted by searching the WHO International Clinical Trials Registry Platform, UK National Research Register Archive and Current Controlled Trials from their inception to October 2012. The reference lists of all the full-text papers were examined to identify any initially omitted studies. Inclusion Criteria Studies were included if they met the following criteria: randomized controlled trials on spine surgery in which tranexamic acid or epsilon-aminocaproic acid was compared with placebo; outcomes: reported at least one of blood loss, blood transfusion, ratio of blood transfusion, incidence of DVT(deep vein thrombosis). Two reviewers independently screened the titles and abstracts for the eligibility criteria. Consensus was reached by discussion. Data extraction Two of the authors independently extracted the following data from each full-text report using a standard data extraction form. The data extracted from studies included authors, year of publication, country, sample size, age, gender, drug dosage, transfusion indication, duration of surgery, total blood loss, blood transfusion, ratio of blood tansfusion, and incidence of DVT. Assessment of methodological quality Following the Cochrane Handbook for Systematic Reviews of Interventions 5.0, the methodological quality of the included studies was independently assessed by two authors. Any disagreements were resolved by discussion. The corresponding author was the adjudicator when no consensus could be achieved. We evaluated the risk of bias of included studies using the Review Manager software (RevMan Version 5.2; The Nordic Cochrane Center, The Cochrane Collaboration, Copenhagen, Denmark),which included the following key domains: Random sequence generation (selection bias); Allocation concealment (selection bias); Blinding of participants and personnel (performance bias); Blinding of outcome assessment (detection bias); Incomplete outcome data (attrition bias); Selective reporting (reporting bias). The publication bias was assessed with funnel plots. Data analysis We performed all of the meta-analyses with the Review Manager software (RevMan Version 5.2; The Nordic Cochrane Center, The Cochrane Collaboration, Copenhagen, Denmark). For continuous outcomes, such as total blood loss and blood tansfusion were pooled to a weighted mean difference (WMD) and 95 % confidence interval (CI). Risk ratios (RRs) and 95 % confidence intervals (CIs) were used to evaluate the dichotomous outcomes, such as ratio of blood tansfusion and incidence of DVT. A P value < 0.05 was considered to be statistically significant. The fixed effect model was used when the test for homogeneity was significant (p> 0. 05), while a P value of <0.05 was considered suggestive of statistical heterogeneity and random effect model was used. The sensitivity analysis was performed by rejecting the studies with higher statistical heterogeneity. Search results A total of 296 titles and abstracts were preli (...truncated)