Efficacy of antifibrinolytic agents on surgical bleeding and transfusion requirements in spine surgery: a meta-analysis

Abstract

Purpose: Spine surgery is usually associated with large amount of blood loss and blood transfusion. Excessive blood loss may cause hypotension, inadequate oxygenation of organs, necessitate allogeneic blood transfusion, and spinal epidural hematoma formation. Aprotinin, TXA, and EACA are antifibrinolytics currently offered as prophylactic agents to reduce surgery-associated blood loss. The purpose of this study was to assess the efficacy of using antifibrinolytic agents in reducing blood loss and blood transfusions in spine surgery.

Methods: PubMed, Embase, and Cochrane-controlled trials register were used to identify RCTs published before April 2015 that examined the effectiveness of intravenous aprotinin, tranexamic acid (TXA), and epsilon-aminocaproic acid (EACA) on reduction of blood loss and blood transfusions, compared with placebo in spine surgery. Randomized controlled trials reported the primary outcome that included total blood loss, intra-operative blood loss, post-operative blood loss, blood transfusion requirements, blood transfusion rate, and incidence of deep vein thrombosis. Meta-analysis was performed using the Stata12.0. Weighted mean difference with 95 % confidence intervals was used to summarize the findings across the trials for continuous outcomes. Dichotomous data were expressed as risk ratios with 95 % confidence intervals. A P < 0.05 was considered statistically significant.

Results: 17 studies involving 1191 patients were identified. Among them, 13 RCTs with 943 patients were included for the evaluation of total blood loss. Compared with the control group, the antifibrinolytic agents reduced total blood loss (SMD = -0.62; 95 % CI -0.75, -0.48; P = 0.000), The aprotinin group (SMD = -0.80; 95 % CI -1.22, -0.37; P = 0.938), The TXA group (SMD = -0.75; 95 % CI -0.93, -0.57; P = 0.000), and the EACA group (SMD = -0.28; 95 % CI -0.54, -0.01; P = 0.185). Thirteen RCTs with eight hundred and ninety four patients were included for the evaluation of intra-operative blood loss. Compared with the control group, the antifibrinolytic agents reduced intra-operative blood loss (SMD = -0.41; 95 % CI -0.55, -0.28; P = 0.010), The aprotinin group (SMD = -0.62; 95 % CI -0.93, -0.30; P = 0.862), The TXA group (SMD = -0.47; 95 % CI -0.64, -0.29; P = 0.005), and the EACA group (SMD = -0.16; 95 % CI -0.42, -0.11; P = 0.897). Eight RCTs with six hundred and seven patients were included for the evaluation of post-operative blood loss. Compared with the control group, the antifibrinolytic agents reduced post-operative blood loss (SMD = -0.68; 95 % CI -0.85, -0.51; P = 0.000), the aprotinin group (SMD = -0.48; 95 % CI -0.85, -0.12; P = 0.036), the TXA group (SMD = -0.80; 95 % CI -1.01, -0.59; P = 0.000), and the EACA group (SMD = -0.32; 95 % CI -0.68, -0.04; P = 0.009). Ten RCTs with seven hundred and twenty twopatients were included for the evaluation of blood transfusion. Compared with the control group, the antifibrinolytic agents reduced blood transfusion (SMD = -0.68; 95 % CI -0.85, -0.51; P = 0.000), the aprotinin group (SMD = -0.80; 95 % CI -1.22, -0.37; P = 0.938), the TXA group (SMD = -0.38; 95 % CI -0.58, -0.18; P = 0.000), and the EACA group (SMD = -0.28; 95 % CI -0.54, -0.01; P = 0.185). Twelve RCTs with eight hundred and fifteenpatients were included for the evaluation of blood transfusion rate. The transfusion rate was 35.6 % in the patients with antifibrinolytic agents and 55.2 % in the patients with placebo (RR = 0.75; 95 % CI 0.63, 0.89; P = 0.939). All studies were included for the evaluation of safety, with a total of eight thromboembolic events reported overall (two in the experimental group and six in the control group).

Conclusions: The antifibrinolytic agents were able to reduce perioperative blood loss and transfusion requirements in spine surgery. TXA appeared more effective than aprotinin and EACA in reducing total blood loss, intra-operative blood loss, and blood transfusion according to the results of this analysis. The three groups in reducing the post-operative blood loss are significantly better than control groups. There was no evidence that the use of antifibrinolytic agents was a risk factor for thromboembolism in spine surgery. Further multicenter, large-sample, double-blind RCTs are required to confirm the efficacy and safety of the three antifibrinolytic agents in spine surgery.

Keywords: Antifibrinolytic agents; Blood loss; Blood transfusion; Meta-analysis; Spine surgery.