Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion

Concerns regarding the safety of transfused blood have led to the development of a range of interventions to minimise blood loss during major surgery. Anti-fibrinolytic drugs are widely used, particularly in cardiac surgery and previous reviews have found them to be effective in reducing blood loss and the need for transfusion. Recently, questions have been raised regarding the comparative performance of the drugs and the safety of the most popular agent, aprotinin. To assess the comparative effects of the anti-fibrinolytic drugs aprotinin, tranexamic acid (TXA), and epsilon aminocaproic acid (EACA) on blood loss during surgery, the need for red blood (RBC) transfusion, and adverse events, particularly vascular occlusion, renal dysfunction, and death. We searched CENTRAL, MEDLINE, EMBASE, and the internet. References in identified trials and review articles were checked and trial authors were contacted to identify any additional studies. The searches were last updated in July 2006. Randomised controlled trials (RCTs) of anti-fibrinolytic drugs in adults scheduled for non-urgent surgery. Eligible trials compared anti-fibrinolytic drugs with placebo (or no treatment), or with each other. Two authors independently assessed trial quality and extracted data. This review summarises data from 211 RCTs that recruited 20,781 participants. Data from placebo/inactive controlled trials, and from head-to-head trials suggest an advantage of aprotinin over the lysine analogues TXA and EACA in terms of operative blood loss, but the differences were small. Aprotinin reduced the probability of requiring RBC transfusion by a relative 34% (relative risk [RR] 0.66, 95% confidence interval [CI] 0.61 to 0.71). The RR for RBC transfusion with TXA was 0.61 (95% CI 0.54 to 0.69) and it was 0.75 (95% CI 0.58 to 0.96) with EACA. When the pooled estimates from the head-to-head trials of the two lysine analogues were combined and compared to aprotinin alone, aprotinin appeared superior in reducing the need for RBC transfusion: RR 0.83 (95% CI 0.69 to 0.99). Aprotinin reduced the need for re-operation due to bleeding: RR 0.48 (95% CI 0.35 to 0.68). This translates into an absolute risk reduction of just under 3% and a number needed-to-treat (NNT) of 37 (95% CI 27 to 56). Similar trends were seen with TXA and EACA, but the data were sparse and the differences failed to reach statistical significance. The blood transfusion data were heterogeneous and funnel plots indicate that trials of a