Fibrin sealants (also referred to as biological glue or fibrin tissue adhesives) have gained increasing popularity as interventions to improve peri-operative (intra- and post-operative) haemostasis and diminish the need for allogeneic red cell transfusion (blood from an unrelated donor).
To examine the efficacy of fibrin sealants in reducing peri-operative blood loss and allogeneic red blood cell (RBC) transfusion.
We identified studies by searching CENTRAL (The Cochrane Library 2007, Issue 3), MEDLINE (1950 to 2008), EMBASE (1980 to 2008), manufacturer web sites (to March 2008), and bibliographies of relevant published articles.
Controlled trials in which adult patients scheduled for elective surgery were randomised to fibrin sealant treatment or to a control group which did not receive fibrin sealant treatment. Trials were eligible if they reported data on the number of patients exposed to allogeneic red cell transfusion, the volume of blood transfused, or blood loss (assessed objectively).
Data collection and analysis
The primary outcomes measured were the: number of patients exposed to allogeneic red cells, amount of blood transfused, and blood loss. Other outcomes measured were: re-operation due to bleeding, infection, mortality, thrombotic events, and length of hospital stay. Treatment effects were pooled using a random-effects model.
Eighteen trials that included a total of 1406 patients reported data on peri-operative exposure to allogeneic RBC transfusion. Fibrin sealant treatment, on average, reduced the rate of exposure to allogeneic RBC transfusion by a relative 37% (relative risk (RR) 0.63, 95% confidence interval (CI) 0.45 to 0.88) and 7% in absolute terms (95% CI 2% to 13%). Fourteen trials, including a total of 853 patients, provided data for post-operative blood loss. In aggregate, fibrin sealant treatment reduced blood loss on average by around 161 ml per patient (95% CI 98.25 to 224.53 ml). In the context of orthopaedic surgery, fibrin sealant treatment reduced post-operative blood loss on average by around 223 ml per patient (95% CI 119.85 to 325.18 ml) and reduced the risk of exposure to allogeneic RBC transfusion by 32% (RR 0.68, 95% CI 0.51 to 0.89). Fibrin sealant treatment was not associated with an increased risk of wound infection (RR 0.61, 95% CI 0.24 to 1.58), any infection (RR 0.93, 95% CI 0.44 to 1.94), haematoma formation (RR 0.46, 95% CI 0.18 to 1.18), or death (RR 0.85, 95% CI 0.38 to 1.89). Hospital length of stay was not reduced in patients treated with fibrin sealant (weighted mean difference (WMD) −0.21 days, 95% CI −0.42 to 0.01 days).
Overall, the results suggest that fibrin sealants are efficacious in reducing both post-operative blood loss and peri-operative exposure to allogeneic RBC transfusion. Although treatment-effect heterogeneity was observed for these primary efficacy outcomes, heterogeneity was generally in terms of the size of effect rather than the direction of effect. Fibrin sealants appeared to demonstrate their greatest beneficial effects in the context of orthopaedic surgery, where blood loss is often substantial. Trials not involving orthopaedic surgery generally showed a trend toward decreased post-operative blood loss but the observed reductions were not clinically significant. The majority of trials included in this review were small, which raises concerns about the potential effects of publication bias. Funnel plot assessment indicates that there is some evidence of publication bias in the form of a missing population of small negative trials. We believe that large, methodologically rigorous, randomised controlled trials of fibrin sealants are needed.