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Three Part Question

In [patients undergoing cardiac surgery] does [topical transexamic acid] reduce the incidence of [post-operative bleeding]?

Clinical Scenario

You have just started a cardiothoracic rotation as a Specialist Registrar and you have been assisting your consultant with a straightforward coronary artery bypass graft case and he has left you to "close the chest". You have achieved meticulous surgical haemostasis and have started suturing the sternum. Your scrub nurse reminds you not to forget the tranexamic acid washout, which the consultant routinely uses for all his cases. You adhere to the consultant's protocols but wonder what evidence is available to justify the routine use of topical tranexamic acid in cardiac surgery.

Search Strategy

Medline 1966-June 2004, Embase 1980-June 2004, CINAHL 1982-June 2004 using the OVID interface. The Cochrane Database of Systematic Reviews, ACP Journal Club, DARE and CENTRAL were also searched.
[exp Cardiovascular surgical procedures/ OR cardiovascular surgical procedures.mp OR exp Thoracic surgery/ OR Thoracic surgery.mp OR exp Coronary Artery Bypass/ OR coronary artery bypass surgery.mp OR CABG.mp OR coronary surgery.mp OR cardiac surgery.mp OR revascularization.mp ] AND [exp Tranexamic acid/ OR tranexamic.mp OR cyklokapron.mp]

Search Outcome

132 papers were found in Medline, 300 papers were found in Embase, 3 papers were found in CINAHL, and 76 papers were found in the combined CDSR, ACP journal club, DARE and CENTRAL databases using the reported search. However only 1 relevant paper was found which is presented in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
De Bonis et al 2000 Italy	40 consecutive patients undergoing primary elective CABG surgery by 2 cardiac surgeons. Tranexamic Acid group (TXA): 20 patients had 1g TXA in 100ml saline poured into mediastinum Placebo: 20 patients had 100ml saline poured into mediastinum Both solutions at room temperature. Fluid was applied, the sternum closed and then the mediastinal drains unclamped	Double blind PRCT (level 2b)	24 hr blood loss	TXA group: 485+/-166mls Placebo group: 641+/-184 mls p=0.01	Blood tests were taken and no systemic tranexamic acid was detected Very small sample size in this study No patients with valve surgery, urgent or emergency surgery, or heparin or aspirin administration pre-operatively
			Total blood loss	TXA group: 573+/-164ml (range 360-1020mls) Placebo group: 739+/-228ml (range 365-1310ml) p=0.01
			Blood usage	TXA group: 3/20 (15%) RBC use Placebo group: 4/20 (20%) RBC use, p =NS

Comment(s)

Despite searching 7 databases, with over 400 abstracts retrieved, only 1 paper was found assessing the use of topical tranexamic acid post-cardiac surgery, for the reduction in post-operative bleeding. Several other papers exist on the use of topical tranexamic acid to reduce bleeding after bladder, dental and gynaecological surgery, however we felt that these studies would not be sufficiently relevant to cardiac surgery, where coagulation is significantly deranged during the procedure. In addition intravenous tranexamic acid has been conclusively shown to reduce bleeding, with multiple studies having been summarized by Fremes et al meta-analysis showing an overall 30% reduction in post-operative bleeding with its use. However these papers are also not relevant in answering the question of whether topical tranexamic acid may possess the same properties. Several experimental studies have demonstrated the molecular basis for the function of Tranexamic acid which acts by binding to the lysine-binding sites of plamin and plasminogen (Longstaff). Saturation of these sites displaces palsminogen from the fibrin surface thus inhibiting fibrinolysis. However again this is not directly relevant to answering our clinical question as to whether topical application is effective. The only study was a double blinded controlled trial performed published by De Bonis et al in 2000. They randomized 40 consecutive patients undergoing primary CABG to have Topical tranexamic acid or placebo. 1g of tranexamic acid was added to 100mls of normal saline and poured into the sternotomy wound prior to closure. The mediastinal drains were clamped during closure, and the clamps were only removed after the operation had been completed. Placebo patients received 100mls of normal saline only. They demonstrated a 36% reduction in bleeding at 3 hours and a 25% reduction at 24 hours. However the absolute differences were small with the mean blood loss being 485mls in the tranexamic acid group and 641mls in the placebo group. In addition no benefit in terms of reduced blood products was demonstrated. This was a small study that did not include urgent or emergency patients, patients undergoing valve or aortic arch procedures, or patients who had been receiving heparin, aspirin or clopidogrel pre-operatively where a greater blood loss might be expected. Thus the absolute benefit found by this study was small. Thus in summary only 1 small RCT exists in this area which demonstrates a clinically small difference in blood loss with topical tranexamic acid and only studied low risk patients. Further RCTs should be performed (and could very easily be set up and conducted) prior to any further use of topical tranexamic acid as a strategy to reduce post-operative bleeding.

Clinical Bottom Line

Only 1 RCT exists to answer this question which demonstrated a clinically small benefit in favour of topical tranexamic acid in low risk patients. Further RCTs should be performed prior to any further use of topical tranexamic acid as a strategy to reduce post-operative bleeding.

References

1. De Bonis M, Cavaliere F, Alessandrini F, Lapenna E, Santarelli F, Moscato U, et al. Topical use of tranexamic acid in coronary artery bypass operations: A double-blind, prospective, randomised, placebo-controlled study. J Thorac Cardiovasc Surg 2000;119:575-80.
2. Fremes SE, Wong BI, Lee E, Mai R, Christakis GT, McLean RF, Goldman BS, Naylor CD. Metaanalysis of prophylactic drug treatment in the prevention of postoperative bleeding. Ann Thorac Surg 1994;58:1580-1588.
3. Longstaff C. Studies on the mechanisms of action of aprotinin and tranexamic acid as plasmin inhibitors and antifibrinolytic agents. Blood Coagul Fibrinolysis 1994;537-42.