Interactive Cardiovascular and Thoracic Surgery 3:489-494(2004)
© 2004 European Association of Cardio-Thoracic Surgery
Best evidence topic - Cardiac general |
Does prophylactic tranexamic acid safely reduce bleeding without increasing thrombotic complications in patients undergoing cardiac surgery?
Sundaramoorthi Thiagarajamurthya,
Adrian Levinea and
Joel Dunningb,*
a Department of Cardiothoracic Surgery, North Staffordshire Royal Infirmary, Stoke, UK
b Department of Cardiothoracic Surgery, Freeman Hospital, Newcastle-upon-Tyne NE7 7DN, UK
moorti{at}hotmail.com adrian_levine{at}hotmail.com * Corresponding author. Tel.: +44-780-1548122
joeldunning{at}doctors.org.uk
Received April 14, 2004;
accepted April 16, 2004
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Abstract
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A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether prophylactic tranexamic acid can safely reduce bleeding without increasing thrombotic complications in patients undergoing cardiac surgery. Altogether 334 papers were found using the reported search, of which 12 represented the best evidence on this topic. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses were tabulated. We conclude that tranexamic acid clearly reduces blood loss, requirement for blood transfusion, and the risk of reoperation for bleeding, and although no study has yet looked directly at vein graft patency with tranexamic acid, no randomized studies have raised concerns over its safety.
Key Words: Evidence-based medicine; Tranexamic acid; Thoracic surgery; Cardiopulmonary bypass; Post-operative complications; Review
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1. Introduction
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A best evidence topic was constructed according to a structured protocol. This protocol is fully described in the ICVTS [1].
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2. Clinical scenario
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You have referred a patient with unstable angina who is on aspirin and a heparin infusion. You take him to theatre for CABG and the anaesthetist gives him tranexamic acid 2 g on induction and 1 g after completion of CPB. After straightforward quadruple bypass grafts he comes off bypass with ease and is transferred to the intensive care unit without any inotropic support. Two hours later the patient develops ST elevation in the inferior leads. Though the patient is haemodynamically stable, a balloon pump is inserted and as arrangements are being made to take him back for re-exploration, the ECG changes revert back to normal and remain so subsequently. Two months later you review this patient who is still getting some angina. An angiogram reveals that two of the vein grafts are now blocked. You wonder whether it was the tranexamic acid that might have caused this complication.
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3. Three-part question
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In [patients undergoing coronary arterial bypass grafting], does [tranexamic acid] administration [compromise graft patency].
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4. Search strategy
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Medline 1966-March 2004 using the Ovid interface [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].
Cochrane database of Systematic Reviews, ACP Journal Club and the Database of Reviews of Effects: search performed using keyword Tranexamic acid in the title.
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5. Search outcome
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One hundred and twenty-seven papers were found in Medline and an additional 207 abstracts were found in the Cochrane database. Sixteen papers were selected for full review but four papers were rejected due to inadequate data on thrombotic complications [2–5]. The 12 remaining papers are presented in Table 1 [6–17].
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6. Discussion
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One meta-analysis, one cohort study and 10 prospective randomized controlled trials were found that documented studies comparing tranexamic acid (TXA) to either aprotinin or placebo with documentation of thrombotic complications. The meta-analysis by Fremes et al. [6] was performed in 1994 and found only two papers on tranexamic acid. They found that either E-aminocaproic acid or tranexamic acid reduced bleeding by 30% and found no increase in perioperative myocardial infarction.
The only study that highlighted anxiety over the safety of tranexamic acid was the cohort study by Ovrum et al. [7] published in 1993. Ovrum routinely used TXA until a patient had an acute thrombosis of all her grafts and adjacent native coronaries. He stopped using it and analysed the results of his next 100 patients compared to the previous 100. He had five MIs with TXA but only one MI without TXA, which was not statistically significant. This is a retrospective, single surgeon study, with extreme bias introduced by a surgeon who will almost certainly be taking far more care with his anastomoses after this change in practise.
The largest PRCT was by Casati et al. [11] who compared aprotinin to Tranexamic acid in 1040 primary elective CABG patients. They found no difference in bleeding, re-operation for bleeding, transfusion or outcome. In addition they documented no difference in perioperative MI, early reoperation for ischaemia, PE, neurological dysfunction or death, although the numbers of positive patients in each of these categories was small. They concluded that tranexamic acid was clinically as effective as aprotinin and was available at a fraction of the cost.
Five PRCTs compared tranexamic acid to placebo. Four of the five clearly showed a reduction in bleeding rates. None of the studies investigated graft patency, but other outcome measures such as MI, PE, and neurological dysfunction were reported, and no concerns were raised as to the safety of tranexamic acid. It is important to note that the incidence of thrombotic complications is low and thus all of these studies are underpowered to exclude the possibility of increased thrombotic complications as the largest was in less than 150 patients.
Thus it is clear that tranexamic acid reduces the incidence of post-operative bleeding, and only one cohort study has raised any concern over its safety in terms of thrombotic complications. No study has looked at vein graft patency after tranexamic acid directly.
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7. Clinical bottom line
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Tranexamic acid clearly reduces blood loss, requirement for blood transfusion, and the risk of reoperation for bleeding, and although no study has yet looked directly at vein graft patency with tranexamic acid, no randomized studies have raised concerns over its safety.
doi:10.1016/j.icvts.2004.04.006
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References
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Abstract
1. Introduction