Different dose regimes and administration methods of tranexamic acid in cardiac surgery: a meta-analysis of randomized trials

Abstract

Background The efficacy of tranexamic acid (TXA) to reduce perioperative blood loss and allogeneic blood transfusion in cardiac surgeries has been proved in previous studies, but its adverse effects especially seizure has always been a problem of concern. This meta-analysis aims to provide information on the optimal dosage and delivery method which is effective with the least adverse outcomes. Methods We searched Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE for all relevant articles published before 2018/12/31. Inclusion criteria were adult patients undergoing elective heart surgeries, and only randomized control trials comparing TXA with placebo were considered. Two authors independently assessed trial quality and extracted relevant data. Results We included 49 studies with 10,591 patients into analysis. TXA significantly reduced transfusion rate (RR 0.71, 95% CI 0.65 to 0.78, P<0.00001). The overall transfusion rate was 35%(1573/4477) for patients using TXA and 49%(2190/4408) for patients in the control group. Peri-operative blood loss (MD − 246.98 ml, 95% CI − 287.89 to − 206.06 ml, P<0.00001) and re-operation rate (RR 0.62, 95% CI 0.49 to 0.79, P<0.0001) were also reduced significantly. TXA usage did not increase risk of mortality, myocardial infarction, stroke, pulmonary embolism and renal dysfunction, but was associated with a significantly increase in seizure attack (RR 3.21, 95% CI 1.04 to 9.90, P = 0.04).The overall rate of seizure attack was 0.62%(21/3378) for patients using TXA and 0.15%(5/3406) for patients in the control group. In subgroup analysis, TXA was effective for both on-pump and off-pump surgeries. Topical application didn’t reduce the need for transfusion requirement, while intravenous delivery no matter as bolus injection alone or bolus plus continuous infusion were effective. Intravenous high-dose TXA didn’t further decrease transfusion rate compared with low-dose regimen, and increased the risk of seizure by 4.83 times. No patients in the low-dose group had seizure attack. Conclusions TXA was effective in reducing transfusion requirement in all kinds of cardiac surgeries. Low-dose intravenous infusion was the most preferable delivery method which was as effective as high-dose regimen in reducing transfusion rate without increasing the risk of seizure. Electronic supplementary material The online version of this article (10.1186/s12871-019-0772-0) contains supplementary material, which is available to authorized users.

Managing the coagulopathy associated with cardiopulmonary bypass

“…Tranexamic acid inhibits plasminogen conversion to plasmin, and a recent meta‐analysis confirmed that it reduces transfusion (relative risk [RR] 0.71, 95% confidence interval [CI] 0.65 to 0.78, P < .01), perioperative blood loss (mean difference −247 ml, 95% CI −288 to −207, P < .01), and re‐operation (RR 0.62, 95% CI 0.49 to 0.79, P < .01), without increasing the risk of mortality, major end organ complications, or thrombotic events 63,64 . In this meta‐analysis, there was a small increase in the risk of seizures (0.62% compared to 0.15% in patients not receiving tranexamic acid), 63 which may be modified by the degree of underlying renal dysfunction and resultant plasma concentrations 64 . In the 12 737‐patient CRASH‐3 trial, rates of seizure were similar between placebo and control groups (RR 1.09 [0.90‐1.33]), while the tranexamic acid group had lower mortality, reinforcing the safety of tranexamic acid in critically ill patients 65 .…”

“…62 tality, major end organ complications, or thrombotic events. 63,64 In this meta-analysis, there was a small increase in the risk of seizures (0.62% compared to 0.15% in patients not receiving tranexamic acid), 63 which may be modified by the degree of underlying renal dysfunction and resultant plasma concentrations. 64 In the 12 737-patient CRASH-3 trial, rates of seizure were similar between placebo and control groups (RR 1.09 [0.90-1.33]), while the tranexamic acid group had lower mortality, reinforcing the safety of tranexamic acid in critically ill patients.…”

Effects of tranexamic acid on the activity of glutamate transporter EAAT3

“…*P < 0.05 compared with control group (tranexamic acid concentration 0 µM). www.anesth-pain-med.org diac surgeries when a high TXA dose was used [10]. TXA-induced seizures occur within several hours of transferring the patient from the operating room to an intensive care unit, a period characterized by a rapid decline of anesthetics with an anticonvulsant effect and high TXA concentration [11].…”

Tranexamic Acid Is Beneficial to Patients Undergoing Open-Wedge High Tibial Osteotomy

“…TXA is a synthetic antifibrinolytic drug that inhibits the activation of plasminogen [ 20 , 21 ]. Relevant studies have confirmed that TXA is effective in reducing perioperative blood loss and transfusion requirements in cardiac, obstetric, and urologic surgery [ 22 – 25 ]. In orthopaedic surgery, a large retrospective cohort study involving over 800000 patients undergoing total hip or knee arthroplasty revealed that the demand for allogeneic or autologous blood transfusions was decreased by up to 69% in the tranexamic acid group [ 26 ].…”