Pharmacokinetics of tranexamic acid in patients undergoing cardiac surgery with use of cardiopulmonary bypass*

Abstract

SummaryWe conducted a study to assess pharmacokinetics of high-dose tranexamic acid for 24 h after administration of the drug in patients undergoing cardiac surgery with cardiopulmonary bypass. High-dose tranexamic acid involved a bolus of 30 mg.kg )1 infused over 15 min followed by a 16 mg.kg.h )1 infusion until chest closure with a 2 mg.kg )1 load within the pump prime. Tranexamic acid followed first-order kinetics best described using a two-compartment model, with a total body clearance that approximated the glomerular filtration rate. Mean plasma tranexamic acid concentrations during the intra-operative period and in the first 6 postoperative hours were consistently higher than the suggested threshold to achieve 100% inhibition and 80% inhibition of tissue plasminogen activator. With recent studies implicating high-dose tranexamic acid as a possible aetiology of postoperative seizures following cardiac surgery, the minimum effective yet safe dose of tranexamic acid in high-risk cardiac surgery needs to be refined. Tranexamic acid, a synthetic antifibrinolytic, is a lysine derivative that competitively inhibits the activation of plasminogen, thereby reducing the conversion of plasminogen to plasmin, an enzyme that degrades fibrin clots, fibrinogen, and other plasma proteins, including the procoagulant factors V and VIII [1]. At higher doses, tranexamic acid directly inhibits plasmin activity [2][3][4][5]. Tranexamic acid thus inhibits fibrinolysis, a putative mechanism of bleeding after cardiopulmonary bypass (CPB) [6]. Hence, this compound is routinely used during cardiac surgery procedures involving CPB, to reduce blood loss [1][2][3][4][5]. Tranexamic acid is considered to have a good safety profile. However, this has been challenged recently as several studies have found an association between high-dose tranexamic acid administration and an increased incidence in postoperative

Tranexamic acid–associated seizures: Causes and treatment

“…Case reports indicate that patients treated with TXA while undergoing dialysis experience generalized seizures and myoclonic movements 10, 70. Interestingly, TXA administered to cardiac surgery patients at doses recommended in the BART Trial resulted in higher than expected plasma concentrations, which exceeded the recommended therapeutic levels 71, 72. Consistent with these findings, lowering TXA doses reduced the frequency of postoperative seizures 20.…”

Major liver resection, systemic fibrinolytic activity, and the impact of tranexamic acid

“…TXA concentration was measured using solid phase microextraction techniques and Tandem liquid chromatography-mass spectrometry as previously described. 39,40 Statistical analysis Descriptive statistics were used to summarize patient demographics and clinical outcomes. Categorical variables were reported as absolute values (N) and frequencies (%) and compared between groups using Fisher's exact test (F-E).…”

Effect of two doses of tranexamic acid on fibrinolysis evaluated by thromboelastography during cardiac surgery

“…Although three previous studies have investigated tranexamic acid pharmacokinetics, little information is available comparing pharmacokinetic data with clinical outcomes, and the optimal dosing regimen is still not known despite widespread clinical use. [3][4][5] We therefore performed a prospective, double-blinded, randomised, controlled pilot study to assess the effect of two tranexamic acid dosing regimens compared with placebo on fibrinolysis and clinical outcomes including bleeding and need for allogeneic transfusions.…”