Letters to the Editor: Letters & Announcements
To the Editor
Murkin et al.1 describes seizures in cardiac surgery patients after high-dose tranexamic acid (100 mg/kg total, or loading doses of 25 to 50 mg/kg followed by infusions of 10 to 25 mg · kg−1 · h−1). Tranexamic acid is used during cardiac surgery primarily to prevent fibrinolysis. The plasma concentration required to suppress fibrinolysis, in vitro, is 10 μg/mL2 and to suppress plasmin-induced platelet activation is 16 μg/mL.3 Fiechtner4 has combined her own studies with others to generate a dosing regime designed to maintain plasma concentrations of >20 μg/mL throughout cardiac surgery (5.4 mg/kg loading dose followed by 5 mg · kg−1 · h−1 with an additional 20 mg/L bypass pump prime).
Once recognized, Murkin describes a change in practice with a reduced dosing regime of 30 mg/kg load followed by an infusion of 15 mg · kg−1 · h−1 and 2 mg/kg in the cardiopulmonary bypass priming solution. This has been associated with a reduction, but not an elimination, of postoperative seizures. Although reduced, this dosing is still 3-fold greater than that required to inhibit fibrinolysis in vitro.
My institution, a specialist adult cardiothoracic hospital performing 1700 to 2000 cardiac cases per year, has used Fiechtner's regime for the last 3 years. We have seen no seizures in the absence of new cerebral ischemic events, nor any fibrinolytic activity as assessed using postoperative thromboelastography.
Mark A. Fox, FRCA
Department of Anaesthesia
The Liverpool Heart and Chest Hospital
Liverpool, United Kingdom
1. Murkin JM, Falter F, Granton J, Young B, Burt C, Chu M. High-dose tranexamic acid is associated with nonischemic clinical seizures in cardiac surgical patients. Anesth Analg 2010; 110:350–3
2. Andersson L, Nilsoon IM, Collen S, Grandstrand B, Melander B. Role of urokinase and tissue activator in sustaining bleeding and the management therof with EACA and AMCA. Ann N Y Acad Sci 1968;146:642–58
3. Soslau G, Horrow J, Brodsky I. Effect of tranexamic acid on platelet ADP during extracorporeal circulation. Am J Hematol 1991;38:113–9
4. Fiechtner BK, Nuttall GA, Johnson ME, Dong Y, Sujirattanawimol N, Oliver WC, Sarpal RS, Oyen LJ, Ereth MH. Plasma tranexamic acid concentrations during cardiopulmonary bypass. Anesth Analg 2001;92:1131–6