This explains the difference between our group TA 10 and the one-time group of Horrow et al. Note that the loading dose in all three groups was given over 15 rather than 30 min. ( B ) The three dosing schemes used in the present study are shown. All others are exact multiples or fractions of that dose. The one-time dose was described previously.
( A ) Five dosing schemes described by Horrow et al.
hr −1(beginning at the end of the loading dose, and continuing for 12 h), the dose identified by Horrow et al. On each plot we provide a simulation (gray line) for 10 mg/kg given over 30 min with a maintenance infusion of 1 mg (See Methods for details of simulations). The beginning and end of CPB are indicated by vertical dotted lines. We assumed that 45 min of surgery would take place before and after CPB. We assumed a patient weight of 80 kg and a 120 min duration of CPB. Tranexamic acid (TA) concentration versus time plots simulated using our best CPB-adjusted pharmacokinetic model and dosing schemes. Nevertheless, the CPB-corrected model provided the best fit to the data, whether for all three groups or when the data from group TA 10 were excluded, as judged by both Schwarz-Bayesian Criterion and visual inspection of plots.įig. Note that inclusion of group TA 10 dramatically increases the variability. ( D ) Data from all three groups were fit to a CPB-corrected model. Note that this resulted in some modest improvement in the fits, particularly at times earlier than 240 min. ( C ) Data from groups TA 50 and 100 were fit to a 2-compartmental model with CPB corrections as described in the text. The model performs reasonably well, and later time points are distributed both above and below the line of identity, indicating a minimal bias. ( B ) Data from groups TA 50 and TA 100 are fit to a simple 2-compartment model without adjustments for CPB. Note that the model performs poorly at later times. ( A ) Data from groups TA 50 and TA 100 are fit to a 1-compartment elimination model. The observed and predicted concentration of tranexamic acid (TA) in blood using different compartmental elimination models is shown. Protamine sulfate 50–100 mg was administered after admission to the ICU if the ACT exceeded 110% of its baseline value.įig. After CPB, protamine sulfate 1 mg/100 U of heparin administered was given to restore the ACT to within 10% of its baseline value. An activated clotting time (ACT) of greater than 400 s was achieved before CPB, and maintained with additional heparin as indicated by the ACT during CPB. Anticoagulation for CPB was provided by heparin 300 U/kg. It was continued for 3 h in ICU at 0.5–3 mg hr −1before transportation to the intensive care unit (ICU). The propofol infusion was continued during CPB at 2–6 mg hr −1, and in some cases, 0.5–2% inhaled isoflurane. Anesthesia was maintained before cardiopulmonary bypass (CPB) with midazolam 0.05–0.1 mg/kg, a propofol infusion at 2–6 mg Tracheal intubation was facilitated by intravenous pancuronium 0.15 mg/kg. 
General anesthesia was induced with 10–15 μg/kg fentanyl, and in some cases, 50–75 mg thiopental intravenously. Peripheral and radial artery cannulae were placed after local anesthesia. Preoperative sedation consisted of lorazepam 1 to 2 mg sublingually approximately 1.5 h before surgery. 9It is likely that CPB will interfere with the elimination kinetics and blood concentration of TA, since such CPB-related effects have been found with ϵ-aminocaproic acid, a closely related compound. All previous studies of the pharmacokinetics of intravenous TA have concentrated on healthy volunteers, 6,7patients with chronic renal disease, 8or older patients undergoing total hip arthroplasties. However, all dosing schedules were chosen without knowledge of TA elimination kinetics in surgical patients undergoing CPB. Some dosing schedules were based on doses previously determined to inhibit plasma fibrinolytic activity 5in settings outside cardiac surgery others were developed empirically. 4The optimum dose of TA for this purpose is debated in the literature, and the doses of TA used in reported studies vary over a 10-fold range. 1–3TA inhibits fibrinolysis, a putative mechanism of bleeding after CPB, by forming a reversible complex with plasminogen. TRANEXAMIC acid (TA) has been shown to significantly reduce blood loss and red blood cell transfusion rates in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).
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