Fig. 3. Tranexamic acid (TA) concentration versus  time plots simulated using our best CPB-adjusted pharmacokinetic model and dosing schemes. We assumed a patient weight of 80 kg and a 120 min duration of CPB. We assumed that 45 min of surgery would take place before and after CPB. The beginning and end of CPB are indicated by vertical dotted lines. (See Methods for details of simulations). On each plot we provide a simulation (gray line) for 10 mg/kg given over 30 min with a maintenance infusion of 1 mg · kg⁻¹· hr⁻¹(beginning at the end of the loading dose, and continuing for 12 h), the dose identified by Horrow et al.  12as the minimum yielding efficacy. (A ) Five dosing schemes described by Horrow et al.  are shown. The one-time dose was described previously. All others are exact multiples or fractions of that dose. (B ) The three dosing schemes used in the present study are shown. Note that the loading dose in all three groups was given over 15 rather than 30 min. This explains the difference between our group TA 10 and the one-time group of Horrow et al.  12. (C ) Risch et al.  27infused 2 g/h for 10 h starting at the beginning of surgery. (D ) Okuyama et al.  28gave a single 160 mg/kg bolus (which we assumed would take 1 min to administer). (E ) Rousou et al.  29administered a 2 g bolus 1 min before CPB, with an 8 g bolus given by “slow infusion” during CPB. We have modeled the slow infusion as starting and ending with CPB. (F ) Dryden et al.  30gave a 10 g loading dose over 30 min concluding at the time of skin incision (our time 0). (G ) Karski et al.  31gave three loading doses (50, 100, and 150 mg/kg, as shown on the plot) over 20 min after induction of anesthesia. (H ) Lambert et al . 32gave three loading doses (20, 50, and 100 mg/kg, as shown on the plot) over 30 min starting after induction of anesthesia. (I ) Shore-Lesserson et al . 33administered a bolus of 20 mg/kg (we assumed that it was given over 1 min) at the start of surgery. A maintenance infusion of 1 mg/kg was given during surgery. (J ) Pinosky et al.  34administered a 15 mg/kg loading dose (we assumed that this took 20 min) at the start of surgery with a 1 mg · kg⁻¹· hr⁻¹maintenance infusion for 6 h. (K ) Pugh et al . 35gave a 2.5 g bolus (we assumed that it took 1 min) at the time of skin incision and added a 2.5 g dose to the CPB priming solution (we assumed mixing would take 2 min after initiation of CPB). (L ) Casati et al.  26gave all patients a 1 g bolus dose 20 min before sternotomy (we assumed that it took 1 min and began at time 0). All patients received a maintenance infusion of 400 mg/h throughout the operation. At the end of surgery, one group received 2 mg · kg⁻¹· hr⁻¹for 12 h, one group received 1 mg · kg⁻¹· hr⁻¹for 12 h, and one group received no additional TA after surgery. There is only limited agreement among investigators as to the amount and infusion rate of TA that is necessary to reduce bleeding during cardiac surgery.