Plasma tranexamic acid concentrations during cardiopulmonary bypass.

UNLABELLED: Although tranexamic acid is used to reduce bleeding after cardiac surgery, there is large variation in the recommended dose, and few studies of plasma concentrations of the drug during cardiopulmonary bypass (CPB) have been performed. The plasma tranexamic acid concentration reported to inhibit fibrinolysis in vitro is 10 microg/mL. Twenty-one patients received an initial dose of 10 mg/kg given over 20 min followed by an infusion of 1 mg. kg(-1). h(-1) via a central venous catheter. Two patients were removed from the study secondary to protocol violation. Perioperative plasma tranexamic acid concentrations were measured with high-performance liquid chromatography. Plasma tranexamic acid concentrations (microg/mL; mean +/- SD [95% confidence interval]) were 37.4 +/- 16.9 (45.5, 29.3) after bolus, 27.6 +/- 7.9 (31.4, 23.8) after 5 min on CPB, 31.4 +/- 12.1 (37.2, 25.6) after 30 min on CPB, 29.2 +/- 9.0 (34.6, 23.8) after 60 min on CPB, 25.6 +/- 18.6 (35.1, 16.1) at discontinuation of tranexamic acid infusion, and 17.7 +/- 13.1 (24.1, 11.1) 1 h after discontinuation of tranexamic acid infusion. Four patients with renal insufficiency had increased concentrations of tranexamic acid at discontinuation of the drug. Repeated-measures analysis revealed a significant main effect of abnormal creatinine concentration (P = 0.02) and time (P < 0.001) on plasma tranexamic acid concentration and a significant time x creatinine concentration interaction (P < 0.001). IMPLICATIONS: A 10 mg/kg initial dose of tranexamic acid followed by an infusion of 1 mg.kg(-1).h(-1)produced plasma concentrations throughout the cardiopulmonary bypass period sufficient to inhibit fibrinolysis in vitro. The dosing of tranexamic acid may require adjustment for renal insufficiency.

Support of mean arterial pressure during tepid cardiopulmonary bypass: effects of phenylephrine and pump flow on systemic oxygen supply and demand.

OBJECTIVE: To examine the effects of phenylephrine infusion and increases in pump flow on systemic oxygen supply and demand when they are used to support mean arterial pressure (MAP) during cardiopulmonary bypass (CPB). DESIGN: Prospective, unblinded study. SETTING: The animal cardiopulmonary laboratory at the Mayo Foundation (Rochester, MN). PARTICIPANTS: Twelve pigs. INTERVENTIONS: Twelve pigs had systemic oxygen delivery (DO2) and consumption (VO2) measured before CPB and then underwent CPB at 35 degrees C. During CPB, measurements of DO2 and VO2 were obtained at an MAP of approximately 50 mmHg and a pump flow of 2.2 L/min/m2. Thereafter, MAP was elevated to 70 mmHg either by increases in pump flow or by a phenylephrine infusion, and the balance between systemic oxygen supply and demand was reassessed. MEASUREMENTS AND MAIN RESULTS: Before CPB, DO2 was 375 +/- 83 mL/min/m2 and decreased with the onset of CPB mainly because of the effects of hemodilution. During CPB, with a pump flow of 2.2 L/min/m2 and an MAP of 53 mmHg, DO2 was 218 +/- 40 mL/min/m2. Increasing perfusion pressure to an MAP of 72 mmHg with phenylephrine and maintaining pump flow constant (2.2 L/min/m2) did not change DO2 (222 +/- 37 mL/min/m2), and the oxygen extraction ratio (OER) was increased relative to pre-CPB levels. In contrast, increasing MAP to 71 mmHg by increasing pump flow to 3.2 L/min/m2 resulted in a significantly greater DO2, and the OER normalized to the pre-CPB value. CONCLUSIONS: During CPB with conventional flow rates, DO2 is decreased. Supporting MAP with increases in pump flow better maintains DO2 than the administration of an alpha-agonist.