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CARDIOVASCULAR ANESTHESIA

Gender Does Not Influence Epsilon-Aminocaproic Acid Concentrations in Adults Undergoing Cardiopulmonary Bypass

Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Address correspondence and reprint requests to Dr. Butterworth, Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1009. Address e-mail to jbutter{at}wfubmc.edu

Epsilon-aminocaproic acid (-ACA) is administered to cardiac surgery patients to reduce blood transfusions. Highly water-soluble drugs, such as -ACA, often have larger distribution volumes in males than in females. We hypothesized that -ACA concentrations using this dosing scheme would differ by gender because of differences in body composition and weight-adjusted volumes of distribution. Ten men and 10 women undergoing elective coronary artery surgery with cardiopulmonary bypass (CPB) received a 50 mg/kg -ACA initial dose over 20 min and a 25 mg · kg^-1 · h^-1 -ACA maintenance infusion for 4 h. The area under the -ACA arterial concentration versus time curves was compared by using analysis of variance. Measured -ACA concentrations were smaller than predicted by the published model, but the area under the concentration versus time curves was not significantly different between men and women. Combining the present concentration data with that previously published, our updated two-compartment model included the following estimated population pharmacokinetic values: V₁ (11.8 L pre-CPB, 14.9 L during and after CPB), V₂ (12.0 L pre-CPB, 15.0 L during and after CPB), Cl₁ (0.125 L/min pre-CPB, 0.037 L/min during CPB, 0.156 L/min after CPB), Cl₂ (0.155 L/min pre-CPB, 0.013 L/min during CPB, 0.193 L/min after CPB).

Implications: The pharmacokinetics of -aminocaproic acid do not differ significantly between males and females; therefore (after correction for weight), a gender-specific dosing scheme is unnecessary. A 70 mg/kg initial dose (given over 20 min) and a maintenance infusion of 30 mg·kg^-1·h^-1should ensure that fewer than 5% of patients will have -aminocaproic acid concentrations <130 mg/L during infusion.

This article has been cited by other articles:

				J. Butterworth, Y. A. Lin, R. C. Prielipp, J. Bennett, J. W. Hammon, and R. L. James Rapid disappearance of protamine in adults undergoing cardiac operation with cardiopulmonary bypass Ann. Thorac. Surg., November 1, 2002; 74(5): 1589 - 1595. [Abstract] [Full Text] [PDF]

				J. C. Lundell, J. Butterworth, and R. James Evidence-Based EACA Dosing? * Response Anesth. Analg., June 1, 2002; 94(6): 1673 - 1673. [Full Text] [PDF]