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CARDIOVASCULAR ANESTHESIA

Is Perioperative Plasma Aprotinin Concentration More Predictable and Constant After a Weight-Related Dose Regimen?

David Royston, FRCA^*, Rebecca Cardigan, PhD, Cornelia Gippner-Steppert, PhD, and Marianne Jochum, PhD

*Department of Anaesthesia, Harefield Hospital, Harefield, Middlesex, United Kingdom; Department of Haematology, University College London Medical School, London, England, United Kingdom; and Division of Clinical Biochemistry in the Department of Surgery, Klinikum Innenstadt der LM-Universität München, Munich, Germany

Address correspondence and reprint requests to Dr. Dave Royston, Department of Anaesthesia, Harefield Hospital, Harefield, Middlesex, UB9 6JH, UK. Address e-mail to Dave{at}tharg.demon.co.uk

To determine whether a weight-related dose had advantages over a fixed, large-dose regimen, we measured plasma concentrations of aprotinin by using an enzyme-linked immunosorbent assay method at set time points in 30 patients having heart surgery with cardiopulmonary bypass. A weight-related dose comprising a preincision bolus injection of 40,000 kallikrein-inhibiting units (KIU)/kg (5.6 mg/kg) with the same amount given in the oxygenator prime was compared with a large-dose regimen of 2 x 10⁶ KIU (280 mg) preincision bolus and addition to prime, together with an infusion of 500,000 KIU/h (70 mg/h). Peak plasma concentration in the Weight-Related group was less variable than with the fixed-dose regimen. Forty percent of patients allocated to the fixed-dose regimen had an aprotinin concentration of more than 400 KIU/mL, compared with none in the Weight-Related group; this suggests a relative overdosing in the early surgical period in the Fixed-Dose group. There was great individual variability between patients in the time-concentration curves for aprotinin, with no difference between the two regimens. The weight-related dose regimen benefited by not requiring an intraoperative infusion while achieving the same plasma concentrations of aprotinin.

Implications: Peak plasma concentrations of aprotinin were less variable with a weight-related dose schedule. This has implications for safety with regard to control of anticoagulation and cost in patients with small body mass. Plasma concentrations varied greatly with time between patients. This observation has implications for determining an optimal dose on the basis of aprotinin’s currently known mechanisms of action.

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