| ||||||||||||||
|
|
|||||||||||||



*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 aprotinins currently known mechanisms of action.
This article has been cited by other articles:
![]() |
M. D. McEvoy, M. J. Sabbagh, A. G. Taylor, J. A. Zavadzkas, C. N. Koval, R. E. Stroud, R. L. Ford, J. E. McLean, S. T. Reeves, R. Mukherjee, et al. Aprotinin Modifies Left Ventricular Contractility and Cytokine Release After Ischemia-Reperfusion in a Dose-Dependent Manner in a Murine Model Anesth. Analg., February 1, 2009; 108(2): 399 - 406. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. A. Olenchock Jr, P. H.U. Lee, T. Yehoshua, S. A. Murphy, J. Symes, and G. Tolis Jr Impact of Aprotinin on Adverse Clinical Outcomes and Mortality up to 12 Years in a Registry of 3,337 Patients Ann. Thorac. Surg., August 1, 2008; 86(2): 560 - 567. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. D. McEvoy, A.-G. Taylor, J. A. Zavadzkas, I. M. Mains, R. L. Ford, R. E. Stroud, L. B. Jeffords, C. U. Beck, S. T. Reeves, and F. G. Spinale Aprotinin Exerts Differential and Dose-Dependent Effects on Myocardial Contractility, Oxidative Stress, and Cytokine Release After Ischemia-Reperfusion Ann. Thorac. Surg., August 1, 2008; 86(2): 568 - 575. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. D. McEvoy, S. T. Reeves, J. G. Reves, and F. G. Spinale Aprotinin in Cardiac Surgery: A Review of Conventional and Novel Mechanisms of Action Anesth. Analg., October 1, 2007; 105(4): 949 - 962. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Dietrich, R. Busley, and M. Kriner High-Dose Aprotinin in Cardiac Surgery: Is High-Dose High Enough?: An Analysis of 8281 Cardiac Surgical Patients Treated with Aprotinin Anesth. Analg., November 1, 2006; 103(5): 1074 - 1081. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Kokoszka, P. Kuflik, F. Bitan, A. Casden, and M. Neuwirth Evidence-Based Review of the Role of Aprotinin in Blood Conservation During Orthopaedic Surgery J. Bone Joint Surg. Am., May 1, 2005; 87(5): 1129 - 1136. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Koster, S. Huebler, F. Merkle, T. Hentschel, M. Grundel, T. Krabatsch, L. Tambeur, M. Praus, H. Habazettl, W. M. Kuebler, et al. Heparin-Level-Based Anticoagulation Management During Cardiopulmonary Bypass: A Pilot Investigation on the Effects of a Half-Dose Aprotinin Protocol on Postoperative Blood Loss and Hemostatic Activation and Inflammatory Response Anesth. Analg., February 1, 2004; 98(2): 285 - 290. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Mossinger, W. Dietrich, S. L. Braun, M. Jochum, H. Meisner, and J. A. Richter High-dose aprotinin reduces activation of hemostasis, allogeneic blood requirement, and duration of postoperative ventilation in pediatric cardiac surgery Ann. Thorac. Surg., February 1, 2003; 75(2): 430 - 437. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. A. Nuttall, D. N. Fass, L. J. Oyen, W. C. Oliver Jr., and M. H. Ereth A Study of a Weight-Adjusted Aprotinin Dosing Schedule During Cardiac Surgery Anesth. Analg., February 1, 2002; 94(2): 283 - 289. [Abstract] [Full Text] [PDF] |
||||
|