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CARDIOVASCULAR ANESTHESIA

Full-Dose Aprotinin Use in Coronary Artery Bypass Graft Surgery: An Analysis of Perioperative Pharmacotherapy and Patient Outcomes

David Royston, FRCA^*, Jerrold H. Levy, MD, Jane Fitch, MD, Wulf Dietrich, MD, Simon C. Body, MBChB, MPH^||, John M. Murkin, MD^¶, Bruce D. Spiess, MD^#, and Andrea Nadel, PhD^**

From the *Department of Anesthesia, Harefield Hospital, London, UK; Department of Anesthesiology, Emory University, Atlanta, Goergia; Department of Anesthesiology, University of Oklahoma, Oklahoma City, Oklahoma; Department of Anesthesiology, German Heart Center Munich, Munich, Germany; ||Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; ¶Department of Anesthesia, University of Western Ontario, London, Ontario, Canada; #Department of Anesthesiology, VCURES Shock Center, Virginia Commonwealth University/Medical College of Virginia Campus, Richmond, Virginia; and **Global Statistics, Bayer Pharmaceuticals Corporation, West Haven, Connecticut.

Address correspondence and reprint requests to David Royston, FRCA, Department of Anaesthesia and Critical Care, Royal Brompton and Harefield NHS Trust, Harefield Hospital, Hill End Road, Harefield, Middlesex, UB9 6JH, UK. Address e-mail to dave{at}tharg.demon.co.uk.

BACKGROUND: Inappropriate activation of hemostasis and inflammation may contribute to postoperative morbidity and mortality. The serine protease inhibitor, aprotinin, has been shown to prevent tissue and organ injury in laboratory and animal studies. In this retrospective analysis, we evaluated the relationship of aprotinin therapy with organ dysfunction in humans undergoing coronary artery bypass graft surgery (CABG).

METHODS: Data from prospective randomized, double-blind, placebo-controlled studies evaluating the safety and efficacy of full-dose aprotinin (2 million KIU load, 2 million KIU pump prime, and 0.5 million KIU/h continuous infusion) to reduce blood loss and transfusion requirements in patients undergoing CABG (placebo, n = 861; aprotinin, n = 862) were examined retrospectively. Primary end-points were death, adverse cerebrovascular outcome, myocardial infarction (MI), and pharmacological interventions (inotropic drugs, vasopressors, and antiarrhythmics).

RESULTS: Univariate analysis showed that relative to placebo, full-dose aprotinin therapy was associated with significant effects on the incidence of adverse cerebrovascular outcome (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.19–0.93; P = 0.03) and use of inotropic drugs (OR 0.79, 95% CI 0.65–0.97; P = 0.02), vasopressors (OR 0.74, 95% CI 0.61–0.90; P < 0.01), and antiarrhythmics (OR 0.79, 95% CI 0.65–0.96; P = 0.02), but not death (OR = 1.00, 95% CI 0.54–1.85; P = 1.0) or MI (OR 0.92, 95% CI 0.64–1.31; P = 0.6). Multivariate analysis confirmed results of univariate analysis.

CONCLUSIONS: This retrospective analysis of data collected from prospective, randomized, placebo-controlled studies in CABG shows that full-dose aprotinin use was associated with a lower risk of adverse cerebrovascular outcomes and a reduced need for use of vasoactive drugs; the risk of death and perioperative MI was not affected by aprotinin therapy.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999