This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Royston, D. Articles by Nadel, A. Search for Related Content PubMed PubMed Citation Articles by Royston, D. Articles by Nadel, A. Related Collections Cardiovascular Complications Pharmacology

---

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.

This article has been cited by other articles:

				X. Wang, Z. Zheng, H. Ao, S. Zhang, Y. Wang, H. Zhang, L. Li, and S. Hu A comparison before and after aprotinin was suspended in cardiac surgery: Different results in the real world from a single cardiac center in China J. Thorac. Cardiovasc. Surg., October 1, 2009; 138(4): 897 - 903. [Abstract] [Full Text] [PDF]

				J. M. Murkin Lessons Learned in Antifibrinolytic Therapy: The BART Trial Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2009; 13(2): 127 - 131. [Abstract] [PDF]

				M. Siepe, U. Goebel, A. Mecklenburg, T. Doenst, C. Benk, P. Stein, F. Beyersdorf, T. Loop, and C. Schlensak Pulsatile Pulmonary Perfusion During Cardiopulmonary Bypass Reduces the Pulmonary Inflammatory Response Ann. Thorac. Surg., July 1, 2008; 86(1): 115 - 122. [Abstract] [Full Text] [PDF]

				M. P. Eaton Antifibrinolytic Therapy in Surgery for Congenital Heart Disease Anesth. Analg., April 1, 2008; 106(4): 1087 - 1100. [Abstract] [Full Text] [PDF]

				P. J. Van der Linden, J.-F. Hardy, A. Daper, A. Trenchant, and S. G. De Hert Cardiac surgery with cardiopulmonary bypass: does aprotinin affect outcome? Br. J. Anaesth., November 1, 2007; 99(5): 646 - 652. [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]

				M. Buerke, D. Pruefer, D. Sankat, J. M. Carter, U. Buerke, M. Russ, A. Schlitt, I. Friedrich, J. Borgermann, C. F. Vahl, et al. Effects of Aprotinin on Gene Expression and Protein Synthesis After Ischemia and Reperfusion in Rats Circulation, September 11, 2007; 116(11_suppl): I-121 - I-126. [Abstract] [Full Text] [PDF]

				G. M. Howard-Alpe, J. de Bono, L. Hudsmith, W. P. Orr, P. Foex, and J. W. Sear Coronary artery stents and non-cardiac surgery Br. J. Anaesth., May 1, 2007; 98(5): 560 - 574. [Abstract] [Full Text] [PDF]

				C. W. Hogue and M. J. London Aprotinin Use During Cardiac Surgery: A New or Continuing Controversy? Anesth. Analg., November 1, 2006; 103(5): 1067 - 1070. [Full Text] [PDF]