Aprotinin in cardiac surgery

Expert Review of Cardiovascular Therapy

Volumn 4, Issue 2, 2006, Pages 151-160

  Sodha, Neel R ^a   Boodhwani, Munir ^a   Bianchi, Cesario ^a   Ramlawi, Basel ^a   Sellke, Frank W ^a  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

Aprotinin; Blood conservation; Blood transfusion; Cardiac surgery; Cardiopulmonary bypass; Coronary artery bypass grafting; Hemostasis; Protease activated receptor; Protease inhibitors

Indexed keywords

ACETYLSALICYLIC ACID; APROTININ; CLOPIDOGREL; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; HISTAMINE H1 RECEPTOR ANTAGONIST; HISTAMINE H2 RECEPTOR ANTAGONIST; PLACEBO; PLASMIN; SERINE PROTEINASE; SERINE PROTEINASE INHIBITOR; STREPTOKINASE; TISSUE PLASMINOGEN ACTIVATOR; UROKINASE; VASOPRESSIN; HEMOSTATIC AGENT;

ANAPHYLACTIC SHOCK; ANTIINFLAMMATORY ACTIVITY; BLEEDING; BLOOD CLOTTING; BLOOD TRANSFUSION; CARDIOPULMONARY BYPASS; CLINICAL TRIAL; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG COST; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG MEGADOSE; ENZYME INHIBITION; FIBRINOLYSIS; FLUSHING; HEART SURGERY; HEMOSTASIS; HUMAN; KIDNEY DYSFUNCTION; LOW DRUG DOSE; NONHUMAN; PERIOPERATIVE PERIOD; REVIEW; SKIN MANIFESTATION; SURGICAL TECHNIQUE; THROMBOSIS; ANIMAL; DRUG MONITORING; ISOLATION AND PURIFICATION;

ANIMALS; APROTININ; BLOOD LOSS, SURGICAL; CARDIAC SURGICAL PROCEDURES; CLINICAL TRIALS; DRUG COSTS; DRUG MONITORING; HEMOSTATICS; HUMANS; SERINE PROTEINASE INHIBITORS;

EID: 33646195467     PISSN: 14779072     EISSN: 17448344     Source Type: Journal    
DOI: 10.1586/14779072.4.2.151     Document Type: Review

References (71)

1. Kraut H, Frey EK, Werie E. Regarding the inactivation of the kallikreins. Hoppe-Seyler's Z. Physiol. Chem. 192, 1-21 (1930).
2. Kunitz M Northrup JH. Isolation from beef pancreas of crystalline trypsinogen, trypsin, a trypsin inhibitor, and an inhibitor trypsin compound. J. Gen. Phys. 19, 991-1007 (1938).
3. Grozinger KH. Pancreatitis: progress in management. Surgery 59, 319-324 (1966).
4. Royston D, Bidstrup BR Taylor KM, Sapsford RN. Effect of aprotinin on need for blood transfusion after repeat open-heart surgery. Lancet 2, 1289-1291 (1987).
5. Cina CS, Clase CM. Coagulation disorders and blood product use in patients undergoing thoracoabdominal aortic aneurysm repair. Transfus. Med. Rev. 19, 143-154 (2005).
6. Vanek T, Jarez M, Fajt T et al. Fibrinolytic inhibitors in off-pump coronary surgery: a prospective, randomized, double-blind TAP study (tranexamic acid, aprotinin, placebo). Eur. J. Cardiothorac. Surg, 28, 563-568 (2005).
7. Bedirhan MA, Turna A, Yagan N, Tasci O. Aprotinin reduces postoperative bleeding and the need for blood products in thoracic surgery: results of a randomized double-blind study. Eur. J. Cardiothorac. Surg. 20, 1122-1127 (2001).
8. Kokoszka A, Kuflik P, Bitan F. Casden A, Neuwirth M. Evidence-based review of the role of aprotinin in blood conservation during orthopaedic surgery. J. Bone Joint Surg. Am. 87, 1129-1136 (2005).
9. Schisano G, Nina P. Aprotinin and hemostasis. J. Neurosurg. 102, 757-758; author reply, 758 (2005).
10. Lentschener C, Roche K, Ozier Y. A review of aprotinin in orthotopic liver transplantation: can its harmful effects offset its beneficial effects? Anesth. Analg. 100, 1248-1255 (2005).
11. Mahdy AM, Webster NR. Perioperative systemic haemostatic agents. Br. J. Anaesth. 93, 842-858 (2004).
12. Sagripanti A, Sarteschi LM, Camici M, Puccetti S, Capri A. Non-transfusional hemostatic agents in the management of bleeding disorders. Int. Med. 9, 10-18 (2001).
13. Levy JH, Bailey JM, Salmenpera M. Pharmacokinetics of aprotinin in preoperative cardiac surgical patients. Anesthesiology 80, 1013-1018 (1994).
14. Levy JH, Sypniewski E. Aprotinin: a pharmacologic overview. Orthopedics 27, S653-S658 (2004).
15. van Oeveren W, Harder MP, Roozendaal KJ, Eijsman L, Wildevuur CR. Aprotinin protects platelets against the initial effect of cardiopulmonary bypass. J. Thorac. Cardiovasc. Surg. 99, 788-796; discussion 796-797 (1990).
16. Khan TA, Bianchi C, Voisine P et al. Aprotinin inhibits protease-dependent platelet aggregation and thrombosis. Ann. Thorac. Surg. 79, 1545-1550 (2005).
17. Landis RC, Haskard DO, Taylor KM. New anti-inflammatory and platelet-preserving effects of aprotinin. Ann. Thorac. Surg. 72, S1808-S1813 (2001).
18. Poullis M, Manning R, Laffan M et al. The antithrombotic effect of aprotinin: actions mediated via the proteaseactivated receptor 1. J, thorac. Cardiovasc. Surg. 120, 370-378 (2000).
19. Day JR, Punjabi PP, Randi AM et al. Clinical inhibition of the seven-transmembrane thrombin receptor (PAR1) by intravenous aprotinin during cardiothoracic surgery. Circulation 110, 2597-2600 (2004).
20. Maquelin KN, Nieuwland R, Lentjes EG et al. Aprotinin administration in the pericardial cavity does not prevent platelet activation. J. Thorac. Cardiovasc. Surg. 120, 552-557 (2000).
21. Sellke FW. Organ Protection in Cardiac Surgery. In: Improving Outcomes in Open Heart Surgery. Sellke FW (Ed.). Interactive Communications, Boston, MA, USA, (2005).
22. Straub A, Azevedo R, Beilerlein W et al. Hypothermia-induced platelet aggregation: no effect of aprotinin (trasylol) but inhibition by eptifibatide (integrilin). Thorac. Cardiovasc. Surg. 53, 80-84 (2005).
23. Bradfield JE Bode AR Aprotinin restores the adhesive capacity of dysfunctional platelets. Thromb. Res. 109, 181-188 (2003).
24. Carr ME Jr, Carr SL, Roa V, McCardell KA, Greilich PE. Aprotinin counteracts heparin-induced inhibition of platelet contractile force. Thromb. Res. 108, 161-168 (2002).
25. Dietrich W. Reducing thrombin formation during cardiopulmonary bypass: is there a benefit of the additional anticoagulant action of aprotinin? J. Cardiovasc. Pharmacol. 1(27 Suppi.), S50-S57 (1996).
26. Alston TA. Aprotinin. Int. Anesthesiol. Clin. 42, 81-91 (2004).
27. Levy JH. Efficacy and safety of aprotinin in cardiac surgery. Orthopedics 27, S659-S662 (2004).
28. Ray MJ, Brown KF, Burrows CA, O'Brien MF. Economic evaluation of high-dose and low-dose aprotinin therapy during cardiopulmonary bypass. Ann. Thorac. Surg. 68, 940-945 (1999).
29. Lemmer JH Jr, Dilling EW, Morton JR et al. Aprotinin for primary coronary artery bypass grafting: a multicenter trial of three dose regimens. Ann. Thorac. Surg. 62, 1659-1667; discussion 1667-1668 (1996).
30. Englberger L, Markart P, Eckstein FS et al. Aprotinin reduces blood loss in off-pump coronary artery bypass (OPCAB) surgery, Eur. J. Cardiothorac. Surg. 22, 545-551 (2002).
31. Ray MJ, Hales MM, Brown L, O'Brien MF. Stafford EG. Postoperatively Administered aprotinin or epsilon aminocaproic acid after cardiopulmonary bypass has limited benefit. Ann. Thorac. Surg 72, 521-526 (2001).
32. Huyzen RJ, Harder MP, Huet RC et al., Alternative perioperative anticoagulation monitoring during cardiopulmonary bypass in aprotinin-treated patients. J. Cardiothorac. Vasc. Anesth. 8, 153-156 (1994).
33. Ganter MT, Dalbert S, Graves K et al. Monitoring activated clotting time for combined heparin and aprotinin application: an in vitro evaluation of a new aprotinin-insensitive test using SONOCLOT. Anesth. Analg. 101, 308-314 (2005).
34. Kim YS, Murkin JM, Adams SJ. In vivo and in vitro evaluation of the heparin management test versus the activated coagulation time for monitoring anticoagulation level in aprotinin-treated patients during cardiac surgery. Heart Surg. Forum 7, E599-E604 (2004).
35. Bidstrup BP, Royston D, Sapsford RN, Taylor KM. Reduction in blood loss and blood use after cardiopulmonary bypass with high dose aprotinin (Trasylol). J. Thorac. Cardiovasc. Surg. 97, 364-372 (1989).
36. Sedrakyan A, Treasure T, Elefteriades JA. Effect of aprotinin on clinical outcomes in coronary artery bypass graft surgery: a systematic review and meta-analysis of randomized clinical trials. J. Thorac. Cardiovasc. Surg. 128, 442-448 (2004).
37. Alderman EL, Levy JH, Rich JB et al. Analyses of coronary graft patency after aprotinin use: results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial. J. Thorac. Cardiovasc. Surg. 116, 716-730 (1998).
38. Diprose P, Herbertson MJ, O'Shaughnessy D, Deakin CD, Gill RS: Reducing allogeneic transfusion in cardiac surgery: a randomized double-blind placebo-controlled trial of antifibrinolytic therapies used in addition to intra-operative cell salvage. Br. J. Anaesth. 94, 271-278 (2005).
39. Akowuah E, Shrivastava V, Jamnadas B et al. Comparison of two strategies for the management of antiplatelet therapy during urgent surgery. Ann. Thorac. Surg. 80, 149-152 (2005).
40. van der Linden J, Lindvall G, Sartipy U. Aprotinin decreases postoperative bleeding and number of transfusions in patients on clopidogrel undergoing coronary artery bypass graft surgery: a double-blind, placebo-controlled, randomized clinical trial. Circulation 112, 1276-1280 (2005).
41. Aprotinin. (Trasylol®, aprotinin injection). Package insert. Bayer Corporation West Haven, CT, USA. (2001).
42. Beierlein W, Scheule AM, Dietrich W, Ziemer G. Forty years of clinical aprotinin use: a review of 124 hypersensitivity reactions. Ann. Thorac. Surg. 79, 741-748 (2005).
43. Dietrich W, Spath P Ebell A, Richter JA. Prevalence of anaphylactic reactions to aprotinin: analysis of two hundred forty-eight reexposures to aprotinin in heart operations. J. Thorac. Cardiovasc. Surg. 113, 194-201 (1997).
44. Williams SR, Denault AY, Pellerin M, Martineau R. Vasopressin for treatment of shock following aprotinin administration. Can. J. Anaesth. 51, 169-172 (2004).
45. Hubner GE, Koch RC, Sprenger KB, Stadler PJ, Golker CF. Examination of the biological safety of a drug derived from mammalian organs. Arzneimittelforschung 46, 657-661 (1996).
46. Shiga T, Wajima Z, Inoue T, Sakamoto A. Aprotinin in major orthopedic surgery: a systematic review of randomized controlled trials. Anesth. Analg. 101, 1602-1607 (2005).
47. D'Ambra MN, Akins CW, Blackstone EH et al. Aprotinin in primary valve replacement and reconstruction: a multicenter, double-blind, placebo-controlled trial. J. Thorac. Cardiovasc. Surg. 112, 1081-1089 (1996).
48. Feindt PR, Walgher S, Volkmer I et al. Effects of high-dose aprotinin on renal function in aortocoronary bypass grafting. Ann. Thorac. Surg. 60, 1076-1080 (1995).
49. Kincaid EH, Ashburn DA, Hoyle JR et al. Does the combination of aprotinin and angiotensin-converting enzyme inhibitor cause renal failure after cardiac surgery? Ann. Thorac. Surg. 80, 1388-1393: discussion 1393 (2005).
50. Frumento RJ, O'Malley CM, Bennett-Guerrero E. Stroke after cardiac surgery: a retrospective analysis of the effect of aprotinin dosing regimens, Ann. Thorac. Surg. 75, 479-483; discussion 483-484 (2003).
51. Harmon DC, Ghorl KG, Eustace NP et al. Aprotinin decreases the incidence of cognitive deficit following CABG and cardiopulmonary bypass: a pilot randomized controlled study. Can. J. Anaesth. 51, 1002-1009 (2004).
52. Asimakopoulos G, Thompson R, Nourshargh S et al. An anti-inflammatory property of aprotinin detected at the level of leukocyte extravasation. J. Thorac. Cardiovasc. Surg. 120, 361-369 (2000).
53. Hill GE, Alonso A, Spurzem JR, Stammers AH, Robbins RA. Aprotinin and methylprednisolone equally blunt cardiopulmonary bypass-induced inflammation in humans. J. Thorac. Cardiovasc. Surg. 110, 1658-1662 (1995).
54. Nader ND, Davidson BA, Tait AR, Holm BA, Knight PR. Serine antiproteinase administration preserves innate superoxide dismutase levels after acid aspiration and hyperoxia but does not decrease lung injury Anesth. Ana1g. 101, 213-219, table of contents (2005).
55. Erdogan M, Kalaycioglu S, Iriz E. Protective effect of aprotinin against lung damage in patients undergoing CABG surgery. Acta Cardiol. 60, 367-372 (2005).
56. Ege T, Arar C, Canbaz S et al. The importance of aprotinin and pentoxifylline in preventing leukocyte sequestration and lung injury caused by protamine at the end of cardiopulmonary bypass surgery. Thorac. Cardiovasc. Surg. 52, 10-15 (2004).
57. Olivencia-Yurvati AH, Wallace WE, Wallace N et al. Intraoperative treatment strategy to reduce the incidence of postcardiopulmonary bypass atrial. fibrillation. Perfusion 17(Suppl.) 35-39 (2002).
58. Gillespie EL, Gryskiewicz KA, White CM et al. Effect of aprotiriin on the frequency of postoperative atrial fibrillation or flutter. Am. J. Health Syst. Pharm. 62, 1370-1374 (2005).
59. Khan TA, Bianchi C, Voisine P et al. Reduction of myocardial reperfusion injury by aprotinin after regional ischemia and cardioplegic arrest. J. Thorac. Cardiovasc. Surg. 128, 602-608 (2004).
60. Bull DA, Maurer J. Aprotinin and preservation of myocardial function after ischemia-reperfusion injury Ann. Thorac. Surg. 75, S735-S739 (2003).
61. Pruefer D, Buerke U, Khalil M et al. Cardioprotective effects of the serine protease inhibitor aprotinin after regional ischemia and reperfusion on the beating heart. J. Thorac. Cardiovasc. Surg. 124, 942-949 (2002).
62. Pruefer D, Makowski J, Dahm M et al. Aprotinin inhibits leukocyte-endothelial cell interactions after hemorrhage and reperfusion. Ann. Thorac. Surg. 75, 210-215; discussion 215-216 (2003).
63. Khan TA Bianchi C, Araujo E et al. Aprotinin preserves cellular junctions and reduces myocardial edema after regional ischemia and cardioplegic arrest. Circulation 112, 1196-1201 (2005).
64. Wachtfogel YT, Kucich U, Hack CE et al. Aprotinin inhibits the contact, neutrophil, and platelet activation systems during simulated extracorporeal perfusion. J. Thorac Cardiovasc. Surg. 106, 1-9; discussion 9-10 (1993).
65. Harmon D, Lan W, Shorten G. The effect of aprotinin on hypoxia-reoxygenation-induced changes in neutrophil and endothelial function. Eur. J. Anaestheriol. 21, 973-979 (2004).
66. Ray MJ, O'Brien MF. Comparison of epsilon aminocaproic acid and low-dose aprotinin in cardiopulmonary bypass: efficiency, safety and cost. Ann. Thorac. Surg. 71, 838-843 (2001).
67. Smith PK, Datta SK, Muhlbaier LH et al. Cost analysis of aprotinin for coronary artery bypass patients: analysis of the randomized trials. Ann. Thorac. Surg. 77, 635-642; discussion 642-643 (2004).
68. Baele PL, Ruiz-Gomez J, Londot C et al. Systematic use of aprotinin in cardiac surgery: influence on total homologous exposure and hospital cost. Acta Anaesthesiol. Belg. 43, 103-112 (1992).
69. Englberger L, Kipfer B, Berdat PA, Nydegger UE, Carrel TP. Aprotinin in coronary operation with cardiopulmonary bypass: does 'low-dose' aprotinin inhibit the inflammatory response? Ann. Thorac. Surg. 73, 1897-1904 (2002).
70. Apeler H, Peters J, Schroder W et al. Expression, purification, biochemical and pharmacological characterization of a recombinant aprotinin variant. Arzneimittelforschung 54, 483-497 (2004).
71. ManganoDT, Tudor IC, Dietzel C et al. The risk associated with aprotinin in cardiac surgery. N. Engl. J. Med. 354, 353-365 (2006).