APROTININ - A REVIEW OF ITS PHARMACOLOGY AND THERAPEUTIC EFFICACY IN REDUCING BLOOD-LOSS ASSOCIATED WITH CARDIAC-SURGERY

Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) experience transient haemostatic defects as a result of adverse changes to their blood components, blood cells and specific coagulation proteins. Aprotinin is a naturally occurring serine protease inhibitor isolated from bovine lung tissue which inhibits kallikrein and plasmin. A high dose aprotinin regimen (aprotinin 280mg loading dose over 20 to 30 minutes after anaesthesia induction followed by 70mg/h for the duration of the operation and 280mg added to the priming fluid of the CPB circuit) has been used during CPB in order to reduce perioperative bleeding. Recent clinical trials confirm the efficacy of high dose aprotinin in reducing blood loss and transfusion requirements associated with primary cardiac procedures such as coronary artery bypass graft (CABG) or heart valve replacement surgery. High dose aprotinin is also effective in procedures known to possess a high risk for excessive blood loss, such as repeat CABG or heart valve replacement surgery, cardiac surgery in patients with infective endocarditis, or in patients receiving aspirin (acetylsalicylic acid) before surgery. Studies indicate that low dose aprotinin (280mg added to CPB pump prime fluid) is effective in reducing blood loss and transfusion requirements in patients undergoing primary CABG surgery. Additionally low dose aprotinin regimens (both 280mg added to CPB pump prime fluid and 50% of the high dose regimen) have shown some benefit in repeat CABG surgery; however more studies are needed to confirm these results. Data from clinical trials indicate that aprotinin is well tolerated. The types and incidences of adverse events reported with aprotinin therapy are generally consistent with those associated with major cardiac surgery, and are not significantly different from those observed in control groups. A trend towards lower graft patency rates, detected by ultrafast computerised tomography (CT), has been observed in aprotinin recipients in 2 US trials. These differences did not reach statistical significance and should be interpreted with caution since the ability of ultrafast CT to deter-mine graft patency has not been validated. Mildly elevated plasma creatinine levels are more commonly observed in aprotinin-treated patients; these changes are transient in the majority of patients. Both high dose and low dose aprotinin regimens (280mg added to CPB pump prime fluid or 50% of the high dose regimen) have reduced blood loss and transfusion requirements in patients undergoing primary and repeat cardiac surgery. The role of aprotinin in paediatric cardiac surgery needs further clarification, while well-designed studies comparing aprotinin with other agents which inhibit fibrinolysis are also awaited with interest. Preliminary pharmacoeconomic assessments of aprotinin appear favourable, and antigenic reactions occur in only a small proportion of patients. However; the achievement of a clear consensus regarding the routine use of aprotinin for primary cardiac surgery requires further clarification of these issues. Nonetheless, it is clear that high dose aprotinin should be considered a valuable adjunct to aggressive blood conservation programmes in patients undergoing cardiac surgery with the potential for excessive blood loss, in patients for whom transfusion is unavailable or in patients who refuse homologous transfusions.