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 change s to their blood components, blood cells and specific coagulation prot eins. Aprotinin is a naturally occurring serine protease inhibitor iso lated 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 dura tion of the operation and 280mg added to the priming fluid of the CPB circuit) has been used during CPB in order to reduce perioperative ble eding. Recent clinical trials confirm the efficacy of high dose aproti nin in reducing blood loss and transfusion requirements associated wit h primary cardiac procedures such as coronary artery bypass graft (CAB G) or heart valve replacement surgery. High dose aprotinin is also eff ective 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 receiv ing aspirin (acetylsalicylic acid) before surgery. Studies indicate th at low dose aprotinin (280mg added to CPB pump prime fluid) is effecti ve in reducing blood loss and transfusion requirements in patients und ergoing primary CABG surgery. Additionally low dose aprotinin regimens (both 280mg added to CPB pump prime fluid and 50% of the high dose re gimen) have shown some benefit in repeat CABG surgery; however more st udies are needed to confirm these results. Data from clinical trials i ndicate that aprotinin is well tolerated. The types and incidences of adverse events reported with aprotinin therapy are generally consisten t with those associated with major cardiac surgery, and are not signif icantly different from those observed in control groups. A trend towar ds lower graft patency rates, detected by ultrafast computerised tomog raphy (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-m ine graft patency has not been validated. Mildly elevated plasma creat inine levels are more commonly observed in aprotinin-treated patients; these changes are transient in the majority of patients. Both high do se and low dose aprotinin regimens (280mg added to CPB pump prime flui d or 50% of the high dose regimen) have reduced blood loss and transfu sion requirements in patients undergoing primary and repeat cardiac su rgery. The role of aprotinin in paediatric cardiac surgery needs furth er clarification, while well-designed studies comparing aprotinin with other agents which inhibit fibrinolysis are also awaited with interes t. Preliminary pharmacoeconomic assessments of aprotinin appear favour able, and antigenic reactions occur in only a small proportion of pati ents. However; the achievement of a clear consensus regarding the rout ine use of aprotinin for primary cardiac surgery requires further clar ification of these issues. Nonetheless, it is clear that high dose apr otinin should be considered a valuable adjunct to aggressive blood con servation programmes in patients undergoing cardiac surgery with the p otential for excessive blood loss, in patients for whom transfusion is unavailable or in patients who refuse homologous transfusions.