Con: the practice of cardiac anesthesia has not significantly changed after the withdrawal of aprotinin.

s S OTHING QUITE RAISES the ire or brings out the torches and the pitchforks in the cardiothoracic anesthesia circles ore than a discussion about aprotinin. Much has been disussed and published regarding the broad-acting serine proease inhibitor. Keen interest in aprotinin began with Royston et l’s1 published report showing that the use of the drug resulted n an 8-fold decrease in the need for blood transfusion in atients undergoing repeat cardiac surgery. Aprotinin came into outine use for repeat coronary artery bypass graft (CABG) urgery after Food and Drug Administration (FDA) approval in 993 as a means to curtail perioperative bleeding. It was later pproved for first-time CABG surgery in 1998 for the same ndication. In the wake of its generally warm reception, aproinin was plagued by concerns regarding thrombosis of venous onduit and arterial coronary grafts as well as native coronary hrombosis.2,3 Additional concerns regarding cardiovascular ollapse because of anaphylaxis, catastrophic systemic thromosis, and renal insufficiency/failure in the setting of deep ypothermic circulatory arrest also had come to light.4 The FDA had been keeping a watchful eye as the developents unfolded, but issues were brought to a head with the angano et al5 article published in the New England Journal of edicine in January 2006. This observational, retrospective, ulticenter study of 4,374 patients compared aprotinin (full or alf-dose) with no agent, tranexamic acid (TA), and epsilon minocaproic acid (EACA) in primary or complex CABG urgery performed with cardiopulmonary bypass (CPB). Priary CABG surgery (n 3013) was defined as elective CABG urgery or angioplasty without prior cardiac or vascular surery. Complex surgery (n 1,361) was defined as CABG urgery with valvular or other cardiac procedure and any repeat ardiovascular procedure. The investigators found a doubling n the risk of renal failure requiring dialysis in the primary and omplex CABG surgery groups treated with aprotinin. Only in he primary CABG surgery group was aprotinin associated ith an increased risk of myocardial infarction or heart failure p 0.001), an increased risk of stroke or encephalopathy (p .001), and increased mortality (p 0.02). Aprotinin showed a ose-response relationship regarding renal, cardiovascular, and omposite outcomes. Despite the fact that the study’s findings ere seen predominantly in the primary surgery cohort, the nvestigators broadly concluded that aprotinin use was not rudent and suggested that other lysine analogs should be used. his brought about widespread concern, and numerous cardiac urgical groups altered their administration of aprotinin based n this study. Amid criticism that this study was an observaional, retrospective study, the Blood Conservation Using Anifibrinolytics in a Randomized Controlled Trial (BART) was lready underway. Meta-analyses of clinical trials had given no ndication of excess risk of death caused by aprotinin, so in 006 the FDA decided not to add a black-box warning to the protinin label. The BART study was a multicenter, doublelinded study comparing full-dose aprotinin with standard-dose ACA or TA in high-risk cardiac surgery (defined as twice the verage mortality for isolated primary CABG surgery and a p