Death aprotinin

During chronic inflammatory disease, inflammatory cells (neutrophils, mast cells, macrophages, and lymphocytes) become increasingly more damaging to tissues. Anti-inflammatory action of Bik reduces cell death mediated by immune cell. Proinflammatory cytokine tumor necrosis factor-a (TNF-q) and interleukin-1 (3 (IL-1) cause expression of multiple inflammatory and innate immunity genes for additional cytokines, chemokines, adhesion molecules, and enzymes. Aprotinin has been reported to cause a reduction in apoptosis in vivo by decreasing inflammatory cytokine expression (IL-1, IL-6, and TNF -a) thus preventing caspase-8 activation [81],... 

Schneeweiss S, Seeger JD, Landon J, Walker AM. 2008. Aprotinin during coronary-artery bypass grafting and risk of death. N. Engl.. Med. 358 771-783. 

Studies showing renal impairment In a systematic review of 11 studies, including 10 that studied renal function and seven that studied deaths, aprotinin w os associated with renal dysfunction (risk ratio, RR — 1.42 95% Cl = 1.13, 1.79) and long-term mortality (HR = 1.22 95% Cl = 1.08, 1.39) [196 ]. Pooled estimates were lower for short-term mortality (RR = 1.16 95% Cl — 0.84, 1.58) and renal failure requiring dialysis (RR = 1.17 95% Cl = 0.99, 1.38). Time on bypass was a significant source of heterogeneity, with a 29% increased risk of renal dysfunction for every 10-minute increase in bypass time. 

In a single-center non-randomized study in patients undergoing primary cardiac operations, 3334 were given aprotinin and 3417 were not [203 ]. The former were older, and had more unstable symptoms, lower ejection fractions, more preoperative hemodynamic support, more urgent operations, and more combined coronary or valvular operations. Postoperative bleeding and blood product transfusion were considerably reduced by aprotinin, as was median duration of mechanical ventilation. Aprotinin was not related to postoperative myocardial infarction, renal insufficiency, neurological dysfunction, or operative death. 

Death In a double-blind, randomized, placebo-controlled trial, 298 patients scheduled for low- or intermediate-risk firsttime cardiac surgery with cardiopulmonary bypass were randomized to tranexamic acid, high-dose aprotinin, or placebo. Neither antifibrinolytic agent increased the incidence of death [209 ]. However, a meta-analysis, updated in the light of these data, still showed increased mortality attributable to aprotinin (OR = 1.50 95% Cl = 1.04, 2.27) piO ]. 

Gagne JJ, Griesdale DE, Schneeweiss S. Aprotinin and the risk of death and renal dysfunction in patients undergoing cardiac surgery a meta-analysis of epidemiologic studies. Pharmacoepidemiol Drug Saf 2009 18(4) 259-68. 

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