Aprotinin does not increase the risk of renal failure in cardiac surgery patients. 2007

Anthony P Furnary, and YingXing Wu, and Loren F Hiratzka, and Gary L Grunkemeier, and U Scott Page
Providence Health System, Portland, Ore, USA. Email tfurnary@starrwood.com

BACKGROUND Aprotinin is frequently used in high-risk cardiac surgery patients to decrease bleeding complications and transfusions of packed red blood cells (PRBC). Transfusions of PRBC are known to directly increase the risk of new onset postoperative renal failure (ARF) in cardiac surgery patients. A recent highly publicized report implicated aprotinin as an independent causal factor for postoperative renal failure, but ignored the potential confounding affect of numerical PRBC data on ARF. We sought to investigate that claim with an analysis that included all perioperative risk factors for renal failure, including PRBC transfusion data. RESULTS Prospectively collected patient data from 12 centers contributing to the Merged Cardiac Registry, an international multicenter cardiac surgery database, operated on between January 2000 and February 2006 were retrospectively analyzed. A previously published risk model for ARF incorporating 12 variables was used to calculate a baseline ARF risk score for each patient in whom those variables were available (n=15,174). After adding transfused PRBC data 11,198 patients remained for risk-adjusted assessment of ARF in relation to aprotinin use. Risk-adjusted multivariable analyses were carried out with, and without, consideration of transfused PRBC. Aprotinin was used in 24.6% (2757/11,198). The overall incidence of ARF was 1.6% (180/11,198) and was higher in the aprotinin subset (2.6%, 72/2757 versus 1.3%, 108/8441; P<0.001). The incidence of ARF directly and significantly increased with increasing transfusions of PRBC (P<0.001). Risk-adjusted analysis without transfused PRBC in the model suggests that aprotinin significantly impacts ARF (P=0.008; OR=1.5). However, further risk adjustment with the addition of the highly significant transfused PRBC variable (P<0.0001; OR=1.23/transfused PRBC) to the model attenuates the purported independent affect of aprotinin (P=0.231) on ARF. CONCLUSIONS The increase in renal failure seen in patients who were administered aprotinin was directly related to increased number of transfusions in that high-risk patient population. Aprotinin use does not independently increase the risk of renal failure in cardiac surgery patients.

UI MeSH Term Description Entries
D007611 Aprotinin A single-chain polypeptide derived from bovine tissues consisting of 58 amino-acid residues. It is an inhibitor of proteolytic enzymes including CHYMOTRYPSIN; KALLIKREIN; PLASMIN; and TRYPSIN. It is used in the treatment of HEMORRHAGE associated with raised plasma concentrations of plasmin. It is also used to reduce blood loss and transfusion requirements in patients at high risk of major blood loss during and following open heart surgery with EXTRACORPOREAL CIRCULATION. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995) BPTI, Basic Pancreatic Trypsin Inhibitor,Basic Pancreatic Trypsin Inhibitor,Bovine Kunitz Pancreatic Trypsin Inhibitor,Kallikrein-Trypsin Inactivator,Kunitz Pancreatic Trypsin Inhibitor,Trypsin Inhibitor, Basic, Pancreatic,Trypsin Inhibitor, Kunitz, Pancreatic,Antilysin,Bovine Pancreatic Trypsin Inhibitor,Contrical,Contrykal,Dilmintal,Iniprol,Kontrikal,Kontrykal,Pulmin,Traskolan,Trasylol,Zymofren,Inactivator, Kallikrein-Trypsin,Kallikrein Trypsin Inactivator
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011183 Postoperative Complications Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. Complication, Postoperative,Complications, Postoperative,Postoperative Complication
D012042 Registries The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. Parish Registers,Population Register,Parish Register,Population Registers,Register, Parish,Register, Population,Registers, Parish,Registers, Population,Registry
D005260 Female Females
D006348 Cardiac Surgical Procedures Surgery performed on the heart. Cardiac Surgical Procedure,Heart Surgical Procedure,Heart Surgical Procedures,Procedure, Cardiac Surgical,Procedure, Heart Surgical,Procedures, Cardiac Surgical,Procedures, Heart Surgical,Surgical Procedure, Cardiac,Surgical Procedure, Heart,Surgical Procedures, Cardiac,Surgical Procedures, Heart
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D012189 Retrospective Studies Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. Retrospective Study,Studies, Retrospective,Study, Retrospective

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