Kidney-specific proteins in patients receiving aprotinin at high- and low-dose regimens during coronary artery bypass graft with cardiopulmonary bypass.
ABSTRACT The aim was to determine whether the administration of aprotinin can cause deleterious effects on renal function in cardiac surgery with cardiopulmonary bypass (CPB).
Sixty consecutive patients with normal preoperative renal function undergoing elective coronary artery bypass surgery with CPB using the same anaesthetic; CPB and surgical protocols were randomized into three groups. Patients received placebo (Group 1), low-dose aprotinin (Group 2) or high-dose aprotinin (Group 3). Renal parameters measured were plasma creatinine, alpha1-microglobulin and beta-glucosaminidase (beta-NAG) excretion. Measurements were performed before surgery, during CPB and 24 and 72 h, and 7 and 40 days postoperatively.
In the three groups, alpha1-microglobulin and beta-NAG excretions significantly increased during CPB, at 24 and 72 h, and 7 days postoperatively (P < 0.05) and had returned to preoperative levels at postoperative day 40. Plasma creatinine levels were within normal values at times recorded. In Groups 2 and 3, alpha1-microglobulin excretion during CPB was significantly higher than in Group 1 (P < 0.001), and 24h after surgery it still remained significantly higher in Group 3 compared to Groups 1 and 2 (P < 0.05).
Aprotinin caused a significant increase in alpha1-microglobulin excretion but not in beta-NAG excretion during CPB, which may be interpreted as a greater renal tubular overload without tubular damage. This effect persisted for 24 h after surgery when high-dose aprotinin doses had been administered. Creatinine plasma levels were not sensitive to detect these prolonged renal effects in our study.
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ABSTRACT: OBJECTIVES: The great difference in side effects of aprotinin was noted in adult and pediatric fields in recent reports because aprotinin was suspended for safety reasons. The aim of this study is to describe associations between aprotinin using and red blood cells transfusion, renal injury, and mortality in pediatric with cardiac surgery. METHODS: We retrospectively reviewed a cohort of 507 consecutive children who received a single dose of aprotinin (March-November 2007 before the FDA's decision for withdrawal of aprotinin) and a cohort of 494 consecutive children who did not receive aprotinin or other antifibrinolytic drugs (December 2007-August 2008). RESULTS: The two groups' demographics were assessed by the Aristotle Basic Complexity (ABC) propensity score. Postoperative blood loss was significantly reduced in the aprotinin group [P < 0.001, 95% confidence intervals (CI): 0.00-0.00], but postoperative red blood cell transfusion was not different between two groups (P = 0.4, 95% CI: 0.393-0.412). No statistical significant differences were noted in postoperative dialysis [0.39% vs 0.40%, P = 0.98, OR: 0.974, 95% CI: 0.137-6.944] and intra-hospital mortality (2.37% vs 1.82%, P:0.547, OR:1.306, 95% CI:0.546-3.129)) and reoperations for bleeding, thrombotic, and respiratory morbidity between two groups; however, the aprotinin group had temporarily a higher rate of 1.5-fold increased creatinine (class R) in the first postoperative 72 h (22.95% vs 13.93%, P < 0.001, OR: 1.840, 95% CI: 1.323-2.560), a longer duration of mechanical intubation [6.50 (4.50-24.00)h vs 6.00 (4.50-22.00)h, P = 0.004, 95% CI:0.002-0.005] and a 0.55% increased clinical mortality (although not statistically significant). More complex surgery had a higher rate of the increased creatinine (class R) in the first postoperative 72 h (ABC level 3 + 4 vs level 1 + 2, P = 0.017, OR:0.599, 95% CI:0.392-0.915). The multivariate analysis showed that age (<1 year), CPB >100 min, and the larger amount of transfusion (≥14 ml·kg(-1) ) were also important risk factors for the postoperative renal dysfunction (class R). CONCLUSIONS: Except reducing postoperative bleeding, we did not find other benefits of aprotinin. However, much higher postoperative creatinine levels, longer duration of mechanical ventilation, not less postoperative RBCs transfusion, and a 0.55% increased clinical mortality (although not statistically significant) were found in the aprotinin populations.Pediatric Anesthesia 11/2012; · 2.44 Impact Factor
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ABSTRACT: Recent studies have suggested increased renal complications and long-term mortality with aprotinin use in coronary artery bypass grafting (CABG) patients. However, these studies have been criticized for including multiple centers and different dosing strategies. We analyzed prospectively collected registry data from a single center hospital utilizing a full-dose aprotinin regimen to evaluate if aprotinin was associated with increased mortality and adverse outcomes compared with Amicar. Data were prospectively collected from 1994 to 2006 at a teaching hospital. Long-term mortality was collected from a Social Security database. To account for differences between aprotinin and Amicar-treated patients, a propensity score was generated and propensity-stratified multivariate model for mortality were performed. Compared with Amicar-treated patients (n = 1,830), aprotinin-treated patients (n = 1,507) were older, more often female, had lower creatinine clearance, and more baseline risk factors. Blood loss was lower in aprotinin-treated patients (median 715 mL vs 918 mL, p < 0.001). Postoperative renal failure was significantly higher in aprotinin patients (6.2% vs 2.7%, p < 0.001). At median 5.4-year follow-up (up to 12.2 years), aprotinin-treated patients had higher mortality versus Amicar-treated patients (Kaplan-Meier failure rates 43.5% vs 23.7% at 8 years, p < 0.0001). In a propensity-stratified model with multivariate adjustment, aprotinin remained associated with increased mortality (hazard ratio 1.62, 95% CI 1.39 to 1.90, p < 0.001). There was a stepwise relationship between weight-based aprotinin dose and mortality (p-trend < 0.001). Among patients undergoing CABG in this registry, aprotinin use was associated with increased renal failure and higher mortality through 12 years in a propensity-stratified analysis. The increased mortality may be related to higher concentrations of aprotinin received.The Annals of thoracic surgery 08/2008; 86(2):560-6; discussion 566-7. · 3.45 Impact Factor
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ABSTRACT: The use of aprotinin in cardiac surgery is associated with overriding safety concerns. Therefore, there is increased research on alternatives. This study investigated the relative benefits of strategic leukofiltration on polymer-coated extracorporeal circuits (ECC), aprotinin, and combined therapy in high-risk patients. Eight hundred and seventy-five patients (EuroSCORE 6+) undergoing coronary revascularization over a 4-year period were prospectively randomized to one of four perfusion protocols: Group 1: polymethoxyethylacrylate (PMEA)-coated circuits + leukocyte filters (n = 214); Group 2: uncoated ECC + full Hammersmith aprotinin (n = 212); Group 3: PMEA-coated ECC + leukofilters + full Hammersmith aprotinin (n = 199); and Group 4: control-no treatment (n = 250). Blood samples were collected at times T1: following the induction of anesthesia; T2: following heparin administration; T3: 15 min after cardiopulmonary bypass (CPB); T4: before cessation of CPB; T5: 15 min after protamine reversal; and T6: in the intensive care unit. The serum interleukin-2 levels were significantly lower at T3, T4, and T5 in all study groups. C3a levels were significantly lower at T3. Creatine kinase MB and lactate levels demonstrated well-preserved myocardia in both leukofiltration groups (P < 0.05). Neutrophil CD11b/CD18 levels were significantly lower for all study groups. Postoperative bleeding and respiratory support time were lower in all study groups. Leukofiltration on coated circuits significantly reduced bleeding and inflammatory response related to CPB with no adverse effects, and may be a possible alternative to pharmacological intervention.Surgery Today 11/2011; 42(4):334-41. · 0.96 Impact Factor