Cost analysis of aprotinin for coronary artery bypass patients: analysis of the randomized trials

BACKGROUND: The full kallikrein-inhibiting dose of aprotinin has been shown to reduce blood loss, transfusion requirements, and the systemic inflammatory response associated with cardiopulmonary bypass graft surgery (CABG). A half-dose regimen, although having a reduced delivery cost, inhibits plasmin and fibrinolysis without substantially effecting kallikrein-mediated inflammation associated with bypass surgery. The differing pharmacologic effects of the two regimens impact the decision-making process. The current study assessed the medical cost offset of full-dose and half-dose aprotinin from short- and long-term perspectives to provide a rational decision-making framework for clinicians. METHODS: To estimate CABG admission costs, resource utilization and clinical data from aprotinin clinical trials were combined with unit costs estimated from a Duke University-based cost model. Lifetime medical costs of stroke and acute myocardial infarction were based on previous research. RESULTS: Relative to placebo, the differences in total perioperative cost for primary CABG patients receiving full-dose or half-dose aprotinin were not significant. When lifetime medical costs of complications were considered, total costs in full-dose and half-dose aprotinin-treated patients were not different relative to that of placebo. Total perioperative cost was significantly lower for repeat CABG patients treated with aprotinin, with savings of $2,058 for full-dose and $2,122 for half-dose patients when compared with placebo. Taking lifetime costs of stroke and acute myocardial infarction into consideration, the cost savings estimates were $6,044 for full-dose patients and $4,483 for half-dose patients, due to substantially higher lifetime stroke costs incurred by the placebo patients. CONCLUSIONS: Using this cost model, use of full-dose and half-dose aprotinin in primary CABG patients was cost neutral during hospital admission, whereas both dosing regimens were significantly cost saving in reoperative CABG patients. Additional lifetime cost savings were realized relative to placebo due to reduced complication costs, particularly with the full-dose regimen. As the full kallikrein-inhibiting dose of aprotinin has been shown to be safe and effective, the current results support its use in both primary and repeat CABG surgery. No demonstrable economic advantage was observed with the half-dose aprotinin regimen.     

Plasma aprotinin concentrations during cardiac surgery: full- versus half-dose regimens

Aprotinin is an effective but expensive drug used during cardiac surgery to reduce blood loss and transfusion requirements. Currently, aprotinin is administered to adults according to a fixed protocol regardless of the patient's weight. The purpose of this study was to determine aprotinin levels in patients receiving full- and half-dose aprotinin regimens by a simple functional aprotinin assay and to design a more individualized aprotinin dosage regimen for cardiac surgical patients. The mean plasma aprotinin concentration peaked 5 min after the initiation of cardiopulmonary bypass (full 401 +/- 92 KIU/mL, half 226 +/- 56 KIU/mL). The mean plasma aprotinin concentration after 60 min on cardiopulmonary bypass was less (full 236 +/- 81 KIU/mL, half 160 +/- 63 KIU/mL). There was large variation in the aprotinin concentration among patients. A statistically significant correlation was found between aprotinin concentration and patient weight (r(2) = 0.67, P < 0.05). Implications: The current dosing schedule for aprotinin results in a large variation in aprotinin plasma concentrations among patients and a large variation within each patient over time. We combined the information provided by our study with that of a previous pharmacokinetic study to develop a potentially improved, weight-based, dosing regime for aprotinin.     

Reduction of blood loss and transfusion requirements after coronary artery bypass grafting: similar efficacy of tranexamic acid and aprotinin in aspirin-treated patients

BACKGROUND: In patients with coronary artery disease, continuation of aspirin may reduce the incidence of unstable angina and preoperative myocardial infarction before surgery, but the risk of perioperative bleeding may be increased. METHODS: The efficacy of aprotinin and tranexamic acid (TXA) was examined in a prospective, randomized, double-blind trial involving 56 patients scheduled for coronary artery bypass grafting and who received aspirin 100 mg/day until the day of the operation. Group I received high-dose aprotinin whereas group II received 10 g of tranexamic acid (TXA) over 20 minutes before sternotomy. Heparinization during cardiopulmonary bypass was controlled with HDTT (high-dose thrombin time) to eliminate interference of aprotinin on ACT (celite activated clotting time). Postoperative blood loss and transfusion requirements were registered during the first 24 hours. RESULTS: The demographics, coagulation, and intraoperative parameters were similar in both groups. Postoperative blood loss (aprotinin 840 mL /24 hours, TXA 880 mL/24 hours, p = 0.481), and transfusion requirements (2.18 units/patient in the aprotinin group, 2.11 units/patient in the TXA group) were not remarkably different between the two regimen protocols. No perioperative myocardial infarction, pulmonary embolism, cerebrovascular event, or other thrombotic events were observed. CONCLUSIONS: In this trial, we were not able to demonstrate any difference in postoperative bleeding in patients pretreated with aspirin after high-dose aprotinin or TXA. From a practical point of view, TXA is safe, less expensive than aprotinin, and easy to handle, and can be recommended in patients pretreated with aspirin to improve postoperative hemostasis.     

A study of a weight-adjusted aprotinin dosing schedule during cardiac surgery.

Aprotinin is effective during cardiac surgery for reducing blood loss and transfusion requirements, but it is expensive. Aprotinin is usually administered to adults according to a fixed protocol regardless of the patient's weight. We previously developed a weight-based dosing protocol for aprotinin. The purpose of this prospective observational study was to determine aprotinin levels in four patient groups (n = 10 each) using the new weight-based aprotinin dosing schedule that should achieve concentrations over 100, 150, 200, and 250 kallikrein inhibitory units/mL compared with full-dose aprotinin regimen (n = 10) by a simple functional aprotinin assay. There was no difference in patient demographic or surgical variables among groups. There was less within patient variation in plasma aprotinin concentrations over time in the new weight-based aprotinin dosing schedule groups compared with the full-dose aprotinin regimen group (P < 0.02 for all comparisons). The mean plasma aprotinin concentration achieved with the new weight-based aprotinin dosing schedule was similar to the desired concentrations, but we were unable to reduce between-patient variability in aprotinin concentrations. IMPLICATIONS: The current dosing schedule for aprotinin results in a large variation in aprotinin plasma concentrations between patients and a large variation within each patient over time. A new weight-based dosing schedule reduced variation of aprotinin concentration over time, but was unable to reduce between-patient variability in aprotinin concentration.     

Effect of aprotinin on postoperative blood loss in off-pump coronary artery bypass surgery

BACKGROUND AND AIM OF THE STUDY: Off-pump coronary artery bypass (OPCAB) enables a reduction in postoperative complications, particularly bleeding and transfusion. Nevertheless, a significant percentage of patients still needs transfusion. The effect of antifibrinolytic therapy on postoperative bleeding as part of OPCAB is still not widely described. The purpose of this study was to investigate the potential benefit of aprotinin in OPCAB. METHODS: We conducted a retrospective comparative study with a historical control group. Consecutive patients undergoing off-pump coronary bypass were divided in two groups: 40 patients were operated without any antifibinolytic drug (group C); 40 patients received aprotinin (group A) during surgery. Patients in group A received a bolus of 2 x 10(6) KIU during 30 minutes, followed by a continuous infusion of 0.5 x 10(6) KIU per hour until the end of surgery. The same protocol was used during the whole study period. RESULTS: Preoperative data of the two groups did not differ except for the number of grafts performed, which was higher in group A. Prothrombin time and activated clotting time increased in both groups after surgery. The use of packed red blood cells or fresh frozen plasma was not significantly different between both groups. Postoperative blood loss was significantly reduced in the aprotinin group (540 mL +/- 320 vs. 770 mL +/- 390, p = 0.006). No increase in postoperative troponin values was found in group A. CONCLUSIONS: Aprotinin significantly reduced postoperative blood loss without reducing the transfusion rate. Aprotinin was not associated with any increase in postoperative complications.     

Efficacy of aprotinin in reducing blood loss in spinal fusion for idiopathic scoliosis

Aprotinin is a proteinase inhibitor with antifibrinolytic properties that has found widespread application during cardiac surgical procedures due to its ability to decrease blood loss and transfusion requirements. Recently it has been used by orthopedic surgeons in hip replacement and other major surgeries except for scoliosis surgery, which is known to be associated with major blood loss. To evaluate the effect of aprotinin in reducing blood loss during spinal fusion surgery for idiopathic scoliosis, a double-blind randomized prospective clinical study was performed. Forty-three patients with idiopathic scoliosis underwent spinal fusion and instrumentation and were divided randomly into two groups. Fifteen patients received aprotinin, whereas 28 patients received placebo. The aprotinin group had less blood loss than the placebo group. The transfusion requirement was less in the aprotinin group than the placebo group. Although the difference was not significant statistically, the benefit of aprotinin in reducing blood loss in spinal surgery for idiopathic scoliosis was consistent.     

Amelioration of the bleeding tendency of preoperative aspirin after aortocoronary bypass grafting

BACKGROUND: Aspirin therapy is widely used in the treatment of cardiac disease. It has been recognized as a causative factor for increased bleeding and blood loss after open heart operations. METHODS: To determine whether high-dose aprotinin maintained its efficacy in reducing blood loss in the presence of aspirin pretreatment in patients undergoing aortocoronary bypass, we performed a double blind study on 60 adult patients. Half received high-dose aprotinin (Trasylol) and half placebo. RESULTS: Total hemoglobin loss, the primary efficacy variable was reduced from 36.1 +/- 31.4 g (mean +/- SD) to 14.1 +/- 16.0 g (p = 0.002). Blood loss was reduced intraoperatively and total loss was reduced from 837.3 mL +/- 404.9 mL to 368.7 mL +/- 164.3 mL (p < 0.001). The number of patients who did not receive any donor blood products was significantly higher in the aprotinin-treated patients (56.7% versus 23.3%, p = 0.008). Activation of the clotting cascade was significantly less in the treated patients toward the end of cardiopulmonary bypass both by measurement of thrombin-antithrombin III complex (p < 0.0001) and prothrombin fragment 1 + 2 (p < 0.0001). D-Dimer generation was significantly less from the onset of bypass and after reversal of heparin in the aprotinin-treated patients (p < 0.0001). CONCLUSIONS: High-dose aprotinin was highly effective in reducing bleeding in this high-risk group of patients. Biochemical analyses suggest the mechanism by which aspirin increases blood loss after cardiopulmonary bypass is different from the blood-preserving effects of aprotinin, which is acting as an antifibrinolytic agent.     

Aprotinin in pediatric neuromuscular scoliosis surgery

Reduction of blood transfusions in patients with neuromuscular scoliosis can decrease potential complications such as immune suppression, infection, hemolytic reaction and viral transmission. Aprotinin (Trasylol^®, Bayer), an antifibrinolytic, has proven to be effective in reducing blood loss in cardiac and liver surgery, but little data exists in patients undergoing spinal fusion for neuromuscular scoliosis. The purpose of this study was to evaluate the safety and efficacy of aprotinin in pediatric neuromuscular scoliosis patients undergoing spinal fusion. The medical records of all patients undergoing initial spinal fusions for neuromuscular scoliosis between January 1999 and March 2003 were reviewed to determine demographic data, perioperative data, wound drainage and number of transfusion required. Cases were compared to a matched group of historical controls. We had 14 patients in the aprotinin group and 17 in the control group. Total blood loss in the aprotinin group was significantly lower compared to the control group (715 vs. 2,110 ml; P = 0.007). Significantly less blood loss occurred in the aprotinin group when blood loss per kilogram was evaluated as well (23 vs. 60 ml/kg, respectively; P = 0.002). Intra-operative packed red blood cell (PRBC) transfusions were also significantly lower in the aprotinin group (1.25 vs. 3.16 units; P = 0.001). No clinical evidence of anaphylaxis, deep vein thrombosis (DVT) or renal failure was observed in the aprotinin group. After considering the price of drug therapy, operating room time, and the cost of blood products, the use of aprotinin saved an average of $8,577 per patient. In our series, the use of aprotinin resulted in decreased blood loss and a decreased rate of transfusions in children with neuromuscular scoliosis undergoing extensive spinal fusion. At out institution, the use of aprotinin is safe and cost effective for patients with neuromuscular scoliosis.     

Effects of minimal dose aprotinin on blood loss and fibrinolytic system-complement activation in coronary artery bypass grafting surgery

BACKGROUND: To determine whether 500,000 KIU aprotinin is effective to reduce blood loss in coronary artery bypass grafting (CABG) and to evaluate the effects of this regimen on hematologic parameters. METHODS: Forty-four patients scheduled for primary CABG were randomly assigned to the aprotinin (n = 24) or control group (n = 20). In aprotinin group, aprotinin was administered in two equal doses (before skin incision and added to the pump prime). Ventilation time, intensive care unit stay, mediastinal tube drainage, hospitalization, transfusion requirements, and postoperative morbidities and mortality were noted. Hematologic markers of fibrinolytic activity and complement activation were also measured pre- and postoperatively. RESULTS: Although less mediastinal drainage occurred in aprotinin group, the difference was not statistically significant. Other postoperative variables like transfusion requirements, morbidities, and mortality were also found to be similar between groups. Among hematologic parameters, only postoperative levels of alpha2-antiplasmin and plasminogen activator inhibitor-1 were significantly higher in aprotinin group. CONCLUSIONS: Although plasmin inhibitors begin to rise at this very low aprotinin dosage, it is not advisable to use this aprotinin regimen in CABG patients.     

The use of antifibrinolytic agents in total hip arthroplasty: a meta-analysis

Total hip arthroplasty is associated with significant blood loss that often requires allogenic blood transfusions. Tranexamic acid and aprotinin have been shown to reduce blood loss and transfusions in clinical trials with variable results. This meta-analysis evaluates whether tranexamic acid and aprotinin significantly reduces blood loss and transfusion requirements in total hip arthroplasty. Thirteen clinical trials were identified. Combined, these agents were significant across all outcome measures in reducing blood loss and transfusions. Separately, only aprotinin was found to be significant. The data also showed that aprotinin (tranexamic acid is inconclusive) is only beneficial in revision total hip arthroplasty. Therefore, only aprotinin is effective in reducing both blood loss and transfusion requirements without an increase in thromboembolic complications in patients undergoing revision total hip arthroplasty.     

Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin versus autologous fresh whole blood transfusion.

Ninety patients undergoing cardiac surgery were randomly divided into three groups of 30 patients to compare the effects on bleeding and transfusion requirements of either intraoperative infusion of high-dose aprotinin (GpI) or reinfusion of autologous fresh whole blood (GpII) versus a control group (GpIII). Standardized anesthetic, perfusion, and surgical techniques were used. Platelet counts, hemoglobin concentration, hematocrit, fibrinogen, and Ivy-Nelson bleeding times determined at fixed times perioperatively did not differ among the three groups. The total loss from the chest drains was significantly reduced in GpI (328 +/- 28 mL; mean +/- SEM) as compared with the loss in GpII and GpIII (775 +/- 75 mL and 834 +/- 68 mL, respectively). There was a threefold difference in the total hemoglobin loss (GpI, 14.2 +/- 1.7 g; GpII, 50.1 +/- 5.0 g; GpIII, 45.0 +/- 5.2 g). GpI patients also received less banked blood: 250 +/- 53 mL versus 507 +/- 95 mL in GpII and 557 +/- 75 mL in GpIII. No GpI patient required transfusion of platelets or fresh frozen plasma. Fresh whole autologous blood transfusions had no significant hemostatic effect and failed to reduce the homologous blood requirement. Conversely, high-dose aprotinin reduced blood loss and transfusion requirements.     

抑肽酶联合控制性降压在脊柱手术中的应用

目的 探讨抑肽酶联合控制性降压在脊柱手术中应用的血液保护效应.方法 45例择期行脊柱手术患者,随机均分为抑肽酶联合控制性降压组(联合组)、单纯控制性降压组(降压组)和对照组.分别在术前、术毕、术后24 h抽血检测血常规和凝血功能.比较三组患者手术失血量、输血量和凝血功能变化.结果 联合组与降压组手术失血量、输血量、术后24 h切口引流量均较对照组明显下降(P<0.01),联合组上述指标低于降压组(P<0.05).与对照组和降压组比较,联合组术后部分凝血活酶时间(APTT)延长(P<0.01),纤维蛋白原(Fib)值偏高(P<0.05).结论 抑肽酶联合控制性降压可明显减少脊柱手术的失血量和异体血的输入量.     

Aprotinin in major orthopedic surgery: a systematic review of randomized controlled trials

Aprotinin therapy is a promising strategy for reducing blood loss and blood transfusion requirements. The efficacy and safety of aprotinin in orthopedic surgery, however, remain controversial. We searched electronic databases for randomized controlled trials on the efficacy and safety of the use of aprotinin in orthopedic surgery. Thirteen trials that included a total of 506 patients who underwent major orthopedic surgery were analyzed. The pooled intraoperative and perioperative blood loss was significantly less in the aprotinin-treated patients than in the control patients (weighted mean difference [WMD] for intraoperative blood loss = -229 mL, 95% confidence interval [CI] = -367 to -91 mL, P = 0.0011; WMD for perioperative blood loss = -557 mL; 95% CI = -860 to -254 mL; P < 0.0001). The pooled amounts of red blood cell (RBC) units (U) transfused intraoperatively and perioperatively were significantly less in the aprotinin-treated patients than in the control patients (WMD for intraoperative RBC U = -1.1 U; 95% CI = -1.7 to -0.4 U; P = 0.0001; WMD for perioperative RBC U = -1.1 U; 95% CI = -1.7 to -0.5 U; P < 0.0001). Aprotinin was not associated with an increased incidence of deep vein thrombosis (odds ratio = 0.39; 95% CI = 0.14 to 1.05, P = 0.061). The authors conclude that aprotinin reduces the intraoperative and perioperative blood loss and allogeneic blood transfusion requirement and may not be associated with increased risk of deep vein thrombosis in the presence of pharmacological or mechanical prophylaxis in patients undergoing major orthopedic surgery.     

Aprotinin and tranexamic acid for high transfusion risk cardiac surgery

BACKGROUND: Studies have shown that aprotinin and tranexamic acid can reduce postoperative blood loss after cardiac operation. However, which drug is more efficacious in a higher risk surgical group of patients, has yet to be defined in a randomized study. METHODS: With informed consent, 80 patients undergoing elective high transfusion risk cardiac procedures (repeat sternotomy, multiple valve, combined procedures, or aortic arch operation) were randomized in a double-blind fashion, to receive either high dose aprotinin or tranexamic acid. Patient and operative characteristics, chest tube drainage and transfusion requirements were recorded. RESULTS: There was no significant difference between the 2 treatment groups with respect to age, cardiopulmonary bypass time, complications (myocardial infarction, stroke, death), chest tube drainage (6, 12, or 24 hours), blood transfusions up to 24 hours postoperatively, total allogeneic blood transfusions for entire hospital stay, or induction/postoperative hemoglobin levels. However, multiple regression analysis revealed a positive relationship between cardiopulmonary bypass time and 24 hour blood loss in the tranexamic acid group (p = 0.001), unlike the aprotinin group where 24 hour blood loss is independent of cardiopulmonary bypass time (p = 0.423). CONCLUSIONS: Overall, there was no significant difference in blood loss, or transfusion requirements, when patients received either aprotinin or tranexamic acid for high transfusion risk cardiac operation. Aprotinin, when given as an infusion in a high-dose regimen, was able to negate the usual positive effect of cardiopulmonary bypass time on chest tube blood loss.     

Combination of acute preoperative plateletpheresis, cell salvage, and aprotinin minimizes blood loss and requirement during cardiac surgery

Acute preoperative plateletpheresis (APP), cell salvage (CS) technique, and the use of aprotinin have been individually reported to be effective in reducing blood loss and blood component transfusion while improving hematological profiles in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). In this prospective randomized clinical study, the efficacy of these combined approaches on reducing blood loss and transfusion requirements was evaluated. Seventy patients undergoing primary coronary artery bypass grafting (CABG) were randomly divided into four groups: a control group (group I, n = 10) did not receive any of the previously mentioned approaches. An APP and CS group (group II, n = 20) experienced APP in which preoperative platelet-rich plasma was collected and reinfused after reversal of heparin, along with the cell salvage technique throughout surgery. The third group (group III, n = 22) received aprotinin in which 5,000,000 KIU Trasylol was applied during surgery, and a combination group (group IV, n = 18) was treated with all three approaches, i.e., APP, CS, and aprotinin. Compared with group I (896+/-278 mL), the postoperative total blood loss was significantly reduced in groups II, III, and IV (468+/-136, 388+/-122, 202+/-81 mL, respectively, p < 0.05). The requirements of packed red blood cells in the three approached groups (153+/-63, 105+/-178, 0+/-0 mL, respectively) also were reduced when compared with group I (343+/-118 mL, p < 0.05). In group I, six patients (6/10) received fresh-frozen plasma and three patients (3/10) received platelet transfusion, whereas no patients in the other three groups required fresh-frozen plasma and platelet. In conclusion, both plateletpheresis concomitant with cell salvage and aprotinin contribute to the improvement of postoperative hemostasis, and the combination of these two approaches could minimize postoperative blood loss and requirement.     

Does aprotinin reduce blood loss in total hip arthroplasty?

This prospective randomized study examined the effects of aprotinin during total hip arthroplasty (THA). Fifty patients who were enrolled in the study received aprotinin or normal saline. Mean intraoperative blood loss was reduced from 1496 mL in the control group to 1073 mL in the aprotinin group. The mean transfusion unit was 1.56 in the aprotinin group and 3.8 in the control group.     

Reduction of blood loss using aprotonin during spinal surgery in children for non-idiopathic scoliosis.

Background Aprotinin, a serine protease inhibitor, reduces surgical blood loss by mechanisms including antifibrinolysis and preservation of platelet function. Its effectiveness has been reported in adult patients undergoing cardiac, major orthopaedic surgery (1) and liver surgery, as well as in paediatric cardiac surgery. Spinal surgery in children with scoliotic deformities involves major blood loss. This may often be more than one circulatory blood volume and therefore results in exposure to blood products and the accompanying risks and problems. Patients with Duchenne muscular dystrophy or other neuromuscular conditions presenting for correction of a spinal deformity pose a particular problem because of their propensity to bleed during surgery. Aprotinin was introduced into the RMCH for the purpose of reducing blood loss in this group of patients in 1999. Administration of aprotinin carries the risk of the formation of aprotinin specific antibodies and anaphylaxis. Re‐exposure carries a greater risk. The aim of this study was to investigate the effect of aprotinin on blood loss during corrective spinal surgery in the neuromuscular patients. Methods We have performed a retrospective review of 33 ASA III cases operated on in period June 1998–September 2000. All notes were studied and data recorded on the intraoperative blood loss and the length of surgical procedure. Aprotinin was used only in children where it was felt that they would be unlikely to be re‐exposed because of their initial presenting diagnosis. Our regimen for aprotinin administration was: test dose 5 ml (50 000 KIU) over 20 min, loading dose 2 ml·kg^?1 (20 000 KIU·kg^?1) infused over 30 min, then maintenance at 0.5 ml·kg^?1·hr^?1 (5 000 KIU·kg^?1·h^?1). Results In the group that had not received aprotinin were 15 patients aged 7–17 years (mean age 13 ± 2 years), measured blood loss was 2849 ± 1802 ml, length of surgery 343 ± 78 min. In the aprotinin group we had 18 patients aged 7–15 years (mean age 12 ± 2 years) with recorded mean blood loss of 1380 ± 1000 ml and duration of procedure 389 ± 142 min. The blood loss in the group that had received aprotinin was significantly reduced (P < 0.01). Discussion Our two groups of patients were similar regarding the age of patients, pathology and clinical presentation. We believe that the use of aprotinin resulted in significant reduction of blood loss and requirements for blood products.     

Blood loss in infants and children for open heart operations: albumin 5% versus fresh-frozen plasma in the prime

BACKGROUND: Infants and children undergoing cardiopulmonary bypass become substantially hemodiluted secondary to the volume used to prime the oxygenator. Fresh-frozen plasma has been included in the prime to lessen dilution of clotting factors and correspondingly minimize blood loss and transfusions. METHODS: We prospectively randomized 56 patients weighing 10 kg or less who required cardiopulmonary bypass to receive either one unit of fresh-frozen plasma or 200 mL of albumin 5% in the prime. After protamine administration, samples for prothrombin time, fibrinogen, platelet count, and thromboelastogram were obtained. Mediastinal chest tube drainage and transfusion requirements were documented. RESULTS: There were no significant differences between groups regarding demographic or surgical characteristics. Blood loss during the first 24 hours was similar in both groups, but total transfusions were significantly greater in those who received fresh-frozen plasma instead of albumin 5% in the prime (8.0 +/- 4.2 versus 6.1 +/- 4.5 U, respectively; p = 0.035). Post hoc analyses suggest that for cyanotic patients and patients undergoing complex operations, fresh-frozen plasma in the prime results in less blood loss than albumin 5%. CONCLUSIONS: Substitution of albumin 5% for fresh-frozen plasma in the prime of acyanotic patients weighing 10 kg or less who undergo noncomplex operations requiring cardiopulmonary bypass significantly reduces perioperative transfusions without increasing blood loss. Further investigation is needed to determine whether increased blood loss is associated with increased transfusions when albumin 5% is substituted for fresh-frozen plasma in the prime of infants and children who are cyanotic or undergoing complex operations.     

Effects of Half-dose Aprotinin in Off-pump Coronary Artery Bypass Grafting

Objective The effects of half-dose aprotinin in off-pump coronary artery bypass (OPCAB) surgery have not yet been described. The present prospective study was designed to investigate its effects in OPCAB. Methods Seventy-six patients were randomized into two groups, receiving aprotinin (1 × 10⁶ Kallikrein-inactivating units [KIU] loading dose before surgery and 5 × 10⁵ KIU/h during surgery, gross dose: 2.5 × 10⁶ KIU, n = 36) and saline solution (control, n = 40) respectively. Perioperative blood samples were collected. Hematologic and hemostatic parameters including platelet adhesion rate, D-dimer, and fibrinopeptide-A (FPA) were analyzed. Perioperative CKMB release was measured. Volume of blood loss, blood transfusion, and other clinical data were recorded throughout the perioperative period. Results Postoperative blood loss was significantly reduced in patients treated with aprotinin (2 hours; median [25th–75th]: aprotinin: 90.0 [70.0–125.0] ml, control: 145.0 [70.0–180.0] ml, P < 0.05; 6 hours: aprotinin: 150.0 [100.0–220.0] ml, control: 225.0 [200.0–347.5.0] ml, P < 0.01; 24 hours: aprotinin: 370.0 [220.0–510.0] ml, control: 655.0 [500.0–920.0] ml, P < 0.01). The number of patients receiving blood transfusion in each group was similar. Levels of D-dimer rose significantly after surgery, and were significantly lower in the aprotinin group than in the controls (end of surgery, aprotinin, 0.4 [0.2–0.5] mg/l versus controls, 1.4 [0.8–2.3] mg/l; 2 hours, aprotinin, 0.3 [0.2–0.4] mg/l versus controls, 0.9 [0.5–1.4] mg/l; 6 hours, aprotinin, 0.3 [0.2–0.5] mg/l versus controls, 0.6 [0.4–0.9] mg/l; 24 hours, aprotinin, 0.3 [0.2–0.4] mg/l versus controls, 0.5 [0.4–0.9] mg/l; ANOVA for repeated measures, P < 0.01). Platelet adhesion rate and FPA levels remained at baseline levels after the operation in the two groups. Early clinical outcomes were similar in the groups. Levels of CKMB were significantly lower in the aprotinin group than in the controls (6 hours after surgery, aprotinin, 10.0 [8.0–16.0] U/l versus controls, 15.5 [11.0–20.3] U/l; 12 hours, aprotinin, 13.5 [10.0–20.0] U/l versus controls, 19.0 [12.8–24.3] U/l; 24 hours, aprotinin, 19.0 [13.5–33.8] U/l versus controls, 25.0 [15.0–43.3] U/l; 72 hours, aprotinin, 13.0 [8.0–18.0] U/l versus controls, 16.0 [10.0–29.0] U/l; ANOVA for repeated measures, P = 0.018). Conclusion The results indicated that half-dose aprotinin limits fibrinolysis and myocardial injury, and reduces blood loss after OPCAB surgery.     

A randomized trial of aprotinin (Trasylol) on blood loss, blood product requirement, and myocardial injury in total arterial grafting

BACKGROUND: Total arterial grafting is increasingly preferred in coronary artery bypass grafting, but it increases blood loss. Aprotinin (Trasylol; Bayer Corp, Leverkusen, Germany) reduces blood loss in cardiac surgery but has not been subjected to a randomized trial in total arterial grafting. METHODS: A single-center, randomized, double blind, placebo-controlled trial of aprotinin administration in total arterial grafting was performed. The primary outcome variable was postoperative blood loss, and the secondary outcome variable was the number of units of donor blood or coagulant products transfused. The incidence of myocardial injury was determined from serial measurements of cardiac troponin T and creatine kinase-MB and renal injury from serum creatinine. RESULTS: The placebo group (n = 34) and aprotinin group (n = 36) were similar with respect to all preoperative and intraoperative comparisons. One patient in each group underwent reexploration for bleeding. Open-label aprotinin was administered to 9 patients in the placebo group (26%) and to 2 patients in the aprotinin group (6%). There was a highly significant reduction in the median (interquartile range) blood loss in the aprotinin group compared with the placebo group (785 mL [590-1025 mL] vs 1525 mL [1175-1920 mL], respectively). Similarly, the aprotinin group demonstrated a marked reduction in the need for blood transfusion (77% vs 39%; P =.0001), the mean number of transfused blood units (2.6 vs 0.8, P <.001), and the number of patients requiring coagulant products (24% vs 3%; P <.001). There was no difference in myocardial injury in the 2 groups. Four patients in the aprotinin group had persistently elevated creatinine levels in the postoperative period (3 of whom had elevated preoperative creatinine levels and perioperative complications). CONCLUSIONS: Aprotinin significantly reduces blood loss and the need for blood component transfusion in patients undergoing total arterial grafting without increasing the risk of myocardial injury. Aprotinin should be considered routinely in patients undergoing total arterial grafting but cautiously in patients with an elevated preoperative creatinine level.