Mechanical methods of reducing blood transfusion in cardiac surgery: randomised controlled trial. A multicenter pilot-randomized controlled trial of the feasibility of an augmented red blood cell transfusion strategy for patients treated with induction chemotherapy for acute leukemia or stem cell transplantation. Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial. Efficacy of cell saver in reducing homologous blood transfusions during OPCAB surgery: a prospective randomized trial. Randomized multicentre trial of the influence of recombinant human erythropoietin on intraoperative and postoperative transfusion need in anaemic patients undergoing right hemicolectomy for carcinoma. Autotransfusion with cell saver for off-pump coronary artery bypass surgery: a randomized trial. Randomized study of aprotinin effect on transfusions and blood loss in primary THA. Blood conservation in small adults undergoing valve surgery. Thromboelastometrically guided transfusion protocol during aortic surgery with circulatory arrest: a prospective, randomized trial. Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials. Randomized, placebo-controlled, double-blind study of an ultra-low-dose aprotinin regimen in reoperative and/or complex cardiac operations. Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage.
To assess the effectiveness of two mechanical methods of blood conservation in reducing the need for allogeneic red blood cells or coagulation products during cardiac surgery.
                Randomised controlled trial.
                Regional cardiac centre in a teaching hospital in Southampton.
                263 adults aged 18-80 years undergoing elective coronary artery bypass surgery entered the study, of whom 252 completed the trial. All patients received routine perioperative care. Patients were allocated to one of three treatment groups: intraoperative cell salvage, intraoperative cell salvage with acute perioperative normovolaemic haemodilution, or no mechanical blood conservation. There were 84 patients in each group.
                Numbers of patients who received allogeneic blood or coagulation products, and the mean number of units of blood transfused per patient.
                Of the patients in the intraoperative cell salvage group, 26 were given a transfusion of allogeneic blood, compared with 43 in the control group (odds ratio 0.43 (95% confidence interval 0.23 to 0.80)). The mean number of units of allogeneic blood transfused per patient in the intraoperative cell salvage group was 0.68 units (SD=1.55), compared with 1.07 (1.56) units in the control group. 32 of the patients in the intraoperative cell salvage group were given any blood product, compared with 47 in the control group (odds ratio 0.47 (0.25 to 0.89); P=0.019). Combining acute perioperative normovolaemic haemodilution with intraoperative cell salvage conferred no additional benefits.
                An intraoperative cell salvage device should be used in elective coronary artery bypass grafting. Pharmacological strategies may achieve further reductions in blood transfusions. Yet further reductions in blood transfusions could be achieved if the lower safe limit of haemoglobin concentration in patients undergoing cardiac surgery were known. Anemia may be an important factor contributing to an increased risk of bleeding, particularly in patients with thrombocytopenia.
                A multicenter, single-blinded pilot randomized controlled trial (RCT) was performed to evaluate the feasibility of conducting a larger RCT to determine the effect of the hemoglobin (Hb) concentration on bleeding risk. Patients with acute leukemia receiving induction chemotherapy or those undergoing stem cell transplantation were assigned to one of two treatment groups: standard transfusion strategy (transfusion of 2 units of red blood cells [RBCs] when their Hb level was less than 80 g/L) or an augmented transfusion strategy (transfusion of 2 units of RBCs when their Hb level was less than 120 g/L).
                Sixty patients were enrolled: 29 in the control group and 31 in the experimental group. The proportions of patients experiencing clinically significant bleeding and the time to first bleed were not significantly different between the control and experimental groups. The experimental group received more RBC transfusions (transfusions/patient-day) than the control group (0.233 vs. 0.151; relative risk, 1.56; 95% confidence interval, 1.16-2.10; p = 0.003). The proportion of patient-days with platelet (PLT) transfusions was not different between the experimental and control groups. The mean number of donor exposures (PLT and RBC transfusions) was not different between experimental and control groups. Bleeding symptoms were systematically documented.
                This pilot study thus indicated that it would be feasible to enroll the required number of patients to enable the performance of a large RCT to investigate the effect of Hb on bleeding risk in thrombocytopenic patients. Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy.
                Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities.
                The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04).
                Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified. Despite the refinements in surgical technique, rates of homologous blood transfusion (HBT) in cardiac surgery remain high. The adverse effects of blood transfusion are well documented. Retransfusion of shed mediastinal blood reduces the requirement for HBTs during conventional coronary artery bypass grafting. However, some studies have found that autotransfusion leads to bleeding diathesis and paradoxical increase in blood transfusions. Through this prospective randomized trial, we have studied the safety and efficacy of this modality in patients undergoing off-pump coronary artery bypass grafting (OPCAB). Fifty patients enrolled in the study and 49 fulfilled the study criteria. They were randomly divided into group C (cell saver) and group N (non-cell saver). Whereas the cell saver group received processed shed autologous blood and homologous blood if necessary, the non-saver group was transfused homologous blood only. The threshold for transfusion was haemoglobin of 9 g dL(-1) in both the groups. The cell saver group required significantly less number of HBTs (1.6 +/- 1.2 vs. 2.4 +/- 1.3 units). The incidence of re-exploration was zero in both the groups. The mean mediastinal drainage in both the groups was not significantly different (355 +/- 196 vs. 316 +/- 119.8 mL). The number of patients requiring any blood transfusion however was very high. All the patients in the non-saver group and 20 (83%) of the patients in the saver group received homologous blood. During OPCAB surgery, the use of cell saver reduced the requirement for HBT. Its use is not associated with any clinically significant bleeding diathesis. The possible immunosuppressive effect of blood transfusion and its influence on survival after surgery for cancer makes it worthwhile to seek methods to avoid transfusion wherever possible. Patients with right-sided colonic cancer are frequently anaemic. Such patients were entered into a study that employed erythropoietin to avoid homologous transfusion.
                In a prospectively randomized double-blind placebo-controlled multicentre trial, patients with moderate anaemia (haemoglobin concentration greater than 8.5 g/dl and less than or equal to 13.5 g/dl) presenting with right-sided colonic cancer and scheduled for hemicolectomy were treated with recombinant human erythropoietin (epoetin beta) 20,000 units/day subcutaneously or placebo for at least 10 days over the operative period.
                Perioperative treatment with epoetin beta was well tolerated and there were no significant differences in morbidity and mortality. Following hemicolectomy, median cumulative blood loss in the two groups was similar (epoetin beta 440 ml versus placebo 345 ml). Sixteen (33 per cent) of 48 patients treated with epoetin beta and 15 (28 per cent) of 54 in the placebo group received perioperative blood transfusions (P not significant). The increase in reticulocyte count between baseline and the last preoperative value was more pronounced in the epoetin beta group than in those receiving placebo (P = 0.036).
                Despite the perioperative administration of 20,000 units erythropoietin per day for at least 10 days, it was not possible to reduce the intraoperative and postoperative transfusion need. None the less, a positive change in the haematological variables of treated patients was clearly discernible. The negative result may be due to the short treatment interval and to iron deficiency, which was present in the majority of patients. The general change of attitude towards allogeneic blood transfusion is demonstrated by the overall low frequency of blood transfusion in this study. Off-pump coronary surgery reduces transfusions, however, many patients still receive blood. This trial aims to clarify the effect of using a cell saver intraoperatively.
                In 60 patients shed blood was collected in the cell saver reservoir intraoperatively; randomization and processing or discharge were performed immediately after surgery. Primary outcome measures: proportion of patients receiving allogeneic blood, and average number of units per patient. Secondary outcome measures: blood loss, hemoglobin levels, complications, and costs.
                Cell saver group versus control group; received transfusions: 17/30 vs. 14/29 (p = 0.28), allogeneic units: median 1 (interquartile range 0 - 2) vs. 2 (IQR 0 - 7) (p = 0.06), intraoperative net blood loss: median 300 ml (IQR 193 - 403) vs. 610 ml (IQR 450 - 928) (p < 0.001). Control group patients had more complications leading to transfusion. Hemoglobin levels and costs were comparable between groups.
                Use of cell saver reduced intraoperative net blood loss and seemed to reduce transfusions by 1 unit per patient, however, this was probably attributable to more complications leading to transfusion in the control group. In the future larger trials are necessary. A projected increase in total hip arthroplasties, shortfalls in blood availability, and awareness of complications of transfusion make blood management in orthopaedic surgery important. In a multicenter, randomized, double-blind, placebo-controlled study, we hypothesized use of aprotinin would reduce blood transfusions (any and allogeneic) and blood loss in total hip arthroplasty. Using an intent-to-treat approach, we recruited 393 patients stratified by preoperative autologous blood donation or none and then randomized them to receive aprotinin (176 patients receiving a 10,000 kallikrein inhibitor units [KIU] test dose, 2 million KIU load, 0.5 million KIU per hour) or placebo (177 patients). We assessed patients at baseline; postoperative days 1, 2, 3, and 7 (or discharge); and 6 +/- 2 weeks. Primary efficacy was percentage of patients having blood transfusion through day 7 or discharge. We based safety on reported adverse events. Aprotinin reduced transfusions by 46% (30 of 176 versus 56 of 177 patients). Aprotinin reduced the total number of any blood units and the number of allogeneic blood units transfused relative to placebo (48 versus 109 units and 30 versus 72 units, respectively). Serious complications were similar in the two groups (placebo, 11%; aprotinin, 10%). Our data suggest full-dose aprotinin is safe and effective in decreasing blood transfusion in total hip arthroplasty. A substantial reduction in transfusion requirements for cardiac surgical procedures has been reported. Many of these reports have been described in patients undergoing coronary artery bypass grafting. Patients suffering from rheumatic heart disease in India are usually small and also anemic. This study was conducted to assess blood conservation methods for cardiac valve surgery in this subset of patients.
                This was a prospective, randomized study.
                The study was performed in a New Delhi tertiary care hospital, and the patients were referred from the northern states of India.
                One hundred fifty consecutive patients undergoing elective valve surgery using cardiopulmonary bypass were included. The mean age was 27.7 years and mean weight was 45.2 kg.
                The patients were divided into three groups of 50 each. Group 1 received autologous fresh blood donated before bypass, and both a cell saver and membrane oxygenator were used. The oxygenator contents at the end of perfusion were processed by cell saver. Group 2 patients were reinfused with autologous blood only, and group 3 was a control group. In groups 2 and 3, the blood that remained in the oxygenator at the conclusion of cardiopulmonary bypass was reinfused. A hematocrit of less than 25% was considered an indication for transfusion in the postoperative period.
                The mean preoperative hematocrit was 35.5%. A mean of 361.1 mL of autologous blood was collected from group 1 and 303.3 mL from group 2. Group 1 required 15 units of bank blood, group 2, 90 units (p < 0.001), and group 3, 102 units (p < 0.001). Seventy-eight percent of group 1 patients did not receive any donor blood. There was no significant difference in chest tube drainage among the three groups.
                In this unique group of patients whose mean body weight was only 45 kg, autologous blood alone did not decrease blood bank requirements but when combined with a cell saver and membrane oxygenator greatly reduced the need for donor blood. Aortic surgical procedures requiring hypothermic circulatory arrest are associated with altered hemostasis and increased bleeding. In a randomized clinical trial, we evaluated effects of thromboelastometrically guided algorithm on transfusion requirements.
                Fifty-six consecutive patients (25 with acute type A dissection) undergoing aortic surgery with hypothermic circulatory arrest were enrolled in a randomized trial during a 6-month period. Patients were randomly allocated to treatment group (n = 27) with thromboelastometrically guided transfusion algorithm or control group (n = 29) with routine transfusion practices (clinical judgment-guided transfusion followed by transfusion according to coagulation test results). Primary end point was cumulative allogeneic blood units (red blood cells, fresh-frozen plasma, and platelets) transfused.
                Transfusion of allogeneic blood was significantly reduced in the thromboelastometry group: median 9.0 units (interquartile range, 2.0-30.0 units) versus. 16.0 units (9.0-23.0 units, P = .02). Most significant decrease was in the use of fresh-frozen plasma (3.0 units, 0-12.0 units, vs 8.0 units, 4.0-18.0 units, P = .005). Postoperative blood loss (890 mL/d, 600-1250 mL/d vs 950 mL/d, 650-1400 mL/d, p = 0.5) and rate of surgical re-exploration (19% vs 24%, P = .7) were similar between groups. Thromboelastometrically guided algorithm significantly decreased need for massive perioperative transfusion (odds ratio, 0.45; 95% confidence interval, 0.2-0.9; P = .03) in multivariable logistic regression analysis.
                Thromboelastometrically guided transfusion is associated with a decreased use of allogeneic blood units and reduced incidence of massive transfusion in patients undergoing aortic surgery with circulatory arrest.
                Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved. Uncontrolled bleeding is a leading cause of death in trauma. Two randomized, placebo-controlled, double-blind trials (one in blunt trauma and one in penetrating trauma) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma.
                Severely bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 microg/kg) or placebo in addition to standard treatment. The first dose followed transfusion of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours later. The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose.
                Among 301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis. In blunt trauma, RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs) was reduced (14% vs. 33% of patients; p = 0.03). In penetrating trauma, similar analyses showed trends toward rFVIIa reducing RBC transfusion (estimated reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7% vs. 19%; p = 0.08). Trends toward a reduction in mortality and critical complications were observed. Adverse events including thromboembolic events were evenly distributed between treatment groups.
                Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rFVIIa was established in these trauma populations within the investigated dose range. High-dose aprotinin is an effective but costly method to reduce transfusions after cardiopulmonary bypass (CPB). Very low doses of aprotinin have been shown to be effective in primary cardiac surgery, but not in patients undergoing procedures associated with the greatest usage of allogeneic blood products after CPB. We evaluated the efficacy of ultra-low-dose aprotinin in this patient population.
                Aprotinin 1 million KIU or placebo was added to the priming solution of the CPB circuit of 52 patients undergoing a reoperation and/or a complex surgical procedure. Dryness of operative field, hemoglobin concentrations, coagulation parameters, chest drainage, and transfusion requirements were compared.
                Total chest drainage was not different between groups, but fewer patients in the aprotinin group required additional protamine postoperatively (35% vs 69% for controls, p = 0.03) and fewer received fresh frozen plasma (FFP; 19% vs 46% for controls, p = 0.04). Red cell transfusion was smaller in the aprotinin group compared to placebo (median 4 and 2 units, respectively, p = 0.04). Transfusion of FFP, platelets, cryoprecipitates was not different between groups. Total number of units transfused tended to be reduced in the aprotinin group compared to control (median 2 and 7 units, respectively, p = 0.06).
                Prophylactic administration of ultra-low-dose aprotinin reduced transfusions in patients undergoing repeat operations or complex procedures. Aprotinin could be used in a more economical manner, even in this patient population at high-risk of receiving allogeneic blood products. Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding and improve trauma outcomes.
                We performed a phase 3 randomized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma. We studied 573 patients (481 blunt and 92 penetrating) who bled 4 to 8 red blood cell (RBC) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management. Patients were assigned to rFVIIa (200 μg/kg initially; 100 μg/kg at 1 hour and 3 hours) or placebo. Intensive care unit management was standardized using evidence-based trauma "bundles" with formal oversight of compliance. Primary outcome was 30-day mortality. Predefined secondary outcomes included blood products used. Safety was assessed through 90 days. Study powering was based on prior randomized controlled trials and large trauma center databases.
                Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis (10.8% vs. 27.5% planned/predicted) and difficulties consenting and enrolling sicker patients. Mortality was 11.0% (rFVIIa) versus 10.7% (placebo) (p = 0.93, blunt) and 18.2% (rFVIIa) versus 13.2% (placebo) (p = 0.40, penetrating). Blunt trauma rFVIIa patients received (mean ± SD) 7.8 ± 10.6 RBC units and 19.0 ± 27.1 total allogeneic units through 48 hours, and placebo patients received 9.1 ± 11.3 RBC units (p = 0.04) and 23.5 ± 28.0 total allogeneic units (p = 0.04). Thrombotic adverse events were similar across study cohorts.
                rFVIIa reduced blood product use but did not affect mortality compared with placebo. Modern evidence-based trauma lowers mortality, paradoxically making outcomes studies increasingly difficult.
The need for blood transfusions corresponded to one half unit of blood saved per patient. It is doubtful whether this effect is worthwhile. The findings do not suggest a need for further placebo-controlled trials of the type reviewed here. A large placebo controlled trial enrolling thousands of patients is needed if one wishes to rule out the possibility that a worthwhile effect on mortality might have been overlooked.