Tranexamic Acid Reduces Bleeding After Cardiopulmonary Bypass When Compared to Epsilon Aminocaproic Acid and Placebo

A bstract Perioperative bleeding following coronary artery bypass grafting (CABG) is associated with increased blood product usage. Although aprotonin is effective in reducing perioperative blood loss, excessive cost prohibits routine utilization. Epsilon aminocaproic acid (EACA) and tranexamic acid (TA) are inexpensive antifibrinolytic agents, which, when give prophylactically, may reduce blood loss. The present study was undertaken to compare the efficacy of TA and EACA in reducing perioperative blood loss. Methods : The study population consisted of first-time CABG patients. Patients were allocated in a prospective double-blind fashion: (1) group EACA (loading dose 150 mg/kg, continuous infusion 10 mg/kg per hour for 6 hours, N = 20); (2) group TA (loading dose 15 mg/kg, continuous infusion 1 mg/kg per hour for 6 hours, N = 20); (3) control group (infusion of normal saline for 6 hours, N = 19). Results : Treatment groups were similar preoperatively. No significant difference in intraoperative blood loss or perioperative use of blood products was noted. D-dimer concentration was elevated in the control group compared to the EACA and TA groups (p < 0.05). Group TA had less postoperative blood loss than the EACA and control groups at 6 and 12 hours postoperatively (p < 0.05). TA had reduced total blood loss (600 ± 49 mL) postoperatively compared to EACA (961 ± 148 mL) and control (1060 ± 127mL, p < 0.05). Conclusion : TA and EACA effectively inhibited fibrinolytic activity intraoperatively and throughout the first 24 hours postoperatively. TA was more effective in reducing blood loss postoperatively following CABG. This suggests that TA may be beneficial as an effective and inexpensive antifibrinolytic in first-time CABG patients.     

Tranexamic acid reduces blood loss and blood transfusions in primary total hip arthroplasty: a prospective randomized double-blind study in 40 patients

INTRODUCTION: We performed a prospective, randomized, double-blind study on 40 patients scheduled for primary total hip arthroplasty due to arthrosis or osteonecrosis to determine the effect of tranexamic acid on per- and postoperative blood losses and on the number of blood transfusions needed. PATIENTS AND METHODS: 40 patients were randomized to tranexamic acid (10 mg/kg given as a bolus intravenous injection, followed by a continuous infusion of 1 mg/kg/hour for 10 hours) or placebo (20 mL saline given intravenously) 15 minutes before the incision. We recorded the peroperative and postoperative blood losses at removal of the drain 24 hours after the operation and the number of blood transfusions. RESULTS: Patients receiving tranexamic acid had a mean peroperative blood loss of 480 mL versus 622 mL in patients receiving placebo (p = 0.3), a postoperative blood loss of 334 mL versus 609 mL (p = 0.001), a total blood loss of 814 mL versus 1231 mL (p = 0.001) and a total need for 4 blood transfusions versus 25 (p = 0.04). No patient in either group had symptoms of deep venous thrombosis, pulmonary embolism or prolonged wound drainage. INTERPRETATION: Transemic acid is effective in reducing the postoperative blood loss, the total blood loss and the need for blood transfusion in primary total hip arthroplasty.     

Tranexamic acid reduces blood loss and blood transfusions in primary total hip arthroplastyA prospective randomized double-blind study in 40 patients

Introduction: We performed a prospective, randomized, double-blind study on 40 patients scheduled for primary total hip arthroplasty due to arthrosis or osteonecrosis to determine the effect of tranexamic acid on per- and postoperative blood losses and on the number of blood transfusions needed. Patients and methods: 40 patients were randomized to tranexamic acid (10 mg/kg given as a bolus intravenous injection, followed by a continuous infusion of 1 mg/kg/hour for 10 hours) or placebo (20 mL saline given intravenously) 15 minutes before the incision. We recorded the peroperative and postoperative blood losses at removal of the drain 24 hours after the operation and the number of blood transfusions. Results: Patients receiving tranexamic acid had a mean peroperative blood loss of 480 mL versus 622 mL in patients receiving placebo (p= 0.3), a postoperative blood loss of 334 mL versus 609 mL (p= 0.001), a total blood loss of 814 mL versus 1231 mL (p= 0.001) and a total need for 4 blood transfusions versus 25 (p= 0.04). No patient in either group had symptoms of deep venous thrombosis, pulmonary embolism or prolonged wound drainage. Interpretation: Transemic acid is effective in reducing the postoperative blood loss, the total blood loss and the need for blood transfusion in primary total hip arthroplasty.     

Pharmacokinetics of [Greek small letter epsilon]-aminocaproic Acid in Patients Undergoing Aortocoronary Bypass Surgery

Background: [Greek small letter epsilon]-Aminocaproic acid (EACA) is commonly infused during cardiac surgery using empiric dosing schemes. The authors developed a pharmacokinetic model for EACA elimination in surgical patients, tested whether adjustments for cardiopulmonary bypass (CPB) would improve the model, and then used the model to develop an EACA dosing schedule that would yield nearly constant EACA blood concentrations.

Methods: Consenting patients undergoing elective coronary artery surgery received one of two loading doses of EACA, 30 mg/kg (group I, n = 7) or 100 mg/kg (group II, n = 6) after CPB, or (group III) a 100 mg/kg loading dose before CPB and a 10 mg [middle dot] kg-1 [middle dot] h-1 maintenance infusion continued for 4 h during and after CPB (n = 7). Two patients with renal failure received EACA in the manner of group III. Blood concentrations of EACA, measured by high-performance liquid chromatography, were subjected to mixed-effects pharmacokinetic modeling.

Results: The EACA concentration data were best fit by a model with two compartments and corrections for CPB. The elimination rate constant k10 fell from 0.011 before CPB to 0.0006 during CPB, returning to 0.011 after CPB. V1 increased 3.8 l with CPB and remained at that value thereafter. Cl1 varied from 0.08 l/min before CPB to 0.007 l/min during CPB and 0.13 l/min after CPB. Cl2 increased from 0.09 l/min before CPB to 0.14 l/min during and after CPB. Two patients with renal failure demonstrated markedly reduced clearance. Using their model, the authors predict that an EACA loading infusion of 50 mg/kg given over 20 min and a maintenance infusion of 25 mg [middle dot] kg-1 [middle dot] h-1 would maintain a nearly constant target concentration of 260 [micro sign]g/ml.     

Autotransfusion management during and after cardiopulmonary bypass alters fibrin degradation and transfusion requirements

The coagulation-fibrinolytic profile during cardiopulmonary bypass (CPB) has been widely documented. However, less information is available on the possible persistence of these alterations when autotransfusion is used in management of perioperative blood loss. This study was designed to explore the influence of autotransfusion management on intravascular fibrin degradation and postoperative transfusions. Thirty patients, undergoing elective primary isolated coronary bypass grafting, were randomly allocated either to a control group (group A; n=15) or an intervention group (group B; n=15) in which mediastinal and residual CPB blood was collected and processed by a continuous autotransfusion system before re-infusion. Intravascular fibrin degradation as indicated by D-dimer generation was measured at five specific intervals and corrected for hemodilution. In addition, chest tube drainage and need for homologous blood were monitored. D-dimer generation increased significantly during CPB in group A, from 312 to 633 vs. 291 to 356 ng/mL in group B (p = .001). The unprocessed residual blood (group A) revealed an unequivocal D-dimer elevation, 4131 +/- 1063 vs. 279 +/- 103 ng/mL for the processed residual in group B (p < .001). Consequently, in the first post-CPB period, the intravascular fibrin degradation was significantly elevated in group A compared with group B (p = .001). Twenty hours postoperatively, no significant difference in D-dimer levels was detected between both groups. However, a significant intra-group D-dimer elevation pre- vs. postoperative was noticed from 312 to 828 ng/mL in group A and from 291 to 588 ng/mL in group B (p < .01 for both). Postoperative chest tube drainage was higher in the patients from group A, which also had the highest postoperative D-dimer levels. Patients in group A perceived a higher need for transfusions of red cells suspensions postoperatively. These data clearly indicate that autotransfusion management during and after CPB suppresses early postoperative fibrin degradation. Keywords: cardiopulmonary bypass, cardiotomy suction, coronary surgery, autotransfusion, fibrin degradation.     

The effect of epsilon aminocaproic acid on blood loss in patients who undergo primary total hip replacement: a pilot study.

OBJECTIVE: To determine if the use of an antifibrinolytic agent (epsilon aminocaproic acid [EACA]) decreased perioperative and postoperative blood loss in patients who underwent total hip arthroplasty (THA). DESIGN: A prospective, double-blind, randomized, controlled clinical trial. SETTING: A university-affiliated tertiary care hospital with a large joint arthroplasty population. PARTICIPANTS: Fifty-five patients who were scheduled for a primary THA. METHOD: Patients were randomly assigned to 2 groups to receive either EACA or saline placebo perioperatively. Preoperatively, the groups were similar with respect to gender, mean age, mean hemoglobin level, operative time and prosthesis type. OUTCOME MEASURES: Blood loss from the start of surgery until the Hemovac drain was removed, and the transfusion rate and hemoglobin levels. RESULTS: Mean (and standard error) total blood loss for patients receiving EACA was 867 (207) mL and for patients receiving placebo was 1198 (544) mL (p < 0.025). Four patients in the EACA group received 7 units of packed red blood cells and 7 patients in the saline group required 12 units. CONCLUSIONS: Patients receiving the placebo sustained greater total blood loss than EACA patients and were more likely to require blood transfusion. In the current climate of concern over blood transfusions during surgery, EACA administration can reduce blood loss and consequently transfusion and transfusion-related risk.     

Pharmacokinetics of epsilon-aminocaproic acid in patients undergoing aortocoronary bypass surgery.

BACKGROUND: Epsilon-aminocaproic acid (EACA) is commonly infused during cardiac surgery using empiric dosing schemes. The authors developed a pharmacokinetic model for EACA elimination in surgical patients, tested whether adjustments for cardiopulmonary bypass (CPB) would improve the model, and then used the model to develop an EACA dosing schedule that would yield nearly constant EACA blood concentrations. METHODS: Consenting patients undergoing elective coronary artery surgery received one of two loading doses of EACA, 30 mg/kg (group I, n = 7) or 100 mg/kg (group II, n = 6) after CPB, or (group III) a 100 mg/kg loading dose before CPB and a 10 mg x kg(-1) x h(-1) maintenance infusion continued for 4 h during and after CPB (n = 7). Two patients with renal failure received EACA in the manner of group III. Blood concentrations of EACA, measured by high-performance liquid chromatography, were subjected to mixed-effects pharmacokinetic modeling. RESULTS: The EACA concentration data were best fit by a model with two compartments and corrections for CPB. The elimination rate constant k10 fell from 0.011 before CPB to 0.0006 during CPB, returning to 0.011 after CPB. V1 increased 3.8 l with CPB and remained at that value thereafter. Cl1 varied from 0.08 l/min before CPB to 0.007 l/min during CPB and 0.13 l/min after CPB. Cl2 increased from 0.09 l/min before CPB to 0.14 l/min during and after CPB. Two patients with renal failure demonstrated markedly reduced clearance. Using their model, the authors predict that an EACA loading infusion of 50 mg/kg given over 20 min and a maintenance infusion of 25 mg x kg(-1) x h(-1) would maintain a nearly constant target concentration of 260 microg/ml. CONCLUSIONS: EACA clearance declines and volume of distribution increases during CPB. The authors' model predicts that more stable perioperative EACA concentrations would be obtained with a smaller loading dose (50 mg/kg given over 20 min) and a more rapid maintenance infusion (25 mg x kg(-1) x h(-1)) than are typically employed.     

High-dose aprotinin modulates the balance between proinflammatory and anti-inflammatory responses during coronary artery bypass graft surgery

OBJECTIVE: To rule out the effect of high-dose aprotinin in respect to the balance of proinflammatory and anti-inflammatory mediators induced by cardiopulmonary bypass (CPB). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: University-affiliated cardiac center. PARTICIPANTS: Twenty patients scheduled for coronary artery bypass graft surgery. INTERVENTIONS: In group A patients (n = 10), high-dose aprotinin was administered (2 x 106 KIU pre-CPB, 2 x 10(6) KIU in prime, 500,000 KIU/hr during CPB). In group C patients (n = 10), placebo was used instead. Proinflammatory interleukin (IL)-6, anti-inflammatory IL-1-receptor antagonist, and clinical parameters were measured 8 times perioperatively. The values are presented as mean +/- SEM. MEASUREMENTS AND MAIN RESULTS: Four hours after CPB, IL-6 concentration reached the maximum value, being significantly lower in group A patients as compared with group C patients (615 +/- 62 pg/mL v 1,409 +/- 253 pg/mL; p = 0.019). On the first postoperative day, the concentration of IL-6 in group A patients remained lower (219 +/- 24 pg/mL v 526 +/- 123 pg/mL; p = 0.015). In contrast, IL-1-receptor antagonist concentration was higher in group A patients as compared with group C patients after CPB (13,857 +/- 4,264 pg/mL v 5,675 +/- 1,832 pg/mL; p = 0.03). Total postoperative blood loss was lower in group A patients as compared with group C patients (648 +/- 64 mL v 1,284 +/- 183 mL; p = 0.002). CONCLUSIONS: High-dose aprotinin treatment reduced the inflammatory reaction and postoperative blood loss. The anti-inflammatory reaction was significantly enhanced in these patients, which suggests that the physiologic reaction of the organism to reduce the deleterious effects from CPB is more pronounced by using high-dose aprotinin.     

Effects of intraoperative plasmapheresis on blood loss in cardiac surgery

Intraoperative platelet-rich plasmapheresis allows autotransfusion of fresh, undamaged platelets and clotting factors at the completion of the operation. To evaluate this technology, we randomly assigned 100 consecutive patients who were to undergo an elective coronary bypass procedure and had normal clotting studies into the experimental (plasmapheresis) or the control group. Characteristics of both groups were similar, including average age (61.4 years versus 61.3 years [experimental versus control group]), sex (78% male versus 74% male), preoperative weight (80.9 kg versus 80.2 kg), preoperative red cell mass (1,989 mL versus 1,890 mL), perfusion time (102 minutes versus 106 minutes), and coagulation studies. Both internal mammary arteries were used in 68% of the patients. All patients had preoperative and postoperative blood volume determinations and complete clotting studies. Sixty-two variables related to bleeding were analyzed. Strict indications for transfusion were a hemoglobin level less than 7 g/100 mL in patients younger than 70 years and a hemoglobin level less than 8 g/100 mL in patients older than 70 years. The group receiving intraoperative plasmapheresis had a significant reduction in operative red cell mass loss (1,050 +/- 43 mL versus 1,226 +/- 61 mL; p = 0.021), a reduction in the average homologous transfusion (0.67 +/- 0.15 unit versus 1.8 +/- 0.25 units; p = 0.0002), and an increase in the percentage of patients not requiring blood transfusions (66% versus 32%; p = 0.001). This technique is useful in reducing postoperative blood loss and homologous transfusions.     

Fibrinolysis in pediatric patients undergoing cardiopulmonary bypass

Thromboelastographic evaluation of the influence of fibrinolysis on blood loss and blood product transfusions in children during cardiac surgery. Prospective study. University-affiliated, pediatric medical center. Two hundred seventy-eight consecutive children undergoing cardiac surgery. Blood sampling for coagulation tests, including native and protamine-modified thromboelastography. Blood coagulation tests were measured before, during, and after cardiopulmonary bypass (CPB). Demographic data, perioperative blood loss, and blood product transfusions were prospectively recorded. Fibrinolysis was defined as thromboelastography of A30/MA less than 0.85 (MA, maximum amplitude; A30, amplitude 30 minutes after MA) and was noted in 3% of children pre-CPB, 16% during CPB, and 3% post-CPB. Fibrinolysis before CPB was associated with poor cardiac output. Fibrinolysis during CPB occurred in young children (aged 350 ± 836 days) undergoing complex surgery with prolonged CPB (119 ± 48.8 minutes) and deep hypothermia (25.6°C ± 4.7°C). These patients received blood products after CPB and were not fibrinolytic after transfusion. They incurred similar blood loss (in mL/kg) and received similar volumes of blood products (mL/kg) as age-matched and surgery-matched patients without fibrinolysis. A group of children at risk for fibrinolysis during CPB was identified. However, fibrinolysis during CPB did not influence blood loss or the total volume of blood products transfused.     

Mechanisms behind operating room blood transfusions in coronary artery bypass graft surgery patients with insignificant bleeding

OBJECTIVE: To investigate situations in cardiac surgery when transfusions are sometimes used for indications other than to compensate for surgical bleeding. DESIGN: Retrospective study. SETTING: Cardiac surgery unit at a university teaching hospital. PARTICIPANTS: Patients scheduled for coronary artery bypass graft surgery (n = 2,469). INTERVENTIONS: A subgroup of patients with surgical bleeding of < or = 400 mL (n = 982) was selected to identify mechanisms leading to perioperative erythrocyte transfusion. MEASUREMENTS AND MAIN RESULTS: Bleeding of >400 mL triggered transfusion. At less than this bleeding volume, other indications were noted: unstable angina, use of blood cardioplegia, and bad surgical outcome, such as inotropic support. After exclusion of these predictors and anemic patients, the strongest predictors were female gender (p < 0.001), weight < or = 70 kg (p < 0.001), cardiopulmonary bypass (CPB) time > or = 90 minutes (p = 0.002), CPB cooling < or = 32 degrees C (p = 0.038), and advanced age (p < 0.001). Results from a more detailed study of medical records showed that within its normal concentration range, the operating room-transfused patients had lower hemoglobin levels. When followed postoperatively in the intensive care unit and ward, these patients continued to receive more transfusions (p < 0.05) even though their bleeding in the intensive care unit did not differ from the control subjects. CONCLUSION: Some patients are transfused because of institutional bias of an anticipated need rather than for true surgical bleeding. A concern of hemodilution from standard CPB circuits suggests a possible advantage with low-priming volume for smaller adult female patients.     

High-dose aprotinin reduces activation of hemostasis,allogeneic blood requirement,and duration of postoperative ventilation in pediatric cardiac surgery

BACKGROUND: Though multiple studies have affirmed the effectiveness of aprotinin in reducing blood loss in adult cardiac surgery, the possible benefit in pediatric cardiac surgery is controversial. METHODS: In a double-blind, randomized, and placebo-controlled study, the efficacy of aprotinin in attenuating the hemostatic and inflammatory activation during cardiopulmonary bypass in 60 patients weighing less than 10 kg was investigated. Secondary endpoints were the influence of aprotinin on the reduction of blood loss and allogeneic blood requirement, as well as postoperative oxygenation and length of mechanical ventilation. Aprotinin was administered in a high-dose of 3 x 10(4) KIU/kg plus a bolus of 5 x 10(5) KIU (not weight adjusted) added to the pump prime. RESULTS: Aprotinin plasma concentration at the end of cardiopulmonary bypass (CPB) was with 184 +/- 45 KIU/mL, within the targeted range of 200 KIU/mL. Coagulation and fibrinolysis were suppressed (F1.2 1 hour after CPB: 5.35 +/- 2.9 nmol/L vs 14.5 +/- 23.1 nmol/L; D-dimer 1 hour after CPB: 0.63 +/- 0.6 ng/mL vs 2.3 +/- 3.1 ng/mL; p < 0.05), inflammatory markers (interleukin [IL]-6, IL-8, IL-10) increased over time without significant differences between the groups, and only complement C3a activation was significantly attenuated at the end of CPB in the aprotinin group. Chest tube drainage was significantly reduced (24 hours: median 13.5 [IQR 12.2] mL/kg vs 19.4 [8.2] mL/kg; p < 0.05). All patients received one unit of packed cells to prime the heart lung machine. A second unit was needed significantly less often in the aprotinin group (13% vs 47%; p < 0.05). Postoperative oxygenation (pO2/FIO2 172 [IQR 128] mm Hg vs 127 [74]; p < 0.05) improved, and the time on ventilator was shorter in the aprotinin group (median 45 hours [IQR 94] vs 101 [IQR 74]; p < 0.05). No side effects were attributable to the use of aprotinin. CONCLUSIONS: High-dose aprotinin effectively attenuated hemostatic activation and reduced blood loss and transfusion requirement in pediatric cardiac surgery. Postoperative ventilation was also shortened in the aprotinin group.     

Effective Use of Heparin-Bonded Circuits and Lower Anticoagulation for Coronary Artery Bypass Grafting in Jehovah's Witnesses

A bstract Despite many advances in blood conservation techniques, a significant proportion of patients undergoing primary coronary revascularization still require homologous transfusions. Based on a large clinical experience with high-risk patients during coronary artery bypass, a comprehensive strategy to diminish perioperative blood loss was developed by integrating many individual components. An integral component in this strategy is the use of lower heparinization (activated clotting time [ACT] > 280 sec) in conjunction with "tip-to-tip" heparin-bonded cardiopulmonary bypass (CPB) circuits (HBC). This technique was prospectively applied to a group of Jehovah's Witnesses (JW) patients who refuse blood transfusion on religious grounds (n = 9). Outcome was compared to a matched group of patients treated with full heparinization (ACT > 480 sec) used with conventional, nonheparin-bonded CPB circuits (NHBC) performed within the same academic year (n = 455). There were no complications in JW patients who had a significantly lower mediastinal and pleural tube output in the first 24 hours (323 67 mL vs 984 616 mL, p < 0.01). In comparison to JW patients who received no transfusions, 68.1% of patients treated with NHBC were transfused (p 0.0001). In summary, HBC in conjunction with lower anticoagulation was effectively and safely applied to JW patients undergoing coronary artery bypass grafting. This technique should be considered for broader clinical use.     

The efficacy of low prime volume completely closed cardiopulmonary bypass in coronary artery revascularization.

PURPOSE: This study was conducted to evaluate and demonstrate the efficacy of low prime volume completely closed cardiopulmonary bypass (LPVP) in arrested coronary artery bypass grafting (CABG). We improved the percutaneous cardiopulmonary support (PCPS) circuit to reduce the deleterious effects of cardiopulmonary bypass (CPB). METHODS: Between April 1999 and May 2003, among 228 isolated CABG procedures, 47 procedures using LPVP (group L) and 86 procedures using standard prime volume open CPB (group S) were compared. The LPVP priming volume was 590 mL; the circuit was completely closed with a soft reservoir. Cardiac arrest was obtained by warm blood cardioplegia. RESULTS: The following average values were obtained: packed red blood cell transfusions, 0.88 +/- 1.4 U (group L) vs. 2.1 +/- 2.5 U (group S); intraoperative lowest hematocrit value, 28.7 +/- 4.6% (group L) vs. 22.4 +/- 3.3% (group S); blood loss over first 24 hours, 439 +/- 242 mL (group L) vs. 599 +/- 409 mL (group S); ventilation time, 5.1 +/- 3.1 hours (group L) vs. 10.4 +/- 14.9 hours (group S). CONCLUSION: Compared to standard prime volume open CPB, LPVP resulted in fewer deleterious operative effects. Less blood loss, fewer blood transfusions, and earlier patient recovery was noted with LPVP. Thus, LPVP is a very efficient form of CPB.     

Intraoperative use of platelet-plasmapheresis in vascular surgery

STUDY OBJECTIVE: To determine, in a pilot study, whether pheresis of plasma and platelets before surgical blood loss, with reinfusion of the autologous plasma and platelets after completion of the aortic reconstruction, will result in decreased bleeding and decreased transfusion of allogenic blood components in patients undergoing elective aortic reconstruction. DESIGN: Randomized study. SETTING: University medical center. INTERVENTIONS: Patients were randomized to perioperative (acute) platelet plasmapheresis (APP group) versus conventional blood component therapy (control group). In the APP group, blood was withdrawn after induction of anesthesia, to sequester approximately 300 mL of platelet rich plasma (PRP); platelet poor plasma (PPP) and red blood cells (RBC) were sequestered as well. An autotransfusion device was used to collect and re-infuse autologous RBC during the course of the operation in both groups. After completion of the aortic reconstruction, autologous PRP and PPP were re-infused in the APP group. Blood loss, volume of blood component transfusions, and preoperative and postoperative hemoglobin (Hb), hematocrit (Hct), platelet, international normalized ratio (INR), and activated partial thromboplastin time (aPTT) were recorded. MEASUREMENTS AND MAIN RESULTS: There was no difference between groups in demographics, preoperative laboratory values, or surgical procedures, although more patients were treated for aneurysms (73% vs. 60%) and fewer for occlusive disease (20% vs. 40%) in the control versus APP group. Also, there were no differences between the control and APP groups in duration of operation, blood loss, volume of colloid infused, or volume of allogenic RBC and plasma transfused. Patients in the APP group received a greater volume of crystalloid solution (9.1 +/- 3.4 L vs. 6.8 +/- 3.0 L; p = 0.002), but fewer units of allogenic platelets than the control group (0.7 +/- 1.0 units vs. 0.2 +/- 0.4 units; p < 0.04). There were no differences in postoperative Hb, Hct, INR, aPTT, or fibrinogen. The platelet count was lower in the APP group than in the control group (123 +/- 40 x 10(3)/mm(3) vs. 182 +/- 51 x 10(3)/mm(3); p = 0.004). CONCLUSIONS: Perioperative platelet plasmapheresis led to fewer allogenic platelet transfusions in patients undergoing elective aortic reconstruction. However, there was no decrease in blood loss and no reduction in transfusion of allogenic RBC or plasma. Perioperative platelet plasmapheresis is not recommended for routine use in elective aortic reconstruction.     

Effect of polymer coating (poly 2-methoxyethylacrylate) of the oxygenator on hemostatic markers during cardiopulmonary bypass in children

OBJECTIVE: Heparin and other oxygenator coatings have been used in attempts to reduce hemostatic activation during cardiopulmonary bypass (CPB). This study evaluated whether an oxygenator coated with poly 2-methoxyethylacrylate (PMEA) (X-coating; Terumo Corporation, Tokyo, Japan) would cause less activation of coagulation and fibrinolytic systems during CPB in children than a noncoated oxygenator. DESIGN: Observational study. SETTING: University-affiliated children's hospital. PATIENTS: Twenty-six patients, 3 months to 5 years old, who underwent congenital heart surgery for repair of a ventricular septal defect, atrial septal defect, or both. INTERVENTIONS: Patients were divided into 2 age-matched groups based on the type of oxygenator used: a noncoated oxygenator (group NC) versus a PMEA-coated oxygenator (group C). MEASUREMENTS AND MAIN RESULTS: Blood samples for coagulation and fibrinolytic markers were compared before, during, and after CPB. Despite increases in thrombin generation markers (F1.2 and TAT) at certain times during CPB in group C compared to group NC, a comparison over all times during CPB were not statistically different between groups. Overall D-dimer concentrations during CPB were elevated in group C compared to group NC (p = 0.02). Active tPA and active PAI-1 were not different between groups during or after CPB. Group C had higher platelet counts (181,000 +/- 29,000) during CPB than group NC (155,000 +/- 57,000, p = 0.04) but not postoperatively. Twelve hours postoperatively, chest tube outputs were 8.8 +/- 3 mL/kg in group C and 19.1 +/- 12 mL/kg in group NC (p = 0.003). The corresponding outputs 24 hours after surgery were 12.4 +/- 3 mL/kg and 24 +/- 11 mL/kg, respectively (p = 0.005). CONCLUSIONS: Except for a somewhat higher platelet count during CPB, there was no indication that PMEA coating resulted in less activation of coagulation and fibrinolytic systems. The lower postoperative chest tube output observed after CPB with PMEA-coated oxygenators needs to be studied further.     

Low-dose aprotinin is ineffective to treat excessive bleeding after cardiopulmonary bypass

BACKGROUND: Uncontrolled clinical experience at our institution suggested that low-dose aprotinin could control excessive bleeding after cardiopulmonary bypass (CPB). A randomized clinical trial was conducted to determine the efficacy of low-dose aprotinin in the treatment of hemorrhage after cardiac surgery. METHODS: One hundred seventy-one patients undergoing cardiac surgery with CPB were included. Forty-four patients (26%) bled significantly in the intensive care unit (>100 mL/h) and received either aprotinin (200,000 KIU bolus + 100,000 KIU/h for 8 hours) or placebo in addition to our standard management of excessive bleeding. RESULTS: Median bleeding before study drug administration was not different between aprotinin (200 mL) and placebo (212.5 mL) groups. Bleeding decreased significantly with time and similarly in both groups. Ninety-five percent of patients required transfusions in both groups. Median blood products transfused were 13 and 8 units per patient in the aprotinin and placebo groups respectively (p = NS). CONCLUSIONS: Routine administration of low-dose aprotinin as part of the treatment protocol to control hemorrhage after CPB does not reduce bleeding or transfusion requirements and, therefore, cannot be recommended.     

Preoperative administration of steroids: influence on adhesion molecules and cytokines after cardiopulmonary bypass

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with tissue damage mediated by adhesion molecules and cytokines. Prebypass steroid administration may modulate the inflammatory response, resulting in improved postoperative recovery. METHODS: Fifty patients undergoing elective coronary operations under normothermic CPB were randomized into two groups: group A (n = 24) received intravenous methylprednisolone (10 mg/kg) 4 hours preoperatively, and group B (n = 26) served as controls. Cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin-2R [IL-2R], IL-6, IL-8), soluble adhesion molecules (sE-selectin, sICAM-1), C-reactive protein, and leukocytes were measured before steroid application, then 24 and 48 hours, and 6 days postoperatively. Adhesion molecules were measured by enzyme-linked immunosorbent assay, cytokines by chemiluminescent immunoassay. Postoperatively, hemodynamic measurements, inotropic agent requirements, blood loss, duration of mechanical ventilation, and intensive care unit stay were compared. RESULTS: Aortic cross-clamp and CPB time was similar in both groups. Prednisolone administration reduced postoperative levels of IL-6 (611 versus 92.7 pg/mL; p = 0.003), TNF-alpha (24.4 versus 11.0 pg/L, p = 0.02), and E-selectin (327 versus 107 ng/mL, p = 0.02). Postoperative recovery did not differ between groups. CONCLUSIONS: Preoperative administration of methylprednisolone blunted the increase of IL-6, TNF-alpha, and E-selectin levels after CPB but had no measurable effect on postoperative recovery.     

Hemostatic effects of aprotinin, tranexamic acid and ε-aminocaproic acid in primary cardiac surgery

Background. The effects of ε-aminocaproic acid (EACA) and tranexamic acid (TA) on bleeding and allogeneic transfusions, and the cost of pharmacological and transfusional treatment were compared to aprotinin (AP).

Methods. We randomized 210 patients subjected to elective cardiac surgery. Of these, 68 patients received EACA (a bolus of 5 g, an infusion of 2 g/h, and 2.5 g in the priming), 72 patients received TA (a bolus of 1 g, an infusion of 400 mg/h, and 500 mg in the priming), and 70 patients received AP (a bolus of 280 mg, an infusion of 70 mg/h, and 280 mg in the priming). Postoperative blood loss and homologous transfusions were collected and the cost of pharmacological treatment and homologous transfusions were calculated.

Results. Bleeding but not allogeneic transfusions was significantly higher in the EACA group (467 ± 234 versus TA, 311 ± 231 versus AP, 283 ± 233; p < 0.001). Costs of pharmacological and transfusional treatment were significantly lower in the TA group ($58.10 ± $105.10) versus the EACA group ($100.70 ± $158.60) versus the AP group ($432.60 ± $118.70) (p < 0.0001).

Conclusions. Compared to AP, TA has the same effects on bleeding and transfusions, but with a significant reduction of costs. Patients treated with EACA showed a significantly higher postoperative bleeding with an increased trend of transfusion requirement.     

Aminocaproic Acid (Amicar) as an Alternative to Aprotinin (Trasylol) in Liver Transplantation

Introduction

This study compared clinical outcomes for a large number of liver transplant patients receiving intraoperative epsilon-aminocaproic acid (EACA), aprotinin, or no antifibrinolytic agent over an 8-year period.

Patients and Methods

Records for deceased donor liver transplants were reviewed. Data included antifibrinolytic agent, blood loss, early graft function, and postoperative complications. Study groups included low-dose aprotinin, high-dose aprotinin, EACA (25 mg/kg, 1-hour infusion), or no antifibrinolytic agent.

Results

Data were included for 1170 consecutive transplants. Groups included low-dose aprotinin (n = 324 [28%]), high-dose aprotinin (n = 308 [26%]), EACA (n = 216 [18%]), or no antifibrinolytic (n = 322 [28%]). EACA had the lowest intraoperative blood loss and required the fewest transfusions of plasma. Patients receiving no agent required the most blood transfusions. Early graft loss was lowest in the EACA group, and 90-day and 1-year patient survival rates were significantly higher for the low-dose aprotinin and EACA groups according to Cox regression. Complications were similar, but there were more episodes of deep vein thrombosis in patients receiving EACA.

Conclusions

These results suggest that transitioning from aprotinin to EACA did not result in worse outcomes. In addition to decreased intraoperative blood loss, a trend toward improved graft and patient survival was seen in patients receiving EACA.