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Ann Thorac Surg 2000;69:808-816
© 2000 The Society of Thoracic Surgeons
a Department of Anesthesia, Sunnybrook and Women’s College Health Science Center, University of Toronto, Toronto, Ontario, Canada
b Division of Cardiovascular Surgery, Sunnybrook and Women’s College Health Science Center, University of Toronto, Toronto, Ontario, Canada
c Department of Clinical Perfusion, Sunnybrook and Women’s College Health Science Center, University of Toronto, Toronto, Ontario, Canada
Address reprint requests to Dr Wong, M3–200, Department of Anesthesia, Sunnybrook and Women’s College HSC, 2075 Bayview Ave, Toronto, ON, Canada M4N 3M5
e-mail: bill.wong{at}utoronto.ca
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Abstract |
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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.
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Introduction |
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The nonendothelial surfaces of the cardiopulmonary bypass (CPB) circuit cause contact activation of the coagulation cascades and of platelets, despite the use of heparin. Thus, CPB is associated with several alterations in the hemostatic mechanisms including: (1) increased fibrinolysis; (2) decreased platelet numbers and function; (3) dilution of clotting factors; and (4) the residual effects of heparin or excess protamine [1]. All patients will lose some blood during and after CPB, and many patients will not require blood transfusions with presently employed blood conservation techniques. However, some patients or operations are at an increased risk for allogeneic transfusions, because of excessive bleeding perioperatively. The risk factors include: (1) repeat cardiac operation; (2) complex procedures, such as multiple valve replacements or aortic arch repairs; and (3) procedures requiring long CPB times, such as combined procedures (valve replacement plus myocardial revascularization) [2]. These patients will benefit the most from the use of pharmacological agents to reduce bleeding.
Pharmacological agents to reduce bleeding have recently gained much interest, since they are readily available, easy to administer, can be used prophylactically, do not require the use of costly equipment, and appear to be very safe and efficacious. The perioperative use of tranexamic acid, 
-aminocaproic acid, and aprotinin have gained acceptance around the world for the prophylactic reduction of allogeneic blood transfusions in cardiac operation patients. Tranexamic acid and -aminocaproic acid are synthetic lysine analogue antifibrinolytics. Tranexamic acid was chosen for this study because it has been more extensively studied in the cardiac operation population. It competitively inhibits the activation of plasminogen to plasmin, and is also a weak noncompetitive inhibitor of plasmin, blocking its action on fibrin. Thus, tranexamic acid is thought to act by preventing the premature dissolution of the normal fibrin clot. It is also possible that tranexamic acid may help to preserve platelet function, by reducing the effect of plasmin on platelet membrane receptors [3]. Aprotinin forms reversible dose-dependent enzyme-inhibitor complexes of proteolytic enzymes, including human trypsin, plasmin, and kallikrein. Thus, it also has an antiplasmin effect, like the antifibrinolytics, inhibiting fibrinolysis and preserving platelet function. However, there may be other beneficial effects such as an antikallikrein effect, which may inhibit the contact phase of coagulation, diminishing the generation of thrombin [3]. Because of its varying actions on different enzyme systems, its exact mechanism(s) of action are still not entirely clear.
Both aprotinin and tranexamic acid appear to be efficacious in reducing blood loss after cardiac operations [4]. Aprotinin is more extensively reported in the literature for all patient subsets. It appears more efficacious in attaining the goal of reducing allogeneic transfusion requirements in the population at risk, while the efficacy of tranexamic acid in high and low-risk populations has more recently been confirmed in the literature [5]. Fortunately, the incidence of complications, such as graft thrombosis leading to myocardial infarction, stroke, renal dysfunction, and allergic reactions is low [6]. There is evidence that the hypercoagulable effects of aprotinin or tranexamic acid may be related to patient risk factors, inadequate anticoagulation, protamine reversal syndrome, and the use of these drugs in the postoperative time frame. Cost is another factor to consider; aprotinin is over three times more expensive than tranexamic acid (CAN$930.00 vs CAN$277.50 per patient). This study will try to determine which drug is the most efficacious. If tranexamic acid can reduce bleeding to the same extent as aprotinin, then it would it would make economic sense to use the less costly drug therapy.
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Patients and methods |
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= 0.05 two-sided test) to detect clinically significant endpoints (200 mL difference in postoperative chest tube blood loss or the transfusion of 2 units of packed red blood cells). A total sample of 80 patients was chosen, to ensure enough patients complete the protocol. The procedures included repeat cardiac operations (aortocoronary bypass [ACB] or valvular operations), combined procedures (valvular operation plus ACB), and other complex procedures (multiple valve replacement, ascending aortic graft). Subjects were excluded if they had recent (< 5 days) acetylsalicylic acid ingestion, thrombolytic therapy (streptokinase, urokinase, or tissue plasminogen activator < 1 day) or anticoagulant therapy (heparin < 4 hours preoperative or warfarin < 3 days preoperatively). As well, subjects with preexisting coagulation defects (including abnormal preoperative coagulogram [prothrombin time (PT) > 18 seconds or partial prothrombin time (PTT) > 50 seconds] or platelet count < 100 x 109/L), preexisting renal dysfunction (serum creatinine > 200 mmol/L), or had autologous predonation of blood, were excluded from the study. Consenting subjects were randomized (double-blinded) to receive either high-dose aprotinin (AP group) or high-dose tranexamic acid (TA group).
Drug administration
The randomization and preparation of the study drugs was performed by the hospital’s department of pharmacy. There was no attempt to stratify the randomization process. The high-dose aprotinin regimen [7] included intravenous infusion of 2 x 106 kallikrein inhibitory units (KIU) of aprotinin-Trasylol ([Bayer AG; Leverkusen, Germany], 10,000 KIU/mL of pure aprotinin in a preservative-free isotonic solution) infused over 20 minutes, after induction of anesthesia and before skin incision. Subsequently, 5 x 105 KIU/h of aprotinin were administered continuously throughout the operation, until skin closure. Additionally, aprotinin (2 x 106 KIU) was added to the priming solution of the CPB circuit. Tranexamic acid was administered as an intravenous bolus dose of 10 g tranexamic acid-Cyklokapron ([Pharmacia & UpJohn Inc, Missisgauga, Ontario, Canada], 0.1 g/mL tranexamic acid) over 20 minutes, after induction of anesthesia and before skin incision [8]. No further tranexamic acid was used, but placebos consisting of 0.9% normal saline solution were used for the continuous infusion, and the addition to the CPB prime solution to mimic aprotinin administration. A test dose of the study solution (1 mL) was given to the patient to help detect any allergic responses before the initial loading dose was given. The prime dose was not added to the CPB prime solution until after the patient safely received the initial loading dose of the study drug.
Anesthetic, surgical, and CPB management
The anesthetic protocol consisted of intravenous fentanyl citrate, midazolam, and pancuronium bromide. Following tracheal intubation, anesthesia was maintained with halothane or isoflurane. The subjects were ventilated to normocapnia with a 50% oxygen/air mixture. Conduct of the operation was carried out in accordance with the usual protocols of the participating surgeons. Exposure was provided by a median sternotomy, and extracorporeal circulation lines consisted of aortic arch and atrial cannulas. A Cobe heart-lung machine (Cobe Cardiovascular Inc, Arvada, CO) with Bentley (Baxter Healthcare Corp, Bentley Laboratories Division, Irvine, CA) tubing and reservoirs were used for CPB, including membrane oxygenators (Maxima Hollow Fiber Oxygenator; Medtronic Blood Systems, Inc, Anaheim, CA) and in-line arterial line filters (Bard H-645 with Biothyl; C. R. Bard, Inc, Murray Hill, NJ). Circuit prime consisted of 1500 mL lactated Ringer’s solution, 100 mL 25% albumin, 25 g mannitol, 50 mEq sodium bicarbonate, and 5000 units heparin sodium. Priming solution was precirculated through a 5 µm prebypass filter (Bentley) before cannulation. CPB was employed with core temperatures of 27° C to 33° C. Nonpulsatile flows of 2.4 L/min/m2 were used at normothermia, and were no lower than 1.8 L/min/m2 at 28° C. Mean arterial pressure was maintained between 50 and 80 mm Hg. Oxygen inflow of 2 to 5 L/min was adjusted for normal oxygenation and alpha-stat acid-base balance.
The study did not intend for the inclusion of cases with deep hypothermic circulatory arrest (DHCA). The procedures did include repairs of the ascending aorta, with or without aortic valve replacement. These cases generally do not employ DHCA at our institution. However, one mitral valve replacement (MVR) with ACB procedure required DHCA, because of an aortic tear secondary to aortic cannulation. This patient (TA group) required DHCA to urgently replace the ascending aorta with a graft. Circulatory arrest lasted 8 minutes at a temperature of 26 °C. This patient was classified as an aortic operation case. Another aortic valve replacement-ascending aortic graft (AP group) required a short (36 second) period of circulatory arrest at 20° C. The other 4 cases, involving the ascending aorta, were performed under moderate hypothermic CPB without circulatory arrest.
Patients were anticoagulated pre-CPB with 300 IU/kg heparin sodium ([Hepalean; Organon Teknika, Toronto, Canada], 1,000 USP U/mL of heparin sodium from porcine intestinal mucosa in 1% benzyl alcohol as preservative in an isotonic aqueous solution), supplemented with 50 to 100 IU/kg as needed, to maintain an activated clotting time (ACT) of greater than 400 seconds during CPB (HemoTec kaolin activator [HemoTec, Inc, Englewood, CO]; note: aprotinin is reported to prolong the ACT, but this effect is felt to result from the use of celite-activated assays and not kaolin-activated test tubes) [9]. Heparin neutralization after termination of CPB was by slow intravenous injection of protamine sulfate ([Lyphomed Canada Inc, Markham, Canada], 10 mg/mL protamine sulfate in preservative free isotonic solution) at a dose of 1 mg/100 IU of estimated active heparin. ACT after protamine administration was monitored with the goal to return to near preheparinization levels (not greater than 10% above baseline).
Blood transfusion protocol
Blood conservation methods used include reinfusion of shed cardiotomy blood during CPB, and autotransfusion of salvaged mediastinal-shed blood for the first 6 hours postoperatively. Blood product transfusion guidelines were used to standardize transfusion practice. Some latitude in the decision to give transfusion products was allowed, since it is often not clinically practical to wait for laboratory tests when a patient is hemorrhaging. During the operation, packed red blood cell (PRBC) concentrates were transfused when the hematocrit/hemoglobin (Hct/Hb) value was less than 0.20/70 g/L. In the postoperative intensive care unit (ICU), the threshold for PRBC transfusion was a Hct/Hb less than 0.25/80. The indication for perioperative random donor platelets, fresh frozen plasma, or cryoprecipitate transfusion was the presence of excessive active bleeding (> 200 mL/h), and a laboratory demonstrated coagulation defect (platelet count < 100 x 109/L, PT or PTT > 1.5 x control value, or fibrinogen level < 1.0 g/L).
Postoperative intensive care
With the exception of protamine to reverse the action of heparin, the nonstudy postoperative use of additional pharmacologic agents to reduce bleeding (antifibrinolytics: aprotinin, tranexamic acid, -aminocaproic acid; coagulation factor enhancers: desmopressin acetate; or agents to preserve platelet function: prostaglandins [PGE1 or PGI2]) were avoided for the first 24 hours in the study. The routine immediate postoperative use of low-dose acetylsalicylic acid (325 mg orally per day) for the protection of ACB graft patency, and low dose intravenous heparin (PTT < 40) for antithrombotic protection of valve prostheses continued, as per usual protocol, when chest tube bleeding had diminished. Full therapeutic anticoagulation (heparin and/or warfarin) for mechanical prosthetic valves was instituted after chest tube removal at 24 to 36 hours postoperatively. In addition, the use of low dose (6 mg/h) intravenous dipyridamole (Persantine; Boehringer Ingelheim (Canada) Ltd, Burlington, Ontario, Canada) to promote arterial patency after coronary endarterectomy was instituted during the operation when indicated.
Data collection
Postoperatively, blood loss from the mediastinal chest tubes was reported at 6, 12, and 24 hours from the time the patient arrived in the ICU. In addition, the volume of autotransfused blood in the first 6 hours was recorded. Blood product transfusion requirements were documented (by type and donor unit exposure) for the entire hospital stay. Hematological and biochemical studies were monitored in the perioperative period. Perioperative events that were noted included perioperative myocardial infarction (new Q-waves on electrocardiogram and elevation of creatinine kinase MB isoenzyme/total creatinine kinase (CK) ratio > 5%), strokes (neurologic examination), reoperation for bleeding, and the surgical diagnosis discovered at reoperation (surgical bleeding, leaking anastomoses; medical bleeding, coagulopathy).
Statistics
Data was analyzed with commercially available software (JMP, SAS Institute Inc; SPSS, SPSS Inc, Chicago, IL). A two-sidedt-test was used to test normally distributed variables. A nonparametric test (Wilcoxon two-sample test) was used on blood transfusion data. The frequency of transfusion was compared with a 
2 test or Fisher’s exact test for small sample sizes. All results are expressed as mean and standard error of the mean, unless otherwise stated. Multiple regression analysis (backwards elimination) was performed to determine if any patient or surgical variables (age, drug group, CPB time, CPB temperature, procedure, and surgeon) impacted on the primary endpoints (blood loss, blood transfusions) of the study.
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Results |
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Only one patient (AP group), who underwent a combined ACB and valve replacement procedure, required reoperation for surgical bleeding. There was no statistically significant difference between the two treatment groups with respect to complications (PMI, stroke, death), 6, 12, or 24 hour chest tube blood loss, blood transfusions up to 24 hours postoperatively, total allogeneic blood transfusions for entire hospital stay, or induction/postoperative hemoglobin levels (Tables 2–4) .
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Multiple regression analysis also revealed that CPB time had a significant effect on 12 and 24 hour blood loss in patients who received tranexamic acid (p = 0.002, p = 0.001 respectively), but not in those who received aprotinin (p = 0.441, p = 0.423 respectively). The p value for the drug-by-CPB time interaction for the 12 and 24 hour blood loss was 0.033 and 0.026, respectively. Linear regression analysis revealed a positive relationship between the 24 hour blood loss and CPB time in the tranexamic acid group (p = 0.0037, analysis of variance), unlike the aprotinin group where 24 hour blood loss is independent of CPB time (p = 0.33, analysis of variance). Further multiple regression analysis did not find any significant interaction between blood loss/transfusions and other variables such as age, gender, surgeon, surgical procedure, preoperative hemoglobin or CPB temperature.
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Comment |
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-aminocaproic acid [4–8, 10] have been shown to reduce blood loss after cardiac operations, when compared to placebo control groups. The use of tranexamic acid in cardiac operations has been reported in more randomized trials than -aminocaproic acid, thus tranexamic acid was chosen as the synthetic antifibrinolytic to compare against aprotinin. Also, a placebo control group was not used for this study since the efficacy of the drugs has been established in the literature. The cost of prophylactic therapy and the incomplete safety data for these drugs [11], has reserved the use of these drugs for high-risk procedures/patients in our institution. The high dose regimens described for these drugs [7, 8] were used to affect a maximum benefit, since these patients are at a higher risk for blood loss. The goal of this study was to determine if either aprotinin or tranexamic acid (in high doses) was more efficacious in reducing blood loss and allogeneic transfusion requirements in high transfusion risk cardiac operation patients.
In the total patient group analysis, the amount of shed mediastinal blood compares favorably with our meta-analysis of previously published studies [4]. The 12 hour chest tube blood loss (mean ± standard error of the mean) in all patients of our study was only 443 ± 36.3 mL, compared to means of 698 to 770 mL in the placebo groups of the meta-analysis. The aprotinin and antifibrinolytic (tranexamic acid or -aminocaproic acid) treatment groups in the meta-analysis did have this amount of blood loss (446 mL, 526 mL, respectively). When one also considers that most of the studies in the meta-analysis were not in the high-risk complex operation category, our results certainly appear to be in line with the expected results with prophylactic antifibrinolytics in cardiac operation. The average duration of CPB in this study (162 ± 5.2 minutes) is much longer that that for routine ACBs (80 to 100 minutes), and this length of CPB contributes to the patient’s risk of postoperative bleeding [2]. Remarkably, only 1 patient (1 of 76, 1.3%) returned to the operating room for postoperative hemorrhaging, similar to the reoperation event rate revealed in the meta-analysis (0.44% to 1.47% in the drug treatment groups).
Multiple regression analysis of chest tube blood loss versus CPB time, reveals a positive relationship between blood loss and CPB time in patients who received tranexamic acid. This trend is not seen in the patients who received aprotinin. Also, the linear regression models for the tranexamic acid is significantly different from a horizontal line at the mean (p < 0.01; analysis of variance). The fact that this trend is only seen in patients who received tranexamic acid suggests that the overall effectiveness of the medication (when only given as a bolus at the beginning of the procedure) may be decreased when CPB is prolonged. Aprotinin is given as a bolus and an infusion, thus compensating for long CPB times. Perhaps, if the tranexamic acid were also given as an infusion, this would help maintain its efficacy for long CPB times. Is it possible that aprotinin given in a high dose regimen is more protective for long CPB times than a single bolus of tranexamic acid? In addition, patients undergoing repeat sternotomy may have a longer period of time between the delivery of the drug and the start of CPB, since the opening of the chest is more tedious secondary to adhesions from the previous sternotomy. Further studies of the pharmacokinetics of these drugs will enable more accurate dosing of the medication to allow for long CPB times.
A power analysis was performed to determine if the study sample had enough power to detect differences in clinically important outcomes. For postoperative blood loss, a difference of at least 200 to 300 mL would be more clinically relevant than a 100 mL difference, since the larger amount may influence decisions to give transfusions or drug therapy. Also, a reduction in the use of PRBCs in the first 24 hours after operation by two units would certainly be clinically important. The patient’s preoperative hemoglobin level may influence the need for one unit of blood perioperatively. Our power calculations (Table 5) demonstrate that there is sufficient power [(1 - ß) > 0.80] to detect a 209 mL blood loss difference at 12 hours and 267 mL blood loss difference at 24 hours in the total group (significance level of = 0.05, two-sided test). Also, there is sufficient power to detect a 1.43 unit difference in the transfusion of PRBCs in the total study. Since our study did not find any significant differences in blood loss or transfusion needs between the two drug groups (small deltas), the power analysis reassures us that clinically important outcomes were not missed by insufficient sample size.
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-aminocaproic acid) (Table 6). The variation in patient population and drug dosages complicates direct comparisons between studies. As expected, most studies did find that aprotinin (11 out of 11), tranexamic acid (4 out of 7), or -aminocaproic acid (2 out of 2) reduced postoperative blood loss when compared to available placebo controls. Only about a third of the studies (5 out of 14) [18, 21, 25, 26, 28] found aprotinin to be superior to tranexamic acid or -aminocaproic acid in reducing postoperative blood loss. Interestingly, none of the studies were able to demonstrate a clear superiority of any of these drugs in reducing the average transfusion requirements. The study by Landymore and colleagues [25] did find that the aprotinin and -aminocaproic acid groups had significantly lower blood transfusions than the tranexamic acid group. Interestingly, only 2 out of 6 studies [19, 26], which reported the data, found aprotinin to be significantly superior to tranexamic acid or -aminocaproic acid in reducing the proportion of patients who required transfusions.
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-aminocaproic acid.
With such a minimal benefit and a large price differential, many centers are using the less expensive drugs for patients at risk. The cost of aprotinin is so large (
CAN$1000, compared to tranexamic acid CAN$100 to CAN$275, and -aminocaproic acid CAN$50), that direct recovery of its cost by reducing blood transfusions is difficult [12]. One of the problems is actually the unnecessary blood transfusions that 27% of patients receive [13]. A recent publication has revealed that the cost per unit of allogeneic blood for inpatient red blood cell transfusion is CAN$210 [14]. This includes the cost of collection, production, distribution, and delivery. However, one must remember that the cost of bleeding includes not only the cost of drug/transfusion therapy, but also the materials and manpower costs of reoperations, prolonged intensive care, and the treatment of complications of large volume allogeneic blood product transfusions. Other problems will always exist in conjunction with blood product transfusions: a limited supply; need for cross-matching; ABO blood group compatibility error; septic unit transfusion; alloimmunization; possible immunosuppression; dilutional coagulopathy; and a short shelf life. These costs are enormous (reported as high as CAN$60,000) in comparison to the cost of the drug therapy [13]. Fortunately, these complications are infrequent, so the added costs are spread out among a large number of patients. Thus by reducing blood transfusions, one can easily realize an economical benefit, better patient care, and reduced stress on a valuable and chronically short-supplied blood banking system.
One cannot discuss the benefits of these hemostatic drugs without discussing their potential risks. It would seem logical that along with increased efficacy, there may be increased thrombotic risk. A large multicenter, randomized, placebo controlled study was commissioned by Bayer to answer the question of early graft occlusion with aprotinin therapy. Alderman and colleagues [15] reported the results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial which involved 13 international sites and enrolled 870 patients in 1994 to 1995. Among 703 patients with assessable saphenous vein grafts, occlusions occurred in 15.4% of aprotinin-treated patients and 10.9% of the placebo group (p = 0.03). The occlusion rate of distal saphenous vein grafts was 7.5% (897 saphenous vein graft insertions studied) in the aprotinin group versus 4.8% (837 studied) in the placebo group (p = 0.02). The conclusion by the authors was that early vein graft occlusion was increased by aprotinin, but this outcome was promoted by multiple risk factors for graft occlusion (mainly small or poor distal vessel quality).
The synthetic antifibrinolytics have not been studied as intensely as aprotinin, but the question of graft thrombosis is just as pertinent. Recently, Karski and associates [16] presented an abstract on their experience with tranexamic acid. They assessed early saphenous vein graft patency (5 to 30 days) with cine magnetic resonance imaging techniques in 146 patients randomized to receive tranexamic acid (n = 76) versus placebo (n = 70). The saphenous vein graft patency was 85.1% in the tranexamic acid group versus 86.3% in the placebo group (clearly no difference but a relatively high graft occlusion rate). In terms of blood sparing effect, 14.3% of the tranexamic acid group required red blood cell transfusions versus 24.0% of the placebo group (p < 0.05). Unfortunately, this study did not use angiography, which is considered the gold standard for patency trials. However, at least there is no early evidence that high dose tranexamic acid is causing harm when given prophylactically (100 mg/kg). Earlier aprotinin trials with ultra-fast computed tomographic or magnetic resonance imaging studies also did not show any difference with graft patency (small groups also). It took a large, multicenter, angiography trial (IMAGE) to show that there can be an increase in graft occlusions when patients receive aprotinin.
As Westaby and Katsuma [17] pointed out in an editorial, "occluded [coronary artery bypass grafts] are a high price to pay for an average blood saving of 250 mL." In the preoperative and postoperative period, we are obsessed with the use of platelet inhibitors and anticoagulants to treat patients with acute coronary ischemia, prosthetic valve implantation, and after ACB operation to promote graft patency. Yet in the operating room, with the onslaught of surgically induced thrombin formation, we are using agents which may combat physiologic fibrinolysis, a vital process to maintain vessel patency. In addition, we are giving agents that promote platelet adhesion and aggregation. A balance must be reached with these two opposing goals. Routine use of these hemostatic agents may lead to an increase in adverse events. A more logical approach may be to reserve these pharmacologic therapies to patients who are at high risk for transfusions, and thus may receive the most benefit at the lowest risk. The recent public scrutiny of Canada’s blood system has certainly increased interest in alternatives to allogeneic blood product transfusions to decrease the risk of transfusion-born infectious diseases. However, like any other therapy, there may be significant risks.
Our report utilized a high-risk group of patients to compare the efficacy of two blood-sparing drugs (aprotinin and tranexamic acid). Patients who are at risk of greater blood loss after cardiac operation have a greater potential to benefit from prophylactic pharmacologic treatment. Aprotinin and tranexamic acid had similar efficacies in reducing blood loss and blood transfusions for our group of high transfusion risk cardiac procedures.
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Acknowledgments |
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-aminocaproic acid in patients having repeated cardiac operations. Anesthesiol 1997;87:1373-1380.[Medline]
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M. A. Bedirhan, A. Turna, N. Yagan, and O. Tasci Aprotinin reduces postoperative bleeding and the need for blood products in thoracic surgery: results of a randomized double-blind study Eur. J. Cardiothorac. Surg., December 1, 2001; 20(6): 1122 - 1127. [Abstract] [Full Text] [PDF]
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