Tranexamic acid and early saphenous vein graft patency in conventional coronary artery bypass graft surgery: a prospective randomized controlled clinical trial

OBJECTIVE: Use of antifibrinolytic agents reduces the risk of bleeding and decreases the need for blood product use in patients undergoing cardiac surgery. The purpose of this study was to determine whether perioperative use of tranexamic acid decreases the rate of saphenous vein graft patency in the early postoperative period after conventional coronary artery bypass grafting surgery. METHODS: A total of 312 patients scheduled for elective coronary artery bypass grafting surgery with cardiopulmonary bypass were randomized to receive either tranexamic acid 100 mg/kg (n = 147) or placebo (n = 165) in a double-blinded fashion before the initiation of cardiopulmonary bypass. Saphenous vein graft patency was assessed with magnetic resonance imaging 5 to 30 days after surgery. RESULTS: Both groups were comparable with respect to baseline demographic data and surgical characteristics. A total of 237 (76%) patients underwent magnetic resonance imaging assessment. A total of 297 saphenous vein grafts were performed and 253 (85.2%; 95% confidence interval, 83.5%-86.9%) were seen in the tranexamic acid group, and 265 saphenous vein grafts were performed and 231 (87.2%; 95% confidence interval, 85.5%-88.9%) were seen in the placebo group (P = .4969). The blood loss and blood product transfusion rates in the tranexamic acid group were significantly lower than in the placebo group. There was no difference between groups with respect to postoperative morbidity and mortality. CONCLUSIONS: The administration of tranexamic acid before cardiopulmonary bypass did not seem to compromise early venous graft patency rates but reduced perioperative blood product transfusion rates. Consequently, tranexamic acid could be advocated for routine use in patients undergoing conventional coronary artery bypass grafting surgery.     

Prophylactic treatment with desmopressin does not reduce postoperative bleeding after coronary surgery in patients treated with aspirin before surgery

The synthetic vasopressin analog desmopressin has hemostatic properties and may reduce postoperative bleeding after coronary artery bypass grafting (CABG). A study on the effects of recent aspirin ingestion on platelet function in cardiac surgery showed a greater impairment of platelet function in patients treated with aspirin <2 days before the operation. We evaluated the effects of desmopressin on postoperative bleeding in CABG patients who were treated with aspirin 75 or 160 mg until the day before surgery. The study was a prospective, randomized, double-blinded, placebo-controlled, parallel group trial. One-hundred patients were included and divided into two groups. One group received desmopressin 0.3 micro g/kg and the other received placebo (0.9% NaCl) after the neutralization of heparin with protamine sulfate. Postoperative blood loss was recorded for 16 h. The mean (SD) bleeding was 606 (237) mL in the desmopressin group and 601 (301) mL in the placebo group (P = 0.93), representing no significant difference (95% confidence interval, -107 to 117 mL). We conclude that desmopressin does not reduce postoperative bleeding in CABG patients treated with aspirin until the day before surgery. IMPLICATIONS: Continuation of aspirin until the day before coronary artery bypass grafting may increase postoperative bleeding. The administration of desmopressin to these patients after the neutralization of heparin with protamine sulfate does not reduce postoperative bleeding.     

Tranexamic acid reduces bleeding after off-pump coronary artery bypass grafting

AIM: To assess the ability of tranexamic acid, compared with an untreated control group, to decrease bleeding and transfusion requirements in patients undergoing coronary artery bypass grafting on the beating heart. METHODS: Forty-nine randomly selected patients were enrolled to elective coronary artery bypass grafting without the use of cardiopulmonary bypass. Of these, 23 received tranexamic acid (bolus of 1 g before surgical incision, followed by infusion 200 mg/hour during surgery) and 26 patients were enrolled into a control group. Preoperative hematological variables, postoperative blood loss at 4 and 24 hours, transfusion requirements of packed red blood cells,and postoperative thrombotic events such as a myocardial infarction, stroke and pulmonary embolism were recorded. RESULTS: The two groups were similar in terms of patients' characteristics. Postoperative bleeding was significantly lower in the tranexamic acid group compared with the control group (median [25th-75th percentiles]): 115 [92-148] vs 230 [170-260] mL at 4 hours, p<0.001; 420 [330-523] vs 550 [500-650] mL at 24 hours, p<0.01). Transfusion requirements were lower in the tranexamic acid group compared with the control group (RBC 9% vs 28%), but the difference was not statistically significant. Treatment with tranexamic acid was not associated with a higher incidence of myocardial ischemia or other thrombotic events. CONCLUSION: Tranexamic acid reduces postoperative blood loss after coronary artery bypass grafting on the beating heart. Evaluation of transfusion requirements warrants further study.     

Effects of tranexamic acid on postoperative bleeding and related hematochemical variables in coronary surgery: Comparison between on-pump and off-pump techniques

OBJECTIVES: Bleeding and inflammation are major complications of extracorporeal circulation. Off-pump coronary artery bypass grafting may reduce the rate of complications, but it can only be applied in selected cases. Pilot studies have shown a potential benefit from the use of antifibrinolytic drugs, but efficacy in randomized double-blind studies evaluating off- and on-pump coronary artery bypass grafting has not been proved. METHODS: We enrolled 102 patients scheduled for on-pump (n = 51) or off-pump (n = 51) coronary artery bypass grafting. Patients were separately double-blind randomly assigned to treatment with tranexamic acid (1 g as 20-minute bolus before skin incision, followed by continuous infusion of 400 mg/h, with 500 mg added to priming in patients undergoing on-pump coronary artery bypass grafting) or placebo (saline solution of equivalent volume). Bleeding in the first 24 postoperative hours was the primary outcome. Requirement for allogeneic transfusions, thrombotic complications, outcomes, and monitoring of coagulation, fibrinolysis, and inflammation were also recorded. RESULTS: Tranexamic acid reduced total postoperative bleeding by 43% in patients undergoing on-pump coronary artery bypass grafting and by 27% in those undergoing off-pump coronary artery bypass grafting (P <.0001), with 80% reduction in bleeding exceeding 600 mL (P <.001), 58% reduction in the requirement for all allogeneic transfusions (P =.07), and no apparent effect on thrombotic complications or outcome. This was associated with a reduction in plasma D-dimer levels (P <.0001), to a greater degree in patients undergoing on-pump coronary artery bypass grafting (P <.0001), and interleukin 6 levels (P <.0001), to a greater degree in patients undergoing off-pump coronary artery bypass grafting (P <.001). CONCLUSIONS: By affecting fibrinolysis, tranexamic acid significantly reduces bleeding both in off- and on-pump coronary artery bypass grafting and may modulate inflammation in these surgical settings.     

Topical use of tranexamic acid in coronary artery bypass operations: a double-blind, prospective, randomized, placebo-controlled study

OBJECTIVES: We sought to investigate the effect of topical application of tranexamic acid into the pericardial cavity in reducing postoperative blood loss in coronary artery surgery. METHODS: A prospective, randomized, double-blind investigation with parallel groups was performed. Forty consecutive patients undergoing primary coronary surgery were randomly assigned to group 1 (tranexamic acid group) or group 2 (placebo group). Tranexamic acid (1 g in 100 mL of saline solution) or placebo was poured into the pericardial cavity and over the mediastinal tissues before sternal closure. The drainage of mediastinal blood was measured hourly. RESULTS: Chest tube drainage in the first 24 hours was 485 +/- 166 mL in the tranexamic acid group and 641 +/- 184 mL in the placebo group (P =.01). Total postoperative blood loss was 573 +/- 164 mL and 739 +/- 228 mL, respectively (P =.01). The use of banked donor blood products was not significantly different between the two groups. Tranexamic acid could not be detected in any of the blood samples blindly collected from 24 patients to verify whether any systemic absorption of the drug occurred. There were no deaths in either group. None of the patients required reoperation for bleeding. CONCLUSIONS: Topical application of tranexamic acid into the pericardial cavity after cardiopulmonary bypass in patients undergoing primary coronary bypass operations significantly reduces postoperative bleeding. Further studies must be carried out to clarify whether a more pronounced effect on both bleeding and blood products requirement might be seen in procedures with a higher risk of bleeding.     

The effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic response after cardiac surgery

Background: Thrombin formation during cardiac surgery could result in disordered hemostasis and thrombosis. The aim of the study was to examine the effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic activity in patients undergoing cardiac surgery. Methods: Data were collected prospectively from 60 patients undergoing coronary artery bypass grafting using cardiopulmonary bypass (CPB). In a randomized sequence, 20 patients received aprotinin, 20 patients received tranexamic acid, and in 20 patients placebo was used. Results: Significant thrombin activity was found in all the studied patients. Thrombin generation was less in the aprotinin group than in the tranexamic acid and the placebo group (thrombin/anti‐thrombin III complexes 33.7 ± 3.6, 53.6 ± 7.0 and 44.2 ± 5.3 µg/l 2 h after CPB and F1 + 2 fragment 1.50 ± 0.10, 2.37 ± 0.37 and 2.04 ± 0.20 nmol/l 6 h after surgery, respectively). The inhibition of fibrinolysis was significant with both anti‐fibrinolytic drugs (d ‐dimers 0.427 ± 0.032, 0.394 ± 0.039 and 2.808 ± 0.037 mg/l 2 h after CPB, respectively). The generation of d ‐dimers was inhibited until 16 h after CPB in the aprotinin group. The plasminogen activation was significantly less in the aprotinin group (plasmin/anti‐plasmin complexes 0.884 ± 0.095, 2.764 ± 0.254 and 1.574 ± 0.185 mg/l 2 h after CPB, respectively). Conclusion: Thrombin formation is inevitable in coronary artery bypass surgery when CPB is used. The suppression of fibrinolytic activity, either with aprotinin or with tranexamic acid interferes with the hemostatic balance as evaluated by biochemical markers. Further investigations are needed to define the role of hemostatic activation in ischemic complications associated with cardiac surgery.     

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.     

Heparin resistance and increased platelet activation in coronary surgery patients treated with enoxaparin preoperatively

Objective: Patients with unstable coronary disease have changes in the hemostatic system. These patients are often treated with low molecular weight heparin. In patients who are accepted for coronary artery bypass grafting, treatment with low molecular weight heparin is frequently continued until surgery. We hypothesized that in coronary artery bypass grafting, the hypercoagulable state seen in unstable patients persists into the intra- and postoperative phase despite preoperative treatment with low molecular weight heparin. The aim of this study was to explore and describe the perioperative hemostatic process in patients with unstable coronary artery disease undergoing coronary artery bypass grafting. Methods: Thirty-two patients with unstable coronary disease treated preoperatively with enoxaparin, and 32 stable control patients not treated with enoxaparin, were included. All patients were taking low dose aspirin until the day before surgery. Before cardiopulmonary bypass, all patients were given tranexamic acid as a bolus injection. Blood samples for analysis of platelet counts, international normalized ratio, activated partial thromboplastin time, fibrinogen, protein S, protein C, prothrombin fragment 1 + 2, thrombin–antithrombin complex, antithrombin, plasmin–antiplasmin complex, D-dimer, neutrophil-activating peptide 2, platelet–monocyte complexes, and heparin concentrations were drawn preoperatively, after 30 min on cardiopulmonary bypass, and 30 min, 3 h, and 20 h postoperatively. Heparin was given during cardiopulmonary bypass to maintain an activated clotting time above 480 s. Results: Patients in the enoxaparin group needed more heparin to maintain an activated clotting time above 480 s, and had higher heparin concentrations and lower antithrombin values compared with control patients. Neutrophil-activating peptide 2 concentrations were higher in the enoxaparin group. Conclusions: Patients treated with enoxaparin before coronary artery bypass grafting showed signs of heparin resistance intraoperatively. Enoxaparin-treated patients also had increased perioperative platelet activation. Reasons for the observed difference in platelet activation remain unclear.     

Tranexamic acid reduces bleeding and the need for blood transfusion in primary myocardial revascularization

BACKGROUND: The objective of this study was to study the effect of low-dose tranexamic acid (TA) on postoperative bleeding and coagulation variables after coronary artery bypass grafting operation. METHODS: Fifty patients undergoing primary coronary artery bypass grafting were randomly assigned to receive either placebo (0.9% NaCl; n = 25) or 10 mg/kg TA followed by infusion of 1 mg/kg per hour during the operation (n = 25). Data measured included blood loss, transfusion, reoperation, fibrinogen level, fibrinogen split products, platelet size, and platelet function. Measurements were made after induction of anesthesia, after heparin administration, during patient warming, after skin closure, and 24 hours after operation. RESULTS: Patients in the TA study group weighed less. Other demographic characteristics were similar between groups. Postoperative bleeding was less in the TA group (194 +/- 135 mL versus 488 +/- 238 mL, p < 0.001), whereas blood requirement was higher in the control group (1.68 +/- 1 versus 0.52 +/- 0.9 U of packed cells per patient, p < 0.001). The percent of patients exposed to blood products was significantly less in the TA group (36% versus 100%, p < 0.001). Fibrinogen split products were lower in the TA group during bypass (p < 0.001). Fibrinogen levels fell in both groups during cardiopulmonary bypass. Platelet number and function were reduced equally in both groups by cardiopulmonary bypass. Other test results were not different between groups. CONCLUSIONS: The use of low-dose TA during coronary artery bypass grafting significantly reduced the coagulopathy-induced postoperative bleeding and allogeneic blood products requirement. The low levels of fibrinogen split products during bypass in the study group reflect the inhibiting effect of TA in fibrinolysis. Tranexamic acid had no effect on platelet function during cardiopulmonary bypass.     

A prospective, randomized study of endothelin and postoperative recovery in off-pump versus conventional coronary artery bypass surgery

OBJECTIVE: The objectives are 2-fold: (1). to serially determine endothelin (ET) levels in arterial vascular compartments in patients undergoing coronary artery bypass surgery using either cardiopulmonary bypass or off-pump techniques, and (2). to define potential relationships between endothelial levels and specific perioperative parameters of patient recovery. METHODS: In a prospective, randomized study, endothelin plasma content was measured from patients undergoing coronary artery bypass grafting using either off-pump techniques (OPCAB group, n = 25) or conventional cardiopulmonary bypass (CPB group, n = 25) before surgery, before and after coronary artery anastomosis, and 6 and 24 hours postoperatively. Specific indices of patient recovery including pulmonary artery pressures, ventilation requirement, and hospital stay were documented for patients in both study groups. RESULTS: Postoperative systemic arterial ET levels were significantly increased by 200% in the CPB group and 50% in the OPCAB group. ET levels remained significantly higher in the CPB group relative to the OPCAB group throughout the postoperative period of observation (p < 0.05). Pulmonary artery pressures, ventilation requirement, and hospital stay were significantly increased in patients in the CPB group. CONCLUSIONS: Postoperative ET levels were higher in patients who underwent CPB for coronary artery bypass surgery. Increased ET in the postoperative period may contribute to a more complex recovery from coronary artery bypass surgery in patients undergoing cardiopulmonary bypass.     

Tranexamic acid in primary CABG surgery: high vs low dose

AIM: Prophylactic administration of tranexamic acid decreases bleeding and transfusions after cardiac procedures but it is still unclear what the best dose and the most appropriate timing to get the best results are. METHODS: We enrolled 250 patients scheduled for elective, primary coronary revascularization. They were randomly divided into 2 groups. Group H received tranexamic 30 mg x kg(-1) soon after the induction of anaesthesia and a further same dose was added to the prime solution of cardiopulmonary bypass (CPB). Group L received tranexamic acid 15 mg x kg(-1) after systemic heparinization followed by an infusion of 1 mg x kg(-1) h(-1) till the end of the operation. Transfusions of bank blood products, bleeding in the postoperative period and coagulation profile were recorded. RESULTS: We did not find any difference between the groups either with respect to transfusion requirements or with respect to blood loss. CONCLUSION: For elective, first time coronary artery bypass surgery, both dosages of tranexamic acid are equally effective. Theoretically, it seems safer to administer it when patients are protected from thrombus formation by full heparinization.     

Off-pump surgery does not eliminate microalbuminuria or other markers of systemic inflammatory response to coronary artery bypass surgery

Objective. To evaluate whether off-pump surgery attenuates microalbuminuria and other markers of systemic inflammatory response to coronary artery bypass surgery as compared to surgery performed using cardiopulmonary bypass. Design. Forty-three adult patients undergoing elective coronary artery bypass grafting surgery were operated on with or without cardiopulmonary bypass (CPB). Microalbuminuria, serum C-reactive protein, and oxygenation and lung function parameters were measured at several time points until the first postoperative morning. Results. The urinary albumin/creatinine ratio was low in both groups before surgery, but reached a maximum level at the end of CPB or just after opening the last coronary artery clamp in the off-pump group (p?<?0.05). The urinary albumin/creatinine ratio remained slightly elevated in both groups until the morning after the operation (p?<?0.05). There were no statistical differences between groups. Serum C-reactive protein remained at the initial level the evening after the operation, but increased by the first postoperative morning in both groups (p?<?0.001). The alveolar-arterial gradient for oxygen partial pressure rose significantly after the operation in the intensive care unit in both groups (p?<?0.0001). The shunt fraction of the pulmonary circulation did not change in either group. Conclusions. Off-pump coronary artery surgery did not prevent the acute phase inflammatory response measured in the present study. The acute phase inflammatory response after coronary artery bypass surgery is more likely a response to the surgical trauma itself rather than to CPB.     

Off-pump surgery does not eliminate microalbuminuria or other markers of systemic inflammatory response to coronary artery bypass surgery

OBJECTIVE: To evaluate whether off-pump surgery attenuates microalbuminuria and other markers of systemic inflammatory response to coronary artery bypass surgery as compared to surgery performed using cardiopulmonary bypass. DESIGN: Forty-three adult patients undergoing elective coronary artery bypass grafting surgery were operated on with or without cardiopulmonary bypass (CPB). Microalbuminuria, serum C-reactive protein, and oxygenation and lung function parameters were measured at several time points until the first postoperative morning. RESULTS: The urinary albumin/creatinine ratio was low in both groups before surgery, but reached a maximum level at the end of CPB or just after opening the last coronary artery clamp in the off-pump group (p<0.05). The urinary albumin/creatinine ratio remained slightly elevated in both groups until the morning after the operation (p<0.05). There were no statistical differences between groups. Serum C-reactive protein remained at the initial level the evening after the operation, but increased by the first postoperative morning in both groups (p<0.001). The alveolar-arterial gradient for oxygen partial pressure rose significantly after the operation in the intensive care unit in both groups (p<0.0001). The shunt fraction of the pulmonary circulation did not change in either group. CONCLUSIONS: Off-pump coronary artery surgery did not prevent the acute phase inflammatory response measured in the present study. The acute phase inflammatory response after coronary artery bypass surgery is more likely a response to the surgical trauma itself rather than to CPB.     

Is cardiopulmonary bypass a reason for aspirin resistance after coronary artery bypass grafting?

OBJECTIVE: 'Off-pump' coronary artery bypass grafting (OPCAB) is an alternative to conventional coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB). While midterm results after OPCAB have become available, systematic studies of changes in platelet function after OPCAB are still missing. Since we have previously shown that oral aspirin treatment (100mg) does not achieve sufficient platelet inhibition in the majority of patients operated on with CPB, we hypothesized that bypass surgery without CPB (off-pump coronary artery bypass, OPCAB) causes less impairment of platelet inhibition by aspirin. The aim of this study was to investigate platelet function and the antiplatelet effect of aspirin after off-pump coronary artery bypass grafting in comparison with conventional on-pump surgery. METHODS: We compared platelet function (in vitro aggregation and thromboxane formation) before and at days 1 and 5 after coronary artery bypass grafting, performed with (n=15) or without (n=14) CPB. Oral aspirin treatment (100mg/d) was started at day 1 after surgery. RESULTS: After a 5 day oral treatment with aspirin, platelet aggregation was inhibited significantly in OPCAB-patients to 55.7+/-16.3% of control before surgery (P<0.05), whereas aggregation remained unchanged after CPB (105.8+/-26.9% of control before surgery; P>0.05). Since aspirin primarily inhibits platelet thromboxane formation, thromoboxane was determined after in vitro aggregation. According to platelet aggregation, thromboxane formation was only inhibited significantly after OPCAB (29.2+/-13.0% of control before surgery, P<0.05), but not after CPB (74.5+/-21.4% of control before surgery, P>0.05). This resistance to aspirin after CPB may be caused by an increased release of new platelets which are competent to form thromboxane, since the number of platelets decreased from 237+/-11x10(3)/microl before CPB to 174+/-13x10(3)/microl at day 1 after surgery and increased significantly the following days reaching 303+/-17x10(3)/microl at day 5. Platelet counts of patients operated on without CPB showed no significant changes (236+/-16x10(3)/microl before OPCAB, 220+/-16x10(3)/microl at day 1 and 266+/-31x10(3)/microl at day 5 after surgery). CONCLUSIONS: The antiplatelet effect of aspirin is largely impaired after CPB, but not after CABG without CPB. Hence, increased platelet turnover after CPB seems to contribute to aspirin resistance, since an increased number of platelets might be competent to form thromboxane within the dosing intervals.     

Beneficial effect of aspirin on renal function in patients with renal insufficiency postcardiac surgery

AIM: Renal function is one of the most important prognostic factors following cardiac surgery. Whether aspirin affects cardiopulmonary bypass related renal injury is investigated in this study. METHODS: Ninety-four patients with impaired renal function (creatinine = or >1.5 mg/dl) undergoing coronary artery bypass grafting (CABG) were categorized into 2 groups according to aspirin administration before surgery. Serum creatinine, urinary output and creatinine clearance along with other perioperative factors were compared between the 2 groups prior to surgery, 24 hours and 48 hours following cardiopulmonary bypass. RESULTS: Creatinine levels increased significantly in the second postoperative day only in the non-aspirin (control) group (3.7+/-1.6 vs 2.9+/-1.7 mg/dl, p=0.03). Aspirin (study) group had lower creatinine levels in day 1 (p=0.03) and day 2 (p=0.001). Furthermore, in the study group creatinine clearance was higher in day 1 (34.3+/-14.3 vs 30.9+/-13.1 ml/min, p=0.01) and in day 2 (32.6+/-13.8 vs 26.4+/-9.8 ml, p<0.0001). Creatinine levels at discharge were elevated compared to the preoperative levels in the control group (p=0.01). However, the study group had lower creatinine levels at discharge (2.6+/-1.4 vs 3.8+/-1.6 mg/dl, p<0.0001). Urinary output was higher in the study group in the first postoperative day compared to the control group (p=0.01). Postoperative bleeding was slightly increased in the study group compared to the control group (760+/-230 ml vs 530+/-210 ml, p=0.01). CONCLUSIONS: Continuation of aspirin administration until the day of surgery may have a protective effect against renal injury resulting from cardiopulmonary bypass, with only a negligible increase in bleeding. Possible explanations for this effect are antiplatelet activity of aspirin during cardiopulmonary bypass causing inhibition of vasoconstrictive agents like thromboxane, and improvement of renal perfusion by reducing blood viscosity.     

Endotoxemia in coronary artery bypass surgery: a comparison of the off-pump technique and conventional cardiopulmonary bypass

OBJECTIVES: The endotoxemia associated with cardiac surgery is thought to be dominantly influenced by the use of cardiopulmonary bypass. The objectives of this study were to assess the relative contribution of cardiopulmonary bypass on endotoxemia apart from cardiac surgical access and to improve our understanding of the potential benefits of off-pump procedures. METHODS: Thirty patients undergoing coronary artery bypass grafting were followed up prospectively. The patients were divided into 2 equal groups: those who underwent bypass grafting through a sternotomy incision without cardiopulmonary bypass (off-pump group) and those who underwent bypass grafting through a sternotomy incision with cardiopulmonary bypass (CPB group). Blood sampling for endotoxin, lactate, and cardiac index measurements were performed during the following time points: (1) after sternotomy; (2) during the coronary occlusion period in the off-pump group and during aortic clamping in the CPB group; (3) after removal of the coronary occlusion sutures in the off-pump group and after removal of the aortic clamp in the CPB group; (4) 30 minutes after the completion of all distal anastomoses in the off-pump group and immediately after weaning from cardiopulmonary bypass in the CPB group; (5) 1 hour postoperatively; and (6) 12 hours postoperatively. RESULTS: Endotoxin and lactate levels were significantly (P <.05) lower in the off-pump group at all sampling time points, except after sternotomy. CONCLUSIONS: In conclusion, this study has shown that endotoxemia during coronary artery bypass surgery seems mainly to be associated with cardiopulmonary bypass procedure. The relatively lower endotoxin levels observed in off-pump surgery might contribute to improved postoperative recovery.     

D-Dimer formation during cardiac and noncardiac thoracic surgery.

The ability to make therapeutic decisions regarding excessive fibrinolysis in the perioperative period is limited by the lack of availability of a near site monitor of fibrinolysis. We investigated the use of a latex agglutination D-dimer assay to detect perioperative fibrinolysis in patients undergoing thoracic surgery with and without extracorporeal circulation. We studied 27 patients who underwent thoracic surgery requiring cardiopulmonary bypass (CPB; coronary artery bypass grafting, n = 12; valvular surgery, n = 15) and a cohort of 20 patients who underwent noncardiac thoracic surgical procedures not requiring CPB. The purpose of this investigation was to determine the relationship among alterations in the latex agglutination D-dimer assay, use of extracorporeal circulation, type of cardiac surgical procedure, and mediastinal and/or chest tube drainage (cardiac surgery only) in patients undergoing thoracic surgery. Perioperative D-dimer levels, measured by latex agglutination, had significant (P < or = 0.05) intragroup changes among patients undergoing cardiac surgery (requiring CPB) and the cohort of patients who underwent noncardiac thoracic surgery without CPB. Although intraoperative D-dimer levels were not increased in patients undergoing noncardiac thoracic surgery, postoperative levels were significantly (P < 0.05) increased (compared with preinduction). In cardiac surgery patients requiring CPB, intraoperative D-dimer formation was significantly (P < or = 0.05) increased but did not demonstrate any intragroup (coronary artery bypass grafting versus valvular surgery) differences. Finally, D-dimer levels were not associated with postoperative mediastinal and/or chest tube accumulative drainage measured at intervals up to 48 h postoperatively in patients undergoing cardiac surgery requiring CPB. Our study indicates that the latex agglutination D-dimer assay can detect excessive fibrinolysis perioperatively, and that extracorporeal circulation can significantly influence the pattern of D-dimer formation in patients undergoing thoracic surgery. IMPLICATIONS: We assessed the ability of a readily available D-dimer assay to detect excessive fibrinolysis in patients undergoing thoracic surgery with and without extracorporeal circulation. The findings demonstrate that the assay used in this investigation reflected variable amounts of fibrinolysis in patients undergoing both types of thoracic surgery.     

Low-dose postoperative aprotinin reduces mediastinal drainage and blood product use in patients undergoing primary coronary artery bypass grafting who are taking aspirin: a prospective, randomized, double-blind, placebo-controlled trial

BACKGROUND: Although low-dose aprotinin administered after cardiopulmonary bypass has been reported to reduce mediastinal blood loss and blood product requirements in patients not taking aspirin, it is unknown whether low-dose postoperative aprotinin has any beneficial effects in patients undergoing coronary artery bypass operations who are at high risk of excessive postoperative bleeding and increased transfusion requirements because of aspirin use until just before the operation. METHODS: Fifty-five patients undergoing primary coronary artery operations with cardiopulmonary bypass who continued taking aspirin (150 mg/d) until the day before the operation were enrolled in a prospective, randomized, double-blind trial to receive a single dose of either placebo (n = 29) or 2 x 10(6) kallikrein inhibiting units of aprotinin (n = 26) at the time of sternal skin closure. RESULTS: Patients in the aprotinin group had a lower rate (28 +/- 18 vs 43 +/- 21 mL/h [mean +/- standard deviation], P <.005) and total volume of mediastinal drainage (955 +/- 615 vs 1570 +/- 955 mL, P <.007), as well as a shorter duration of mediastinal drain tube insertion (24.4 +/- 13.8 vs 31.3 +/- 16.5 hours, P <.05). In addition, a smaller proportion of patients receiving aprotinin required a blood product (31% vs 62%, P =.03), resulting in a reduction in the use of packed cells by 47% (P =.05), platelets by 77% (P =.01), fresh frozen plasma by 88% (P =.03), and total blood products by 68% (P =.01) in this group. CONCLUSIONS: These results suggest that postoperative administration of low-dose aprotinin in patients taking aspirin until just before primary coronary artery operations with cardiopulmonary bypass not only reduces the rate and total amount of postoperative mediastinal blood loss but also lowers postoperative blood product use.     

A double-blind, placebo-controlled trial of epsilon-aminocaproic acid for reducing blood loss in coronary artery bypass grafting surgery

BACKGROUND: Epsilon-aminocaproic acid is a plasmin inhibitor that potentially reduces perioperative bleeding when administered prophylactically to cardiac surgery patients. To evaluate the efficacy of epsilon-aminocaproic acid, a prospective placebo-controlled trial was conducted in patients undergoing primary coronary artery bypass grafting surgery. STUDY DESIGN: One hundred patients were randomly assigned to receive either epsilon-aminocaproic acid (100 mg/kg before skin incision followed by 1 g/hour continuous infusion until chest closure, 10 g in cardiopulmonary bypass circuit) or placebo, and the efficacy of epsilon-aminocaproic acid was evaluated by the reduction in postoperative thoracic-drainage volume and in donor-blood transfusion up to postoperative day 12. RESULTS: Postoperative thoracic-drainage volume was significantly lower in the epsilon-aminocaproic acid group compared with the placebo group (epsilon-aminocaproic acid, 649 +/- 261 mL; versus placebo, 940 +/- 626 mL; p=0.003). There were no significant differences between the epsilon-aminocaproic acid and placebo groups in the percentage of patients requiring donor red blood cell transfusions (epsilon-aminocaproic acid, 24%; versus placebo, 18%; p=0.62) or in the number of units of donor red blood cells transfused (epsilon-aminocaproic acid, 2.2 +/- 0.8 U; versus placebo, 1.9 +/- 0.8 U; p=0.29). Epsilon-aminocaproic acid did not reduce the risk of donor red blood cell transfusions compared with placebo (odds ratio: 1.2, 95% confidence interval; 0.4 to 3.2, p=0.63). CONCLUSIONS: Prophylactic administration of epsilon-aminocaproic acid reduces postoperative thoracic-drainage volume by 30%, but it may not be potent enough to reduce the requirement and the risk for donor blood transfusion in cardiac surgery patients. This information is useful for deciding on a therapy for hemostasis in cardiac surgery.     

Tranexamic acid reduces postoperative bleeding in off-pump coronary artery bypass grafting

OBJECTIVE: Tranexamic acid (TA) reduces blood loss in coronary artery surgery with cardiopulmonary bypass. The present prospective study was designed to investigate its hemostatic effect in off-pump coronary artery bypass (OPCAB). METHOD: Seventy-six patients undergoing elective OPCAB were randomized into two groups, received TA (0.75 g loading dose before surgery and 250 mg/h during surgery, gross dose: 1.5 g, n=36) and saline solution (control, n=40), respectively. Perioperative blood samples were collected. Hematochemical parameters including platelet adhesion rate, D-dimer and fibrinopeptide-A (FPA) were analysis. Volume of blood loss, blood transfusion and other clinical data were recorded throughout the perioperative period. RESULTS: Cumulative blood loss was significantly reduced in the TA group as compared to the controls postoperatively (6 hrs (median [25th-75th]): TA: 200.0 [140.0-230.0] ml, Control: 225.0 [200.0-347.5.0] ml, p=0.009; 24 hrs: TA: 440.0 [270.0-605.0] ml, Control: 655.0 [500.0-920.0] ml, p<0.001). Number of patients received blood transfusion in each group was similar. Levels of D-dimer rose significantly after surgery, and were significantly lower in the TA group than that in controls. Platelet adhesion rate and FPA levels remained at baseline levels after the operation in two groups. Early clinical outcomes were similar between groups. CONCLUSION: The results indicated that tranexamic acid limits fibrinolysis and reduces blood loss after off-pump coronary artery bypass surgery.