Platelet activity and aspirin efficacy after off-pump compared with on-pump coronary artery bypass surgery: results from the prospective randomized trial PRAGUE 11-Coronary Artery Bypass and REactivity of Thrombocytes (CABARET).

OBJECTIVES: Changes in hemostasis after off-pump coronary artery bypass grafting are still being discussed. There is a lack of information about platelet activity and aspirin efficacy after coronary artery bypass grafting. The aim of this study was to assess and compare platelet activity and aspirin efficacy early and late after off-pump and on-pump coronary artery bypass grafting. METHODS: Eighty patients were enrolled in a prospective randomized study. Platelet activity was determined based on membrane expression of antigen CD62P (P-selectin) by means of flow cytometric analysis. Aspirin efficacy was assessed by using arachidonic acid-induced platelet aggregation. Blood samples were collected before the operation, immediately postoperatively, and on days 1, 2, 5, and 30. RESULTS: In the off-pump group expression of P-selectin was markedly increased in comparison with preoperative values, with a maximum difference observed on day 2 (+53%, P = .02), and it was significantly higher compared with that seen in the on-pump group on days 2 and 5 (+53% vs +4%, P = .004, and +20% vs -16%, P = .005). On day 30, P-selectin expression was similar both between the groups and in comparison with the preoperative values. Arachidonic acid-induced platelet aggregation was gradually decreasing until day 30, but on day 2, there was an unexpected increase in aggregation that was more expressed in the off-pump group. CONCLUSIONS: The platelet activity is higher in the early postoperative period in off-pump compared with on-pump coronary artery bypass grafting. The present aspirin strategy seems to be insufficient in the early postoperative period, irrespective of the surgical technique used.

Postoperative blood loss in coronary surgery. No real impact of fibrinolysis detected by thromboelastography and D-dimers. A prospective, randomized study.

Although in many cardiac surgery centers pharmacological strategies based on fibrinolytic inhibitors are used on a routine basis, detailed knowledge of fibrinolysis during various settings of coronary surgery is still limited. Sixty-five patients scheduled for coronary surgery were randomized into 3 groups: group A--conventional coronary artery bypass grafting, group B--off-pump surgery, and group C--coronary artery bypass grafting with modified, rheoparin coated cardiopulmonary bypass with the avoidance of reinfusion of cardiotomy blood into the circuit. The sampling time points for rotation thromboelastographic evaluations were as follows: preoperatively, 15 minutes after sternotomy, on the completion of peripheral bypass anastomoses, at the end of the procedures, and 24 hours after the end of surgery. D-dimer levels were evaluated before surgery, at the end of procedures, and 24 hours after surgery. Thromboelastographic signs of fibrinolysis (evaluated by Lysis Onset Time-intergroup differences at 60 and 150 minutes of assessment: P = 0.003 and P < 0.001, respectively) were clearly detectable during cardiopulmonary bypass in group A, but not at any time in groups B and C. At the other sampling times all thromboelastographic parameters were similar in all groups. In group A, no exceptional bleeding tendency (during 24 hours), as compared to groups B and C (geometric means and 95% confidence intervals: group A: 686.7 [570.8; 826.1] mL, group B: 555.3 [441.3; 698.9] mL, group C: 775.6 [645.1; 932.3] mL, P = 0.157), and no significant correlations between Lysis Onset Time, postoperative blood loss, and D-dimer levels were found. No significant differences in postoperative blood loss related to cardiac surgeons and assistant surgeons were detected. Thromboelastographic signs of increased fibrinolysis were detectable in the important proportion of coronary surgery patients operated on with the use of conventional cardio-pulmonary bypass, but not in off-pump patients and those operated on with the biocompatible surface-modified circuit without reinfusion of cardiotomy suction blood. These signs resolved spontaneously at the end of surgery and were not associated with increased postoperative bleeding. No significant correlation with D-dimer levels was found.

Fibrinolysis in coronary artery surgery: detection by thromboelastography.

Sixty-five patients scheduled for coronary surgery were randomized into three groups: A - conventional coronary artery bypass grafting, B - off-pump surgery, C - coronary artery bypass grafting with modified, rheoparin coated cardiopulmonary bypass with the avoidance of re-infusion of cardiotomy blood into the circuit. On the completion of peripheral bypass anastomoses, highly significant inter-group differences were found in the thromboelastographic parameter lysis of set time at 60 min of assessment (P=0.003) and at 150 min of assessment (P<0.001), the mean values of these parameters were significantly lower in group A as compared with both groups B and C, which were statistically indistinguishable. Lysis on set time on the completion of peripheral bypass anastomoses <50% was detected in 12 patients (52.2%) originating from group A. At the other sampling times (preoperatively, 15 min after sternotomy, at the end of the procedures, and 24 h later) thromboelastographic parameters were similar in all groups. In group A no significant correlations between lysis on set time, postoperative blood loss and D-dimer levels were found. Based on our results, thromboelastographic signs of fibrinolysis were clearly detectable during cardiopulmonary bypass in group A, but not at any time in groups B and C.

Off-pump versus on-pump coronary artery surgery.

The aim of this preliminary, prospective, randomized study was to compare rotation thromboelastography (roTEG) results and D-dimer levels in off-pump versus on-pump coronary surgery in order to identify the activation of fibrinolysis. Twenty patients scheduled for coronary bypass grafting were assessed (off-pump group A, n = 10; on-pump group B, n = 10). Blood samples for roTEG examination were taken preoperatively (t0), 15 minutes after sternotomy (t1), on the completion of peripheral bypass anastomoses (t2), and at the end of procedures (t3). The time points for D-dimer levels analyses were before operation, at the end of procedures, and 24 hours later. A certain degree of roTEG signs of fibrinolysis was noticed at time t2 in both groups and in group B these marks were quite widely, but not significantly expressed (P for intergroup differences for Lysis on Set Time at 60 and 150 minutes were P = 0.190 and P = 0.122, respectively), borderline differences were found for Maximum Clot Firmness (P = 0.082) with a lower mean value for group B (arithmetic means [95% confidence intervals]--57.7 [54.2; 61.2] mm). Completely expressed roTEG signs of hyperfibrinolysis were observed in 2 patients from group B. In group B also the highest geometric means of D-dimers (1326.0 [943.5; 1863.6] ng mL(-1)) and thus a dramatic intergroup difference (P < 0.001) were observed at the end of surgery; 24 hours later the significantly elevated D-dimer levels in both groups (A: 1070.0 [723.5; 1582.6] versus B: 1093.3 [732.0; 1632.9] ng mL(-1)) were equalized (P = 0.932). Our roTEG results display a slightly greater, but fairly subtle activation of fibrinolysis during the course of cardiopulmonary bypass, compared to off-pump cardiac surgery.

Fibrinolytic inhibitors in off-pump coronary surgery: a prospective, randomized, double-blind TAP study (tranexamic acid, aprotinin, placebo).

OBJECTIVE: To evaluate and compare hemostatic effects of tranexamic acid vs. aprotinin vs. placebo in off-pump coronary artery bypass (OPCAB) surgery and, in addition, to assess the safety of fibrinolytic inhibitors therapies. METHODS: In a prospective, randomized, double-blind study finally 91 patients undergoing OPCAB were investigated (group A, n=32, tranexamic acid 1g before skin incision and continuously 200mg/h; group B, n=29, aprotinin 1,000,000IU before skin incision and 250,000IU/h; group C, n=30, placebo). RESULTS: Highly significant inter-group differences were found in cumulative blood loss within 4h (geometric means [95% confidence intervals]-group A: 89.3 [72.7, 109.8] mL, group B: 72.3 [49.2, 106.3] mL and group C: 192.3 [151.8, 243.5] mL) (P<0.001), within 8h (group A: 152.1 [120.7, 191.6] mL, group B: 130.3 [88.1, 192.8] mL and group C: 283.8 [226.0, 356.3] mL) (P=0.001), and within 24h postoperatively (group A: 410.3 [337.6, 498.6] mL, group B: 345.8 [256.0, 398.2] mL and group C: 619.8 [524.3, 732.8] mL) (P<0.001). At all time points, placebo group C was significantly distinct from the groups treated with fibrinolytic inhibitors (groups A and B). However, no differences between groups A and B were found. Both mean hemoglobin and hematocrit values 24h postoperatively were different between the groups (P=0.018 and P=0.077, respectively), acheiving the lowest value in group C. Number of re-transfuzed patients was highest in group C, but without statistical significance (either packed red blood cells, P=0.119 or fresh-frozen plasma, P=0.118). We observed one postoperative myocardial infarction in aprotinin treated group B and one temporary postoperative myocardial ischemia in placebo group C, no cerebrovascular or pulmonary embolism was noticed. Treated groups A and B did not demonstrate postoperative increase in mean levels of myocardial enzymes, compared with group C. Significantly higher mean values of D-dimer were found in group C 24h postoperatively (P<0.001). CONCLUSIONS: Both tranexamic acid and aprotinin seem to be similarly effective in the reduction of postoperative blood loss in OPCAB. Tranexamic acid appears to be cost-effective and safe alternative to aprotinin.

Use of recombinant activated factor VII in cardiac surgery for an effective treatment of severe intractable bleeding.

Experience gained with administration of supranormal-therapeutic doses (90 microg/kg) of recombinant activated factor VII in 7 cardiac surgery patients is presented. The patients were given recombinant activated factor VII postoperatively for intractable bleeding, 5 of them after surgical revision. Administration of recombinant activated factor VII was associated with significant reduction in blood loss (P < 0.05) and shortening of INR and aPTT in laboratory tests. None of the patients needed reoperation. Administration of recombinant activated factor VII proved highly effective in management of massive hemorrhage in cardiac surgery.

Less invasive cardiac anesthesia: an ultra-fast-track procedure avoiding thoracic epidural analgesia.

BACKGROUND AND OBJECTIVE: A new "less invasive" technique avoiding thoracic epidural analgesia has be en tested for suitability as a routine procedure for cardiac anesthesia. Early postoperative extubation is an important step in this fasttrack procedure. MATERIALS AND METHODS: Consecutive patients (n = 547; age, 35-82 years; mean age, 64 year s; male to female ratio, 3.5) underwent general anesthesia with ultra-short-acting opiates and then underwent coronary surgery (n = 465), valve surgery (n = 38), or combined and other procedures (n = 44) a r;. In 51.4% cases, coronary artery bypass grafting was performed off pump. The percentage of patients extubated within 10 minutes after skin closure was the primary end point. In addition, we attempted to identify the limiting factors of the procedure tested. RESULTS AND DISCUSSION: Of the 547 patients, 499 (91%) were extubated within 10 minutes after skin closure. Early extubation failed in 48 (9%) of the patients. The mortality rate was 1.5%. One (0.2%) of the patients needed early reintubation because of pneumothorax. Postoperative myocardial ischemia was recorded in 10 (1.8%) of the patients. Ninetysix (17.5%) of the patients were treated pharmacologically for newly developed atrial fibrillation. None of the patients needed hemodialysis. Transient neurological disorders were recorded in 10 (1.8%) of the patients. The early extubation failure group showed statistically significantly higher rates of preoperative lung dysfunction, use of extracorporeal circulation, administration of inotropic drugs in the operating room, and statistically significantly longer duration of surgery. CONCLUSION: Early extubation proved suitable as a routine procedure for the vast majority of patients. With a good postoperative analgetic protocol, there is no need for thoracic epidural analgesia. Such avoidance of thoracic epidural analgesia is a further step in minimizing invasiveness in cardiac surgery.