Patrick Treanor

Effect of Anticoagulation Protocol on Outcome in Patients Undergoing CABG With Heparin-Bonded Cardiopulmonary Bypass Circuits

BACKGROUND We have demonstrated that the use of heparin-bonded cardiopulmonary bypass circuits (HBCs) combined with a lower anticoagulation protocol as an adjunct to an integrated blood conservation strategy decreases the incidence and magnitude of homologous transfusion and improves clinical outcome in patients undergoing primary coronary artery bypass grafting. It is not known whether it is the lower anticoagulation protocol that influences outcome in patients treated with HBCs. Furthermore, the thrombogenic risk of using lower anticoagulation with HBCs still is debated. METHODS To answer these questions, a prospective randomized study was conducted in which 244 patients undergoing primary coronary artery bypass grafting were treated with HBCs and randomized to undergo either a full (activated clotting time, > 450 seconds) or a lower (activated clotting time, > 250 seconds) anticoagulation protocol. In addition to clinical outcome, levels of thrombin generation markers during and after cardiopulmonary bypass were assessed in a consecutive subset of 58 patients (full anticoagulation profile = 28, lower anticoagulation profile = 30) by measuring thrombin-antithrombin complexes and prothrombin fragment 1.2. Levels of these markers also were correlated with the activated clotting time during cardiopulmonary bypass. RESULTS Preoperative and intraoperative risk profiles and other characteristics were similar in both groups, with more than 60% of patients undergoing nonelective operation. Compared with the full anticoagulation protocol group, patients in the lower anticoagulation protocol group were less likely to require blood products (24.2% versus 35.8%, respectively; p = 0.047) and received substantially fewer homologous donor units (0.50 +/- 0.92 versus 1.08 +/- 2.10 U, respectively; p = 0.005). Clinical outcomes were uniformly outstanding (but similar) in both treatment groups, with a modest reduction in the length of the hospital stay in the lower anticoagulation protocol group (5.26 +/- 1.23 versus 5.63 +/- 1.73 days, respectively; p = 0.05). The use of HBCs with a lower anticoagulation protocol was not associated with any adverse clinical events. Thrombin generation increased during cardiopulmonary bypass in both treatment groups, but was unrelated to the anticoagulation protocol or the activated clotting time (r2 = 0.03). No differences between the full and lower anticoagulation protocol groups were noted in the number of microemboli detected by transcranial Doppler analyses during cardiopulmonary bypass (n = 40) or in the postoperative neurologic and neuropsychologic outcomes (n = 30). CONCLUSIONS This study definitively demonstrates that, when used appropriately, patients who are treated with HBCs and a lower anticoagulation protocol have a lower incidence and magnitude of homologous transfusion and are not at any added risk for clinical, hematologic (thrombin-antithrombin complex and fragment 1.2 measurements), or microscopic (transcranial Doppler analyses) thromboembolic complications or for neurologic or neuropsychologic deficits.

Reduction of Allogeneic Blood Transfusions After Open Heart Operations by Lowering Cardiopulmonary Bypass Prime Volume

BACKGROUND Despite recent advances in blood conservation techniques, up to 30% to 80% of patients undergoing open heart operations require allogeneic blood transfusions. A prospective, randomized study was performed to test the effect of lowering cardiopulmonary bypass prime volume (as an additional component of an integrated blood conservation strategy) on clinical outcome and allogeneic blood transfusion. METHODS One hundred fourteen patients undergoing open heart operations were randomized to either full prime (FP) volume (1,400 mL of Plasmalyte solution) or reduced prime (RP) volume (600 to 800 mL). The reduction of prime volume was achieved by slowly draining the cardiopulmonary bypass circuit into a cell-saving device before the initiation of bypass. Firm transfusion thresholds were observed. RESULTS There were no significant differences between the groups with respect to baseline characteristics, body surface area, type and urgency of the procedures, perfusion technique, and hematologic profile. Mortality (FP, 1.7%; RP, 0%; p approximately 1.0) and overall morbidity (FP, 28.1%; RP, 22.8%; p = 0.53) were similar. However, transfusion requirements were significantly lower in the RP group: total donor exposure, 3.8 +/- 10.1 versus 1.0 +/- 2.4 units (p = 0.044); percentage of patients transfused, 54% (n = 31) versus 35% (n = 20) (p = 0.036). Twenty-four-hour chest tube drainage was similar: 455 +/- 223 mL for FP versus 472 +/- 173 mL for RP (p = 0.66). The lowest hematocrit on bypass was significantly higher in the RP group: 29.3% +/- 4% versus 26.3% +/- 5.3% (p = 0.009). CONCLUSIONS Lowering cardiopulmonary bypass prime volume resulted in a significant decrease in allogeneic blood product use. Because postoperative 24-hour chest tube drainage was similar in both groups, and hematocrit during bypass was higher in the RP group, the reduction in allogeneic blood transfusions appears to be related to a decrease in prime-induced hemodilution. This technique is effective, simple, and safe. It therefore should be strongly considered for patients undergoing operations using normothermic or near-normothermic cardiopulmonary bypass who are at high risk for allogeneic blood transfusion.

Role of leukocyte depletion during cardiopulmonary bypass and cardioplegic arrest

BACKGROUND Leukocyte depletion (LD) has been shown to be beneficial during the reperfusion of acutely ischemic myocardium; however, its role during cardiopulmonary bypass (CPB) in hearts protected with blood cardioplegia (BCP) is unknown. This experimental study sought to determine whether LD filters inserted in the CPB circuit before cardioplegic arrest and in the BCP circuit during arrest would decrease ischemic myocardial damage. METHODS In 20 pigs, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of BCP arrest and 180 minutes of reperfusion on CPB. In 5 pigs, LD filters were inserted in both the CPB and BCP circuits (LD-CPB+BCP). Five pigs had LD during BCP (LD-BCP), 5 pigs had LD during CPB (LD-CPB), and 5 pigs had no LD. Ischemic damage was assessed by wall motion scores using two-dimensional echocardiography and the area of necrosis/area of risk. RESULTS The LD-CPB and LD-CPB+BCP groups had the highest wall motion scores and the lowest area of necrosis/area of risk. The addition of LD to BCP alone did not significantly alter wall motion scores or the area of necrosis/area of risk. CONCLUSION Leukocyte depletion filters significantly reduce ischemic damage during acute surgical revascularization and appear to be most effective when placed in the CPB circuit before cardioplegic arrest.

Heparin-Bonded Circuits Decrease Myocardial Ischemic Damage: An Experimental Study

BACKGROUND Heparin-bonded cardiopulmonary bypass circuits reduce complement activation, but their effect on myocardial function is unknown. This study was undertaken to determine whether heparin-bonded circuits reduce myocardial damage during acute surgical revascularization. METHODS In 16 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion with the snares released. During the period of coronary occlusion, all animals were placed on percutaneous bypass followed by standard cardiopulmonary bypass during the periods of cardioplegic arrest and reperfusion. In 8 pigs, heparin-bonded circuits were used, whereas 8 other pigs received nonbonded circuits. RESULTS Animals treated with heparin-bonded circuits had the best preservation of wall motion scores (3.5 +/- 0.3 versus 2.3 +/- 0.2; 4 = normal to -1 = dyskinesis; p < 0.05), least tissue acidosis (change in pH = -0.31 +/- 0.02 versus -0.64 +/- 0.08; p < 0.05), smallest increase in lung H2O (1.7% +/- 0.7% versus 6.1% +/- .5%; p < 0.05), and the lowest area of necrosis/area of risk (20.3% +/- 2.2% versus 40.4% +/- 1.6%; p < 0.05). CONCLUSIONS We conclude that heparin-bonded circuits significantly decrease myocardial ischemic damage during acute surgical revascularization.

Enhanced recovery of ischemic myocardium by combining percutaneous bypass with intraaortic balloon pump support

Although percutaneous bypass (PB) can support the failing myocardium, regional ischemic damage may still occur beyond a coronary occlusion. This study sought to determine whether the addition of intraaortic balloon pump (IABP) support to PB would result in more optimal salvage of ischemic myocardium. In 30 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 30 minutes of cardioplegic arrest and 3 hours of reperfusion with the snares released. During the period of coronary artery occlusion, 10 pigs were placed on PB, 10 pigs received PB plus IABP support, and 10 pigs received no support (the unmodified group). The hearts treated with the combination of PB and IABP support exhibited the highest wall motion scores (3.3 +/- 0.20 for the PB plus IABP group [p < 0.05 from the unmodified group and from the PB group]; versus 1.40 +/- 0.30 for the PB group versus 1.37 +/- 0.33 for the unmodified group), the least tissue acidosis (change in pH, -0.30 +/- 0.2 for the PB plus IABP group [p < 0.05 from the PB group] versus -0.60 +/- 0.10 for the PB group versus -0.41 +/- 0.13 for the unmodified group), and the least area of necrosis (25% +/- 5% for the PB plus IABP group [p < 0.05 from the unmodified group and from the PB group]; versus 43% +/- 2% for the PB group [p < 0.05 from the unmodified group] versus 73% +/- 3% for the unmodified group).(ABSTRACT TRUNCATED AT 250 WORDS)

Heparin‐bonded Circuits Improve Clinical Outcomes in Emergency Coronary Artery Bypass Grafting

Abstract Compared to patients undergoing elective or urgent coronary artery bypass grafting (CABG), those undergoing emergency CABG (EM‐CABG) have a higher morbidity and mortality. The use of heparin‐bonded circuits (HBC) has been shown to improve clinical outcomes in nonemergent CABG patients. It is not known, however, whether the improved hemostasis and attenuation of the inflammatory response to cardiopulmonary bypass, conferred by HBC, can overcome the high incidence of comorbid risk factors in (EM‐CABG) patients and improve their outcomes. A retrospective analysis of 206 consecutive patients undergoing EM‐CABG over 4 years (1993–1997) at one institution was performed. Eighty‐one patients were treated with conventional non‐heparin‐bonded circuits (NHBC) with full anticoagulation protocol (FAR, activated clotting time [ACT] > 480 sec); 125 patients were treated with HBC and a lower anticoagulation protocol (LAP, ACT > 280 seconds). Outcomes and results were collected prospectively and are presented as mean ± SD. Preoperative risk profiles were similar in both treatment groups. Postoperatively, compared with the NHBC group, patients treated with HBC/LAP required fewer homologous donor units (4.1 ± 10.7 vs 8.2 ± 13.6 units, p = 0.005), were less likely to require inotropic support (18.6% vs 38.3%, p = 0.005), and had a lower incidence of perioperative myocardial infarction (Ml, 3.2% vs 12.3%, p = 0.04) and pulmonary complications (4.0% vs 12.3%, p = 0.04). The use of HBC/LAP resulted in a decreased incidence of postoperative complications (12.8% vs 28.4%, p = 0.01, odds ratio 0.37 with 95% confidence interval [Cl] 0.18‐0.76). This resulted in a shorter duration of ventilatory support (30.5 ± 54.0 vs 72.8 ± 16.7 hours, p = 0.009), ICU stay (38.2 ± 36.5 vs 91.5 ± 68.7 hours, p = 0.009), hospital stay (8.0 ± 7.1 vs 11.0 ± 8.9 days, p = 0.008), and therefore cost. In conclusion, the use of HBC/LAP in EM‐CABG resulted in a reduction of homologous transfusion and postoperative complications associated with decreased hospital stays and cost.

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

Abstract 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 Jehovahs 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.

Enhanced Blood Conservation in Primary Coronary Artery Bypass Surgery Using Heparin-Bonded Circuits with Lower Anticoagulation

Abstract Background: Despite many advances in blood conservation techniques, a significant proportion of patients undergoing primary coronary revascularization still require homologous transfusions. A comprehensive strategy to diminish perioperative blood loss was developed by integrating many individual components to create an improved blood conservation environment and was prospectively applied to 557 patients undergoing primary coronary artery bypass grafting (CABG) procedures performed in our medical center over a 14‐month period. Methods: The first 455 patients were treated with conventional, nonheparinbonded circuits (NHBCs) and full anticoagulation (activated clotting time [ACT] > 480 sec). We wanted to test the hypothesis of whether “tip‐to‐tip” heparin‐bonded circuits (HBCs) used in conjunction with lower anticoagulation (ACT > 280 sec) when added to our current blood conservation environment can further enhance clinical outcomes. We prospectively applied this technique to a consecutive group of patients (n = 102). Results: Compared to patients treated with NHBCs, patients treated with HBCs had a significantly lower mediastinal and pleural chest tube output in the first 24 hours (683 ± 561 mL vs 984 ± 616 mL, p < 0.00001) were less likely to be transfused (52% vs 68.1%, p < 0.01) and had a lower exposure to different blood donor units (4.1 ± 8.4 vs 9.3, ± 10.3, p < 0.000003). There were no complications directly related to HBCs used in conjunction with lower anticoagulation. Morbidity and mortality rates were similar in both treatment groups. Conclusion: In summary, HBCs in conjunction with lower anticoagulation were safely applied in patients undergoing primary CABG with marked improvement in blood conservation, and should be considered for broader clinical use.

Combining percutaneous bypass with coronary retroperfusion limits myocardial necrosis

After an acute coronary occlusion that results in hemodynamic instability, the institution of percutaneous bypass (PB) can effectively support the failing myocardium. However, PB cannot augment coronary blood flow, and substantial regional myocardial necrosis can still occur. This experimental study was undertaken to determine whether combining PB with coronary venous retroperfusion using pressure-controlled intermittent coronary sinus occlusion (PICSO) would limit myocardial necrosis after an acute coronary occlusion. In 30 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 30 minutes of cardioplegic arrest and 180 minutes of reperfusion with the snares released. During the period of coronary occlusion, 10 pigs were placed on PB, 10 pigs received PB+PICSO, and 10 pigs received no support (unmodified). Hearts treated with the combination of PB+PICSO had the highest wall motion scores (unmodified, 1.4 +/- 0.3; PB, 1.4 +/- 0.3; PB+PICSO, 2.8 +/- 0.3 [p < 0.05 versus unmodified and PB]) and the lowest area of necrosis in the area at risk (unmodified, 73% +/- 3%; PB, 43% +/- 2%; PB+PICSO, 14% +/- 2% [p < 0.05, PB and PB+PICSO versus unmodified; p < 0.05, PB+PICSO versus PB]). We conclude that combining PB with coronary venous retroperfusion significantly limits myocardial necrosis.

Decreased incidence of arterial thrombosis using heparin-bonded intraaortic balloons

BACKGROUND This experimental study sought to determine whether heparin-bonding of intraaortic balloons (IAB) would decrease the incidence of arterial thrombosis in the absence of systemic heparinization. METHODS In 25 adult pigs, a 9F, 40-mL IAB was inserted into the femoral artery and positioned just below the takeoff of the left subclavian artery for 9 hours. Five animals received systemic heparin, 10 animals had no heparin, and another 10 animals received no heparin but the IAB was heparin-bonded (Duraflo II). Thrombus formation was assessed using a numerical scoring system (0 = no thrombosis to 3 = thrombus >5 cm or evidence of luminal compromise). RESULTS Animals receiving heparin and heparin-bonded IAB had no thrombus formation around the IAB (mean +/- SE; 0 +/- 0.00 heparin versus 1.55 +/- 0.29 no heparin versus 0 +/- 0.00 heparin-bonded; p < 0.005), at the insertion site (0 +/- 0.00 heparin versus 1.55 +/- 0.29 no heparin versus 0 +/- 0.0 heparin-bonded; p < 0.005), and in the distal femoral artery (0 +/- 0.00 heparin versus 2.00 +/- 0.23 no heparin versus 0 +/- 0.00 heparin-bonded; p < 0.005). CONCLUSIONS Heparin-bonding of the IAB significantly decreases thrombus formation in the absence of systemic heparinization.