Decreased blood loss after cardiopulmonary bypass using heparin-coated circuit and 50% reduction of heparin dose.

In a randomized, double-blind study of patients undergoing elective coronary artery grafting, the effect of heparin-coated circuit combined with 50% reduction of systemic heparin bolus was investigated. Ten patients comprised group HC (heparin-coated) and ten group C (controls). The mean total doses of heparin were 172 IU/kg in group HC and 416 IU/kg in group C and the respective protamine doses were 0.96 and 3.96 mg/kg (both p < 0.001). Activated clotting times during cardiopulmonary bypass were significantly shorter in group HC, and both intra- and postoperative bleeding was significantly less than in group C (7.7 vs. 11.7 ml/kg, p = 0.036, and 6.9 vs. 9.7 ml/kg, p = 0.004). Hemoglobin loss via the drains was 22.5 g in group HC and 43.7 g in group C (p < 0.005). Hemolysis at the end of bypass was significantly greater in group C. Apart from one perioperative myocardial infarction in group HC the postoperative course was uneventful. Use of a heparin-coated circuit is concluded to permit complication-free reduction of heparin and protamine doses and to decrease both intra- and postoperative bleeding, which may favorably influence the outcome of coronary artery grafting.     

Heparin management protocol for cardiopulmonary bypass influences postoperative heparin rebound but not bleeding.

A group of 63 adult patients undergoing cardiac surgical procedures requiring cardiopulmonary bypass (CPB) were studied to examine the relationship between heparin doses administered and postoperative bleeding. Patients were randomly assigned either to receive heparin 200 U/kg and additional heparin as needed to reach and maintain an activated clotting time (ACT) greater than 400 s for CPB (group A, n = 30), or to receive heparin 400 U/kg and additional heparin as needed to reach and maintain a whole blood heparin concentration greater than 4.0 U/ml for CPB (group H, n = 33). Groups were compared for the amount of postoperative bleeding, heparin rebound, homologous transfusion requirements, and standard laboratory coagulation tests. In the last 33 patients studied, additional tests of platelet aggregation and plasma levels of beta thromboglobulin (BTG), antithrombin III, and several markers of fibrinolysis were measured and compared by group. The mean heparin dose was 28,000 +/- 4,800 U for group A and 57,000 +/- 10,700 U for group H (P less than 0.05 for group A vs. group H). At 8 and 24 h postoperatively, mediastinal drainage did not differ significantly between groups (mean 24-h drainage +/- SD = 901 +/- 414 ml in group A, 1035 +/- 501 ml in group H), nor did the incidence of transfusion with homologous blood products.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coagulofibrinolysis during heparin-coated cardiopulmonary bypass with reduced heparinization.

BACKGROUND: We examined the safety of reduced systemic heparinization during heparin-coated cardiopulmonary bypass by measuring coagulofibrinolitic indices, including fibrinopeptide A, which directly reflects fibrinogenesis. METHODS: Twenty-four patients who had elective cardiac operations were perfused using a circuit coated with covalently bonded heparin. Twelve patients received 300 U/kg of heparin and the remaining 12 patients received 150 U/kg. Blood was obtained for the measurement of thrombin-antithrombin III complexes, fibrinopeptide A, plasmin-alpha 2 plasmin inhibitor complexes, and D-dimer preoperatively; after heparin administration; 10, 60, and 90 minutes after the start of bypass; after protamine administration; and 1, 3, 6, 12, and 24 hours after the end of bypass. RESULTS: Preoperative, intraoperative, and postoperative variables including postoperative bleeding were not significantly different between the two groups. Further, there were no complications in either group. No significant differences between the two groups were noted for any hematologic index at any time point. CONCLUSIONS: Reduced systemic heparinization combined with a heparin-coated cardiopulmonary bypass circuit is biochemically and clinically safe but does not reduce postoperative bleeding.     

Improving cardiopulmonary bypass: heparin-coated circuits

Heparin-coated circuits have been repeatedly proven to reduce the inflammatory response and foreign surface activation triggered upon initiation of cardiopulmonary bypass (CPB). In recent years, increasing numbers of studies are proving significant reductions in postoperative blood loss and transfusion requirements and improvements in clinical outcomes as a result of heparin-coated circuits. These results are promising steps in our efforts to improve CPB, as our patient population gets older and more complicated.     

Coronary artery bypass surgery with heparin-coated perfusion circuits and low-dose heparinization.

OBJECTIVE: To evaluate the safety and efficacy of heparin-coated perfusion circuits with low-dose heparinization and centrifugal pumping compared with the standard method during coronary artery bypass grafting. DESIGN: Prospective, randomized, single-blind clinical trial. SETTING: A primary care institution. PATIENTS: Ninety patients who underwent first-time elective coronary artery bypass grafting were eligible for the study. After giving informed consent, they were randomly assigned to 1 of 3 groups (30/group). INTERVENTIONS: Perfusion on regular uncoated bypass equipment with a roller pump and full-dose heparinization (300 IU/kg bolus, activated clotting time [ACT] > 400 s) (group 1), on a heparin-coated oxygenator with a centrifugal pump and full-dose heparinization (group 2) and on fully heparin-coated bypass equipment with a centrifugal pump and low-dose heparinization (100 IU/kg bolus, ACT of 180-400 s) (group 3). Standard coronary artery bypass grafting was performed. OUTCOME MEASURES: Postoperative bleeding, transfusion requirements and clinical outcomes. RESULTS: There were no complications related to the study protocol. Study groups were similar in terms of postoperative bleeding, transfusion requirements and clinical outcomes. CONCLUSIONS: Heparin-coated cardiopulmonary bypass with low-dose heparinization and centrifugal pumping is a safe practice but showed no advantages over the use of regular uncoated bypass circuits for coronary bypass surgery.     

Platelet-rich plasma reduces postoperative blood loss after cardiopulmonary bypass

To study the effect of plasma sequestration and reinfusion of platelet-rich plasma on blood loss after cardiopulmonary bypass, 18 patients undergoing heart operations were randomly selected either to have collected or not to have collected approximately 250 ml of platelet-rich plasma before initiating cardiopulmonary bypass with the use of the Haemonetics Plasma Saving System (Haemonetics Corporation, Braintree, Mass.). All patients had standardized anesthesia and cardiopulmonary bypass. After reversal of heparin, autologous platelet-rich plasma was reinfused in nine patients. Thrombocyte counts, hemoglobin, and hematocrit were calculated before, during, and after cardiopulmonary bypass, and 24 and 48 hours postoperatively. Blood loss and total number of transfusions were recorded. Although 9% of the total platelet volume was removed, there were no hemodynamic complications related to the use of the Haemonetics Plasma Saving System. In both groups, significant low levels of thrombocytes, hemoglobin, and hematocrit were seen after cardiopulmonary bypass. Platelet-rich plasma-reinfused patients had a significantly higher number of platelets after heparin reversal. They also had significantly less blood loss after the operation, necessitating 65% less banked blood products (p less than 0.05). We concluded that reinfusion of autologous platelet-rich plasma may serve as an effective and safe way to restore some of the hematologic derangements after cardiopulmonary bypass.     

Quantitative evaluation of heparin-coated versus non-heparin-coated bypass circuits during cardiopulmonary bypass

The extracorporealization of blood activates various elements of the fibrinolytic, coagulation, and complement systems. It is theorized that advancements in biocompatibility ameliorate many of the changes leading to improved patient management. The purpose of this study was to determine if heparin-coated circuit (HCC) utilization during cardiopulmonary bypass enhances patient outcomes in a cost-effective manner. A search of the English medical literature was completed to identify all clinical, prospective, randomized trials comparing HCC and non-HCC in patients undergoing coronary artery bypass grafting or valvular surgery. Twenty-six papers consisting of a sample size of 1515 patients were identified and included in the study parameters. The study distinguished between Duraflo II and Carmeda coating techniques and matched papers with different heparin loading doses, as well as use of a heparin-coated cardiotomy. Study parameters were matched for all papers and analyzed according to the availability of data. Statistically significant benefits of HCC were found in postoperative blood loss, time in the ICU, end bypass C3a, time to extubation, end bypass lactoferrin, and end platelet count, but not with respect to postoperative chest tube drainage, red blood cell transfusions, and end bypass TAT complex, D-dimers, and BTG. Data comparing the use of coated or uncoated cardiotomy utilization failed to demonstrate a benefit to heparin coating. Several immunological variables were ameliorated when Carmeda HCC was utilized, although data were insufficient to establish a cost-benefit analysis. In conclusion, heparin-coated circuitry provided statistically better results when compared to noncoated circuitry.     

Aprotinin reduces intraoperative and postoperative blood loss in membrane oxygenator cardiopulmonary bypass.

To determine whether aprotinin can provide a significant improvement of hemostasis in cardiopulmonary bypass using a membrane oxygenator, we tested this drug in a prospective, randomized, double-blind, placebo-controlled clinical trial. The subjects were 80 male patients undergoing cardiopulmonary bypass for coronary artery bypass grafting. Forty patients received aprotinin and 40 patients served as placebo controls. Aprotinin (4 x 10(6) KIU) was given as a continuous infusion, starting before operation and continuing until after cardiopulmonary bypass; additionally, 2 x 10(6) KIU aprotinin was added to the pump prime. Intraoperative and postoperative bleeding, respectively two thirds and one third of the total perioperative blood loss, were both significantly reduced in the aprotinin-treated group (p less than 0.01). The total average perioperative blood loss, corrected to a hemoglobin concentration of 7 mmol/L, was 550 mL in the aprotinin-treated patients versus 900 mL in the control patients. This reduction in blood loss, furthermore, significantly decreased the amount of postoperative blood transfusions (p less than 0.05) and increased the percentage of patients who did not receive postoperative donor blood from 42% to 68%. Aprotinin increased the activated clotting time significantly during cardiopulmonary bypass, which led to a reduction in heparin usage. The improved hemostasis during operation, despite the prolonged activated clotting time, might even abolish the need for heparin conversion with protamine at the end of cardiopulmonary bypass, thus allowing retransfusion through cardiotomy suction to be continued, which saves the blood that is currently lost with vacuum suction.     

Successful management after cardiopulmonary bypass without administration of protamine in a patient with severe food allergy--beneficial result with the use of heparin-coated bypass circuit

We experienced the anesthetic management for cardiac surgery without the administration of protamine in a patient with severe food allergy. The patient, a 15-year-old boy, who had been avoiding many kinds of food including fish due to severe food allergy, received a correction of ventricular septal defect under cardiopulmonary bypass (CPB). To detect intraoperative drugs, including protamine, which might induce allergic reaction, we performed intradermal tests and prick tests. We used heparin-coated bypass circuit to minimize the amount of heparin necessary for anticoagulation during CPB. After CPB, hemostasis was achieved without the administration of protamine, and the patient received neither transfusion nor blood product throughout the perioperative period. Avoidance of protamine is advisable if the patient is allergic to food especially fish. The use of heparin-coated bypass circuit should be considered to establish hemostasis without protamine after CPB and to reduce blood products.     

氨甲环酸减少体外循环手术后出血的临床观察

目的 评价氨甲环酸(TA)在减少体外循环心脏手术后出血的效果.方法 2009年3月至2011年10月间接受体外循环心脏手术者160例,随机分为氨甲环酸组(TA组,80例)和对照组(80例),在体外循环术中,TA组静脉注射TA,对照组注射等量的0.9%生理盐水.比较两组在肝素化前、鱼精蛋白中和肝素后和术后24h三个时间点血小板数量、凝血指标及血浆D-D二聚体水平,同时比较术后6h、24h纵隔心包引流量及术后输血量.结果 体外循环术后24h TA组的总失血量(250±117)ml,显著少于对照组的(840±353)ml,且术中、术后输血量TA组显著少于对照组.术后对照组的血浆D-D二聚体水平显著增加.而TA组的D-D二聚体水平无显著变化.结论 与对照组相比,TA可以发挥抗纤溶作用,并能够有效地降低体外循环术后出血.     

Effect of intraoperative aprotinin administration on postoperative bleeding in patients undergoing cardiopulmonary bypass operation.

To study the hemostyptic effect of aprotinin (Trasylol) in patients undergoing extracorporeal circulation for coronary artery bypass operations, we randomized 12 of 24 patients to receive aprotinin in high dosage (about 800 mg) during extracorporeal circulation. From the resulting two groups each, one patient was excluded from the study because of postoperative myocardial infarction (control group) and surgical hemorrhage (aprotinin group) leading to a second operation. Although heparin was used for anticoagulation in all 22 patients, all had a marked increase in plasma levels of thrombin-antithrombin III complexes during extracorporeal circulation, indicating an intravasal activation of coagulation. By monitoring the plasma levels of fibrin degradation products in patients without aprotinin therapy, we recorded a concomitant hyperfibrinolysis significantly less pronounced in patients receiving aprotinin (p less than 0.005). The mean total postoperative blood loss was lower in patients receiving aprotinin (620 ml) than in control patients (1000 ml; p less than 0.03). The results confirm previous reports of a hemostyptic effect of aprotinin in cardiac operations. This effect is probably due to a prevention of hyperfibrinolysis.     

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.     

Low activated coagulation time during cardiopulmonary bypass does not increase postoperative bleeding

The activated coagulation time (ACT) is widely used to monitor adequacy of anticoagulation during cardiopulmonary bypass despite absence of data establishing an ACT below which adverse outcomes occur. For anticoagulation before cardiopulmonary bypass, we administered a single dose of heparin (300 U/kg) to 193 patients and measured ACT and heparin levels at intervals after administration. No additional heparin was administered to any patient. Clot formation in the cardiopulmonary bypass circuit and excessive postoperative chest tube drainage were considered outcomes indicating inadequate anticoagulation. Cardiopulmonary bypass averaged 59 +/- 23 minutes (range, 30 to 138 minutes). Activated coagulation time values at every sampling period were normally distributed. In 51 patients (26.4%) ACT values were less than 400 seconds, including 4 less than 300 seconds, at some sampling time after heparinization. Patients with low ACT values did not bleed more postoperatively than those with high ACT values, nor was bleeding related to heparin level. No clots were found in any perfusion circuit. We conclude that a minimum ACT value for adequacy of heparinization is not yet defined but that it is less than 400 seconds.     

Safety of heparin-coated circuits in primates during deep hypothermic cardiopulmonary bypass

The purpose of this study is to evaluate the biologic impact of heparin-coated circuits without systemic heparinization during deep hypothermia. Baboons (n=6) were placed on a heparin-coated pediatric closed-circuit cardiopulmonary bypass (CPB) system and cooled to 18 degrees C. A control group (n=7) underwent similar protocol with a non heparin-coated circuit and received systemic heparin. Either low flow at 0.5 L/min/m 2 (n=8; 4 in each group) or circulatory arrest (n=5; 2 in experimental group and 3 in control group) was used during deep hypothermia. Samples for complete blood count (CBC), hepatic and renal function tests, activated clotting time (ACT) and thrombelastogram (TEG) were obtained before, during, and after bypass. Cerebral blood flow was measured using Xenon-133 and autopsies were performed to assess end-organ damage. The ACT returned to baseline in both groups, and renal and hepatic function were within normal limits. There was no significant difference between the TEG values between the groups post bypass. Fibrin split products were absent and fibrinogen levels were normal in both groups following bypass. Cerebral blood flows were equivalent in both groups before and after bypass, although in the heparin-coated group cerebral blood flows were significantly higher during CPB. There were no brain histologic changes in the heparin-coated group and one focal cortical infarct in the control group. This study suggests that hypothermia induced a state of anticoagulation that did not result in thrombus formation or end organ dysfunction during CPB with a heparin-coated circuit.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recent experiences with hexadimethrine for neutralizing heparin after cardiopulmonary bypass.

Hexadimethrine bromide was used for the neutralization of heparin during cardiac surgery in the late 1950s. For some years, this institution has used it for patients who may be allergic to protamine. In view of the recent renewal of interest in hexadimethrine, we present four cases outlining its use during cardiac procedures in such patients. Other drugs for reversing the action of heparin such as heparinase or platelet factor IV are not yet widely available.