Heparin-coated cardiopulmonary bypass circuits reduce circulating complement factors and interleukin-6 in paediatric heart surgery

Children are sensitive to the inflammatory side effects of cardiopulmonary bypass (CPB). Our intention was to investigate if the biocompatibility benefits of heparin-coated CPB circuits apply to children. In 20 operations, 19 children were randomized to heparin-coated (group HC, n = 10) or standard (group C, n = 10) bypass circuits. Plasma levels of acute phase reactants, interleukins, granulocytic proteins and complement factors were measured. All were significantly elevated after CPB. Levels of complement factor C3a (851 (791-959)ng/ml [median with quartiles] in group C, 497 (476-573)ng/ml in group HC, p < 0.001), Terminal Complement Complex (114 (71-130) AU/ml in group C, 35.5 (28.9-51.4) AU/ml in group HC, p < 0.001), and interleukin-6 (570 (203-743) pg/ml in group C, 168 (111-206)pg/ml in group HC, p = 0.005), were significantly reduced in group HC. Heparin-coated CPB circuits improve the biocompatibility of CPB during heart surgery in the paediatric patient population, as reflected by significantly reduced levels of circulating complement factors and interleukin-6.     

Changes in Platelet, Granulocyte, and Complement Activation During Cardiopulmonary Bypass Using Heparin-coated Equipment

Abstract: The effects of heparin-coated cardiopulmonary bypass (CPB) systems on platelet, granulocyte, and complement activation were investigated during cardiopulmonary bypass. Thirty patients underwent coronary artery bypass surgery with a heparin-coated (Carmeda Bio-Active Surface, CBAS, Medtronic, U.S.A.) CPB system (HC group, n = 10), a heparin-coated oxygenator and uncoated CPB circuit (HO group, n = 10), or an uncoated system (UC group, n = 10). In the HO group, plasma C3a (1667 ± 632 ng/ml) and C4a (1088 ± 319 ng/ml) concentrations were significantly (p < 0.05) lower than in the UC group (2846 ± 1045 ng/ml and 1494 ± 480 ng/ml, respectively) 10 min after the administration of protamine, but there were no significant differences in the platelet or granulocyte counts. In the HC group, granulocyte elastase concentrations 120 min after the onset of CPB (365 ± 177 μg/L) and 10 min after the administration of protamine (676 ± 314 μg/L) were significantly (p < 0.05) lower than in the other 2 groups (820 ± 341 and 893 ± 303 μg/L and 1365 ± 595 and 1,258 ± 622 μg/L). In addition, the increase in the plasma C3a concentration in the HC group 60 (p < 0.05) and 120 min after the onset of CPB (p < 0.05) was significantly less than in the other 2 groups. The C3a and C4a concentrations 10 min after the administration of protamine were significantly (p < 0.005 and p < 0.05) less in the HC group than in the UC group. Platelet counts 10 min after the administration of protamine were significantly higher (p < 0.05) and plasma β-throm-boglobulin concentrations during CPB were significantly lower in the HC group than in the other 2 groups 5 (p < 0.05), 60, and 120 min (p < 0.005) after the onset of CPB. Postoperative blood loss during the first 12 h in the HC group was significantly (p < 0.05) less than that in the UC group. The heparin-coated oxygenator and uncoated CPB circuit reduced complement activation but demonstrated no significant effects on the platelet and granulocyte systems. However, the heparin-coated CPB circuit (with all components making blood contact) reduced platelet, granulocyte, and complement activation and significantly reduced postoperative blood loss. Therefore, heparin coating of CPB systems improves biocompatibility.     

Circulating Cytokines and Granulocyte-Derived Enzymes During Complex Heart Surgery: A Clinical Study with Special Reference to Heparin-Coating of Cardiopulmonary Bypass Circuits

Blood contact with artificial surfaces during cardiopulmonary bypass (CPB) triggers a systemic inflammatory response in which complement, granulocytes and cytokines play a major role. Heparin-coated CPB circuits were recently shown to reduce complement and granulocyte activation in such circumstances. The present study comprised 20 complex heart operations, 10 with heparin-coated circuits (group HC) and 10 controls (group C), with evaluation of changes in terminal complement complex, the granulocyte enzymes myeloperoxidase and lactoferrin, and the cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8). Standard heparin dose and uncoated cardiotomy reservoir were used in all cases. In both groups the levels of enzymes and terminal complement complex rose significantly, beginning at conclusion of CPB, above base values, without significant intergroup differences. IL-6 and IL-8 also increased significantly, but tended to be lower in the HC group, starting at CPB end and continuing until 20 hours postoperatively: for IL-6 the difference was significant at CPB end (83 ± 18 vs 197 ± 39 μg/1, p = 0.21). Significantly increased inflammatory response was thus found during complex heart operations even with use of heparin-coated CPB sets. The heparin-coating of circuits seems to diminish cytokine production.     

A new poly-2-methoxyethylacrylate-coated cardiopulmonary bypass circuit possesses superior platelet preservation and inflammatory suppression efficacy

BACKGROUND: Poly-2-methoxyethylacrylate (PMEA) is a new coating material, and several studies have revealed that PMEA-coated cardiopulmonary bypass (CPB) circuits have good biocompatibility. This study sought to compare this biocompatibility with those of heparin-coated and noncoated circuits. METHODS: Forty-five patients undergoing coronary artery bypass grafting were randomly assigned to PMEA-coated (group P, n = 15), heparin-coated (group H, n = 15), or noncoated (group N, n = 15) circuit groups. Clinical data and the following markers were analyzed: (1) platelet preservation by number of platelets; (2) complement (C) activation by C3a and C4a levels; (3) inflammatory response by interleukin-6 (IL-6) and interleukin-8 (IL-8) levels. RESULTS: Platelet numbers were significantly preserved in group P compared with groups N and H. Postoperative blood loss did not differ among the groups. During CPB, C3a values were significantly lower in group H (536 +/- 145 ng/mL) than in group P (1,458 +/- 433 ng/mL, p < 0.01) and group N (1,815 +/- 845 ng/mL, p < 0.01). The C4a values did not differ 60 minutes after CPB initiation among the groups. The IL-6 and IL-8 levels were significantly lower in group P and group H than in group N. CONCLUSIONS: The PMEA coating was superior to heparin coating and noncoating in preserving platelets, and was equivalent to heparin coating in terms of the perioperative clinical course and inhibition of inflammatory cytokines, but slightly inferior in reducing complement activation.     

Biocompatibility of Heparin-Coated Circuits in Pediatric Cardiopulmonary Bypass

Abstract: In this study, we evaluated the biocompatibility of heparin-coated circuits in pediatric cardiopulmonary bypass (CPB). Eight patients were divided into 2 groups: the control group (Group C) and heparin-coated group (Group H). In Group H, CPB circuits, including the arterial pump, oxygenator, and cannulas were heparin-coated. Before, during, and after CPB, blood samples were obtained to assess the platelet counts (Plat), α2-plasmin plas-minogen inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), C3 activation products (C3a), inter-leukin (IL)-6, IL-8, and polymorphonuclear neutrophil leukocyte (PMN) elastase. There was no significant difference in Plat, PIC, or TAT between groups. Group H showed significantly low levels of C3a (during and after CPB), PMN elastase (during CPB), and IL-6 (after CPB). These data demonstrated that in pediatric CPB, heparin-coated CPB circuits reduced the activation of complements and the production of PMN elastase and IL-6, suggesting the superior biocompatibility of the heparin-coated circuits.     

Heparin-coated Cardiopulmonary Bypass Circuits in Coronary Bypass Surgery

Abstract: Cardiopulmonary bypass (CPB) is a nonphysiologic environment for an organism. The damage of blood components may also lead to organ dysfunction, sometimes recognized as postperfusion syndrome. One possible way to diminish the risk of these complications would be to reduce the thorombogenicity and to improve the biocompatibility of the artificial surfaces by using a heparin-coated CPB circuit. In this study, we compared a heparin-coated CPB circuit with a noncoated CPB circuit in terms of biocompatibility in 20 patients undergoing elective coronary bypass surgery. We employed a Dura-flo II (n = 10) as a heparin-coated CPB circuit and a Univox IC (n = 10) as control subjects. Ten patients (Group C) were operated on using the heparin-coated CPB circuit. A total of 10 patients were given heparin in a reduced dose (2.0 mg/kg), and additional heparin was given if the activated clotting time (ACT) was below 400 s. The control group also included 10 patients (Group NC), who were operated on with noncoated devices. They received 2.5 mg/kg of heparin, and additional heparin was given if the ACT was below 450 s. All patients had normal coagulation parameters and did not receive blood transfusion. We measured complement activation levels (C3a, C4a), platelet count, thrombin-antithrombin III complex levels, D-dimer levels, and ACT during CPB and respiratory index postoperatively. The concentration of C3a in group NC was significantly higher than that in group C. Platelet reduction in group NC was significantly greater than that in group C. There were no significant differences in the remaining parameters between the 2 groups. We concluded that heparin-coated CPB circuits improved biocompatibility by reducing complement activation and platelet consumption and enabled us to reduce the dose of heparin required for systemic heparinization.     

Biocompatibility of poly2methoxyethylacrylate coating for cardiopulmonary bypass.

The systemic inflammatory response to cardiopulmonary bypass (CPB) may contribute to the development of postoperative complications. Heparin-coated circuits and poly2methoxyethylacrylate (PMEA)-coated circuits have been developed to reduce the risk of such complications. We compared the biocompatibility of these circuits. Twelve patients scheduled to undergo elective coronary artery bypass grafting (CABG) with CPB were assigned to CPB with a PMEA-coated circuit (PMEA-coated group, n=6) or a heparin-coated circuit (heparin-coated group, n=6). The plasma concentrations of the following inflammatory markers were measured before CPB and just after, 4 hours after, and 24 hours after the termination of CPB: cytokines (interleukin [IL]-6, IL-8, IL-10), complement factor (C3a), polymorphonuclear elastase (PMNE), and coagulofibrinolytic factors (thrombin-antithrombin III complex [TAT], D-dimer). Postoperative clinical response was evaluated on the basis of respiratory index, blood loss, and the postoperative and preoperative body-weight percent ratio. There were no significant differences between the groups in the plasma concentrations of IL-6, IL-10, C3a, PMNE, TAT, or D-dimer. Plasma IL-8 concentrations were below the assay detection limits at all time points in both groups. Clinical variables did not differ significantly between the groups. In conclusion, PMEA-coated CPB circuits are as biocompatible as heparin-coated CPB circuits and prevent postoperative organ dysfunction in patients undergoing elective CABG with CPB.     

Inflammatory response after coronary revascularization: off-pump versus on-pump (heparin-coated circuits and poly2methoxyethylacrylate-coated circuits).

OBJECTIVE: Off-pump coronary artery bypass grafting (OPCAB) may reduce the inflammatory response associated with cardiopulmonary bypass (CPB) and contribute to minimizing postoperative complications. Heparin-coated circuits and poly2methoxyethylacrylate (PMEA)-coated circuits were developed to reduce such complications. We compared the postoperative inflammatory response with or without CPB. METHODS: Eighteen consecutive patients undergoing isolated coronary artery bypass grafting (CABG) were divided into three groups: OPCAB group (n=6), heparin-coated circuits group (n=6), PMEA-coated circuits group (n=6). The plasma concentrations of the following inflammatory markers were measured: cytokines [interleukin (IL-10)], polymorphonuclear elastase (PMNE), coagulofibrinolytic factor [thrombin-antithrombin III complex (TAT)], complement factor (C3a). RESULTS: At the end of CPB, IL-10 and TAT concentrations were significantly different among the three groups (OPCAB group < PMEA-coated group < heparin-coated group). The PMNE concentration was significantly lower in the OPCAB group and the heparin-coated group as compared to the PMEA-coated group both at the end of CPB and 4 hours after CPB. C3a concentration was significantly lower in the OPCAB group than in the CPB groups at the end of CPB. Clinical variables did not differ significantly among the three groups. CONCLUSION: Off-pump CABG is associated with a reduction in the inflammatory response when compared with on-pump CABG, using either PMEA-coated or heparin-coated circuits.     

Reduced complement activation with heparin-coated oxygenator and tubings in coronary bypass operations.

Complement activation after cardiopulmonary bypass is correlated with postoperative organ dysfunction. Heparin coating of the entire blood-contact surface of the cardiopulmonary bypass circuit has proved to reduce complement activation in vitro. A membrane oxygenator and tubing setup coated with functionally active heparin was compared with an uncoated, otherwise identical setup in 20 patients undergoing routine coronary bypass operations. The concentrations of C3 activation products and the terminal complement complex were measured in sensitive and specific enzyme immunoassays. Peak concentrations of C3 activation products were 90.1 (74.7 to 107.4) AU/ml (medians and 95% confidence intervals) and 52.4 (35.7 to 76.4) AU/ml with the uncoated and coated setups, respectively (p = 0.02). The corresponding concentrations of the terminal complement complex were 26.2 (20.1 to 37.5) AU/ml and 13.7 (11.1 to 25.1) AU/ml (p = 0.03). Blood loss from the mediastinal drains during the first 12 postoperative hours was 533 (416 to 975) ml in patients treated with the uncoated setup and 388 (313 to 579) ml in the coated treatment group (p = 0.06) and was significantly correlated with peak concentrations of the terminal complement complex (p = 0.01). There were no differences in neutrophil counts nor platelet numbers between the treatment groups. The approximate 45% reduction in complement activation with the heparin-coated cardiopulmonary bypass device indicates a substantial improvement of biocompatibility.     

Cardiopulmonary bypass with modified fluid gelatin and heparin-coated circuits

We have assessed the efficacy of cardiopulmonary bypass (CPB) using normal colloid oncotic pressure (COP) in a randomized, controlled study of 20 patients undergoing elective coronary artery surgery using heparin-coated circuits. For CPB, we used either crystalloid priming 1650 ml (n = 10) or colloid priming 1650 ml (2.4% modified fluid gelatin, n = 10). While COP did not change during bypass in the colloid group, a decline was observed in the crystalloid group (P = 0.005). By the end of bypass, the decrease in COP compared with baseline (delta COP) was 8.5 (S.D. 1.1) mm Hg in the crystalloid group compared with 1.5 (2.1) mm Hg in the colloid group (P = 0.0001). delta COP correlated positively with fluid balance during bypass (r2 = 0.41, P = 0.002). Similar increments in complement factors C3b/c and C4b/c, tumour necrosis factor-alpha and neutrophil elastase, but not endotoxins, were found in both groups as indicators of a systemic inflammatory response. A clinical performance score composed of fluid balance, postoperative duration of intubation and the difference between rectal temperature and skin temperature was more favourable in patients treated with colloid priming (P = 0.03). Median postoperative hospital stay was 7 (range 5-16) days in the crystalloid group compared with 5 (4-8) days in the colloid group (P = 0.016). Regression analysis indicated that CPB time, fluid balance during operation and postoperative PO2/FlO2 ratio were independent factors that predicted postoperative hospital stay. From these preliminary results we conclude that in the absence of endotoxaemia, use of a normal COP during CPB with modified fluid gelatin in heparin-coated circuits resulted in an improved postoperative course an a reduction in hospital stay.      

Heparin-Coated Equipment Reduces Complement Activation during Cardiopulmonary Bypass in the Pig

Complement activation was studied during cardiopulmonary bypass (CPB) in the pig. One group of animals was perfused for 2 h using a standard extracorporeal circuit including a hollow fiber membrane oxygenator with full systemic heparinization. Another group was treated in the same way, except that bypass was performed through a heparin-coated CPB circuit (Carmeda Bio-Active Surface, CBAS) and systemic heparinization was reduced by 75%. It was found that complement activation during CPB, measured as changes in the ratio C3d/C3, was significantly less in the CBAS group, most probably reflecting a better biocompatibility.     

Biocompatibility of Heparin-Coated Membrane Oxygenator During Cardiopulmonary Bypass

Abstract: The biocompatibility of the cardiopulmonary bypass (CPB) circuit, in which an oxygenator is solely heparinized, was assessed by systemic inflammatory reactions as an indicator during CPB. Fourteen patients, 11 males and 3 females, underwent coronary artery bypass surgery and were randomly divided into 2 groups of 7 patients each. For the heparin–coated oxygenator group (Group H), a heparin–coated membrane oxygenator was used in the CPB circuit, and in the control (Group C) an uncoated membrane oxygenator was employed. Systemic inflammatory reactions, such as platelet activation, prostaglandin production, complement activation, and activated granulocyte released substance, were measured prior to, during, and 6 h after CPB. The number of platelets decreased after protamine administration in both groups (14. 5 ±4. 7 times 10⁴/μl in Group H and 13. 8 ± 8. 7 times 10⁴/μd in Group C) and returned to baseline levels in Group H while it remained decreased in Group C at 6 h after CPB. The platelet factor 4 level was significantly lower in Group H (181 ± 40 ng/ml) than in Group C (297 ±131 ng/ml) after protamine administration. Thromboxane–B₂ (TXB₂) rose during CPB in both groups; however, there were significantly different levels of TXB₂ between the 2 groups at 60 min after CPB (293±258 pg/ml in Group H versus 408 ± 120 pg/ml in Group C) and after protamine administration (259 ± 122 pg/ml in Group H versus 709 ± 418 pg/ml in Group C). Plasma concentrations of granulocyte elastase were significantly lower in Group H at 30, 60 and 90 min, immediately after, and post–CPB than those of Group C. Although the oxygenator was solely heparinized in the CPB circuit, it was sufficiently effective to reduce inflammatory reactions during coronary artery bypass operation, and the heparin–coated surface seems to be more endothelium–like.     

Heparin-coated circuits reduce activation of granulocytes during cardiopulmonary bypass. A clinical study.

Activated granulocytes release highly active enzymes such as myeloperoxidase and lactoferrin, which can be involved in tissue destruction mediated by oxygen free radicals. Cardiopulmonary bypass has been reported to activate granulocytes. Bypass circuits coated with heparin have been shown to reduce release of granulocyte factors in experimental studies. In the present study, heparin-coated circuits were compared with noncoated circuits. In seven patients undergoing coronary bypass, heparin-coated circuits were used (group HC), and seven served as control patients (group C). In group HC the heparin dose was reduced to 75% (225 IU/kg). Group C had the standard dose of 300 IU/kg. No preoperative differences in myeloperoxidase and lactoferrin were observed between the groups. At the end of bypass in both groups, there was a significant increase of these enzymes (p less than 0.001) followed by a later decrease. In group HC, however, the release of myeloperoxidase was significantly lower than in group C (215 +/- 24 versus 573 +/- 133 micrograms/L, mean +/- standard error of the mean). The release of lactoferrin was significantly lower in group HC than in group C both at the end of cardiopulmonary bypass (659 +/- 79 versus 1448 +/- 121 micrograms/L) and 3 hours after bypass (224 +/- 37 versus 536 +/- 82 micrograms/L). Granulocytes as well as total number of leukocytes continued to increase until 1 hour after bypass (p less than 0.001) and then manifested a slow decrease. It was concluded that the use of heparin-coated circuits reduced the release of granulocyte factors because of lower activation of leukocytes.     

Thrombin Generation During Cardiopulmonary Bypass Using Heparin-Coated or Standard Circuits

For quantitative comparison of thrombin generation during cardiopulmonary bypass (CPB) with heparin-coated vs conventional CPB circuits, thrombin-antithrombin III complex (TAT) and prothrombin fragment 1+2 (F₁₊₂) were analyzed in 20 patients undergoing combined heart valve surgery and coronary artery bypass grafting (CABG), in ten cases with heparin-coated circuits (COMB-HC) and in ten with standard circuits (COMB-C). Extensive thrombin generation was found in both groups, with maximal TAT and F₁₊₂ levels at the end of CPB. Of 15 operations with only CABG, seven were performed with heparin-coated circuits and heparin dose 40% of normal (CABG-HC), and eight with standard circuits and normal heparin doses (CABG-C). TAT was maximal at the end of CPB and F₁₊₂ peaked 3 hours after protamine injection. At the end of CPB both levels were significantly higher in the CABG-HC than in the CABG-C group, though thrombin generation was less than in the COMB groups. The abundant thrombin generation during CPB thus was much more pronounced during complex operations. Use of heparin-coated circuits did not reduce thrombin generation, which was increased by 60% reduction of the systemic heparin dose. The clinical implications are still unknown, as no complications were observed.     

Cardiac interleukin-6 release and myocardial recovery after aortic crossclamping. Crystalloid versus blood cardioplegia

BACKGROUND: Pro-inflammatory cytokines may play an important role in patient response to cardiopulmonary bypass (CPB). Since the myocardium is proposed to be a major source of cytokines, we studied the influence of the cardiolpegia type on interleukin-6 release and early myocardial recovery. METHODS: Experimental design: prospective, randomized study. Setting: university hospital, operative and intensive care. Patients: 20 consecutive patients (3 females) scheduled for elective coronary artery bypass grafting (CABG), mean age 62.8+/-5 years, history of myocardial infarction 11/20, left ventricular ejection fraction 62.9+/-15%. Interventions: patients were operated on using randomly either cold blood cardioplegia (B, n = 10) or cold crystalloid cardioplegia (C, n = 10). Measures: plasma levels of interleukin-6 (IL-6) were measured prior to CPB, after aortic declamping, after CPB, 1 hour, 6 hours and 12 hours postoperatively. RESULTS: Groups were comparable with respect to demographic data, left ventricular function, number of grafts, CPB and aortic crossclamp time. Group B patients demonstrated significant lower IL-6 levels after 1 hour (210+/-108 vs. 578+/-443 pg/ml), 6 hours (204+/-91 vs. 1210+/-671 pg/ml) and 12 hours (174+/-97 vs. 971+/-623 pg/ml). Post-CPB cardiac index was superior in group B (3.9+/-0.3 vs. 3.2+/-0.3 l/min/m2, p<0.05) with similar doses of inotropes. Group B patients could earlier be weaned off respirator (10+/-4 vs. 13+/-4 hours, p<0.05) and showed minor blood loss (635+/-211 vs. 918+/-347 ml, p<0.05). CONCLUSIONS: Inflammatory response to CPB is associated with delayed myocardial recovery. The use of blood cardioplegia may attenuate inflammatory reactions.     

Effects of Heparin Coating of Cardiopulmonary Bypass Circuits on In Vitro Oxygen Free Radical Production During Coronary Bypass Surgery

Abstract During cardiopulmonary bypass (CPB) oxygen free radicals (OFR) are formed, which can mediate reactions damaging tissue components. Blood contact with artificial surfaces during CPB leads to an activation of leukocytes, which are one of the sources of the OFR. Heparin coating of the CPB circuit reduces granulocyte activation. In the present study, the heparin-coated circuits with noncoated cardiotomy reservoirs (Group HC) were compared with noncoated, otherwise similar CPB sets (Group C). In each group, 8 patients were operated on for coronary revascularization. The release of granulocyte granule proteins myeloperoxidase (MPO) and lac-toferrin (LF) was evaluated. Production of OFR in the whole blood and in the granulocyte suspension were measured by chemiluminescence (CL). In both groups the whole blood CL declined during CPB. The whole blood CL induced by serum-opsonized zymosan, when enhanced by luminol, was significantly lower in Group HC at 45 min after CPB start (68 ± 6% of initial values in Group HC vs. 87 ± 6% in Group C, mean ± SEM) and 30 min after protaminization (54 ± 6% of initial values in Group HC vs. 72 ± 6% in Group C, mean ± SEM), and CL was significantly higher in Group HC at CPB end (83 ± 5% of initial values in Group HC vs. 67 ± 5% in Group C, mean ± SEM) when enhanced by lucigenin. CL of isolated granulocytes showed no significant differences between the groups. Release of MPO at CPB end and of LF 45 min after start of CPB and at CPB end were significantly lower in the heparin-coated CPB circuits.     

Comparative Study of the Effect on Clinical Outcome of the Use of an Open Circuit and the Use of a Closed Circuit in Cardiopulmonary Bypass for a Graft Replacement of the Descending Thoracic or Thoracoabdominal Aorta

Purpose. We studied the benefits of reduced systemic heparinization in a heparin-coated cardiopulmonary bypass (CPB) system for graft replacement of the descending thoracic (TA) or thoracoabdominal aorta (TAA). Methods. Fifty-five patients were assigned to two groups: one group in which closed CPB circuits with reduced heparinization by elimination of the hard shell reservoir were used (group A, n = 36) and one group in which open circuits with full heparinization were used (group B, n = 19). Results. The transfusion requirement tended to be greater as the duration of CPB increased, even in group A. The incidences of renal dysfunction in two groups were not significantly different. Only the incidence of pulmonary dysfunction was significantly higher in group B. A reduction of systemic heparinization had no benefit for perioperative bleeding. In the TAA operation, the total amount of hemorrhaging in group A was greater than that in group B, but the difference was not significant. Conclusions. No beneficial effects of the use of heparin-coated CPB circuits on the amount of perioperative bleeding and postoperative organ damage, including renal dysfunction, were found in this study. However, our findings suggest that it may be better to avoid the use of closed CPB circuits in operations with a prolonged duration of CPB, such as a TAA operation.     

Reducing hemostatic activation during cardiopulmonary bypass: a combined approach

Interventions such as heparin-coated circuits, epsilon-aminocaproic acid, and reduced shed blood reinfusion have shown mixed results when applied individually for limiting hemostatic activation during cardiopulmonary bypass (CPB). We compared coagulation and fibrinolytic activation during conventional CPB (control) (CTRL) using noncoated circuits, no antifibrinolytics, and open cardiotomy with a combined strategy (HAC) that used heparin-coated circuits, epsilon-aminocaproic acid, and closed cardiotomy. Blood samples were drawn before, during, and after CPB for primary coronary bypass grafting surgery from 9 CTRL patients and 10 HAC patients. Thrombin-antithrombin complex and fibrinopeptide A levels (markers of thrombin and fibrin generation) were reduced in the HAC versus CTRL group after 30 min of CPB (P < 0.05). Average tissue plasminogen activator (tPA) levels were significantly lower in the HAC group by 30 min on CPB (P < 0.05), resulting in preservation of plasminogen activator inhibitor (PAI)-1 during CPB (P < 0.05). D-Dimer, a measure of intravascular fibrin formation and removal, was reduced in the HAC group during and after CPB (P < 0.005). Overall, the combined strategy was associated with a reduction in CPB-induced increases in markers of thrombin generation, fibrin formation, tPA release, and fibrin degradation and better preservation of PAI-1. IMPLICATIONS: A combined approach during cardiopulmonary bypass (CPB) that uses heparin-coated circuits, epsilon-aminocaproic acid, and limited reinfusion of shed pericardial blood is associated with reduced activation of the coagulation and fibrinolytic systems that typically occurs during conventional CPB.     

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.     

Biocompatibility of heparin-coated extracorporeal bypass circuits: new heparin bonded bioline system

Biocompatibility of a new type of heparin-coated cardiopulmonary bypass equipment, the Bioline, was evaluated in coronary artery bypass surgery cases. The heparin-coated (H) group (n = 15; Quadrox Bioline oxygenator/reservior and Carmeda BioMedicus BP-80 centrifugal pump) was compared with the nonheparin-coated (N) group (n = 12; uncoated, otherwise similar oxygenator, centrifugal pump, tubing, and filter set). Both groups used full systemic heparinization. The peak values of neutrophil elastase, C3a, IL-6, and IL-8 at 2 h after cardiopulmonary bypass (CPB), and C3a levels at the end of CPB and at 2 h after CPB were significantly reduced in the H group compared with those of the N group. However, no statistically significant intergroup differences were observed in thrombin-antithrombin complex, D-dimer, beta-thromboglobulin, or platelet factor-4. No significant differences were observed in hemostasis time, postoperative 12 h blood loss, required amount of blood transfusion, or intubation time. In conclusion, the Bioline demonstrated partially improved biocompatibility, in terms of leukocyte and complement activation, and proinflammatory cytokine production. However, it did not improve platelet activation, coagulation, or fibrinolysis cascade under full systemic heparinization. As a result, the clinical beneficial impact seemed to be the minimum.