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Objectives: Bioactive Carmeda® heparin-coated extracorporeal circuits (ECCs) have been shown to reduce contact phase and coagulation activation during cardiopulmonary bypass (CPB). Heparin coating is therefore effective in safely reducing coagulation during routine CPB. Balance® Biosurface is a new, recently developed biopassive coating containing negatively charged sulphonated polymers. This study sought to compare the clotting activation and thromboresistance of the Balance® (B) circuit with that of the Carmeda® (C) with full-dose systemic heparin (FDH) and reduced-dose systemic heparin (RDH)., Methods: This ex vivo study set-up comprising 40 experiments consisted of simplified ECC and circulation of freshly donated human blood. RDH and FDH regimens were obtained with 0.5 IU/ml and 1 IU/ml heparin administered to reach target activated clotting times (ACTs) of 250 and 500 s, respectively. The study design comprised four groups: FDH-C, FDH-B, RDH-C and RDH-B (all n = 10). Blood was sampled prior to and during the 2-h CPB. Coagulation activation was assessed (FXIIa, F1.2) and electron microscope scan imaging of oxygenators enabled determination of adhesion scores., Results: With a biopassive compared with bioactive surface, mean ACT was lower, regardless of the heparin regimen applied (P < 0.001), whereas the total heparin dose required to maintain ACT was above target level (P < 0.001). However, FXIIa and F1.2 values were similar in all groups throughout, as were pressure gradients among oxygenators. All groups demonstrated similar adhesion scores following ultrastructural oxygenator assessment., Conclusions: In the absence of surgical-related haemostatic disturbances and based on target ACT levels under reduced- or full-dose heparin, the clotting process was similar to heparin-coated and new sulphonated polymer-coated ECC, both demonstrating similar thromboresistance., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The role of complement activation on the cerebral vasculature after cardiopulmonary bypass (CPB) is unclear. The goal of the study was to assess whether heparin-coated CPB reduces complement activation, and influences cerebral blood flow velocities (CBFV). Twenty-four patients undergoing coronary surgery were randomly allocated to non-coated (NC-group) or heparin-coated (HC-group) CPB. Complement activation was assessed by measuring sC5b-9. Transcranial Doppler (TCD) was performed on middle cerebral arteries before and after CPB. Systolic (SV), diastolic (DV) and mean (MV) CBFV were measured. Significant increase of sC5b-9 (p=0.003) was observed in the NC-group and CBFV increased after CPB (SV by 27%, p=0.05; DV by 40%, p=0.06; MV by 33%, p=0.04) whereas no changes were detected in the HC-group. TCD values were higher in the NC-group than in the HC-group (SV, p=0.04; DV, p=0.03; MV, p=0.03) although cardiac index, systemic vascular resistance, haematocrit and pCO(2) were similar. Postoperative SV, DV and MV were significantly correlated with sC5b-9 (r=0.583, p=0.009; r=0.581, p=0.009; r=0.598, p=0.007, respectively). Increased CBFV after CPB are correlated to the level of complement activation and may be controlled by heparin-coated circuits.

Background: The impact of the postoperative inflammatory response on the central nervous system after cardiac surgery is uncertain. The goal of the study was to evaluate the role of complement activation on cellular brain injury in patients undergoing coronary artery bypass grafting. In addition, neuropsychological functioning was assessed., Methods: We randomly assigned 30 patients to undergo surgery using either standard noncoated or heparin-coated extracorporeal circuits. Closed cardiopulmonary bypass and controlled suctions of pericardial shed blood were standardized in both groups. Complement activation and cellular brain injury were assessed by measuring sC5b-9 and protein s100beta. Neuropsychometric tests were performed at least 2 weeks before operation and at discharge. They served to calculate z scores of cognitive domains and changes in neuropsychological functioning., Results: Peak value of sC5b-9 at the end of cardiopulmonary bypass in the noncoated group was significantly higher than in the heparin-coated group (p = 0.005). Changes in the heparin-coated group were not significant. Glial injury started after initiation of surgery and peaked at the end of cardiopulmonary bypass with significantly higher concentration of s100beta in the noncoated than in the heparin-coated group (p = 0.008). Values of s100beta and of sC5b-9 were significantly correlated (p = 0.03). Although no statistically significant between group difference was detected, z scores of attention and flexibility or executive functions were lowered postoperatively within the noncoated group (p = 0.033 and p = 0.028), whereas z scores were unchanged within the heparin-coated group., Conclusions: Inhibition of complement activation by heparin-coated cardiopulmonary bypass reduced brain cell injury and was associated with preserved neuropsychological functioning after coronary artery bypass grafting.

Previous reports have highlighted the disparity in biocompatibility of two differently engineered heparin coatings during the cardiopulmonary bypass (CPB) procedure. The aim of this prospective study was to evaluate the impact of the difference in haemocompatibility provided by either the Duraflo II equipment or the Carmeda equipment in the terminal inflammatory response observed after coronary artery surgery. Thirty patients were randomly allocated to two groups to be operated on using either Duraflo II equipment (group I) or Carmeda equipment (group 2) for extracorporeal circulation (ECC). Initial inflammatory response was assessed by terminal complement complex activation (SC5b-9). The late inflammatory response observed in the postoperative period was assessed by measuring cytokine production (tumour factor necrosis (TNF alpha), interleukin IL-6, interleukin IL-8) and circulating concentrations of adhesion molecules (ELAM-1, ICAM-1). The release of SC5b-9 after CPB and after protamine administration was lower in group 2 than in group 1 (p = 0.0002 and p = 0.006, respectively). A significant production of cytokines was detected in both groups with peak values observed within the time range of 4-6 h after the start of CPB.

Objective: Heparin coating reduces complement activation on the surface of extracorporeal circuits. In this study we investigated its effect on activation of the contact system in 30 patients undergoing coronary artery bypass grafting with the use of a heparin-coated (Duraflo II, Baxter Healthcare Corp., Edwards Division, Santa Ana, Calif.; n = 15) or an uncoated extracorporeal circuit (n = 15)., Methods: Plasma markers that reflect activation of contact (kallikrein-C1-inhibitor complexes), coagulation (prothrombin fragments F1 + 2), or fibrinolytic (plasmin-alpha 2-antiplasmin complexes) systems were determined before and during the operation. The generation of kallikrein-C1-inhibitor complexes was reduced by 62% (p = 0.06) after the onset of cardiopulmonary bypass and by 43% (p = 0.026) after the cessation of bypass in the group in which a heparin-coated circuit was used compared with the group in which the circuit was uncoated. Generation was reduced by 58% (p = 0.06) when the ratio of kallikrein-C1-inhibitor to prekallikrein after onset of bypass was considered. We detected significant increases in F1 + 2 levels in both groups and increases in plasmin-alpha 2-antiplasmin complexes in the heparin-coated group at cessation of bypass, but no intergroup differences were observed. Thus use of heparin-coated extracorporeal circuits during cardiac operations reduces formation of kallikrein-C1-inhibitor complexes when compared with use of uncoated circuits. The heparin coating is not accompanied by similar reductions in coagulation or fibrinolysis, suggesting that thrombin and plasmin formation during cardiopulmonary bypass occurs mainly independently of the contact system activation.

Objectives: To evaluate whether the application of heparin treated circuits for elective coronary artery surgery improves postoperative recovery, a European multicenter randomised clinical trial was carried out., Methods: In 11 European heart centers, 805 low-risk patients underwent cardiopulmonary bypass (CPB) with either an untreated circuit (n = 407) or an identical but heparin treated circuit (n = 398, Duraflo II)., Results: Significant differences were found among participating centers with respect to patient characteristics, blood handling procedures and postoperative care. The use of heparin treated circuits revealed no overall changes in blood loss, blood use, time on ventilator, occurrence of adverse events, morbidity, mortality, and intensive care stay. These results did not change after adjustment for centers and (other) prognostic factors as analysed with logistic regression. In both groups no clinical or technical (patient or device related) side effects were reported. Because female gender and aortic cross clamp time appeared as prognostic factors in the logistic regression analysis, a subgroup analysis with these variables was performed. In a subpopulation of females (n = 99), those receiving heparin treated circuits needed less blood products, had a lower incidence of rhythm disturbances and were extubated earlier than controls. In another subgroup of patients with aortic cross clamp time exceeding 60 min (n = 197), the amount of patients requiring prolonged intensive care treatment (> 24 h) was significantly lower when they received heparin treated circuits versus controls., Conclusion: These findings suggest that improved recovery can be expected with heparin treated circuits in specific higher risk patient populations (e.g. females) and when prolonged aortic cross clamp time is anticipated. Further investigations are recommended to analyses the clinical benefit of heparin treated circuits in studies with patients in different well defined risk categories and under better standardised circumstances.

Background: This study was performed to evaluate whether the combination of heparin-coated extracorporeal circuits (ECC) and aprotinin treatment reduce blood activation during coronary artery operations., Methods: Sixty patients were prospectively divided into two groups (heparin-coated ECC and uncoated ECC groups), which were comparable in terms of age, sex, left ventricular function, preoperative aspirin use and consequent intraoperative aprotinin use, number of grafts, duration of aortic cross-clamping, and duration of cardiopulmonary bypass. Blood activation was assessed at different times during cardiopulmonary bypass by determination of complement activation (C3 and C4 activation products C3b/c and C4b/c and terminal complement complex), leukocyte activation (elastase), coagulation (scission peptide fibrinopeptide 1 + 2), and fibrinolysis (D-dimers)., Results: Univariate analysis showed that heparin-coated ECC, under conditions of standard heparinization, did not reduce perioperative blood loss and need for transfusion. Heparin coating, however, reduced maximum values of C3b/c (446 +/- 212 nmol/L versus 632 +/- 264 nmol/L with uncoated ECC; p = 0.0037) and maximum C4b/c values (92 +/- 48 nmol/L versus 172 +/- 148 nmol/L with uncoated ECC; p = 0.0069). Levels of terminal complement complex, elastase, fibrinopeptide 1 + 2, and D-dimers were not significantly modified by the use of heparin-coated ECC. Multivariate analysis showed that the intergroup differences in maximum C3b/c and C4b/c values were more pronounced in women in part with high baseline values of C3b/c. We also found that aprotinin contributed to the reduction of maximum values of fibrinopeptide 1 + 2 and D-dimers, whereas heparin coating had no significant influence on these parameters., Conclusions: We found no evidence of combined properties of heparin-coated ECC and aprotinin in reducing complement activation, coagulation, and fibrinolysis. We therefore recommend use of both together to achieve maximal reduction of blood activation during cardiopulmonary bypass for coronary artery operations.

In this prospective randomized trial, we studied whether heparin-coated extracorporeal circuits (ECC), known to reduce complement activation, could improve the clinical outcome of 200 patients undergoing coronary artery surgery. Patients have been divided into two groups (heparin-coated ECC and uncoated ECC groups) which were similar in terms of age, gender, left ventricle function, preoperative aspirin use and consequent intraoperative aprotinin use, number of grafts, duration of aortic cross-clamping and cardiopulmonary bypass. Univariate analysis showed that heparin coating did not reduce significantly postoperative bleeding (640 +/- 311 versus 682 +/- 342 ml with uncoated ECC) nor the need for transfusion (19% of patients versus 25% with uncoated ECC). Adverse events, including all mortality and morbidity noticed during the five first postoperative days, occurred in 20 patients of the uncoated ECC group and in eight patients of the heparin-coated ECC group (p = 0.013). The most frequent complications were supraventricular arrhythmias that occurred in 13 patients of the uncoated ECC group and in four patients of the heparin-coated ECC group (p = 0.02). Multivariate analysis by stepwise logistic regression showed that only heparin coating of the ECC was shown as a significant predictive factor of adverse events reduction (p = 0.01; odds ratio = 0.34). These data suggest that heparin coating reduced postoperative complications in patients undergoing coronary artery surgery.

Background: The biocompatibility of an extracorporeal circuit is improved by heparin bonding onto its inner surface. To determine the effect of heparin-coated circuits for cardiopulmonary bypass with aprotinin prime on postoperative recovery and resource utilization, a prospective study was done in 102 patients undergoing coronary artery bypass grafting with full systemic heparinization., Methods: Patients were randomly allocated to be treated with either a heparin-coated circuit (n = 51) or an uncoated circuit (n = 51). Differences in blood loss, need for blood transfusion, morbidity, and intensive care stay were analyzed., Results: No differences in blood loss and need for blood transfusion were found between the groups. The relative risk for adverse events in the heparin-coated group was 0.29 (95% confidence interval ranging from 0.10 to 0.80). Adverse events included myocardial infarction (2 patients in the uncoated group versus 0 in the heparin-coated group), rethoracotomy for excessive bleeding (1 versus 2), rhythm disturbance (7 versus 2), respiratory insufficiency (4 versus 0), and neurologic dysfunction (2 versus 0). The lower incidence of adverse events in the heparin-coated group was associated with a shorter intensive care stay (median, 2 days; range, 2 to 5 days) compared with the uncoated group (median, 3 days; range, 2 to 19 days, p = 0.03). The cost savings of 1 day of intensive care stay counterbalanced the additional costs of heparin-coated circuits., Conclusions: The use of heparin-coated circuits for cardiopulmonary bypass with aprotinin prime resulted in a significant reduction in mobidity in the early postoperative phase and a concomitant decrease in intensive care stay, resulting in important cost savings.