Noncoated Circuits Research Articles

Heparin-coated vs. Non-coated Cardiopulmonary Bypass Circuits: Comparing Immediate Results with Different Target Activated Clotting Time.

ObjectiveTo compare immediate postoperative results in patients receiving heparin-albumin-coated and non-coated circuits.MethodsA total of 241 patients undergoing on-pump cardiac surgery were divided into two groups: those receiving heparin-coated circuits (Bioline®, Maquet Cardiopulmonary AG., Hirrlingen, Germany) and those receiving non-coated circuits (Maquet Cardiopulmonary AG., Hirrlingen, Germany).ResultsActivated clotting times (ACT) during cardiopulmonary bypass (CPB) were significantly shorter in the heparin-albumin-coated group than in the non-coated group (355.64±34.12 vs. 560.38±90.20, respectively, P=0.001). In-hospital mortality and postoperative stroke rates and lengths of intensive care unit stay were similar between the groups; in contrast, in the heparin-albumin-coated group, patients had significantly better outcomes for hospital stay, drainage, and need for erythrocyte transfusion.ConclusionHeparin-coated circuits and reduced level of systemic heparinization with 300 seconds of target ACT level in cardiac surgery under CPB are safe and result in a very satisfactory clinical course.

Effects of phosphorylcholine coating on extracorporeal circulation management and postoperative outcome: a double-blind randomized study

The aim of the study was to evaluate the effects of phosphorylcholine coating (PC) on intra-operative extracorporeal circulation (ECC) management and perioperative outcome. One hundred and twenty consecutive cardiac surgery patients were enrolled for the study. Patients were randomly assigned to ECC with PC circuits (60 patients) or to corresponding non-coated circuits (60 patients). Trans-oxygenator pressure drop, blood flows, flow resistances and ECC parameters were recorded at surgery before ECC institution and every 10 min thereafter until ECC discontinuation. Postoperative variables (hematological parameters, drainage blood loss, mechanical ventilation time, incidence of atrial fibrillation, use of blood products) were also assessed and compared between groups. No differences were found between the two groups in terms of demographics, operative, and hematological profiles. PC showed, at equal pump flows, to significantly (P<0.01) attenuate pressure drop across oxygenators and to reduce oxygenator inlet pressures during ECC. Postoperatively, PC showed to remarkably reduce platelet consumption. Coating showed also to reduce postoperative blood loss, although the difference did not reach statistical significance. No differences between the two groups were found in terms of additional perioperative effects. The use of PC in low-risk elective cardiac surgery patients enhances ECC management, by means of a less restrictive trans-oxygenator blood flow.

Database Review: Clinical Outcomes Of Non-Coated And Multi-Coated Cardiopulmonary Bypass Circuits In Infants

Database Review: Clinical Outcomes Of Non-Coated And Multi-Coated Cardiopulmonary Bypass Circuits In Infants

In Vivo Comparison Study of FDA-Approved Surface-Modifying Additives and Poly-2-Methoxyethylacrylate Circuit Surfaces Coatings During Cardiopulmonary Bypass

The purpose of this double-blind prospective and randomized study was to examine the effects of surface-modifying additives (SMAs) and poly-2-methoxyethylacrylate (PMEA) circuits on platelet count, platelet function (Sonoclot), postoperative chest tube drainage volume, peri- and postoperative blood product use, extubation time, and intensive care time. Terumo noncoated, Terumo-coated (PMEA), Cobe noncoated, and Cobe coated (SMA) circuits were evaluated to find the most cost-effective way to improve patient outcomes. We aimed to find if an additional charge for a coated CPB circuit would be recovered by reducing other patient costs (blood transfusions, intensive care unit time, and bring back postoperative bleeding). An initial literature review revealed the comparison of PMEA circuits vs. noncoated circuits and SMA circuits vs. noncoated circuits in both adult and porcine models. Both SMA- and PMEA-coated circuits decreased platelet consumption, platelet factor release, and the overall perioperative inflammatory response while on cardiopulmonary bypass (CPB). The question not answered in an initial search was simply, “which coated circuit is best for the patient: SMA or PMEA?” Research comparing the above coated circuits each other was not found. The study was approved by the Institutional Review Board. Thirty patients were scheduled for elective coronary artery bypass grafting and/or valvular repair or replacement surgery. These 30 patients were randomized as 10 patients to Terumo X-Coating (PMEA surface coating) (CT), 10 patients to Cobe Smart-X coating (SMA surface coating; CC), 5 patients to Terumo noncoated tubing (NCT), and 5 patients to Cobe noncoated tubing (NCC). Informed consent was obtained from each patient before surgery. The data showed no statistically significant relationship between platelet counts, platelet function (Sonoclot), postoperative chest tube drainage volume, peri- and postoperative blood products, intensive care unit time, or total hospital length of stay. Analysis revealed statistically significant clinical associations of extubation time and protamine dose with treatment group. This study provided evidence that SMA- and PMEA-coated circuits do not improve platelet consumption or decrease blood product use for patients undergoing CPB. There was statistical significance with a reduction in extubation time and total protamine requirement needed to return activated clotting time (ACT) to baseline post-CPB. Although the use of SMA and/or PMEA circuits during CPB has clinical benefit to the CPB patient, an additional charge for the specialty circuit may not be realized.

Effects of poly-2-methoxyethylacrylate (PMEA)-coating on CPB circuits

Objectives. In this study, the immuno- and neuroprotective effect of a novel cardiopulmonary bypass coating was investigated. Design. Thirty nine patients scheduled for elective coronary artery bypass grafting were randomly assigned to either PMEA-coated (n = 19) or non-coated CPB circuits (n = 20). Pericardial suction blood was separated and retransfused only if needed at the end of operation. Neurocognitive functions were examined preoperatively and 7–10 days postoperatively using a standard neuropsychological test battery. Assuming an inflammatory etiology, the most cogent inflammatory markers were perioperatively analyzed. Results. Postoperatively, patients of the PMEA-coated group performed better in Go/NoGo and Mini-Mental-test than patients of the non-coated group (p < 0.04). Other neurocognitive testing did not reveal significant differences between the groups. Although most inflammatory parameters showed a significant intraindividual increase during or shortly after CPB, there was no difference in inflammatory alteration between the groups. Conclusions. PMEA-coating of cardiopulmonary bypass surfaces revealed some minor benefits in preservation of neurocognitive functions after surgery. The immediate inflammatory response remained mostly unaffected. Suction blood separation may additionally contribute to proper postoperative outcome.

PMEA Polymer-Coated PVC Tubing Maintains Anti-Thrombogenic Properties during in vitro Whole Blood Circulation

Poly(2-methoxyethylacrylate) (PMEA) is a new coating material that appears to reduce protein and platelet adsorption. However, the exact performance of PMEA coated circuit remains to be revealed in well-controlled experiments. Therefore, we compared its hemocompatibility with covalent-bound heparin-, and non-coated circuits during 6 hours of in vitro circulation, using donor blood from six volunteers. In our model, simple tubing circuits containing one-way ball valve were placed on the rotary table, which moved alternatively to generate pulsatile recirculation of heparinized human blood inside the tubing. Using this model, we expected fine assessment of the material surface, because we could reduce blood damage by avoiding air and a blood pump. Moreover, the small capacity of circuit allowed us to compare three kinds of circuits using a single unit of donor blood, eliminating effects by possible variations between blood donors. The anti-thrombin capacity of the PMEA-coated circuits was maintained even after six hours blood circulation, whereas surface thrombin generation increased markedly after use in non-coated circuits (P<0.05). Deposition of fibrin onto PMEA circuits was reduced more than 30% compared with heparin and non-coated circuits (P<0.05). However, the increase of plasma Factor XIIa was similar in all circuits. Increase of CD11b expression on circulating leukocytes and of plasma C3a was ameliorated in the heparin- and PMEA-coated circuits (P<0.05). PMEA-coated circuits appear to maintain their anti-thrombogenicity during use, otherwise PMEA-coated and heparin-coated circuits showed a similar character in hemocompatibility. This long-standing anti-thrombogenicity might be attributable to less adsorption of activated blood components onto the surface.

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 groupH 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.

Clinical performance and biocompatibility of poly(2-methoxyethylacrylate)—coated extracorporeal circuits

Background. Poly(2-methoxyethylacrylate) is an amphiphilic organic polymer consisting of a hydrophobic backbone with pendant hydrophilic groups that has been reported to reduce protein and platelet adsorption in in vitro and ex vivo studies. Methods. Sixty patients undergoing three-vessel coronary artery bypass grafting were divided into two equal groups. Group 1 had operation with Capiox poly(2-methoxyethylacrylate) coated SX18R oxygenators with noncoated circuits, and group 2 had operation with all noncoated circuits. Hemodynamic variables, blood and urine test results, hematologic variables, complement fractions, C3a and C4d, and interleukin-6 levels were documented preoperatively (T1), on cardiopulmonary bypass (T2), before cessation of cardiopulmonary bypass (T3), after protamine sulfate reversal (T4), and on the first postoperative day (T5). Protein electrophoresis was performed at T1 and T5. Blood cell adhesion and aggregation on fibers were analyzed with optical microscopy, and desorbed protein was evaluated quantitatively by a spectrophotometer using samples obtained when the oxygenators were dismantled after cardiopulmonary bypass. Results. Platelet counts in group 1 demonstrated significant differences at T3, T4, and T5 ( p < 0.05) versus group 2 and white blood cell counts in group 1 versus group 2, at counts T4 and T5. Albumin levels were significantly better preserved in group 1 at T4, and T5 and fibrinogen levels, at T3 and T5 ( p < 0.05). On electrophoresis, the postoperative albumin level was 57.9% ± 3% in group 1 versus 50.2% ± 3% in group 2 ( p < 0.05). Postoperative hemorrhage was 452 ± 35 mL in group 1 and 612 ± 35 mL in group 2 ( p < 0.05). Duration of intubation was significantly lower ( p < 0.05) in group 1, as was need of blood transfusion ( p < 0.01). More platelet adhesion and aggregation were demonstrated on noncoated oxygenator fibers. The amount of desorbed protein was 0.13 ± 0.01 mg/dL versus 0.012 ± 0.001 mg/dL ( p < 0.001) on noncoated versus coated fibers, respectively. Conclusions. Poly(2-methoxyethylacrylate)—coated oxygenators reduce platelet adhesion, platelet aggregation and protein adsorption. This surface provides a better perioperative clinical status through platelet-, albumin-, and fibrinogen-sparing effects.

Veno-venous bypass in liver transplantation: heparin-coated perfusion circuits reduce the activation of humoral defense systems in an in vitro model.

We studied the effects of bypass circuit surface heparinization on kallikrein-kinin, coagulation, fibrinolytic and complement activation in a closed model system for simulating veno-venous bypass (WBP) in orthotopic liver transplantation (OLT). The circuits were identical to those in routine use during clinical OLT in our institution. Fresh whole human blood diluted 1:2 with Ringer's acetate was circulated at a non-pulsatile flow (2 l/min) and at a constant temperature (37.5 degrees C) for 12 h. In 10 experiments, the entire inner surface of the circuits was coated with end-point attached heparin (HC). In the remaining 10, non-treated PVC tubing was used (NC). Components of the plasma kallikrein-kinin, coagulation, fibrinolytic and complement systems were analyzed using functional techniques (chromogenic peptide substrate assays) and enzyme immunoassays at baseline, 3 and 12 h. Significant activation of the initial (C3bc) and terminal (TCC) components of the complement system were found in both the NC and HC groups after 3 and 12 h: C3bc: NC: baseline = 4 (3.5-7.7), 3 h = 17.3* (12.5-27), 12h = 31* (17.7-63.6), HC: baseline = 4.9 (3.2-6.8), 3h = 9* (6-14.4), 12h = 13.7* (7.4-18.1). TCC: NC: baseline = 0.4 (0.2-0.6), 3h = 5*(0.8-11.9), 12 h: 13.1* (4.2-25.7). HC: baseline = 0.5 (0.1-0.6), 3 h = 0.6* (0.1-0.8), 12 h = 1.2* (0.3-2) AU/ml; median and range (*: p < 0.05). The C3bc and TCC concentrations were significantly higher in the NC group at 3 and 12 h, compared to the HC group: C3bc (NC vs. HC group): 3 h, p < 0.001; 12 h, p < 0.001. TCC (NC vs. HC group): 3h, p < 0.001; 12 h, p < 0.001. Significant increases in the values of thrombin-antithrombin complexes (p = 0.003), prothrombin fragment 1 + 2 (p = 0.006) and plasmin-alpha2-antiplasmin complexes (p = 0.016) were found in the non-coated group, but not in the heparin-coated group during the observation period, showing that the coagulation and fibrinolytic systems were activated in the non-coated circuits. We conclude that heparin-coating of the internal surface of the extracorporeal perfusion circuit used for WBP reduces activation of the plasma cascade systems in a closed venous system in vitro.

THE EFFICACY OF X-COATED CARDIOPULMONARY BYPASS CIRCUIT SYSTEMS IN PATIENTS WITH OPEN HEART SURGERY

[Background] We have reported the efficacy of a new coating material, poly-2-methoxyethyl acrylate (PMEA) for cardiopulmonary bypass (CPB) circuit in porcine PCPS models. In this study, we evaluated the efficacy of PMEA coating (X coating®) in patients with open heart surgery. [Methods and Materials] Twenty-one patients underwent valve surgeries under X-coated CPB circuits (group X, n=5), non-coated circuits (group C, n=8) or heparin (ionically bound-heparin, Hepaface®)-coated circuits (group H, n=8). We analyzed the complement system, inflammatory system, platelet system and coagulofibrinolytic system in blood samples, after anesthesia induction, 10min after heparin administration, 30min after extracorporeal circulation establishment, 60min after protamine administration. We also examined plasma proteins adsorbed onto the hollow fibers of the oxygenators after CPB in each group. [Results]Platelet system: Platelet counts decreased gradually during CPB in all groups. There were no significant differences between 3 groups. The plasma levels of platelet factor 4 and P-selectin were lower in group X than in group C. Complement system: The elevations in plasma C3a levels were less in group X than in group C. They were equal to in group H. Coagulofibrinolytic system: The plasma levels of TAT complex and D-dimer were lower in group X than in group C. Inflammatory system: The plasma levels of IL-6 and IL-8 were lower in group X than group C. Adsorbed plasma proteins, especially fibrinogen were markedly less in group X than in group C and H. [Conclusion] In this clinical study, the superior biocompatibility of X-coating was confirmed as CPB coating material, and its efficacy seemed to be compatible to heparin coating as for various chemical reactions induced by CPB. In addition, it may exceed the heparin coating as for suppression of the adsorption of plasma proteins such as fibrinogen. X coating may be suitable for the improvement of biocompatibility of CPB in the clinical settings.

Heparin-coated cardiopulmonary bypass circuit: clinical effects in pediatric cardiac surgery.

Heparin-coated cardiopulmonary bypass (CPB) circuits have been reported to reduce complement activation and the inflammatory response associated with CPB. We retrospectively compared patients utilizing heparin-coated perfusion circuits with those using noncoated circuits to determine the clinical effects of the different circuits in pediatric cardiac surgery. Between July 1995 and July 1997, 203 patients weighing < 10 kg underwent cardiac surgery, 153 patients using heparin-coated bypass circuits and 50 patients using noncoated circuits. The 50 patients operated on with the noncoated circuit (Group N) were matched to 100 patients operated on with coated circuits (Group H) in age, weight, and type of procedure. Urine output during bypass, blood products used after bypass, postoperative ventilation days, hospital stay, morbidity, and mortality were compared between these groups. Body weight, perfusion time, and procedure time were not different between the two groups. Urine output during bypass was notably greater in Group H than in Group N (11.3 +/- 10.5 mL/kg per hour vs 4.8 +/- 3.1 mL/kg per hour, respectively, p < 0.0001). Postoperative mechanical ventilation markedly decreased in Group H (Group H vs N = 2.8 +/- 2.7 days vs 5.1 +/- 7.5 days, respectively, p < 0.05). Red blood cell usage, hospital stay, morbidity, and mortality were not statistically different, although there was a tendency toward decreased transfusion of red cell and platelets in Group H (Group H vs N = 61.2 +/- 121.1 mL/kg vs 102.0 +/- 176.7 mL/kg, respectively, in red cell, p = 0.15; and Group H vs N = 7.9 +/- 13.7 mL/kg vs 13.2 +/- 24.5 mL/kg, respectively, in platelets, p = 0.16). Patients operated on with the use of heparin-coated circuits had increased urine output during bypass and required less time postoperatively on the ventilator. These results suggest a reduction in the acute inflammatory response, capillary leakage, and overall systemic edema. We now routinely use coated circuits on all pediatric pump cases.

Coating-techniques to improve the hemocompatibility of artificial devices used for extracorporeal circulation.

Extracorporeal circulation procedures have been shown to induce complement and leukocyte activation, release of endotoxin and inflammatory mediators, including cytokines, nitric oxide, oxygen free radicals, and platelet activating factors. The contact between the blood and the various artificial surfaces of the extracorporeal system results in an unspecific post-perfusion syndrome. For diminishing these negative side effects several coating-techniques have been developed to create devices with improved hemocompatibility. This review deals with the current knowledge of heparin-coated and otherwise surface-modified perfusion systems. The pathway how heparin-coated surfaces work is discussed and techniques for surface-coatings, both clinically introduced as well as newly developed are presented. Numerous clinical studies compared heparin-coated versus non-coated circuits. Heparin-bonded devices showed lessened humoral and cellular activation, in particular a reduced complement activation with a reduced inflammatory post-perfusion syndrome. Also platelet protection and more favorable post-operative lung function are of particular note. Recent clinical trials demonstrated shortened hospital stays, less drainage bleeding, and reduced cerebral complications using heparin-coated oxygenation systems. The diminished expression of the leukocyte adhesion molecules CD 11b/c in CBAS devices points to a decreased activation of neutrophils. In addition, one research group found a reduced production of oxygen radicals. Heparin-bonding minimizes oxygenator failure by a significant reduced pressure gradient across the oxygenator, probably caused by decreased fibrin and platelet deposition at the hollow fiber surfaces. A meta analysis examined the impact of heparin-bonded systems on clinical outcomes and resulting costs. Using heparin-bonded circuits led to total cost savings from US $1000 to 3000. Several authors demonstrated reduced blood loss and better clinical outcome by reduction of systemic heparinization and the employment of heparin-coated devices. Above and beyond the long-term applications, routine heart operations have also markedly begun to utilize heparin-coated devices. This trend will assuredly continue in the coming years and is an important step toward higher hemocompatibility of blood-contacting surfaces in the ECC device. Heparin-coatings are merely the beginning of improved hemocompatibility for all materials that come into contact with human blood or tissues. Intelligent materials with almost completely physiological surfaces will be at the surgeon's disposal within the next few years.

Heparin coating reduces cell activation and mediator release in an in vitro venovenous bypass model for liver transplantation

We used an in vitro model for venovenous bypass in a prospective, randomized study to analyze the effect on leukocytes cell activation after coating the total blood contact surface with covalently bound heparin. In ten experiments heparin-coated circuits were used, and in ten other experiments noncoated circuits were used. Monocyte cytokine production and neutrophil myeloperoxidase release were analyzed. Monocytes were isolated using anti-CD14 paramagnetic beads, and oligo(dT)25 beads were used to isolate mRNA before subsequent reverse transcription and semiquantitative amplification of various cytokines in order to determine time-related changes in expression during bypass. After 2 h, mRNAs for IL-1β and IL-6 were highly upregulated in noncoated compared to heparin-coated circuits. Little or no change was seen in the expression of other cytokines. IL-1β and IL-6 were measured in plasma after 12 h and reflected the upregulated mRNAs in noncoated circuits. A significantly reduced release of myeloperoxidase was observed in coated versus noncoated circuits. This indicates that heparin-coated surfaces reduce cellular activation and the release of inflammatory mediators.

Heparin-coated bypass circuits: effects on inflammatory response in pediatric cardiac operations

Background. This study was designed to investigate whether clinical signs of the inflammatory response in pediatric cardiac patients are reduced by heparin-coated cardiopulmonary bypass circuits and how this could be explained by differences in the pathophysiologic mechanisms involved. Methods. In a randomized, prospective study 19 patients underwent cardiopulmonary bypass either with Carmeda BioActive Surface bypass circuits (n = 9) or with identical noncoated circuits (control, n = 10). Clinical parameters were recorded during the first 48 hours after the start of operation. Blood samples for determination of terminal complement complex, soluble form of E-selectin, and beta-thromboglobulin were obtained perioperatively up to 24 hours after operation. Results. All clinical and inflammatory mediators showed a tendency in favor of the group with heparin-coated circuits. When analyzed on a point-by-point basis there were significant differences in postoperative central body temperature, soluble E-selectin levels, and beta-thromboglobulin levels (all p < 0.05). Conclusions. These data suggest that the use of heparin-coated cardiopulmonary bypass offers clinical benefit and tends to reduce the release of inflammatory mediators.

Activation of the Clotting System: Heparin-Coated versus Non Coated Systems for Extracorporeal Circulation

The purpose of this experimental study was to compare heparin-coated versus non-coated systems for extracorporeal membrane oxygenation (ECMO), to investigate the dynamic course of clotting activation in both groups. Eight pigs weighing 19.7 (+/- 1.3) kg, each underwent ECMO for 24 hours. Two groups were formed: in group 1, heparin-coated circuits were used with low dose heparinization (10 IU/kg/hr), whereas in group 2 non-coated circuits with high dose heparinization (60 IU/kg/hr) were used. Coagulation was monitored by measuring prothrombin time, partial thromboplastin time, fibrinogen, antithrombin III (AT III) and specific markers of clotting activation (thrombin-antithrombin III complexes (TAT) and D-dimer). Furthermore, platelet count, hematocrit, activated clotting time (ACT), and plasma heparin concentration were determined regularly The dynamic course of the specific coagulation activation markers showed some differences: whereas TAT and D-dimer increased quickly in group 2, the increase in group 1 was delayed. Activation marker values tended to be lower in group 1 during the first six hours, after which no more differences between the groups were seen. After 24 hours of ECMO, TAT and D-dimer had nearly returned to baseline values. Platelets showed a continuous decrease throughout the experiment, which was very similar in both groups. The heparin coated system showed a distinct delay in clotting activation during the first six hours of ECMO. After six hours there were no more differences between the groups.

Influence of Duraflo II heparin-treated extracorporeal circuits on the systemic inflammatory response in patients having coronary bypass

Cardiopulmonary bypass generates a systemic inflammatory response, including the activation of leukocytes, contributing to postoperative morbidity. To evaluate whether the use of heparin-treated extracorporeal circuits could reduce the inflammatory reaction in patients undergoing cardiopulmonary bypass, we conducted a prospective clinical study on 14 patients having coronary artery bypass in whom perfusion was done randomly with either Duraflo II heparin-treated circuits or with nontreated circuits. In both groups systemic heparinization was performed before cardiopulmonary bypass. The use of heparin-treated circuits resulted in a reduction of systemic inflammatory activation during cardiopulmonary bypass. This was reflected by lower plasma levels of soluble tumor necrosis factor receptors ( p < 0.05) and of interleukin-6 and interleukin-8 ( p < 0.05), manifest after release of the aortic crossclamp. Furthermore, 6 and 12 hours after aortic crossclamp release significantly lower levels of the soluble E-selectin ( p < 0.05) were observed in the Duraflo II group. In patients in whom noncoated circuits were used, a significant decrease in circulating soluble intercellular adhesion molecule 1 ( p < 0.05) was found early during bypass. All these observations suggest that the use of a heparin-treated extracorporeal circuit reduces the systemic inflammatory activation and may alter the leukocyte-endothelium interaction. (J T HORAC C ARDIOVASC S URG 1995;110:1633-41)

The Influence of Heparin-Coated and Uncoated Extracorporeal Circuits on Blood Rheology During Cardiac Surgery

The effect of heparin-coated perfusion circuits on blood trauma during clinical cardiopulmonary bypass (CPB) was studied in order to find out if traumatic changes in the blood could be minimized. Twenty-four patients undergoing coronary artery bypass surgery were randomized prospectively to CPB with heparin-coated circuits (HCC) or non-coated circuits (NCC). The trauma to blood was assessed by measuring damage to blood cells by estimating red and white cell rheology changes. These were measured as red cell filtration rate (RFR) and white cell filtration rate (WFR) using standard microfiltration methods. Furthermore, changes in plasma hemoglobin (P-Hb), whole blood and plasma viscosity were simultaneously assessed. The RFR was significantly reduced in both groups during CPB by 10% in the HCC and 32% in the NCC groups (p&lt;0.01). When comparing the HCC and NCC groups, a significant difference was first seen after 30 minutes ofbypass (p&lt;0.05) and increased at the end ofCPB (p&lt;0.01). Similar results were seen regarding WFR (15% and 36%, p&lt;0.01). After 30 minutes ofbypass, a significant difference was seen between HCC and NCC groups (p&lt;0.05). Furthermore, a significant increase in P-Hb levels were seen during CPB in both patient groups. At the end of CPB, there was a significant difference in P-Hb levels (HCC 305±90 mg/L; NCC 455±78 mg/L, p&lt;0.01) when comparing the two groups. When comparing HCC and NCC regarding corrected blood viscosity at shear rate 92 s-1, there were significantly higher viscosity values in the NCC group starting at 30 minutes of bypass (p&lt;0.05). Plasma viscosity (PV) at shear rate 583 s-1 , showed similar results (p&lt;0.05). This study suggests that heparin-coated extracorporeal circuits are less damaging to the rheological properties of blood and would therefore be better suited for clinical use during cardiac surgery using CPB.

Heparin-coated circuits reduce activation of granulocytes during cardiopulmonary bypass

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.

Heparin-coated cardiopulmonary bypass circuits reduce blood cell trauma Experiments in the pig

Blood cell trauma and postoperative bleeding remain important problems in cardiopulmonary bypass (CPB). We compared heparin-coated with non-coated circuits in the pig. Twenty animals were perfused for 2 h at normothermia using membrane oxygenators (Bentley Bos 50). Two groups were studied. In the non-coated group (NC, n = 11) the CPB circuits used were without a heparin coating. This group had systemic heparinization of 400 IU/kg to maintain an ACT (activated clotting time) of over 400 s during CPB. In the coated group (C, n = 9), all surfaces exposed to blood in the CPB circuits were heparin-coated. This group had the heparin dose reduced to 25% (100 IU/kg) without further administration regardless of ACT. During CPB, group C displayed shorter ACT (per definition), higher platelet count, platelet adhesion and lower fibrinolysis and haemolysis (P less than 0.05) as compared to group NC. No thromboembolic events were detected during CPB. Three animals in group NC and 4 animals in group C were weaned from CPB and protaminized. Four hours postoperatively, the leucocyte consumption was two-fold greater and blood loss about four-fold greater in group NC as compared with group C (P less than 0.05). Perfusion with heparin-coated surfaces reduces blood cell trauma. The decreased postoperative blood loss observed in group C is probably explained by the reduced dosages of heparin and protamine.

Heparin Coated Cardiopulmonary Bypass Circuits in Coronary Artery Surgery - A Clinical Study

Cardiopulmonary bypass with systemic heparinization causes trauma to blood cells and coagulation defects. Artificial surfaces could be coated by end-linkage binding of heparin (Carmeda Bioactive Surface CBAS™). The use of such surfaces during cardiopulmonary bypass in animals resulted in less postoperative blood loss and better preservation of blood cells. Heparin-coated circuits were employed during coronary artery grafting in seven patients (Group C). Concomitantly, the heparin dose was reduced by 25% and an ACT of 300 sec was accepted. An additional seven patients were operated with non-coated circuits (Group NC), requiring an ACT above 400 sec with normal doses of heparin. There was no thrombo-embolic complications in Group C. The postoperative bleeding was generally low and without significant intergroup differences. Coagulation parameters displayed a significantly lower ACT and anti-Factor Xa during bypass in Group 1C. A tendency towards less blood cell trauma was observed with heparin-coated circuits, although the differences did not reach statistical significance. The protamine dose could be reduced by 50%, which significantly reduced the protamine/heparin quotient. This study indicates that routine cardiopulmonary bypass could safely be performed with heparin-coated circuits and reduced intravenous doses of heparin and protamine. It is suggested that the use of heparin-coated circuits may lead to less blood cell trauma.