Heparin-coated Cardiopulmonary Bypass Circuits Research Articles

`High dose' aprotinin and heparin-coated circuits: clinical efficacy and inflammatory response

Heparin-coated cardiopulmonary bypass circuits reduce the inflammatory response to cardiopulmonary bypass circuit, improve biocompatibility and may protect the postoperative hemostasic mechanisms in routine coronary bypass operations. `High-dose' aprotinin reduces blood-loss, transfusion needs, and re-explorations as a result of bleeding, and may have an additional role in reducing the inflammatory response of the body to cardiopulmonary bypass circuit. It has not been established, however, if the addition of a heparin-coated circuit to the intraoperative administration of `high dose' aprotinin further reduces the whole-body inflammatory response to cardiopulmonary bypass circuit and improves the postoperative clinical course of the patients who are undergoing coronary surgery. Thirty patients undergoing primary elective coronary artery bypass grafting were studied. All the patients received, intraoperatively, the serine-protease inhibitor aprotinin according to the `Hammersmith' protocol and full heparin dose. Patients were randomly allocated to be treated either with a circuit completely coated with surface-bound heparin ( n=15) or with an uncoated, but otherwise identical, circuit ( n=15). Differences in the clinical course of the two groups of patients, as well as differences in the behavior of hematological and inflammatory (interleukin-6 (IL-6) and C-reactive protein) factors before, during and after bypass, were analyzed. There were no significant differences between the two groups in terms of bleeding and transfusional requirements, the time spent on a ventilator, or in duration of stay in the intensive care unit (ICU). In all patients, a significant increase in the total white blood cell count, neutrophils, serum IL-6 and C-reactive protein occurred in relation to cardiopulmonary bypass. This was not influenced by heparin precoating of the circuit. In addition, there was an increase in the monocyte count during follow-up, and there was a trend towards higher monocyte counts in the patients who were treated with heparin-coated circuits. These results suggest that the addition of a heparin-coated circuit to the intraoperative `high-dose' aprotinin therapy probably had little influence on the clinical course and on the time-course of the inflammatory parameters of the adult patients undergoing primary coronary surgery with a full heparinization protocol.

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.

Heparin-coated bypass circuits (Carmeda) suppress the release of tissue plasminogen activator during normothermic coronary artery bypass graft surgery

Objectives: To study fibrinolysis in a homogenous first-time coronary artery bypass surgery (CABG) population in whom heparin-coated circuits were used.Design: A prospective, blinded, randomized, placebocontrolled study.Setting: A university hospital, tertiary care, intraoperative and postoperative intensive care unit.Participants: Twenty-one adult elective primary CABG patients.Interventions: Randomized circuit-type centrifugal pump, membrane oxygenator, rigid cardiotomy reservoir, either placebo (n = 10) or heparin-coated (n = 11) (Carmeda; Medtronic Inc., Anaheim, CA).Measurements and Main Results: Blood samples were analyzed for tissue plasminogen activator (TPA) activity, TPA antigen, plasminogen activator inhibitor-1 (PAI-1) activity, prothrombin complex F1.2, and antithrombin III (AT-III) at the following times: before cardiopulmonary bypass (CPB), during CPB (30 and 60 minutes), post-CPB, and day 1 postsurgery. TPA activity and antigen increased fivefold in the placebo group during CPB, whereas it did not even double in the heparin-coated group. PAI-1, F1.2, and AT-III were not different between groups.Conclusions: Heparin-coated CPB circuits reduced TPA release in this homogenous CABG population with routine heparin/protamine management.

Inflammatory Response to Cardiopulmonary Bypass: Mechanisms Involved and Possible Therapeutic Strategies

Recent study of the inflammatory reactions occurring during and after cardiopulmonary bypass (CPB) has improved our understanding of the involvement of the inflammatory cascade in perioperative injury. However, the exact mechanisms of this complex response remain to be fully determined. Literature on the inflammatory response to CPB was reviewed to define current knowledge on the possible pathways and mediators involved, and to discuss recent developments of therapeutic interventions aimed at attenuating the inflammatory response to CPB. CPB has been shown to induce complement activation, endotoxin release, leukocyte activation, the expression of adhesion molecules, and the release of many inflammatory mediators including oxygen-free radicals, arachidonic acid metabolites, cytokines, platelet-activating factor, nitric oxide, and endothelins. Therapies aimed at interfering with the inflammatory response include the administration of pharmacologic agents such as corticosteroids, aprotinin, and antioxidants, as well as modification of techniques and equipment by the use of heparin-coated CPB circuits, intraoperative leukocyte depletion, and ultrafiltration. Improved understanding of the inflammatory reactions to CPB can lead to improved patient outcome by enabling the development of novel therapies aimed at limiting this response.

P35 Heparin-coated cardiopulmonary bypass circuit with low-dose heparin reduces postoperative bleeding early

P35 Heparin-coated cardiopulmonary bypass circuit with low-dose heparin reduces postoperative bleeding early

Haemostasis at Low Heparin Dosage During Cardiopulmonary Bypass with Heparin-coated Circuits in Pigs

Cardiopulmonary bypass (CPB) causes activation of cascade systems. Although heparin coating of CPB circuits improves biocompatibility, the effects on coagulation remain controversial. Theoretically, heparin coating should permit the reduction of systemic anticoagulation during CPB. We investigated influences on haemostatic variables in animal CPB, comparing heparin-coated circuits and reduced systemic heparinization (group HC) with uncoated circuits and full heparinization (group C). Twenty pigs underwent 2-h CPB. Seven (HC, n = 4; C, n = 3) were weaned from CPB and studied for up to 4 h. Total administered heparin was 470 ± 6 IU/kg (mean ± SEM) in group C and 100 ± 0 IU/kg in group HC. Protamine dosage was significantly reduced in group HC. In group C, levels of prothrombin complex, factor VIII and adhesive platelets were reduced significantly during CPB, and postoperatively there were significantly lower values of prothrombin complex, fibrinogen, antithrombin III, factor VIII and adhesive platelets but a significantly increased concentration of von Willebrand factor and cumulative bleeding after 4 h. In conclusion, heparin-coated CPB circuits combined with lowered heparin dosage reduced coagulation factor consumption and preserved platelet function, possibly contributing to improved postoperative haemostasis.

Clinical evaluation of totally heparin-coated cardiopulmonary bypass circuits on coagulation, fibrinolysis, platelets, and complement system

Clinical evaluation of totally heparin-coated cardiopulmonary bypass circuits on coagulation, fibrinolysis, platelets, and complement system

Case 5—1996 thrombosis after the use of a heparin-coated cardiopulmonary bypass circuit in a patient with heparin-induced thrombocytopenia

A 64-year-old, 165-cm, 58-kg woman was admitted to the hospital with an inferior myocardial infarction. She underwent an emergent percutaneous transluminal coronary angioplasty (PTCA) complicated by an early reocclusion necessitating a second PTCA. The second PTCA complicated itself by the dissection of the right coronary artery (RCA), necessitating the placement of four stents in the RCA. The patient was then treated with porcine heparin (H) for 7 days. Warfarin was progressively titrated to a prothrombin time of 23% (international normalized ratio = 3.8), and heparin was then stopped. After 3 days of effectwe warfarin treatment, she suddenly developed cardiogenic shock with third-degree atrioventricular block, necessitating resuscitation maneuvers, intubation, placement of an intra-aortic balloon pump, and a pacemaker. After this resuscitation, she recovered well except for a right hemiparesis that was attributed to a prolonged hypotensive state. Coronary angiography disclosed a reocclusion of the RCA. Fibrinolytic therapy was then administered, and a continuous infusion of heparin was reintroduced. Forty-eight hours after her ischemic event, a cerebral computed tomography (CT) scan was normal, and she had no neurologic sequelae. Nine days later, despite receiving a continuous infusion of heparin, she became ischemic in the right coronary artery territory, and an emergent coronary revascularization was planned. While evaluating the patient's files, the attending anesthesiologist found that the platelet level was below 35,000/mm 3 from the beginning of the second heparin administration 10 days earlier (Fig 1), and he suspected a syndrome of heparin-induced thrombocytopenia (HIT). Because of the presence of four stents in the patient's RCA and owing to her history of the repetitive coronary occlusions, the cardiologists refused to stop the heparin infusion. This infusion was therefore stopped in the operating room. A central venous catheter was already in place, a radial arterial catheter was then placed under local anesthesia, and both were flushed with 0.9% saline without heparin. Anesthesia was induced with etomidate and sufentanil, and muscle paralysis achieved with pancuronium. Anesthesia was maintained with midazolam, and a continuous infusion of sufentanil, 2 Ixg/kg/hr. Iloprost is not available in Belgium; neither are the heparin substitutes proposed in the literature. The anesthesiologist had no experience with the use of low-molecularweight heparin (LMWH) during bypass. Therefore, he elected to use a heparin-coated cardiopulmonary bypass (CPB) circuit (HC-CPB) (Durafio II; Bentley [Englewood, CO], because of its theoretical advantages of biocompatibility and protection of platelets against activation caused by contact with the artificial surfaces. Only 50 IU/kg of porcine heparin were administered in place of the usual 300 IU/kg. Two saphenous grafts were sutured on the RCA. The procedure was performed under normothermia and intermittent antegrade warm blood cardioplegia. Aortic crossclamp time was 34 minutes, and CPB lasted 55 minutes. No pharmacologic support was needed to come off bypass. The platelet level was 34,000/mm 3 before surgery and 39,000/mm 3 after 50 IU/kg of H. It decreased to 22,000/ mm 3 after 7 minutes of CPB, possibly because of hemodilution, and returned to 39,000/mm 3 after discontinuation of CPB. Activated coagulation times with kaolin (ACT) (Hemotec; Medtronic [Uden, The Netherlands]) were 151 seconds before heparin administration, 231 seconds after 50 IU/kg of H, 445 and 443 seconds during CPB, and 295 seconds after CPB. Only 10 mg (2,000 IU) of protamine were then administered, and ACT returned to 148 seconds (Fig 2). After administration of another 1,000 IU of protamine, the ACT was 82 seconds. Despite this, the patient was still bleeding actwely. It was then judged that no more heparin was circulating at that time, and it was decided that it would

Biocompatibility of heparin-coated extracorporeal bypass circuits: A randomized, masked clinical trial

Cardiopulmonary bypass circuits cause morbidity during cardiac operations. Plasma proteins and cellular components are stimulated by contact with the cardiopulmonary bypass circuit and can cause bleeding and postperfusion syndrome. This is especially true in patients undergoing reoperative cardiac procedures, which carries a higher risk of postoperative bleeding and prolonged ventilation compared with primary cardiac surgical procedures. Recently, cardiopulmonary bypass circuit surfaces have been coated with antithrombotic agents to improve their biocompatibility. This study evaluated the effect of a heparin-coated cardiopulmonary bypass system (Duraflo II, Baxter Bentley Healthcare Systems, Irvine, Calif.) on thrombin formation, platelet stimulation, and leukocyte activation in patients undergoing reoperative coronary artery bypass grafting or valve operation. Fifty patients were selected and randomly assigned to a standard noncoated control system ( n = 26) or the Duraflo heparin-coated system ( n = 24). Similar heparin doses were used in both groups (3 mg/kg). The heparin-coated group used a completely heparin-coated bypass circuit including the cardiotomy reservoir; arterial filters were heparin-coated in both groups. Samples were obtained before cardiopulmonary bypass, 30 minutes into cardiopulmonary bypass, 5 minutes after crossclamp removal, and 5 minutes after protamine administration. Thrombin formation (thrombin-antithrombin III by enzyme-linked immunosorbent assays) and platelet activation (β-thromboglobulin by enzyme-linked immunosorbent assays; P-selectin expression by flow cytometry) were assayed. Leukocyte activation was determined by quantitative and qualitative analysis of arterial filters by scanning electron microscopy in six patients from each group. In both circuits, thrombin values increased markedly 30 minutes into cardiopulmonary bypass compared with baseline values ( p < 0.001) (heparin-coated, 7 ± 5 to 96 ± 115 ng/ml; noncoated, 10 ± 9 to 115 ± 125 ng/ml). Platelet activation as measured by β-thromboglobulin (heparin-coated, 104 ± 100 to 284 ± 166 IU/ml; noncoated, 81 ± 74 to 288 ± 277 IU/ml) and P-selectin expression (heparin-coated, 1.5% ± 1.5% to 6.4% ± 6.1%; noncoated, 1.4% ± 1.1% to 6.2% ± 4.3%) also significantly increased 30 minutes into cardiopulmonary bypass compared with baseline values ( p < 0.001). Platelet activation and thrombin generation did not differ between the two circuits at any time. Granulocyte activation and platelet deposition did not differ between the two circuits when arterial filters were evaluated. Both groups had similar heparin and protamine administration, blood transfusions, postoperative alveolar-arterial oxygen gradient, time to extubation, length of intensive care unit stay, and overall morbidity and mortality. Clinical outcome and blood loss did not differ between the groups. We conclude that heparin-coated cardiopulmonary bypass circuits did not improve biochemical or clinical markers of biocompatibility in a reoperative patient population. (J T horac C ardiovasc S urg 1996;112:472-83)

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

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 micrograms/L) and 10 min after the administration of protamine (676 +/- 314 micrograms/L) were significantly (p < 0.05) lower than in the other 2 groups (820 +/- 341 and 893 +/- 303 micrograms/L and 1365 +/- 595 and 1,258 +/- 622 micrograms/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 beta-thromboglobulin 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.

Heparin-bonded surfaces in extracorporeal membrane oxygenation for cardiac support

Development of increasingly complex perfusion devices with bonded heparin allowed for significant improvement of thromboresistance of most basic components required for cardiopulmonary bypass. In his recent review of heparin-coated cardiopulmonary bypass circuits, Gravlee cited 91 references dealing with heparin-coated surfaces, and far more can be found if the search includes material technology or heparin-coated devices not designed for cardiopulmonary bypass (eg, ventricular assist devices, hemofilters, catheters). The present review is focused on long-term application of heparin-coated equipment in conjunction with basic work on heparin bonding relevant for extracorporeal membrane oxygenation. Experimental open chest cardiopulmonary bypass using heparin-coated equipment without systemic heparinization up to 36 hours has shown improved thromboresistance, and better platelet preservation was demonstrated for perfusion with heparin-coated cardiopulmonary bypass equipment up to 5 days in the experimental set-up. Similar findings were reported for roller pump perfusion with heparin-coated tubing and centrifugal pump perfusion with heparin-coated pump heads. More recently, heparin bonding was also made available for oxygenators with true membranes that preclude plasma leakage. The available knowledge on clinical applications of heparin-coated perfusion equipment is mainly based on short-term applications like ours, which now includes more than 300 patients. Reduced postoperative blood loss and as a result fewer transfusions were the main benefits of heparin-coated equipment allowing for perfusion with low systemic heparinization. There are only a few reports on long-term use of heparin-coated equipment for prolonged circulatory support. However, the longest clinical application of a single device is that of an intravascular gas exchanger that remained fully functional during a 29-day implantation period. Finally, it appears, that circulating protamine interacts with surface-bound heparin. Protamine administration should therefore be avoided during perfusion with heparin-bonded equipment to maintain the improved thromboresistance.

The evaluation of the clinical usefulness of heparin-coated cardiopulmonary bypass circuits

The evaluation of the clinical usefulness of heparin-coated cardiopulmonary bypass circuits

High and low heparin dose with heparin-coated cardiopulmonary bypass: Activation of complement and granulocytes

Cardiopulmonary bypass with heparin-coated circuits allows reduced amounts of systemic heparin. Heparin inhibits activation of the complement cascade experimentally, but the effects of different levels of systemic heparin on activation of complement and granulocytes in patients have remained unknown. Fifty-two patients undergoing coronary artery bypass procedures were studied. Cardiopulmonary bypass circuits completely coated with surface-bound heparin were used for one group given low-dose heparin (n = 17) (activated clotting time > 250 seconds), and was compared with a second group having normal high-dose heparin (activated clotting time > 480 seconds) (n = 18). A third control group was perfused with ordinary uncoated circuits and a full heparin dose (n = 17). During cardiopulmonary bypass, the C3 activation products C3b, iC3b, and C3c increased markedly in all three groups compared with baseline, but significantly less in the two heparin-coated groups (high dose, median maximal increase 58 arbitrary units (AU)/mL; low dose, 48 AU/mL) compared with the uncoated control group (74 AU/mL) (p < 0.01). The difference between the two coated groups was not significant. Similarly, the maximal increase in terminal SC5b-9 complement complex was considerably lower in the heparin-coated groups (high dose, 2.5 AU/mL; low dose, 2.6 AU/mL) compared with the level observed in the uncoated control group (5.3 AU/mL) (p < 0.01). The release of the granulocyte activation enzymes myeloperoxidase and lactoferrin increased from the beginning of the operation, with peak levels at the end of cardiopulmonary bypass (p < 0.01). The concentration of lactoferrin was significantly (p < 0.01) reduced in the low heparin dose group compared with the two other groups receiving normal high heparin doses, indicating that circulating heparin is an important granulocyte agonist, acting independently of the presence or absence of heparin-coated surfaces. Also for myeloperoxidase a higher level was observed in the high heparin dose group. Complement activation was significantly reduced in both heparin-coated groups and was independent of the level of systemic heparinization, whereas granulocyte activation was reduced only in patients who received low doses of systemically administered heparin. The results indicate that a moderate reduction of the systemic heparin dose may be an advantage with regard to improved biocompatibility when using heparin-coated cardiopulmonary bypass circuits.

Reduction of the inflammatory response and renal tubular injury by heparin-coated cardiopulmonary bypass circuits

Different platelet preparation techniques have not previously been compared directly and simultaneously with respect to in vivo platelet viability. Using a dual-label technique with 111In and 114mIn, platelet apheresis was compared with the platelet-rich plasma (PRP) procedure with respect to platelet recovery and survival (n=4). Furthermore, a continuous flow cell separator (Cobe 2997) and an intermittent apheresis system (Haemonetics V50) were compared with each other (n=4). No differences in platelet viability were found between the PRP-platelets and the apheresis-platelets. Also no differences were found between the two apheresis systems. Although different platelet preparation methods result in a varying degree of platelet activation, no difference in platelet viability has been observed.

Completely heparinized cardiopulmonary bypass and reduced systemic heparin: Clinical and hemostatic effects

When heparinized circuits are used for cardiopulmonary bypass, the amounts of heparin and protamine administered systemically can be reduced. However, it is not entirely known what effects this reduction in systemic anticoagulation has on clinical performance and on the coagulation and fibrinolytic systems. Two hundred three patients undergoing first-time elective myocardial revascularization were prospectively randomized either to a group in which a completely heparin-coated circuit was used for perfusion (group H; n = 101 patients) and in which a reduced heparin dose was given (activated clotting time, > 250 seconds) or to a control group (group C; n = 102 patients) in which an uncoated, but otherwise identical, circuit was used and in which full systemic heparinization was induced (activated clotting time, > 480 seconds). Indicators of thrombin generation, platelet activation, and fibrinolytic activity were studied in a subset of 34 patients. The total amount of postoperative mediastinal drainage was significantly reduced in group H (median, 575 mL) compared with that in group C (median, 635 mL; p = 0.002). Two patients in group C but none in group H received homologous red blood cell transfusions (p = not significant). The loss of hemoglobin in group H was a median of 21 g/L, and this was significantly lower than the 25 g/L noted in the control group (p = 0.006). During cardiopulmonary bypass, the plasma levels of thrombin-antithrombin complex and prothrombin fragment 1.2 increased in both groups. At the end of cardiopulmonary bypass the plasma levels of these markers of thrombin formation were significantly higher in group H, although the increase was modest compared with the major increase observed 2 hours after operation in both groups. There were no significant intergroup differences in the platelet counts, the concentration of beta-thromboglobulin, or the plasma levels of fibrinogen and D-dimer. No differences in perioperative morbidity, the postoperative kidney function, or the intubation time were observed, and there were no hospital deaths. The combination of complete heparin-coated cardiopulmonary bypass circuits and low systemic heparinization is safe for patients undergoing elective coronary artery bypass procedures and reduces the perioperative blood loss. There was no evidence of increased thrombogenicity, fibrinolytic activity, or consumption of coagulation factors. No clinical or technical side effects were observed.

Haemocompatibility of a Heparin-Coated Cardiopulmonary Bypass Circuit: A Prospective Randomised Trial

Haemocompatibility of a Heparin-Coated Cardiopulmonary Bypass Circuit: A Prospective Randomised Trial

Heparin-coated cardiopulmonary bypass circuits: Hemostatic alterations and postoperative blood loss

This prospective, randomized study involving patients undergoing isolated coronary artery bypass grafting investigated whether the use of heparin-coated bypass circuits with an uncoated cardiotomy reservoir (n = 10) compared with standard uncoated bypass circuits (n = 10) resulted in differences in patient outcome and hemostatic alterations. There were no differences in postoperative blood loss, transfusion requirements, and routine coagulation test results between groups. Immunoassays for platelet alpha-granule constituents platelet factor 4 and beta-thromboglobulin, thrombin generation byproduct F1.2, fibrinopeptide A, thrombin-antithrombin complex, and fibrinolysis by-product d-dimer also demonstrated no significant differences between groups, although trends for lower platelet secretion with heparin coating were noted. Increases were found in betathromboglobulin and platelet factor 4 concentrations at 10 ( p < 0.03) and 30 minutes ( p < 0.001) of CPB, respec tively, and continuing throughout CPB ( p < 0.001) for both groups versus values measured before incision. No significant differences were seen between levels 5 minutes prior to aortic cross-clamp release and those obtained 8 and 45 minutes after cross-clamp release. Conversely, no significant increases in F1.2, thrombin-antithrombin complex, and d-dimer were seen prior to release of the aortic cross-clamp, but afterward increases occurred that were highly significant ( p < 0.001). The temporal data suggest that platelet activation occurs primarily as a result of contact with the cardiopulmonary bypass circuitry, whereas thrombin generation and fibrinolytic activity are not significant until reperfusion of the heart and lungs. This latter effect may be due to reperfusion injury, humoral mediators generated by blood—biomaterial contact, or rewarming and increased use of cardiotomy suction and return of shed mediastinal blood.

Safe use of heparin-coated bypass circuits incorporating a pump-oxygenator

Durable, covalently bonded, heparin-coated cardiopulmonary bypass (CPB) circuits with oxygenators have been developed. Proposed advantages of heparin-coated CPB circuits include improved biocompatibility and thromboresistance. The purpose of this study was to evaluate our experience with heparin-coated CPB circuits in 20 patients. Heparin was given to maintain an activated clotting time equal to or greater than 200 seconds, while flow rates were kept equal to or greater than 2 L/min. Indications for use of this circuit included recent stroke, posttraumatic injuries, recent gastrointestinal bleeding, protamine allergies, combined cardiac and noncardiac procedures, and ventricular assist. Mean heparin dosage was 0.50 ± 0.18 mg/kg and protamine dosage was 57.14 ± 39.36 mg. Postoperative blood loss and transfusion requirements were minimal. Postoperative complement levels of C3a and C5a were normal, suggesting excellent biocompatibility. There were no deaths or perioperative complications. Heparin-coated CPB circuits using a pump oxygenator can be used safely with low-dose heparin administration in select patients requiring CPB.

The blood compatibility of heparin-coated cardiopulmonary bypass circuits

The blood compatibility of heparin-coated cardiopulmonary bypass circuits

Heparin-coated bypass circuits reduce pulmonary injury

Heparin coating of the extracorporeal circuit not only reduces heparin requirements during cardiac operations but also may reduce organ injury associated with cardiopulmonary bypass (CPB). To examine this possibility, pulmonary injury and neutrophil adhesion molecule expression after CPB were studied in pigs undergoing CPB with a standard extracorporeal circuit (group S, n = 6) or a heparin-coated CPB circuit (Carmeda BioActive Surface) (group HC, n = 6). Pigs received heparin sodium (300 U/kg intravenously) and then underwent 90 minutes of hypothermie (28 °C) CPB using membrane oxygenators, followed by 2 hours of observation. Blood samples were obtained for determination of neutrophil number and expression of the neutrophil adhesion molecule subunit CD18 (by immunofluorescence flow cytometry). The CPB-associated injury was less in group HC. Two hours after CPB, the arterial oxygen tension group was higher in group HC (597.2 ± 31.2 versus 220.5 ± 42.3 mm Hg; p < 0.0001), the pulmonary vascular resistance was lower in these animals (408.6 ± 69.4 versus 1,159.8 ± 202.4 dyne · s · cm −5; p = 0.02), and the static compliance was higher in group HC (66.4 ± 5.4 versus 39.8 ± 5.8 mL/mm Hg; p = 0.004). After 60 minutes of CPB, both groups had similar increases in expression of the neutrophil adhesion molecule subunit CD18 (29.4% ± 19.5% versus 26.0% ± 24.4%, group S and group HC, respectively) and similar decreases in neutrophil counts (6,056 ± 1,285 to 2,453 ± 979 cells/μL versus 6,010 ± 1,748 to 3,197 ± 1,225 cells/μL, group S and group HC, respectively). This study demonstrates that heparin coating improves pulmonary function after CPB and that this effect is not mediated by altered neutrophil kinetics or adhesion molecule expression.