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.     

Hyaluronan based heparin free coated open and closed extracorporeal circuits for high risk coronary revascularization

This prospective randomized study compares the inflammatory response and fibrinolytic activation of fully coated/uncoated and open/closed extracorporeal circuits (ECC) in high risk patients. Over a 2-month period, 48 patients with EuroSCOREs 6 or greater undergoing coronary revascularization were prospectively randomized to one of the four perfusion protocols: Group 1: Closed and totally hyaluronan based heparin free coated (Vision HFO-GBS-HF, Gish Biomedical, Rancho Santa Margarita, CA) ECC with a soft-shell coated venous reservoir (SVR11S2-HFC, Gish Biomedical) and a hard-shell cardiotomy (CAPVRF44, Gish Biomedical) (n = 12); Group 2: Closed and totally uncoated identical ECC with soft-shell uncoated venous reservoir and a hard-shell cardiotomy (n = 12); Group 3: Open, totally hyaluronan based heparin free coated ECC (n = 12); and Group 4: Control-open, uncoated ECC (n = 12). Blood samples were collected at T1: Baseline; T2: 15 minutes after cardiopulmonary bypass (CPB) initiation; T3: before cessation of CPB; T4: 15 minutes after protamine reversal, and T5: in the intensive care unit. Serum IL-6 levels were significantly lower at T2 in all study groups, at T3 for coated groups, and T4 for closed+coated group (p < .05 versus control). Creatine kinase M-band (MB) levels in coronary sinus blood demonstrated well preserved myocardium after CPB in both coated groups versus Control (p < .05). Neutrophil CD11b/CD18 levels were significantly lower for all study groups versus control at T2, for both coated groups at T3 and only for closed + coated group at T4 (p < .05). Postoperative hemorrhage (mL) was 510 +/- 40 in closed + coated and 536 +/- 40 in open + coated groups (control: 784 +/- 48, p < .05). No significant differences in thrombin-antithrombin complex and free plasma hemoglobin were observed. Desorbed protein amount on ECC (mg/dL) was 1.7 +/- .01 in closed+coated, 2.01 +/- .01 in open+coated, and 3.3 +/- .015 in control groups (p < or = .05). Use of a closed and completely heparin free coated ECC may reduce neutrophil degradation, cytokine release characterized by improved clinical outcomes including reduced blood loss, reduced requirement for inotropes, and reduced atrial fibrillation.     

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.     

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.     

The effect of cardiotomy suction on the brain injury marker S100beta after cardiopulmonary bypass

BACKGROUND: An increase of S100beta in serum during cardiopulmonary bypass (CPB) has been interpreted as a sign of brain injury. Cardiotomy suction may cause fat embolization, and its role in the S100beta increase was examined. METHODS: Twenty coronary artery operation patients were randomly assigned to two groups, 10 with suction during CPB to cardiotomy reservoir (CR), 10 to cell saving device (CS). S100beta was measured (immunoassay) in blood from the patients and from cell saving device after processing. In 7 additional patients S100beta was measured in the cell saving device before processing and directly from the wound at sternotomy. RESULTS: Before anesthesia, serum S100beta was 0.03+/-0.06 microg/L. At the end of CPB it was 2.47+/-1.31 microg/L and 0.44+/-0.27 microg/L (CR vs CS; p < 0.001). S100beta was 33+/-12 microg/L in CS reservoir and 42+/-18 microg/L in blood from the wound. CONCLUSIONS: Most serum S100beta after CPB with cardiotomy suction may be of extracerebral origin. S100beta after CPB with cell saving device was the same as after off-pump operation. The interpretation that an increase in S100beta during CPB in patients reflects cerebral injury must be questioned.     

Low dose systemic heparinization combined with heparin-coated extracorporeal circulation. Effects related to platelets

BACKGROUND: A heparin coated cardiopulmonary bypass system combined with full and low dose systemic heparinization in coronary bypass surgery was investigated in a prospective, randomised study. Roller pumps, coronary suction and an open cardiotomy reservoir were used. METHODS: One hundred and nineteen patients were divided into 3 groups: group A (n=39) had a standard uncoated extracorporeal circulation (ECC)-set and systemic heparin was given in an initial dose of 400 IE/kg body weight. During ECC activated clotting time (ACT) was kept at = or >480 sec. Group B (n=42) had the same ECC-set completely coated with low molecular weight heparin, i.v. heparin was administered in the same dose as in group A, ACT was again kept at = or >480 sec. Group C (n=38) had the same coated ECC set as group B, but i.v. heparin was reduced to 150 IE/kg and during ECC ACT was maintained of = or >240 sec. RESULTS: Platelet decrease was significantly less in both groups utilizing coated circuitry as compared to control group A. Activation of thrombocytes as marked by b-thromboglobulin (not PF4) was significantly decreased in patients treated with coated circuits combined with low dose systemic heparinization and postoperative bleeding was significantly reduced. CONCLUSIONS: We conclude that in heparin coated extracorporeal circulation combined with either full dose or reduced systemic heparinization compared to uncoated circuits platelet count reduction is significantly less. Platelet activation as marked by b-thromboglobulin and postoperative blood loss are decreased with coated equipment and low i.v. heparinization.     

Reduced Granulocyte Activation with a Heparin–Coated Device in an In Vitro Model of Cardiopulmonary Bypass

Granulocyte activation during cardiopulmonary bypass (CPB), resulting in degranulation, may have adverse effects. Fresh whole human blood and priming solution was circulated through oxygenator/tubing sets coated with functional heparin (n = 7) and through uncoated sets (n = 7) in model CPB. Plasma concentrations of the primary granule protein myeloperoxidase (MPO) and the secondary granule protein lactoferrin (LF) were measured in radioimmunoassays, and the neutrophils were counted. After 120 min, seven to nine times baseline concentrations of LF (p less than 0.0001) were observed with both devices. Increases of MPO were also significant, but significantly larger (p less than 0.01) with the uncoated devices. There was an equivalent reduction in neutrophil numbers in both groups. MPO did not bind to heparin-coated Sephadex particles in gel chromatography. Thus, the heparin coating most likely prevented the release of potentially harmful primary granule proteins, indicating improved biocompatibility. Adhesion of neutrophils and exocytosis of LF, which may be involved in adhesion, were unaffected.     

Clinical Study of Totally Roller Pumpless Cardiopulmonary Bypass System

Abstract: We have developed a low negative pressure vacuum suction system in which cardiotomy suction is performed by the negative pressure of the venous reservoir controlled by a vacuum controller. We have employed this vacuum suction system with a centrifugal pump as a totally roller pumpless cardiopulmonary bypass (CPB) system. In this study, the clinical availability and hemocompatibility of our totally roller pumpless CPB system were evaluated by a randomized prospective study. Thirty patients undergoing aortocoronary bypass grafting were assigned to the study. Data from seventeen patients treated with a totally roller pumpless CPB system were compared with data from 13 treated with a conventional roller pump CPB system. Totally roller pumpless CPB reduces hemolysis, showing lower plasma free hemoglobin levels (81.8 ± 25.0 versus 42.0 ± 16.3 at 30 min after CPB initiation, p < 0.05). higher plasma haptoglobin levels (37.8 ± 36.6 versus 77.2 ± 31.3 at 120 min after CPB, p < 0.05), and lower blood lactate dehydrogenase (LDH) levels (1391 ± 497 versus 972 ± 187, p < 0.01) than those of CPB with a roller pump suction with no significant difference between platelet counts. Arterial blood oxygen tension after using a totally roller pumpless CPB system was slightly better than that with a roller pump (396 ± 48 versus 437 ± 43, p = 0.069): however, there was no significant difference in intubation times between groups. A totally roller pumpless CPB system provides sufficient biocompatibility for the blood to reduce hemolysis significantly and simplifies and rniniaturizes the entire CPB system to achieve good visuality and handling for control as well.     

Elimination of fat microemboli during cardiopulmonary bypass

BACKGROUND: Fat emboli have been implicated in cerebral dysfunction after cardiopulmonary bypass (CPB). We sought to identify the source of fat emboli during CPB and devise a technique for their elimination. METHODS: Patients undergoing CPB were prospectively randomized to either cardiotomy suction (n = 7) or cell-saving suction device (n = 6). Blood was collected at various intervals during CPB, and the fat emboli were identified using oil red O stain. These emboli were grouped based on their diameter into 10- to 50-microm and more than 50-microm particles. The number of fat emboli per slide examined was graded according to the following scale: 1 (1 to 10), 2 (11 to 20), 3 (21 to 30), and 4 (> 30 emboli). In the second phase of the experiment, a 21-microm filter was attached in series, distal to the cardiotomy reservoir (n = 6), and fat emboli were quantified. RESULTS: Blood from the pericardial well was saturated with fat emboli of both sizes. Patients randomized to the cardiotomy suction had a significantly higher number of fat emboli at the end of CPB when compared with those randomized to the cell-saving suction device and dual-filter group. Processed blood from both the cardiotomy reservoir and cell-saving device was noted to have an abundance of fat emboli when compared with blood processed through the dual filters. CONCLUSIONS: Processed blood from both the cardiotomy reservoir and cell-saving device appear to have an abundance of fat emboli that are completely eliminated by using a 21-microm arterial filter in series with the cardiotomy reservoir. This intervention could potentially reduce neurocognitive dysfunction associated with CPB.     

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.     

Processing scavenged blood with a cell saver reduces cerebral lipid microembolization

BACKGROUND: Microembolization during cardiopulmonary bypass (CPB) can be detected in the brain as lipid deposits that create small capillary and arteriolar dilations (SCADs) with ischemic injury and neuronal dysfunction. SCAD density is increased with the use of cardiotomy suction to scavenge shed blood. Our purpose was to determine whether various methods of processing shed blood during CPB decrease cerebral lipid microembolic burden. METHODS: After hypothermic CPB (70 minutes), brain tissue from two groups of mongrel dogs (28 to 35 kg) was examined for the presence of SCADs. In the arterial filter (AF) group (n = 12), shed blood was collected in a cardiotomy suction reservoir and reinfused through the arterial circuit. Three different arterial line filters (Pall LeukoGuard, Pall StatPrime, Bentley Duraflo) were used alone and in various combinations. In the cell saver (CS) group (n = 12), shed blood was collected in a cell saver with intermittent preocessing (Medtronic autoLog model) or a continuous-action cell saver (Fresenius Continuous Auto Transfusion System) and reinfused with and without leukocyte filtration through the CPB circuit. RESULTS: Mean SCAD density (SCAD/cm2) in the CS group was less than the AF group (11 +/- 3 vs 24 +/- 5, p = 0.02). There were no significant differences in SCAD density with leukocyte filtration or with the various arterial line filters. Mean SCAD density for the continuous-action cell saver was 8 +/- 2 versus 13 +/- 5 for the intermittent-action device. CONCLUSIONS: Use of a cell saver to scavenge shed blood during CPB decreases cerebral lipid microembolization.     

Heparin management during cardiac surgery with respect to various blood-conservation techniques.

BACKGROUND. Various methods to reduce blood consumption are used in cardiac surgery. This study was designed to investigate the influence of various blood-conservation techniques on heparin plasma levels and coagulation variables in the perioperative period. METHODS. Anticoagulation was achieved by application of 300 units/kg bovine heparin before cardiopulmonary bypass (CPB). Ninety patients undergoing coronary bypass surgery were randomly divided into six groups according to different blood-conservation methods: group 1, blood during and after CPB was concentrated by a cell saver (CS); group 2, blood was concentrated by means of a hemofiltration device (HF); group 3, acute normovolemic hemodilution (ANH) was performed in combination with the CS technique (ANH-CS); group 4, ANH was carried out in combination with an HF during CPB (ANH-HF); group 5, acute plasmapheresis (APP) was performed and a CS was used during CPB (APP-CS); and group 6, APP was used in combination with an HF device (APP-HF). RESULTS. Heparin plasma concentration during CPB did not differ significantly among the six groups, ranging from 1.60 to 2.03 units/ml. Antagonization with protamine sulfate after termination of bypass in a 1:1 ratio decreased heparin concentration almost to baseline values. Fibrinogen concentration and antithrombin-III level were lowest in the CS group but were not decreased critically during the entire investigation period. Activated clotting time differed widely among the patients (range 383 to 807 seconds) and showed no significant correlation to heparin plasma levels. Partial thromboplastin time was higher than 300 seconds during the entire period of CPB, also indicating sufficient anticoagulation. Blood loss until day 1 after surgery was significantly most pronounced in the CS group and least in the APP-HF group. CONCLUSIONS. The blood conservation techniques used in this study were safe with regard to sufficient anticoagulation during CPB. No insufficient antagonization with protamine could be observed in the postbypass period.     

Technique for routine use of heparin bonded circuits with a reduced anticoagulation protocol

The use of heparin-bonded cardiopulmonary bypass circuits (HBCs) with reduced anticoagulation protocol during cardiac surgery attenuates some of the adverse pathophysiologic responses to cardiopulmonary bypass (CPB). The strategies of how to maximize improvements in clinical outcomes using this technique are still debated. This article describes in detail a comprehensive approach to strategies developed at Boston Medical Center and the West Roxbury Veteran Affairs Medical Center in over 4000 cases in which HBC with a reduced anticoagulation protocol is used routinely. Important elements of this technique include elimination of cardiotomy reservoir during coronary artery bypass graft surgery (CABG), autologous blood priming, normothermic CPB, and precise heparin and protamine titration. Adaptation and variation in this technique to specific clinical situations is also highlighted.     

The impact of heparin-coated cardiopulmonary bypass circuits on pulmonary function and the release of inflammatory mediators

Reduction of the inflammatory reaction with the use of heparin coating has been found during and after cardiopulmonary bypass (CPB). The question remains whether this reduced reaction also decreases the magnitude of CPB-induced pulmonary dysfunction. We therefore evaluated the effects of a heparin-coated circuit versus a similar uncoated circuit on pulmonary indices as well as on inflammatory markers of complement activation (C3b/c), elastase-alpha(1)-antitrypsin complex, and secretory phospholipase A(2) (sPLA(2)) during and after CPB. Fifty-one patients were randomly assigned into two groups undergoing coronary artery bypass grafting with either a heparin-coated (Group 1) or an uncoated (Group 2) circuit. During CPB, a continuous positive airway pressure of 5 cm H(2)O and a fraction of inspired oxygen (FIO(2)) of 0.21 were maintained. Differences in favor of the coated circuit were found in pulmonary shunt fraction (P < 0.05), pulmonary vascular resistance index (P < 0.05), and PaO(2)/FIO(2) ratio (P < 0.05) after CPB and in the intensive care unit. During and after CPB, the coated group demonstrated lower levels of sPLA(2). After CPB, C3b/c and the elastase-alpha(1)-antitrypsin complex were significantly less in the coated group (P < 0.001). The coated circuit was associated with a reduced inflammatory response, decreased pulmonary vascular resistance index and pulmonary shunt fraction, and increased PaO(2)/FIO(2) ratio, suggesting that the coated circuit may have beneficial effects on pulmonary function. The correlation with sPLA(2), leukocyte activation, and postoperative leukocyte count suggests reduced activation of pulmonary capillary endothelial cells. IMPLICATIONS: Heparin coating of the extracorporeal circuit reduces the inflammatory response during cardiopulmonary bypass. Analysis of indices of pulmonary function indicates that use of heparin coating may result in less impaired gas exchange.     

New application of heparin-bonded extracorporeal membrane oxygenation in difficult neurosurgery

We wished to evaluate the safety and the advantages of using heparin-bonded extracorporeal membrane oxygenation (ECMO) to replace conventional cardiopulmonary bypass (CPB) in deep hypothermic circulation for complex cerebral aneurysm surgery.Heparin-bonded ECMO without the bridging tube and the cardiotomy reservoir was set up through the femoral vessels. Limited heparin was infused. In deep hypothermia, the ECMO blood flow was temporarily decreased as low as the neurosurgeons' request. It was applied to 4 patients with difficult intracranial aneurysms who were selected for the procedure. Clipping, wrapping, or vascular bypass was implemented to manage the aneurysms under deep hypothermia. The total heparin dosage used in the whole procedure was 9,875 +/- 1,625 U, and the mean ECMO time was 270 +/- 105 min. The blood consumption was packed red blood cell 3.0 +/- 0.5 U and fresh frozen plasma 3.8 +/- 2.3 U. Compared with our previous experiences using conventional CPB, ECMO did need less heparin and blood transfusions. Clipping was applied in 2 patients, wrapping in 1, and venous graft interposition was performed in 1. Mortality occurred in 1 patient (25%) due to brain herniation. This preliminary study suggested that the heparin-bonded ECMO without reservoir in deep hypothermia could be safe in cerebral aneurysm surgery under a low flow circuit.     

Retransfusion of pericardial blood does not trigger systemic coagulation during cardiopulmonary bypass

Objective: During cardiopulmonary bypass (CPB), systemic coagulation is believed to become activated by blood contact with the extracorporeal circuit and by retransfusion of pericardial blood. To which extent retransfusion activates systemic coagulation, however, is unknown. We investigated to which extent retransfusion of pericardial blood triggers systemic coagulation during CPB. Methods: Thirteen patients undergoing elective coronary artery bypass grafting surgery were included. Pericardial blood was retransfused into nine patients and retained in four patients. Systemic samples were collected before, during and after CPB, and pericardial samples before retransfusion. Levels of prothrombin fragment F₁₊₂ (ELISA), microparticles (flow cytometry) and non-cell bound (soluble) tissue factor (sTF; ELISA) were determined. Results: Compared to systemic blood, pericardial blood contained elevated levels of F₁₊₂, microparticles and sTF. During CPB, systemic levels of F₁₊₂ increased from 0.28 (0.25–0.37; median, interquartile range) to 1.10 (0.49–1.55) nmol/l (p = 0.001). This observed increase was similar to the estimated (calculated) increase (p = 0.424), and differed significantly between retransfused and non-retransfused patients (1.12 nmol/l vs 0.02 nmol/l, p = 0.001). Also, the observed systemic increases of platelet- and erythrocyte-derived microparticles and sTF were in line with predicted increases (p = 0.868, p = 0.778 and p = 0.205, respectively). Before neutralization of heparin, microparticles and other coagulant phospholipids decreased from 464 μg/ml (287–701) to 163 μg/ml (121–389) in retransfused patients (p = 0.001), indicating rapid clearance after retransfusion. Conclusion: Retransfusion of pericardial blood does not activate systemic coagulation under heparinization. The observed increases in systemic levels of F₁₊₂, microparticles and sTF during CPB are explained by dilution of retransfused pericardial blood.     

Heparin-coated circuits reduce the formation of TNFα during cardiopulmonary bypass

Background: Cardiopulmonary bypass (CPB) causes a systemic intlammatory response. TNFα, which is a major inflammatory mediator, has been found in the circulation during and after CPB. Although previous studies have shown that heparin coating of the extracorporeal circuits reduces complement and granulocyte activation, and the inflammatory response, the possible effect of heparin coating on TNFα formation and the inflammatory response has not been fully investigated.
Methods: Eighteen patients scheduled for coronary artery bypass grafting were divided randomly into two groups. One group of patients had extracorporeal perfusion using heparin coated circuits (HC group, n = 9). The other group had extra-corporeal perfusion using an identical circuit that was not coated (UC group, n = 9). Blood samples were drawn before, during, and after CPB for measurement of plasma TNFα, plasma IL-8, neutrophil count, and neutrophil elastase.
Results: Plasma levels of TNFα increased during CPB in the UC group but not in the HC group. Plasma concentrations of IL-8 increased similarly during and after CPB in both groups. Coating the circuits with heparin did not affect the levels of IL-8. In both groups, the neutrophil count increased after the release of the aortic cross clamp and remained elevated for three days. In the HC group, however, the increase of neutrophil count was significantly lower compared with the UC group. Plasma concentrations of neutrophil elastase were significantly increased during and after CPB in both groups. However, the levels of elastase were significantly lower at certain time points in the HC group.
Conclusion: From these observations, we conclude that heparin coating of the extracorporeal circuits reduces the TNFα formation during CPB, which may reduce neutrophil activation.     

Reduced transfusion requirements with a closed cardiopulmonary bypass system

AIM: The aim of this investigation is to reduce blood transfusion in cardiac surgery patients with preoperative conditions predictive for transfusion requirements. We compared the amount of blood transfused in two groups of patients undergoing cardiopulmonary bypass (CPB) with two different circuit systems. METHODS: Sixty patients undergoing cardiac surgery were randomly assigned to two groups: in group A (N=30) cardiopulmonary bypass was accomplished with an open circuit and in group B (N=30) with a closed circuit. The open circuit consisted of a cardiotomy reservoir, a membrane oxygenator and an arterial line filter, while the closed circuit was made up of a collapsible venous reservoir, a membrane oxygenator, an arterial line filter and a cardiotomy reservoir. The amount of transfused packed red cells in each patient was measured until discharge from the hospital. RESULTS: Groups were similar regarding age, gender, body surface area (BSA), New York Heart Association (NYHA) class and comorbidity risk factors. Moreover, there were no significant differences between groups regarding the type of procedures, CPB and aortic cross-clamp times, total amount of cardioplegia and urinary output during CPB. Priming volume was 1180+/-84 mL (group A) and 760+/-72 mL (group B) (P<0.001). Significant differences in transfusion requirements emerged in the two groups: the total volume of packed red cells transfused for each patient was significantly higher in the open system group compared to the closed system group (717+/-486 mL versus 378+/-364 mL) (P=0.003). Clinical outcomes were similar in both groups. CONCLUSION: In patients with preoperative conditions predictive for the need of transfusions, the use of a closed cardiopulmonary bypass circuit can diminish the amount of transfused blood products.     

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

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

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

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