Effects of halothane and fentanyl anesthesia on plasma beta-endorphin immunoreactivity during cardiac surgery

We studied the effects of halothane anesthesia (n = 6) and fentanyl anesthesia (n = 9; 50-100 micrograms/kg) on plasma beta-endorphin immunoreactivity as a measure of stress response during coronary artery bypass grafting, including cardiopulmonary bypass. Plasma levels of beta-endorphin immunoreactivity measured prior to induction, after induction, after intubation, after skin incision, during cardiopulmonary bypass, and on leaving the operating room were significantly higher in patients given halothane during cardiopulmonary bypass and on leaving the operating room than they were in patients given fentanyl.     

Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group

BACKGROUND: Cardiac surgery patients' hematocrits frequently fall to low levels during cardiopulmonary bypass. METHODS: We investigated the association between nadir hematocrit and in-hospital mortality and other adverse outcomes in a consecutive series of 6,980 patients undergoing isolated coronary artery bypass graft surgery. The lowest hematocrit during cardiopulmonary bypass was recorded for each patient. Patients were divided into categories based on their lowest hematocrit. Women had a lower hematocrit during bypass than men but both sexes are represented in each category. RESULTS: After adjustment for preoperative differences in patient and disease characteristics, the lowest hematocrit during cardiopulmonary bypass was significantly associated with increased risk of in-hospital mortality, intra- or postoperative placement of an intraaortic balloon pump and return to cardiopulmonary bypass after attempted separation. Smaller patients and those with a lower preoperative hematocrit are at higher risk of having a low hematocrit during cardiopulmonary bypass. CONCLUSIONS: Female patients and patients with smaller body surface area may be more hemodiluted than larger patients. Minimizing intraoperative anemia may result in improved outcomes for this subgroup of patients.     

Changes in whole blood lactate levels during cardiopulmonary bypass for surgery for congenital cardiac disease: an early indicator of morbidity and mortality

OBJECTIVE: Our objective was to evaluate the change in lactate level during cardiopulmonary bypass and the possible predictive value in identifying patients at high risk of morbidity and mortality after surgery for congenital cardiac disease. METHODS: We prospectively studied lactate levels in 174 nonconsecutive patients undergoing cardiopulmonary bypass during operations for congenital cardiac disease. Arterial blood samples were taken before cardiopulmonary bypass, during cardiopulmonary bypass (cooling and rewarming), after cardiopulmonary bypass, and during admission to the cardiac intensive care unit. Complicated outcomes were defined as open sternum as a response to cardiopulmonary instability, renal failure, cardiac arrest and resuscitation, extracorporeal membrane oxygenation, and death. RESULTS: The largest increment in lactate level occurred during cardiopulmonary bypass. Lactate levels decreased between the postbypass period and on admission to the intensive care unit. Patients who had circulatory arrest exhibited higher lactate levels at all time points. Nonsurvivors had higher lactate levels at all time points. A change in lactate level of more than 3 mmol/L during cardiopulmonary bypass had the optimal sensitivity (82%) and specificity (80%) for mortality, although the positive predictive value was low. CONCLUSIONS: Hyperlactatemia occurs during cardiopulmonary bypass in patients undergoing operations for congenital cardiac disease and may be an early indicator for postoperative morbidity and mortality.     

Brain SPECT imaging and neuropsychological testing in coronary artery bypass patients

Background. Cognitive deficits appear frequently after cardiac operation. While the etiology remains unclear, alterations in cerebral perfusion during cardiopulmonary bypass may be causative. Single photon emission computed tomography (SPECT) scanning utilizes a radiopharmaceutical to provide images of cerebral perfusion. We proposed to study the cerebral circulation of patients during coronary artery bypass operation employing cardiopulmonary bypass.

Methods. Thirty-five neurologically normal patients underwent preoperative SPECT brain scanning and neuropsychological testing. A second SPECT brain perfusion scan was obtained by administering the radioisotope during cardiopulmonary bypass, with subsequent scanning upon completion of the procedure. Postoperative neuropsychological testing was performed prior to discharge.

Results. Fourteen (40%) of patients demonstrated significant neuropsychological decline. Patients who suffered cognitive impairment were no different in demographic, general health, or surgical variables. Patients who demonstrated neuropsychological decline had significantly poorer cerebral perfusion both at baseline and during operation.

Conclusions. Impaired cerebral perfusion at baseline may identify patients at risk for cognitive injury after cardiac operation. Alterations in cerebral perfusion during cardiopulmonary bypass is common, and may be a factor in neuropsychological deficits seen after cardiac operation.     

The influence of cardiopulmonary bypass on the size of human platelets.

Large and small platelets are present in the bloodstream in nearly equal proportions and comprise about 30 per cent of the normal platelet population. The assumption that cardiopulmonary bypass may alter this platelet population distribution was investigated. Platelet volume distribution curves during and after cardiopulmonary bypass were examined in 12 patients undergoing various intracardiac operation by an electronic particle-sizing apparatus based on the Coulter counter. Mean platelet volume (MPV) was 8.6 +/- 0.7 cubic microns prior to cardiopulmonary bypass. Ten minutes after commencement of cardiopulmonary bypass the MPV decreased to 85 per cent of control levels. A further decrease, reaching a plateau at 75 per cent of prebypass MPV, was reached after 50 minutes on bypass. MPV returned to 87 per cent of prebypass levels 2 hours after discontinuation of cardiopulmonary bypass. Since it is known that platelet count is markedly reduced on cardiopulmonary bypass, a simultaneous 25 per cent decrease in MPV can be explained only by a highly selective disappearance of the large platelets from the circulation. As the larger platelets are younger and functionally more potent than the smaller ones, the selective disappearance of large platelets may thus provide an explanation for the observed alteration in platelet adhesiveness caused by cardiopulmonary bypass.     

Optimal perfusion during extra-corporeal circulation

A multivariate analysis of 130 consecutive patients operated during one month in our hospital was carried out to determine the influence of age and blood flow during cardiopulmonary bypass on the renal response to cardiac surgery. The postoperative level of serum creatinine could be related to three variables: preoperative serum creatinine, age and lowest blood flow during cardiopulmonary bypass. A higher blood flow is needed during cardiopulmonary bypass in older patients and in patients with a raised pre-operative serum creatinine to prevent deterioration in renal function postoperatively. A nomogram is given for the lowest blood flow during CPB, corrected for age and the pre-operative serum creatinine level, which will result in a desired postoperative serum creatinine of 110 mumol/l.     

Pathophysiology of Cardiopulmonary Bypass: Current Issues

Much of the research related to cardiopulmonary bypass in recent years has been directed toward defining the changes in plasma and blood cells during bypass. In this review, recent information is reexamined for six areas of current interest. These areas are complement activation, immune response, anaphylactic reactions, coagulation, and cerebral dysfunction. Complement may be activated by either the classical or alternate pathway during cardiopulmonary bypass and protamine administration. Membrane oxygenators appear to diminish the degree of complement activation. Complement is a major factor in the whole body inflammatory response; which often accompanies cardiopulmonary bypass. A product of complement activation, C5a- desArg, causes activation and aggregation of granulocytes. Other products of complement activation lead to lysis of blood cells including granulocytes and red cells. Bubble oxygenators appear to have a distinct disadvantage compared to membrane oxygenators regarding infection. Airborne microorganisms are more likely to be entrained into circulating blood with bubble oxygenators than with membrane oxygenators. Bubble oxygenators cause a greater decrease in leukocyte number and function than membrane oxygenators. Anaphylactic reactions have been associated with use of antibiotics, blood products, protamine, and volume expanders during cardiopulmonary bypass. Protamine reactions may be on an immunological basis or due to direct toxicity of the drug. Free radicals including superoxide, hydrogen peroxide, and the hydroxyl radical may be generated during cardiopulmonary bypass and reperfusion. Free radical scavengers including; vitamin E, coenzyme Q, vitamin C, mannitol, and glutathione have been studied. The avoidance of blood transfusion because of risk of transmitted infection including AIDS has become a major goal in cardiac surgery. Factors that correlate with increased transfusion requirement include low hematocrit, female gender, increased age, small body size, low ejection fraction, reoperation, and emergency operation. Heparin resistance due to antithrombin III deficiency is being recognized more commonly. Antithrombin III deficiency may be corrected with fresh frozen plasma. Patients with heparin induced thrombocytopenia may be difficult to manage. Several management protocols are suggested. The most straightforward appears to be the use of aspirin preoperatively and platelet transfusions postoperatively. The incidence of cerebral dysfunction after cardiopulmonary bypass depends on the sensitivity of the test or indicator used. Perioperative stroke is associated with intrinsic cerebrovascular disease and atherosclerosis of the ascending aorta. Retinal angiograms during cardiopulmonary bypass show that microemboli are very common. Cerebroplegia has been shown to extend the period of safe circulatory arrest in animals. Much of the new knowledge concerning cardiopulmonary bypass is the result of close collaboration between cardiac surgeons and nonsurgical scientists.     

体外循环中肝素、鱼精蛋白对血小板的激活及抑肽酶的抑制作用

目的研究在体外循环中肝素化及鱼精蛋白中和时血小板的激活以及应用抑肽酶对这种激活的抑制作用。方法２０例心脏瓣膜置换术患者随机等分为两组：对照组和抑肽酶组，分别于肝素化及应用鱼精蛋白前后检测血小板胞浆游离钙浓度，磷脂酶Ａ２活性及血浆血栓素水平。结果上述指标在肝素化及鱼精蛋白中和后均显著升高，其中鱼精蛋白中和时升高幅度更大，应用抑肽酶对肝素及鱼精蛋白所引起的上述改变均有显著抑制作用。结论抑肽酶对肝素和鱼精蛋白所致的血小板激活有显著抑制作用，这可能与抑肽酶在体外循环中的止血作用有关。     

Fenoldopam: renal and splanchnic effects in patients undergoing coronary artery bypass grafting

Impairment of renal and splanchnic perfusion during and after cardiopulmonary bypass may be responsible for acute renal failure and endotoxin-mediated systemic inflammation, respectively. We hypothesised that fenoldopam, a selective dopamine receptor agonist, would preserve renal function after cardiopulmonary bypass through its selective renal vasodilatory and natriuretic effects, and increase gastrointestinal mucosal perfusion by selective splanchnic vasodilation. We examined the effects of fenoldopam on haemodynamic parameters, creatinine clearance, fractional excretion of sodium, urine output, free water clearance and gastric mucosal pH in 31 patients undergoing elective coronary revascularisation. Patients were randomly assigned to receive continuous infusions of fenoldopam 0.1 microg x kg(-1) x min(-1) (n = 16) or placebo (n = 15). Renal parameters were measured: during a 24-h period before hospital admission, during cardiopulmonary bypass, from completion of cardiopulmonary bypass until 4 h later, from 4 to 8 h after cardiopulmonary bypass, and from 8 to 14 h after cardiopulmonary bypass. Gastric intramucosal pH was measured using a gastric tonometer before, during and after cardiopulmonary bypass. In the placebo group, but not the fenoldopam group, mean (SD) creatinine clearance decreased after separation from cardiopulmonary bypass, from 107 (36) to 71 (22) ml x min(-1) (p < 0.01) and from 107 (36) to 79 (26) ml x min(-1) (p < 0.01) for the 0-4 h and 4-8 h intervals after cardiopulmonary bypass, respectively. Changes in intramucosal pH were similar in both groups. The findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect in patients undergoing cardiopulmonary bypass.     

Antifibrinolytic therapy with tranexamic acid in cardiac operations.

To demonstrate its antifibrinolytic effects and establish an effective regimen of tranexamic acid for hemostasis, the authors measured alpha2-plasmin inhibitor-plasmin complexes, thrombin-antithrombin III complexes and postoperative blood loss in three groups undergoing different regimens during cardiac operations. Forty-six patients undergoing coronary artery bypass grafting or valve replacement were enrolled in this study. They were divided into three groups of drug administration. A bolus infusion of 50 mg/kg tranexamic acid was given to 17 patients at the end of cardiopulmonary bypass (control group) and to 14 patients at the beginning of cardiopulmonary bypass (group A). In addition to the same bolus infusion at the beginning of cardiopulmonary bypass as group A, a continuous infusion of 10 mg/kg per h, starting at the time of skin incision and maintained for 6 h after cardiopulmonary bypass was given to 15 patients (group B). The marked increase in alpha2-plasmin inhibitor-plasmin complexes at the end of cardiopulmonary bypass in the control group was significantly reduced in group A (P < 0.01) and a further reduction was observed in group B (P < 0.001). The difference in postoperative blood loss only reached significant levels between the control group and group B (P < 0.05). Although a significant increase in thrombin-antithrombin III complexes during cardiopulmonary bypass was similarly observed in all groups, no thromboembolic events occurred in any group, nor was any difference seen in graft patency. From the tranexamic acid therapy regimens tested in this study, a continuous infusion of 10 mg/kg per h starting at the time of skin incision to 6 h after cardiopulmonary bypass, with a bolus infusion of 50 mg/kg at the beginning of cardiopulmonary bypass, proved to be the most effective.     

Plasma vitamin E and A changes during cardiopulmonary bypass and in the postoperative course

BACKGROUND: Cardiopulmonary bypass induces a generalized inflammatory reaction accompanied by free radical generation. Depletion of antioxidants could result and is reported for vitamin E and C. We investigated the effect of cardiopulmonary bypass on plasma concentrations of alpha-tocopherol, retinol, and biochemical variables (e.g., triacylglycerol, cholesterol, and C-reactive protein). PATIENTS AND METHODS: Plasma levels of all parameters were investigated by serial sampling in ten men undergoing elective coronary artery bypass grafting. Samples were taken before, during, and up to 48 h after bypass to obtain time profiles of the laboratory indices. RESULTS: alpha-Tocopherol and retinol decreased during cardiopulmonary bypass when not adjusted for confounders. After adjustment for hemodilution and lipids, no significant change was noted during bypass. However, a reduction in retinol was observed 48 h postoperatively. CONCLUSIONS: These data indicate that vitamin E and A analysis to ascertain links to their consumption via the production of free radicals under conditions of cardiopulmonary bypass may be inappropriate. Specifically, during bypass a reduction in systemic vitamin E and A seems to be a response to changes in blood volume and liver function.     

Monitoring oxygenator expiratory isoflurane concentrations and the bispectral index to guide isoflurane requirements during cardiopulmonary bypass

OBJECTIVE: The purpose of this study was to measure the changes in isoflurane requirements during the rewarming phase of cardiopulmonary bypass with moderate hypothermia. DESIGN: An observational study. SETTING: University hospital, single center. PARTICIPANTS: Forty patients undergoing elective coronary artery bypass surgery with cardiopulmonary bypass. INTERVENTIONS: Isoflurane requirements were quantified by measuring the concentrations in the oxygenator expiratory gas. Anesthesia was guided by bispectral index monitoring. MEASUREMENTS AND MAIN RESULTS: Isoflurane concentrations required to maintain the bispectral index between 40 and 50 during the rewarming phase of cardiopulmonary bypass were measured. There was a progressive increase in expiratory isoflurane requirements during rewarming from 30 degrees C to 37 degrees C, with a Pearson correlation coefficient of 0.78. There was a significant difference in the concentration required at 30 degrees C (0.41% +/- 0.14%) compared with 37 degrees C (1.00% +/- 0.12%). CONCLUSION: Isoflurane requirements are reduced during hypothermic cardiopulmonary bypass. Monitoring anesthetic concentrations in the oxygenator expiratory gas may be a useful adjunct to monitoring the depth of anesthesia.     

Brain microvascular function during cardiopulmonary bypass

Emboli in the brain microvasculature may inhibit brain activity during cardiopulmonary bypass. Such hypothetical blockade, if confirmed, may be responsible for the reduction of cerebral metabolic rate for glucose observed in animals subjected to cardiopulmonary bypass. In previous studies of cerebral blood flow during bypass, brain microcirculation was not evaluated. In the present study in animals (pigs), reduction of the number of perfused capillaries was estimated by measurements of the capillary diffusion capacity for hydrophilic tracers of low permeability. Capillary diffusion capacity, cerebral blood flow, and cerebral metabolic rate for glucose were measured simultaneously by the integral method, different tracers being used with different circulation times. In eight animals subjected to normothermic cardiopulmonary bypass, and seven subjected to hypothermic bypass, cerebral blood flow, cerebral metabolic rate for glucose, and capillary diffusion capacity decreased significantly: cerebral blood flow from 63 to 43 ml/100 gm/min in normothermia and to 34 ml/100 gm/min in hypothermia and cerebral metabolic rate for glucose from 43.0 to 23.0 mumol/100 gm/min in normothermia and to 14.1 mumol/100 gm/min in hypothermia. The capillary diffusion capacity declined markedly from 0.15 to 0.03 ml/100 gm/min in normothermia but only to 0.08 ml/100 gm/min in hypothermia. We conclude that the decrease of cerebral metabolic rate for glucose during normothermic cardiopulmonary bypass is caused by interruption of blood flow through a part of the capillary bed, possibly by microemboli, and that cerebral blood flow is an inadequate indicator of capillary blood flow. Further studies must clarify why normal microvascular function appears to be preserved during hypothermic cardiopulmonary bypass.     

Relief of bronchial obstruction using a Fogarty catheter in a patient with bronchomalacia

Tracheobronchomalacia can be latent without showing any clinical manifestations and may be incidentally found during anesthesia. In such cases, hypoxia may occur during anesthesia. We experienced obstruction of the left main bronchus caused by bronchomalacia that was incidentally found during open-heart surgery in a 4-yr-old patient. We could not reopen the airway by routine techniques, such as positive pressure, and had great difficulty in weaning the patient from cardiopulmonary bypass. The use of a Fogarty catheter allowed the relief of airway obstruction and weaning from cardiopulmonary bypass.     

Heparin resistance after intraoperative platelet-rich plasma harvesting.

Records of anticoagulation for cardiopulmonary bypass from 58 patients who underwent elective coronary artery revascularization were analyzed to determine whether the harvesting of autologous platelet-rich plasma produces heparin resistance. The effect of preoperative heparin therapy on anticoagulation for cardiopulmonary bypass after harvesting of platelet-rich plasma was also evaluated. Patients were grouped by presence of preoperative heparin therapy and type of blood component harvested before cardiopulmonary bypass, including platelet-rich plasma, autologous whole blood, both, or neither. The dose of heparin required to initiate and to maintain anticoagulation for cardiopulmonary bypass was determined for each patient, and the groups were compared by two-way analysis of variance. Significantly more heparin was required to maintain anticoagulation for cardiopulmonary bypass in the platelet-rich plasma group than in the groups receiving autologous whole blood or no blood products. More heparin was also required to initiate and to maintain anticoagulation for cardiopulmonary bypass after preoperative heparin therapy. These results reinforce the concept that anticoagulation during cardiopulmonary bypass must be carefully monitored, and increased vigilance may be warranted in patients after harvesting of platelet-rich plasma.     

Comparative study of cefazolin, cefamandole, and vancomycin for surgical prophylaxis in cardiac and vascular operations. A double-blind randomized trial.

Three-hundred twenty-one adults undergoing cardiac or major vascular operations were randomized to receive intravenous cefazolin, cefamandole, or vancomycin for prophylaxis against surgical infection in a double-blind trial. All three regimens provided therapeutic blood levels throughout operation in patients studied undergoing cardiopulmonary bypass. The prevalence of surgical wound infection was lowest with vancomycin (4 infections [3.7%] versus 14 [12.3%] and 13 [11.5%] in the cefazolin and cefamandole groups, respectively; p = 0.05); there were no thoracic wound infections in cardiac operations in the vancomycin group (p = 0.04). The mean duration of postoperative hospitalization was lowest in the vancomycin group (10.1 days; p < 0.01) and highest in the cefazolin group (12.9 days). Prophylaxis with vancomycin or cefamandole, compared with cefazolin, did not prevent nosocomial cutaneous colonization by methicillin-resistant coagulase-negative staphylococci; colonization or infection with vancomycin-resistant staphylococci or enterococci was not detected. Adverse effects attributable to the prophylactic regimen were infrequent in all three groups. Eight patients given vancomycin became hypotensive during administration of a dose, despite infusion during a 1-hour period; however, slowing the rate of administration and pretreating with diphenhydramine allowed vancomycin to be resumed and prophylaxis completed uneventfully in five of the patients. We conclude that administration of vancomycin (approximately 15 mg/kg), immediately preoperatively, provides therapeutic blood levels for surgical prophylaxis throughout most cardiac and vascular operations, resulting in protection against postoperative infection superior to that obtained with cefazolin or cefamandole. Vancomycin deserves consideration for inclusion in the prophylactic regimen (1) for prosthetic valve replacement and prosthetic vascular graft implantation, to reduce the risk of implant infection by methicillin-resistant coagulase-negative staphylococci and enterococci; (2) for any cardiovascular operation if the patient has recently received broad-spectrum antimicrobial therapy; and (3) for all cardiovascular operations in centers with a high prevalence of surgical infection with methicillin-resistant staphylococci or enterococci. Guidelines for dosing and administration of vancomycin for cardiovascular surgical prophylaxis are provided.     

Endothelial dysfunction in cerebral microcirculation during hypothermic cardiopulmonary bypass in newborn lambs

Objectives: Inflammatory stimuli or mechanical stresses associated with hypothermic cardiopulmonary bypass could potentially impair cerebrovascular function, resulting in inadequate cerebral perfusion. We hypothesize that hypothermic cardiopulmonary bypass is associated with endothelial or vascular smooth muscle dysfunction and associated cerebral hypoperfusion. Therefore we studied the cerebrovascular response to endothelium-dependent vasodilator, acetylcholine, endothelium-independent nitric oxide donor, sodium nitroprusside, and vasoactive amine, serotonin, in newborn lambs undergoing hypothermic cardiopulmonary bypass (nasopharygeal temperature = 18° C). Methods: Studies were performed on 13 newborn lambs equipped with a closed cranial window, allowing for direct visualization of surface pial arterioles. Six animals were studied while undergoing hypothermic cardiopulmonary bypass, whereas seven served as nonbypass, warm (37° C) controls. Pial arteriolar caliber (range = 111 to 316 μm diameter) was monitored using video microscopy. Results: Topical application of acetylcholine caused a dose-dependent increase in arteriolar diameter in the control group that was absent in animals undergoing hypothermic cardiopulmonary bypass. Hypothermic cardiopulmonary bypass did not alter the vasodilation in response to sodium nitroprusside. Furthermore, the contractile response to serotonin was fully expressed during hypothermic cardiopulmonary bypass. Conclusions: The specific loss of acetylcholine-induced vasodilation suggests endothelial cell dysfunction rather than impaired ability of vascular smooth muscle to respond to nitric oxide. It is speculated that loss of endothelium-dependent regulatory factors in the cerebral microcirculation during hypothermic cardiopulmonary bypass may enhance vasoconstriction, and impaired cerebrovascular function may be a basis for associated neurologic injury during or after hypothermic cardiopulmonary bypass. (J thorac Cardiovasc Surg 1998;15:1047-54)     

Effects of Duraflo II heparin-coated cardiopulmonary bypass circuits on the coagulation system, endothelial damage, and cytokine release in patients with cardiac operation employing aprotinin and steroids

The effects of Duraflo II heparin coated cardiopulmonary bypass circuits, low-dose aprotinin, and steroids on the coagulation system, endothelial damage, and cytokine release were evaluated by comparing those treated with low-dose aprotinin and steroids. Twenty-four adult patients undergoing coronary artery bypass grafting, aortic valve replacement, or valve repair surgery were randomly assigned to 2 groups: either heparin-coated (Duraflo group, n = 12) or noncoated equipment (noncoated group, n = 12) groups. In the Duraflo group, the cardiopulmonary reservoir was also coated with heparin. There were no significant differences in age at the time of operation, aortic cross-clamp time, cardiopulmonary bypass time, and rectal temperature during cardiopulmonary bypass. Standard systemic heparinization was performed. Methylpredonisolone and low-dose aprotinin were given in both groups of patients. Serum XIIa factor, TAT, and IL-6 were significantly higher in the control group than in the Duraflo group during cardiopulmonary bypass (p < 0.01). Serum IL-8 was significantly higher in the control group than in the Duraflo group at 24 h after cardiopulmonary bypass (p < 0.05). No significant difference was found in serum thrombomodulin and TNF-alpha; both were within normal during the study period. These results indicate that the use of Duraflo II heparin coated equipment and a heparin-coated cardiopulmonary reservoir suppressed excess coagulation and inflammatory reaction induced by cardiopulmonary bypass.     

Effect of ultrafiltration on plasma colloid oncotic pressure and red cell volume during cardiopulmonary bypass

Forty cardiopulmonary bypass patients were randomized into two matchable groups, an ultrafiltration and an control group. We have concluded that change of plasma colloid oncotic pressure may be a more sensitive parameter of monitoring the effect of ultrafiltration during cardiopulmonary bypass.     

Pharmacologic platelet anesthesia by glycoprotein IIb/IIIa complex antagonist and argatroban during in vitro extracorporeal circulation

OBJECTIVE: Contact between blood and the synthetic surfaces of a cardiopulmonary bypass circuit leads to platelet activation, and resultant platelet dysfunction contributes to postoperative bleeding. We compared the effects of various platelet inhibitors on preservation of platelet function during simulated cardiopulmonary bypass circulation. METHODS: Fresh human blood was recirculated in an in vitro cardiopulmonary bypass model circuit. We measured various platelet activation markers including expressions of PAC-1 and P-selectin, annexin V binding, and microparticle formations by means of whole-blood flow cytometry. RESULTS: Two types of glycoprotein IIb/IIIa complex antagonists, peptide-mimetic FK633 and abciximab and prostaglandin E(1), significantly prevented platelet loss and the increase in binding of PAC-1, an antibody specific for fibrinogen receptor on activated platelets, during extracorporeal circulation of heparinized blood. These antagonists significantly suppressed but did not abolish P-selectin expression, annexin V binding, and microparticle formation. Anti-von Willebrand factor monoclonal antibody and aurin tricarboxylic acid (an inhibitor of glycoprotein Ib) had no effect on platelet activation during simulated cardiopulmonary bypass circulation. These data suggest that inhibition of fibrinogen binding glycoprotein IIb/IIIa complex is partly effective in attenuating platelet activation in a heparinized cardiopulmonary bypass model circuit. The direct thrombin inhibitor argatroban prevented platelet loss and expression of P-selectin significantly more than did heparin. A combination of FK633 with argatroban as a substitute for heparin further prevented platelet loss and platelet secretion during simulated cardiopulmonary bypass circulation, although the inhibition of microparticle formation was less. CONCLUSION: The inhibition of both platelet adhesion and thrombin may be effective to preserve platelet number and function during cardiopulmonary bypass circulation.