Impact of ultrafiltration on blood use for atrial septal defect closure in infants and children

BACKGROUND: Infants and children undergoing open cardiac operations have a high incidence of blood product transfusion. Ultrafiltration has been shown to reverse hemodilution and improve myocardial function and hemodynamics after cardiopulmonary bypass (CPB). METHODS: The effect of ultrafiltration on the amount of blood transfusion and hospital charge in 39 consecutive patients who underwent elective atrial septal defect repair was examined. Patients in group I (n=26) had a conventional cardiopulmonary circuit prime with blood, whereas 13 patients had bloodless prime (group II). Ultrafiltration was used immediately after weaning from CPB in group II. The patients in group I received blood products after discontinuation of CPB to achieve a hematocrit of 30%. The amount of blood product used, hematocrit immediately after CPB and on arrival in intensive care unit, postoperative hemodynamics and saturations, total operating room charge, blood charge, hospital stay, and hospital charge were compared. RESULTS: Mean body weight (15.8 kg in group I versus 17.5 kg in group II) and preoperative hematocrit values (35.6% in group I versus 34.2% in group II) were similar. Mean hematocrit immediately after CPB was 22% and 14% in group I and II, respectively (p < 0.0001). The mean hematocrit upon arrival to the intensive care unit was 34% in group I and 22% in group II (p < 0.0001). The amount of blood product transfusion was 32 mL/kg in group I and 3 mL/kg in group II patients (p < 0.0001). The patients in group II had significantly less blood bank charges; however, operating room charges and total hospital charges were similar between the two groups. CONCLUSIONS: Elective atrial septal defect repair was performed with no blood product transfusion without increased morbidity or hospital stay. Ultrafiltration can be used to reverse hemodilution resulting from a bloodless CPB prime without an increase in hospital charge.     

Temperature-dependent formation of a conjugate between tris(hydroxymethyl)aminomethane buffer and the malondialdehyde-DNA adduct pyrimidopurinone

OBJECTIVE: To examine the effects of cardiopulmonary bypass (CPB) on total and unbound plasma concentrations of propofol and midazolam when administered by continuous infusion during cardiac surgery. DESIGN: Prospective clinical study. SETTING: University hospital. PARTICIPANTS: Twenty-four adult patients undergoing cardiac surgery. INTERVENTIONS: Patients received either propofol or midazolam to supplement fentanyl anesthesia. Twelve patients received a propofol bolus (1 mg/kg) followed by an infusion of 3 mg/kg/hr. A second group received midazolam, 0.2 mg/kg bolus, followed by an infusion of 0.07 mg/kg/hr. MEASUREMENTS AND MAIN RESULTS: Blood sample were collected from the radial artery cannula at 0, 2, 4, 8, 8, 10, 15, 20 minutes and then every 10 minutes before CPB, at 1, 2, 3, 4, 6, 10, 15, 20 minutes and then each 10 minutes during CPB. On weaning from CPB samples were collected at 0, 5, 10 and 20 minutes. Plasma binding, total and unbound propofol and midazolam concentrations were determined by ultrafiltration and high-pressure liquid chromatography (HPLC). CPB resulted in a fall in total propofol and midazolam plasma concentrations, but the unbound concentrations remained stable. The propofol unbound fraction increased from 0.22 +/- 0.06% to 0.41 +/- 0.17%. The midazolam unbound fraction increased from 5.6 +/- 1.0% to 11.2 +/- 2.1%. CONCLUSIONS: Unbound concentrations of propofol and midazolam are not affected by cardiopulmonary bypass. Total intravenous anesthesia algorithms do not need to be changed to achieve stable unbound plasma concentrations when initiating CPB.     

A population pharmacokinetic study of alminoprofen penetration into synovial fluid

BACKGROUND: Transfusing fresh autologous blood during cardiac surgery may improve hemostasis and decrease the need for transfusion. STUDY DESIGN AND METHODS: A prospective randomized study was performed with fresh whole blood (WB) obtained by intraoperative hemodilution (IH) and with platelet-rich plasma (PRP) obtained by perioperative apheresis from adult cardiac surgery patients. RESULTS: Seventy patients were randomly assigned to three arms: 24 to the PRP arm, 18 to the IH arm, and 28 to serve as controls. A mean of 924 +/- 130 mL of WB was collected from the IH group, and a mean of 650 +/- 124 mL of PRP was collected from the PRP group (mean, 1.42 +/- 0.74 x 10(11) platelets); these components were transfused after bypass. Preoperative measures were similar among groups. Intraoperatively, the groups did not differ in bypass time, estimated blood loss, number of transfusions, or proportion receiving transfusion(s). Postoperatively, control patients had more mediastinal drainage (736 mL vs. 476 mL [IH] and 463 mL [PRP]; p = 0.014), but there was no difference in the proportion of patients requiring red cell transfusion (p = 0.87), the hemoglobin at discharge (p = 0.20), or the length of hospitalization (p = 0.57). CONCLUSION: Although a hemostatic benefit manifested as reduced postoperative bleeding was observed, this study does not support the use of fresh blood components obtained by IH or PRP collection during low-risk cardiac surgery. Additional studies are needed to assess whether more aggressive component collection or the use of these techniques in high-risk cases may have a greater impact on clinical outcome variables, including transfusion.     

Surgical treatment of laryngotracheal stenosis: a review of 60 cases

STUDY OBJECTIVE: To determine the influence of temperature and duration of cardiopulmonary bypass (CPB) on blood loss and transfusion requirements. DESIGN: Retrospective chart review. SETTING: Tertiary care, academic medical institution. MEASUREMENTS AND MAIN RESULTS: The charts of 378 patients who had undergone primary elective coronary artery bypass graft surgery were studied. Systemic perfusion of CPB had been conducted between 20 degrees C and 37 degrees C in all patients. Patient demographic, temperature during CPB, duration of CPB, blood loss, and transfusion requirements were all recorded. Hypothermic CPB patients had minor increases in requirements for transfusion of red blood cells (RBC; p = 0.01), fresh frozen plasma (FFP; p = 0.01), platelets (PLT; p = 0.003), and total (allogeneic and autologous) blood products (p < 0.001). Multivariate analysis revealed that decreased temperature after adjusting for duration was predictive of allogeneic (RBC, FFP, PLT, and cryoprecipitate) and total (allogeneic and autologous) transfusion requirements. The duration of CPB correlated with decreased temperature (r = -0.455; p < 0.0001). After adjusting for temperature, duration was only predictive of total (allogeneic and autologous) transfusion requirements. CONCLUSIONS: The institution of warm CPB has many ramifications for clinical practice. The hypothermic induced platelet dysfunction and increased duration associated with cold CPB may contribute to the minor increases in transfusion requirements. However, temperature appears to be a weak factor, neither supporting nor refuting the use of warm or cold CPB.     

Effect of blood conservation in open-heart surgery: a comparison of 3 different methods

Conventional blood conservation techniques have been insufficient to decrease blood transfusion requirement in open-heart surgery. Blood conservation and erythropoietin administration were performed to avoid homologous blood transfusion. Intraoperative autotransfusion has been routinely used in cardiac operations with cardiopulmonary bypass in our hospital. To evaluate the effect of conservation techniques, 286 patients were divided into four groups. In group I (23 patients), autologous whole blood was drawn and saved one to two weeks before operation. In group II (50 patients), erythropoietin preparation was given subcutaneously once a week and autologous blood conservation was also performed in the same manner as group I. In group III (48 patients), intra-operative hemodilutional autologous blood transfusion was performed. In group IV, as a control group (165 patients), only intra-operative autotransfusion was used. Homologous blood transfusion was avoided in 83% of group I patients, in 90% of group II, in 82% of group III, and 29% of group IV. In addition, in group II the hemoglobin value at the time of discharge was significantly higher than those of other groups (p < 0.05-0.01). Thus, conventional blood conservation techniques plus subcutaneous administration of erythropoietin was very effective to increase the rate of "non-blood" open-heart surgery.     

Strategies of myocardial protection for operation in chronic model of cyanotic heart disease

BACKGROUND: Cyanotic congenital hearts have an increased susceptibility to ischemia and subsequent reperfusion. The role of platelet-activating factor antagonism and mechanical neutrophil depletion with leukocyte-depleting filters for control of ischemia-reperfusion injury was assessed in corrective surgical procedures for cyanotic heart disease. METHODS: A swine model of cyanotic heart disease was evaluated with three study groups: a control group; a group given a platelet-activating factor antagonist (PAFA group); and a group with leukocyte-depleting filtration (LDF group). The cyanotic model was created with a left atrial appendage-pulmonary artery fistula with peripheral banding through a left anterior thoracotomy in weanling swine. The experimental procedure was performed 5 to 7 weeks later when body weight was greater than 20 kg and oxygen saturation was 85% or less. The corrective procedure was performed through a median sternotomy on cardiopulmonary bypass with repair of the shunt. Myocardial protection was accomplished with hypothermic blood-crystalloid (4:1) cardioplegia; the period of ischemic arrest was 90 minutes. In the PAFA group, the platelet-activating factor antagonist CV-6209 was delivered intravenously 15 to 20 minutes before aortic cross-clamping. In the LDF group, Pall leukocyte-depleting filters were used in the CPB arterial line. Hemodynamic data were taken before operation and 10 and 30 minutes after CPB with impedance ventriculography. RESULTS: There were four deaths in the control group within 30 minutes after CPB; all animals in the treated groups survived longer than 60 minutes (p < 0.05). The ventricular assessment of end-systolic elastance revealed superior performance in the LDF group 30 minutes after CPB compared with the control group (p < 0.05) (controls, 4.0+/-9; PAFA group, 6.5+/-3.7; and LDF group, 12.0+/-4.6). CONCLUSIONS: Both leukocyte-depleting filters and platelet-activating factor antagonism provided myocardial protection, and the filters afforded superior postoperative myocardial contractility.     

Effect of veno-venous ultrafiltration on myocardial performance immediately after cardiac surgery in children. A prospective randomized study

OBJECTIVES: This study sought to evaluate the effects of veno-venous ultrafiltration on myocardial contractility in children undergoing cardiopulmonary bypass (CPB) for repair of congenital heart defects. BACKGROUND: Ultrafiltration (UF) is currently used to diminish postoperative fluid accumulation following CPB in children. Previous reports indicate improvement in hemodynamics immediately after UF, but the mechanism of its action is unknown. METHODS: Twenty-three patients (ages 2 months to 9.1 years; 13 males, 10 females) underwent UF for 10 min after CPB. Twelve patients underwent UF immediately after CPB (Group A). They were studied: (1) before and (2) after CPB, (3) after UF, and (4) 10 min after UF. Eleven patients underwent UF 10 min after CPB (Group B). They were studied: (1) before and (2) after CPB, (3) after a 10-min delay before UF, and (4) after UF. Contractility was determined by the difference in the observed and predicted velocity of circumferential fiber shortening for the measured wall stress, using transesophageal echocardiography. Left ventricular wall thickness was also measured. RESULTS: There was significant improvement in contractility after UF in both groups (mean+/-SD, Group A: -0.28+/-0.13 to -0.01+/-0.21 circ/s, p < 0.05; Group B: -0.26+/-0.16 to -0.11+/-0.17 circ/s, p < 0.05). Myocardial thickness to cavity dimension decreased in both groups following UF (Group A: 0.19+/-0.04 to 0.14+/-0.03, p < 0.05; Group B: 0.18+/-0.04 to 0.14+/-0.03, p < 0.05). CONCLUSIONS: UF improves hemodynamics by improving contractility and possibly by reducing myocardial edema in children following cardiac surgery. Enhanced patient outcome after ultrafiltration may in part be due to these changes.     

Effects of concomitant usage of milrinone and catecholamine for weaning from cardiopulmonary bypass

To estimate the effectiveness of concomitant usage of milrinone and catecholamine for weaning from cardiopulmonary bypass (CPB), a clinical study was made, in elective coronary artery bypass grafting (CABG) cases. 24 consecutive patients underwent elective CABG in our institute. In all cases, moderate hypothermia and cardioplegic(St. Thomas solution) cardiac arrest were performed. In 12 cases, continuous intravenous 0.25 microgram/kg/min of milrinone, 3 micrograms/kg/min of dobutamine (DOB) and dopamine (DOA) as the initial doses, were used concomitantly as inotropic agents (Group-I). The same initial doses of catecholamine (DOB and DOA) as the Group-I were administered in another 12 patients (Group-II). When the pump flow of CPB decreased to a half, these drugs were administered in both groups. Hemodynamic data were measured before CPB, just after operation, 3, 6, 12, 24, 48, and 72 hours after operation. There were no significant differences in aortic and pulmonary artery pressure between both groups. However, cardiac index (CI) of the Group-I demonstrated significantly (p < 0.01) higher values than that of Group-II until 24 hours after surgery. Systemic vascular resistance index (SVRI) of the Group-I demonstrated significantly (p < 0.01) lower value than that of Group-II from 3 to 12 hours after operation. There were no significant differences in oxygen delivery (DO2) and oxygen consumption (VO2) between both groups. These results suggested that concomitant usage of milrinone and low dose catecholamine increased CI and decreased SVRI, and made weaning from CPB very easy, demonstrating excellent hemodynamics. This high potential phosphodiesterase inhibitor may be suitable for not only weaning from CPB but also post-cardiotomy cardiogenic shock.     

Antithrombin III during cardiac surgery: effect on response of activated clotting time to heparin and relationship to markers of hemostatic activation

This study was designed to determine if, and to what extent, antithrombin III (AT) levels affect the response of the activated clotting time (ACT) to heparin in concentrations used during cardiac surgery, and to characterize the relationship between AT levels and markers of activation of coagulation during cardiopulmonary bypass (CPB). After informed consent, blood specimens obtained from eight normal volunteers (Phase I) were used to measure the response of the kaolin and celite ACT to heparin after in vitro addition of AT (200 U/dL) and after dilution with AT-deficient plasma to yield AT concentrations of 20, 40, 60, 80, and 100 U/dL. In Phase II, blood specimens collected before the administration of heparin and prior to discontinuation of CPB, were used to measure the response of the kaolin ACT to heparin (preheparin only), AT concentration, and a battery of coagulation assays in 31 patients undergoing repeat or combined cardiac surgical procedures. In Phase I, strong linear relationships were observed between kaolin (slope = 1.04 AT - 2, r2 = 0.78) and celite (slope = 1.36 AT + 6, r2 = 0.77) ACT slopes and AT concentrations below 100 U/dL. In the pre-CPB period of Phase II, only factors V (partial r = -0.49) and VIII (partial r = -0.63) were independently associated with heparin-derived slope using multivariate analysis; an inverse relationship was observed between AT and fibrinopeptide A levels (r = -0.41) at the end of CPB. Our findings indicate that the responsiveness of whole blood (ACT) to heparin at the high concentrations used with CPB is progressively reduced when the AT concentration decreases below 80 U/dL. Because AT is variably, and sometimes extensively, reduced in many patients before and during CPB, AT supplementation in these patients might be useful in reducing excessive thrombin-mediated consumption of labile hemostatic blood components, excessive microvascular bleeding, and transfusion of blood products. IMPLICATIONS: Heparin, a drug with anticoagulant properties, is routinely given to patients undergoing cardiac surgery to prevent clot formation within the cardiopulmonary bypass circuit. However, when levels are reduced, heparin is not as effective. Findings within this study indicate that administration of antithrombin III may help to preserve the hemostatic system during cardiopulmonary bypass.     

Noradrenaline release and the effect of endogenous activation of the phospholipase C/protein kinase C signalling pathway in rat atria

Coagulopathies in children after cardiopulmonary bypass (CPB) are complex. There are very limited data correlating coagulation tests with postoperative bleeding. We evaluated coagulation changes after CPB and after the administration of coagulation products to 75 children. Baseline coagulation tests were obtained and repeated after protamine administration, after transfusion of individual coagulation products, and on arrival in the intensive care unit (ICU). Regression analysis demonstrated no baseline coagulation test to predict postoperative chest tube drainage. Weight and duration of CPB were determined to be the only predictors of bleeding. Further analyses demonstrated that children <8 kg had more bleeding and required more coagulation products than children >8 kg. Postprotamine platelet count and fibrinogen level correlated independently with 24-h chest tube drainage in children <8 kg, whereas postprotamine platelet count and thrombelastographic values did so in patients weighing >8 kg. Platelet administration alone was found to restore effective hemostasis in many patients. With ongoing bleeding, cryoprecipitate improved coagulation parameters and limited blood loss. Fresh-frozen plasma administration after platelets worsened coagulation parameters and was associated with greater chest tube drainage and more coagulation product transfusions in the ICU. Objective data to guide post-CPB component therapy transfusion in children are suggested. Implications: Children <8 kg can be expected to have more severe coagulopathies, require more coagulation product transfusions, and bleed more after cardiopulmonary bypass. Correlations between coagulation tests and postoperative chest tube drainage are defined. Platelets and, if necessary, cryoprecipitate optimally restore hemostasis. Fresh-frozen plasma offers no benefits in correcting postcardiopulmonary bypass coagulopathies in children.     

Effect of modified ultrafiltration in high-risk patients undergoing operations for congenital heart disease

BACKGROUND: Modified ultrafiltration (MUF) after cardiopulmonary bypass (CPB) in children decreases body water, removes inflammatory mediators, improves hemodynamics, and decreases transfusion requirements. The optimal target population for MUF needs to be defined. This prospective, randomized study attempted to identify the best candidates for MUF during operations for congenital heart disease. METHODS: Informed consent was obtained from 100 consecutive patients with complex congenital heart disease undergoing operations with CPB. They were randomized into a control group (n = 50) of conventional ultrafiltration during bypass and an experimental group using dilutional ultrafiltration during bypass and venovenous modified ultrafiltration after bypass (MUF group, n = 50). Postoperative arterial oxygenation, duration of ventilatory support, transfusion requirements, hematocrit, chest tube output, and time to chest tube removal were compared between the groups stratified by age and weight, CPB technique, existence of preoperative pulmonary hypertension, and diagnosis. RESULTS: There were no MUF-related complications. In patients with preoperative pulmonary hypertension, MUF significantly improved postoperative oxygenation (445 +/- 129 mm Hg versus control: 307 +/- 113 mm Hg, p = 0.002), shortened ventilatory support (42.9 +/- 29.5 hours versus control: 162.4 +/- 131.2 hours, p = 0.0005), decreased blood transfusion (red blood cells: 16.2 +/- 18.2 mL/kg versus control: 41.4 +/- 27.8 mL/kg, p = 0.01; coagulation factors: 5.3. +/- 6.9 mL/kg versus control: 32.3 +/- 15.5 mL/kg, p = 0.01), and led to earlier chest tube removal. In neonates (< or =30 days), MUF significantly reduced transfusion of coagulation factors (5.4 +/- 5.0 mL/kg versus control: 39.9 +/- 25.8 mL/kg, p = 0.007), and duration of ventilatory support (59.3 +/- 36.2 hours versus 242.1 +/- 143.1 hours, p = 0.0009). In patients with prolonged CPB (>120 minutes), MUF significantly reduced the duration of ventilatory support (44.7 +/- 37.0 hours versus 128.7 +/- 133.4 hours, p = 0.002). No significant differences were observed between MUF and control patients for any parameter in the presence of ventricular septal defect without pulmonary hypertension, tetralogy of Fallot, or aortic stenosis. CONCLUSIONS: Modified ultrafiltration after CPB is safe and decreases the need for homologous blood transfusion, the duration of ventilatory support, and chest tube placement in selected patients with complex congenital heart disease. The optimal use of MUF includes patients with preoperative pulmonary hypertension, neonates, and patients who require prolonged CPB.     

A rapid method for DNA extraction from fine-needle aspiration biopsies of thyroid tumors, and subsequent RET mutation analysis

In 22 consecutive patients with tetralogy of Fallot (TF), a total correction was attempted without the use of a homologous blood transfusion from September 1995 to March 1997. The 22 patients were divided into two groups according to their surgical procedures; namely, either a simple correction (group I: n = 14) or a complex correction including the relief of peripheral pulmonary stenosis and/or the division of a previous systemic-pulmonary shunt (group II: n = 8). In 77% of all patients, surgery was performed without a homologous blood transfusion. No differences were found in the non-transfusion rate and the hematocrit (Ht) values between the two groups and, as a result, we thus confirm that this additional procedure is not a risk factor for surgery without a homologous blood transfusion. According to the correlation of the red blood cell volume before and after surgery, the preoperative Ht value corresponding to the postoperative Ht of 30% could be accurately predicted. The calculated Ht values were 41.0% in the patient weighing 15 kg, 42.5% in those weighing 10 kg, and 46.9% in those weighing 5 kg. These data suggest that a surgical correction without a homologous blood transfusion can therefore be safely performed in almost all patients with TF.     

Crossed quadrant homonymous hemianopsia in a case of multiple sclerosis

Prevention of hyperacute rejection is a difficult and unsolved problem in xenotransplantation. Natural antibodies and complement activation have been known to play an important role in the xenotransplantation between discordant species pairs. In the present study, total blood exchange (TBE) was performed with pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP) solution (Ajinomoto Co., Inc., Kawasaki, Japan) before cardiac xenotransplantation in order to remove the immunoglobulins and prolong xenograft survival time. Guinea pigs and rats were used as the discordant species combination for donor and recipient. Two groups were established: Group 1, untreated control (n = 8) and Group 2, TBT with PHP solution (n = 8). The exchange blood transfusion was carried out at the rate of 15-20 ml/h utilizing PHP solution using a blood pump. After the blood exchange was processed, hematocrit (Ht) levels dropped to 4 or 5%, and a cardiac xenotransplantation was performed within 24 h. The levels of serum IgA, IgM, and IgG were decreased to less than 25, 25, and 10% of the base line, respectively, after blood exchange. A mean xenograft survival time in Group 2 was prolonged to 472 +/- 74 min and to 10.4 +/- 1.8 min in Group 1 (p < 0.01). A titer of the anti-guinea pig lymphocytotoxic antibody in rat serum was decreased to almost nil. The data from this study suggest that total blood exchange with PHP solution may be useful in preoperative removal of xenograft antibodies in xenotransplantation.     

Surgery of aortic arch aneurysm combined with other cardiovascular lesion

From 1995 to 1996, we performed aortic arch replacement using antegrade cerebral perfusion under deep hypothermia in 7 patients, in whom 4 cases accompanied with cardiac lesion which treated simultaneously and 3 cases had abdominal aortic aneurysm. We compared the surgical results between cases with (group II, n = 4) and without (group I, n = 3) combined cardiovascular lesion. There is no difference between two groups in the cerebral perfusion time and the amount of bleeding and blood transfusion. The cardiac ischemic time and bypass time were insignificantly longer in group II than in group I. We experienced no early death and no cardiac and brain complication in both groups. Three cases with abdominal aortic aneurysm had two-staged operation successfully after arch surgery within a half year. In conclusion, we successfully treated aortic arch aneurysm even in patients combined with other cardiovascular lesion as well as in patients without that.     

Hereditary persistence of alpha-fetoprotein. Case report and review of the literature

BACKGROUND: The issue of performing simultaneous pulmonary resection and cardiac surgery in patients with coexisting lung carcinoma and ischaemic heart disease remains controversial. We report our experience and review the literature. METHODS: Thirteen patients (male ten, female three; mean age 65 years) underwent simultaneous cardiac surgery and pulmonary resection. Lung pathology consisted of primary lung carcinoma (n = 10), benign disease (n = 2) and carcinoid (n = 1). Lung resections included pneumonectomy (n = 3), lobectomy (n = 4), segmentectomy (n = 1) and local excision (n = 5). Cardiac procedures consisted of coronary artery bypass grafting (CABG) in 11, aortic valve replacement in one and mitral valve repair with CABG in one patient. In all but one case the lung resection was performed prior to heparinization and cardiopulmonary bypass (CPB). In two patients, with suitable coronary anatomy, myocardial revascularization without CPB was performed to reduce morbidity. RESULTS: There was no hospital mortality. Postoperative blood loss and ventilation requirements were reduced in the patients who were operated on without CPB. Prolonged ventilatory support was required in two cases. All patients with benign pathology are alive. In the lung cancer group there have been five late deaths: disseminated metastatic disease (n = 3), anticoagulant related haemorrhage (n = 1) and broncho-pleural fistula (n = 1). Of the remaining five patients four are alive and disease free 7-23 months post-operatively; one patient has recurrent disease 40 months post-operatively. CONCLUSIONS: Simultaneous pulmonary resection and cardiac surgery is associated with acceptable operative morbidity and mortality. In patients with lung carcinoma long-term survival was determined by tumour stage. The avoidance of CPB may be advantageous by decreasing blood loss and ventilation requirements.     

Quality of diabetes care, diabetes knowledge and risk of severe hypoglycaemia one and four years after participation in a 5-day structured treatment and teaching programme for intensified insulin therapy

PURPOSE: Cardiopulmonary bypass (CPB) is characterized by translocation of intestinal endotoxin and subsequent endogenous production of the pro-inflammatory cytokine interleukin-6 (IL-6). Plasma lipid fractions, especially high density lipoproteins, bind and neutralize endotoxin and, therefore, inhibit endotoxin-induced macrophage cytokine production, including IL-6. Increased IL-6 plasma levels have been implicated in adverse consequences associated with CPB. Previous studies demonstrated large interpatient variability in IL-6 plasma levels after CPB. The purpose of this study was to evaluate the relationship between plasma lipid concentrations and the concentrations of IL-6 following CPB in humans. METHODS: In a prospective study, a group of 15 patients selected to exclude variables known to influence post-CPB plasma levels of IL-6 (preoperative left ventricular ejection fraction > 45%, similar durations of aortic cross clamping and total CPB time, similar temperature control during CPB, and avoidance of platelet transfusion and shed mediastinal blood re-infusion), IL-6 was measured at baseline, one and 24 hr post-CPB. RESULTS: Interleukin-6 plasma concentrations (mean +/- SD) increased at one (142 +/- 89 pg.ml-1, P < 0.05) and 24 (129 +/- 82 pg.ml-1, P < 0.05) hr post-CPB compared with baseline (1.5 +/- 1 pg.ml-1) concentrations. An inverse correlation was found between IL-6 plasma concentrations at one hour post-CPB and plasma cholesterol concentrations (r = -0.592, P = 0.02), high density lipoprotein (r = -0.595, P = 0.02), and low density lipoprotein (r = -0.656, P = 0.01). CONCLUSIONS: These results suggest that plasma lipids attenuate the production of IL-6 during CPB and may partly explain the variability of interpatient levels of IL-6 reported post-CPB by others.     

Evaluation of platelet function by Sonoclot analysis compared with other hemostatic variables in cardiac surgery

Platelet function can be easily measured as time to peak (TP) by Sonoclot Coagulation & Platelet Function Analyzer (Sienco Inc., Morrison, CO) analysis. However a correlation between Sonoclot analysis and platelet aggregation, which is accepted as a test of platelet function, has not been established. In this study, we compared TP and collagen-induced whole blood platelet aggregation in 15 patients undergoing cardiac surgery. Two or three blood samples were randomly obtained from each patient before and after cardiopulmonary bypass (CPB). Sonoclot analysis, collagen-induced whole blood aggregation, and laboratory measurement (including platelet count and coagulation profile) were measured. Seventy-two samples were obtained (35 before CPB and 37 after CPB). TP was correlated with collagen-induced whole blood aggregation (r = -0.652), platelet count (r = -0.671), fibrinogen level (r = -0.598), prothrombin time (r = 0.394), activated partial thromboplastin time (r = 0.486), and use of CPB (r = 0.380). Significant predictors of TP for multiple linear regression modeling were collagen-induced whole blood aggregation, platelet count, and fibrinogen level (r = 0.742). In conclusion, Sonoclot analysis TP predicts approximate platelet function in patients undergoing cardiac surgery. IMPLICATIONS: Approximate platelet function can be easily measured as time to peak by Sonoclot analysis. In this study, time to peak was predicted by platelet count, whole blood platelet aggregation, and fibrinogen level for multiple linear regression modeling.     

Gabexate mesilate, a new synthetic serine protease inhibitor: a pilot clinical trial in valvular heart surgery

OBJECTIVE: To assess the effects of gabexate mesilate ([GM], Foy, ONO Pharmaceutical Co, Osaka, Japan) on blood loss in cardiac valve replacement surgery and to establish whether GM reduces blood loss or transfusion requirements after this surgery. DESIGN: Randomized single-blind trial in 30 patients receiving either GM (2 mg/kg/h in a central venous catheter), or no GM, after heparin. SETTING: Department of Anesthesia and Intensive Care, Cardiac Surgery, in a hospital in Italy. PARTICIPANTS: Consent patients. INTERVENTIONS: Cardiac valve replacement surgery. MEASUREMENT AND MAIN RESULTS: Intraoperative and postoperative bleeding, blood transfusion, hemoglobin, and hematocrit were compared. In the GM group bleeding was reduced and no transfusions were required. CONCLUSION: GM appears to play a useful role in reducing blood loss during extracorporeal circulation in cardiac surgery.     

The role of autologous blood transfusion in the the Federal Republic of Germany. Results of a 1993 questionnaire. 1. The reunited Germany

The objective of the study was to evaluate the role of autologous blood transfusion in current clinical practice in the Federal Republic of Germany after reunification. METHODS: Questionnaires were sent to the anaesthesia departments of 684 German hospitals in January 1993. The sample consisted of 400 randomly selected hospitals from the former West Germany ("old federal states") and 284 hospitals from the former German Democratic Republic ("new federal states"). Only hospitals with more than 25 surgical beds were included in the study. The questionnaire contained 36 questions related to (1) general information on the hospital, (2) preoperative autologous blood donation (PABD), (3) preoperative plasmapheresis, (4) isovolaemic haemodilution, (5) perioperative blood salvage, and (6) general management of blood transfusion. RESULTS: A total of 502 completed questionnaires (73%) were returned, 305 from hospitals in the "old federal states" and 197 from hospitals in the former German Democratic Republic. Nine per cent of the responding hospitals were running their own transfusion services, and 56% were located in the vicinity of a regional blood bank. The overall proportion of surgical procedures requiring perioperative blood transfusion ranged from 1% to 90% (median 10%). PABD was performed "not at all" in 18%, "rarely" in 20% "occasionally" in 27%, "frequently" in 17%, and "mostly" in 16% of the responding hospitals. The principal use of PABD was in orthopaedic surgery and cardiac surgery (83% and 70% of the departments in question, respectively). In more than 50% of the hospitals reporting, the PABD service was run by the anaesthesia department. Patients not meeting the established criteria for homologous blood donors were accepted for autologous blood donation "frequently" and "mostly" in 20% and 12% of the hospitals, respectively, but at most "occasionally" in 63% of the hospitals. Preoperative plasmapheresis was performed in 12% of the responding hospitals. Autologous fresh frozen plasma predominantly was used for volume replacement, and for prevention of coagulation disorders when major blood loss was anticipated. Isovolaemic haemodilution was performed "not at all" in 28%, "rarely" in 19%, "occasionally" in 28%, "frequently" in 16%, and "mostly" in 8% of the responding hospitals. The reasons most frequently invoked for not performing haemodilution were "too time consuming" and "too little blood-saving effect". Cell separators for perioperative blood salvage were available in 30% of the responding hospitals. Of the other hospitals not equipped with cell-washing devices, 11% performed perioperative blood salvage of unprocessed blood by means of simple collection devices. Some 80% of those hospitals using intraoperative autotransfusion devices also performed blood salvage postoperatively. The principal use of perioperative blood salvage was in cardiac surgery, orthopaedics, and vascular surgery (90%, 54%, and 54% of departments, respectively). Some 48% of the responding anaesthetists "mostly" considered haemoglobin levels of 8-10 g/dl acceptable in patients without cardiopulmonary disease, but only 18% did so in patients with cardiopulmonary disease. CONCLUSIONS: Although available in the majority of hospitals surveyed, the simple techniques of both PABD and isovolaemic haemodilution are unduly neglected in routine clinical practice. The consistent use of both of these techniques, and the careful weighing up of the indication for every single blood transfusion, would not only effectively reduce homologous blood transfusions, but also enable even small hospitals to run successful autologous transfusion programmes without expensive cell-washing and plasmapheresis devices.     

The effects of epsilon-aminocaproic acid on fibrinolysis and thrombin generation during cardiac surgery

Despite the efficacy of antifibrinolytic drugs in reducing bleeding after cardiac surgery, concerns remain regarding their potential to promote thrombosis. We examined the effect of the antifibrinolytic drug, epsilon-aminocaproic acid (EACA) on fibrinolysis and thrombin generation during cardiac surgery. Forty-one adults undergoing primary coronary artery bypass graft surgery requiring cardiopulmonary bypass (CPB) were prospectively randomized in a double-blind trial to receive either saline or EACA. A loading dose of 150 mg/kg EACA was given before anesthetic induction, followed by a 15 mg x kg(-1) x h(-1) infusion, which continued until 3 h after CPB. Plasma samples for the measurement of D-dimer, thrombin-antithrombin III, and soluble fibrin were obtained before surgery, 1 h on CPB, and 3 and 20 h after CPB. In the EACA group, fibrinolytic activity, as measured by D-dimer, was significantly decreased 3 h after CPB, (0.51 +/- 0.15 mg/L vs 1.13 +/- 0.14 mg/L, P < 0.005). Decreased fibrinolytic activity was accompanied by decreased bleeding in the EACA group (660 +/- 127 mL vs 931 +/- 113 mL, P < 0.05). No differences in the generation of thrombin or soluble fibrin were apparent between the two groups. Suppression of fibrinolytic activity in the absence of concomitant reductions in thrombin generation suggests that EACA could potentiate a hypercoagulable prethrombotic state in the perioperative setting. Implications: In a randomized, prospective trial of primary cardiac surgery, we demonstrated that the synthetic antifibrinolytic drug epsilon-aminocaproic acid suppresses fibrinolysis with no effects on thrombin generation. These results suggest the potential for synthetic antifibrinolytic drugs to induce a hypercoagulable prethrombotic state in the perioperative setting.