Hemostatic effects of antithrombin III supplementation during cardiac surgery: results of a prospective randomized investigation.

Failure to suppress thrombin generation during cardiac surgery promotes fibrin generation, fibrinolysis, and a consumptive coagulopathy. Acquired deficiencies of antithrombin III may play a contributory role. We hypothesized that antithrombin III supplementation to normal physiologic concentrations would decrease thrombin generation and potentially reduce peri-operative bleeding. Twenty patients undergoing coronary artery bypass graft surgery were randomized for this prospective, double-blind, placebo-controlled study. Ten patients received antithrombin III supplementation (50 U/kg) by intravenous infusion prior to incision, and 10 patients received a placebo. Blood samples were obtained pre-operatively, at 1 and 2 h following initiation of cardiopulmonary bypass (CPB), and at 1, 3, and 24 h after completion of CPB. Samples were analyzed for antithrombin III, thrombin-antithrombin III (TAT) complex, and D-dimer concentrations. Cumulative blood loss was recorded at 6 and 12 h after CPB. No statistically significant differences in patient demographics or total heparin dose administered were observed between groups. As expected, plasma antithrombin III concentrations were maintained near pre-operative values in the treatment group, but not in the placebo group. Despite this difference, no statistically significant alterations in generation of TAT complex, D-dimer, or blood loss occurred between groups. Antithrombin III supplementation to maintain normal physiologic concentrations during CPB did not alter significantly thrombin generation, fibrinolytic activity, or blood loss in adults undergoing elective cardiac surgery.     

Antithrombin and protein C in systemic inflammatory response syndrome

Coronary artery bypass grafting with cardiopulmonary bypass can induce systemic inflammatory response syndrome. To assess the prevalence of preoperative antithrombin and protein C deficiencies in relation to the incidence of this syndrome, antithrombin and protein C levels were measured in 130 patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. Systemic inflammatory response syndrome developed in 36 (27.7%) patients who were predominantly male, had a lower EuroSCORE, longer cardiopulmonary bypass time, higher pre-bypass temperature, and shorter activated coagulation time. Logistic regression showed that predictive factors included bypass duration and pre-bypass temperature; however, low antithrombin levels appeared to be a negative predictive factor. Antithrombin levels were < 80% in 33.8% of patients, and 11.6% had protein C levels < 80%. Postoperative antithrombin and protein C deficiencies are not uncommon in adults undergoing cardiac surgery with cardiopulmonary bypass, but detection of these deficits did not identify patients at increased risk of systemic inflammatory response syndrome.     

Changes in the coagulation and fibrinolytic systems during and after cardiopulmonary bypass surgery

Components of the coagulation and fibrinolytic systems were determined in patients undergoing open heart surgery with cardiopulmonary bypass. The variables studied included prothrombin, antithrombin-III, spontaneous plasmin activity, plasminogen and functional antiplasmin activity. The variables were measured using chromogenic peptide substrate assays. A marked, transitory, increase in spontaneous plasmin activity prior to cardiopulmonary bypass, but after heparin injection was found. A decrease in antiplasmin activity during bypass was observed, while actual plasminogen level, when correcting for hemodilution, was unchanged. Both prothrombin and antithrombin-III paralleled the decrease in hemoglobin concentration during bypass. These findings suggest that the injection of heparin induced a transient activation of the fibrinolytic system, whereas no detectable consumption of the measured coagulation variables was observed.     

Complement activation during cardiac and thoracic vascular operations

To study complement activation, we evaluated nine patients who underwent cardiac operations requiring cardiopulmonary bypass (CPB) and nine other patients who underwent thoracic vascular operations without CPB. Concentration of C3, as measured by radioimmunoassay, was used as an indicator of complement activation (C3a is a complement-degradation product). In the CPB patients, the C3a level increased tenfold (from baseline value) after the onset of bypass, and continued to increase during bypass. Protamine produced an additional twofold increase in the C3a value, to a peak of 5461 +/- 1360 ng/ml. By 12 hours after surgery, the C3a level had decreased to normal (400 ng/ml). In the non-CPB patients, C3a remained at baseline levels until the administration of protamine, which caused a tenfold increase to a peak of 2281 +/- 293 ng/ml; C3a levels returned to normal 6 hours after operation. The peak postprotamine C3a levels were significantly higher (p < 0.01) in the CPB group than in the non-CPB group. This finding was due to the fact that, during CPB, complement activation occurs via the alternative pathway; the administration of protamine then causes additional activation via the classical pathway. During thoracic vascular operations, however, complement activation occurs only in response to protamine, via the classical pathway.     

Comparative analysis of antioxidant defense during on-pump and off-pump cardiac surgery

INTRODUCTION AND OBJECTIVES: The transient myocardial ischemia that occurs during cardiac surgery leads to oxidative stress and the production of free radicals. The resulting damage can be reduced if cardiopulmonary bypass is avoided. We obtained indirect measures of the oxidative damage occurring during cardiac surgery by monitoring the glutathione system and we studied the influence of cardiopulmonary bypass. PATIENTS AND METHOD: The study included 19 patients undergoing cardiac surgery. Cardiopulmonary bypass was used in 9 (47.4%). Blood samples were obtained from each patient at different times during and after surgery. Total, oxidized and reduced glutathione levels were measured, as was the activity of related enzymes (i.e., glutathione peroxidase, glutathione reductase, and glutathione transferase). RESULTS: The total glutathione level decreased more in patients in whom cardiopulmonary bypass had been used. In addition, the oxidized glutathione level was reduced in these patients, which suggests that antioxidant defense was not fully effective. In contrast, the oxidized glutathione level tended to increase in patients in whom cardiopulmonary bypass had not been used. There was no significant difference in enzymatic activity between the two groups. CONCLUSIONS: In this study, patients who underwent off-pump cardiac surgery had a better antioxidant profile. The implication could be that cardiac surgery without cardiopulmonary bypass has a less damaging effect on ischemic myocardium.     

Is hyperamylasemia after cardiac surgery due to cardiopulmonary bypass?

Although hyperamylasemia has been reported in a large proportion of patients undergoing cardiac surgery with cardiopulmonary bypass, its clinical significance and pathogenetic mechanisms remain poorly understood. The study was designed to investigate whether avoidance of cardiopulmonary bypass would limit amylase elevation. Serum levels of amylase and lipase were measured preoperatively as well as 24 and 48 hours postoperatively in 58 patients undergoing elective coronary artery bypass grafting. Three surgical approaches were used: cardiopulmonary bypass (n = 32) and off-pump through a median sternotomy (n = 14) or a left minithoracotomy (n = 12). There was no hospital mortality or postoperative abdominal complications. Transient hyperamylasemia occurred in 14 patients: 7 (22%), 5 (36%), and 2 (17%) in the respective groups. The increase in amylase levels was similar among the groups. However, no lipase elevation was detected in any patient. There was no clear correlation between hyperamylasemia and increased creatinine levels. Perioperative plasma calcium levels were normal in patients who had hyperamylasemia. Our results indicate that hyperamylasemia after bypass surgery is not related to the use of cardiopulmonary bypass or the mode of surgical access.     

Minor infection encouraged by steroid administration during cardiac surgery

The aim of this study was to investigate whether steroid administration would increase the risk of postoperative infection. Sixty adults who underwent elective cardiac surgery under cardiopulmonary bypass were prospectively randomized into two groups. Thirty-one patients received hydrocortisone (50 mg x kg(-1)) before and after cardiopulmonary bypass, the other 29 served as controls. Various hemodynamic and pulmonary measurements were obtained perioperatively, and the white blood cell counts and levels of C-reactive protein were checked up to the 14(th) postoperative day. Steroid administration did not have any favorable effects during the perioperative period. Re-administration of antibiotics was needed in 7 patients (22.6%) after the 7(th) postoperative day in the steroid group, and in 3 (10.3%) in the control group. The peak white cell counts and C-reactive protein levels after the 7(th) postoperative day were significantly higher in the steroid group. Steroid administration offered no clinical benefit to patients undergoing cardiac surgery with cardiopulmonary bypass, and it may encourage minor infections in the late postoperative period.     

Phlebotomy via the pulmonary artery catheter introducer for intraoperative autotransfusion

Fear of the acquired immune deficiency syndrome and other blood-transmitted diseases has created a revival of autologous transfusion during cardiac surgery. The present report is of 200 patients undergoing cardiopulmonary bypass during cardiac surgery in whom phlebotomy was performed via the sideport of the introducer for the pulmonary artery catheter for later reinfusion. Each unit of phlebotomized blood was replaced with 500 mL of normal saline. Cardiac output and mean arterial blood pressure decreased significantly after phlebotomy (P < 0.05) and returned toward control values after administration of the sodium chloride. The autologous blood was replaced after cardiopulmonary bypass. Fresh frozen plasma and platelets were not administered to the patients in the operating room. Eleven patients undergoing coronary artery bypass grafting received fresh frozen plasma in the recovery room because they were receiving aspirin and dipyridamole up to the day of surgery. Prolonged duration of cardiopulmonary bypass in two double-valve replacements, and one coronary artery bypass graft patient who required insertion of an intra-aortic balloon, accounted for the administration of fresh frozen plasma and platelets in three patients. The average volume of phlebotomized blood was 875 mL, which resulted in a decrease of the hematocrit from 40.5% ± 0.5% (P < 0.05) to 29.75% ± 0.5% and 30.5% ± 0.5% at the end of surgery and at discharge from the hospital, respectively. Phlebotomy via the Y port of the introducer of the pulmonary artery catheter is an easy, simple, and cost-effective way to remove autologous blood in patients undergoing cardiac surgery.     

Increased levels of basic fibroblast growth factor are found in the cross-clamped heart during cardiopulmonary bypass

BACKGROUND: High concentrations of fibroblast growth factors (FGFs) are found in the heart. Even higher levels are measured during ischemia. Exogenous administration of FGF to ischemic myocardium promotes synthesis of collateral coronary circulation and induces local myocardial hypertrophy. The kinetics and the contribution of the heart and lungs to circulating basic FGF (bFGF) levels during cardiac surgery were characterized. PATIENTS AND METHODS: Plasma bFGF levels were measured in seven adults undergoing coronary artery bypass operations and 11 neonates undergoing congenital cardiac anomaly repair during cardiopulmonary bypass. RESULTS: In both the adult and the neonatal groups, bFGF plasma levels increased significantly immediately after removal of the aortic cross-clamp (adult group 15.43+/-6.3 aorta cross-clamped versus 29+/-4.1 after release, P=0.011; neonatal group 17.09+/-9.43 aorta cross-clamped versus 43.55+/-14.25 after release, P=0.004) and declined thereafter. In the adult group, higher levels of bFGF were recorded in blood recovered from the coronary sinus than in the aortic root during aortic cross-clamping (63.14+/-14.42 versus 43.86+/-12.05, P=0.011), and in both, levels were significantly higher than the peripheral measurements. CONCLUSIONS: Plasma bFGF levels increase during cardiopulmonary bypass. The source of this elevation is the lungs and heart.     

Increased circulating bradykinin during hypothermia and cardiopulmonary bypass in children.

To determine whether cold could activate the kallikrein-kinin system in vivo as it does in vitro, the circulating systemic concentrations of bradykinin were serially measured in 10 cyildren with congenital diseases of the heart undergoing corrective cardiac surgery. Bradykinin was measured by radioimmunoassay in blood samples obtained before, during and after profound hypothermia (to 18 degrees C) and cardiopulmonary bypass. The circulating concentrations of bradykinin increased significantly as body temperature decreased during surface cooling. The increase in circulating bradykinin was associated with a decrease in the circulating level of bradykininogen, the precursor of bradykinin. With the onset of cardiopulmonary bypass and hence, removal of the lung and pulmonary converting enzyme from the circulation, there was a further rise in the already elevated concentrations of bradykinin. This is the first in vivo demonstration that hypothermia leads to an increase in the circulating concentrations of bradykinin.     

不同酸碱度对鱼精蛋白中和肝素的影响

目的:探讨心脏手术后患者不同酸碱度对鱼精蛋白中和肝素的影响。方法:我院2009年10月至2010年5月期间对352例心脏病患者行体外循环手术,麻醉后即测正常活化凝血时间(ACT)值,在打开心包后按2.5 mg/kg从中心静脉给予肝素,在体外循环结束时,鱼精蛋白的剂量从肝素的1.5倍开始在升主动脉根部给药,测量中和后的ACT值,并依此作为追加鱼精蛋白量的参考。按体外循环结束时其酸碱度不同分为3组,观察比较各组肝素与鱼精蛋白总量之比、中和后ACT值,并观测3组术后6 h、12 h及24 h引流量及术后总引流量。结果:在酸性环境下,鱼精蛋白中和肝素剂量及术后引流量高于其他2组,差异有统计学意义(P<0.05)。在非酸性环境下,鱼精蛋白和肝素比平均值为1.63∶1;在pH<7.31或剩余碱(BE)<-6时,鱼精蛋白的用量显著增加,鱼精蛋白和肝素比平均值为2.33∶1。结论:不同酸碱度对鱼精蛋白拮抗肝素有较大影响,酸性环境下鱼精蛋白的中和作用会减弱,鱼精蛋白用量增加,术后引流量也会增多。在体外循环结束时,测得pH<7.31或BE<-6时,建议纠正酸碱平衡的同时适量追加鱼精蛋白。     

Intraoperative cardiac troponin T release and lactate metabolism during coronary artery surgery: comparison of beating heart with conventional coronary artery surgery with cardiopulmonary bypass

OBJECTIVE: To compare cardiac troponin T release and lactate metabolism in coronary sinus and arterial blood during uncomplicated coronary grafting on the beating heart with conventional coronary grafting using cardiopulmonary bypass. DESIGN: A prospective observational study with simultaneous sampling of coronary sinus and arterial blood: before and 1, 4, 10, and 20 minutes after reperfusion for analysis of cardiac troponin T and lactate. Cardiac troponin T was also analysed in venous samples taken 3, 6, 24, 48, and 72 hours after surgery. SETTING: Cardiac surgical unit in a tertiary referral centre. PATIENTS: 18 patients undergoing coronary grafting on the beating heart (10 single vessel and eight two-vessel grafting) and eight undergoing two-vessel grafting with cardiopulmonary bypass. RESULTS: Cardiac troponin T was detected in coronary sinus blood in all patients by 20 minutes after beating heart coronary artery surgery before arterial concentrations were consistently increased. Peak arterial and coronary sinus cardiac troponin T values on the beating heart during single (0.03 (0 to 0. 05) and 0.09 (0.07 to 0.16 microg/l, respectively) and two-vessel grafting (0.1 (0.07 to 0.11) and 0.19 (0.14 to 0.25) microg/l) were lower than the values obtained during cardiopulmonary bypass (0.64 (0.52 to 0.72) and 1.4 (0.9 to 2.0) microg/l) (p < 0.05). The area under the curve of venous cardiac troponin T over 72 hours for two-vessel grafting on the beating heart was less than with cardiopulmonary bypass (13 (10 to 16) v 68 (26 to 102) microg.h/l) (p < 0.001). Lactate extraction began within one minute of snare release during beating heart coronary surgery while lactate was still being produced 20 minutes after cross clamp release following cardiopulmonary bypass. CONCLUSIONS: Lower intraoperative and serial venous cardiac troponin T concentrations suggest a lesser degree of myocyte injury during beating heart coronary artery surgery than during cardiopulmonary bypass. Oxidative metabolism also recovers more rapidly with beating heart coronary artery surgery than with conventional coronary grafting. Coronary sinus cardiac troponin T concentrations increased earlier and were greater than arterial concentrations during beating heart surgery, suggesting that this may be a more sensitive method of intraoperative assessment of myocardial injury.     

Practical approach to anticoagulation for cardiopulmonary bypass in the patient with congenital prolonged activated partial thromboplastin time

Patients with rare, congenital deficiencies of contact proteins (e.g., factor XII, prekallikrein, high-molecular-weight kininogen) present an important challenge with regard to safe anticoagulation during cardiopulmonary bypass. Specifically, activated coagulation time values are obtained with devices that utilize contact protein activators to generate thrombin and assess the efficacy of heparin-mediated antithrombin activation, with an activated coagulation time value of 480 s considered 'safe'. Patients with contact protein deficiencies will routinely have activated coagulation time values that exceed normal baseline values to an unpredictable extent, which, when coupled with heparin administration may well exceed 480 s but still potentially not reflect adequate antithrombin activation. We present the successful management of anticoagulation of a patient with either a prekallikrein or kininogen deficiency during cardiopulmonary bypass for coronary artery bypass graft surgery with Hepcon-based heparin concentration determinations. This approach, and the other alternatives previously mentioned, can be utilized to safely care for these rare patients in the setting of cardiac surgery.     

Effect of cardiopulmonary bypass on circulating concentrations of leucocyte elastase and free radical activity

Circulating concentrations of leucocyte elastase and free radical activity were measured in 11 adults undergoing cardiopulmonary bypass. In all patients the bypass procedure was associated with pronounced changes in plasma elastase concentrations, and peak enzyme concentrations correlated closely with the duration of bypass (r = 0.91, p less than 0.001). Serial measurement of octadeca-9, 11-dienoic acid, a non-peroxide marker of free radical activity, showed significant changes only in the plasma free fatty acid fraction, suggesting a direct relation to the action of heparin rather than to the bypass procedure as such. These studies support the hypothesis that neutrophil activation plays a central role in the organ dysfunction that may complicate cardiopulmonary bypass and suggest that elastase release rather than free radical generation may be the appropriate marker of the event.     

Cardiac troponin I after heart surgery corrective operation in infancy and childhood

BACKGROUND: Perioperative myocardial damage is an important determinant for postoperative cardiac function and recovery. Cardiac troponin I (cTNI) is a specific marker for myocardial damage. The aim of our study was to evaluate pre- and postoperative cTNI levels, the pattern of elevation in the first four postoperative days and the prognostic value after pediatric cardiac operation. METHODS: Cardiac troponin I levels were measured in 115 children mean age 36 +/- 45 months (range 4 days to 189 months) undergoing elective operation of a congenital heart defect. Routine measurements were made preoperatively, immediately after cardiopulmonary bypass and serially 8, 18, 42, 90, 138 hours thereafter. Data from 13 patients undergoing surgery without cardiopulmonary bypass served as controls. Postoperative cTNI levels were correlated with intra- and postoperative parameters (such as duration of aortic crossclamping, cardiopulmonary bypass time and need for postoperative inotropic support). RESULTS: All preoperative cTNI levels were in the normal range. Postoperatively, the highest median cTNI levels were found in patients after repair of tetralogy of Fallot (TOF), atrioventricular septal defect (AVSD) and implantation of a homo- or xenograft. Postoperative cTNI levels correlated significantly with duration of cardiopulmonary bypass and aortic crossclamping, operative approach (ventriculotomy versus atriotomy) and inotropic support (p < 0.0001). Peak cTNI levels were found immediately after surgery in 77.4% of our patients, 8 hours postoperative in 13.9% and at 18 hours after the surgery in 5.2% of the patients. In three children cTNI continued to increase; a secondary increase was found in one patient. Two of these children died, two had a prolonged postoperative recovery. CONCLUSION: The postoperative level of cardiac troponin I could be used as a marker of perioperative myocardial injury caused by ischemia and operative trauma. Peak levels usually could be obtained immediately after surgery, but a further increase of cTNI during the following 18 hours may occur and is not necessarily related to impaired recovery. However still increasing cTNI levels after 18 hours postoperatively and a secondary increase as well may be used as indicators of poor outcome.     

Perforated peptic ulcer after cardiac surgery

Although there are many causes of ulcer disease in postoperative period, hypoperfusion during cardiopulmonary bypass and advanced age are two key causes. We came across two cases of peptic ulcer perforation after coronary bypass graft surgery where these two common factors were absent. We have discussed various aetiolofical factors responsible for genesis of gastrointestinal ulcers in patients undergoing cardiac surgery using cardiopulmonary bypass.     

Bivalirudin, blood loss, and graft patency in coronary artery bypass surgery

A safe and effective alternative is needed for patients in whom unfractionated heparin (UFH) or protamine is contraindicated (e.g., those with heparin-induced thrombocytopenia or allergy to protamine). Furthermore, choice of anticoagulant may influence graft patency in coronary surgery and may therefore be important even when there is no contraindication to UFH. Direct thrombin inhibitors have several potential advantages over UFH, demonstrated in acute coronary syndromes. However, there are also potential difficulties with their use related to lack of reversal agents and paucity of clinical experience in monitoring their anticoagulant activity at the levels required for cardiac surgery with cardiopulmonary bypass (CPB). In the first prospective randomized trial of an alternative to heparin in cardiac surgery, we compared bivalirudin (a short-acting direct thrombin inhibitor) with UFH in 100 patients undergoing off-pump coronary artery bypass (OPCAB) surgery. Blood loss for the 12 hours following study drug initiation in the bivalirudin group was not significantly greater than in the heparin group. Median graft flow was significantly higher in the bivalirudin group. We concluded that anticoagulation for OPCAB surgery with bivalirudin was feasible without a clinically important increase in perioperative blood loss. A larger study is needed to investigate the impact of improved graft patency on other clinical outcomes after cardiac surgery.     

Quantitative analysis of procalcitonin after pediatric cardiothoracic surgery

Procalcitonin appears to be an early and sensitive marker of bacterial infection in a variety of clinical settings. The use of levels of procalcitonin to predict infection in children undergoing cardiac surgery, however, may be complicated by the systemic inflammatory response that normally accompanies cardiopulmonary bypass. The aim of our study was to estimate peri-operative concentrations of procalcitonin in non-infected children undergoing cardiac surgery. Samples of serum for assay of procalcitonin were obtained in 53 patients at baseline, 24, 48, and 72 hours following cardiac surgery. Concentrations were assessed using an immunoluminetric technique. Median concentrations were lowest at baseline at less than 0.5 nanograms per millilitre, increased at 24 hours to 1.8 nanograms per millilitre, maximized at 48 hours at 2.1 nanograms per millilitre, and decreased at 72 hours to 1.3 nanograms per millilitre, but did not return to baseline levels. Ratios of concentrations between 24, 48 and 72 hours after surgery as compared to baseline were 6.15, with 95 percent confidence intervals between 4.60 and 8.23, 6.49, with 95 percent confidence intervals from 4.55 to 9.27, and 4.26, with 95 percent confidence intervals between 2.78 and 6.51, respectively, with a p value less than 0.001. In 8 patients, who had no evidence of infection, concentrations during the period from 24 to 72 hours were well above the median for the group. We conclude that concentrations of procalcitonin in the serum increase significantly in children following cardiac surgery, with a peak at 48 hours, and do not return to baseline within 72 hours of surgery. A proportion of patients, in the absence of infection, had exaggerated elevations post-operatively.     

Effect of total++ time of extracorporeal circulation in in myocardial revascularization surgery on urinary urea nitrogen loss]

Cardiopulmonary bypass probably should be an important factor increasing surgical stress when heart surgery is focused. This study was undertaken in order to evaluate the role of cardiopulmonary bypass in proteic catabolism. Study group consisted of patients who underwent cardiac aortic bypass graft as an isolated procedure. Inclusion criteria were elective surgery and absence of comorbidities after a rigorous preoperatory evaluation. One hundred and five patients were studied prospectively and urinary nitrogen loss was measured in the first 24 hour postoperative period. Operations performed were standard cardiopulmonary bypass procedures, under cardiopulmonary bypass, moderate hypothermia and hemodilution. Saphenous veins and mammary artery grafts were performed in all cases. Correlation and multiple linear regression were used. There was found no correlation between urinary nitrogen loss and age, gender and time under cardiopulmonary bypass. A positive correlation was found between number of grafts and increased urinary nitrogen loss. Further studies comparing cardiac aortic bypass graft with and without cardiopulmonary bypass are suggested.