Thrombotic complications in beating heart operations.

BACKGROUND: Off-pump coronary artery operations have recently gained popularity among the community of cardiac surgeons. Because the use of cardiopulmonary bypass is avoided, full anticoagulation is generally not sought to decrease perioperative blood loss and transfusion needs. Traditionally, patients undergoing coronary artery bypass operations with cardiopulmonary bypass are not considered at risk of having venous or arterial thromboembolic complications, and prophylaxis is generally not recommended. METHODS AND RESULTS: We have reviewed our experience with off-pump coronary bypass operations, focusing on thromboembolic complications with clinical manifestations, and compared these findings with our experience with cardiopulmonary bypass operations. In our series of 500 off-pump cases, thromboembolic complications occurred in 1%, causing death in 1 patient, whereas in a contemporary cohort of 1476 patients operated on with cardiopulmonary bypass, thromboembolic complications resulted in stroke in 0.5% of the cases. This difference did not reach statistical significance. CONCLUSIONS: Thromboembolic complications in off-pump coronary bypass operations are comparable with those in cardiopulmonary bypass operations. Although the prevalence of this complication remains low, the associated morbidity should lead to reconsideration of prophylactic measures.

Reinfusion of mediastinal blood after heart surgery.

BACKGROUND: Several authors studying autotransfusion of shed mediastinal blood in patients undergoing heart operations have published conflicting results regarding reduction of the need for homologous blood transfusion. The effect on coagulation parameters is also unclear. METHODS: In a prospective randomized study, 198 patients who underwent coronary artery bypass grafting or a valvular operation were divided into 2 groups: a group with autotransfusion of shed mediastinal blood after an operation and a control group. Continuous reinfusion of mediastinal blood was done until no drainage was present or for a period of 12 hours after the operation. The amount of blood lost and autotransfused, the number of homologous blood products transfused, and the coagulation parameters were monitored. RESULTS: The number of patients requiring homologous blood transfusion was significantly different between the 2 groups (54/98 [55%] in autotransfused patients vs 73/100 [73%] in the control group, P =.01). The number of re-explorations for excessive bleeding was similar in the 2 groups (7/98 [7.1%] vs 8/100 [8%]), but the amount of blood collected postoperatively was higher in the autotransfused patients compared with control patients (1200 +/- 201 mL vs 758 +/- 152 mL, P =.0007). Coagulation parameters analyzed and complication rates were similar in the 2 groups after the operations. CONCLUSION: Autotransfusion of shed mediastinal blood reduces the need for homologous blood transfusion in patients undergoing various cardiac operations. The cause of increased shed blood in patients undergoing autotransfusion remains unclear.

Effect of mycophenolate mofetil in heart transplantation.

OBJECTIVE: To study the effect of mycophenolate mofetil (MMF), a new immunosuppressive drug that acts by inhibiting de novo pathways of purine synthesis, and rabbit antithymocyte globulin (RATG) on the lymphocyte subpopulation after heart transplantation. DESIGN: A review of clinical and laboratory records. SETTING: The Montreal Heart Institute. PATIENTS: Thirty-one patients who underwent heart transplantation. In 9 patients, neoral cyclosporine, prednisone and azathioprine were administered (group 1). In 14 patients RATG was added during the first 3 postoperative days (group 2) and in 8 patients RATG and combination immunosuppression was given, but MMF was used instead of azathioprine (group 3). The demographic characteristics of donors and recipients were similar among the 3 groups. MAIN OUTCOME MEASURES: The proportion of CD2, CD4 and CD8 receptor-positive lymphocytes, expressed as a mean (and standard deviation) percentage of the total lymphocyte population, measured at 7, 15 and 30 days and 6 months after transplantation. RESULTS: At 7 days after transplantation, CD2 lymphocytes averaged 55% (18%), 16% (15%) and 14% (11%) in groups 1, 2 and 3 respectively (p < 0.05), CD4 averaged 36% (11%), 9% (12%) and 7% (8%) in groups 1, 2 and 3 (p < 0.05), and CD8 averaged 14% (6%), 4% (3%) and 4% (3%) in groups 1, 2 and 3 (p < 0.05). At 15 days after transplantation CD2 averaged 69% (10%), 42% (16%) and 47% (20%) in groups 1, 2 and 3 respectively (p < 0.05), and CD8 averaged 16% (7%), 16% (6%) and 19% (7%) (p = NS). At 30 days after transplantation the percentages of CD2, CD4 and CD8 lymphocytes were similar among the groups. The freedom rate from acute rejection averaged 22% (14%), 9% (8%) and 50% (18%) (p < 0.05) in groups 1, 2 and 3 at 6 months after transplantation, and the freedom rate from infection averaged 56% (17%), 36% (13%) and 38% (17%) for the 3 groups at this time period (p = NS). CONCLUSIONS: A short course of RATG causes severe, transitory depletion of CD2, CD4 and CD8 lymphocyte subpopulations. MMF decreases the incidence of early acute rejection after heart transplantation without affecting the lymphocyte subpopulation when compared with azathioprine.

Low-dose aprotinin is ineffective to treat excessive bleeding after cardiopulmonary bypass.

BACKGROUND: Uncontrolled clinical experience at our institution suggested that low-dose aprotinin could control excessive bleeding after cardiopulmonary bypass (CPB). A randomized clinical trial was conducted to determine the efficacy of low-dose aprotinin in the treatment of hemorrhage after cardiac surgery. METHODS: One hundred seventy-one patients undergoing cardiac surgery with CPB were included. Forty-four patients (26%) bled significantly in the intensive care unit (>100 mL/h) and received either aprotinin (200,000 KIU bolus + 100,000 KIU/h for 8 hours) or placebo in addition to our standard management of excessive bleeding. RESULTS: Median bleeding before study drug administration was not different between aprotinin (200 mL) and placebo (212.5 mL) groups. Bleeding decreased significantly with time and similarly in both groups. Ninety-five percent of patients required transfusions in both groups. Median blood products transfused were 13 and 8 units per patient in the aprotinin and placebo groups respectively (p = NS). CONCLUSIONS: Routine administration of low-dose aprotinin as part of the treatment protocol to control hemorrhage after CPB does not reduce bleeding or transfusion requirements and, therefore, cannot be recommended.

A 10-year experience with intravenous thymoglobuline in induction of immunosuppression following heart transplantation.

BACKGROUND: Intravenous thymoglobuline (125 mg a day for 3 days, Institut Mérieux, France) has been used to induce immunosuppression following heart transplantation. Cyclosporine and prednisone, with and without azathioprine or mycophenolate mofetil were used as maintenance immunosuppression. OBJECTIVE: The objective of the study was to determine the clinical effect of antibody induction of immunosuppression following heart transplantation. METHODS: A retrospective analysis of the clinical experience at the Montreal Heart Institute. From 1988 to 1998, 163 patients were administered a 3-day course of intravenous thymoglobuline immediately following heart transplantation (Group 1). From 1983 to 1987 and during an isolated period in 1994, intravenous and oral cyclosporine was used immediately following heart transplantation in 48 patients (Group 2). Routine endomyocardial biopsies were performed in all patients and only moderate and severe rejection was treated. RESULTS: One, 5- and 10-year actuarial survival rate averaged 85%+/-3, 77%+/-4 and 67%+/-5 in Group 1 compared with 88%+/-5, 81%+/-6 and 76%+/-6 in Group 2 (p = 0.5). At 1 year, the freedom rate from an episode of acute rejection averaged 43%+/-4 in Group 1 and 30%+/-7 in Group 2 (p = 0.03) and the freedom rate from an episode of infection averaged 44%+/-4 in Group 1 and 31%+/-7 in Group 2 (p = 0.2). At 1, 5 and 10 years, the freedom rate from graft coronary artery disease averaged 93%+/-2, 68%+/-5 and 50%+/-7 in Group 1 compared with 93%+/-4, 58%+/-8 and 30%+/-8 in Group 2 (p = 0.1) and the freedom rate from cancer averaged 98%+/-1, 91%+/-3 and 67%+/-8 in Group 1 compared with 100%, 95%+/-3 and 77%+/-8 in Group 2 (p = 0.2). There was no side-effect related to the systemic injection of thymoglobuline. CONCLUSION: In a cyclosporine based protocol of immunosuppression, induction with an initial 3-day course of intravenous thymoglobuline is associated with a lower rate of acute rejection. Moreover, the risk of infection and of developing cancer is not increased whereas there was a trend towards a lower incidence of coronary atherosclerosis 5 and 10 years after transplantation.

[Organization of care : specialized psychiatric clinic or general psychiatric clinic ? A debate between Louis Guérette and Jean-Pierre Rodriguez.]. / Organisation des soins par cliniques psychiatriques spécialisées ou par cliniques de psychiatrie générale? Un débat entre Louis Guérette et Jean-Pierre Rodriguez.

The author reports on the opinions of doctors Louis Guérette and Jean-Pierre Rodriguez, both psychiatrists - one working at the Pavillon Notre-Dame of the Centre hospitalier universitaire de Montréal (CHUM) - the other at the Pavillon Albert-Prévost (PAP) of the Hôpital du Sacré-Coeur de Montréal, - on the place of specialized psychiatric clinics in the organization of care in psychiatry. Dr Guérette who practices general psychiatry thinks specialized clinics are not an appropriate mode of care delivery. Dr Rodriguez, answering to Dr Guérette's arguments, presents the organizational system of specialized clinics put in place at the PAP. The questions raised by the author and the psychiatrists' answers are reported. Finally, the author, a resident doctor in psychiatry, presents his own personal opinion on the issue.

Prophylactic tranexamic acid and epsilon-aminocaproic acid for primary myocardial revascularization.

BACKGROUND: The efficacy of prophylactic epsilon-aminocaproic acid and tranexamic acid to reduce transfusions after primary myocardial revascularization was evaluated in a teaching hospital context. METHODS: Patients (n = 134) received either epsilon-aminocaproic acid (15-g bolus + infusion of 1 g/h), high-dose tranexamic acid (10-g bolus + placebo infusion), or normal saline solution in a double-blind fashion. Anticoagulation and conduct of cardiopulmonary bypass were standardized. RESULTS: Tranexamic acid and epsilon-aminocaproic acid produced a significant reduction in postoperative blood loss compared with placebo (median loss, 438 mL, 538 mL, and 700 mL, respectively). Transfusion of red cells was similar in all three groups. Nonetheless, the percentage of patients receiving hemostatic blood products was significantly decreased in the epsilon-aminocaproic acid group compared with the placebo group (20% versus 43%; p = 0.03). Both tranexamic acid and epsilon-aminocaproic acid significantly decreased total exposure to allogeneic blood products compared with placebo (p = 0.01 and p = 0.05, respectively), and this reduction was clinically important (median exposure, 2, 2, and 7.5 units, respectively). Fibrinolysis was inhibited significantly in both treatment groups. CONCLUSIONS: We conclude that either high-dose tranexamic acid or epsilon-aminocaproic acid effectively reduces transfusions in patients undergoing primary, elective myocardial revascularization.

Randomized, placebo-controlled, double-blind study of an ultra-low-dose aprotinin regimen in reoperative and/or complex cardiac operations.

BACKGROUND AND AIM OF THE STUDY: High-dose aprotinin is an effective but costly method to reduce transfusions after cardiopulmonary bypass (CPB). Very low doses of aprotinin have been shown to be effective in primary cardiac surgery, but not in patients undergoing procedures associated with the greatest usage of allogeneic blood products after CPB. We evaluated the efficacy of ultra-low-dose aprotinin in this patient population. METHODS: Aprotinin 1 million KIU or placebo was added to the priming solution of the CPB circuit of 52 patients undergoing a reoperation and/or a complex surgical procedure. Dryness of operative field, hemoglobin concentrations, coagulation parameters, chest drainage, and transfusion requirements were compared. RESULTS: Total chest drainage was not different between groups, but fewer patients in the aprotinin group required additional protamine postoperatively (35% vs 69% for controls, p = 0.03) and fewer received fresh frozen plasma (FFP; 19% vs 46% for controls, p = 0.04). Red cell transfusion was smaller in the aprotinin group compared to placebo (median 4 and 2 units, respectively, p = 0.04). Transfusion of FFP, platelets, cryoprecipitates was not different between groups. Total number of units transfused tended to be reduced in the aprotinin group compared to control (median 2 and 7 units, respectively, p = 0.06). CONCLUSIONS: Prophylactic administration of ultra-low-dose aprotinin reduced transfusions in patients undergoing repeat operations or complex procedures. Aprotinin could be used in a more economical manner, even in this patient population at high-risk of receiving allogeneic blood products.

Measurement of heparin concentration in whole blood with the Hepcon/HMS device does not agree with laboratory determination of plasma heparin concentration using a chromogenic substrate for activated factor X.

UNLABELLED: Measurement of circulating heparin concentration has been suggested to optimize anticoagulation during cardiopulmonary bypass. The Hepcon/HMS device (Medtronic HemoTec, Inc., Parker, Colo.) uses heparin/protamine titration to quantitatively determine heparin concentration. Extensive validation of this instrument is still lacking. METHODS: Agreement between heparin concentrations measured by the Hepcon/HMS system and by laboratory determination was evaluated in 16 patients undergoing cardiac operations. For laboratory determinations, plasma heparin concentration was derived from the measure of anti-Xa activity by means of chromogenic substrate technique. The Hepcon/HMS instrument and cartridges measured whole blood heparin concentration. Samples were analyzed 5 minutes after administration of heparin, 15 and 30 minutes after the start of cardiopulmonary bypass, 5 minutes after aortic unclamping, at the end of cardiopulmonary bypass, and after administration of protamine. Data were plotted and interpreted according to the method of Bland and Altman: First, a difference less than 1.4 U/ml (i.e., +/- 0.7 U/ml) was chosen as acceptable, because it would not cause major difficulties in clinical interpretation; second, the difference between the two measurement techniques was plotted against the mean of the two measures. RESULTS: The mean difference (bias) between heparin concentrations derived by the Hepcon/HMS device and those obtained by laboratory determination was as expected for measures performed on whole blood versus plasma (1.45 U/ml). Nevertheless, heparin concentrations derived by the Hepcon/HMS device may be as much as 2.76 U/ml above or 6.17 U/ml below the concentrations measured in the laboratory, differences well outside the predetermined limits of agreement and clearly unacceptable for clinical purposes. CONCLUSION: We conclude that heparin concentrations determined with the Hepcon/HMS instrument do not agree with laboratory determination of heparin concentration. Monitoring of heparin concentrations during bypass with the Hepcon/HMS device cannot be recommended.

Intramural delivery of agent via a novel drug-delivery sleeve. Histological and functional evaluation.

BACKGROUND: The infusion sleeve is a novel drug-delivery catheter system designed to deliver an agent under controlled conditions into the arterial wall at the site of angioplasty. The purpose of the present study was to characterize the delivery agent via the infusion sleeve in ex vivo and in vivo models. METHODS AND RESULTS: The delivery of horseradish peroxidase via the infusion sleeve was studied in a porcine explanted heart model. Under physiological conditions, arteries underwent balloon injury (approximately 10% overstretch), after which horseradish peroxidase (2.5 mL) was delivered at specific pressures. Cross-sectional analysis demonstrated greater staining when the agent was delivered at increasing pressures. The infusion sleeve was evaluated in an in vivo canine coronary model. With an infusion sleeve loaded over a standard dilatation catheter through a 9F guide, overstretch balloon injury was performed, after which fluoresceinated heparin was delivered. Animals were killed 2 hours after delivery. Fluoresceinated heparin-treated segments demonstrated high fluorescence signals, localizing with smooth muscle cell nuclei with less activity in the interstitium. The functional significance of intramural heparin delivery was studied in a porcine carotid model. In the presence of 111In-labeled platelets, arteries underwent overstretch injury followed by delivery of heparin (50 or 100 units/kg) or vehicle. Platelet deposition was reduced at 30 minutes (57%, P < .01) and 12 hours (39%, P = .06) compared with saline controls. CONCLUSIONS: Agent delivery via the infusion sleeve is pressure dependent; transmural delivery is possible with minimal disruption of arterial wall architecture; the infusion sleeve is compatible with standard angioplasty equipment; and heparin delivery at the site of balloon injury significantly reduces platelet deposition in a porcine model for a minimum of 12 hours.

Antithrombin-III plasma activity during and after prolonged use of heparin in unstable angina.

Heparin effectively prevents the complications of unstable angina but disease reactivation has been documented following its discontinuation. To investigate whether this could be related to antithrombin-III depletion, 50 patients with unstable angina had serial determinations of activated partial thromboplastin time and of the plasma levels of heparin, antithrombin-III activity and of the thrombin-antithrombin-III complex before, during and, in a subgroup of 8 patients, 4 hours after heparin discontinuation. Heparin was administered intravenously at therapeutic doses for a mean of 7.6 +/- 4.1 days. Plasma antithrombin-III activity decreased rapidly from 1.05 +/- 0.03 to 1.0 +/- 0.03 U/ml (p < 0.03) following heparin initiation with no further significant subsequent decrease. Antithrombin-III activity returned to the control values 4 hours after the discontinuation of heparin. Thus, heparin treatment is associated with small, non-cumulative and rapidly reversible decrease in antithrombin-III activity. Reactivation of unstable angina after discontinuation of heparin must be explained by a mechanism other than antithrombin-III deficiency.

Low-dose aprotinin infusion is not clinically useful to reduce bleeding and transfusion of homologous blood products in high-risk cardiac surgical patients.

A high-dose regimen of aprotinin 5-6 million KIU is effective in reducing bleeding and the need for homologous blood products (HBP) associated with cardiopulmonary bypass (CPB). These high doses aim at achieving plasmin and plasma kallikrein concentrations which in vitro are inhibitory but, theoretically, smaller doses could suffice in vivo. Also, aprotinin is an expensive drug, so efficiency requires using the smallest effective dose. Therefore, the efficacy of prophylactic aprotinin 1 million KIU (the maximal dose approved currently) was evaluated in a patient population at high risk of bleeding and of being transfused. Forty-one patients undergoing reoperation or a complex surgical procedure were included in a prospective, randomized, placebo-controlled, double-blind study. Before skin incision, a bolus of 200,000 KIU aprotinin was administered in 20 min, followed by an infusion of 100,000 KIU.hr-1 over eight hours. Control patients received an equal volume of saline. Dryness of the operative field, chest drainage, transfusion of HBP, haemoglobin concentrations, and coagulation variables (including bleeding time) were compared. There were no differences between aprotinin and placebo-treated patients for all clinical and laboratory variables. The apparent ineffectiveness of aprotinin may be explained by the use of an insufficient dose, by a different protocol of administration (e.g., no bolus in CPB prime), or by the inability of aprotinin to decrease bleeding and transfusions any further. Also, the number of patients studied does not exclude the possibility of a Type II error.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of immunosuppression with rabbit antithymocyte globulin: five-year experience in cardiac transplantation.

Perioperative induction of immunosuppressive treatment with rabbit antithymocyte globulin (RATG) and late introduction of cyclosporine was used in a group of 77 patients to prevent early renal dysfunction related to cyclosporine. Peak value in plasma creatinine during hospitalization for transplantation averaged 148 +/- 49 mmol/L in patients treated with RATG compared with 215 +/- 21 mmol/L in 39 patients initially treated without RATG induction (P = 0.01). Of patients treated with RATG, 65 +/- 6% remained free from acute rejection at six months versus 40 +/- 8% of untreated patients (P = 0.03). Rates of freedom from infection, from allograft coronary artery disease and from cancer are similar in both groups. Actuarial survival rates were identical in the two groups. The total number of lymphocytes, the percentage of T lymphocytes and of helper T cells were significantly lower when RATG was used. In conclusion, RATG prophylaxis given immediately after transplantation was well tolerated without complication and resulted in adequate immunosuppression to allow delayed introduction of maintenance treatment with cyclosporine.

Lipoprotein (a) blood levels in unstable angina pectoris, acute myocardial infarction, and after thrombolytic therapy.

Lipoprotein (a) [Lp(a)] appears to be involved in atherogenesis and in vitro studies have suggested that it may interfere with thrombolysis. In this study, Lp(a) serum levels were determined by radioimmunoassay in 124 patients with ischemic heart disease. Of these, 47 had acute myocardial infarction, 13 had unstable angina, and 64 were age-matched patients with stable angina. Of the 60 patients with acute coronary artery disease, 34 received thrombolysis and 26 did not. In addition to Lp(a), serum plasminogen, alpha 2 antiplasmin, fibrinogen, and D-dimer (cross-linked fibrin degradation products) levels were measured. These tests were repeated after 6 hours in patients with myocardial infarction and unstable angina. No significant difference was found for admission Lp(a) levels among patients with myocardial infarction (0.324 +/- 0.047 g/liter), unstable angina (0.435 +/- 0.123 g/liter) and stable angina (0.431 +/- 0.023 g/liter), between patients with myocardial infarction with or without thrombolytic treatment, nor between late and early measurements in patients with unstable angina and acute myocardial infarction. Plasminogen, alpha 2 antiplasmin and fibrinogen values decreased significantly after thrombolytic treatment. The size of this decrease correlated positively with higher Lp(a) blood levels (p less than 0.05). Patients with Lp(a) greater than 0.25 g/liter had a 66% decrease in fibrinogen and a 53% decrease in anti-plasmin, compared with 35 and 32%, respectively, in patients with Lp(a) level less than or equal to 0.25 g/liter (p less than 0.05). Plasminogen levels revealed a similar trend, with a 61% decrease for the higher values and a 45% decrease for the lower values.(ABSTRACT TRUNCATED AT 250 WORDS)

The stratification of cardiac surgical procedures according to use of blood products: a retrospective analysis of 1480 cases.

The use of blood products in 1480 consecutive cases of adult cardiac surgical procedures over a period of 15 mth was studied retrospectively using the database of the Department of Anaesthesia of the Institut de Cardiologie de Montréal. Use of blood products was compared in patients having (1) coronary artery bypass grafting, (2) valvular surgery, (3) or a combination of 1 and 2. First operations were compared with reoperations. Overall, the use of homologous blood products was greatest in patients of Group 3, intermediate in patients of Group 2, and smallest in patients of Group 1. Reoperations were associated with an increase in intraoperative transfusion of packed red blood cells, but postoperative chest drainage was similar to first operations. When all blood products (packed red blood cells, fresh frozen plasma and platelets) were taken into consideration, patients undergoing primary CABG or valve surgery were the least exposed to homologous blood donors (five and six units transfused respectively). Repeat CABG was associated with an intermediate exposure to homologous blood products (eight units). Finally, primary and repeat combined procedures, and repeat valve surgery were associated with the greatest exposure to foreign blood products (10, 13 and 10 units respectively). The data presented in this study provide a rational basis for stratification of procedures according to the expected use of blood products, particularly in view of future studies which may be planned to examine the efficiency of blood conservation strategies.

The presence of two forms of the phosphocarrier protein HPr of the phosphoenolpyruvate:sugar phosphotransferase system in streptococci.

The protein, HPr, a necessary component of the phosphoenolpyruvate phosphotransferase system (PTS) in bacteria, was purified from Streptococcus salivarius by column chromatography. The purified preparation gave only one band when analyzed by sodium dodecylsulfate gel electrophoresis or by isoelectric focusing in polyacrylamide gel (pI = 4.85). However, electrophoresis in Tris-containing buffers under non-denaturing conditions revealed 2 bands that could be phosphorylated by PEP in the presence of enzyme I of the PTS or by ATP with the HPr kinase. Homogeneous preparations of these 2 forms could be obtained by preparative electrophoresis. Each preparation exhibited only 1 band when analyzed by electrophoresis under non-denaturing conditions, indicating that the doublet observed before preparative electrophoresis was not an electrophoretic artefact. The electrophoretic mobility of each protein was not modified following heat-treatment at 100 degrees C for 20 min or storage at -40 degrees C for several months. Both HPr proteins catalyzed in vitro the PEP-dependent phosphorylation of glucose, but at a rate slightly lower than that observed with a preparation of HPr containing both forms of the protein. Both forms were also able to transfer the phosphate group from PEP to the other specific PTS proteins known in S salivarius. Rabbit polyclonal antibodies directed against each form reacted with both proteins. The presence of the 2 forms of HPr was detected in fresh cellular extracts of S salivarius; however, their intracellular ratio varied according to growth conditions. A doublet was also found in many other streptococcal species tested (S mutans, S sobrinus, S sanguis, S thermophilus, S bovis, S rattus) and also in L lactis.(ABSTRACT TRUNCATED AT 250 WORDS)