Use of intraoperative transesophageal echocardiography to predict atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Postoperative atrial fibrillation in coronary artery bypass graft surgery occurs in 10-40% of patients. It is associated with a significant degree of morbidity and results in prolonged lengths of stay in both the intensive care unit and hospital. METHODS: The authors prospectively evaluated patients undergoing coronary artery bypass with detailed transesophageal echocardiography examinations conducted before and after cardiopulmonary bypass to study whether risk factors for atrial fibrillation could be identified. Demographic and surgical parameters were also included in the analysis. Selected variables were subjected to univariate and subsequent multivariate analyses to test for their independent or joint influence on atrial fibrillation. RESULTS: Seventy-nine patients had assessable transesophageal echocardiography examinations. Significant univariate predictors of atrial fibrillation included advanced age (P = 0.002), pre-cardiopulmonary bypass left atrial appendage area (P = 0.04), and post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio (P = 0.03). When these three factors were considered together in a multiple logistic regression analysis, left upper pulmonary vein systole/diastole velocity ratio was a significant predictor (P < 0.05), as was the joint effect of age plus pre-cardiopulmonary bypass left atrial appendage area (P = 0.005). The probability of developing atrial fibrillation for the combination of age = 75 yr, post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio = 0.5, and left atrial appendage area = 4.0 cm was 0.83 (95% confidence interval, 0.51-0.96). CONCLUSIONS: Early identification of patients at risk for postoperative atrial fibrillation may be feasible using the parameters identified in this study.

Endotoxin-neutralizing capacity of serum from cardiac surgical patients.

OBJECTIVE: To determine if endotoxin core antibody (EndoCAb) from the serum of cardiac surgical patients neutralizes endotoxin in an ex vivo biologic assay. DESIGN: Prospective blinded cohort study. SETTING: Academic medical center. PARTICIPANTS: Patients (n = 203) undergoing cardiac surgery. INTERVENTIONS: Sera were obtained from patients preoperatively. MEASUREMENTS AND MAIN RESULTS: EndoCAb levels were determined by enzyme-linked immunosorbent assay. Sera were incubated for 15 minutes at 37 degrees C with varying concentrations of endotoxin from a clinically relevant bacterium (Escherichia coli serotype O18), then tested for the presence of endotoxin activity using the validated Limulus amebocyte lysate assay. Median (interquartile range) IgM and IgG EndoCAb levels were 118 median units (range, 31 to 259 median units) and 208 median units (range, 108 to 401 medium units). Increasing levels of IgM EndoCAb were associated with increased neutralization of endotoxin (p < 0.0001). Increasing levels of IgG EndoCAb were associated with increased neutralization of endotoxin (p < 0.0001). An additive effect of IgM and IgG EndoCAb levels on endotoxin neutralization was observed without evidence of synergistic or plateau effects. EndoCAb levels did not completely predict serum neutralization capacity. CONCLUSION: Anti-EndoCAbs of both classes (IgM and IgG) were able to neutralize lipopolysaccharide from a clinically relevant bacterium in an ex vivo model. Neither Igm nor IgG appeared to be more capable of neutralization in this model. These antibodies did not completely predict neutralization capacity; other endogenous factors in human serum must be capable of lipopolysaccharide neutralization.

An investigation of a new activated clotting time "MAX-ACT" in patients undergoing extracorporeal circulation.

UNLABELLED: Activated clotting time (ACT) is a test used in the operating room for monitoring heparin effect. However, ACT does not correlate with heparin levels because of its lack of specificity for heparin and its variability during hypothermia and hemodilution on cardiopulmonary bypass (CPB). A modified ACT using maximal activation of Factor XII, MAX-ACT (Actalyke MAX-ACT; Array Medical, Somerville, NJ), may be less variable and more closely related to heparin levels. We compared MAX-ACT with ACT in 27 patients undergoing CPB. We measured ACT, MAX-ACT, temperature, and hematocrit at six time points: baseline; postheparin; on CPB 30, 60, and 90 min; and postprotamine. Additionally, we assessed anti-Factor Xa heparin activity and antithrombin III activity at four of these six time points. With institution of CPB and hemodilution, MAX-ACT and ACT did not change significantly but had a tendency to increase, whereas concomitant heparin levels decreased (P = 0.065). Neither test correlated with heparin levels. ACT and MAX-ACT did not differ during normothermia but did during hypothermia, and ACT was significantly longer than MAX-ACT (P = 0.009). At the postheparin time point, ACT-heparin sensitivity (defined as [ACT postheparin - ACT baseline]/[heparin concentration postheparin - heparin concentration baseline]) was greater than MAX-ACT-heparin sensitivity (analogous calculation for MAX-ACT; 520 [266 - 9366] s. U(-1). mL(-1) vs 468 [203 - 8833] s. U(-1). mL(-1); P = 0.022). IMPLICATIONS: MAX-ACT (a new activated clotting time [ACT] test) uses more maximal clotting activation in vitro and, although it is less susceptible to increase because of hypothermia and hemodilution than ACT, lack of correlation with heparin levels remains a persistent limitation.

Anticoagulation for cardiac surgery in patients receiving preoperative heparin: use of the high-dose thrombin time.

UNLABELLED: Patients receiving heparin infusions have an attenuated activated clotting time (ACT) response to heparin given for cardiopulmonary bypass (CPB). We compared patients receiving preoperative heparin (Group H) to those not receiving heparin (REF group) with respect to ACT, high-dose thrombin time (HiTT), and markers of thrombin generation during CPB. Sixty-five consecutive patients (33 Group H, 32 REF group) undergoing elective CPB were evaluated. ACT and HiTT were measured at multiple time points. Plasma levels of thrombin-antithrombin III complex and fibrin monomer were determined at baseline, during CPB, and after protamine administration. Transfusion requirements and postoperative blood loss were measured and compared. ACT values after heparinization increased less in Group H and were significantly lower than those in the REF group (P < 0.01). HiTT values did not differ significantly between the two groups. Blood loss and transfusion requirements were not significantly different between the two groups. Plasma levels of thrombin-antithrombin III complexes and fibrin monomer also did not differ between groups at any time, despite a lower ACT in Group H after heparinization and during CPB. Our data suggest that thrombin formation and activity are not enhanced in patients receiving heparin therapy, despite a diminished ACT response to heparin. The utility of ACT and the threshold values indicative of adequate anticoagulation for CPB are relatively undefined in patients receiving preoperative heparin. HiTT should be investigated as a safe and accurate monitor of anticoagulation for CPB in patients receiving preoperative heparin therapy. IMPLICATIONS: The diminished activated clotting time response to heparin, in patients receiving preoperative heparin therapy, poses difficulties when attempting to provide adequate anticoagulation for cardiopulmonary bypass. Current data suggest that heparin resistance is not observed when high-dose thrombin time is used to monitor anticoagulation and that a lower activated clotting time value in these patients may be safe.

Exposure to bacteroides fragilis endotoxin during cardiac surgery.

UNLABELLED: Although endotoxemia has been observed during cardiac surgery, the identity of endotoxins to which patients are exposed is unknown. We tested the hypothesis that antibodies to Bacteroides fragilis (an anaerobic gut commensal and a common pathogen) decrease during cardiac surgery, thereby reflecting systemic exposure to this type of endotoxin. Serum antiendotoxin antibody levels were measured in 55 patients during routine cardiac surgery at the following times: Preoperatively, Pre-CPB (immediately before initiation of cardiopulmonary bypass [CPB]), Pre-CPB+5 (5 min after initiation of CPB), and End (end of surgery). Antiendotoxin antibody levels were determined by using enzyme-linked immunosorbent assay. Total immunoglobulin M (IgM) levels were measured by using laser nephelometry and decreases in total IgM levels were used to control changes in antiendotoxin antibody levels attributable to hemodilution. Median (interquartile range) hemodilution corrected IgM anti-B fragilis antibody levels decreased by 12% (5%-20%) from Preoperatively to End of surgery (P < 0.001). In contrast, median hemodilution corrected anti-B fragilis antibody levels did not change significantly from Pre-CPB to Pre-CPB+5, validating the correction for hemodilution. Immunoglobulin G anti-B fragilis antibody levels and IgM and immunoglobulin G anticore antibody levels decreased similarly during surgery. Intraoperatively, levels of anti-B fragilis endotoxin antibodies decreased significantly out of proportion to hemodilution. These results suggest that cardiac surgical patients are exposed to B fragilis endotoxin. IMPLICATIONS: We prospectively measured hemodilution-corrected antiendotoxin antibody levels in 55 cardiac surgical patients. We observed significant decreases in hemodilution-corrected levels of antibody to both Bacteroides fragilis and the core of endotoxin.

Platelet-activated clotting time does not measure platelet reactivity during cardiac surgery.

BACKGROUND: Platelet dysfunction is a major contributor to bleeding after cardiopulmonary bypass (CPB), yet it remains difficult to diagnose. A point-of-care monitor, the platelet-activated clotting time (PACT), measures accelerated shortening of the kaolin-activated clotting time by addition of platelet activating factor. The authors sought to evaluate the clinical utility of the PACT by conducting serial measurements of PACT during cardiac surgery and correlating postoperative measurements with blood loss. METHODS: In 50 cardiac surgical patients, blood was sampled at 10 time points to measure PACT. Simultaneously, platelet reactivity was measured by the thrombin receptor agonist peptide-induced expression of P-selectin, using flow cytometry. These tests were temporally analyzed. PACT values, P-selectin expression, and other coagulation tests were analyzed for correlation with postoperative chest tube drainage. RESULTS: PACT and P-selectin expression were maximally reduced after protamine administration. Changes in PACT did not correlate with changes in P-selectin expression at any time interval. Total 8-h chest tube drainage did not correlate with any coagulation test at any time point except with P-selectin expression after protamine administration (r = -0.4; P = 0.03). CONCLUSIONS: The platelet dysfunction associated with CPB may be a result of depressed platelet reactivity, as shown by thrombin receptor activating peptide-induced P-selectin expression. Changes in PACT did not correlate with blood loss or with changes in P-selectin expression suggesting that PACT is not a specific measure of platelet reactivity.

Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery.

UNLABELLED: Transfusion therapy after cardiac surgery is empirically guided, partly due to a lack of specific point-of-care hemostasis monitors. In a randomized, blinded, prospective trial, we studied cardiac surgical patients at moderate to high risk of transfusion. Patients were randomly assigned to either a thromboelastography (TEG)-guided transfusion algorithm (n = 53) or routine transfusion therapy (n = 52) for intervention after cardiopulmonary bypass. Coagulation tests, TEG variables, mediastinal tube drainage, and transfusions were compared at multiple time points. There were no demographic or hemostatic test result differences between groups, and all patients were given prophylactic antifibrinolytic therapy. Intraoperative transfusion rates did not differ, but there were significantly fewer postoperative and total transfusions in the TEG group. The proportion of patients receiving fresh-frozen plasma (FFP) was 4 of 53 in the TEG group compared with 16 of 52 in the control group (P < 0.002). Patients receiving platelets were 7 of 53 in the TEG group compared with 15 of 52 in the control group (P < 0.05). Patients in the TEG group also received less volume of FFP (36 +/- 142 vs 217 +/- 463 mL; P < 0.04). Mediastinal tube drainage was not statistically different 6, 12, or 24 h postoperatively. Point-of-care coagulation monitoring using TEG resulted in fewer transfusions in the postoperative period. We conclude that the reduction in transfusions may have been due to improved hemostasis in these patients who had earlier and specific identification of the hemostasis abnormality and thus received more appropriate intraoperative transfusion therapy. These data support the use of TEG in an algorithm to guide transfusion therapy in complex cardiac surgery. IMPLICATIONS: Transfusion of allogeneic blood products is common during complex cardiac surgical procedures. In a prospective, randomized trial, we compared a transfusion algorithm using point-of-care coagulation testing with routine laboratory testing, and found the algorithm to be effective in reducing transfusion requirements.

Tranexamic acid reduces transfusions and mediastinal drainage in repeat cardiac surgery.

The administration of tranexamic acid (TA) prior to cardiopulmonary bypass (CPB) has been associated with reduced bleeding during and after cardiac surgery. In a prospective, randomized, controlled, double-blind clinical trial, adult patients undergoing repeat open heart surgery received TA (n = 17) or an equal volume of saline placebo (n = 13). In the TA group, a 20-mg/kg intravenous (IV) initial dose of TA at akin incision was followed by an infusion of 2 mg.kg-1.h-1, which continued for the duration of the surgical procedure. Identical transfusion guidelines were followed in both groups. Routine coagulation tests, D-dimer levels, mediastinal tube drainage, and transfusion requirements were compared. Cumulative postoperative mediastinal tube drainage measured at 24 h was 649 +/- 391 mliter (mean +/- SD) in the TA group compared with 923 +/- 496 mliter in the placebo group (P < 0.01). Forty-eight-and 72-h mediastinal tube drainage were also significantly less in the TA group (P < 0.01). Seven of 17 TA patients received to transfusion of allogeneic blood products compared with 1 of 13 placebo patients (P = 0.047). The incidence and volumes of platelet and fresh frozen plasma transfusion in the TA group were not significantly different in comparison with the placebo group. The perioperative increase in D-dimer levels (post-CPB minus pre-CPB) in the placebo group (median difference = 675 ng/mliter, range 125-1648) was significantly more than in the TA group (median difference = 182 ng/mliter, range -426-1950; P = 0.003). Sternal closure occurred in 41 +/- 21 min in the TA group and 61 +/- 49 min in the placebo group (P = 0.14), and the subjective bleeding score was less in the TA group than in the placebo group (2.38 +/- 0.78 vs 3.08 +/- 1.04; P = 0.045). The data from the current study support the prophylactic use of TA in patients undergoing repeat cardiac surgery. TA administered prior to CPB reduced the incidence of allogeneic transfusions and postoperative mediastinal tube drainage, and improved the subjective assessment of post-CPB hemostasis in a group of patients at moderately high risk for perioperative bleeding.

Cardiopulmonary bypass for adult patients: a survey of equipment and techniques.

OBJECTIVES: The techniques and equipment used for cardiopulmonary bypass for adult cardiac surgery vary among institutions and may change over time. This study sought to document the changing patterns of practice. DESIGN: Voluntary survey of meeting participants. SETTING: 13th Annual San Diego Cardiothoracic Surgery Symposium (February 1993). PARTICIPANTS: There were 331 responses from perfusionists (79.5%), cardiac surgeons (11.2%), and anesthesiologists (6.3%). The majority of these participants were from institutions where more than 1,000 cardiac operations were performed annually. MEASUREMENTS AND MAIN RESULTS: It was found that 91.5% of the respondents used membrane oxygenators currently, compared with 5% in 1982 (as reported in a previous survey). Over 80% of the institutions surveyed used some type of perioperative cell-salvaging technique. Arterial line filters were used by 92% of the respondents compared with 64% in 1982. Also, 80% of the respondents were aware of the availability of leukocyte-depleting filters. CONCLUSIONS: The probable reasons for the increased utilization of membrane oxygenators and arterial line filters include less damage to the formed elements of blood, fewer gaseous microemboli, and better control of carbon dioxide elimination and oxygenation. The authors anticipate that future surveys will document increased use of leukocyte-depleting filters because of the literature implicating neutrophils as mediators of tissue destruction in various disease processes, including myocardial reperfusion injury.

Aspirin does not increase homologous blood requirements in elective coronary bypass surgery.

Studies have demonstrated increased homologous blood product requirements in patients on aspirin (ASA) undergoing cardiac surgery. We reexamined the influence of ASA therapy on hemorrhage and transfusion requirements in patients undergoing elective coronary artery bypass (CAB) surgery in light of recent transfusion-sparing practices and autologous cell salvaging techniques. Records from 197 patients who underwent reinfusion of postoperatively shed mediastinal autologous whole blood were retrospectively reviewed, including 87 patients who received ASA within 1 wk prior to surgery and 110 control patients. Patients undergoing repeat cardiac operations were excluded from the study. Cardiopulmonary bypass (CPB) duration, procedure length, aortic cross-clamp time, and number of grafts performed did not differ significantly between groups. None of the patients required reexploration for bleeding. There was significantly more mediastinal tube drainage in the ASA group (27%), but it did not affect homologous blood component requirements because this blood was autotransfused. In addition, there were no significant differences in platelet, fresh frozen plasma, and cryoprecipitate use between the groups. Thus, ASA did increase bleeding but did not increase homologous blood transfusion requirements in elective CAB surgery.

Comparison of bedside coagulation monitoring tests with standard laboratory tests in patients after cardiac surgery.

We compared portable bedside tests of whole blood coagulation with standard laboratory plasma coagulation tests to assess the accuracy and precision of the bedside tests in a clinical setting (postcardiac surgery). The Ciba Corning 512 Coagulation Monitor (Ciba Corning Diagnostics Corp., Medfield, MA) and the Hemochron 801 (International Technidyne Corp., Edison, NJ) were tested. One hundred forty-one patients who underwent cardiac surgery requiring cardiopulmonary bypass were evaluated upon arrival in the intensive care unit. Nine milliliters of fresh whole blood were used to obtain the prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and the heparin-neutralized thrombin time (HNTT) that were measured by bedside coagulation monitors. TT and HNTT were only measured by the Hemochron method. Blood from the same sample was also sent to the Hospital Stat Laboratory for simultaneous comparison of bedside results and standard coagulation tests. For PT and aPTT testing, an accuracy of +/- 10% and a precision of +/- 25% were considered clinically acceptable. Both of the PT tests met the dual criteria for clinical acceptability, but the aPTT tests did not meet either criterion. The difference between Hemochron TT and Hemochron HNTT correlated weakly, but significantly, with laboratory aPTT ratio (r = 0.52, P < 0.001). The slope of the regression line indicated that a TT-HNTT difference > 30 s correlated with an aPTT > 1.5 x control. We conclude that, in the postoperative cardiac surgical patient, PT was both accurate and precise in two commercially available tests, but aPTT was not.(ABSTRACT TRUNCATED AT 250 WORDS)