Optimal Management of Bleeding and Transfusion in Patients Undergoing Cardiac Surgery

Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are at increased risk for excessive perioperative blood loss requiring transfusion of blood products. Point-of-care evaluation of platelets, coagulation factors, and fibrinogen can enable physicians to rapidly assess bleeding abnormalities, facilitate the optimal administration of pharmacological and transfusion-based therapy, and also identify patients with surgical bleeding. The ability to reduce the unnecessary use of blood products in this setting has important implications for emerging issues in blood inventory and blood costs. The ability to decrease surgical time, along with exploration rates, has important consequences for health care costs in an increasingly managed health care environment.     

Post cardiopulmonary bypass bleeding: an introductory review.

Cardiac surgery requiring cardiopulmonary bypass (CPB) has increased in both number and safety over the past four decades. Postoperative bleeding continues to be a major cause of perioperative morbidity. The reported incidence varies from 4-32%. This paper reviews the preoperative evaluation and specific hemostasis defects associated with cardiac surgery and extracorporeal circulation. Monitoring of anticoagulation and coagulation, methods to decrease the alterations of the coagulation system, as well as the specific therapy for and risks of post-CPB bleeding are also discussed.     

D-Dimer formation during cardiac and noncardiac thoracic surgery.

The ability to make therapeutic decisions regarding excessive fibrinolysis in the perioperative period is limited by the lack of availability of a near site monitor of fibrinolysis. We investigated the use of a latex agglutination D-dimer assay to detect perioperative fibrinolysis in patients undergoing thoracic surgery with and without extracorporeal circulation. We studied 27 patients who underwent thoracic surgery requiring cardiopulmonary bypass (CPB; coronary artery bypass grafting, n = 12; valvular surgery, n = 15) and a cohort of 20 patients who underwent noncardiac thoracic surgical procedures not requiring CPB. The purpose of this investigation was to determine the relationship among alterations in the latex agglutination D-dimer assay, use of extracorporeal circulation, type of cardiac surgical procedure, and mediastinal and/or chest tube drainage (cardiac surgery only) in patients undergoing thoracic surgery. Perioperative D-dimer levels, measured by latex agglutination, had significant (P < or = 0.05) intragroup changes among patients undergoing cardiac surgery (requiring CPB) and the cohort of patients who underwent noncardiac thoracic surgery without CPB. Although intraoperative D-dimer levels were not increased in patients undergoing noncardiac thoracic surgery, postoperative levels were significantly (P < 0.05) increased (compared with preinduction). In cardiac surgery patients requiring CPB, intraoperative D-dimer formation was significantly (P < or = 0.05) increased but did not demonstrate any intragroup (coronary artery bypass grafting versus valvular surgery) differences. Finally, D-dimer levels were not associated with postoperative mediastinal and/or chest tube accumulative drainage measured at intervals up to 48 h postoperatively in patients undergoing cardiac surgery requiring CPB. Our study indicates that the latex agglutination D-dimer assay can detect excessive fibrinolysis perioperatively, and that extracorporeal circulation can significantly influence the pattern of D-dimer formation in patients undergoing thoracic surgery. IMPLICATIONS: We assessed the ability of a readily available D-dimer assay to detect excessive fibrinolysis in patients undergoing thoracic surgery with and without extracorporeal circulation. The findings demonstrate that the assay used in this investigation reflected variable amounts of fibrinolysis in patients undergoing both types of thoracic surgery.     

Mechanisms and attenuation of hemostatic activation during extracorporeal circulation.

Patients undergoing cardiac surgery with cardiopulmonary bypass are at risk for excessive microvascular bleeding, which often leads to transfusion of allogeneic blood and blood components as well as reexploration in a smaller subset of patients. Excessive bleeding after cardiac surgery is generally related to a combination of several alterations in the hemostatic system pertaining to hemodilution, excessive activation of the hemostatic system, and potentially the use of newer, longer-acting antiplatelet or antithrombotic agents. Although several nonpharmacologic strategies have been proposed, this review summarizes the role of pharmacologic interventions as means to attenuate the alterations in the hemostatic system during CPB in an attempt to reduce excessive bleeding, transfusion, and reexploration. Specifically, agents that inhibit platelets, fibrinolysis, factor Xa and thrombin, as well as broad-spectrum agents, have been investigated with respect to their role in reducing consumption of clotting factors and better preservation of platelet function. Prophylactic administration of agents with antifibrinolytic, anticoagulant, and possibly antiinflammatory properties can decrease blood loss and transfusion. Although aprotinin seems to be the most effective blood conservation agent (which is most likely related to its broad-spectrum nature), agents with isolated antifibrinolytic properties may be as effective in low-risk patients. The ability to reduce blood product transfusions and to decrease operative times and reexploration rates favorably affects patient outcomes, availability of blood products, and overall health care costs.     

Evidence based coagulation monitors: heparin monitoring, thromboelastography, and platelet function

The hemostatic management of patients undergoing cardiac surgery is a unique challenge. Since its inception, cardiopulmonary bypass (CPB) has required meticulous attention to maintaining adequate anticoagulation. New anticoagulants and alternative monitoring techniques present an opportunity to investigate potential advances in the area of anticoagulation for CPB. Hemostasis after CPB is still a vexing problem, and the addition of antiplatelet medication to the platelet defect already incurred during CPB has led to hemorrhagic complications in cardiac surgery. The two opposing processes of anticoagulation and hemostasis must be managed carefully and modified with respect to the patient's hematologic status and desired hemostatic outcome. Cardiac surgical patients consume a much larger fraction of perioperative blood transfusions than the percentage of the surgical population they represent. Thus, during CPB, careful attention must be paid to optimal anticoagulation, platelet quiescence, biocompatible circuitry and interventions, and to monitoring hemostasis. The multifactorial etiology of the CPB-induced hemostatic defect requires a multimodal approach to blood conservation and hemostasis monitoring, including heparin maintenance and sophisticated point-of-care hemostasis monitoring. Each technology has its own attributes and each may be suitable for different populations based upon the expected defects being measured. This article reviews the evidence supporting the use of point-of-care monitors in coagulation and hemostasis management in cardiac surgical patients.     

Management of massive operative blood loss

Coagulopathy associated with massive operative blood loss is an intricate, multicellular and multifactorial event. Massive bleeding can either be anticipated (during major surgery with high risk of bleeding) or unexpected. Management requires preoperative risk evaluation and preoperative optimization (discontinuation or modification of anticoagulant drugs, prophylactic coagulation therapy). Intraoperatively, the causal diagnosis of the complex pathophysiology of massive bleeding requiring rapid and specific coagulation management is critical for the patient's outcome. Treatment and transfusion algorithms, based on repeated and timely point-of-care coagulation testing and on the clinical judgment, are to be encouraged. The time lapse for reporting results and insufficient identification of the hemostatic defect are obstacles for conventional laboratory coagulation tests. The evidence is growing that rotational thrombelastometry or modified thrombelastography are superior to routine laboratory tests in guiding intraoperative coagulation management. Specific platelet function tests may be of value in platelet-dependent bleeding associated e.g. with extracorporeal circulation, antiplatelet therapy, inherited or acquired platelet defects. Therapeutic approaches include the use of blood products (red cell concentrates, platelets, plasma), coagulation factor concentrates (fibrinogen, prothrombin complex, von Willebrand factor), pharmacological agents (antifibrinolytic drugs, desmopressin), and local factors (fibrin glue). The importance of normothermia, normovolemia, and homeostasis for hemostasis must not be overlooked. The present article reviews pathomechanisms of coagulopathy in massive bleeding, as well as routine laboratory tests and viscoelastic point-of-care hemostasis monitoring as the diagnostic basis for therapeutic interventions.     

Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary bypass

BACKGROUND: Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test-based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding. METHODS: The authors performed a randomized prospective trial comparing allogeneic transfusion practices in 92 adult patients with abnormal bleeding after CPB. Patients with abnormal bleeding were randomized to one of two groups: a control group following individual anesthesiologist's transfusion practices and a protocol group using a transfusion algorithm guided by coagulation tests. RESULTS: Among 836 eligible patients having all types of elective cardiac surgery requiring CPB, 92 patients developed abnormal bleeding after CPB (incidence, 11%). The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB (median, 0 units; range, 0-7 units) than the control group (median, 3 units; range, 0-10 units) (P = 0.0002). The median number of platelet units transfused in the operating room after CPB was 4 (range, 0-12) in the algorithm group compared with 6 (range, 0-18) in the control group (P = 0.0001). Intensive care unit (ICU) mediastinal blood loss was significantly less in the algorithm group. Multivariate analysis demonstrated that transfusion algorithm use resulted in reduced ICU blood loss. The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding (11.8% vs. 0%; P = 0.032). CONCLUSIONS: Use of a coagulation test-based transfusion algorithm in cardiac surgery patients with abnormal bleeding after CPB reduced non-erythrocyte allogeneic transfusions in the operating room and ICU blood loss.     

Coagulation monitoring during extracorporeal membrane oxygenation: the role of thrombelastography

Patients undergoing extracorporeal membrane oxygenation (ECMO) are at an increased risk for developing coagulopathies due to the adverse effects of extracorporeal circulation on the hemostatic mechanism. Methods of determining causative factors of bleeding diathesis are often inconsistent and non-specific. ECMO patients require aggressive transfusion therapy with autogenic blood products to stabilize and maintain hemostasis. The present study evaluated the coagulation status of newborn patients undergoing ECMO therapy, using a viscoelastic monitor (Thrombelastograph -TEG) that measures functional aspects of clot development and stabilization. Seventeen neonatal patients undergoing ECMO for severe respiratory dysfunction were entered into this study. Serial blood samples were obtained and routine coagulation assessment including fibrinogen concentration, platelet count and ionized calcium was performed. In addition, fibrin(ogen) degradation products (FDP), d-Dimers, antithrombin III and plasma free hemoglobin were measured. Transfusion indicators were established and total transfusion requirements recorded. TEG profiles were determined with the use of heparinase, an enzyme that degrades heparin but has little effect on other coagulation factors. The most commonly encountered complication was hemorrhaging which was diagnosed by laboratory and clinical assessment in 11 of 17 patients. Transfusion requirements (measured in ml/kg/ECMO hour) were the following: packed red blood cells--1.34 +/- 0.5; platelets--0.71 +/- 0.57; fresh frozen plasma--0.09 +/- 0.12; cryoprecipitate 0.05 +/- 0.05. Thrombelastograph profiles reflected hemostatic conditions that ranged from severe coagulopathies (DIC) to hypercoagulability. Interpretation of TEG profiles identified hemostatic abnormalities in 57 of 101 profiles (46.5%), with the most common etiology related to platelet dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glutamine administration in patients undergoing cardiac surgery and the influence on blood glutathione levels

Background: Cardiac surgery with an extracorporeal circulation cardiopulmonary bypass (CPB) is characterized by an oxidative stress response. Glutathione (GSH) belongs to the major antioxidative defense. In metabolic stress, glutamine (GLN) may be the rate-limiting factor of GSH synthesis. Decreased GLN plasma levels were observed after various critical states. We evaluated, in patients undergoing open heart surgery with CPB, the effects of a peri-operative GLN supplementation on GSH in whole blood and assessed their influence on the Sequential Organ Failure Assessment score and the intensive care unit length of stay.
Methods: In this prospective, randomized, double-blinded study, we included 60 patients (age older than 70 years, ejection fraction <40% or mitral valve replacement) undergoing an elective cardiac surgery with CPB. We randomly assigned each subject to receive an infusion with either GLN (0.5 g/kg/day, group 1) or an isonitrogeneous, isocaloric, isovolemic amino acids solution (group 2) or saline (group 3).
Results: From the first post-operative day GLN plasma levels in group 1 were significantly increased compared with the other groups. With saline GSH the levels decreased significantly post-operatively compared with GLN. We observed a significant correlation between GLN delivery and GSH levels.
Conclusions: A peri-operative high-dose GLN infusion increased plasma GLN concentrations and maintained the GSH levels after cardiac surgery with CPB.     

Thrombography reveals thrombin generation potential continues to deteriorate following cardiopulmonary bypass surgery despite adequate hemostasis

The intrinsic and extrinsic activation pathways of the hemostatic system converge when prothrombin is converted to thrombin. The ability to generate an adequate thrombin burst is the most central aspect of the coagulation cascade. The thrombin-generating potential in patients following cardiopulmonary bypass (CPB) may be indicative of their hemostatic status. In this report, thrombography, a unique technique for directly measuring the potential of patients' blood samples to generate adequate thrombin bursts, is used to characterize the coagulopathic profile in post-CPB patients. Post-CPB hemostasis is typically achieved with protamine reversal of heparin anticoagulation and occasionally supplemented with blood product component transfusions. In this pilot study, platelet poor plasma samples were derived from 11 primary cardiac surgery patients at five time points: prior to CPB, immediately post-protamine, upon arrival to the intensive care unit (ICU), 3 hours post-ICU admission, and 24 hours after ICU arrival. Thrombography revealed that the Endogenous Thrombin Potential (ETP) was not different between [Baseline] and [PostProtamine] but proceeded to deteriorate in the immediate postoperative period. At the [3HourPostICU] time point, the ETP was significantly lower than the [Baseline] values, 1233 +/- 591 versus 595 +/- 379 nM.min (mean +/- SD; n=9, p < .005), despite continued adequacy of hemostasis. ETPs returned to baseline values the day after surgery. Transfusions received, conventional blood coagulation testing results, and blood loss volumes are also presented. Despite adequate hemostasis, thrombography reveals an underlying coagulopathic process that could put some cardiac surgical patients at risk for postoperative bleeding. Thrombography is a novel technique that could be developed into a useful tool for perfusionists and physicians to identify coagulopathies and optimize blood management following CPB.     

Current concepts of hemostasis: implications for therapy

The revised model of coagulation has implications for therapy of both hemorrhagic and thrombotic disorders. Of particular interest to anesthesiologists is the management of clotting abnormalities before, during, and after surgery. Most hereditary and acquired coagulation factor deficiencies can be managed by specific replacement therapy using clotting factor concentrates. Specific guidelines have also been developed for perioperative management of patients using anticoagulant agents that inhibit platelet or coagulation factor functions. Finally, recombinant factor VIIa has been used off-label as a hemostatic agent in some surgical situations associated with excessive bleeding that is not responsive to conventional therapy.     

The protein C system in patients undergoing cardiopulmonary bypass

Fifteen men undergoing extracorporeal circulation for aorta-coronary bypass grafting were investigated for alterations of the plasma levels of cross-linked fibrin degradation products, protein C, free protein S, coagulation factor II, immunoglobulin G, and albumin. Although all patients were given heparin, a progressive increase of cross-linked fibrin degradation products was recorded during extracorporeal circulation, which indicates an activation of the plasmatic coagulation system. This increase was most pronounced in the late phase of extracorporeal circulation after reperfusion of the lung and in the early postoperative period. The levels of all other investigated plasma proteins decreased drastically after the patient was connected to the bypass circuit, which was primed with saline solution. These levels increased after termination of extracorporeal circulation and administration of fresh-frozen plasma. To study the consumption of protein C, protein S, and factor II during extracorporeal circulation, we formed ratios of the values of these parameters to the value of immunoglobulin G. After this volume correction, protein C was found to decrease significantly in the late phase of extracorporeal circulation, remaining low in the early postoperative period; protein S increased significantly soon after the onset of extracorporeal circulation and decreased after termination of extracorporeal circulation; factor II was unaffected by extracorporeal circulation, showing only a slight, insignificant increase in the postoperative phase. These results suggest a disturbance of the protein C system by extracorporeal circulation, which is possibly linked to the reported high bleeding tendency in patients undergoing operations with extracorporeal circulation.     

Homologous fresh frozen plasma in heart surgery. Myth or necessity

Routine administration of homologous fresh frozen plasma (FFP) is widely carried out in cardiac surgery although the risks of blood transfusion can never be excluded. The effect of two units of FFP (430 +/- 11 ml) given after the end of extracorporeal circulation (ECC) (group 1, n = 20) was compared to a control group (n = 20) without FFP in elective aorto coronary bypass patients. Various laboratory parameters, including coagulation data, were measured before and after the end of ECC up to the 1st postoperative day. The patients were comparable with regard to biometric data, anesthesia, and surgical procedure. The major result of this study shows, that routine administration of FFP has no beneficial effect with respect to hemostatic balance. In comparison to a control group, the increase in elastase and decrease in paO2 was even more pronounced in the FFP group. Both blood loss and the need for blood transfusion did not differ between the groups. It can be concluded that a bleeding tendency in cardiac surgery may be caused by ECC itself and by perioperative plasma loss. The routine administration of a relatively small amount of FFP has no positive influence on hemostasis. Substitution therapy in this situation should be guided by the results of coagulation studies.     

Comparison of Two Miniaturized Cardiopulmonary Bypass Systems Regarding Inflammatory Response

Cardiopulmonary bypass (CPB) is a known mediator of systemic inflammatory response. Extracorporeal circulations are undergoing continuous modifications and optimizations to achieve better results. Hence we aim to compare the inflammatory response associated with two recent miniature extracorporeal circulation systems during normothermic CPB. We measured plasma levels of cytokines including interleukin (IL)‐1β, IL‐6, IL‐10, tumor necrosis factor‐α, migration inhibitory factor (MIF), receptor for advanced glycation endproduct, and cluster of differentiation 40 ligand in 60 consecutive patients during the first 24 h after CPB. The patients were prospectively randomized to one of three trial groups: patients in group A were operated with the minimal extracorporeal circulation circuit (MECC, Maquet, Rastatt, Germany), group B operated with the extracorporeal circulation circuit optimized (ECC.O, Sorin, Italy), and group C operated with a conventional extracorporeal circuit (CECC, Maquet). Arterial blood samples were collected at intervals before, 30 min after initiation, and after termination of CPB. Further samples were collected 6 and 24 h after CPB. IL‐10 levels were significantly raised in the CECC group as compared with either of the mini ECC‐circuits with a peak concentration at 6 h postoperatively. Human MIF concentrations were significantly higher in the CECC group starting 30 min after CPB and peaking at the end of CPB. The overall reduction in cytokine concentrations in the mini‐ECC groups correlated with a lower need for blood transfusion in MECC and a shorter mechanical ventilation time for ECC.O. Normothermic CPB using minimally invasive extracorporeal circulation circuits can reduce the inflammatory response as measured by cytokine levels, which may be beneficial for perioperative preservation of pulmonary function and hemostasis in low risk patients.     

Impact of off-pump coronary artery bypass surgery on postoperative bleeding: current best available evidence

Cardiopulmonary bypass (CPB) is a prerequisite for open-heart surgery, and is a procedure routinely used. CPB exposes blood to artificial surfaces, to mechanical trauma from the pump, to alterations in temperature, and to dilution with fluids, whole blood, plasma products, and drugs, and leads to the activation of platelets, coagulation, and fibrinolysis. Coagulopathy during cardiac surgery with CPB results in impairment in hemostasis and subsequently higher morbidity and mortality. Recent advances in surgical techniques and postoperative management have aimed at reducing postoperative morbidity and mortality. Off-pump coronary artery bypass (OPCAB) surgery is one such advance that attempts to avoid the deleterious effects of extracorporeal circulation by performing myocardial revascularization without CPB. Emerging evidence from several randomized controlled trials (RCTs) as well as large registries such as the Society of Thoracic Surgeons (STS) database suggests that OPCAB reduces the postoperative morbidity and mortality. This review article attempts to evaluate the current best available evidence from RCTs on the impact of OPCAB on postoperative bleeding and transfusion requirements.     

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.     

Coagulation tests predict bleeding after cardiopulmonary bypass

To determine the accuracy of coagulation profile laboratory tests, thromboelastography, and Sonoclot (SCT) values for predicting microvascular bleeding after cardiopulmonary bypass (CPB). A prospective, blinded trial. A large academic medical center. Eighty-two adult patients undergoing elective cardiac surgery. Ten minutes after CPB, thromboelastography, SCT, and coagulation profile tests (bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin split products, platelet count, mean platelet volume, and platelet hematocrit) were determined from a whole blood sample taken from an existing arterial catheter. Patients were subjectively defined as “bleeders” or “non-bleeders” by blinded clinical observers. Preoperative baseline tests were also obtained.

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Thirty of the 82 patients (36.6%) were characterized as bleeders. Coagulation profile tests had the best correlation with intraoperative and postoperative blood loss. The specificity, sensitivity, and negative and positive predictive values were determined by receiver operating characteristic analysis, and the test values that differentiated normal from abnormal (bleeding) patients were determined. The coagulation profile laboratory tests had the greatest maximal sensitivity and specificity for predicting bleeding. These predictive values were outside the normal range for these laboratory tests. The thromboelastography values that produced maximal sensitivity and specificity were in the normal range for that test. Contrary to previous studies, coagulation profile tests had the greatest sensitivity and specificity to differentiate patients with excessive bleeding (abnormal) from those without excessive bleeding (normal) after CPB. Therefore, these tests should be used to guide transfusion therapy in patients who have excessive bleeding after CPB.     

Blood conservation in cardiac operations. Cell separation versus hemofiltration

The effects of hemoconcentration performed during and after extracorporeal circulation by either centrifugation (cell separation group, n = 20) or hemofiltration (n = 20) were investigated in 40 patients undergoing elective aorta-coronary bypass grafting. Interest was focused on the quality of the blood concentrated from the blood remaining in the extracorporeal circuit and on the reaction of the patients after retransfusion of the concentrated products. Hemofiltration was easy to perform and produced whole blood quicker than the cell separation technique. Coagulation studies revealed no significant differences in heparin concentration, levels of fibrinogen and antithrombin III, or platelet counts. Various coagulation parameters tended to normalize completely and more quickly after hemofiltration than after centrifugation. None of the patients had severe bleeding postoperatively. Free hemoglobin levels were not affected by hemofiltration; elastase concentration was higher only immediately after retransfusion of the concentrated blood, with no effect on organ function. We conclude that both methods were effective means of hemoconcentration during extracorporeal circulation and in salvaging the diluted pump blood after extracorporeal circulation. Loss of plasma fraction is an important disadvantage in the centrifugation technique, which can be avoided by hemofiltration; derangement in colloid osmotic pressure and coagulation parameters was less pronounced after hemofiltration. Costs were lower, as well. Therefore, when a high volume of cardioplegic solution and two-stage cannulation are used, hemofiltration seems to be the method of choice for blood conservation during cardiac operations.     

The effects of aprotinin on platelet function in blood exposed to eptifibatide: an in vitro analysis

The preoperative use of platelet inhibitors has increased the risk of bleeding during cardiac surgery. Aprotinin has been shown to preserve hemostatic function in patients undergoing CPB. The purpose of this study was to investigate the effect of aprotinin on coagulation in blood exposed to eptifibatide. Freshly collected bovine blood was used in an in vitro model of extracorporeal circulation. Blood was separated into two groups: activated (60 minutes exposure to bubble oxygenation) and nonactivated. Within each group there were four subgroups: control (n = 3), eptifibatide (2.8 microg/mL, n = 3), aprotinin (250 KIU/mL, n = 3), and eptifibatide with aprotinin (2.8 microg/mL, 250 KIU/mL, n = 3). Twenty-four modified extracorporeal circuits utilizing a hard-shell venous reservoir and cardioplegia heat exchangers were used. Blood flow was maintained at a rate of 1.25 L/min for a total of 170 minutes, at 37 +/- 1 degree C. Samples were collected at 0, 20, 50, and 110 minutes with the following variables measured: thromboelastograph (TEG), activated clotting time (ACT), and hematocrit (Hct). Results demonstrated that at 110 minutes, the TEG index (TI) was decreased by four-fold in the activated group compared to the nonactivated group (-4.6 +/- 1.2 vs. 1.4 +/- 1.5, p < .05). The administration of aprotinin resulted in preservation of the TI as compared to eptifibatide-treated blood (-4.9 +/- 1.2 vs. -7.9 +/- 1.2, p < .05). Aprotinin combined with eptifibatide reduced coagulation derangements when compared to eptifibatide alone (-5.2 +/- 1.2 vs. -7.9 +/- 1.2, p < .05). In conclusion, aprotinin attenuated the platelet inhibition effect of eptifibatide during in vitro CPB, resulting in improved coagulation.     

Efficacy of a Simple Intraoperative Transfusion Algorithm for Nonerythrocyte Component Utilization after Cardiopulmonary Bypass

Background: Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test-based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding.

Methods: The authors performed a randomized prospective trial comparing allogeneic transfusion practices in 92 adult patients with abnormal bleeding after CPB. Patients with abnormal bleeding were randomized to one of two groups: a control group following individual anesthesiologist's transfusion practices and a protocol group using a transfusion algorithm guided by coagulation tests.

Results: Among 836 eligible patients having all types of elective cardiac surgery requiring CPB, 92 patients developed abnormal bleeding after CPB (incidence, 11%). The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB (median, 0 units; range, 0-7 units) than the control group (median, 3 units; range, 0-10 units) (P = 0.0002). The median number of platelet units transfused in the operating room after CPB was 4 (range, 0-12) in the algorithm group compared with 6 (range, 0-18) in the control group (P = 0.0001). Intensive care unit (ICU) mediastinal blood loss was significantly less in the algorithm group. Multivariate analysis demonstrated that transfusion algorithm use resulted in reduced ICU blood loss. The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding (11.8%vs. 0%;P = 0.032).