Bruce D. Spiess

Variability in transfusion practice for coronary artery bypass surgery persists despite national consensus guidelines : A 24-institution study

BACKGROUND An estimated 20% of allogeneic blood transfusions in the United States are associated with cardiac surgery. National consensus guidelines for allogeneic transfusion associated with coronary artery bypass graft (CABG) surgery have existed since the mid- to late 1980s. The appropriateness and uniformity of institutional transfusion practice was questioned in 1991. An assessment of current transfusion practice patterns was warranted. METHODS The Multicenter Study of Perioperative Ischemia database consists of comprehensive information on the course of surgery in 2,417 randomly selected patients undergoing CABG surgery at 24 institutions. A subset of 713 patients expected to be at low risk for transfusion was examined. Allogeneic transfusion was evaluated across institutions. Institution as an independent risk factor for allogeneic transfusion was determined in a multivariable model. RESULTS Significant variability in institutional transfusion practice was observed for allogeneic packed red blood cells (PRBCs) (27-92% of patients transfused) and hemostatic blood components (platelets, 0-36%; fresh frozen plasma, 0-36%; cryoprecipitate, 0-17% of patients transfused). For patients at institutions with liberal rather than conservative transfusion practice, the odds ratio for transfusion of PRBCs was 6.5 (95% confidence interval [CI], 3.8-10.8) and for hemostatic blood components it was 2 (95% CI, 1.2-3.4). Institution was an independent determinant of transfusion risk associated with CABG surgery. CONCLUSIONS Institutions continue to vary significantly in their transfusion practices for CABG surgery. A more rational and conservative approach to transfusion practice at the institutional level is warranted.

A Multicenter, Double-Blind, Placebo-Controlled Trial of Aprotinin for Reducing Blood Loss and the Requirement for Donor-Blood Transfusion in Patients Undergoing Repeat Coronary Artery Bypass Grafting

BACKGROUND Aprotinin is a serine protease inhibitor that reduces blood loss and transfusion requirements when administered prophylactically to cardiac surgical patients. To examine the safety and dose-related efficacy of aprotinin, a prospective, multicenter, placebo-controlled trial was conducted in patients undergoing repeat coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS Two hundred eighty-seven patients were randomly assigned to receive either high-dose aprotinin, low-dose aprotinin, pump-prime-only aprotinin, or placebo. Drug efficacy was determined by the reduction in donor-blood transfusion up to postoperative day 12 and in postoperative thoracic-drainage volume. The percentage of patients requiring donor-red-blood-cell (RBC) transfusions in the high- and low-dose aprotinin groups was reduced compared with the pump-prime-only and placebo groups (high-dose aprotinin, 54%; low-dose aprotinin, 46%; pump-prime only, 72%; and placebo, 75%; overall P = .001). The number of units of donor RBCs transfused was significantly lower in the aprotinin-treated patients compared with placebo (high-dose aprotinin, 1.6 +/- 0.2 U; low-dose aprotinin, 1.6 +/- 0.3 U; pump-prime-only, 2.5 +/- 0.3 U; and placebo, 3.4 +/- 0.5 U; P = .0001). There was also a significant difference in total blood-product exposures among treatment groups (high-dose aprotinin, 2.2 +/- 0.4 U; low-dose aprotinin, 3.4 +/- 0.9 U; pump-prime-only, 5.1 +/- 0.9 U; placebo, 10.3 +/- 1.4 U). There were no differences among treatment groups for the incidence of perioperative myocardial infarction (MI). CONCLUSIONS This study demonstrates that high- and low-dose aprotinin significantly reduces the requirement for donor-blood transfusion in repeat CABG patients without increasing the risk for perioperative MI.

Platelet transfusions during coronary artery bypass graft surgery are associated with serious adverse outcomes

BACKGROUND:  Platelet (PLT) transfusions are administered in cardiac surgery to prevent or treat bleeding, despite appreciation of the risks of blood component transfusion. The current analysis investigates the hypothesis that PLT transfusion is associated with adverse outcomes associated with coronary artery bypass graft surgery (CABG).

Changes in transfusion therapy and reexploration rate after institution of a blood management program in cardiac surgical patients

A retrospective study was performed to determine the impact of a coagulation and transfusion management program on blood utilization in 1,079 sequential patients for myocardial revascularization and open ventricle or combined procedures. Four hundred and eighty-eight patients (group 1) before, and 591 patients (group 2) after institution of thromboelastography (TEG)-guided coagulation were studied and compared for transfusion requirements, donor exposure, and the incidence of reoperation for hemorrhage. Group 2 patients had a significantly lower incidence of overall transfusion (78.5% v 86.3%) during hospitalization and in total transfusion in the operating room (57.9% v 66.4%). The incidence of each transfusion subtype was also significantly lower in group 2 patients. Actual total median donor exposure was 8 in group 1 patients and 6 exposures in group 2 patients. Mediastinal reexploration for hemorrhage was 5.7% before institution of TEG-based coagulation monitoring and 1.5% in TEG-monitored patients. Use of TEG monitoring before reexploration has decreased the cost and potential risk for patients undergoing CABG surgery.

Thromboelastography as an indicator of post-cardiopulmonary bypass coagulopathies

Postoperative hemorrhage in patients undergoing open-heart surgery is a major cause of morbidity and mortality. Monitoring of coagulation in these patients has routinely involved the activated clotting time. Thromboelastography is currently used as a monitor of coagulation during liver transplantation. The thromboelastogram, by providing information on the interaction of all the coagulation precursors, gives more clinically useful information on coagulation than that available from the coagulation profile or the activated clotting time alone. This study was done to assess the usefulness of thromboelastography in open-heart surgery. Thirty-eight patients (29 undergoing coronary artery bypass grafting and 9 undergoing valve replacement) were studied with activated clotting time, thromboelastography, and coagulation profiles during three periods: before bypass, during bypass, and after protamine administration. Thromboelastography was a significantly better predictor (87% accuracy) of postoperative hemorrhage and need for reoperation than was the activated clotting time (30%) or coagulation profile (51%). Thromboelastography is easy to use and provides diagnostic data within 30 minutes of blood sampling.

Effect of pulmonary artery catheterization on outcome in patients undergoing coronary artery surgery.

Previous studies have suggested that low-risk cardiac surgical patients may be safely managed without pulmonary artery catheterization (PAC). However, no prospective studies have determined whether PAC improves outcome in higher risk patients compared with that following central venous pressure (CVP) monitoring alone. The authors prospectively examined the incidence of and factors related to perioperative morbidity and mortality in 1094 consecutive patients undergoing coronary artery surgery managed with elective PAC (n = 537) or with CVP (n = 557). Perioperative risk factors and demographics that predict morbidity and mortality after cardiac surgery were used to quantify risk classification. Outcome was judged by length of ICU stay, occurrence of postoperative myocardial infarction, in-hospital death, major hemodynamic aberrations, and significant noncardiac systemic complications. No significant differences in any outcome variables were noted in any group of patients with similar quantitative risk classification managed with or without PAC, including those in the highest risk class. In addition, there were no significant differences in outcome among the 39 patients who would have been managed with CVP monitoring only, but who subsequently developed a clinical need for PAC based on the occurrence of serious hemodynamic events compared to patients who had PAC performed electively. This study suggests that PAC does not play a major role in influencing outcome after cardiac surgery, that even high-risk cardiac surgical patients may be safely managed without routine PAC, and that delaying PAC until a clinical need develops does not significantly alter outcome, but may have an important impact on cost savings.

Does Choice of Anesthetic Agent Significantly Affect Outcome after Coronary Artery Surgery

A prospective study of 1094 consecutive adult patients undergoing coronary revascularization was undertaken to determine the effect of anesthetic technique on outcome. Patients received one of five primary techniques: high-dose fentanyl (> 50 μg/kg), moderate-dose fentanyl (<50 μg/kg), sufentanil (3

Comparison of viscoelastic measures of coagulation after cardiopulmonary bypass.

Postoperative hemorrhage remains a major cause of morbidity after cardiopulmonary bypass (CPB). Treatment remains empiric because of the need for immediate correction and the lack of availability of rapid intraoperative coagulation monitoring (except for ACT) at most institutions. Thrombelastography (TEG) and Sonoclot analysis (SCT) are measures of viscoelastic properties of blood which allow rapid intraoperative evaluation of coagulation factor and platelet activity as well as overall clot integrity from a single blood sample. Routine coagulation tests (RCT) including activated clotting time (ACT), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen level (FIB), and platelet count (PLT) were determined and compared to TEG and SCT to assess which best predicted clinical hemostasis after CPB. Forty-two patients prospectively felt to be at high risk for excessive post-CPB bleeding had blood obtained for RCT, TEG, and SCT analysis before systemic heparinization and 30 min after protamine administration. Nine of 42 patients had excessive chest tube drainage, but no reoperations were required. After CPB, mean values for RCT were normal, but there were abnormalities in TEG and SCT parameters that reflect platelet-fibrin interaction. Both TEG and SCT were 100% accurate in predicting bleeding in these nine patients and, overall, both tests were significantly better predictors of postoperative hemorrhage than RCT. We conclude that viscoelastic determinants of clot strength may be abnormal after CPB and that SCT and TEG are, therefore, more useful than RCT for the detection and management of coagulation defects associated with CPB.

Effects of Progressive Blood Loss on Coagulation as Measured by Thrombelastography

The effects of progressive blood loss on coagulation were studied in 87 adults (age 23–66 yr) undergoing a variety of operations under general anesthesia. None had preoperative alterations in coagulation or liver function and none were receiving anticoagulant or antiplatelet medication. Whole blood coagulation status was quantitated using thrombelastography (TEG). Blood samples for TEG were obtained 5 min before and 15 min after induction of anesthesia, after each increment of blood loss (EBL) equalling 5% of estimated blood volume (EBV), at the end of surgery, and 2 hr postoperatively. Patients with EBL exceeding 0.15 EBV were given packed red cells and crystalloid solution. Patients with EBL less than 0.15 EBV received only crystalloid. Thrombelastography analysis showed a trend toward increased coagulability with progressive blood loss. Two of four patients with 80% loss of EBV maintained normal to enhanced coagulation status, although the other two developed clinical and thrombelastographic evidence of coagulopathy. Thrombelastography allowed rapid intraoperative diagnosis and specific treatment of loss of platelet activity in the latter two patients. We conclude that during moderate to massive blood loss, use of supplemental fresh frozen plasma and/or platelets should be reserved for patients with documented defects in coagulation. Thrombelastography is useful for the detection and management of coagulation defects associated with intraoperative blood loss.

Progress in the development of RBC substitutes.

Volume 41, February 2001 TRANSFUSION 287 www.transfusion.org Considerable progress has been made in the development of RBC substitutes in the last decade, with several preparations advancing from the preclinical stage of testing to Phase III clinical trials. Although the primary focus has been on the development of a pharmacologic substitute that could carry and deliver oxygen (O2) in the place of banked blood, the unique properties of the RBC substitutes under study have led to the exploration of applications beyond the conventional use of RBCs in transfusions. The term “RBC substitute,” although widely used (including in medical literature databases), does not convey the diverse properties of, and potential clinical applications for, these materials. The availability of O2-carrying therapeutic agents for clinical use could have a significant impact on the practice of blood banking and transfusion medicine. This review describes the various substitutes under development and the progress that has been made in clinical trials, and considers some of the potential implications of their use. Several recent comprehensive reviews provide additional details regarding the scientific progress in developing these new products.1-6 RBCs have several unique properties. First, they contain a very high concentration of Hb and protect it from degradation, which would be rapid if the Hb were free in the plasma. Second, since Hb is contained within the cell, it does not come in direct contact with tissues, where it might otherwise release its heme and damage the tissue. Third, the intraerythrocytic environment prevents oxidation of Hb to methemoglobin, which is not capable of transporting O2 and may promote injurious oxidative reactions. 7