A phase II dose-response study of hemoglobin raffimer (Hemolink) in elective coronary artery bypass surgery

BACKGROUND: We performed this study to determine the dose-response of hemoglobin raffimer administered in conjunction with intraoperative autologous donation in patients undergoing coronary artery bypass grafting surgery. A secondary objective was to evaluate hemoglobin raffimer for reducing the incidence of allogeneic red blood cell transfusions. METHODS: This was a phase II, single-blind, multicenter, placebo-controlled, open-label study. Patients undergoing coronary artery bypass grafting with cardiopulmonary bypass and intraoperative autologous donation were randomized to receive a single dose of hemoglobin raffimer or control (10% pentastarch). Patients were sequentially enrolled in a dose block of 250, 500, 750, and 1000 mL. RESULTS: Sixty patients received hemoglobin raffimer (n = 30) or control (n = 30). Hemoglobin raffimer was well tolerated. Most (98%) adverse events were mild or moderate in severity. There was an expected dose-dependent increase in the incidence of blood pressure increases and jaundice in hemoglobin raffimer-treated patients. In a dose-pooled analysis of hemoglobin raffimer versus control, increased blood pressure (43% vs 17%), nausea (37% vs 33%), and atrial fibrillation (37% vs 17%) were the most frequently reported adverse events. All serious adverse events were considered unrelated or unlikely to be related to study drug. No hemoglobin raffimer-treated patient required an intraoperative allogeneic red blood cell transfusion, compared with 5 (17%) pentastarch-treated patients (P =.052). This advantage of hemoglobin raffimer was maintained at 24 hours after surgery (7% vs 37%; P =.010) and up to 5 days after surgery (10% vs 47%; P =.0034). CONCLUSIONS: Hemoglobin raffimer was not associated with any serious adverse events in patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass and intraoperative autologous donation in a dose-response study up to 1000 mL. Hemoglobin raffimer was effective in facilitating decreased exposure or avoidance of allogeneic red blood cell transfusions when used in conjunction with intraoperative autologous donation.     

Transfusion practice in coronary artery bypass surgery in Denmark: a multicenter audit

Transfusion rates in coronary artery bypass grafting (CABG) continue to vary substantially, although guidelines for allogeneic transfusion have been developed. In order to evaluate ongoing transfusion practices, we performed a multicenter audit in four Danish hospitals regarding the use of allogeneic blood products among patients undergoing first-time CABG. Data on patient characteristics, peri- and postoperative factors were retrieved from 600 patient records (150 records per hospital). Substantial differences were seen regarding preoperative intake of antiplatelet drugs, perioperative use of antifibrinolytic drugs, use of cardiopulmonary bypass (CPB), cross-clamp time, time on CPB, lowest hemoglobin during CPB, and number of distal anastomoses. The percentage of patients transfused with allogeneic red blood cells ranged from 30.0% to 64.2%. Several patients (12.1-42.7%) transfused with red blood cells were discharged with a hemoglobin concentration >7 mmol/l, indicating inappropriate transfusions. The relative risk of receiving an allogeneic blood transfusion was 2.1 (95% CI: 1.6-2.7) in the hospital with the highest transfusion rate, after adjustment for patient-, drug-, and procedure-related factors. Interesting differences in transfusion rates exists in Danish hospitals and these differences may reflect true variations in transfusion practices. Audits create a basis for educational efforts among surgeons and anesthesiologists to standardize transfusion practices.     

Reducing allogeneic transfusion in cardiac surgery: a randomized double-blind placebo-controlled trial of antifibrinolytic therapies used in addition to intra-operative cell salvage

Background. The transfusion of allogeneic red blood cells andallogeneic coagulation products is associated with risk to thepatient and the depletion of an increasingly scarce resource.This prospective, randomized, double-blind, placebo-controlledtrial investigated practices to avoid transfusion in patientsundergoing first-time cardiac surgery. Methods. Patients were randomized to one of three treatmentgroups: an aprotinin group, a tranexamic acid group, and a controlgroup receiving normal saline. Intra-operative cell salvagewas used for all patients. The primary outcomes were the numberof patients exposed to allogeneic red blood cells, allogeneiccoagulation products or any allogeneic transfusion (allogeneicred blood cells and/or allogeneic coagulation products). Results. Patients were 2.5 times more likely to receive anyallogeneic transfusion in the tranexamic group than in the aprotiningroup (21 patients out of 60 compared with nine out of 60, respectively).The relative risk of any allogeneic transfusion comparing aprotininwith tranexamic acid was 0.43 (95% confidence interval 0.21–0.86;P=0.019). Patients in the control group were four times morelikely to receive any allogeneic transfusion when compared withthe aprotinin group (37 patients out of 60 compared with nineout of 60, respectively). The relative risk of any allogeneictransfusion comparing aprotinin with control was 0.24 (95% confidenceinterval 0.13–0.46; P<0.001). Conclusions. When used in addition to intra-operative cell salvage,aprotinin is the most efficacious pharmacological therapy forreducing patient exposure to any allogeneic transfusion duringfirst-time cardiac surgery.     

Transfusions in patients undergoing cardiac surgery with autologous blood

PURPOSE: Determinants of allogeneic blood use in cardiac surgery include preoperative factors such as female sex, age, body weight, hematocrit and red cell volume. We verified if these variables also predicted the need for allogeneic transfusions when autologous blood is predonated. METHODS: Demographic and intraoperative variables, hemoglobin concentrations and transfusion requirements in patients undergoing cardiopulmonary bypass with autologous blood predonation were reviewed. Multivariate logistic regression and RECPAM tree-growing analyses were applied to identify the preoperative predictors of allogeneic transfusion in these patients. RESULTS: Data from 230 patients included in our autologous blood program between 1995 and 1998 were analysed. Patients undergoing complex/reoperative surgical procedures and patients over age 64yr with a low red cell volume (<2070ml) undergoing simple procedures were more likely to require allogeneic red cells. Younger patients with a low red cell volume undergoing simple procedures carried an intermediate risk. Allogeneic transfusion was avoided in 95% of patients undergoing simple procedures when red cell volume > or = 2070ml. CONCLUSIONS: In our institution, complex/reoperative surgery, low red cell volume and increased age are the main factors associated with the need for allogeneic red cell transfusion despite autologous blood predonation. Knowledge of the factors that limit the effectiveness of predonation with respect to allogeneic blood exposure should help clinicians decide which cardiac surgical patients should be included in autologous blood programs.     

The Impact of Introducing an Autologous Intraoperative Transfusion Device to a Community Hospital

The purpose of this study was to determine the benefits and disadvantages of transfusing autologous blood during abdominal aortic aneurysm (AAA) surgery at a district general hospital with an intraoperative autologous transfusion device (Haemoccel ABT 350). In this retrospective study, 128 patients underwent abdominal aortic aneurysm repair between 1992 and 1999 by a single vascular surgeon. Ninety-three patients (60 autologous and 33 allogeneic) had elective AAA repair (group A) and 25 patients (4 autologous and 21 allogeneic) had emergency AAA repair (group B). Nine group A patients (7.6%) received their own salvaged blood and no other allogeneic blood. Although the mean estimated blood loss was higher in the autologous group of patients (NS), the intraoperative autologous transfusion device did not significantly reduce allogeneic blood usage in patients who had autologous transfusion in both elective and emergency groups. There was no difference in postoperative hemoglobin and hematocrit, ICU stay or hospital stay. In this study, red cell salvage was significantly more expensive than blood bank usage (p < 0.0001), yet it did not significantly reduce the needs of allogeneic blood. We concluded that the intraoperative autologous transfusion device is underused, not cost-effective and requires formulation of local guidelines.     

Safety and preliminary efficacy of hemoglobin raffimer for patients undergoing coronary artery bypass surgery

OBJECTIVE: To evaluate the safety and preliminary efficacy of escalating doses of hemoglobin raffimer (Hemolink) with intraoperative autologous blood donation for coronary artery bypass graft (CABG) surgery. DESIGN: Randomized, controlled, single-blind phase II dose escalation trial. SETTING: Multi-institutional university setting. PARTICIPANTS: Adult patients (n = 60) undergoing elective CABG surgery. INTERVENTIONS: After induction of anesthesia, autologous whole blood was collected to achieve a hemoglobin of 7 g/dL on cardiopulmonary bypass. Patients were randomized to receive either hemoglobin raffimer (treatment) or 6% hetastarch (control) in sequential escalating dose blocks of 250 mL, 500 mL, or 750 mL. After return of autologous blood, allogeneic red blood cells were transfused according to predetermined hemoglobin triggers. MEASUREMENTS AND MAIN RESULTS: Safety parameters (vital signs, hematology, blood chemistry, coagulation, and adverse events) were monitored from randomization through week 4 postdischarge. Serious adverse events were distributed evenly between the 2 groups of patients. Elevated blood pressure was more frequent in the treatment group (16/28 mmHg v 9/32 mmHg, p = 0.036). In the group of 40 patients in the 750-mL dose block, 8 of the 18 treatment patients and 4 of the 22 control patients avoided allogeneic red blood cell transfusion (p = 0.093). Median volume of allogeneic red blood cells transfused was lower in treated subjects compared with controls (p = 0.042). CONCLUSION: Hemoglobin raffimer is well tolerated and may be effective in reducing transfusion for patients undergoing CABG surgery. Although perioperative hypertension was more frequent in the treated patients, blood pressure management prevented serious adverse sequelae. Definitive evaluation of efficacy in a larger phase III trial is warranted.     

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.     

Randomized Trial of Diaspirin Cross-linked Hemoglobin Solution as an Alternative to Blood Transfusion after Cardiac Surgery

Background: Risks associated with transfusion of allogeneic blood have prompted development of methods to avoid orreduce blood transfusions. New oxygen-carrying compounds such as diaspirin cross-linked hemoglobin (DCLHb) could enable more patients to avoid allogeneic blood transfusion.

Methods: The efficacy, safety, hemodynamic effects, and plasma persistence of DCLHb were investigated in a randomized, active-control, single-blind, multicenter study in post-cardiac bypass surgery patients. Of 1,956 screened patients, 209 were determined to require a blood transfusion and met the inclusion criteria during the 24-h post-cardiac bypass period. These patients were randomized to receive up to three 250-ml infusions of DCLHb (n = 104) or three units of packed erythrocytes (pRBCs; n = 105). Further transfusions of pRBCs or whole blood were permitted, if indicated. Primary efficacy end points were the avoidance of blood transfusion through hospital discharge or 7 days postsurgery, whichever came first, and a reduction in the number of units of pRBCs transfused during this same time period. Various laboratory, physiologic, and hemodynamic parameters were monitored to define the safety and pharmacologic effect of DCLHb in this patient population.

Results: During the period from the end of cardiopulmonary bypass surgery through postoperative day 7 or hospital discharge, 20 of 104 (19%) DCLHb recipients did not receive a transfusion of pRBCs compared with 100% of control patients (P < 0.05). The overall number of pRBCs administered during the 7-day postoperative period was not significantly different. Mortality was similar between the DCLHb (6 of 104 patients) and the control (8 of 105 patients) groups. Hypertension, jaundice/hyperbilirubinemia, increased serum glutamic oxalo-acetic transaminase, abnormal urine, and hematuria were reported more frequently in the DCLHb group, and there was one case of renal failure in each group. The hemodynamic effects of DCLHb included a consistent and slightly greater increase in systemic and pulmonary vascular resistance with associated increases in systemic and pulmonary arterial pressures compared with pRBC. Cardiac output values decreased more in the DCLHb group patients after the first administration than the control group patients. At 24 h postinfusion, the plasma hemoglobin level was less than one half the maximal level for any amount of DCLHb infused.     

Activated recombinant factor VII after cardiopulmonary bypass reduces allogeneic transfusion in complex non-coronary cardiac surgery: randomized double-blind placebo-controlled pilot study

Background. Receiving an allogeneic transfusion may be an independentpredictor of mortality for patients undergoing cardiac surgery.Furthermore, these patients utilize 15% of all donated bloodin the UK. In our unit, 80% of patients undergoing complex non-coronarycardiac surgery requiring cardiopulmonary bypass (CPB) receivean allogeneic transfusion. Activated recombinant FVII (rFVIIa)may be effective in reducing this need for transfusion. Methods. Twenty patients undergoing complex cardiac surgerywere randomized to receive rFVIIa or placebo after CPB and reversalof heparin. Results. Two patients in the rFVIIa group received 13 unitsof allogeneic red cells and coagulation products compared witheight patients receiving 105 units of allogeneic red cells andcoagulation products in the placebo group (relative risk ofany transfusion 0.26; confidence interval 0.07–0.9; P=0.037).The groups did not differ for adverse events. Conclusion. Despite major limitations (underpowered study andprone to type I error), we have shown that rFVIIa significantlyreduces the need for allogeneic transfusion in complex non-coronarycardiac surgery without causing adverse events.      

Randomized trial of diaspirin cross-linked hemoglobin solution as an alternative to blood transfusion after cardiac surgery. The DCLHb Cardiac Surgery Trial Collaborative Group

BACKGROUND: Risks associated with transfusion of allogeneic blood have prompted development of methods to avoid or reduce blood transfusions. New oxygen-carrying compounds such as diaspirin cross-linked hemoglobin (DCLHb) could enable more patients to avoid allogeneic blood transfusion. METHODS: The efficacy, safety, hemodynamic effects, and plasma persistence of DCLHb were investigated in a randomized, active-control, single-blind, multicenter study in post-cardiac bypass surgery patients. Of 1,956 screened patients, 209 were determined to require a blood transfusion and met the inclusion criteria during the 24-h post-cardiac bypass period. These patients were randomized to receive up to three 250-ml infusions of DCLHb (n = 104) or three units of packed erythrocytes (pRBCs; n = 105). Further transfusions of pRBCs or whole blood were permitted, if indicated. Primary efficacy end points were the avoidance of blood transfusion through hospital discharge or 7 days postsurgery, whichever came first, and a reduction in the number of units of pRBCs transfused during this same time period. Various laboratory, physiologic, and hemodynamic parameters were monitored to define the safety and pharmacologic effect of DCLHb in this patient population. RESULTS: During the period from the end of cardiopulmonary bypass surgery through postoperative day 7 or hospital discharge, 20 of 104 (19%) DCLHb recipients did not receive a transfusion of pRBCs compared with 100% of control patients (P < 0.05). The overall number of pRBCs administered during the 7-day postoperative period was not significantly different. Mortality was similar between the DCLHb (6 of 104 patients) and the control (8 of 105 patients) groups. Hypertension, jaundice/hyperbilirubinemia, increased serum glutamic oxalo-acetic transaminase, abnormal urine, and hematuria were reported more frequently in the DCLHb group, and there was one case of renal failure in each group. The hemodynamic effects of DCLHb included a consistent and slightly greater increase in systemic and pulmonary vascular resistance with associated increases in systemic and pulmonary arterial pressures compared with pRBC. Cardiac output values decreased more in the DCLHb group patients after the first administration than the control group patients. At 24 h postinfusion, the plasma hemoglobin level was less than one half the maximal level for any amount of DCLHb infused. CONCLUSIONS: Administration of DCLHb allowed a significant number (19%) of cardiac surgery patients to avoid exposure to erythrocytes postoperatively.     

Impact of autotransfusion after coronary artery bypass grafting on oxygen transport

Background: Autotransfusion of shed mediastinal blood after coronary artery bypass grafting (CABG) has been shown to reduce the requirement for allogeneic blood. We have previously demonstrated in non-randomized studies that the oxygen capacity of shed mediastinal blood is similar to the patient's circulating blood and better than stored allogeneic blood. Therefore, we wanted to examine the influence of autotransfusion of shed mediastinal blood on oxygen transport capacity in patients undergoing CABG.
Methods: A prospective, randomized, controlled study involving 120 patients having elective, uncomplicated CABG was performed. The autotransfusion group received transfusion of shed mediastinal blood for 18 h. Both groups received allogeneic red cells if their hemoglobin concentration decreased below 5 mmol/L. Red blood cell 2, 3-diphosphoglycerate (2, 3-DPG) was measured preoperatively and at intervals up to the hospital discharged. Hemodynamic measurements as well as blood gas and hemoglobin measurements from samples of arterial and mixed venous blood were used for calculation of oxygen transport capacity.
Results: During the autotransfusion period only 2 patients (4%) in the autotransfusion group required allogeneic blood compared to 11 patients (20%) in the control group. The 2, 3-DPG levels in the autotransfusion group were unchanged before and after autotransfusion (4.4 vs. 4.3 umol/ml erythrocyte). In the control group, 2, 3-DPG levels decreased from 4.3 to 3.9 umol/ ml erythrocyte during the same period. There were no differences in the other measured parameters for oxygen transport capacity between the groups.
Conclusion: Autotransfusion of shed mediastinal blood conserves the 2, 3-DPG level of the red blood cells, while transfusion of stored blood leads to a decrease in 2, 3-DPG levels. Autotransfusion had no effect on hemodynamic parameters, oxygen delivery or oxygen extraction.     

Platelet-rich plasma sequestration, with therapeutic platelet yields, reduces allogeneic transfusion in complex cardiac surgery

Platelet dysfunction is the most common cause of nonsurgical bleeding after cardiopulmonary bypass (CPB). We hypothesized that reinfusion of a therapeutic quantity of platelets sequestered before CPB would decrease the need for allogeneic platelet transfusion, as well as decrease bleeding and total allogeneic transfusion, in cardiac surgery patients at moderately high risk for bleeding. Fifty-five patients undergoing either reoperative coronary artery bypass (CABG) or combined CABG and valve replacement were randomized to control or platelet-rich plasma sequestration (pheresis) groups. All patients received intraoperative epsilon-aminocaproic acid infusions. There was no significant difference between groups with respect to preoperative characteristics, duration of CPB, or target postoperative hematocrit. Mean platelet yields were 6.2 +/- 2.1 units (3.1 x 10(11) platelets). Mean pheresis time was 44 min. Allogeneic platelets (range = 6-12 units) were transfused to 28% of control patients, compared with 0% of pheresis patients (P < 0.01). Allogeneic packed red blood cells were transfused to 45% of control patients (1.2 units per patient) versus 31% of pheresis patients (0. 7 unit per patient) (P = 0.35). Total allogeneic units transfused were significantly reduced in the pheresis group (P < 0.02). Mediastinal chest tube drainage was not significantly decreased in the pheresis group. In this prospective, randomized study, therapeutic platelet yields were obtained before CPB. In contrast with recent studies with low platelet yields, these data support the conclusion that platelet-rich plasma sequestration is effective in reducing allogeneic platelet transfusions and total allogeneic units transfused in cardiac surgery patients at moderately high risk for post-CPB coagulopathy and bleeding. IMPLICATIONS: Transfusion of allogeneic blood products, including platelets, is common during complex cardiac surgical procedures. In the present prospective, randomized study, a significant reduction in allogeneic platelet transfusion and total allogeneic units transfused was observed after the reinfusion of a therapeutic quantity of autologous platelets sequestered before cardiopulmonary bypass.     

Blood loss from coronary angiography increases transfusion requirements for coronary artery bypass graft surgery

OBJECTIVE: To determine the blood loss associated with coronary angiography and its impact on hemoglobin and transfusion requirements for subsequent coronary artery bypass graft (CABG) surgery. DESIGN: Retrospective chart review. SETTING: Tertiary-care, academic medical center. PARTICIPANTS: A total of 506 adult patients undergoing coronary angiography and CABG surgery. INTERVENTIONS: None (observational study). MEASUREMENTS AND MAIN RESULTS: Coronary angiography was associated with a reduction in hemoglobin of 1.8 g/dL. This reduction in hemoglobin was a significant predictor of allogeneic red blood cell transfusion. CONCLUSION: Coronary angiography contributes to a 1.8 g/dL reduction in hemoglobin concentration before CABG surgery and was associated with increased transfusion of allogeneic blood products. Measures aimed at maintaining red cell volume during coronary angiography, increasing erythropoiesis, or delaying surgery beyond 2 weeks may result in a decrease in transfusion requirements for patients undergoing CABG surgery.     

Pentastarch versus albumin in cardiopulmonary bypass prime: impact on blood loss

Background: Albumin is commonly used as a volume expander in cardiopulmonary bypass (CPB) prime. Pentastarch, a low molecular weight hetastarch, may provide similar efficacy at decreased cost but is known to alter coagulation profiles. Infectious concerns forced the temporary withdrawal of albumin in our institution. Therefore we evaluated pentastarch as an alternative with regards to perioperative hemostasis and blood loss. Methods: One hundred consecutive adult patients undergoing first-time aorto-coronary bypass were given 750 mL of 10% pentastarch (represented as P in calculations) diluted in 1000 mL of Ringer's solution added in their CPB prime. A similar control group of 100 consecutive patients had received 200 mL of 25% albumin (represented as A in calculations) diluted in 1500 mL of Ringer's solution. Results: Postoperative prothrombin time (PT) was slightly higher with pentastarch (P: 14.9 ± 1.5 seconds, A: 14.2 ± 1.3 seconds, p = 0.003). Postoperative bleeding was also increased (P: 2337 ± 1242 mL, A: 1981 ± 1121 mL, p = 0.0341, mostly because of recirculated shed mediastinal blood (P: 834 ± 499 mL, A: 640 ± 388, p = 0.002) rather than lost pleural tube blood (P: 1503 ± 821 mL, A: 1341 ± 824 mL, p = 0.16). Overall net blood loss (P: 2014 ± 914 mL, A: 2061 ± 1015, p = 0.73) was similar. Blood-product transfusion requirements and postoperative daily hematocrits did not differ. Conclusion: The diminished coagulability associated with this dose of pentastarch resulted in increased postoperative bleeding. However, with recirculation of shed mediastinal blood, there was no net increase in blood loss. In this setting, pentastarch may serve as a suitable alternative to albumin.     

Perflubron emulsion (AF0144) augments harvesting of autologous blood: a phase II study in cardiac surgery

OBJECTIVE: To assess tolerance and preliminary efficacy of a perfluorocarbon emulsion (AF0144) used with acute normovolemic hemodilution to reduce allogeneic blood transfusion for patients undergoing coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB). DESIGN: Controlled, single-blind, parallel-group phase II dose escalation trial. SETTING: Single-institution university medical center. PARTICIPANTS: Adult patients undergoing elective CABG surgery (n = 36). INTERVENTIONS: A calculated volume of autologous whole blood was harvested for each patient with a target on-bypass hematocrit of 20% to 22%. Placebo, low-dose (1.8 g/kg) AF0144, or high-dose (2.7 g/kg) AF0144 was infused. During CPB, blood was transfused at protocol-defined triggers (hematocrit <15%, PvO(2) <30 mmHg, SvO(2) <60%). After CPB, all autologous whole blood was reinfused. Allogeneic red blood cells were transfused if a trigger was reached. MEASUREMENTS AND MAIN RESULTS: Safety assessments (vital signs, hematology, blood chemistry, coagulation, and adverse events) were monitored through postoperative day 21. Efficacy endpoints included percentage of patients reaching a transfusion trigger and number of allogeneic units of red blood cells transfused. During CPB, <25% of subjects reached a transfusion trigger. During hospitalization, significantly fewer (p < 0.01) high-dose subjects (33%) reached a trigger than did control patients (91%). Allogeneic red blood cell transfusion did not differ significantly among groups. Safety assessments indicated AF0144 was well tolerated. CONCLUSION: The data suggest that AF0144 when used with acute normovolemic hemodilution is well tolerated and may be effective when used to enhance oxygen delivery for patients undergoing CABG surgery. Confirmation of safety and efficacy in a larger phase III clinical trial is warranted.     

Efficacy of a criterion-driven transfusion protocol in patients having pediatric cardiac surgery

OBJECTIVES: Low-hematocrit bypass is one technique used to prevent allogeneic transfusion during cardiopulmonary bypass. The purpose of this study is to determine the efficacy of a criterion-driven transfusion protocol and the effect of low-hematocrit bypass with moderate hypothermia in pediatric cardiac surgery. METHODS: Seventy-five children who underwent cardiopulmonary bypass with low-hematocrit bypass for repair of congenital heart disease were studied. Criteria for red blood cell transfusion included anemia with a hematocrit level of less than 15% during bypass and 20% after bypass. During cardiopulmonary bypass, venous oxygen saturation, hematocrit values, and regional cerebral oxygenation were continuously monitored. Arterial lactate levels were measured postoperatively. RESULTS: All patients had an uncomplicated perioperative course, and no perioperative death occurred. Twenty-two patients (29.3%) received a transfusion, and 53 (70.7%) patients did not. The hematocrit levels before and after modified ultrafiltration in the transfused group (21.6 +/- 5.5%, 26.6 +/- 6.5%) were significantly higher than those in the nontransfused group (18.9 +/- 3.7%, 23.1 +/- 4.1%) (P <.05). There was no significant difference between the group's arterial lactate levels immediately after admission to the intensive care unit and 1 day after the operation. The arterial lactate levels 6 hours after the admission to the intensive care unit for the nontransfused patients were higher than with the transfused patients (4.3 +/- 3.0 versus 2.5 +/- 1.5 mmol/L, (P <.05). For arterial lactate level, the relation with patients' weight had the highest correlation (R = 0.678, P <.0001). CONCLUSIONS: A criterion-driven transfusion program can be effective, and low-hematocrit bypass with a hematocrit value below 20% may affect lactate production or clearance from the body.     

Institutional variability in red blood cell conservation practices for coronary artery bypass graft surgery. Institutions of the MultiCenter Study of Perioperative Ischemia Research Group

OBJECTIVE: To assess whether substantial institutional variability exists in red blood cell conservation practices associated with coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, randomized patient enrollment and data collection. SETTING: Twenty-four U.S. academic institutions participating in the Multicenter Study of Perioperative Ischemia. PARTICIPANTS: A well-defined subset of primary CABG surgery patients (n = 713) expected to be at low risk for bleeding and exposure to allogeneic transfusion. INTERVENTIONS: None (observational study). MEASUREMENTS AND MAIN RESULTS: Frequency of use of red blood cell conservation techniques was determined among institutions. Correlation was determined between use of each technique and transfusion of allogeneic red blood cells and between use of each technique and median institutional blood loss. Significant variability (p < 0.01) was detected in institutional transfusion practice with respect to the use of predonated autologous whole blood, normovolemic hemodilution, red cell salvage, and reinfusion of shed mediastinal blood. The frequency of institutional use of these techniques was not associated with allogeneic transfusion (r2 < 0.15) or blood loss (r2 < 0.10) in the low-risk population of patients examined. CONCLUSIONS: Institutions vary significantly in perioperative blood conservation practices for CABG surgery. Further study to determine the appropriate use of these techniques is warranted.     

A simple mathematical approach to calculate blood loss in radical prostatectomy

INTRODUCTION: The aim of this study was to apply a simple mathematical approach to calculate blood loss in 126 patients undergoing radical retropubic prostatectomy (RRP). MATERIALS AND METHODS: Perioperative red blood cell loss (RBCL) was estimated by adding the difference in circulating red blood cells from before to after surgery to the allogeneic red blood cells transfused in the same period. RESULTS: Mean preoperative hematocrit was 45 +/- 4% and mean perioperative RBCL was 574 +/- 297 ml, corresponding to a mean equivalent whole blood loss (WBL) of 1,479 +/- 831 ml. Twenty of 126 patients (15.9%) received 42 units of allogeneic packed red blood cells (PRBC), for a mean of 2.1 +/- 1.2 U/patient. The transfusion rate was higher in patients with a preoperative hematocrit of 40% or less (45 vs. 13%, p = 0.014). CONCLUSIONS: Anatomical RRP is still associated with appreciable operative blood loss. Owing to the high preoperative hematocrit values, the allogeneic blood transfusion rate is low and the transfusion requirement of the majority of patients is limited to about 2 units of PRBC. Preoperative autologous blood augmentation strategies may not be routinely needed for patients with a basal hematocrit of >40%.     

Intraoperative moderate acute normovolemic hemodilution associated with a comprehensive blood-sparing protocol in off-pump coronary surgery

We evaluated the blood-sparing effects of intraoperative moderate acute normovolemic hemodilution (ANH) combined with intraoperative tranexamic acid treatment and shed blood reinfusion in patients undergoing off-pump coronary artery bypass (OPCAB). One-hundred consecutive OPCAB patients (baseline hematocrit >34%) were prospectively randomized to tranexamic acid treatment (control group; 50 patients) or to tranexamic acid treatment plus normovolemic (1:1 replacement with colloids) withdrawal of 17% +/- 2% of the circulating blood volume (ANH group; 50 patients). All patients had shed blood reinfused with intraoperative bleeding in excess of 250 mL. The requirement for allogeneic transfusions, based on strict a priori defined criteria, was the primary end point of the study. Hematochemical evaluations, bleeding, major complications, and other outcomes were also recorded. Demographics, baseline hematochemical data, and operative characteristics were similar in the two groups. Patients in the ANH group had a median of 850 mL of blood withdrawn and showed a lower intraoperative minimum hematocrit (31% vs 37%; P < 0.0001). Two patients in the ANH group versus 10 patients in the control group (odds ratio, 0.17; 95% confidence interval, 0.03-0.89; P = 0.028) required transfusion of a significantly smaller number of packed red blood cell units (5 vs 24; P < 0.001). Postoperative hematochemical variables, bleeding, and outcomes were similar in the two groups of patients. Moderate ANH, combined with tranexamic acid administration and on-demand shed blood reinfusion, may reduce allogeneic transfusion requirements in OPCAB patients. IMPLICATIONS: We studied the blood-sparing effects of moderate acute normovolemic hemodilution (ANH) in 100 patients undergoing off-pump coronary surgery (OPCAB). Combined with tranexamic acid administration and shed blood reinfusion when the intraoperative bleeding exceeded 250 mL, ANH was effective in reducing the number of OPCAB patients who required allogeneic transfusions and the number of packed red blood cell units transfused.     

Predictors of transfusion requirements for cardiac surgical procedures at a blood conservation center

BACKGROUND: Previous studies defining perioperative risk factors for allogeneic transfusion requirements in cardiac surgery were limited to highly selected cardiac surgery populations or were associated with high transfusion rates. The purpose of this study was to determine perioperative risk factors and create a formula to predict transfusion requirements for major cardiac surgical procedures in a center that practices a multimodality approach to blood conservation. METHODS: We performed an observational study on 307 consecutive patients undergoing coronary artery bypass grafting, valve, and combined (coronary artery bypass grafting and valve) procedures. An equation was derived to estimate the risk of transfusion based on preoperative risk factors using multivariate analysis. In patients with a calculated probability of transfusion of at least 5%, intraoperative predictors of transfusion were identified by multivariate analysis. RESULTS: Thirty-five patients (11%) required intraoperative or postoperative allogeneic transfusions. Preoperative factors as independent predictors for transfusions included red blood cell mass, type of operation, urgency of operation, number of diseased vessels, serum creatinine of at least 1.3 mg/dL, and preoperative prothrombin time. Intraoperative factors included cardiopulmonary bypass time, three or fewer bypass grafts, lesser volume of acute normovolemic hemodilution removed, and total crystalloid infusion of at least 2,500 mL. The derived formula was applied to a validation cohort of 246 patients, and the observed transfusion rates conformed well to the predicted risks. CONCLUSIONS: A multimodality approach to blood conservation in cardiac surgery resulted in a low transfusion rate. Identifying patients' risks for transfusion should alter patient management perioperatively to decrease their transfusion rate and make more efficient use of blood resources.