The effect of SANGUINATE® (PEGylated carboxyhemoglobin bovine) on cardiopulmonary bypass functionality using a bovine whole blood model of normovolemic hemodilution.

BACKGROUND: Cardiac surgery using cardiopulmonary bypass carries a high risk of bleeding and need for blood transfusion. Blood administration is associated with increased rates of morbidity and mortality. Perioperatively, strategies are often employed to reduce blood transfusions in high-risk patients or in situations where blood transfusion is contraindicated. Normovolemic hemodilution is a blood conservation technique used during cardiac surgery that involves replacement of blood with fluids. SANGUINATE® (PEGylated carboxyhemoglobin bovine) is a novel hemoglobin-based oxygen carrier that can deliver oxygen effectively to tissues in the presence of severe hypoxia. The use of a hemoglobin-based oxygen carrier during hemodilution may augment tissue oxygen delivery and reduce blood transfusion. METHODS: Six standardized cardiopulmonary bypass runs simulating normovolemic hemodilution using varying proportions of bovine whole blood and SANGUINATE were performed. Pump speed, flow rate, line pressures, hemoglobin concentration, oxygenation, and degree of anticoagulation were assessed at regular intervals. Membrane oxygenators and arterial line filters were inspected for evidence of clotting following each run. RESULTS: Increases in the pressure drop across the membrane oxygenator were detected during runs 5 and 6. Median activated clotting time values were able to be maintained at goal during the runs, and SANGUINATE did not appear to be thrombogenic. Hemoglobin concentration decreased following the addition of SANGUINATE. Oxygenation was maintained during all runs that included SANGUINATE. CONCLUSION: SANGUINATE does not impact the performance of the cardiopulmonary bypass circuit in a bovine whole blood model. The results support further evaluation of SANGUINATE in the setting of normovolemic hemodilution and cardiopulmonary bypass.

Society of Cardiovascular Anesthesiologists Clinical Practice Improvement Advisory for Management of Perioperative Bleeding and Hemostasis in Cardiac Surgery Patients.

Bleeding after cardiac surgery is a common and serious complication leading to transfusion of multiple blood products and resulting in increased morbidity and mortality. Despite the publication of numerous guidelines and consensus statements for patient blood management in cardiac surgery, research has revealed that adherence to these guidelines is poor, and as a result, a significant variability in patient transfusion practices among practitioners still remains. In addition, although utilization of point of care coagulation monitors and the use of novel therapeutic strategies for perioperative hemostasis, such as the use of coagulation factor concentrates, has increased significantly over the last decade, they are still not widely available in every institution. Therefore, despite continuous efforts, blood transfusion in cardiac surgery has declined only modestly over the last decade, remaining at 50% or greater in high-risk patients. Given these limitations and in response to new regulatory and legislature requirements, the Society of Cardiovascular Anesthesiologists has formed the Blood Conservation in Cardiac Surgery Working Group in order to organize, summarize, and disseminate the available best-practice knowledge in patient blood management in cardiac surgery. The current publication includes the summary statements and algorithms designed by the working group, after collection and review of the existing guidelines, consensus statements, and recommendations for patient blood management practices in cardiac surgery patients. The overall goal is creating a dynamic resource of easily accessible educational material that will help to increase and improve compliance with the existing evidence-based best practices of patient blood management by cardiac surgery care teams.

Society of Cardiovascular Anesthesiologists Clinical Practice Improvement Advisory for Management of Perioperative Bleeding and Hemostasis in Cardiac Surgery Patients.

Bleeding after cardiac surgery is a common and serious complication leading to transfusion of multiple blood products and resulting in increased morbidity and mortality. Despite the publication of numerous guidelines and consensus statements for patient blood management in cardiac surgery, research has revealed that adherence to these guidelines is poor, and as a result, a significant variability in patient transfusion practices among practitioners still remains. In addition, although utilization of point-of-care (POC) coagulation monitors and the use of novel therapeutic strategies for perioperative hemostasis, such as the use of coagulation factor concentrates, have increased significantly over the last decade, they are still not widely available in every institution. Therefore, despite continuous efforts, blood transfusion in cardiac surgery has only modestly declined over the last decade, remaining at ≥50% in high-risk patients. Given these limitations, and in response to new regulatory and legislature requirements, the Society of Cardiovascular Anesthesiologists (SCA) has formed the Blood Conservation in Cardiac Surgery Working Group to organize, summarize, and disseminate the available best-practice knowledge in patient blood management in cardiac surgery. The current publication includes the summary statements and algorithms designed by the working group, after collection and review of the existing guidelines, consensus statements, and recommendations for patient blood management practices in cardiac surgery patients. The overall goal is creating a dynamic resource of easily accessible educational material that will help to increase and improve compliance with the existing evidence-based best practices of patient blood management by cardiac surgery care teams.

Noninvasive Continuous Hemoglobin Monitoring: Role in Cardiovascular Surgery.

Blood transfusions in the operating room are associated with increased morbidity and mortality as well as increased cost. The technology exists for continuous noninvasive hemoglobin monitoring (SpHb), which could allow for the rapid diagnosis and treatment of acute blood loss anemia secondary to surgical bleeding. However, the accuracy of this technology has been called into question. SpHb in the operating room could reduce cost by decreasing lab draws, unnecessary transfusions, and the morbidity associated with blood transfusions. This review examines the accuracy of noninvasive hemoglobin monitoring as well as the role it may play in the operating room.

Perfluorocarbons: Knowledge Gained From Clinical Trials.

Research into potential use of perfluorocarbons for liquid ventilation and as oxygen delivery agents in humans has been underway since the 1960s. While partial liquid ventilation with perfluorocarbons showed promise in animal models and early human investigation, randomized controlled human trials failed to show benefit and an elevated rate of adverse events. Initial approval of Fluosol-DA (Green Cross Corporation, Osaka, Japan) by the United States Food and Drug Administration as an oxygen delivery agent for use in high-risk coronary angioplasty represents the only approved application of these compounds to supplement tissue oxygenation, but the compound was rendered obsolete and removed from the market with the development of advanced angioplasty catheters in the 1990s. Second-generation perfluorocarbons were developed with a higher capacity to increase the amount of oxygen dissolved in the fluid phase of blood. Early clinical trials of perflubron emulsion in non-cardiac and cardiac surgery were promising, but dose restriction and the requirement for high inspired oxygen concentration to maximize oxygen delivery for prolonged periods of time limited the clinical utility as a replacement for the oxygen carrying capacity of red blood cells. Identification of excess serious adverse events in treated patients resulted in discontinuation of pivotal clinical trials. Continued research investigating different formulations of perfluorocarbons has shown promise in animal studies, but continued research is necessary to prove safety and efficacy in humans.

Comparison of visually estimated blood loss with direct hemoglobin measurement in multilevel spine surgery.

BACKGROUND: Estimates of blood loss in the operating room are typically performed as a visual assessment by providers, despite multiple studies showing this to be inaccurate. Use of a less subjective measurement of blood loss such as direct measurement of the hemoglobin (Hb) mass lost from the surgical field may better quantify surgical bleeding. The objective of this investigation was to compare anesthesiologist estimates of intraoperative blood loss with measured Hb loss. STUDY DESIGN AND METHODS: Sixty patients undergoing posterior spine surgery were enrolled in a prospective, randomized trial comparing intraoperative blood loss using unipolar cautery alone or with use of a bipolar tissue sealant device. Hb concentration and fluid volume were measured from all surgical sponges, suction canisters, and the cell salvage device. Using the volume and concentration of Hb from each solution allowed calculation of Hb mass, which was converted into volume of blood lost and compared with estimates of blood loss documented by the anesthesia team. A single-sample t test of no difference was used to compare estimated with measured blood loss. RESULTS: Mean estimated blood loss exceeded measured blood loss by 246 mL (860 mL vs. 614 mL, p < 0.0001). CONCLUSION: Estimated blood loss exceeded measured blood loss by 40% on average. The likely etiology of this discrepancy relates to the inability to visually determine Hb concentration of sanguineous solutions in suction canisters and surgical sponges. Ramifications of excessive bleeding estimates include unnecessary transfusion and overadministration of intravenous fluids, both of which may have deleterious effects.

Bipolar tissue sealant device decreases hemoglobin loss in multilevel spine surgery.

BACKGROUND: Traditional techniques for obtaining hemostasis during orthopedic surgery, such as conventional electrocautery and sealants, have limited clinical effectiveness in reducing hemoglobin (Hb) loss and requirement for transfusion. The bipolar tissue sealant device studied in this trial combines radiofrequency energy with saline irrigation to hemostatically seal both cut bone and soft tissue, potentially aiding hemostasis. STUDY DESIGN AND METHODS: Sixty patients undergoing multilevel posterior lumbar instrumentation and fusion were randomly assigned to unipolar cautery alone (control group) or unipolar cautery plus use of the bipolar tissue sealant device (treatment group). Hb loss from the surgical field was measured (rather than estimated) and compared between the two groups. The primary hypothesis was that the treatment group would lose significantly less Hb than the control group. RESULTS: The control group experienced a mean Hb loss of 102.4 g while the treatment group showed a significantly lower mean Hb loss of 66.2 g (p = 0.0004). No significant difference was found between groups with respect to secondary endpoints including length of surgery, number of red blood cell units transfused, number of total blood component units transfused, transfusion avoidance, length of stay, or serious adverse events. CONCLUSION: Use of a bipolar tissue sealant device in addition to unipolar cautery significantly decreased Hb loss during multilevel, posterior lumbar spinal instrumentation and fusion when compared with unipolar cautery alone.

Hepatic parenchymal transection with vascular staplers: a comparative analysis with the crush-clamp technique.

BACKGROUND: This retrospective study compares the safety and efficacy of hepatic parenchymal transection using vascular staplers (VS) and the crush-clamp (CC) technique. METHODS: Demographics, clinicopathologic data, treatments, and postoperative outcomes from patients who underwent VS or CC hepatic parenchymal transection were compared. RESULTS: From 1996-2006, 99 and 112 patients underwent hepatic transection with VS and CC, respectively. Compared to CC, VS transection was associated with less operative time (median 210 vs 275 minutes), blood loss (median 250 vs 500 mL), and postoperative red blood cell (RBC) transfusion (29% vs 44%), all P < .05. VS transection was not associated with RBC transfusion on multivariate analysis. There were no differences in rates of positive resection margins (9% vs 13%), postoperative mortality (2% vs 4%), overall morbidity (32% vs 29%), and severe morbidity (20% vs. 23%), all P > .05. CONCLUSION: Hepatic parenchymal transection with VS can be accomplished with similar safety and efficacy as CC transection.

Addition of bevacizumab to irinotecan- and oxaliplatin-based preoperative chemotherapy regimens does not increase morbidity after resection of colorectal liver metastases.

BACKGROUND: Although commonly used in combination with irinotecan or oxaliplatin (iri/oxal) for treatment of colorectal liver metastases before extirpation, the effects of preoperative bevacizumab on surgical outcomes are not established. The objective of this retrospective study was to determine if addition of bevacizumab to iri/oxal preoperative chemotherapy increases morbidity after hepatic resection. STUDY DESIGN: We compared demographics, clinicopathologic data, treatments, and postoperative outcomes between patients given preoperative iri/oxal with and without bevacizumab and patients who underwent hepatic resection within and after 8 weeks from the last dose of bevacizumab. RESULTS: From 1996 to 2006, 96 patients were treated with preoperative iri/oxal; 39 (40.6%) received concurrent bevacizumab. Preoperative bevacizumab treatment was associated with less blood loss (median 425 mL versus 600 mL, p=0.01) and lower RBC transfusion rates (43.9% versus 23.1%, p=0.06) after partial hepatectomy on univariable analysis. Only age>or=70 years (hazard ratio=8.52, 95% CI [2.00 to 36.45]) and concurrent extrahepatic procedures (hazard ratio=4.12, 95% CI [1.49 to 11.39]) independently predicted RBC transfusion and overall complications, respectively. There were no differences in overall (43.6% versus 38.6%), severe (28.2% versus 24.6%), hepatic (17.9% versus 26.3%), wound (10.3% versus 7%), or thromboembolic or bleeding (2.6% versus 5.3%) complications (all p > 0.05). For patients treated with iri/oxal and bevacizumab, overall complications were more common when resection was performed within 8 weeks after the last bevacizumab dose (62.5% versus 30.4%), but this difference was not statistically significant (p=0.06). CONCLUSIONS: If discontinued at least 8 weeks before hepatic resection, addition of bevacizumab to preoperative iri/oxal does not increase morbidity after hepatic resection.

Effects of extreme hemodilution during cardiac surgery on cognitive function in the elderly.

BACKGROUND: Strategies for neuroprotection including hypothermia and hemodilution have been routinely practiced since the inception of cardiopulmonary bypass. Yet postoperative neurocognitive deficits that diminish the quality of life of cardiac surgery patients are frequent. Because there is uncertainty regarding the impact of hemodilution on perioperative organ function, the authors hypothesized that extreme hemodilution during cardiac surgery would increase the frequency and severity of postoperative neurocognitive deficits. METHODS: Patients undergoing coronary artery bypass grafting surgery were randomly assigned to either moderate hemodilution (hematocrit on cardiopulmonary bypass >or=27%) or profound hemodilution (hematocrit on cardiopulmonary bypass of 15-18%). Cognitive function was measured preoperatively and 6 weeks postoperatively. The effect of hemodilution on postoperative cognition was tested using multivariable modeling accounting for age, years of education, and baseline levels of cognition. RESULTS: After randomization of 108 patients, the trial was terminated by the Data Safety and Monitoring Board due to the significant occurrence of adverse events, which primarily involved pulmonary complications in the moderate hemodilution group. Multivariable analysis revealed an interaction between hemodilution and age wherein older patients in the profound hemodilution group experienced greater neurocognitive decline (P = 0.03). CONCLUSIONS: In this prospective, randomized study of hemodilution during cardiac surgery with cardiopulmonary bypass in adults, the authors report an early termination of the study because of an increase in adverse events. They also observed greater neurocognitive impairment among older patients receiving extreme hemodilution.

Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline.

BACKGROUND: A minority of patients having cardiac procedures (15% to 20%) consume more than 80% of the blood products transfused at operation. Blood must be viewed as a scarce resource that carries risks and benefits. A careful review of available evidence can provide guidelines to allocate this valuable resource and improve patient outcomes. METHODS: We reviewed all available published evidence related to blood conservation during cardiac operations, including randomized controlled trials, published observational information, and case reports. Conventional methods identified the level of evidence available for each of the blood conservation interventions. After considering the level of evidence, recommendations were made regarding each intervention using the American Heart Association/American College of Cardiology classification scheme. RESULTS: Review of published reports identified a high-risk profile associated with increased postoperative blood transfusion. Six variables stand out as important indicators of risk: (1) advanced age, (2) low preoperative red blood cell volume (preoperative anemia or small body size), (3) preoperative antiplatelet or antithrombotic drugs, (4) reoperative or complex procedures, (5) emergency operations, and (6) noncardiac patient comorbidities. Careful review revealed preoperative and perioperative interventions that are likely to reduce bleeding and postoperative blood transfusion. Preoperative interventions that are likely to reduce blood transfusion include identification of high-risk patients who should receive all available preoperative and perioperative blood conservation interventions and limitation of antithrombotic drugs. Perioperative blood conservation interventions include use of antifibrinolytic drugs, selective use of off-pump coronary artery bypass graft surgery, routine use of a cell-saving device, and implementation of appropriate transfusion indications. An important intervention is application of a multimodality blood conservation program that is institution based, accepted by all health care providers, and that involves well thought out transfusion algorithms to guide transfusion decisions. CONCLUSIONS: Based on available evidence, institution-specific protocols should screen for high-risk patients, as blood conservation interventions are likely to be most productive for this high-risk subset. Available evidence-based blood conservation techniques include (1) drugs that increase preoperative blood volume (eg, erythropoietin) or decrease postoperative bleeding (eg, antifibrinolytics), (2) devices that conserve blood (eg, intraoperative blood salvage and blood sparing interventions), (3) interventions that protect the patient's own blood from the stress of operation (eg, autologous predonation and normovolemic hemodilution), (4) consensus, institution-specific blood transfusion algorithms supplemented with point-of-care testing, and most importantly, (5) a multimodality approach to blood conservation combining all of the above.

Efficacy of single-dose, multilevel paravertebral nerve blockade for analgesia after thoracoscopic procedures.

BACKGROUND: Although video-assisted thoracoscopic surgery for pulmonary resection is increasingly chosen over thoracotomy, the optimal analgesia regimen for thoracoscopy is unknown. The purpose of this trial was to compare the efficacy of analgesia from preoperative bupivacaine paravertebral nerve blockade with that from placebo injections. METHODS: Eighty adult patients undergoing unilateral thoracoscopic procedures were enrolled in a prospective, double-blinded, randomized clinical trial of preoperative, multilevel, single-dose paravertebral nerve blockade. Patients received six paravertebral injections with 5 ml of either 0.5% bupivacaine with 0.0005% epinephrine (treated, n = 40) or preservative-free saline (control, n = 40). Cumulative weight-adjusted intraoperative fentanyl and postoperative patient-controlled morphine usage, visual analog pain scores, and spirometry were used to compare efficacy of analgesia between groups. RESULTS: The treated group received significantly less intraoperative fentanyl compared with the control group (P = 0.003) and had a 31% smaller cumulative patient-controlled morphine dose (P = 0.03) in the 6 h after block placement. Within 6 h, treated patients also reported lower maximum pain scores (P = 0.02) and demonstrated less pain score variability (P = 0.01). No statistically significant difference in cumulative morphine usage existed at 12 or 18 h after block placement. No significant difference in spirometry, cortisol levels, or cytokine production was found between treatments. CONCLUSIONS: Single-dose paravertebral nerve blockade with bupivacaine is effective in reducing pain after thoracoscopic surgery, but only during the first 6 h after nerve blockade. Because of the limited duration of effect with currently available local anesthetic agents, the current data suggest that, at present, this technique is not indicated in the setting of thoracoscopic surgery.

Cerebral physiology of cardiac surgical patients treated with the perfluorocarbon emulsion, AF0144.

BACKGROUND: Perfluorooctyl bromide is a biologically inert compound with short biologic retention and high oxygen solubility. The purpose of this study was to assess the effect of the perfluorocarbon emulsion, AF0144 (Perflubron, Alliance Pharmaceutical Corp, San Diego, CA), used in conjunction with acute normovolemic hemodilution on cerebral blood flow and cerebral emboli measurements during coronary artery bypass grafting with cardiopulmonary bypass. METHODS: Thirty-six adult cardiac surgical patients were enrolled in a single-institution, randomized, controlled, single-blind dose escalation trial. Autologous whole blood was harvested from each patient to target an on-bypass hematocrit of 20% to 22%. Placebo, low dose (1.8 g/kg) or high dose (2.7 g/kg) AF0144 was administered. Transcranial Doppler ultrasonography was used to quantitate cerebral emboli and xenon-133 clearance was used to measure cerebral blood flow. RESULTS: Cerebral blood flow was increased in both AF0144-treated groups compared with placebo (p = 0.006, low dose vs control; p = 0.036, high dose vs control). Numbers of cerebral emboli were greater in the high-dose AF0144-treated group versus control during the time periods from aortic cannulation through aortic cross-clamp placement (p = 0.026) and from aortic cross-clamp placement through cross-clamp removal (p = 0.008). CONCLUSIONS: The perfluorocarbon emulsion, AF0144, increased cerebral blood flow during cardiopulmonary bypass. In addition, total cerebral emboli load during bypass was greater in patients receiving high-dose AF0144.

Use of hemoglobin raffimer for postoperative life-threatening anemia in a Jehovah's Witness.

PURPOSE: To describe the successful treatment of acute, life-threatening anemia with the oxygen therapeutic agent, hemoglobin (Hb) raffimer. CLINICAL FEATURES: A 53-yr-old female Jehovah's Witness developed severe anemia following total hip replacement. Due to prior patient directive, red blood cells were not transfused. Tachycardia, hypotension, electrocardiographic abnormalities and mental status changes developed with a nadir Hb concentration of 3.2 g x dL(-1). Hb raffimer is a purified, cross-linked, human Hb solution developed as a substitute for red blood cell Hb. After obtaining informed consent as well as Food and Drug Administration and Institutional Review Board approval for compassionate use, 2 L of Hb raffimer (Hemolink, Hemosol, Inc., Toronto, ON, Canada) were administered along with ferrous sulfate and epoetin alfa therapy. The patient's Hb level rose to 5.5 g x dL(-1) with resolution of symptoms. To allow recovery of red blood cell mass while maintaining Hb level > 4.5 g x dL(-1), additional 1000 mL doses of Hb raffimer were administered on postoperative days three, five and seven (total dose = 500 g Hb). The patient developed no serious adverse events related to treatment with Hb raffimer. By postoperative day 14, the patient's Hb level increased to 6.5 g x dL(-1) with a hematocrit of 23%. The patient was discharged. CONCLUSIONS: Use of Hb raffimer as a bridge to recovery of this patient's red blood cell mass may have prevented adverse clinical outcome. Because this product is a purified Hb solution devoid of other cellular components, it may be accepted as therapy by patients who, due to religious conviction, refuse allogeneic red blood cell transfusion.

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.

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.