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Ann Thorac Surg 1998;65:125-136
© 1998 The Society of Thoracic Surgeons
Departments of Cardiothoracic Surgery and Anesthesiology, The New York Hospital–Cornell Medical Center, New York, New York, USA
Department of Cardiothoracic Surgery, Albert Einstein College of Medicine, New York, New York, USA
Accepted for publication July 10, 1997.
Dr Rosengart, Department of Cardiothoracic Surgery, Cornell University Medical College, 525 E 68th St, New York, NY 10021.
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Abstract |
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 Top Abstract IntroductionMaterial and MethodsResultsCommentAcknowledgmentsAppendix 1Appendix 2Appendix 3References |
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Methods. One hundred consecutive patients undergoing coronary artery bypass grafting were prospectively enrolled in a risk factor–based multimodality blood conservation program (MMD group). To evaluate the relative efficacy and safety of this comprehensive approach, comparison was made with a similar group of 90 patients undergoing coronary artery bypass grafting to whom the multimodality blood conservation program was not applied but in whom an identical set of transfusion guidelines was enforced (control group). To evaluate the cost effectiveness of the multimodality program, comparison was also made between patients in the MMD group and a consecutive series of contemporaneous, diagnostic-related group–matched patients.
Results. One hundred consecutive patients in the MMD group underwent coronary artery bypass grafting without allogeneic transfusion. This compared favorably with the control population in whom a mean of 2.2 ± 6.7 units of allogeneic blood was transfused per patient (34 patients [38%] received transfusion). In addition, the volume of postoperative blood loss at 12 hours in the control group was almost double that of the MMD group (660 ± 270 mL versus 370 ± 180 mL [p < 0.001]). Total costs for the MMD group in each of the three major diagnostic-related groups were equivalent to or significantly less than those in the consecutive series of diagnostic-related group–matched patients.
Conclusions. Comprehensive risk factor–based application of multiple blood conservation measures in an optimized, integrated, and algorithmic manner can significantly decrease bleeding and need of allogeneic transfusion in coronary artery bypass grafting in a safe and cost-effective manner.
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Introduction |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsAppendix 1Appendix 2Appendix 3References |
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The need to avoid transfusion in Jehovah’s Witnesses undergoing complex open-heart operations led us [6] to develop a comprehensive multimodality approach to cardiac surgical blood conservation. The successful implementation of this program in this specific population encouraged us to extend the approach to the general cardiac surgical population. To achieve the increasingly important goals of cost and resource efficiency, however, this extension required a fundamental alteration in strategy. It was clear that rather than comprehensive application of all measures to all patients, selective algorithmic application of measures on the basis of patient risk factors for transfusion was required. Such a selective approach was particularly important in regard to the appropriate utilization of the newer and more expensive pharmacologic agents such as erythropoietin and aprotinin.
To judge the efficacy of this selective but comprehensive approach, we prospectively applied a risk factor–based multimodality algorithm to 100 consecutive patients undergoing primary coronary artery bypass grafting (CABG) (MMD group). To assess the effects of this comprehensive blood conservation algorithm on bleeding, transfusion reduction, and safety, we compared the results with those achieved in a similar group of patients to whom an identical set of transfusion guidelines was applied but in whom a more limited set of blood conservation measures was used (control group). To assess cost efficiency, we compared total hospital costs incurred by the MMD group with those in a consecutive series of diagnostic-related group (DRG)–matched patients undergoing CABG at our institution during the period immediately preceding initiation of the MMD protocol.
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Material and Methods |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsAppendix 1Appendix 2Appendix 3References |
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Preoperative Period
On admission to the hospital, oral iron therapy (iron sulfate, 325 mg orally four times a day) was begun. Vitamin C (500 mg orally twice a day) was given concurrently to aid in absorption of iron (in its reduced ferric form) from the gut. Colace (docusate sodium) (300 mg orally once a day), folic acid (1 mg orally once a day), and vitamin B12 (1 mg orally once per day) were administered as well. For patients with a preoperative hematocrit of 35% or less, a red cell mass of less than 1,600 mL, or both, a regimen of high-dose recombinant erythropoietin (Procrit; Ortho Biotech, Raritan, NJ) was begun as previously described [6][7]. This was given as an initial combined intravenous and subcutaneous induction dose (300 U/kg intravenously, 500 U/kg subcutaneously) and then continued subcutaneously (500 U/kg every other day) until the time of operation. Because of time constraints and administrative complexity, patients admitted within 4 hours of the operation (including "same-day surgery") with hematocrit or red blood cell mass indices meeting the criteria for erythropoietin use were excluded from the study (5 patients).
Aspirin use was discontinued 5 days before the operation whenever possible. Pediatric blood collection tubes were used for all laboratory tests, the number of which was minimized. Preoperative crystalloid use was minimized to help avoid unnecessary hemodilution.
Intraoperative Period
A peripheral arterial line was placed and a baseline hematocrit was obtained on the patient’s arrival in the operating room (OR). A 9.0F wide-bore side-port catheter (Arrow International Inc, Reading, PA) was inserted in the internal jugular vein, and intraoperative autologous blood collection (intraoperative autologous donation [IAD]) was initiated. The volume of blood withdrawn was calculated using two equations that take into consideration the patient’s estimated blood volume (determined using a height-weight-sex nomogram), the cardiopulmonary bypass (CPB) circuit prime volume, the initial hematocrit value obtained in the OR, and a target hematocrit during CPB of 18% (Appendix 1) as described previously [8]. The calculated blood volume was then removed by gravity into standard citrate-phosphate-dextrose (CPDA-1) collection bags (Baxter Healthcare Corp, Deerfield, IL). Bags were filled while resting on an electronic scale to ensure proper filling and maintenance of the proper ratio of blood to citrate-phosphate-dextrose (450 g of blood per bag). Blood was stored with gentle agitation at room temperature (25°C) until the time of infusion. Systolic blood pressure was maintained higher than 95 mm Hg during the blood collection period with simultaneous crystalloid infusion through a distal pulmonary artery catheter port or peripheral line, typically in a 1.5–2:1 ratio of crystalloid to blood removed. As in the preoperative period, unnecessary crystalloid use was avoided. Crystalloid infusion was augmented by 
-adrenergic agent support (phenylephrine, 0.1 mg bolus injections) when hemodynamically indicated.
A half Hammersmith Hospital regimen of aprotinin (Trasylol; Bayer, New Haven, CT) (initial 1 million KIU or 140 mg bolus over 15 minutes, 1 million units added to the pump prime, 250,000 KIU/h or 35 mg continuous infusion) was administered to patients who met criteria for increased bleeding risk (aspirin <5 days preoperatively, heparin <48 hours preoperatively). Aprotinin infusion was begun after an initial test dose and after collection of the full IAD blood volume to avoid introduction of aprotinin into the blood collection bags [9]. Aprotinin infusion was continued after CPB until return of all IAD and intraoperatively salvaged blood had been accomplished.
The CPB circuit included a hollow-fiber membrane oxygenator (Capiox SX; Terumo Inc, Tokyo, Japan) and either a roller pump (COBE Laboratories, Inc, Lakewood, CO) or centrifugal pump (Bio-Medicus, Eden Prairie, MN). The circuit was primed with 1,400 mL of a crystalloid-colloid solution (100 mL of 25% albumin, 0.3 mg/kg of mannitol, 1,100 mL of crystalloid). Patients were anticoagulated with heparin sulfate, either 3 mg/kg (nonaprotinin patients) or 4 mg/kg (aprotinin patients) after IAD removal but before CPB. The activated clotting time was checked every 15 minutes during CPB, and additional heparin was administered as needed to maintain an activated clotting time of at least 480 seconds in nonaprotinin patients and 750 seconds in aprotinin patients. Aprotinin patients received an additional fixed heparin dose 50 minutes after initiation of CPB (1 mg/kg) and an additional fixed dose (0.5 mg/kg) every 30 minutes thereafter.
Retrograde autologous priming of the CPB circuit, whereby blood from the patient’s body was used (by retrograde drainage through the arterial and venous cannulas) to displace the crystalloid circuit prime immediately prior to initiation of CPB, was performed to a maximum displaced volume of 1,100 mL, as previously described [10]. Intraoperative salvage was performed continuously throughout the bypass run using a centrifugal salvage device (Haemonetics Corp, Braintree, MA).
All autologous and allogeneic blood products were transfused according to a specific set of transfusion guidelines (Appendix 2). Briefly, these guidelines first required that all available red blood cells from the centrifugal salvage device be returned for a hematocrit of 15% or lower during CPB. If this volume was judged insufficient or repeat hematocrit remained 15% or lower, one-unit aliquots of IAD blood were returned as necessary to restore the hematocrit to higher than 15%. During separation from CPB, the remaining CPB circuit whole blood was returned to the patient as permitted by hemodynamic considerations. Immediately after separation from CPB and reversal of heparin with protamine sulfate (2 mg/kg) infusion of IAD blood was initiated through a blood-warming device at 38°C (Hot Line; Level 1, Inc, Rockland, MA). Infusion of this blood was completed within 20 to 30 minutes after CPB and was immediately followed by the remainder of the residual circuit blood, which was processed through the centrifugal cell salvage device. After this period of rapid autologous blood infusion, the hematocrit was immediately checked, and allogeneic packed red blood cells were transfused for a hematocrit of 19% or less.
A shed mediastinal blood reinfusion bag (Pleur-evac ATS; Deknatel Inc, Fall River, MA) was attached to the mediastinal chest tube immediately after tube placement, and a second blood-collection bag was attached to the pleural tube if major pleural drainage developed.
All patients were warmed to more than 36°C before separation from CPB, and patient temperature was maintained during the intraoperative period after CPB through the use of warming blankets placed below the patient, aggressive room warming, and warming of all infused fluids to 38°C, when possible.
Postoperative Period
On arrival in the postoperative intensive care unit, patients were placed on a liquid warming blanket and immediately covered with a convection-air warming blanket. Shed mediastinal blood from the Pleur-evac ATS was returned to all patients every 3 hours until the 3-hour collected volume dropped to less than 100 mL. Crystalloid and colloid use was minimized to decrease unnecessary hemodilution, and all fluids were given through a warming device at 38°C. A specific transfusion protocol based on the rate and magnitude of blood loss as well as clinical considerations was applied to all patients with excessive postoperative blood loss (Appendix 3; see Appendix 2). According to this protocol, hemostatic blood products were ordered but given only for persistent bleeding unaffected by associated supportive measures such as patient warming, blood pressure control, positive end-expiratory pressure, 
-aminocaproic acid (Amicar) (only patients without aprotinin), desmopressin acetate (patients with renal insufficiency), and early return to the OR for suspected surgical bleeding.
A repeat induction dose of erythropoietin was given on arrival in the intensive care unit if the 8-hour postoperative hematocrit was less than 24%, with continued subcutaneous doses on postoperative days 2 and 5. Erythropoietin was continued thereafter only if the patient’s hematocrit was less than 25%. Erythropoietin therapy was also begun postoperatively empirically in any patient requiring reoperation for postoperative bleeding or extended mechanical ventricular support. Blood loss through laboratory sampling was minimized by using pediatric blood tubes, returning all arterial line flushes, and minimizing laboratory sampling.
Data Collection and Analysis
A series of 85 demographic and preoperative, intraoperative, and postoperative variables was assessed for all patients enrolled in the protocol. Hematocrit and platelet count were measured on admission and then serially until the time of discharge. Postoperative bleeding was quantified by the volume of chest tube drainage. Major perioperative events (eg, stroke, new-onset atrial fibrillation, and respiratory failure) were recorded.
To judge the relative efficacy and safety of the multimodality program, data collected from the 100 patients in the MMD group were compared with those obtained from 90 consecutive patients in whom primary CABG was performed in the period March to June 1994 (control group). Compared with the MMD group, important characteristics of this control group included the use of an identical set of selection criteria, the application of an identical set of transfusion guidelines, provision of care by the same set of cardiac surgeons and anesthesiologists, and the use of a more limited but specific set of blood conservation measures (small-to moderate-volume IAD, standard-volume CPB circuit, intraoperative Cell Saver salvage, and shed mediastinal blood reinfusion) (Table 3). The MMD and control groups were compared in respect to all established risk factors for transfusion as well as several other potentially important variables. Outcomes were analyzed in respect to allogeneic transfusion requirement, postoperative bleeding, perioperative hematocrit and platelet counts, and multiple variables delineating safety and efficacy.
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All data were analyzed using analysis of variance, Student’s t test, 
2 test, and Fisher’s exact test where applicable. Results are expressed as either the percentage of the total or the mean ± the standard deviation.
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Results |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsAppendix 1Appendix 2Appendix 3References |
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One (1%) patient in the MMD group was returned to the OR for bleeding (surgical source) versus 2 patients (2%) in the control group (one surgical source, one nonsurgical source). The mean postoperative chest tube drainage volume was significantly less at all time points in the MMD group than in the control group (Fig 3). In fact, chest tube drainage in the MMD group was approximately one half that of the control group 12 hours postoperatively (370 ± 180 mL versus 660 ± 270 mL; p < 0.001). It is unlikely that this decrease in chest tube drainage was due to more meticulous intraoperative hemostasis in the MMD group than in the control group because the chest closure time (time from discontinuation of CPB to end of operation) between the two groups was equivalent (56 ± 16 minutes versus 52 ± 14 minutes, respectively; p = 0.5).
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Comment |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsAppendix 1Appendix 2Appendix 3References |
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The use of an algorithmic blood conservation strategy in the present study resulted in the performance of CABG in 100 consecutive patients without the need of allogeneic transfusion in a safe and cost-effective manner. In comparison to a well-matched control population treated with a more limited blood conservation program, the application of this algorithmic program resulted in approximately a 50% reduction in postoperative bleeding and the preservation of the equivalent of 2 units of red blood cell mass without an appreciable increase in hospital cost. Several aspects of this program merit further discussion.
Preoperative Blood Conservation Measures
Preoperative blood conservation strategies are directed primarily toward optimizing available red blood cell mass and minimizing bleeding risk. Blood loss from laboratory sampling and interventional procedures is minimized, and unnecessary hemodilution is eliminated. To minimize bleeding risk, administration of drugs such as aspirin and heparin is discontinued as far in advance of the operation as possible.
When existing red blood cell mass, hematocrit, or both are insufficient to avoid excessively low hematocrits on bypass and obligatory transfusion (usually hematocrit <36% or red blood cell mass <1,600 mL), patients are given high-dose recombinant erythropoietin (r-HuEpo). To achieve maximum erythropoiesis, a high-dose r-HuEpo regimen that provides for erythropoietin blood levels similar to those seen during the natural erythropoietic response to acute profound anemia is used [6][7]. This regimen has been applied successfully and without adverse event to Jehovah’s Witnesses. The study presented here provides an algorithm for selective r-HuEpo use in the general cardiac surgical population with low preoperative red cell variables. As opposed to prolonged preoperative therapy in the study involving Jehovah’s Witnesses [6], the short-term administration of r-HuEpo in this study likely results in primarily prophylactic benefits: by initiating bone marrow stimulation before the operation, faster red blood cell regeneration is possible during the postoperative period. In patients with excessively low preoperative hematocrits (excluded from the present study), the cost and inconvenience of prolonged r-HuEpo therapy required to reduce transfusion risk would need to be weighed against the desirability of avoiding transfusion. Until the cost of r-HuEpo is reduced, prolonged therapy is probably warranted only in those patients with relative or absolute contraindications to transfusion (eg, rare blood types, multiple antibodies, or religious abstention).
Intraoperative Blood Conservation Measures
Intraoperative autologous donation, the removal of an individually calculated "maximum" volume of blood in the OR, is a critical component of our intraoperative blood conservation algorithm that has been demonstrated to decrease red cell transfusions (although not coagulation factor transfusions) in CABG patients [8]. Between one quarter to one third of the blood volume can be withdrawn with this technique, thus "preserving" this red blood cell mass before the institution of CPB.
Reducing the priming volume requirements of the CPB oxygenator and circuitry by downsizing this apparatus and minimizing intraoperative crystalloid administration are other critical components of the intraoperative conservation protocol [12]. Retrograde autologous priming, or retropriming, is a technique applied to nearly all MMD patients that further reduces the CPB crystalloid prime by displacing the prime with autologous blood drained from the patient through the venous and aortic cannulas [10]. Both are essentially cost-free techniques that are easily applied and well tolerated and that have been shown to independently reduce transfusion requirements in CABG patients [10][12]. The reduction in pump prime crystalloid volume substantially minimizes the net increase in intravascular volume (patient blood volume + circuit volume) associated with CPB, thereby decreasing the volume of fluid into which the patient’s fixed red blood cell mass is diluted. The direct result of reduced circuit volume is higher hematocrits during CPB, thereby providing an increased margin of safety in patients with low preoperative red blood cell mass, hematocrit, or both and decreasing allogeneic red cell requirements. Higher hematocrit levels during CPB also act synergistically to allow more IAD blood to be removed during the period preceding CPB, which further decreases transfusion requirements.
Another critical intraoperative blood conservation measure is the acceptance of the lowest safe level of anemia during and after CPB. Although this value has never been definitively established and although transfusion triggers used during CPB by surgeons and institutions differ widely, a recent analysis at our institution suggested that a 15% transfusion trigger is safe but that a trigger of 18% should be used when comorbidities are present [13][14][15][16]. In the present study, only 8 patients experienced hematocrits of less than 16% during CPB (and no patient reached the 22% postoperative trigger). In these 8 patients, in whom no neurologic or other complication was noted, transfusion to a hematocrit of 16% or higher with available autologous blood (IAD or cell salvage device) was accomplished. By our adhering to the stated triggers as well as to the autologous blood infusion protocol, all 8 patients were spared potentially unnecessary allogeneic transfusion. The frequency of lower hematocrits would be expected to be increased in patients with lower baseline hematocrits, and the appropriate use of red cell transfusion triggers in these patients would be expected to have an accordingly more important impact on minimizing transfusions.
Intraoperative pharmacologic therapy was limited to the use of aprotinin, which was applied on the basis of the presence of risk factors for increased postoperative bleeding, thereby minimizing potential adverse effects associated with this agent [17]. In this regard, the half Hammersmith Hospital regimen was chosen for the primary CABG patients in this study, both to limit potential adverse effects (graft thrombosis, renal insufficiency) and to control costs. The significant reductions in postoperative blood loss and the absence of adverse sequelae in the MMD group suggest that the risk factor–based use of this moderate-dose regimen was appropriate and effective. It should be noted that although excluded from the present study, high-risk patients (eg, those having reoperation, Jehovah’s Witnesses, or those with known bleeding disorders) continue to receive the full Hammersmith Hospital regimen of aprotinin at our institution.
Postoperative Blood Conservation Measures
The elimination of two primary contributing factors to excessive bleeding—hypothermia and hypertension—is a critical component of our postoperative protocol. In the event of excessive postoperative bleeding, several pharmacologic and technical interventions are indicated in the MMD protocol (see Appendix 2Appendix 3). Importantly, allogeneic platelets and coagulation factors are not transfused until after all alternative nontransfusion measures have been appropriately instituted and the patient continues to bleed at a clinically significant rate [18]. By withholding platelet and coagulation factor transfusions in this manner, it has been our experience that the coagulopathy associated with CPB resolves in the majority of patients, thereby eliminating (inappropriate) transfusion of these patients and helping to identify those patients requiring return to the OR for control of a mechanical source of bleeding. In the present study, no MMD patient required platelet or coagulation factor transfusion, and only 1 patient required return to the OR for excessive postoperative bleeding, where prompt reoperation was accomplished without transfusion or hematologic compromise.
Shed mediastinal blood infusion was also included in the multimodality program because potential benefits in terms of salvage of red blood cell mass in patients who did bleed postoperatively were thought to outweigh the risks of aggravating coagulopathic bleeding attributed to this technique [19][20].
Alternative Strategies
A number of strategies were not included in our algorithm based on cost, efficacy, or resource efficiency considerations. For example, preoperative autologous donation (PAD) appears to decrease allogeneic transfusions, but effective PAD means that sufficient time after donation and before operation be allowed for red blood cell mass regeneration; otherwise PAD restricts the performance of IAD, which is a relatively simpler and less expensive technique that very likely provides an equivalent or superior transfusion product [21]. Further, anemia may induce myocardial ischemia, and sufficient time for proper performance of PAD is often not available in the CABG population. On the other hand, use of r-HuEpo in conjunction with PAD has proven useful in accelerating red blood cell regeneration and may allow increased use of PAD in the future, particularly if erythropoietin costs are reduced.
Additional technical measures were similarly not incorporated into our intraoperative blood conservation program because in our opinion their utility was uncertain or because cost/benefit ratios were unclear. These included platelet plasmapheresis, heparin-coated and other biocompatible circuitry, hemofiltration, and leukocyte filtration devices [22][23][24]. Several potentially useful hemostatic agents were also not included in our protocol. Amicar and tranexamic acid were excluded as primary agents because they are probably less effective than aprotinin at decreasing postoperative bleeding, although a substantially lower cost and a potentially more favorable safety profile clearly make their use an attractive option [25]. Amicar is, in fact, used at our institution for patients with a mildly increased bleeding risk and for patients with absolute or relative contraindications to aprotinin. Similarly, the use of desmopression is reserved for patients with increased bleeding during the postoperative period, particularly in the setting of renal failure [26].
Limitations of Study Design
One limitation of the present study is that because of the integrated nature of the algorithmic protocol, it is not possible to specifically attribute the results of this study in terms of blood conservation to any one of the included interventions. The effectiveness of each of these blood conservation measures has, however, been previously described, as referenced in this text. The primary limitation of this study is that it was not conducted as a randomized trial. The comparisons with a "historical" control group are therefore not definitive in describing the relative efficacy of the MMD protocol. Nevertheless, the control group used in this study does represent a cohort of well-characterized, consecutively enrolled patients who in comparison with the MMD group were specifically distinguished by the use of identical selection criteria, a clearly delineated set of blood conservation measures, an identical set of transfusion guidelines, the same set of participating study attending surgeons and anesthesiologists, and similarly comprehensive data collection. Consequently, surgical practices in the control and MMD groups were kept relatively constant. Because costs were less reliably stabilized in this rapidly changing cost environment, we compared patients in the MMD group with DRG–matched patients undergoing CABG during the period immediately prior to initiation of the MMD protocol. The use of DRG–matching provides a control for cost or length of stay outliers or both. This again is less definitive than the comparison that would be available with a randomized trial, but it provides nearly contemporaneous cost data and an approximate reference for the MMD interventions.
Another potential design limitation of this study is that its nonblinded nature might have introduced a bias toward more careful, hemostatic surgical technique in the MMD patients. However, the comparison of closure times between these patients and the control group suggests this was not the source of improved results in the MMD group.
Finally, our use of exclusion criteria that eliminated very anemic patients (hematocrit < 33%) prohibits concluding that the MMD strategy will result in the avoidance of transfusion in all CABG patients. Nevertheless, the baseline mean preoperative hematocrit of 39% in the MMD group suggests that selection criteria did not overtly bias the study population toward those patients with disproportionately high hematocrits.
It appears reasonable to conclude on the basis of these data that the MMD protocol yielded decreased bleeding and transfusion requirements in a safe and cost-effective manner, at least in reference to the recent clinical practice at our institution. It is also likely that similar results can be obtained in most general CABG populations. Table A2Table A3
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Acknowledgments |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsAppendix 1Appendix 2Appendix 3References |
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We thank Christopher Fang, MD, MPH, for his assistance with statistical analysis.
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Appendix 1 |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsAppendix 1Appendix 2Appendix 3References |
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Appendix 2 |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsAppendix 1Appendix 2Appendix 3References |
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Appendix 3 |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsAppendix 1Appendix 2Appendix 3References |
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References |
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TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsAppendix 1Appendix 2Appendix 3References |
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 K. A. Eagle, R. A. Guyton, R. Davidoff, G. A. Ewy, J. Fonger, T. J. Gardner, J. P. Gott, H. C. Herrmann, R. A. Marlow, W. C. Nugent, et al. ACC/AHA guidelines for coronary artery bypass graft surgery: A report of the American College of Cardiology/ American Heart Association task force on Practice Guidelines (Committee to revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery) J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1262 - 1347. [Full Text] [PDF]
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 D. Savarese, H. Waitkus, F. M. Stewart, and M. Callery Bloodless Medicine and Surgery J Intensive Care Med, January 1, 1999; 14(1): 20 - 33. [PDF]
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W. J. DeBois and T. K. Rosengart Retrograde autologous priming reduces blood use Ann. Thorac. Surg., September 1, 1998; 66(3): 987 - 987. [Full Text] [PDF]
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