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Ann Thorac Surg 1996;62:1373-1378
© 1996 The Society of Thoracic Surgeons


Original Article: Cardiovascular

Plateletpheresis Before Redo CABG Diminishes Excessive Blood Transfusion

Jan T. Christenson, MD, PhD, Jeanine Reuse, RN, Pierre Badel, MD, François Simonet, MD, Martin Schmuziger, MD

Cardiovascular Surgery Unit, Hôpital de la Tour, Meyrin-Geneva, Switzerland

Accepted for publication June 7, 1996.


    Abstract
 Top
 Footnotes
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Background. Blood conservation remains an important element for patients undergoing cardiac operations with cardiopulmonary bypass. Preoperative platelet-rich plasma (PRP) harvest is an autologous blood conservation method. The efficacy of preoperative PRP harvest and post-cardiopulmonary bypass reinfusion on postoperative bleeding and need for postoperative blood transfusion was evaluated in patients undergoing redo coronary artery bypass grafting in a prospective, randomized manner.

Methods. All adult patients admitted for redo coronary artery bypass grafting entered into the study. The PRP harvest aim was 20% or more of the total estimated circulating platelets. Immediately preoperatively three sequestration cycles were performed. The PRP was reinfused after weaning from cardiopulmonary bypass. One hundred seven parameters/patient were recorded. There were 20 patients in the PRP group and 20 controls (without PRP harvest).

Results. Patient characteristics, operative data, and preoperative hematologic parameters did not differ between the groups. In the PRP group, the mean platelet count in the PRP was 864 ± 139 x 103/µL, and the platelet yield was 27% ± 5% (range, 20% to 37%). The average total chest tube blood loss was 423 mL (PRP) compared with 1,462 mL (controls; p < 0.001). Fourteen patients in the control group required blood transfusions postoperatively compared with only 1 patient in the PRP group (p < 0.001). Postoperative fluid requirements were also significantly greater in the control group (p < 0.001). Postextubation gas exchange was significantly better in the PRP group compared with controls (p < 0.01). Postoperative ventilation time and intensive care stay were significantly shorter in patients in the PRP group.

Conclusions. A preoperative PRP harvest of 20% or more of the total platelets and reinfusion of the PRP after cardiopulmonary bypass resulted in significantly less postoperative blood loss and decreased fluid and blood transfusion requirements compared with controls. Postextubation gas exchange, ventilation time, and time required in the intensive care unit were also better, and the method was found cost-effective.


    Introduction
 Top
 Footnotes
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
See also page 1378.

Postoperative hemorrhage due to deleterious effects associated with cardiopulmonary bypass [1, 2] and the risks of homologous blood product transfusion [3] have kept blood conservation methods high on the agenda in cardiac surgery. Many methods, pharmacologic as well as mechanical, have been introduced over the years. Plasmapheresis, plasma sequestration, platelet-rich plasma (PRP) harvest, or plateletpheresis is an aggressive autologous blood conservation method, the effectiveness of which is still debated [4]. The vast majority of earlier studies on plasmapheresis and PRP reinfusion in patients undergoing cardiac operations have shown positive results with decreased postoperative blood loss and reduced transfusion requirements [1, 57], and only a few studies have been unable to show any positive effect of the treatment [8, 9]. The main reason for absence of positive measurable effects of the plasmapheresis has been an insufficient sequestration yield of platelets. Several authors have demonstrated that plasmapheresis and PRP reinfusion is only effective when a minimum of 20% of the patient's platelet plasma volume has been collected before heparinization and the start of cardiopulmonary bypass (CPB) and later reinfused after termination of CPB and return to normal activated clotting times [1, 2]. Several plasmapheresis devices are available on the market, with variations in methodology. However, a recent comparative study of three devices failed to demonstrate significant differences in the postoperative patient parameters studied [2].

The number of reoperations for coronary artery disease is increasing. It has become the second most common procedure in the field of cardiac surgery. Redo coronary artery bypass grafting (CABG) has a higher mortality than primary CABG [10] and has also been reported to be associated with an increased risk of postoperative bleeding [11]. Redo CABG is therefore a target group in any blood-saving program.

In the present study we have evaluated, in a prospective, randomized manner, the effectiveness of platelet sequestration on postoperative blood transfusion requirement, after sequestration of a minimum of 20% of the patient's platelet plasma volume, in patients undergoing redo CABG. The cost-effectiveness of the method was also calculated.


    Patients and Methods
 Top
 Footnotes
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Between September 1, 1995, and March 1, 1996, all adult cardiac patients with coronary artery disease referred to us for reoperative CABG were submitted to this study. The exclusion criteria were: transfusion of any blood products 7 days or less preoperatively, preoperative platelet count less than 150,000/µL, preoperative hematocrit less than 35%, and patients with a body weight less than 50 kg. In addition, patients with unstable angina at the time of the operation and induction of anesthesia were excluded, as well as patients requiring rethoracotomy due to postoperative surgical bleeding and patients in whom the platelet-rich plasma contained less than 20% of the estimated circulating platelets.

All patients received standard anesthetic management, and the same surgical techniques were employed in all patients, using the sequential bypass grafting technique previously described [10]. All patients received prophylactic antibiotics (cefazoline) intravenously for 48 hours postoperatively. Antifibrinolytic therapy such as aprotinin, tranexamic acid, and {epsilon}-aminocaproic acid was not used during this study. Early extubation was aimed at in all instances. Normothermic (35° to 37°C) CPB [12] was conducted with a roller-pump arterial drive system (Gambro; Jostra Mediczintecknik GmbH & Co KG, Hirrlingen, Germany) and a hollow-fiber membrane oxygenator (Maxima; Medtronic Inc, Minneapolis, MN) in all patients. Autotransfusion with the Elmd-500 (Medtronic Inc, Parker, CO) was employed, and ultrafiltration was included when deemed necessary by the perfusionist. Nonpulsatile perfusion was carried out at cardiac indices between 2.0 and 2.4 L•min-1•m-2, maintaining mean arterial pressures between 60 and 70 mm Hg.

The myocardial revascularization was performed after cold cardioplegic arrest (St. Thomas' II, 4° to 6°C) and topical hypothermia with slush. Cardioplegia infusion into the aortic root was repeated every 30 minutes or whenever electrical activity recommenced. Before declamping of the aorta, reperfusion with a mixture of warm cardioplegic solution and venous blood (50/50) + 100 mg allupurinol (Zyloric; Wellcome Ltd, London, UK) was employed in all patients. Activated clotting time was maintained at or greater than 450 seconds and routinely measured every 30 minutes throughout CPB.

One hundred seven parameters were measured for each patient. This included patient demographics, surgical factors, anesthetic factors, postoperative complications, hematologic parameters (preoperatively; 24, 48, and 72 hours postoperatively; and on the seventh postoperative day), and blood loss as well as fluid and blood transfusion requirements operatively and postoperatively. Forty patients entered into the study and were randomly assigned either to undergo preoperative PRP harvest (n = 20) or not (controls, n = 20). None of the patients were excluded from the study because of rethoracotomy for surgical bleeding or poor PRP yield (<20%).

Preoperative Platelet-Rich Plasma Harvest
Platelet-rich plasma harvesting was achieved using an Elmd-500 autotransfusion/platelet sequestration device (Medtronic Inc, Parker, CO). The unit separates the blood into platelet-poor plasma, red blood cells, and concentrated PRP. The method consists of withdrawing blood directly from the patient and processing the blood using a centrifuge speed of 5,000 rpm at a blood flow rate of 50 to 100 mL/min. Each blood withdrawal sequence and sequestration cycle yielded approximately 500 mL of platelet-poor whole blood and 150 mL of highly concentrated PRP. To achieve a significant therapeutic result, the target objective, according to the manufacturer, should be 20% to 30% of the patient's total estimated circulating platelets (estimated blood volume x platelet count).

The PRP sequestration started immediately after induction of anesthesia and was performed during harvesting of veins and, if applicable, the internal mammary artery. A total of three sequestration cycles was performed, following the specifications of the device, to obtain sufficient platelet yield. Blood for the first sequestration cycle was obtained from a venous catheter placed in the brachial vein, whereas for the two following cycles blood was received from a central venous catheter. The reason for using two different lines for harvesting was to save time. After the concentrated PRP volume had been separated, all components except the PRP were reinfused to the patient immediately in case of hemodynamic instability or a hematocrit less than 20%; otherwise, the plasma was saved and transfused at the end of the operation. The average time required for the entire sequestration procedure was 72 minutes. The PRP product was sampled for platelet count, fibrinogen level, and protein level and stored at room temperature with periodic agitation. Infusion of the PRP commenced after heparin reversal with protamine as confirmed by return to preoperative activated clotting time values and was in all cases completed well within 6 hours of sequestration.

Transfusion Algorithm
Patients were transfused with coagulation factors from the blood bank (fresh frozen plasma or platelet concentrate) only when bleeding was uncontrollable, and then according to the following protocol: fresh frozen plasma was transfused when the partial thromboplastin times were greater than 35 seconds and platelet concentrate when platelet counts were less than 50,000/µL. Red blood cells were transfused exclusively for a hematocrit less than 20%.

Statistical Analysis
Student's t test and Fischer's exact test were employed to assess differences between groups for statistical significance, where appropriate. Differences were considered significant at a probability level of p less than 0.05.


    Results
 Top
 Footnotes
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Results in relation to the platelet sequestration procedure were as follows: The mean calculated total blood volume was 5,334 ± 923 mL (range, 3,900 to 6,975 mL) (body weight in kg x 70 mL/kg). The mean platelet count was 206 ± 29 x103/µL (range, 151 to 261 x103/µL), and the estimated total number of platelets was 11.1 ± 1.7 trillion (range, 8.4 to 13.4 trillion). A mean of 348 ± 95 mL (range, 230 to 680 mL) of PRP was collected, following our sequestration protocol. The mean platelet count in the PRP was 864 ± 139 x103/µL (range, 594 to 996 x103/µL), corresponding to a platelet yield of 3.0 ± 0.6 trillion or 27% ± 5% (range, 20% to 37%) of the total estimated circulating platelets. Fibrinogen and protein levels in the PRP were within normal range. No attempted PRP harvest had to be stopped because of hemodynamic instability during the study period.

There were no differences in patient population between the PRP and control groups when preoperative patient characteristics were compared. The mean age was 63.4 years (range, 42 to 80 years), 83% were men, and the mean preoperative Canadian Cardiovascular Society angina class was 3.5 ± 0.5. Eight percent of the operations were urgent. All patients had triple-vessel coronary artery disease. There were no statistically significant differences in the incidence of preoperative anticoagulation or platelet aggregation inhibitory therapy between the two groups. The majority of the patients (85%) were receiving aspirin (Bayer AG, Leverkusen, Germany), 100 mg daily, preoperatively in both groups. Some preoperative hematologic and coagulation parameters are listed in Table 1Go, showing no group differences. Other parameters such as S-protein level, S-fibrinogen level, and activated clotting time revealed similar values in both groups.


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Table 1. . Hematologic and Coagulation Parameters in Patients Undergoing Preoperative Platelet-Rich Plasma Harvest and Controlsa
 
The mean cardiopulmonary bypass time (97 ± 37 minutes) and ischemia time (69 ± 25 minutes) did not differ between the groups; neither did the mean number of distal coronary anastomoses per patient (3.7 ± 1.2). The internal mammary artery was used as a conduit in 68% of the patients, without group differences. Ultrafiltration was employed in 5 and 6 patients, respectively (PRP and controls).

Other operative parameters such as administered amount of heparin before CPB (30 ± 7 x103 units for PRP versus 27 ± 6 x103 units for controls), crystalloids (5.5 ± 2.0 x103 mL for PRP versus 5.1 ± 1.4 x103 mL for controls), and protamine sulfate to reverse the heparin effect after CPB did not differ statistically between the groups. The total amount of operative nonblood colloid was greater in the PRP group (1,318 ± 557 mL) compared with controls (975 ± 421 mL; p = 0.034).

The total blood loss through chest tubes (two per patient, placed in a standardized manner in all patients), blood transfusion, and total intravenous fluid requirements postoperatively were significantly less in the PRP group than in controls (Table 2Go).


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Table 2. . Total Blood Loss, Blood Transfusion, and Fluid Requirements Postoperatively in Patients Undergoing Redo Coronary Artery Bypass Grafting With and Without Preoperative Platelet-Rich Plasma Harvesta
 
In the PRP group extubation was successfully accomplished after a mean intubation period of 20.6 ± 5.7 hours (range, 12 to 39 hours), whereas extubation in the control group was done on average 29.5 ± 7.8 hours (range, 22 to 48 hours) postoperatively (p < 0.001). The postextubation gas exchange was also significantly better in the PRP group compared with the control group: arterial oxygen tension was 125 ± 23 mm Hg in the PRP group versus 93 ± 28 mm Hg (in the control group), (p = 0.009), and arterial oxygen tension/inspired oxygen fraction ratio 236 ± 44 mm Hg (for the PRP group) versus 192 ± 54 mm Hg (for the control group), (p = 0.043). The mean stay required in the intensive care unit was shorter in the PRP group (40 ± 9 hours; range 24 to 48 hours) than in the control group (52 ± 12 hours; range, 40 to 94 hours) (p < 0.001) (Table 3Go).


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Table 3. . Intubation Period, Postextubation Gas Exchange, and Arterial Oxygen Tension/Inspired Oxygen Fraction in Patients Undergoing Redo Coronary Artery Bypass Grafting With and Without Preoperative Platelet-Rich Plasma Harvesta
 
There was only one hospital death, in the control group, on the 11th postoperative day, due to multiple organ failure after a gastrointestinal complication (acute gangrenous cholecystitis). There were few other postoperative complications, and no statistically significant group differences.

Patients in the PRP group had significantly greater hemoglobin and hematocrit values on the third to seventh postoperative days. Platelet count, prothrombin time, fibrinogen level, and antithrombin III level during the first 7 days postoperatively were numerically greater in the PRP group, but did not differ significantly between the groups (see Table 1Go).

The mean total hospitalization period did not reveal any statistically significant difference between the PRP group (10.5 ± 2.9 days; range, 8 to 22 days) and the controls (12.2 ± 2.9 days; range, 9 to 20 days), although it nearly reached significance.

Cost-benefit analysis revealed a reduction in the total cost for redo CABG using PRP harvest as a blood conservation method: there was a saving of 2,768 Swiss Francs ($3,100 US) per patient, taking all direct and indirect costs into consideration.


    Comment
 Top
 Footnotes
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Nonsurgical hemorrhage and homologous blood transfusions with their inherent risks still present a major problem in cardiac operations, particularly in redo CABG [11]. Postoperative bleeding also increases the risk of hypovolemic hypotension, resulting in increased mortality and morbidity, eg, gastrointestinal complications [13]. Even though improvements in cardiac surgical techniques have resulted in reduced requirements for homologous transfusion both intraoperatively and postoperatively, cardiac surgical patients still remain one of the major groups using bank blood [14]. Blood conservation methods have therefore been introduced, to various degrees, in most hospitals performing cardiovascular operations. The use of intraoperative autotransfusion devices and postoperative collection of chest tube drainage have been shown to be effective in salvaging shed blood, which can be used for reinfusion [15, 16].

Pharmacologic intervention to minimize postoperative bleeding, eg, the proteinase inhibitor aprotinin in high doses, has been used for years in cardiac operations to ameliorate hemostasis. Although there can be no doubt about aprotinin's efficacy in limiting excessive blood transfusion [2, 17] and with very few negative reports, there is a lack of consensus concerning the routine use of this drug for all cardiac procedures requiring CPB. The cost of a full-dose aprotinin regimen is substantial, even though in a recent report it was demonstrated to be cost-effective [18]. On the other hand, a recent report in which aprotinin was used in coronary reoperations suggested that aprotinin was associated with decreased early graft patency [19]. Other blood conservation methods, such as preoperative autologous blood donation, intraoperative hemodilution, and postoperative shed mediastinal blood retransfusion, all have their limitations and do not seem to solve the problem entirely.

Plasmapheresis or PRP harvest was recently introduced as a blood conservation method in cardiovascular surgery. The technique has long been a well-accepted blood banking method. Intraoperative plasma sequestration will remove the platelets undamaged before CPB. Harvesting the platelets before CPB and reinfusing them immediately after CPB should make them readily available for hemostasis. A comparison of platelet-poor plasma and PRP harvest and post-CPB retransfusion showed that the platelet counts were greater in the PRP group, and only PRP retransfusion improved platelet aggregability significantly [20]. The advantage of plateletpheresis in comparison with whole blood draw is that red cells can be returned at any time the hemodynamic condition of the patient necessitates. Platelet-rich plasma, with all its clotting factors, is reinfused after reversal of heparin with protamine, at a time when the best possible blood coagulation is necessary.

The effects of PRP infusion have been shown to reduce patient exposure to homologous blood products, preserve platelets and protein fractions from exposure to the extracorporeal circuit during CPB, reduce activation of polymorphonuclear neutrophils, and avoid exposure to artificial surfaces [1, 2, 5, 7]. After the reinfusion of autologous PRP, patients have responded with higher operative platelet counts, decreased postoperative bleeding, and higher fibrinogen and antithombin III concentrations [7].

There are presently several techniques for plasmapheresis [2]. In the present study we have used an autotransfusion device that can be used for both plasma sequestration and routine cell washing during cardiac procedures, using one single set of tubing. This platelet sequestration technique was found to be efficient, safe, and cost-effective. The mean yield of platelets in our study was 3.0 x1011, which represents 27% of the circulating platelets and is harvested as efficiently as the yields of 2 to 3 x1011 obtained from more expensive and time-consuming machinery used in blood bank single-donor platelet collections [20]. We experienced no adverse effects of the sequestration procedure, taking into account all exclusion criteria mentioned above. No patients had to be excluded retrospectively due to failure to achieve the minimum of 20% sequestered platelets or due to postoperative surgical bleeding. To theoretically achieve a significant therapeutic result, the target objective should follow the recommendations set forth by the American Blood Banks Association, which recommends a minimum effective yield of 3 x1011 platelets as a quality control guideline for the single-donor product. This has been achieved in several previous studies [1, 7, 20]. Two recent articles of critical nature regarding platelet sequestration, claiming that the technique does not reduce the postoperative blood transfusion needs, both failed to reach 20% of the patients' total platelet plasma volume. One reaching a calculated PRP yield of 15% [9], the other a platelet yield of only 11% [8], and this is the most likely explanation why these authors could not demonstrate a positive effect of PRP harvest.

Bacterial and endotoxin contamination of blood from cell conservation devices used for autologous transfusion during cardiac operations is frequent, but no episodes of sepsis or endotoxic shock were diagnosed, and transient bacteremia was rarely detected in a recent study [21]. In the present study no sequestration-related infection complications occurred.

Patients in the PRP group had significantly greater hemoglobin and hematocrit values on the third to seventh postoperative days. The platelet count, prothrombin time, and fibrinogen levels during the first 7 days postoperatively were numerically greater in the PRP group, but there were no statistically significant differences between the groups.

Even though the sequestration procedure is time-consuming (average, 72 minutes), it has to be emphasized that the PRP harvest is performed parallel to the preparation of the patient for CPB (placement and calibration of monitoring devices, harvesting of veins and internal mammary artery, and thoracotomy), thus leading to an almost negligible additional time required in the operating room.

Cost is also an important consideration. An uncomplicated perioperative course is the key to cost savings in major heart operations. At our institution the reduction in the total cost for redo CABG per patient using PRP harvest was calculated to be more than $3,100 US or 2,500 Swiss Francs per patient, thus making this method highly cost-effective.

In addition, we found improved pulmonary function and the possibility of earlier extubation in the PRP group. One explanation for the improved pulmonary function after PRP harvest could be that the platelet sequestration actually avoids the CPB-induced secretion of various mediators affecting the lung. Both transfusion of blood components, particularly platelets, and CPB are known to alter pulmonary function adversely, thus influencing postoperative convalescence and recovery [22]. Harvest of PRP not only reduced chest tube drainage and postoperative fluid and blood transfusion requirements, but also resulted in a significant improvement in pulmonary function in our series. It also significantly shortened the stay required in the intensive care unit and the total hospitalization compared with controls.

In conclusion, the present study confirms PRP harvest to be an efficient blood conservation technique in reducing patient homologous blood exposure. Intraoperative plateletpheresis offers the cardiac surgical patient a safe and more convenient method of autologous transfusion, which may help to avoid homologous blood exposure and may avoid adverse effects of pharmacologic interventions. The benefits of the technique are decreased postoperative bleeding, reduced blood bank dependence, reduced postoperative intravenous fluid requirement, earlier extubation, and better pulmonary function. Combining both sequestration and autotransfusion on one machine, with a single set of disposables, makes this blood conservation technique both safe, efficient, and cost-effective.


    Acknowledgments
 Top
 Footnotes
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
This study was supported by grants from Fumedica AG, Muri, Switzerland, and Medtronic Europe SA, Woluwe, Belgium.


    Footnotes
 Top
 Footnotes
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Address reprint requests to Dr Christenson, Cardiovascular Surgery Unit, Hôpital de la Tour, 1 av J.-D. Maillard, CH-1217 Meyrin-Geneva, Switzerland.


    References
 Top
 Footnotes
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Davies GG, Wells DG, Mabee TM, Sadler R, Melling NJ. Platelet-leukocyte plasmapheresis attenuates the deleterious effects of cardiopulmonary bypass. Ann Thorac Surg 1992;53:274–7.[Abstract]
  2. Rasmussen CR, Stammers AH, Kratz JM, et al. Plasmapheresis techniques during cardiac surgery. J Extracorp Technol 1992;24:12–9.
  3. Ward JW, Holmberg SD, Allen JR. Transmission of human immuno-deficiency virus (HIV) by blood transfusion screened as negative for HIV antibody. N Engl J Med 1988;318:473–8.[Abstract]
  4. Stover EP, Siegel LC. Platelet-rich plasmapheresis in cardiac surgery: efficacy may yet be demonstrated [Letter]. J Thorac Cardiovasc Surg 1994;108:1148.[Free Full Text]
  5. Giordano GF Sr, Giordano GF Jr, Rivers SL, et al. Determinants of homologous blood usage utilizing autologous platelet-rich plasma in cardiac operations. Ann Thorac Surg 1989;47:897–902.[Abstract]
  6. Jones JW, McCoy TA, Rawitscher RE, Lindsley DA. Effect of intraoperative plasmapheresis on blood loss in cardiac surgery. Ann Thorac Surg 1990;49:585–90.[Abstract]
  7. Stammers AH, Kratz J, Johnson T, Crumbley J, Merrill J. Hematological assessment of patients undergoing plasmapheresis during cardiac surgery. J Extracorp Technol 1993;25:6–13.
  8. Ereth MH, Olivier WC, Beynen MK, et al. Autologous platelet-rich plasma does not reduce transfusion of homologous blood products in patients undergoing repeat valvular surgery. Anesthesiology 1993;79:540–7.[Medline]
  9. Tobe CE, Vocelka C, Sepulvada R, et al. Infusion of autologous platelet rich plasma does not reduce loss and product use after coronary artery bypass. A prospective, randomized, blinded study. J Thorac Cardiovasc Surg 1993;105:1007–14.[Abstract]
  10. Schmuziger M, Christenson JT, Maurice M, Mosimann E, Simonet F, Velebit V. Reoperative myocardial revascularization: an analysis of 458 reoperations and 2645 single operations. Cardiovasc Surg 1994;2:623–9.[Medline]
  11. Salomon NW, Page US, Bigelow JC, Krause AH, Okies JE, Metzdorff MT. Reoperative analysis of 6591 patients undergoing primary bypass and 508 patients undergoing reoperative coronary artery bypass. J Thorac Cardiovasc Surg 1990;100:250–60.[Abstract]
  12. Christenson JT, Maurice M, Simonet F, Velebit V, Schmuziger M. Normothermic versus hypothermic perfusion during primary coronary artery bypass grafting. Cardiovasc Surg 1995;3:519–24.[Medline]
  13. Christenson JT, Schmuziger M, Maurice J, Simonet F, Velebit V. Gastrointestinal complications after coronary artery bypass grafting. J Thorac Cardiovasc Surg 1994;108:899–906.[Abstract/Free Full Text]
  14. Yeh T, Shelton L, Yeh TJ. Blood loss and bank blood requirements in coronary bypass surgery. Ann Thorac Surg 1978;28:11–6.
  15. Giordano GF, Rivers SL, Chung GKT, et al. Autologous platelet-rich plasma in cardiac surgery. Effect on intraoperative and postoperative transfusion requirements. Ann Thorac Surg 1988;46:416–9.[Abstract]
  16. Morris JJ, Tan YS. Autotransfusion: is there a benefit in a current practice of aggressive blood conservation? Ann Thorac Surg 1994;58:502–8.[Abstract]
  17. Parlari A, Antona C, Germetta P, et al. The effect of "high-dose" aprotinin and other factors on bleeding and revisions for bleeding in adult coronary and valve operations: an analysis of 2190 patients during a five-year period (1987–1991). Eur J Cardiothorac Surg 1995;9:77–82.[Abstract]
  18. Lathi KG, Hariawala M, Fotouhi F, Symes JF. Economics of aprotinin in cardiac surgery [Abstract]. Anesth Analg 1995;80:SCA119.
  19. Cosgrove DM III, Heric B, Lytle BW, et al. Aprotinin therapy for reoperative myocardial revascularization: a placebo-controlled study. Ann Thorac Surg 1992;54:1031–8.[Abstract]
  20. Boldt J, Kling D, Zickmann B, Jacobi M, Dapper F, Hemplemann G. Acute preoperative plasmapheresis and established blood conservation techniques. Ann Thorac Surg 1990;50:62–8.[Abstract]
  21. Bland LA, Villarino ME, Arduino MJ, et al. Bacteriologic and endotoxin analysis of salvaged blood used in autologous transfusions during cardiac operations. J Thorac Cardiovasc Surg 1992;103:582–8.[Abstract]
  22. Westaby S. Organ dysfunction after cardiopulmonary bypass. A systemic inflammatory reaction initiated by the extracorporeal circuit. Crit Care Med 1987;13:89–95.

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