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Ann Thorac Surg 1996;62:1373-1378
© 1996 The Society of Thoracic Surgeons
Cardiovascular Surgery Unit, Hôpital de la Tour, Meyrin-Geneva, Switzerland
Accepted for publication June 7, 1996.
| Abstract |
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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 |
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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 |
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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
-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 Lmin-1m-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 |
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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 1
, 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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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 2
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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 1
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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 |
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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 |
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| Footnotes |
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| References |
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