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J Thorac Cardiovasc Surg 1994;107:1210-1214
© 1994 Mosby, Inc.


CARDIOPULMONARY BYPASS,
MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

Reduction of homologous blood requirements by blood-pooling at the onset of cardiopulmonary bypass

A. F. Petry, MDa, T. Jost, a, H. Sievers, MDb


Kiel and Lübeck, Germany

Received for publication May 19, 1993. Accepted for publication Aug. 20, 1993. Address for reprints: A. F. Petry, MD, Clinic for Anesthesiology/University of Kiel, Schwanenweg 21, 24105 Kiel, Federal Republic of Germany.

Abstract

This study was done to investigate whether an intraoperative autologous blood donation (pooling) at the onset of cardiopulmonary bypass can reduce homologous blood requirements during and after operations for myocardial revascularization. Ninety patients were assigned equally to two groups. In group C, serving as the control group, cardiopulmonary bypass was done with a membrane lung primed with 1500 ml of Ringer's solution. The cardiopulmonary bypass flow ranged between 2.4 L/min per square meter in normothermia and 1.5 L/min per square meter in moderate hypothermia of 30° to 32° C. In group P the same devices were used as in group C; however, at the onset of cardiopulmonary bypass 500 to 1000 ml of heparinized blood was "pooled" in a bag and substituted by the same volume of Ringer's solution. The lower hemodilution limit was set to a hematocrit value of 20%. The pooled blood was retransfused after the aorta was decannulated. The main parameter of interest was the total volume of red cell concentrates and fresh frozen plasma required during the operation and the subsequent stay in the hospital. The results were that group C received on average 792 ± 639 ml and group P 337 ml ± 382 ml of red cell concentrates. Very small amounts of fresh frozen plasma were used on average: group C, 56 ml; group P, 0 ml. These differences were highly significant (p < 0.001). Remarkably, 44% of patients in group P did not require any homologous blood products compared with 16% in group C. In conclusion, modern oxygenators, which provide sufficient oxygen transport capacity, make it feasible to decrease the hematocrit to 20% by "pooling" blood at the beginning of cardiopulmonary bypass and replacing it with saline solution. This procedure led to a highly significant saving of homologous blood. (J THORAC CARDIOVASC SURG 1994;107:1210-4)

In recent years the risk of hepatitis or human immunodeficiency virus infections has substantially affected the indication for perioperative homologous blood transfusions in major operations. For the same reason the reduction of blood loss should be a permanent objective in modern heart operations in which cardiopulmonary bypass (CPB) techniques are used. Different procedures, such as high-dose administration of aprotinin, preoperative autologous blood donation, and the hemofiltration or separation of the remaining oxygenator blood have proved to be feasible. Go Go 1-4 However, little information is available about the influence of different bypass techniques on banked blood requirements. Go 5

According to our experience in a previous investigation, the reduction of the pump priming volume from 2000 ml to 1500 ml by cutting all the connecting tubes to a minimum length did not significantly reduce homologous blood transfusions. Therefore this study was done to investigate the efficiency of an intraoperative autologous blood donation technique before the onset of CPB, which was called the "pooling procedure."

METHODS

The study retrospectively included 90 consecutive patients undergoing coronary artery bypass grafting operations, which were done by three primary surgeons in the period from November 1990 to December 1991. The including criteria were elective operation, venous grafts (arteria mammaria excluded because rarely done at that time), age 40 to 80 years, body height 160 to 180 cm, body weight 50 to 85 kg, and preoperative hematocrit greater than 33%. The excluding criteria were previous chest operation, severe liver or kidney disease, abnormal hemostasis, thrombocytopenia, pretreatment with acetylsalicylic acid, and major intraoperative surgical complications (such as aortic rupture or anastomosis insufficiency).

The patients were assigned to two groups of 45 each. In group C (control group), CPB was done with a membrane lung (Monolyth, Sorin, Italy) primed with 1500 ml of Ringer's solution. The pump flow was nonpulsatile and ranged between 2.4 L/min per square meter in normothermia and 1.5 L/min per square meter in moderate hypothermia of 30° to 32° C. Anticoagulation was done by administration of heparin 300 IE/kg before insertion of the aortic cannula. An additional 10,000 IE heparin was applied to the pump prime.

In group P (pooling group) the same devices and techniques were used as in group C. However, at the onset of CPB the first 500 to 1000 ml of heparinized blood drained from the two-stage venous catheter was separated (pooled) in a bag and simultaneously substituted by the same volume of Ringer's solution via the roller pump of the CPB machine. Hemodilution down to hematocrit values of 20% were accepted because the oxygen transport capacity of the Monolyth oxygenator had been sufficient even on higher flow velocities in preliminary investigations. The pooled blood was later retransfused via an intravenous line after the aorta was decannulated and neutralization of heparin performed.

An analysis of the arterial and venous blood gases, hematocrit, and serum electrolytes was done every 10 to 15 minutes during CPB with the semi-on-line analyzer GEM 6 (Mallinckrodt, St. Louis, Mo.). Additionally, the venous lactate concentration was evaluated before CPB, 5 minutes after onset of CPB, and after removal of the aortic crossclamp to get an indicator for eventually occurring peripheral hypoxemia.

In the intensive care unit (ICU) the same parameters and measurements of the hemostatic system were obtained every 4 hours. A routine enzyme analysis was made at 6- to 12-hour intervals.

The anesthetic technique was the same in the two groups: for premedication all patients received an intramuscular injection of 5 mg midazolam 10 minutes before transportation to the operating room. Anesthesia was induced by a loading dose of fentanyl 7 µg/kg and flunitrazepam 14 µg/kg over a period of 10 to 15 minutes. After administration of vecuronium 0.1 mg/kg, the trachea was intubated and the patient's lungs were mechanically ventilated with inspired oxygen fraction 0.5, positive end-expiratory pressure 0, and end-expiratory carbon dioxide tension 30 mm Hg. Anesthesia was maintained by a continuous infusion of fentanyl 7 to 21 µg/kg per hour and flunitrazepam, 14 to 42 µg/kg per hour, if necessary, sublimated with 0.6 to 1.2 vol% isoflurane for a short span (e.g., sternotomy). Relaxation was achieved by application of pancuronium 0.1 to 0.2 mg/kg. At termination of CPB inotropic drugs (epinephrine, dopamine) were given if necessary.

The main parameter of interest was the total volume, or the number of units, of packed red cells and fresh frozen plasma required during the operation and the subsequent stay in the hospital (ICU and peripheral wards). One unit consisted of 300 ml red cells in a saline-adenine-glucose-mannitol solution; the hematocrit value of the units was 60%.

The decision for transfusion of homologous blood products was made by physicians not involved in the study, according to the general clinical practice in our hospital's department of heart surgery, which means the hematocrit should be greater than 27% at the end of CPB and greater than 30% during anesthesia after CPB and after the operation.

Statistical methods
Statistical analysis was done with the Statistical Package for the Social Sciences (SPSS/PC Windows, Chicago, Ill.). Differences between the group means were evaluated with Student's t test; p < 0.05 was considered statistically significant. All results are reported as means plus or minus the standard deviation (SD).

RESULTS

The two groups did not differ significantly with regard to the means of operation time (C: 190 ± 39 minutes, P: 199 ± 39 minutes), bypass time (C: 73 ± 24 minutes, P: 68 ± 25 minutes), crossclamping time (C: 40 ± 13 minutes, P: 36 ± 14 minutes), body weight (C: 76 ± 9 kg, P: 77 ± 6 kg), or body surface area (C: 1.9 ± 0.1 m2, P:1.9 ± 0.1 m2). However, a difference occurred between the means of age (C: 61 ± 9 years, P: 56 ± 8 years), but that was not considered clinically relevant. The assignment of the patients to the different surgical teams was uniform in both the groups.

GoTable I points out the average hematocrit values at different time points, indicating the different degree of hemodilution and the volume of the postoperative blood loss, the latter being not significantly different between the groups. The higher initial hematocrit value of group C has to be kept in mind for the interpretation of the total requirement of banked blood (Fig. 1).


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Table I. Hematocrit values and volume of postoperative blood loss
 



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Fig. 1. Mean volume of packed red cells (±standard deviation) transfused in each group uncorrected (top) and corrected (bottom) for hematocrit difference.

 
There were no significant differences between the hemostatic parameters of the groups at each time point of measurement. The serum lactate levels (in milligrams per 100 milliliters) in group C were 9.4 before CPB (a), 14.0 after 5 minutes of CPB (b), and 14.6 after crossclamp removal (c). The corresponding values for group P, (a) 10.6, (b) 13.9, and (c) 15.9, were on the same level. In both groups arterial oxygen saturation was 100% at each point of measurement during CPB and in no patient did mixed venous saturation go below the value of 60%, which is considered as a border line for sufficient peripheral oxygenation. In no patient did hematocrit value go below the threshold of 20% at any time during CPB.

Fig. 1 depicts the total volume of homologous packed red cell transfusion and reveals a highly significant difference between groups C and P. Taking into account the higher initial hematocrit value of group P, the following correction was applied: the difference between the initial hematocrit value and the one at hospital discharge was calculated for each patient in group P. From these values the mean difference between hematocrit values at the same time points for group C was subtracted and converted into a virtual volume of packed red cells, assuming 80 ml/kg total blood volume for each patient and a hematocrit value of 60% in each unit of packed red cells. The results were added to the definitely applied volume, therefore indicating the real blood loss (Fig. 1, bottom) in comparison with that in group C. Again a highly significant difference could be evaluated (p < 0.001).

In Fig. 2 the distribution of the patients by the number of transfused homologous blood units is shown. Remarkably, only 16% of group C, but 44% of group P, did not require any homologous blood and, in turn, amounts of more than 5 units were transfused in 9% of group C compared with none of group P.



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Fig. 2. Homologous blood requirements for coronary artery bypass grafting operation. Distribution of patients within two groups by amount of transfused blood units.

 
Very small amounts of fresh frozen plasma were used on average: group C, 56 ml; group P, 0 ml. No significant differences between the groups were observed with regard to blood gas analysis, serum electrolyte levels, or enzyme levels, which were in the normal ranges during anesthesia and the entire stay in the ICU.

DISCUSSION

This study was done retrospectively to eliminate any "alert effects" from surgeons and anesthetists and thus represents the real conditions of our clinical practice. Implications caused by variations in the surgical or anesthetic techniques during the span of investigation can be disregarded. The regimen of banked blood transfusion also did not differ significantly between the physicians involved in the postoperative care. Our results, therefore, indicate that the requirements of homologous blood for operations with CPB can be reduced significantly by an intraoperative autologous blood donation (pooling procedure) before the onset of the CPB. Because the first hematocrit value during CPB on average was 4.7% above the limit of 20% in group P, the sequestered blood volume might have been somewhat larger (the upper limit for the pooling volume was 1000 ml at the time of this study) to maximize the blood-saving effect. However, to accept hemodilution to hematocrit values of 20%, a powerful oxygenator is a basic requirement, because the lower oxygen delivery leads to a higher extraction rate and thus a lower venous saturation. Although venous saturations below 60% had been a problem with older oxygenators that were unable to provide a 100% saturation on the arterial side, especially with higher flow rates under these circumstances, the newer membrane lung (Monolyth) performed flawlessly. Elevated serum lactate levels as an indirect indicator of a temporary state of low oxygen supply in the peripheral tissue or a mixed venous saturation less than 60% never occurred in the pooling group (or in the control group). The other basic requirement is a device for blood gas analysis and hematocrit measurements with a very short delay in displaying its results (on-line or semi-on-line analyzers). This ensures the possibility of a quick retransfusion of the pooled blood in case of an accidentally too low hematocrit value or insufficient oxygenation of the arterial blood.

Under these circumstances the pooling procedure is considered safe, because (unlike during preoperative autologous blood donations) CPB can be started immediately in case of hemodilution-induced hemodynamic problems, thus preventing any myocardial ischemia or damage. Compared with preoperative autologous blood donation the pooling procedure is less cost-intensive and requires much less effort for organization. Because there were no differences between the groups with regard to hemostasis and the postoperative shed blood volume, the mechanism by which this technique works must be substantially based on the dilution effect, causing a lower hemoglobin loss during the bypass period and the subsequent span of the operation after bypass. However, the method theoretically should have the advantage that the pooled blood never comes in contact with the CPB surfaces. Therefore the autologous whole blood transfusion without activation of platelets or leukocytes should provide a better hemostatic status, but this could not be confirmed by the routine tests done in this study.

In the literature there are many reports of other blood-saving procedures. Reinfusion of shed autologous blood, for example, was reported by Vedrinne and associatesGo 6 to be without effect on total blood requirements. Bidstrup and colleaguesGo 3 also could not determine any benefit from autologous blood donation. These authors prefer the administration of high-dose aprotinin, which repeatedly has led to remarkable savings of homologous blood.Go Go Go Go 1-3,6-8 The main effect of aprotinin seems to be its inhibition of the fibrinolytic system.Go 9 This, in turn, may be the reason for its major drawback besides its cost: the building of thrombi. Youngberg Go 10 and Bohrer and associatesGo 11 reported thrombus formations on pulmonary artery catheters. Whether the patency rate of the grafts is also affected remains controversial in the literature.Go 8 Another adverse effect of aprotinin is its possible capability of triggering anaphylactoid reactions.Go Go 8,12

Thus, in conclusion, especially because of its negligible side effects, the pooling procedure is the first-choice method in our clinic to reduce homologous blood transfusions. The results of this study show that we were in the same range of banked blood requirements (1.51 units per patient) as other clinics reported by Roysten. Go 8 Whether an additional administration of aprotinin can further reduce blood loss will be the objective of future studies.

Footnotes

From the Clinic for Anesthesiology and Operative Intensive Care Medicine, University of Kiel,a and the Department of Cardiovascular Surgery, University of Lübeck,b Germany. Back

References

  1. Dietrich W, Barankay A, Hahnel C, Richter JA. High-dose aprotinin in cardiac surgery: three years' experience in 1,784 patients. J Cardiothorac Vasc Anesth 1992;6:324-7.[Medline]
  2. Baele PL, Ruiz-Gomez J, Londot C, Sauvage M, Van-Dyck MJ, Robert A. Systematic use of aprotinin in cardiac surgery: influence on total homologous exposure and hospital cost. Acta Anaesthesiol Belg 1992;43:103-12.[Medline]
  3. Bidstrup BP, Royston D, Sapsford RN, Taylor KM. Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin (Trasylol). J THORAC CARDIOVASC SURG 1989;97:364-72.[Abstract]
  4. Behr W, Doukas K, Lang H, Plahl M, Struck E. Is preservation of erythrocyte concentrates with added solutions an alternative to deep freezing in heart surgery autologous blood donation? Beitr Infusionther 1990;26:252-6.
  5. Honek T, Horvath P, Kucera V, Kostelka M, Hucin B, Stark J. Minimisation of priming volume and blood saving in paediatric cardiac surgery. Eur J Cardiothorac Surg 1992;6:308-10.[Abstract]
  6. Vedrinne C, Girard C, Jegaden O, et al. Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin versus autologous fresh whole blood transfusion. J Cardiothorac Vasc Anesth 1992;6:319-23.[Medline]
  7. van Oeveren W, Harder MP, Roozendahl KJ, Eijsman L, Wildevuur CR. Aprotinin protects plateletes against the initial effect of cardiopulmonary bypass. J THORAC CARDIOVASC SURG 1990;99:788-96.[Abstract]
  8. Roysten D. High-dose aprotinin therapy: a review of the first year's experience. J Cardiothorac Vasc Anesth 1992;6:76-100.[Medline]
  9. Marx G, Pokar H, Reuter H, Doering V, Tilsner V. The effects of aprotinin on hemostatic function during cardiac surgery. J Cardiothorac Vasc Anesth 1991;5:467-74.[Medline]
  10. Youngberg JA. Aprotinin and thrombus formation on pulmonary artery catheters: a piece of the coagulation puzzle. J Cardiothorac Anesth 1990;4:155-8.[Medline]
  11. Bohrer H, Fleischer F, Lang J, Vahl C. Early formation of thrombi on pulmonary artery catheters in cardiac surgical patients receiving high-dose aprotinin. J Cardiothorac Anesth 1990;4:222-5.[Medline]
  12. Bohrer H, Back A, Fleischer F, Lang J. Adverse effects of high-dose aprotinin in a paediatric cardiac surgical patient. Anaesthesia 1990;45:853-4.[Medline]



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