Impact of autologous blood transfusion on the use of pack of red blood cells in coronary artery bypass grafting surgery

1. Anesthesiologist, MD, MSc. University Hospital of Santa Maria (HUSM). Post-Graduate Program on Health Sciences Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil. Study design, data collection, anesthesia of the patients, writing, and review. 2. Medical Student. Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil. Data collection, structuring of the database, and review. 3. Perfusionist Nurse. University Hospital of Santa Maria (HUSM), Santa Maria, RS, Brazil. Data collection, management of perfusion of patients, and review. 4. Cardiovascular Surgeon, MD. University Hospital of Santa Maria (HUSM), Santa Maria, RS, Brazil. Surgeon who operated on patients, structuring of the database, review. 5. Anesthesiologist, MD, PhD. Associate Professor of Anesthesiology. Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil. Coorientation of the study, review. 6. Anesthesiologist, MD, TSA. Chief, Division of Anesthesiology. University Hospital of Santa Maria (HUSM), Santa Maria, RS, Brazil. Study design, coorientation to the study, anesthesia of the patients and review. 7. MD, PhD. Attending Physician, Division of Hematology-Oncology. University Hospital of Santa Maria (HUSM). Supervisor Professor at Post-Graduate Program on Health Sciences Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil. Orientation of the study, review of data collected, review.


INTRODUCTION
Cardiovascular diseases are the leading causes of mortality not only in Brazil but also throughout the world [1,2], with acute myocardial infarction (AMI) being the main cause of death.The AMI surgical treatment through coronary artery bypass grafting surgery is an usual procedure, which is frequently associated with cardiopulmonary bypass (CPB) and high rates of homologous blood transfusion, varying from 40 to 90% in most publications [3][4][5].Transfusion therapy is associated with several unfavorable outcomes, such as renal dysfunction, cardiac, neurological and immunological complications, among others [6].
There is no consensus regarding an ideal value of hemoglobin or hematocrit which suggests transfusion in cardiac surgeries.The American Society of Anesthesiologists (ASA) recommends that pRBC transfusion in patients with serum level of hemoglobin between 6 and 10 g/dL be based on the risk of developing complications or organic lesion by inappropriate oxygenation [7].The latest consensus concerning perioperative transfusion in cardiac surgery identified six variables as being important risk indicators of pRBC transfusion: old age, small total amount of red blood cells (anemia or small body size), use of antiplatelet or antithrombotic drugs, reoperation or complex procedures, emergency procedures and non-cardiac comorbidity.This same study stated, with a level A of evidence (class I), that all measures of pre and perioperative blood conservation must be taken into this group of patients, since they correspond to the greatest part of hemocomponent transfusions [8].
Among mechanical strategies to reduce the necessity of homologous pRBC transfusion, we find the so-called Cell Saver (CS).It is a specialists' consensual opinion (level C of evidence and class IIb recommendation) that the use of autologous blood transfusion through mechanisms such as Cell Saver is reasonable, during surgeries with cardiopulmonary bypass [8].However, there are few studies related to the impact of this practice on the real necessity of pRBC transfusion in cardiac surgeries with CPB, especially in coronary artery bypass grafting surgeries.The present study aims to evaluate the impact of Cell Saver on the necessity of pRBC use in coronary artery bypass grafting surgeries associated with miniCPB which were carried out at the University Hospital of Santa Maria (HUSM).

METHODS
We carried out a retrospective cross-sectional study in patients who had their health care provided by the Division of Cardiac Surgery of HUSM, undergoing CABG surgery from January 2011 to October 2012.All patients were operated by the same surgical team, with right atrial and aortic cannulation, mild hypothermia and blood cardioplegia, and perfusion managed by only one professional.The same group of anesthesiologists was in charge of all patients' anesthesia care, following the indicative criteria of pRBC transfusion: metabolic acidosis, bad peripheral perfusion, cerebrovascular disease, peripheral vascular disease, hemodynamic instability and mixed venous saturation (SvO 2 ) <75%.
Patients with ischaemic heart disease undergoing CABG associated with miniCPB, either using hemocomponents or not in the intra or postoperative periods were included in the study.The exclusion criteria were: combined cardiac surgery, previous cardiac surgery, emergency surgery, surgery indication for non-ischaemic heart disease and the use of hemocomponents in priming constitution in the circuit in miniCPB.
To determine the minimum sample size, we collected a pilot sample of 10 cases from the group without CS use (without-CS) and 14 cases in the group with CS use (with-CS), considering a 5% significance level, a power of 80% and a sample error (e 0 ) of 0,5 pRBC bags, with standard deviations estimates of 1.287 and 0.938, respectively, totalizing 44 patients in each group.Upon the necessary minimum sample size, we selected the last 44 patients who underwent coronary artery bypass grafting surgery with miniCPB and did not make use of CS, as well as the first 43 that used it.As randomized selection of patients was not used in the study, the occurrence of sample selection bias is possible.However, we intended to minimize it through a linear selection of patients, in which the first half did not use CS and the second half did.There was no change in the anesthetic-surgical technique in both groups of patients.
The Cell Saver System (autoLog ® Autotransfusion System, Medtronic) is composed of a console which is responsible for its operation and programming, as well as a disposable set which includes a vaccum, cardiotomy reservoir, centrifugation reservoir, waste bag, blood collection reservoir bag, which is assembled in each surgery.The CS operation was managed by the same perfusionist who was responsible for performing the cardiopulmonary bypass.This system has been used as a routine in cardiac surgeries which are carried out at HUSM since the end of the year 2011.
We investigated cardiovascular surgical risk factors such as hypertension, smoking, diabetes mellitus, COPD, renal dysfunction and previous AMI through an instrument for collecting data, developed for this specific purpose.We also collected information related to the surgical procedure (CPB time and aortic clamp, the amount of grafted blood vessels) and the anesthetic procedure (ASA classification, blood typing and Rh factor, left ventricular ejection fraction and previous and postoperative hematocrit and hemoglobin), as well as the use or not of hemocomponents in the intra and immediate postoperative periods (up to 24h).To evaluate whether there was some difference in the use of pRBC, the c 2 test was applied in the groups, using the program called Statistica v. 9.1 (Statsoft Inc., Tulsa, OK, USA).The present study was approved by the UFSM Research Ethics Committee (N o .36,523, June 13 th 2012) in compliance with 196/96 National Health Council Resolution (Conselho Nacional de Saúde).

RESULTS
Patients' profile in both groups related to cardiovascular surgical risk factors, previous AMI, value of LV ejection fraction, as well as frequencies referred to blood typing, Rh factor and ASA classification may be seen in Table 1.The data are not only frequency-based, but also expressed through mean, standard deviation and significance level.There was no statistically significant difference between the two groups in relation to researched cardiovascular surgical risk factors.The values of hematocrit and early hemoglobin (presurgical) are also found in Table 1.
The groups without-CS and with-CS showed, respectively, mean values of 89.52±20.23minand 86.58±24.90min of CPB time and 72.02±20.91minand 67.37±21.21minaortic clamp time.The mean number of grafted blood vessels (distal anastomosis) was 3.00±0.71 in the group without-CS and 2.81±0.85blood vessels in the group with-CS.There was not also a statistically significant difference between the groups for these variables, confirming the global sample homogeneity.
When we evaluated the use of intraoperative pRBC or not, there was a statistically significant difference between the two groups (P=0.00008).In the group without-CS, 21 patients (47.7%) received intraoperative pRBC, whereas in the group with-CS, only four patients (9.3%) received homologous pRBC besides the one processed by Cell Saver.Such results show that the pRBC volume processed by CS significantly decreased the necessity of homologous pRBC use in the group that made use of this system (Table 2).
The pRBC mean volume processed by Cell Saver in the patients that used it was 503.34±148.90ml,ranging from 183ml to 872ml.Considering that the mean pRBC volume which is processed by each unit and recommended by the Brazilian Ministry of Health is 220-280ml, it is possible to infer that CS was able to avoid, on average, the transfusion of approximately two homologous pRBC units in each patient.
When homologous pRBC volumes used in the intraoperative period were evaluated, the patients from the group without-CS showed significantly higher volumes (198.65±258.65ml)than the homologous pRBC ones used in the patients from the group with-CS (35.06±125.67ml)(P=0.000117).
The mean values of postoperative hematocrit and hemoglobin of both groups may be seen in Table 3.In relation to the hemoglobin variable, there was positive correlation between the groups of a 5% significance level (P=0.016),showing that the patients from the group that used the blood volume processed by CS had superior mean values of hemoglobin compared to the mean values of patients from the group without-CS.The postoperative mean values of hematocrit were also superior in the group with-CS, but not reaching statistical significance (P=0.057).
Upon analyzing the postoperative data, there was no statistically significant difference in the absolute use of pRBC in the immediate postoperative period (up to 24h) (P=0.739),not even in the pRBC volumes used (P=0.642401) between the two groups.
Such results show that Cell Saver is efficient in the reduction of absolute use and in the reduction of pRBC mean volume used in intraoperative coronary artery bypass grafting surgery, when associated with miniCPB.

DISCUSSION
The use of hemotransfusions in patients undergoing cardiac surgeries is frequent, due to higher morbidity of this population and the complexity of the procedure itself.It is estimated that 20% of all blood transfusions in the United States are linked to cardiac surgeries [3].For this reason, there is great interest in developing mechanisms and techniques which are able to reduce this great necessity.
CPB has a considerable impact on the systemic inflammatory response and on the induction of circulatory diseases [9], which may be attenuatted through miniaturization of its circuit (miniCPB).With miniCPB, it was possible to diminish the patient's hemodilution, as well as reducing the blood contact surface with non-endothelial structures, resulting in a lower necessity of hemocomponents transfusion compared to the conventional use of CPB, with significant impact on cardiac surgeries outcome [10].
Autotransfusion through devices which can process intraoperative bleeding and promotes hemoconcentration, with posterior reinfusion to the patient, has been the most used method currently in elective cardiac surgeries [11,12].The benefits in using this kind of system are considerable, as they diffuse in different steps of the global process of hemotransfusion.Perhaps the best characteristic of this system is the elimination of all steps of processing, storage and later distribution of pRBC in blood banks, since the final pRBC volume is processed and reinfused in the patient inside the surgical environment.Thus, it is possible to avoid a bag switch, contamination in processing, and other potential errors while managing the product.Another benefit is a better proven viability of processed red blood cells due to the absence of the storage process, which causes a decrease in 2.3-DPG levels, besides morphological alterations in the erythrocyte cytoskeleton [13,14].CS is also safer in terms of transmission of external infectious agents [15], besides significantly diminishing all the other risks and immunological complications or not related to blood transfusion therapy [16].
Since the 1970s, studies have been carried out to evaluate the CS performance related to the necessity of blood transfusion, especially in surgeries with a high risk of bleeding, for instance, cardiac surgeries.The use of CS in cardiac surgeries has already been compared to the use of associated cardiopulmonary bypass or not, showing that, regardless of CPB use, there was a lower necessity of homologous blood transfusion in relation to the group who did not use it [17].In our study, we chose to include only patients who underwent CABG with miniCPB because of advantages previously discussed.
Another study evaluated the new hemoconcentration technique, which is used in CS, in the necessity of hemocomponents transfusion in patients undergoing coronary artery bypass grafting surgery [18].This study evaluated two groups of patients, one using the hemoconcentrator and the other not using it, investigating the quantity of blood used during CPB and in the immediate postoperative period.The group that used the hemoconcentrator showed a lower necessity of blood transfusions during CPB, as well as lower mean volumes of used blood in the intraoperative period.
In 2009, an important meta-analysis evaluated the efficiency of CS use in cardiac surgeries, showing that it reduces the necessity of exposure to hemocomponents and pRBC in this population when compared to the non-use of CS, indicating the benefit of applying this system in bleeding throughout the intraoperative period [19].
Another study comparing the use of CS in immediate postoperative outcomes of 288 patients who underwent cardiac surgeries with CPB showed advantages in the use of CS, especially in an increase of postoperative hemoglobin levels and no hospitalization time in ICU [20].The same study also evaluated the blood volume which was reinfused in each patient by CS, resulting in a mean of 426ml pRBC, a slightly inferior value in relation to the one found in our study (mean of 503.34ml).However, the former study evaluated cardiac surgeries with conventional CPB, not with miniCPB as in our study.The use of miniCPB may have highly contributed to obtain more significant results, showing that it may provide more favorable outcomes.
On the other hand, other authors reported that the use of CS may not have clinical benefits in certain groups of patients.They state that with the proper control of intraoperative hemostasis in patients with low risk of bleeding during cardiac surgeries, the use of CS may not have a reasonable cost-benefit [8], not reducing the use of homologous transfusion [21].Nevertheless, the technical complexity, which is inherent in cardiac surgeries, associated with a higher morbidity of patients undergoing such procedure per se would be potential indicators of the necessity of pRBC homologous transfusion.
Our study showed an important reduction in the use of pRBC in the intraoperative period of coronary artery bypass grafting surgery with miniCPB associated with CS.With the reinfusion of autologous pRBC processed by the system during the intraoperative period, there was a lower necessity of homologous pRBC in these patients.The mean volume of pRBC processed by CS was 503.34±148.90ml,corresponding approximately to two homologous pRBC units.This pRBC volume, which was reinfused, avoided the use and, consequently, specific risks related to homologous hemotransfusion, which have already been previously discussed.The analysis of such risks was not the objective of the present study, but they are important variables which deserve attention and must be evaluated in further studies.The postoperative values of hemoglobin and hematocrit in the patients who used CS were also higher in relation to the other group.In addition, the population of patients who received autotransfusion benefited from a pRBC with superior viability in relation to the stored homologous pRBC.
Taking in consideration that it was a cross-sectional study, our research shows a range of methodological limitations, which were, to some extent, minimized throughout its development.However, we were able to show that the use of CS led to an important impact in terms of reducing homologous pRBC use in CABG with miniCPB, possibly being as basis for new investigations related to cost-effectiveness, cost-benefit, mortality, long-term risks and complications by using this system in such surgical procedures.

CONCLUSION
The use of Cell Saver was efficient in reducing the necessity of intraoperative use of homologous packed red blood cells in patients undergoing coronary artery bypass grafting surgery associated with miniCPB.When it was necessary, the homologous pRBC volume used was significantly greater than the group of patients who did not use CS, showing that the autologous pRBC volume processed by CS and reinfused in the patient was also efficient in reducing this necessity.
Silva LLM, et al.-Impact of autologous blood transfusion on the use of pack of red blood cells in coronary artery bypass grafting surgery

Table 1 .
Patients' profile stratified by group Silva LLM, et al. -Impact of autologous blood transfusion on the use of pack of red blood cells in coronary artery bypass grafting surgery BSA: body surface area; SAH: systemic arterial hypertension; DM: diabetes mellitus; COPD: chronic obstructive pulmonary disease; AMI: acute myocardial infarction; LVEF: left ventricular ejection fraction; ASA: clinical classification of American Society of Anesthesiologists; BT: blood type; Rh: Rh factor; Ht: hematocrit; Hb: hemoglobin; Clamp T.: aortic clamp time; CPB T.: cardiopulmonary bypass time

Table 3 .
Postoperative mean values of hematocrit and hemoglobin in both groups PO: postoperative; Ht: hematocrit; Hb: hemoglobin

Table 2 .
Necessity of intra and postoperative packed red blood cells in both groups Silva LLM, et al. -Impact of autologous blood transfusion on the use of pack of red blood cells in coronary artery bypass grafting surgery