1. NABM James D. Ferguson Seattle, Washington September 8 th -10 th,2011

2. The 4 Major Components of Blood The AABB recommendations and STS Guidelines for cell salvaging “Shed Blood” What are the make-up and components of “Shed Blood” “Shed Blood” “Cardiotomy blood” Clearly identify what is “Shed Blood” and what is “Cardiotomy blood”

3. “SHED BLOOD”: It’s time for Perfusion and the Cardiac Surgery arena to clearly define the term “SHED BLOOD”: I propose the following definitions: “Cardiotomy Blood” “Cardiotomy Blood” – is the franc whole blood that accumulates inside the pericardium coming directly from a great vessel or the open heart itself and should be returned via the cardiotomy suction (Pump Sucker) “Shed Blood” “Shed Blood” – is the blood that has accumulated OUTSIDE the pericardium including chest tube drainage or blood lost from other wound sites and is collected until the patient stops bleeding and should be returned via a Cell Washer

4. Lost Blood Shed Blood Sent to the Cell Washer Washed and Filtered Returned to Patient via Anesth Cardiotomy Blood Returned to the Heart Lung Machine Directly returned to patient circulation

5. ?Any Blood Lost Outside the Body During Cardiac Surgery?

8.  Mortality & Morbidity  TRALI (Tx Related Acute Lung Injury)  LOS – infection, CA  Immunomodulation : the immune system is “Hyper- activated”  Increased # & length of ICU stays, ventilator times  Poor wound healing  Rehabilitation times & Readmissions  “Patients who receive multiple transfusions are at risk for iron toxicity when the iron-carrying capacity of the blood is exceeded” -Aryeh Shander, MD Director of Care, Englewood Hospital & Medical Center

9. In cardiac surgery some patients require blood transfusions to compensate for the large blood loss (Shed Blood) that occurs during the procedure 2 common techniques exist to limit the amount of “shed blood”: pump sucker 1. The use of a pump sucker that returns the blood back to the cardiopulmonary bypass (heart lung machine) pump for quick return to general or systemic circulation “cell salvaging” 2. The alternative technique is the use of a “cell salvaging” device that collects, washes and re- infuses RBC’s to the patient also known as a Autotransfusion system (ATS)

10. Are there components found in shed blood that are harmful? Do they pose a threat if re-infused back into the patient’s circulation? Is it of clinical significance? or are these biological markers transient and reversible in the patient?

15. The beneficial effects of shed blood reinfusion have been subject to scrutiny concerning its benefits and consequences Specifically, looking at the properties of shed blood, techniques for safe reinfusion and potential patients benefits. A review of the current literature considering the use of shed blood during (CPB) cardiopulmonary bypass will benefit the cardiac surgical team in providing safe patient care, and help to enhance patient outcomes. “should shed blood be used during cardiac surgeries, and if so, how to utilize it effectively and safely to benefit the cardiac patient.” Clinical Perfusion Education University of Nebraska Medical Center

16. -Proinflammatory mediators -Proinflammatory mediators -Cytokines -Cytokines -Activated cells and cellular debris -Activated cells and cellular debris -Creatine Kinase-MB -Creatine Kinase-MB -Increased plasma free hemoglobin -Increased plasma free hemoglobin -Positive bacterial cultures -Positive bacterial cultures

17. Debris present in the surgical field may be intentionally or unintentionally aspirated into the cardiotomy reservoir and/or cell salvage devices.  Heparin or other Anticoagulants  Clot formations  Fibrin Strands  Lipid Emboli  Tissue  Antibiotics  Leukocytes  Plasma Free Hgb  Bacterium  Bone JECT 2003;35:28-34

18.  Should we discard cardiotomy suction blood?  What measures can we take to avoid the use of cardiotomy suction blood?  Is it possible to “treat” cardiotomy suction blood?

20. -Significant literature suggests that the use of shed blood returned directly to the cardiotomy should only be used when extremely necessary. ( Journal of Cardiothoracic and Vascular Anesthesia 2004;21: 519-523) -The increased concentrations of thrombin-antithrombin III complex and fibrin degradation products indicated renewed systemic clotting and fibrinolysis as a direct result of the retransfusion of suctioned blood. (Ann Thorac Surg 1996;62:717-23) -“The retransfusion of highly activated suctioned blood during CPB exacerbates wound bleeding.” (Ann Thorac Surg 1995; 59: 901-07) -Furthermore, coronary surgery without retransfusion of cardiotomy suction blood and mediastinal shed blood reduces the postoperative systemic inflammatory response. (Journal of Cardiothorac and Vasc Anesth 2004;21: 519- 523) Cardiotomy Blood Concerns

21. “Recent studies have focused on the origins of thrombotic stimulus and the possible role of retransfused suctioned blood from the thoracic cavities on the activation of the extrinsic coagulation pathway.” Microembolization during cardiopulmonary bypass (CPB) can be detected in the brain as lipid deposits that create small capillary and arteriolar dilations (SCADs) with ischemic injury and neuronal dysfunction. – SCAD density is increased with the use of cardiotomy suction to scavenge shed blood. – Use of a cell washer to scavenge shed blood during CPB decreases cerebral lipid microembolization. More Cardiotomy Blood Concerns Ann of Thorac Surg 2000;70: 1296-1300

22. Webb, et al, looked at the infusion of such particles after the shed blood was washed and then passed the blood through a series of lipid and leukocyte filters – Their findings indicate that the use of processed blood should be employed with consideration of at least a 40μm filter, and a filter with adequate microaggregate retention capabilities. – Additionally, The use of such filters (lipid/leukocyte) of at least 40μm would significantly reduce the potential exposure to these microemboli Brinke et al. in 2005 – Concluded that use of a continuous autotransfusion system stabilizes the performance of the transfusion leukocyte- depletion filter and significantly enhances its leukocyte and platelet removal efficiency. In particular, neutrophils are efficiently removed

23. risk of stroke postoperatively is approximately 1-5%., vary markedly depending on the detection method, although typically it is reported in at least 10%  “The risk of stroke postoperatively is approximately 1-5%. Incidences rates for neurocognitive deficit, however, vary markedly depending on the detection method, although typically it is reported in at least 10% of Patients during cardiac surgery depends upon the surgical team’s ability to minimize operative emboli of any source including GME from entering the patient’s circulation  Reducing cerebral injury during cardiac surgery depends upon the surgical team’s ability to minimize operative emboli of any source including GME from entering the patient’s circulation (Venous line air) eliminating these microemboli are essential before reinfusing the product  To utilize shed blood effectively, eliminating these microemboli are essential before reinfusing the product into the patient. Clinical Perfusion Education University of Nebraska Medical Center

24. Separate Chamber Venous and Cardiotomy Reservoir and Cardiotomy Reservoir Sorin  D903 Avant 

25. Dr Stump’s research on cardiotomy blood is what changed how Perfusion and the entire Cardiac arena practices Dr Stump’s research on cardiotomy blood is what changed how Perfusion and the entire Cardiac arena practices What Caused the Change, How it Changed, and Why it Changed????? What Caused the Change, How it Changed, and Why it Changed?????

27.  To improve the quality of shed blood prior to its autotransfusion during CPB.  Two potential strategies: - Arterial line filtration (Cardiotomy) - Processing blood with a cell washer (ATS) Annals of Thoracic Surgery 2000;70:1296-1300

28.  Approved by the Wake Forest University School of Medicine Animal Care and Use Committee.  24 mongrel dogs (28-35 kg) were studied.  IV anesthesia with fentanyl and diazepam.  Median sternotomy, left subclavian arterial and bi-caval cannulation. Annals of Thoracic Surgery 2000;70:1296-1300

29.  Initiated CPB and cooled the dogs to 28 0 C and after 40 minutes CPB, rewarmed to 36 0 C. arterial circuit  Cardiotomy suction reservoir blood, OR processed cell saver blood, returned through arterial circuit  After 10 minutes recirculation of shed blood, dogs euthanized, brains harvested, analyzed for SCAD density. Annals of Thoracic Surgery 2000;70:1296-1300 Is it common to add the cardiotomy blood to the arterial circuit??? Or should it be added to the venous side ???

30. Number of Cerebral Lipid Microemboli and Shed Blood Return 70 60 50 40 30 20 10 4  111  3 66  19 24  5 No Shed Blood Cell Saver CS Arterial Filter Sample Taken From Shed Blood Returned Annals of Thoracic Surgery 2000;70:1296-1300 SCADs s/cm 2

32. Scavenged blood is a source of cerebral lipid microemboli. Use of a cell washer to retrieve and process scavenged blood appears to decrease microembolic burden compared to cardiotomy suction blood passing through arterial line filters used in CPB. But are Lipids Normal? Annals of Thoracic Surgery 2000;70:1296-1300

33. A national survey conducted Just in Canada demonstrated significant variation in the handling and utilization of cardiotomy blood in various Cardiac surgery centers – 42% routinely wash cardiotomy blood, 58% performed no processing, and 6% utilized additional filtration Perfusion 2005; 20(5):237-41

34. CONCLUSIONS: Prospective longitudinal neuropsychological performance of patients with coronary artery bypass grafting did not differ from that of a comparable nonsurgical control group of patients with coronary artery disease at 1 or 3 years after baseline examination. This finding suggests that previously reported late cognitive decline after coronary artery bypass grafting may not be specific to the use of cardiopulmonary bypass, but may also occur in patients with similar risk factors for cardiovascular and cerebrovascular disease.

35. Methods – 71 patients were enrolled undergoing isolated CABG procedures. A Doppler ultrasound was recorded every 8 milliseconds of the inflow and outflow of the CPB circuit. S100B were measured before surgery and 48 hours after surgery. Results – Emboli leaving the CPB circuit was detected in 67 patients. The distribution of microemboli varied across patients. Most patient had elevated S100B levels following surgery. The authors showed an association between the neurologic injury measured as S100B levels and microemboli detected in the CPB circuit. They suggest reductions in neurologic injury may result from redesign of the CPB circuit to prevent emboli leaving the circuit Conclusion – The authors showed an association between the neurologic injury measured as S100B levels and microemboli detected in the CPB circuit. They suggest reductions in neurologic injury may result from redesign of the CPB circuit to prevent emboli leaving the circuit

36. Methods: Methods: Seven Adult pigs were used. A shed blood surrogate and radioactive triolein was produced to generate a lipid embolic load. The surrogate blood was transfused to the R. atrium. The animals arterial, pulmonary, R. and L. atrial pressures along with cardiac output and dead space were measured. At the end an increase in CO and Pulmonary pressure were pharmacologically induced to try and flush out the lipid particles from the lungs Results: Results: A more than 30 fold increase in pulmonary vascular resistance was observed with subsequent increase in pulmonary artery pressure and decrease in CO and arterial pressure. Conclusion: Infusion of blood containing lipid micro-emboli on the venous side leads to acute, severe hemodynamic responses that can be life threatening. Lipid particles will be trapped in the lungs, leading to persistent effects on the pulmonary vascular resistance. Journal of Cardiothoracic Surgery 2009;4:48

37.  The study showed Shed Mediastinal Blood (SMB) contains high levels of enzymes that determine cardiac injury and infusion of this blood markedly increased these levels  There was also increased levels of Plasma Free-Hgb and immature neutrophils  The authors concluded the results support the idea that SMB does cause a coagulopathy in some patients and has other clearly undesirable consequences  Although, the study clearly showed that the authors collected blood/fluid from the pleural space and this increased the volume collected from this source rather than the heart and mediastinum leading to high levels of Free-Hgb, Neutrophils, and Cardiac enzymes

38.  Background – Processing of pericardial shed blood with a cell-saving device was claimed to prevent lipid microembolization and to protect from neurocognitive dysfunction after CPB  Methods - Forty patients, 65 yrs and older, were prospectively randomized to processing of pericardial shed blood with a cell-saving device or to conventional use of a standard closed venous reservoir where cardiotomy blood was collected and reinfused through the arterial circuit for the control group. Near-infrared Spectroscopy before surgery and at the time of discharge from the hospital. The also looked at protein S100B in all patients.  Results – The protein S100B levels averaged 0.06 ± 0.03 before surgery and 0.51 ± 0.23 30 minutes after surgery compared with 0.076 ± 0.04 before surgery and 1.48 ± 0.66 in the control patients. The S100B was significantly higher in the control group vs. the cell saver group. Although the use of the cell-saving device was NOT associated with higher brain oxygen saturation nor changes in the stroke score but it was associated with lesser release of nonspecific markers of brain injury  Conclusions – The S100B was significantly higher in the control group vs. the cell saver group. Although the use of the cell-saving device was NOT associated with higher brain oxygen saturation nor changes in the stroke score but it was associated with lesser release of nonspecific markers of brain injury

39. Current evidence suggests that the use of a cell saver reduces exposure to allogenic blood products or red blood cell transfusions for patients undergoing cardiac surgery. Sub- analyses suggest that a cell saver may be beneficial only when it is used for shed blood and/or residual blood or during the entire operative period. Processing cardiotomy suction blood with a cell saver only during CPB has no significant effect on blood conservation and increases fresh frozen plasma transfusion. The Meta-Analysis contained 31 randomized studies and 2282 patients

40. Cell washing should be kept to a minimum and limited to the pre- and post- heparinization period. Coronary suckers are a safe alternative to use during the period of heparinization to preserve franc autologous whole blood and return it back to circulation. A waste sucker should be kept in the field of surgery for undesirable shed blood and irrigant solutions. Shander A, Moskowitz D, Rijhwani TS. The safety and efficacy of "bloodless" cardiac surgery. Semin Cardiothorac Vasc Anesth. 2005;9(1):53-63.

41. Abstract Objective: During cardiopulmonary bypass (CPB), systemic coagulation is believed to become activated by blood contact with the extracorporeal circuit and by retransfusion of pericardial blood. To which extent retransfusion activates systemic coagulation, however, is unknown. We investigated to which extent retransfusion of pericardial blood triggers systemic coagulation during CPB. Methods: Thirteen patients undergoing elective coronary artery bypass grafting surgery were included. Pericardial blood was retransfused into nine patients and retained in four patients. Systemic samples were collected before, during and after CPB, and pericardial samples before retransfusion. Levels of prothrombin fragment F1+2 (ELISA), microparticles (flow cytometry) and non-cell bound (soluble) tissue factor (sTF; ELISA) were determined. Results: Compared to systemic blood, pericardial blood contained elevated levels of F1+2, microparticles and sTF. During CPB, systemic levels of F1+2 increased from 0.28 (0.25—0.37; median, interquartile range) to 1.10 (0.49—1.55) nmol/l ( p = 0.001). This observed increase was similar to the estimated (calculated) increase ( p = 0.424), and differed significantly between retransfused and non- retransfused patients (1.12 nmol/l vs 0.02 nmol/l, p = 0.001). Also, the observed systemic increases of platelet- and erythrocyte-derived microparticles and sTF were in line with predicted increases ( p = 0.868, p = 0.778 and p = 0.205, respectively). Before neutralization of heparin, microparticles and other coagulant phospholipids decreased from 464 mg/ml (287—701) to 163 mg/ml (121—389) in retransfused patients ( p = 0.001), indicating rapid clearance after retransfusion. Conclusion: Retransfusion of pericardial blood does not activate systemic coagulation under heparinization. The observed increases in systemic levels of F1+2, microparticles and sTF during CPB are explained by dilution of retransfused pericardial blood

42. Objective: Elimination of cardiotomy suction increases reliance on cell-saver blood-conservation techniques. Reinfusion of processed cell-saver blood (PCSB) even without using cardiotomy field suction may contribute to thrombin, cytokines, platelet activators, and hemolytic factors measured systemically. Design: This study was designed as a prospective, un-blinded observational study of patients undergoing first time, non-emergent on-pump coronary artery bypass graft surgery. Setting: A university medical center. Participants: Fourteen patients were enrolled after informed consent. Interventions: Arterial blood was sampled (1) before cardiopulmonary bypass, (2) immediately after bypass, and (3) 4 hours after bypass. PCSB, using the AutoLog (Medtronic, Inc, Minneapolis, MN), was sampled after bypass. Measurements and Main Results: Blood and PCSB levels of prothrombin fragments 1.2, -thromboglobulin, interleukin- 6, interleukin-8, polymorphonuclear leukocyte-elastase, neuron-specific enolase, and S-100 were assayed by using enzyme-linked immunosorbent assay. Paired comparisons were performed by using paired t tests. Compared with post-bypass blood, processed cell-saver blood (prepatient infusion) had higher levels of polymorphonuclear leukocytelastase, interleukin-8, neuron-specific enolase, and S-100 (p < 0.05). Conclusions: Reinfusion of PCSB directly and independently contributes to systemic elevations in interleukin-8, polymorphonuclear elastase, neuron-specific enolase, and S-100B, augmenting and perhaps accentuating the postoperative inflammatory response. Further evaluation and improvement in cell-salvaging technology and processing techniques are warranted.

43. Munir Boodhwani, Howard J. Nathan, Fraser D. Rubens On behalf of the Cardiotomy Investigators Scientific Sessions 2006 Chicago, Illinois November 13, 2006 The authors have no conflicts of interest to disclose

44.  Processing of cardiotomy blood through ATS washing and filtration results in coagulation abnormalities: Increased PTT and TT Increased INR Decreased Fibrinogen Decreased Clotting factors Decreased Important Plasma Proteins  Cardiotomy blood processing results in increased intra-operative and post-operative blood product use:  ~ 0.43 PRBC units/patient  ~ 0.94 non-RBC units/patient

45. Conclusions from Study Contrary to expectations, processing of cardiotomy blood before reinfusion results in greater blood product use with greater postoperative bleeding in patients undergoing cardiac surgery. There is no clinical evidence of any neurologic benefit with this approach in terms of postoperative cognitive function. In the absence of a proven benefit in terms of neurological protection or hemodynamic stability, we believe that there is little to justify the routine use of this technique. Munir Boodhwani, MD & Fraser D. Rubens, MD

46. Recent Evidence-Based Guidelines (JTCVS Aug 2006;132(2):283) – “Direct reinfusion to the CPB circuit of unprocessed blood exposed to pericardial and mediastinal surfaces should be avoided (Class I, Level B) – “Blood cell processing and secondary filtration can be considered to decrease the deleterious effects of reinfused shed blood (Class IIb, Level B) This is the largest randomized, double-blinded study examining the effects of cardiotomy blood processing and can be used to inform the guidelines Demonstrates the feasibility of double-blinding in trials comparing interventions related to CPB

47. Blood salvage interventions:  Routine use of red cell salvage using centrifugation is helpful for blood conservation in cardiac operations using CPB - (Level of evidence A) I – A (When used appropriately)  During CPB, intraoperative autotransfusion, either with blood directly from cardiotomy suction or recycled using centrifugation to concentrate red cells, may be considered as part of a blood conservation program - (Level of evidence C) IIb  Consensus suggests that some form of pump salvage and reinfusion of residual pump blood at the end of CPB is reasonable as part of a blood management program to minimize blood transfusion - IIa (C)  Centrifugation of pump-salvaged blood, instead of direct infusion, is reasonable for minimizing post-CPB allogenic red blood cell (RBC) transfusion - IIa (A)

48.  So what can we determine from all of these studies??  Cell Salvaging is good in a limited amount for lipid removal?  Shed blood Contains a plethora of bad stuff and Should this be reinfused? Or Maybe not?

49.  AABB recommends the following general indications for Cell Saving (CS): 1. The anticipated blood loss is 20% or more of the patients estimated blood volume 2. Blood would ordinarily be cross-matched 3. More than 10% of patients undergoing the procedure require transfusion 4. The mean transfusion for the procedure exceeds 1 unit 5. This defines every Cardiac Surgery patient Transfusion 2004;44:40S-44S

50. Abstract: Cell salvage devices are routinely used to process and wash red blood cells (RBCs) shed during surgical interventions. Although the principle theory of cell saving is the same, the actual process to achieve this is very different from one device to another. The purpose of this study was to compare the quality of washed, concentrated RBC produced by five very different cell saving devices, specifically the Cobe BRAT 2, Medtronic Sequestra 1000, Haemonetics Cell Saver 5, Medtronic Autolog, and the Fresenius CATS. Reservoir and washed red blood cells were analyzed for hematocrit (Hct), platelets (PLT), leukocytes (WBC), potassium (K+), heparin, plasma-free hemoglobin (PFH), RBC mass recovery and recovery rate. The Haemonetics and BRAT 2 had the highest RBC recovery. All devices adequately removed heparin and potassium. The Medtronic Autolog had the highest removal of platelets and PFH; whereas, the BRAT had the lowest. Although the Autolog had the highest leukocyte removal, leukocytes were not adequately washed out by any of the autotransfusion devices. In Conclusion, although all cell- saving devices use the same theory of centrifugation, the actual quality of the washed RBC product differs widely from one device to another.

51.  Provides intraoperative means of cell conservation  Helps to reduce Lipid microembolization in blood  Helps reduce some inflammatory response  Can serve as an autologous source of RBC’s reducing the need for RBC transfusions  Used by religious groups and others who refuse blood transfusions

52. “If only the processed red cells are replaced and no consideration is given to the plasma or platelets lost, increased bleeding may occur due to the dilution of the clotting factors and the loss of platelets.” The potential problems that are found in processed shed blood are that the platelets and WBC’s that remain in the end product are now activated by the centrifugation process as well as the potential emboli these device may create or enhance. Lastly the viable platelet, clotting factors and plasma proteins are now washed away. Autotransfusion Pitfalls

53. AdvantagesDisadvantages 1. Higher red cell concentration 2. Higher 2,3 DPG content 3. Reduced osmotic fragility 4. Reduction in foreign debris 5. Reduction in inflammatory mediators 1. Potential for bacterial contamination 2. Platelet damage 3. Loss of plasma and coagulation factors 4. Loss of proteins COP 5. Higher concentration of neutrophils Perfusion 2003; 18: 115-121

54. Remove 70-90% of soluble contaminants from salvaged blood Fibrin(ogen) Split Products D-Dimers Activated Complement Free Hgb Activate Fibrinolytic Particles Activated WBC – 30%-70% of activated WBC’s are removed with a cell washer (the Medtronic Autolog system removed the most) 11 Proteolytic Enzymes Anticoagulants Marker Enzymes (CPK) Fats Stroma, Cell Fragments Bacteria and Endotoxins Transfusion 2004;44:35S-39S

55.  Conclusions:  Little or no benefit in inhibiting inflammatory response  No reduction in rate of neurological injury  Biological marker numbers reduced but no clinical benefit  Evidence of increased transfusion rates and blood loss during cardiac surgery

56.  Quality improves by process change: 1. Reduce RBC packing 2. Increase wash volume 3. Increase wash period 4. Increase wash frequency 5. Remove operator subjectivity  The longer we wash the better the product of RBC’s with the most bad stuff removed ???

57. “SHED BLOOD”: It’s time for Perfusion and the Cardiac Surgery arena to clearly define the term “SHED BLOOD”: I propose the following definitions: “Cardiotomy Blood” “Cardiotomy Blood” - is the franc whole blood that accumulates inside the pericardium coming directly from a great vessel or the open heart itself and should be returned via the cardiotomy suction (Pump Sucker) “Shed Blood” “Shed Blood” – is the blood that has accumulated OUTSIDE the pericardium including chest tube drainage or blood lost from other wound sites and is collected until the patient stops bleeding and should be returned via a Cell Washer

58.  We are at a conundrum in cardiac surgery about dealing with blood lost outside of the patient  Current mind set is that everything goes to a cell washer instead of trying to save the whole blood  We have swung the pendulum in the other direction so far with Dr. Stump’s work dealing with blood salvaging and we are still giving a plethora of blood products  We need to swing back to the middle and find a way to preserve the whole blood and all it’s components

59. Thank You For Your Attention!

60. 1. Belway, D., Rubens, F., Wonzy, D., Henley, B., & Nathan, H. (2005). Are we doing everything we can to conserve blood during bypass? A national survey. Perfusion, 20, 237-241. 2. Brinke, M. T., Weerwind, P., Teerenstra, S., Feron, J., Meer, W. V., & Brouwer, M. (2005). Leukocyte removal efficiency of cell-washed and unwashed whole blood: an invitro study. Perfusion, 20, 335-341. 3. Carrier, M., Denault, A., Lavoie, J., & Perrault, L. P. (2006). Randomized controlled trial of pericardial blood processing with a cell-saving device on neurological markers in elderly patients undergoing coronary artery bypass graft surgery. Annals of Thoracic Surgery, 82, 51-56. 4. Daane, C. R., Golab, H. D., Meeder, J. H., Wijers, M. J., & Bogers, A. J. (2003). Processing and transfusion of residual cardiopulmonary bypass volume: effects on haemostasisl, complement activation, postoperative blood loss and transfusion volume. Perfusion, 18, 115-121. 5. Eyjolfsson, A., Plaza, I., Broden, B., Johnsson, P., Dencker, M., & Bjursten, H. (2009). Cardiorespiratory effects of venous lipid micro embolization in an experimental model of mediastinal shed blood reinfusion. Journal of Cardiothoracic Surgery, 48, 1-9. 6. Groom, R. C., Quinn, R. D., Lennon, P., Welch, J., Kramer, R. S., & Ross, C. S. et al. (2010). Microemboli from cardiopulmonary bypass are associated with a serum marker of brain injury. Journal of Extracorporeal Technology, 42, 40-44.

61. 7. Haan, J. D., Boonstra, P. W., Monnink, S. H., Ebels, T., & Van Oeveren, W. (1995). Retransfusion of suctioned blood during cardiopulmonary bypass impairs hemostasis. Annals of Thoracic Surgery, 59, 901-907. 8. Kincaid, E. H., Jones, T. J., Stump, D. A., Brown, W. R., Moody, D. M., & Deal, D. D. et al. (2000). Processing scavenged blood with a cell saver reduces cerebral lipid microembolization. Annals of Thoracic Surgery, 70, 1296-1300. 9. Rubens, F. D., Boodhwani, M., Mesana, T., Wozny, D., Wells, G., & Nathan, H. J. (2007). The cardiotomy trial: a randomized, double blinded study to assess the effect of processing of shed blood during cardiopulmonary bypass on transfusion and neurocognitive function. Circulation, 116, I-89 - I-97. 10. Selnes, O. A., Grega, M. A., Borowicz, L. M., Barry, S., Zeger, S., & Baumgartner, W. A. et al. (2005). Cognitive outcomes three years after coronary artery bypass surgery: A comparison of on-pump coronary artery bypass graft surgery and nonsurgical controls. Annals of Thoracic Surgery, 79, 1201-1209. 11. Serrick, C. J., Scholz, M., Melo, A., Singh, O., & Noel, D. (2003). Quality of red blood cells using autotransfusion devices: a comparative analysis. Journal of Extracorporeal Technology, 35, 28-34. 12. Shander, A., Moskowitz, D., & Rijhwani, T. S. (2005). The safety and efficacy of “Bloodless” cardiac surgery. Seminars in Cardiothoracic and Vascular Anesthesia, 9, 53-63.

62. 13. Shann, K. G., Likosky, D. S., Murkin, J. M., Baker, R. A., Baribeau, Y. R., & DeFoe, G. R. et al. (2006). An evidence-based review of the practice of cardiopulmonary bypass in adults: A focus on neurologic injury, glycemic control, hemodilution, and the inflammatory response. The Journal of Thoracic and Cardiovascular Surgery, 132, 283-293. 14. Takayama, H., Soltow, L. O., & Aldea, G. S. (2007). Differential expression in markers for thrombin, platelet activation, and inflammation in cell saver versus systemic blood in patients undergoing on-pump coronary artery bypass graft surgery. Journal of Cardiothoracic and Vascular Anesthesia, 21, 519-523. 15. Van den Goor, J. M., Nieuwland, R., Rutten, P. M., Tijssen, J. G., Hau, C., & Sturk, A. et al. (2007). Retransfusion of pericardial blood does not trigger systemic coagulation during cardiopulmonary bypass. European Journal of Cardio-thoracic Surgery, 31, 1029-1036. 16. Vertrees, R. A., Conti, V. R., Lick, S. D., Zwischenberger, J. B., McDaniel, L. B., & Shulman, G. (1996). Adverse effects of postoperative infusion of shed mediastinal blood. Annals of Thoracic Surgery, 62, 717-723. 17. Wang, G., Brainbridge, D., Martin, J., & Cheng, D. (2009). The efficacy of an intraoperative cell saver during cardiac surgery: A meta-analysis of randomized trials. Anesthesia and Analgesia, 109, 320-330. 18. Waters, J. H. (2004). Indications and contraindications of cell salvage. Transfusion, 44, 40S-44S.