1. CORONARY ARTERY BYPASS Paul J. Corso, M.D., FACS, FACC Chief Cardiovascular Surgery, Washington Hospital Center

2. Coronary Revascularization - Surgical Historical Review: 1946VinebergIMA implant into cardiac muscle 1954MurrayExperimental anastomosis (IMA/SVG) 1962SabistonFirst CABG (SVG to RCA) 1964GarrettFirst CABG to LAD without pump 1967KolessovLima-LAD, thoracotomy 1968FavaloroInitial experience with SVG with pump 1970JohnsonExpanded experience CABG 1972AnkeneyUSA 1 st Single graft series w/o CPB

3. Classic Procedure (Same Operation For All) 1.Sternotomy 2.IMA Harvest 3.SVG 4.Cannulation for CP Bypass 5.Arrest Heart 6.Anastomosis Heparin 7.Wean From Bypass 8.Reverse heparin and Stop Bleeding

4. 21 st Century CABG 1.On pump with sternotomy 2.Off pump with sternotomy 3.Small incisions on pump 4.Small incisions off pump

11. CORONARY ARTERY BYPASS GRAFTING WITHOUT CARDIOPULMONARY BYPASS Complications of cannulation/clamping Bleeding – aorta and atrium Dissection Embolization

12. CORONARY ARTERY BYPASS GRAFTING WITHOUT CARDIOPULMONARY BYPASS Consumption of coagulation factors Platelet damageBleeding Leukocyte damage (pyrogen)Fever Leukocyte & platelet-mediated endothelial damageEdema (increased Complement-induced increased interstitial H2O) vascular permeability BradykininVasoconstriction Platelet & fibrin microemboliOrgan dysfunction

13. CPB – Causes of Neurological Abnormalities Platelet micro-emboli Air emboli Atherosclerotic emboli Aortic cross clamping Aortic cannulation Proximal graft placement

14. COMPLICATIONS OF CABG 1.Death 2.MI 3.CVA 4.Infection 5.Bleeding 70% Related to use of CP Bypass

15. Bleeding is a Significant Aspect of CABG 300,000 Operations 46% received blood and/or blood products 2.5% returned to OR for bleeding SOURCE – STS Database

16. Complications of Blood Transfusion Death! – “With non-leukocyte reduced transfusions in randomized trials, multiorgan failure and death may occur in up to 10% of transfused intensive care unit patients versus 5% in recipients of leukocyte reduced blood transfusions” => at least 5% of patients may die as a result of blood transfusions!!! Leukocyte-related target organ injury in 2 to 5% Transfusion-related acute lung injury (TRALI) may be the most common complication!!

17. Intraoperative RBC Tx Increases Risk of Low Output Failure 8004 Patients, Northern New England Cardiovascular Disease Study Group Included only patients with <=3 units RBCs nadir hematocrit associated with LOF (p<.02) RBC TX also INDEPENDENTLY associated with LOF (p=0.047)!! Surgenor, et al. Circulation 2006;114:43- 48

18. Adverse outcomes of Blood transfusion after cardiac surgery Vamvakas et al Transfusion 2000 Prolonged need for mechanical ventilation Habib et al Ann thorac surg 1996 Impaired wound healing Chmell et al J surg onc 1996 Multiple organ system failure Tran et al Nephro Trans 1994 Prolonged length of stay in hospital Vamvakas et al Trans 2000 Increased postoperative mortality Watering et al Circ 1998

19. Transfusion in CABG is associated with Reduced long term Survival Blackstone et al Ann Thorac Surg 2006 Cleveland Clinic 10,289 patients from 1995 to 2002 Blood transfusion rate of 49%, Platelets in 9 %,FFP in 2.5 % and Cryo in 0.5 % Risk adjusted: Increased early hazard at 6 months (p< 0.0001) and late hazard at 10 years ( p<0.0001) Decreased survival is “dose dependant” i.e. no. of units Unadjusted risk: 5-year survival in non- transfused vs. transfused was 80 % and 63 %

20. Transfusion in coronary artery bypass grafting is associated with reduced long-term survival. Colleen Gorman Koch, Liang Li, Andra I Duncan, Tomislav Mihaljevic, Floyd D Loop, Norman J Starr, Eugene H Blackstone. Ann Throac Surg 2006;81(5):1650-7. Landmark observational study – 10,289 isolated CABG patients Outcomes: Blood Transfusion

21. Morbidity and mortality risk associated with red cell and blood-component transfusion in isolated coronary artery bypass grafting. Colleen Koch, Liang Li, Andra Duncan, Tomislav Mihaljevic, Delos Cosgrove, Floyd Loop, Norman Starr, Eugene Blackstone. Crit Care Med 2006;34(6):1-9. First large-scale study (10,949 patients) to closely examine isolated CABG surgery related transfusions and outcomes Each unit of packed red blood cells transfused was associated with an increased risk of: Outcomes: Blood Transfusion

22. Predictors of Postoperative Bleeding – The Big 6 1)Advanced age 2)Small body size or preoperative anemia (low RBC volume) 3)Anti-platelet & anti-thrombotic drugs. 4)Prolonged operation (CPB time) – high correlation with OR type. 5)Emergency operation 6)Other co-morbidities (CHF, COPD, HTN, PVD, renal failure, etc.) Ferraris VA, et al. STS Guidelines. Ann Thorac Surg. 2005;79:1454-61.; Ferraris VA, et al. Ann Surg. 2002;235:820-7.

23. Does Aspirin Cause Increased Postoperative Bleeding 21 studies reviewed the effect of aspirin on postoperative bleeding. 5 of 6 randomized trials showed increased bleeding due to aspirin (Level A evidence). Evidence less convincing in 15 observational studies (Level B or C evidence). Ferraris VA, et al. STS Guidelines. Ann Thorac Surg. 2005;79:1454-61.

24. Postoperative Bleeding and Aspirin Can estimate the amount of bleeding after operation due to aspirin 200-400cc of increased chest tube blood loss 0.5 to 1.0 unit of blood transfusion due to aspirin. Lower doses of aspirin protect just as well and are associated with less bleeding. Ferraris VA, et al. STS Guidelines. Ann Thorac Surg. 2005;79:1454-61.

25. STS Evidence-Based Workforce Blood conservation writing group WriterOrganization Victor A. Ferraris, M.D., Ph.D. (Chair, Blood Conservation Taskforce) University of Kentucky Suellen P. Ferraris, Ph.D.University of Kentucky Sibu P. Saha, M.D., M.B.A.University of Kentucky Constance K. Haan, M.D.University of Florida B. David Royston, M.D.Harefield Hospital, UK Charles R. Bridges, M.D., Sc.D. (Chair, Evidence-Based Workforce) University of Pennsylvania Robert S.D. Higgins, M.D.Rush Presbyterian, St. Luke’s Medical Center George J. Despotis, M.D.Washington University

26. Blood Conservation Interventions – Class I Recommendations: “Is Recommended” Identify high risk preoperatively. High dose aprotinin; Low-dose aprotinin Lysine Analogs Cell saver Blood transfusion algorithm w/ point-of- care testing. Multimodality approach. Ferraris VA, et al. STS Guidelines on blood conservation. Ann Thorac Surg, May 2007;83:S27-89

27. Blood Conservation - Class IIA Recommendations: “Is Reasonable” Preoperative Epogen Intervention in Patients with thrombocytopenia Autologous predonation Off pump Bypass Alternatives to Blood sampling Total Quality Management Discontinue plavix 5 to 7 days preop RBC Transfusion for Hemoglobin < 6: Higher trigger in elderly, CVA, cardiac dysfunction, ischemia Blood component transfusion for clinical bleeding Ferraris VA, et al. STS Guidelines on blood conservation. Ann Thorac Surg, May 2007;83:S27-89

28. Mangano & co-workers Conclusion ‘Association between aprotinin & serious end- organ damage indicates that continued use is not prudent. In contrast, the less expensive generic medications, EACA & TXA, are safe alternatives.’ Mangano, 2006, NEJM

29. ‘…data mostly representing level A evidence suggests that high-dose aprotinin has an acceptable risk-benefit profile and is indicated for blood conservation (class I, level A) in patients at increased risk for bleeding.’ Aprotinin – Workforce on Evidence Based Surgery Response NEJM Ferraris, Bridges and Anderson, 2006, NEJM

30. Evidence-Based Blood Conservation Strategies: Pennsylvania Hospital Top 4 Preoperative interventions Epogen: Hgb =16 ideally Limit anti-thrombotic & anti-platelet drug effect. Limit blood loss during operation High-dose aprotinin or anti-fibrinolytics Meticulous hemostasis Speed of operation Perfusion strategies (minipump) Salvage & sequester blood (not as helpful in high-risk) Cell saver, pump salvage, RAP, AAP, etc. Normovolemic Hemodilution (predonation) Manage blood resources (process of care variables) Multimodality approach including postop epogen/iron Transfusion algorithm & point-of-care testing.

31. PAH Cardiac Surgery Blood Conservation Protocol Pre Operative measures Consult Bloodless Medicine Team for all patients Outpatients seen by Bloodless Medicine on the same day of Cardiac visit Erythropoetin administration: 40,000 U SQ weekly (caution in renal failure, cancer) In selected cases, acute Coronary syndromes may be stabilized with stenting culprit vessel and elective CABG/Hybrid approach Courtesy of Dr. Bridges

32. PAH Cardiac Surgery Blood Conservation protocol Pre operative measures Avoid daily labs in the Inpatients awaiting surgery Serum Ferritin levels in all patients Bloodless Medicine will decide the need for Ferrlecit 125 mg IV/day 3 times Angio - Seal recommended for all patients who may need surgery in the next 48 hrs ( blood loss upto 1 to 2 gms Hb from cath site reported) Vitamin K 10 mg oral for selected patients pre operatively Courtesy of Dr. Bridges

33. PAH Cardiac Surgery Blood Conservation protocol Manage risk factors for transfusion Coumadin – normalize INR preoperatively; convert to Lovenox as needed Stop Lovenox 24-48 hrs prior to surgery Aspirin (low risk patients/Jehovah’s witnesses), Plavix to discontinue for 5 to 7 days Celebrex Ginka and other herbal supplements Garlic, Vitamin E, Saw Palmeto No Alcohol for at least 1 week Pre operative anemia – major risk factor for transfusion Courtesy of Dr. Bridges

34. PAH Cardiac Surgery Blood Conservation Protocol Intra operative measures Trasylol ( Aprotinin) to be used in high risk patients ex: Plavix, combined procedures, aortic surgery, JW Auto donation: ( Normovolemic hemodilution) Red cell volume > 900 - 1 unit Red cell volume > 1100- 2 units Red cell volume > 1400- 3 units “One sponge technique” Blood returned to the patient after cardiopulmonary pass Fibrillatory arrest for redo AVR patients with patent IMA Courtesy of Dr. Bridges

35. PAH Cardiac Surgery Blood Conservation Protocol Intra Op measures- Bypass circuit Miniature Cardiopulmonary Bypass Circuits CELL SAVER ONLY Leg elevation, chair position improves venous drainage Antegrade and Retrograde priming Smaller venous line 3/8 as opposed to ½ - less prime ‘Follow through’–retrieve all blood from bypass circuit Full rewarming to 36 deg before weaning bypass Courtesy of Dr. Bridges

36. 1. Reduces systemic inflammatory response syndrome and preserves platelet function. Aprotinin enhances this effect 2.Decreases Blood Loss 3.Avoids Reduced Graft Patency of Off Pump Bypass 4.Applicable to all situations Best Strategy: Optimize Cardiopulmonary Bypass Technology

37. Low Prime Circuits: Benefits Reduced Priming Volume Reduced hemodilution Decreased blood component usage Reduced foreign surface area Less contact activation (systemic inflammatory response)

38. Demonstrated safety and efficiency Proven results regarding clinical factors that influence patient outcomes (nadir HCT/Frequency of blood transfusions) Confirmed cost avoidance Low impact to surgical technique Procedure independent – can by utilized on all procedures requiring CPB Summary – Low Prime Circuits

39. PAH Cardiac Surgery Blood conservation Protocol Intra Op measures– Hemostatic agents Thrombin, Gelfoam, Surgicel for sternum Bio Glue and Fibrin glue ( ex Tissel) as needed ‘Point Of Care Testing’ to be evaluated Courtesy of Dr. Bridges

40. PAH Blood Conservation Program Post op measures – bleeding patients Coagulation profile- Protamine as needed Correct temperature Replace volume with 5% Albumin Positive Airway Pressure Cryoprecipitate Early re exploration Courtesy of Dr. Bridges

41. PAH Cardiac Surgery Blood Conservation Protocol Post op measures – Minimize labs Avoid routine labs Use peripheral lines Small “pediatric” tubes Stable patients – labs on alternate days Courtesy of Dr. Bridges

42. Conclusions A multimodality approach to blood conservation is essential Guidelines are useful to help guide therapy and reduce variability in practice. Aprotinin is an important adjunct to a comprehensive cardiac surgery blood conservation program in high risk patients, Jehovah’s witnesses, and other “transfusion free” cardiac surgery patients The avoidance of blood transfusion in cardiac surgery patients decreases costs, morbidity and is likely to decrease mortality as well.