1. Advances in Transfusion and Blood Conservation Arman Kilic, MD Division of Cardiac Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, MD No relevant financial relationships to disclose.

2. Overview 1. Why should we care? 2. What is the evidence? 3. How should we (healthcare professional, institution) proceed with regards to blood transfusion practice?

3. Utilization of Blood Products in Cardiac Surgery in the United States million 10-20%

4. Total Costs Associated With Transfusion Shander A et al. Transfusion 2010; 50: 753-65.

5. Transfusion Related Adverse Events Ferraris VA et al. Ann Thorac Surg 2007; 83: S27-86.

6. Immunomodulation – Increasing Risk of Major Infection Horvath KA et al. Ann Thorac Surg 2013; 95: 2194-201. Cardiothoracic Surgical Trials Network (n=5,158) Major infections within 65 days of surgery

7. Other Postoperative Morbidity Associated with Transfusions in Cardiac Surgery Atrial fibrillation Respiratory failure ARDS Reintubation Prolonged mechanical ventilation Acute renal failure Neurologic adverse events Gastrointestinal complications

8. Variability in Transfusion Rates in CABG Bennett-Guerrero E et al. JAMA 2010; 304: 1568-75. STS Adult Cardiac Surgery Database Ranged from 8% to 93% Hospital characteristics and case mix accounted for 11% and 20% of the variation

9. Utilization of Intraoperative Blood Products in Cardiac Surgery Snyder-Ramos SA et al. Transfusion 2008; 48: 1284-99.

10. Utilization of Postoperative Blood Products in Cardiac Surgery Snyder-Ramos SA et al. Transfusion 2008; 48: 1284-99.

11. Overview 1. Why should we care? 2. What is the evidence? 3. How should we (healthcare professional, institution) proceed with regards to blood transfusion practice?

12. Pre- or Intraoperative Anemia is a Risk Factor for Adverse Outcomes Kilic A et al. Ann Thorac Surg 2014; 97: 726-34. Pre- or intraoperative anemia = increased mortality and morbidity

13. Postoperative Anemia is a Risk Factor for Adverse Outcomes Kilic A et al. Ann Thorac Surg 2014; 97: 726-34. Postoperative anemia = increased mortality and morbidity

14. Blood Transfusions are a Risk Factor for Adverse Outcomes Kilic A et al. Ann Thorac Surg 2014; 97: 726-34. Regardless of hemoglobin level, blood transfusions = increased mortality and morbidity

15. Not Transfused Transfused Not Anemic ? ? The Dilemma

16. The Answer There are 5 randomized controlled trials that specifically address blood transfusions in the face of anemia: TRICC FOCUS UGI bleed TRACS TITRe2

17. 838 ICU patients with hgb <9 Restrictive (tx if hgb <7, maintain at 7-9) Liberal (tx if hgb <10, maintain at 10-12) NO DIFFERENCE

18. 2,016 hip fracture patients, hgb <10 (mean age = 81 years!!) Restrictive (tx if hgb <8) Liberal (tx if hgb <10)

19. 17 secondary outcomes: no difference (including MI, angina, stroke)

20. 921 patients with severe UGI bleed Restrictive (tx if hgb <7) Liberal (tx if hgb <9) Restrictive group: Absolute 4% survival benefit at 45 days

21. 512 patients undergoing cardiac surgery with CPB Restrictive (maintain hct >24%) Liberal (maintain hct >30%) Hajjar LA et al. JAMA 2010; 304: 1559-67. NO DIFFERENCE IN SURVIVAL

22. 2,003 patients undergoing nonemergent cardiac surgery with hgb <9 Restrictive (tx if hgb <7.5) Liberal (tx if hgb <9) TITRe2 Trial

23. Primary outcome: serious infection or ischemic event Restrictive 33%, Liberal 35% (p=0.30) Secondary outcomes Individual infections, ischemic events, all-cause mortality 90-day all-cause mortality REDUCED in the liberal group (2.6% versus 4.2%, p=0.045)!!

24. Overview 1. Why should we care? 2. What is the evidence? 3. How should we (healthcare professional, institution) proceed with regards to blood transfusion practice?

25. Ferraris VA et al. Ann Thorac Surg 2007; 83: S27-86.

26. Ferraris VA et al. Ann Thorac Surg 2011; 91: 944-82.

27. Blood Conservation Intervention Class of Recommendation (Level of Evidence) Preoperative Interventions Discontinue drugs that inhibit platelet P2Y12 receptor EPO in patients who are anemic preoperatively I (B) IIa (B) Intraoperative Blood Management Use of lysine analogues (Amicar) to reduce blood loss I (A) Blood Salvage Interventions Some form of pump salvage and reinfusion of residual pump blood at end of CPB Centrifugation of pump-salvaged blood, instead of direct infusion, to reduce allogeneic RBC transfusions IIa (C) IIa (A) Minimally Invasive Procedures TEVAR for descending aortic pathology to reduce bleeding and transfusions Off pump CABG provided risk of conversion low I (B) IIa (A) Perfusion Interventions Minicircuits to reduce hemodilution, especially in those at high risk (Jehovah’s) Use of modified ultrafiltration I (A) Topical Hemostatic Agents Use of such agents at anastomotic sites Antifibrinolytic agents poured into the surgical wound after CPB to limit CT drainage IIb (C) IIa (B) Creation of a Multidisciplinary Blood Management Team IIa (B)

28. Benefits of a Blood Product Use Protocol Lapar DJ et al. JTCVS 2013; 145: 769-804. Intraoperative transfusion triggers: Hgb <6 or hct <18% on CPB in addition to one of the following: Low oxygen saturation (<60 mmHg) Elevated lactate (>2.2 mmol/L) Elevated base deficit (>3 mEq/L) Low serum bicarbonate level (<22 mEq/L) Postoperative transfusion triggers: Hgb <7 or hct <21% in addition to one of the following: Elevated oxygen requirement Systemic hypotension End-organ dysfunction Persistent bleeding

29. Implementation of a Blood Product Use Protocol Lapar DJ et al. JTCVS 2013; 145: 769-804. Intraoperative blood use by 26% Postoperative blood use by 16% Improvement in clinical outcomes Reduction in costs

30. Transfusion Coordinators Freedman J et al. Transfusion 2008; 48: 237-50. Transfusion coordinators placed in 23 Ontario hospitals Knee arthroplasty, CABG, AAA

31. Transfusion Coordinators Freedman J et al. Transfusion 2008; 48: 237-50. CABG Knee AAA And in CABG, decrease in LOS and no change in mortality 15% patients receiving blood

32. Disclosure of Transfusion Behavior Beaty CA et al. Ann Thorac Surg 2013; 96: 2168-74. Transfusion trigger of hgb <8 g/dl 3 time periods No feedback Weekly feedback of group transfusion behavior Weekly feedback with identification of individual surgeon transfusion behavior

33. Disclosure of Transfusion Behavior Beaty CA et al. Ann Thorac Surg 2013; 96: 2168-74. 50% in inappropriate transfusions

34. Take Home Point #1 Blood transfusions can be lifesaving.

35. Take Home Point #2 Pre-, intra-, and postoperative anemia are independently associated with worse outcomes in cardiac surgery.

36. Take Home Point #3 Blood transfusions are independently associated with worse outcomes in cardiac surgery.

37. Take Home Point #4 Blood transfusions cost money.

38. Take Home Point #5 Multiple evidence-based blood conservation techniques (preoperatively, intraoperatively, and postoperatively) should be employed.

39. Take Home Point #6 Most importantly, every institution needs a multidisciplinary, agreed upon transfusion protocol with continued monitoring of adherence.

40. Acknowledgements Glenn Whitman, M.D.

41. Advances in Transfusion and Blood Conservation Arman Kilic, MD Division of Cardiac Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, MD