1. CASE I. 40 years old male, car accident. Several fractures, hematothorax. Treatment in sufficient progress (OR). No active bleeding. No coagulopathy. No relevant medical history. At what Hemoglobin concentration (cHb) do you transfuse red cells? A = ≤ 7.0 B = ≤ 8.0 C = ≤ 9.0 D = ≤ 10.0 g/dl

2. CASE II. 80 years old female. Hemihepatectomy for cancer treatment. No active bleeding. No coagulopathy. Adequate mental conditions. No cardiac history. At what Hemoglobin concentration (cHb) do you transfuse red cells? A = ≤ 7.0 B = ≤ 8.0 C = ≤ 9.0 D = ≤ 10.0 g/dl

3. Red Cell Transfusion

4. Sepsis patients (21): one hour after Red Cell transfusion Sadaka F et al.: Ann Intens Care 2011;1:46

5. Vamvakas EC, Blajchman MA. Transfus Med Rev 2010;(2)24:77 “Blood still kills!”

6. Wiriya Maisat Arraya Watanitanon Benno von Bormann Anesthesiology, Siriraj Hospital Transfusion of red cells 1. Outcome, 2. Benefit, 3. Alternatives 3rd July 2012

7. I. Outcome

8. ………………...16. Offner PJ, Moore EE, Biffl WL, et al: Increased rate of infection associated with transfusion of old blood after severe injury. Arch Surg 2002; 137:711–716, 17. Zallen G, Offner PJ, Moore EE, et al: Age of transfused blood is an independent risk factor for postinjury multiple organ failure. Am J Surg 1999; 178:570–572 18. Claridge JA, Sawyer RG, Schulman AM, et al: Blood transfusions correlate with infections in trauma patients in a dose-dependent manner. Am Surg 2002; 68:566–572 19. Malone DL, Dunne J, Tracy JK, et al: Blood transfusion, independent of shock severity, is associated with worse outcome in trauma. J Trauma 2003; 54:898–905 20. Dunne JR, Malone DL, Tracy JK, et al: Allogenic blood transfusion in the first 24 hours after trauma is associated with increased systemic inflammatory response syndrome (SIRS) and death. Surg Infect 2004; 5:395–404 21. Silverboard H, Aisiku I, Martin GS, et al: The role of acute blood transfusion in the development of acute respiratory distress syndrome in patients with severe trauma. J Trauma 2005; 59:717–723 22. Croce MA, Tolley EA, Claridge JA, et al: Transfusions result in pulmonary morbidity and death after a moderate degree of injury. J Trauma 2005; 59:19–23 23. Ciesla DJ, Moore EE, Johnson JL, et al: A 12-year prospective study of postinjury multiple organ failure: Has anything changed? Arch Surg 2005; 140:432–438 24. Dawes LG, Aprahamian C, Condon RE, et al: The risk of infection after colon injury. Surgery 1986; 100:796–803 25. Tartter PI: Blood transfusion and infectious complications following colorectal cancer surgery. Br J Surg 1988; 75:789– 792 26. van Lawick van Pabst WP, Langenhorst BL, Mulder PG, et al: Effect of perioperative blood lo ss and perioperative blood transfusions on colorectal cancer survival. Eur J Cancer Clin Oncol 1988; 24:741–747 27. Wobbes T, Bemelmans BL, Kuypers JH, et al: Risk of postoperative septic complications after abdominal surgical treatment in relation to perioperative blood transfusion. Surg Gynecol Obstet 1990; 171:59–62 28. von Doersten P, Cruz RM, Selby JV, et al: Transfusion, recurrence, and infection in head and neck cancer surgery. Otolaryngol Head Neck Surg 1992; 106:60–67 29. Jahnson S, Andersson M: Adverse effects of perioperative blood transfusion in patients with colorectal cancer. Eur J Surg 1992; 158: 419–425 30. Vignali A, Braga M, Dionigi P, et al: Impact of a program of autologous blood donation on the incidence of infection in patients with colorectal cancer. Eur J Surg 1995; 161:487–492 31. Ford CD, VanMoorleghem G, Menlove RL: Blood transfusions and postoperative wound infection. Surgery 1993; 113:603–607 32. Mynster T, Nielsen HJ: The impact of storage time of transfused blood on postoperative infectious complications in rectal cancer surgery. Scan J Gastroenterol 2000; 35:212–217 33. Mynster T, Christensen IJ, Moesgaard F, et al: Effects of the combination of blood transfusion and postoperative infectious complications on prognosis after surgery for colorectal cancer. Br J Surg 2000; 87:1553–1562 34. Chang H, Hall GA, Geerts WH, et al: Allogeneic red blood cell transfusion is an independent risk factor for the development of postoperative bacterial infection. Vox Sang 2000; 78:13–18 35. Lebron-Gallardo M, Herrera Gutierrez ME, Seller PG, et al: Risk factors for renal dysfunction in the postoperative course of liver transplant. Liver Transpl 2004; 10:1379 –1385 36. Vamvakas EC, Carven JH: Transfusion and postoperative pneumonia in coronary artery bypass graft surgery: Effect of the length of storage of transfused red cells. Transfusion 1999; 39:701–710 37. Vamvakas EC, Carven JH: Allogeneic blood transfusion and postoperative duration of mechanical ventilation: Effects of red cell supernatant, platelet supernatant, plasma components and total transfused fluid. Vox Sang 2002; 82:141–149 38. Leal-Noval SR, Rincon-Ferrari MD, Garcia-Curiel A, et al: Transfusion of blood components and postoperative infection in patients undergoing cardiac surgery. Chest 2001; 119:1461–1468 39. Chelemer SB, Prato BS, Cox PM Jr, et al: Association of bacterial infection and red blood cell transfusion after coronary artery bypass surgery. Ann Thorac Surg 2002; 73: 138–142 Blood transfusion and postoperative infection in orthopedic patients. Transfusion…………………………. Blood transfusion and adverse effects. Mounting evidence Blood Transfusion in Cardiac Surgery A Silent Epidemic Revisited James D. Rawn, Circulation 2007;116:2523 Editorial

9. Retrospective cohort study 8,516 patients with Cardiac Surgery in 1996 – 2003 Data from three well maintained data sources 1. PATS*, linked to 2. hematology, 3. blood bank databases Infection and ischemic outcome, LOS, death Impact of LK-Depletion (since 1999) Propensity score, Multivariate regression *Patient Analysis and Tracking System, London, UK (started 1996) Murphy GJ et al.: ‘Increased Mortality, Postoperative Morbidity, and Cost After Red Blood Cell Transfusion in Patients Having Cardiac Surgery.’ Circulation 2007;116:2544

10. Red Cell Transfusion increased dose dependently Mortality, Morbidity, LOS, Cost No impact of Nadir Hct or LK-Depletion Murphy GJ et al.: Circulation 2007;116:2544 Summary of results

11. Murphy GJ et al.: Circulation 2007;116:2544

12. Cardiac surgery patients – retrospective cohort study. Murphy GJ et al.: Circulation 2007;116:2544

13. Cardiac surgery patients – retrospective cohort study. Murphy GJ et al.: Circulation 2007;116:2544

14. Limitations Retrospective Particular indications unknown Strength Transfusion Data from independent source Groups: Well balanced prognostic factors Propensity analysis Nadir Hct without effect in both groups RBC effect similar in high- and low risk

15. Glance LG et al.: ‘Association between Intraoperative Blood Transfusion and Mortality and Morbidity in patients Undergoing Noncardiac Surgery.’ Anesthesiology 2011;114:283 Retrospective – multicenter 11,000 patients: General, Vascular, Orthopedic NSQIP* Database Anemic patients (Hct < 30%) - max. 2 U RBC Thus blood loss not relevant Multivariate analysis (MVA) *American College of Surgeons National Surgical Quality Improvement Program

16. Surgical patients with preoperative anemia Glance LG et al.: Anesthesiology 2011;114:283 P < 0.005 P < 0.01 P < 0.001 P < 0.05

17. Limitations Transfused patients worse MVA is no 100% ‘cure’ Particular indications unknown Strength Quality of data base, (p value) Number of patients Max. 2 U of PRC transfused

18. Marik PE et al.: ‘Efficacy of red cell transfusion in the critically ill: A systematic review of the literature’ Crit Care Med 2008;36:2667 571 observational studies screened 45 selected (30,915 patients total) MVA mandatory Endpoints: Mortality and severe morbidity Benefit of RC-transfusion outweighs risk?

19. PRC transfusion and outcome on ICU 45 Studies, 687 patients each (mean) Marik PE. Crit Care Med 2008;36:2667

20. 1 st Conclusion Red Cell Transfusion deteriorates patients outcome

21. II. Is there any scientific proof of the benefit of allogeneic Red Cells?

22. Lessons learned from von Bormann B: Anaesthesist 2007;56:380 Identical Outcome ► Surgery (All) ► Transplantation ► Intensive Care ► Trauma ► Oncology

23. Severely ill.

24. . ‘A multicenter, randomized, controlled clinical trial of Transfusion requirements in critical care‘ Hébert PC et al. New Engl J Med 1999;340:409 Enrolled: 838 patients out of 6,451 (25 facilities) Normovolemic; initial cHb ≤ 9 g/dl Randomization to alternative transfusion triggers cHb either ≤ 7.0 or ≤ 10.0 g/dl Extensive Statistics

25. Hébert PC et al.: New Engl J Med 1999;340:409 P < 0.05 P < 0.01

26. Hébert et al.: Subgroup analysis. Similar Results for Patients with myocardial ischemia. Hébert PC et al.: Crit Care Med 2001;29(2):231

27. Infants.

28. Lacroix J et al.: New Engl J Med 2007;356:1609 P < 0.001

29. 2 nd Conclusion Red Cell Transfusion has no proven benefit for the recipient incl. high-risk patients

30. CATS™ (Fresenius) PAD IAT III. Autologous Alternatives Preoperative Autologous Deposit (PAD) Intraoperative Autotransfusion (IAT)

31. Author (Year)PatientsSpecific effect of PAD Reduction in homolo- gous PRC - transfusion Anders MJ (1996) Hip- and Knee- arthroplasty Less deep vein thrombosis 92% Dietrich W (2005) CABG 80% Heiss MM (1993) Colectomy for cancer treatment Halving SSI 50% Flordal PA (1997) Pancreatectomy for cancer treatment 50% Nagino M (2005) Hepatobiliary resection for cancer treatment Halving postoperative morbidity 86% Preoperative autologous Deposit (PAD) in surgery.

32. Author (Year) PatientsSpecific effect of IAT Reduction in homologous PRC-transfusion Lorentz (2000) Hip- Arthroplasty 45% Goel P (2007) CABG25% Brown CV (2010) Trauma with massive blood loss 50% Ubee SS (2011) Radical open prostatectomy (cancer) LOS shorter; no influence on relapse rate 84% Intraoperative autotransfusion (IAT) in surgery.

33. 3 rd Conclusion Autologous Transfusion is an appropriate alternative. Cooperation between departments* involved is mandatory! * Transfusion Medicine, Surgery, Anesthesiology.

34. Transfusion mistreatment – who’s fault? Or: who goes to jail? The one who does it, probably You! Finally: Legal aspects. Current situation in Europe

35. SURVEY - again CASE I. 40 years old male, car accident. Several fractures, hematothorax. Treatment in sufficient progress (OR). No active bleeding. No coagulopathy. No relevant medical history. At what Hemoglobin concentration (cHb) do you transfuse red cells? A = ≤ 7.0 B = ≤ 8.0 C = ≤ 9.0 D = ≤ 10.0 g/dl

36. CASE II. 80 years old female. Hemihepatectomy for cancer treatment. No active bleeding. No coagulopathy. Adequate mental conditions. No cardiac history. At what Hemoglobin concentration (cHb) do you transfuse red cells? A = ≤ 7.0 B = ≤ 8.0 C = ≤ 9.0 D = ≤ 10.0 g/dl

37. Conclusion – Message “It’s time for a change toward better patient care.” Donat Spahn: Anesthesiology 2011;114(2):234 Thank you!

39. The following slides could serve for discussion in case these issues are raised.

40. IAT and Tumor surgery HANSEN E: Transfusion 1999;39:608

41. 100 consecutive hepatobiliary resections Nagino M et al.: Surgery 2005;137(2):148 P < 0.001

42. IAT in open radical prostatectomy. [Two equal groups, each n = 25] Ubee SS et al.: Ann R Coll Surg Engl 2011;93(2):157 P < 0.001

43. Patients with gastrectomy. Chen G et al.: J Zheijang Univ SciB 2007;8:560