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Blood Transfusion: New Guidelines

Blood Transfusion: New Guidelines Joint Surgery and Anesthesiology Grand Rounds July 2, 2009 Paul Picton MD Lena M. Napolitano MD Andrew Rosenberg MD Perioperative Transfusion Triggers Paul Picton MD MRCP FRCA Assistant Professor Director, Transplant Anesthesia

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Blood Transfusion: New Guidelines

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  1. Blood Transfusion: New Guidelines Joint Surgery and Anesthesiology Grand Rounds July 2, 2009 Paul Picton MD Lena M. Napolitano MD Andrew Rosenberg MD

  2. Perioperative Transfusion Triggers Paul Picton MD MRCP FRCA Assistant Professor Director, Transplant Anesthesia

  3. Changes in cardiac output (A) oxygen extraction (B) oxygen delivery (C) and oxygen consumption (D) as hemoglobin decreases in humans and animals Klein HG, et al. Lancet 2007; 370:415-426

  4. Anemia in Healthy Awake Volunteers • Critical hemoglobin threshold unknown in humans • At 5 g/dL - VO2 maintained but ST changes (5%) and memory formation impaired • At 6 g/dL - decline in cognitive function Lieberman, et al. Anesthesiology 2000

  5. Do Nothing Study • Retrospective study of 300 JW who underwent surgery from 1981 - 1994 • Even after adjusting for age, cardiovascular disease and APACHE score, odds of death increased by 2.5 times for each gram of Hb below 8 g/dL Transfusion. 2002 Jul;42(7):812-8

  6. Do Nothing Study • Retrospective study of 300 JW who underwent surgery from 1981 - 1994 • Even after adjusting for age, cardiovascular disease and APACHE score, odds of death increased by 2.5 times for each gram of Hb below 8 g/dL Transfusion. 2002 Jul;42(7):812-8

  7. Herbert PC, et al. NEJM 1999 Enrolled 838 euvolemic, anemic, critically ill pts who were admitted to 1 of 25 Canadian ICUs Patients were stratified according to center and disease severity (APACHE II) and placed into one of two groups Restrictive group: Transfuse if Hb < 7 and maintain between 7 and 9 Liberal group: Transfuse if Hb < 10 and maintain between 10 and 12 The primary outcome measure was death from all causes in the 30 days after randomization The TRICC Study

  8. TRICC - Design

  9. The TRICC Study No difference 30 day mortality In “healthy” (APACHE II < 20)and young(<55yrs)patients Transfusion increased mortality Herbert PC, et al. NEJM 1999

  10. The TRICC Study 5.7% vs 13.0% 8.7% vs 16.1% Herbert PC, et al. NEJM 1999

  11. The TRICC Study • Average red cell units per patient: 2.6 ± 4.1 vs. 5.6 ± 5.3 (p < 0.01) • Average daily Hb concentrations: 8.5 ± 0.7 g/dl vs. 10.7 ± 0.7 g/dl (p < 0.01)

  12. TRICC Sub Group Analyses Trauma (n = 203) McIntyre LA, et al. J Trauma 2004;57:563-568 Moderate to severe head injury (n = 67) McIntyre LA, et al. Neurocrit Care 2006;05:4-9 Cardiovascular disease (n = 357) Herbert PC, et al. Crit Care Med 2001; 29(2):227-234 Mechanical ventilation (n = 713) Hebert PC, et al. Chest 2001 June;119(6):1851. No difference in outcomes

  13. “A restrictive red blood cell transfusion strategy generally appears to be safe in most critically ill patients with cardiovascular disease… with the possible exception of patients with acute myocardial infarction and unstable angina.”

  14. CRIT Study • Prospective, multiple center, observational cohort study of 4,892 ICU pts in the US • Propensity score matched • Designed to examine the relationship of anemia and RBC transfusion with clinical outcomes • Almost 95% of patients admitted to the ICU have a Hb level below “normal” by day 3 • In total, 11,391 RBC units were transfused. • Overall, 44% of pts admitted to the ICU received one or more RBC units while in the ICU Crit Care Med. 2004 Jan;32(1):39-52

  15. CRIT Results 35% of Blood transfused in patients with Hgb  9 RBC transfusion was independently associated with higher mortality (OR 1.65 CI 1.35-2.03). OR 2.62 if 3-4 units transfused p < 0.0001 The mean pre-transfusion Hb was 8.6 ± 1.7 g/dL

  16. ST Sx Hematocrit versus Postop Morbidity & Ischemia n = 27 high-risk pts undergoing infra-inguinal arterial bypass Nelson A, Fleischer L, et al. Crit Care Med 1993

  17. 2001 • Retrospective cohort • Cooperative Cardiovascular Project • 78,974 patients ≥ 65 yrs acute MI • 30 day mortality

  18. Blood transfusion associated with ↓ mortality if Hct < 30%

  19. Analysis of 24,112 enrollees in 3 large international trials of patients with acute coronary syndromes • Association between transfusion and outcome • Cox proportional hazards modeling • Main outcome = 30 day mortality Rao SV et al. JAMA. 2004;292:1555-1562

  20. Blood Transfusion and Clinical Outcome in Acute Coronary Syndrome Transfusion Adjusted hazard ratio 3.94 (3.26-4.75) No Transfusion Rao SV et al. JAMA. 2004;292:1555-1562

  21. Meta-analysis of observational studies • 45 studies - 272,596 patients • Multivariate analysis correcting for age and illness severity • Outcome measures: • Mortality • Infection • Multi-organ dysfunction • ARDS Crit Care Med 2008;36(9):2667-74

  22. Results Association between blood transfusion and the risk of death (OR & 95% CI). Pooled OR 1.7 (95% CI 1.4-1.9) Association between blood transfusion and the risk of infectious complications (OR & 95% CI). Pooled OR 1.8 (95% CI 1.5-2.2) Crit Care Med 2008;36(9):2667-74

  23. Results Association between blood transfusion and the risk of ARDS (OR & 95% CI). Pooled OR 2.5 (95% CI 1.6-3.3) Crit Care Med 2008;36(9):2667-74

  24. Financial Burden Millions Based on data from UMHHC cost accounting system. Cost includes cost of blood products and allocated costs of labor

  25. Summary • Post op Hct 15 - very high mortality • At Hct 18 - cognitive dysfunction in healthy volunteers • Utilization of a transfusion trigger 21 (mean Hct 25)- confers survival benefit for those < 55 yrs and those with an APACHE < 20 • A liberal transfusion policy - trigger 30(mean Hct 32) does not benefit patients on critical care • AtHct 27 - ST changes in high risk patients.

  26. Summary • Transfusion may benefit patients during acute coronary syndromes if Hct < 25-29 • There is only rarely an indication to transfuse ANY patient with a Hct ≥ 30 • Blood transfusions are not risk free • Decreasing transfusion may not only decrease cost but also improve outcome

  27. Closing Comments • Good prospective data limited to critical care setting • Considerable scope for differences in opinion • Concerning intra-operative transfusion - best to come to some agreement pre op and remain in communication • Give RBC’s as single units when possible • Treat the patient not the Hct

  28. Univ. Michigan Adult Blood Transfusion Guidelines: 2009 Lena M. Napolitano MD, FACS, FCCP, FCCM Professor of Surgery Division Chief, Acute Care Surgery Department of Surgery University of Michigan Ann Arbor, MI

  29. Adult Blood Transfusion Clinical Guidelines

  30. Plan and Guideline endorsed by ECCA on March 24, 2009

  31. Project Overview & Scope Of Work Blood Utilization lean project work was commissioned by both OCA & Hospital Administration, under the oversight ofDr. Skip Campbell Team Make-Up Project Goal: To develop standard policies & practices leading to: improved patient outcomes through the appropriate use of blood products and gain process efficiencies by removing waste and delays in the blood dispensing & administration process

  32. Guidelines for Blood Transfusion: PRBCs • These guidelines are intended to ensure that the most appropriate, efficient and safe use of the blood supply is achieved • To establish evidence-based criteria for the transfusion of blood components • Every indication for the use of blood products cannot be anticipated • These guidelines are not intended to override physician judgement

  33. Guidelines for Blood Transfusion: PRBCs • Hemodynamically stable anemia without acute coronary syndrome: hemoglobin trigger less than 7 g/dL, with a transfusion goal to maintain hemoglobin 7 – 9 g/dL. • Acute hemorrhage with evidence of hemodynamic instability or inadequate oxygen delivery • Symptomatic (tachycardia, tachypnea, postural hypotension) anemia (Hb < 10 g/dL) not explained by other causes • Chronic Tx-dependent bone marrow syndromes: Hb < 10 g/dL. • Transfusion or exchange transfusion for severe sickle syndromes. • Hemodynamically stable anemia with ischemic heart disease: current evidence does not support routine transfusion in non-ST segment elevation acute coronary syndromes; although in ST-segment elevation myocardial infarction Tx may be beneficial.

  34. Guidelines for Blood Transfusion: PRBCs • RBCs should be administered as single units for most operative and inpatient indications (transfuse and reassess strategy) except for ongoing blood loss with hemodynamic instability. • Tx decisions are clinical judgments that should be based on the overall clinical assessment of the individual patient. Transfusion decisions should not be based on laboratory parameters alone. • Routine premedication is not advised unless the patient has a history of previous transfusion reactions. Premedication has not been shown to reduce the risk of transfusion reactions.

  35. EAST / SCCM Blood Tx Guidelines In press. November 2009 Crit Care Med

  36. Risks of Blood Transfusion • Viral transmission • Acute transfusion reactions • Immunosuppression • Acute inflammatory response Noninfectious Hazards Immunosuppression Infection

  37. Decline in HIV, HBV, HCV Risks of Transmission via Blood Tx HIV HCV 1:100 1:1000 1:10,000 1:100,000 1:1,000,000 1:10,000,000 HBV Risk of Infection per Unit Transfused 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 Year Non-A, Non-B Hepatitis Surrogate Testing p24 AntigenTesting HCV and HIVNucleic AcidTesting Revised DonorDeferral Criteria HIV AntibodyScreening HCV AntibodyScreening Busch MP, et al. JAMA. 2003;289:959-62.

  38. Risks of Transfusion: Infectious Disease • HIV = 1 in 1.8 million • HCV = 1 in 1.6 million • HBV = 1 in 220,000 HIV = human immunodeficiency virus. HCV = hepatitis C virus. HBV = hepatitis B virus. Busch MP, et al. JAMA. 2003;289:959-62.

  39. Transfusion-transmitted infections Post-transfusion purpura 3% Acute lung injury 6% 8% Graft vs host disease 2% Incorrect blood/ componenttransfused 14% 53% Delayed transfusion reaction 15% Acute transfusion reaction Based on 366 spontaneously-reporteddeaths/major complications between October 1996 and September 1998 in the UK and Ireland. Serious Hazards of Transfusion Williamson LM, et al. BMJ. 1999;319:16-9.

  40. Risks of Blood Transfusion TRALI 1:5,000 HTLV = human T-cell leukemia-lymphoma virus. Klein HG. Am J Surg. 1995. 170;6A(suppl):21S-26S.

  41. Immune Effects of Blood • Immunologic effects of autologous and allogenic blood transfusions: • Decreased T-cell proliferation • Decreased CD3, CD4, CD8 T-cells • Increased Soluble cytokine receptor • sTNF-R, sIL-2R • Increased Serum neopterin • Increased Cell-mediated lympholysis • Increased TNF-alpha • Increased suppressor T-cell activity • Reduced natural killer cell activity TRIM – Transfusion-associated Immunomodulation McAlister FA, et al, British Journal of Surgery 1998; 85: 171-178 Innerhofer et al. Transfusion 1999 Oct;39(10):1089

  42. Blood Tx Increases Risk of Postoperative Bacterial Infection • 20 peer-reviewed studies, 1986-2000 • N = 13,152 (Tx 5215, No-Tx 7937) • Association of Blood Tx to Infection • Common OR 3.45 (range 1.43-15.15) • 17 of 20 studies with p < 0.05 • Trauma subgroup • Common OR 5.26 (range 5.03-5.43) • All studies with p < 0.05 (0.005 – 0.0001) • Blood Tx associated with greater risk in trauma pts Hill GE, Minei JP et al. J Trauma 2003;54:908-914

  43. Prospective cohort study, n=2085 • Project Impact • Nosocomial Infections: 14.3% vs. 5.8%, p < 0.001 Taylor RW et al. Crit Care Med 2006; 34:2302–2308

  44. 15,592 Cardiovascular operations • Infection endpoints bacteremia, SSI • 55% of pts received PRBCs, 21% plts, 13% FFP, 3% cryoprecipitate • Increased RBC tx associated with increased infection (p < 0.0001), confirmed by logistic regression analysis. J Am Coll Surg 2006;202:131-138

  45. Leukoreduction does not diminish tx-associated Microchimerism Reed W, et al.Semin Hematol 2007:44:24-31 Utter G et al. Transfusion 2006 Nov;46(11):1863-9

  46. Gould S et al. Am J Crit Care; Jan 2007;16(1):39-48

  47. Why is blood transfusionNOT associated withimproved outcome?

  48. Stored RBCs • Decreased RBC deformability • Decreased 2,3, DPG • Metabolic acidosis • Altered oxygen carrying capacity • Increased red cell death with increased age of blood (~30% dead) • No improvement in oxygen utilization at the tissue level

  49. Age of Blood

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