2/11/2014. Blood Transfusion - Why?

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1 Blood Transfusion - Why? Paul Marik, MD,FCCM,FCCP First human to human blood transfusion by James Blundell Lancet 1828 Packed Red Blood Cells Black Box Warning Packed Red Blood Cells Black Box Warning Why TRANSFUSE???? Why TRANSFUSE???? To increase oxygen delivery To increase oxygen release in tissues To increase tissue oxygen tension To increase tissue oxygen utilization 1

2 DO 2 = CO x [(Hb x Sat x 1.34) x PaO 2 ] CO 20% (5-6 L/min) DO 2 ± 18% PaO 2 20% (60-72 mmhg) DO 2 ± 6% Hb 20% (10-12 g/dl) DO 2 ± 18% Clinical Benefits of Blood Transfusion Age of transfused blood (storage lesion) Leukodepletion Baseline Hemoglobin Microcirculatory abnormality (sepsis) Coronary artery disease? Co-morbidities Old Red Cells? Alteration of RBC s with Storage Day 1 Day 21 Presumed mechanisms of storage lesion Alterations of RBC s with Storage inflammation coagulation infection infarction Loss of ATP stiff hemolysis RBC 2,3-DPG decreases to 0 after 14 days Reduces ability to offload O2 Decreased RBC ATP Dephosphorolation & oxidation of spectrin Loss of membrane lipid with microvesicles More spherocytic RBC less deformable inflammation 2

3 Unloading Oxygen P50 of normal RBC is 26 mmhg Unload at max 26% of oxygen load P50 of RBC stored 28 days 6-11 mmhg Unload < 6% of oxygen load Blood Banks do not issue blood in random order. The standard practice is to dispense the OLDEST blood available in order to reduce potential waste (and lost revenue) Average Age of t/f blood in US =23 days 23 pts severe sepsis with increased lactate Hb < 10 g/dl 3 units PRB s VO 2 indirect calorimetry and Fick Gastric intramucosal ph Pts followed 6 hours post transfusion mls/min/m2 Change in DO2I and VO2I JAMA 1993;269:3024 JAMA 1993;269:3024 Variable Pretransfusion Posttransfusion Hb g/dl 8.3 ± ± 0.3 DO2 ml/min/m2 482 ± ± 32* VO2 ml/minm2 124 ± ± 10 Lactate meq/l 4.6 ± ± 1.3 * < JAMA 1993;269:3024 Conrad SA, et al. Circ Shock 1990;31:419 3

4 Baseline After transfusion DO2 ml/min/m * VO2 ml/min/m Thenar tissue O2 saturation (%) Muscle Oxygen consumption *p<0.05 Crit Care 2009;13:S11 J Trauma 2009; 67:29 NEJM 2008; 358:1229 NEJM 2008; 358:1229 ANZICS 575 t/f patients Donadee C, et al. Circulation 2011;124:465 4

5 Janz DR, et al. Crit Care Med 2013;41 Marik PE. Br J Hosp Med 2008; 69:234 JAMA 2002:289:959 Prothrombotic Release of CD 40 ligand (plaque rupture) Increased PAI-1 Decreased NO Release of proinflammatory mediators Decreased immune reactivity Marik PE. Br J Hosp Med 2008; 69:234 5

6 Transfusion Related Immune Modulation Phosphatidylserine expressing microvesicles that activate thrombin R time of Thromboelastograph (TEG) Presence or absence of autologous HLA-DR Ag on the leucocytes of the donor Release of bioactive and immunomodulating substances from WBC Microchimerism Immune status of host Number of WBC transfused Anti-neutrophil antibodies Transfusion 2009; 49:1569 Blood t/f and WBC s 10 8 to donor leucocytes/unit Primitive hematopoietic stem cells Committed progenitor cells Transplant Proc 1973;1:253 Pre-operative blood t/f and renal-allograft survival: A RCT Survival of donor WBC in severe trauma patients Quantitative allele-specific PCR 2 year survival (%) % 34% t/f No t/f Lancet 1980;I:1104 Blood 1999;93:3127 6

7 Mixed Lymphocyte Culture 3 Groups women +/- 26 years Exchange t/f at birth 2.46 Association between nosocomial bacterial infection and transfusion with leukodepleted blood # RBC OR 1.18 Storage time cofounder OR 1.25 T/f in previous 5 years 2.43 No pregnancies or t/f 3.75 p < Blood Transfusion Benefits Transfusion of RBC stored for more than 14 days was associated with infection in trauma patients (odds ratio 1.038, [95% CI: ], p=0.036 Risks Blood Trans 2012;10:290 All cause mortality JAMA Int Med 2013;173:132 7

8 Myocardial Infarction JAMA Int Med 2013;173:132 0 units 1 unit 2 units 3-5 units > 6 units OR for venous TED 1.6 ( ) OR for arterial TED 1.55 ( ) OR for Death 1.34 ( ) Ann Thoracic Surg 2006;81:1650 Arch Intern Med 2008; 168:2377 DEATH Crit Care Med 2008;36:2667 Crit Care Med 2008;36:2667 8

9 INFECTION ARDS Crit Care Med 2008;36:2667 Crit Care Med 2008;36: patients Hb < 9 Restrictive T/f HB < 7 g/dl HB 7-9 g/dl Liberal T/f Hb < 10 g/dl Hb g/dl Hb <7 Hb < 9 NEJM 2013;368:11-21 NEJM 2013;368:

10 NEJM 2013;368:11-21 Crit Care Med 2013;41:2354 Surgical Hip Fracture Repair p=0.07 History of cardiovascular disease Post-operative Hb < 10 with 3 days of surgery 2600 pts T/F to keep Hb > 10 T/F for symptoms of anemia and/or Hb < 8 Crit Care Med 2013;41:2354 Death Distance walked at 60 days Angina/AMI Carson JL, et al. NEJM 2011;365:2453 < 7g/dl vs < 9-10 g/dl trigger Carson JL, et al. NEJM 2011;365:2453 Am J Med 2014;127:124 10

11 Physiologic Adaptations to Anemia How low can you go! Increased cardiac output Decreased afterload Increased contractility Tachycardia Increased oxygen release Increased oxygen extraction Shift oxyhemoglobin dissociation curve Graded hemodilution and cardiac function with coronary stenosis CVS response to acute isovolemic anemia g/dl g/dl SVRI HR SVI CI DO2 ml/kg/min VO2 ml/kg/min Lactate Art ph Am J Physiol 1993:265:340 JAMA 1998:279:217 Effect of blood t/f on survival 4g/dl 626 Kenyan children Hb < 5 g/dl 375 t/f, 251 no t/f 80% malaria AnesthAnalg 1992;75:818 Lancet 1992;340:524 11

12 Ann Intern Med 2012;157:49 Ann Intern Med 2013;159:770 DANGER Blood Transfusion in progress 12

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