1. Ré-évaluation du seuil transfusionnel Philippe Van der Linden MD, PhD CHU Brugmann-HUDERF, Université Libre de Bruxelles

2. Blood Transfusion Practice in Patients Undergoing Cesarean Section Clinical scenario 30-year-old woman Cesarean section accompanied by profuse bleeding Hemodynamically stable after crystalloid resuscitation Evidence of a slow ongoing blood loss Questions At what hemoglobin concentration would you transfuse the patient ? At this threshold, how many units of RBCs would you transfuse? Would you measure Hb concentration before transfusing? P VdL

3. Blood Transfusion Practice in Patients Undergoing Cesarean Section From Matot I et al. Am J Obstet Gynecol 190:462-7, 2004. p<0.01p<0.05 P VdL

4. E.U. prospective study (1999) 146 units; 3534 patients P VdL

6. Risks associated with anemia Risks associated with blood transfusion Effectiveness of blood transfusion P VdL

7. Patient Outcome With Very Low Hb Level Retrospective cohort study Surgery from 1981 to 1994 Postop Hb level: 8 g/dl or less 1° outcome: 30-day mortality 2° outcome: 30-day morbidity From Carson JL et al. Transfusion 42:812-818, 2002. 0 2 4 6 8 10 12 9,4 7,4 6,6 1,2 1,6 Complications (%) Congestive heart failure Arrhythmia Pneumonia Wound infection Myocardial infarction P VdL

9. Patient Outcome With Very Low Hb Level Retrospective cohort study Surgery from 1981 to 1994 Postop Hb level: 8 g/dl or less 1° outcome: 30-day mortality 2° outcome: 30-day morbidity From Carson JL et al. Transfusion 42:812-818, 2002. 0 2 4 6 8 10 12 9,4 7,4 6,6 1,2 1,6 Complications (%) Congestive heart failure Arrhythmia Pneumonia Wound infection Myocardial infarction After adjusting for age, CVD,& APACHE II score, the OR of death for each gram decrease Hb was 2.1 (95% CI 1.7-2.6) P VdL

11. Anemia, Cardiovascular Disease (CVD), and Surgical Mortality Adjusted odds ratio for mortality by CVD and preop Hb Preoperative hemoglobin (g/dl) From Carson JL et al. Lancet 348:1055-1060, 1996. 16 13 10 7 4 1 6789 1112+ 1981-1994 All surgeries except open-heart procedures (N=1958) No CVD CVD P VdL

15. Influence of Hemodilution on Outcome After Hypothermic Cardiopulmonary Bypass Score 140 120 100 80 60 Psychomotor Dev index (N=109) Mental Dev index (N=112) p=0.008 p=0.36 From Jonas RA et al. J Thorac Cardiovasc Surg 126:1765-1774, 2003. RCT: infants < 9 months - Hct 21.5 ± 2.9 % (N=74) - Hct 27.8 ± 3.2 % (N=73) Blood product use: similar Fluid balance: 519 ± 343 vs337 ± 222 ml p<0.001 60 min after CPB Lower nadir CI Higher lactate in the low hct group P VdL

16. O 2 Extraction Cardiac Output Tissue O 2 Demand P VdL

19. Risks associated with anemia Risks associated with blood transfusion Effectiveness of blood transfusion P VdL

20. Transfusion Triggers: a Systematic Review 10 randomized trials comparing the effects of "liberal" vs "restrictive" transfusion strategy based on a specified hemoglobin (or hematocrit) concentration on short-term outcome (N=1780 patients) Surgical patients (N=5) Acute blood loss (N=3) ICU patients (N=2) Transfusion triggers: hemoglobin between 7 and 10 g/dl From Carson JL et al. Transfus Med Rev 16:187-199, 2002. P VdL

23. Blood Transfusion and The Heart Retrospective analysis (N=78974) Blood transfusion decreased 30-day mortality in elderly patients with a primary diagnosis of AMI if their admission hematocrit was less than 33% (Wu WC et al. N Engl J Med 345:1230-1236, 2001) Observational study using prospectively collected data (N=24111) Blood Transfusion in the setting of acute coronary syndrome is not associated with improved survival when nadir hematocrit values are 20-25% (Rao SV et al. JAMA 292:1555-1562, 2004) P VdL

24. Effects of Blood Transfusion on Survival From Lackritz EM et al. Lancet 340:524-528, 1992. 1.0 0.8 0.6 0.4 0.2 0 012345 Probability of mortality Admission hemoglobin (g/dl) Transfused on day of admission vsnot transfused Threshold Hb: 3.9 g/dl For Hb< 3.9 g/dl For Hb> 3.9 g/dl n=194 n=149 OR: 0.30 (0.14-0.61) OR: 1.88 (0.51-6.84) P VdL

25. Blood Transfusion For Severe Anemic Children Observational study (N=9968) Severely anemic children: 13% Transfused: 65% (984/1516) Mortality (multiple logistic regression) prostration OR: 7.4 (4.2-13.1) respiratory distress: OR: 4.1 (2.2-7.4) profound anemia: OR: 2.5 (1.4-4.5) blood transfusion: OR: 0.28 (0.15-0.53) 0 20 40 60 80 100 89 23 Mortality (%) Not transfusedTransfused Children with prostration, respiratory distress and Hb < 4 g/dl From English M et al. Lancet 359:494-495, 2002. p=0.0002 P VdL

29. From Bell EF et al. Pediatrics 115:1685-1691, 2005. Transfusion Strategy in Preterm Infants Intravent hhage or periventricular leukomalacia Subjects with > 1 apnea / day 0 10 20 30 40 50 0 20 12 43 p=0.012 p=0.017 % LiberalRestrictive Before transfusion After transfusion 0,4 0,6 0,8 1 1,2 1,4 1,6 Apnea episodes in 24 hours NS p=0.003 P VdL

32. Blood Transfusion: "Storage Effects" Decreased 2, 3 - diphosphoglycerate (~ 0 after 15 days) Increased affinity of hemoglobin for oxygen Decreased in red blood cell ATP change in RBC shape (discoid to spherocytic) reduced cellular deformability Decreased tissue oxygen availability endothelial swelling and tissue edema in sepsis reduce capillary luminal diameter P VdL

33. Double-blind RCT Euvolemic anemic (8.5 ± 0.8 g/dl) critically ill patients LD RBC transfusion: 2 U - "fresh" blood: 2 days (2 - 3); N=10 - "old" blood: 28 days (22 - 32); N=12 No difference in any global oxygenation parameters RBC Transfusion and Tissue Oxygenation: Effects of Storage Time From Walsh TS et al. Crit Care Med 32:364-371, 2004. PgCO 2 -PaCO 2 (kPa) pHi Lactate (mM/l) -0,500,51 RBC< 5 days RBC > 20 days P VdL

39. Transfusion Triggers Dyspnea Tachycardia Hypotension ST-T Abnormalities PvO 2, SvO 2, O 2 ER Others (lactate) ? Central venous O 2 saturation ? P VdL

41. Perioperative Transfusion Trigger Transfusion (%) 100 0 > 30% Hematocrit < 20% Adapted from Janvier G et Annat G. Ann Fr Anesth Réanim 14:9-20, 1995. P VdL

42. Conclusions Humans exhibit a high tolerance to acute anemia, providing that "normovolemia" is maintained. It is unlikely that any level of hemoglobin can be used as a universal threshold for transfusion. Don't treat numbers, but patients using the available monitoring AND your clinical judgment P VdL