Liberale versus restriktive EK-Transfusion
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1 SWISSTRANSFUSION 2016 Thursday, August 25, 2016; 11:00 11:30 am Liberale versus restriktive EK-Transfusion Reto Schüpbach Dokumentenname Datum Seite 0
2 Pull out, you hit the artery! Dokumentenname Datum Seite 1
3 Fundamentalism and religion IS: Flag Dokumentenname Datum Seite 2
4 Red cell transfusion Religion? + - Anemia is a disease(?) - Performance increases with hemoglobin - Severe anemia is lethal - - Transfusion is costly - Transfusion kills Dokumentenname Datum Seite 3
5 Severe anemia can result in death Hb 10-20g/L: Mortality 100% Hb 20-30g/L: Mortality 54% Hb 30-40g/L: Mortality 27% Hb 40-50g/L: Mortality 34% Hb 50-60g/L: Mortality 9% Hb 70-80g/L: Mortality <1% Source: Data base APACHEII Dokumentenname Datum Seite 4
6 damage Harm caused by anemia normal range Hb [g/l] Dokumentenname Datum Seite 5
7 Compensatory mechanisms for anemia O 2 delivery - DO2 = Arterial oxygen content x Cardiac Output x 10 [Hb x 1.39 ml/gm x Sat.] + [PaO2 x ] Additional complex adaptions - Matching of O 2 affinity in hemoglobin, myoglobin and mitochondrial proteins - Alteration in rheology - Alteration of flow profile (no TC marginalization) - Alteration in endothelial adherence Dokumentenname Datum Seite 6
8 damage Harm caused by anemia normal range Hb [g/l] Dokumentenname Datum Seite 7
9 Severe anemia is harmful BMJ VOLUME DECEMBER 2003 Dokumentenname Datum Seite 8
10 damage Is transfusion harmful Hb Dokumentenname Datum Seite 9
11 Harm caused by transfusion (incidence) Ann Intern Med. 2012;157: Dokumentenname Datum Seite 10
12 Nevertheless: The product matters Lacroix, NEJM 2015 Dokumentenname Datum Seite 11
13 damage Between liberal and restrictive, there is an optimum Just right! Hb Dokumentenname Datum Seite 12
14 Leverage the sweet spot Quality of the product Quantity of the products Safety of the product Ability to compensate for anemia Coping with transfusion Dokumentenname Datum Seite 13
15 Focus #1: Patient with risk factors Do you transfuse a patient with cardiovascular risk factors undergoing surgery? Dokumentenname Datum Seite 14
16 Focus #1: Patient with risk factors What about a patient potentially not able to increase cardiac output? DO2 = Arterial oxygen content x Cardiac Output x 10 Dokumentenname Datum Seite 15
17 Patients with risk factors undergoing surgery Dokumentenname Datum Seite 16
18 Hip fracture >50 y of age >CV risk or history Randomization if Hb < 10g/dL Liberal (n=1007) Restrictive (n=1009) Maintain Hb > 10g/dL Outcome: Combined: Death or inability to walk 60 days post op Trigger Hb < 8g/dL or symptoms Dokumentenname Datum Seite 17
19 Transfusion among stable high risk patients: Good Job! Dokumentenname Datum Seite 18
20 But poor results! Dokumentenname Datum Seite 19
21 How to stimulate POWER? Dokumentenname Datum Seite 20
22 Driving Power? 100% 7 90% 6 80% 70% 5 60% 4 50% 3 40% Sample size Between group difference Homogeneity 30% 2 20% 1 10% 0 0% Category 1 Category 2 Category 1 Category 2 Series 2 Series 1 Dokumentenname Datum Seite 21
23 Transfusion in stable high-risk surgical patients: But poor results! Dokumentenname Datum Seite 22
24 Transfusion in stable high-risk surgical patients: But poor results! Power 16%; für 80% wären pro Gruppe 8768 Patienten notwendig Dokumentenname Datum Seite 23
25 In stable patients, 80g/L is the sweet spot Trigger at < 80g/L safe However symptomatic patients have been transfused More bleeding at lower trigger Dokumentenname Datum Seite 24
26 Focus #2: Cardiac surgery Triggers for patients undergoing cardiac surgery? Dokumentenname Datum Seite 25
27 Cardiac surgery? Dokumentenname Datum Seite 26
28 >16 y of age No emergency cardiac surgery Randomization if Hb < 9g/dL Liberal (n=1000) Trigger Hb < 9 g/dl Restrictive (n=1003) Trigger Hb < 7.5 g/dl Outcome: Infection or ischemic event within 3 months Dokumentenname Datum Seite 27
29 Transfusion in cardiac surgery Dokumentenname Datum Seite 28
30 Transfusion in cardiac surgery Dokumentenname Datum Seite 29
31 What about secondary endpoints? (=mortality!) Dokumentenname Datum Seite 30
32 Did we get to the of bottom it? Trigger of < 75g/L not inferior to 90g/L Potentially more death in restrictive transfusion group No shunt patients Dokumentenname Datum Seite 31
33 Focus #3: Cardiac ischemia What is safe in patients with myocardial infarction? Dokumentenname Datum Seite 32
34 Transfusion in patients with myocardial infarction (Less is more) Chatterjee S, JAMA, 2013, 173, 2, Dokumentenname Datum Seite 33
35 Problems with case control data Salisbury AC, JACC 2014, 64; 8, Dokumentenname Datum Seite 34
36 Challanges in case control data Salisbury AC, JACC 2014, 64; 8, Dokumentenname Datum Seite 35
37 Adjusted models Hb range Unadj. Adj. Hb < 7g/dL 0.52 ( ) 0.59 ( ) Hb 7-8.9g/dL 0.73 ( ) 0.65 ( ) Hb g/dL 0.97 ( ) 0.74 ( ) Hb > 11g/dL 6.28 ( ) 1.97 ( ) Salisbury AC, JACC 2014, 64; 8, Dokumentenname Datum Seite 36
38 Potential benefit for symptomatic patients Carson JL; Am Heart J Jun;165(6): Dokumentenname Datum Seite 37
39 Transfusion strategy in myocardial infarction Restrictive triggers established (less is more; JAMA2013) However bias might drive safety Propensity analyses in databases of patients with MI favor of more liberal triggers Small studies support trigger of > 100g/L before catheter therapy Dokumentenname Datum Seite 38
40 damage Individual safety profiles required? Hb [g/l] Dokumentenname Datum Seite 39
41 What about long term risk (FOCUS) Dokumentenname Datum Seite 40
42 Dokumentenname Datum Seite 41
43 Cost efficiency? Cost / Unit: $ 320 liberal: restrictive: P value Transfusionen $ 713 $ 479 <0.001 Spital $ $ n.s. Spital / survival $ $ n.s. Gavin, JM, NEJM 2015; 372, 11; Dokumentenname Datum Seite 42
44 Est ultra! Villanueva NEJM, 2013 Dokumentenname Datum Seite 43
45 Severe acute upper GI bleeding n=921 (screened 1610) Liberal (n=460) Trigger Hb < 9 g/dl Restrictive (n=461) Trigger Hb < 7 g/dl Outcome: Death within 45 days Villanueva NEJM, 2013 Dokumentenname Datum Seite 44
46 Est ultra! Villanueva NEJM, 2013 Dokumentenname Datum Seite 45
47 damage Optimal trigger Hb Dokumentenname Datum Seite 46
48 Conclusion: Triggers are individual parameters and depend on performance Aim for the sweet spot Transfusion of erythrocytes carry few risks Patients at risk for cardiac ischemia and unable to compensate for anemia should be transfused more liberal Patients with activated endothelium (e.g. hepatopathy) should be transfused with caution Cost saving by just reducing transfusion policy is challenging Dokumentenname Datum Seite 47
49 Thank you for your attention! Dokumentenname Datum Seite 48
50 Forest plot of myocardial infarctions in low risk of bias trials Power 35% Holst LB, BMJ 2015; 350:h1354 Dokumentenname Datum Seite 49
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