Transfusion & Mortality. Philippe Van der Linden MD, PhD
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1 Transfusion & Mortality Philippe Van der Linden MD, PhD
2 Conflict of Interest Disclosure In the past 5 years, I have received honoraria or travel support for consulting or lecturing from the following companies: Nordic Pharma SA Fresenius-Kabi GmbH Janssen-Cilag SA
3 Blood Transfusion in Cardiac Surgery Patients: Effects on Mortality, Morbidity & Cost ü Retrospective cohort study (04/ /2003; N=8,598) ü Primary outcomes Infection: respiratory, wound infection or septicemia Ischemia: myocardial infarction, permanent or transient stroke, renal complication (creat > 200 mmol/l or requirement for dialysis) ü Costs: ICU and hospital stay, blood products ü Associations estimated by regression modeling with adjustment for potential confounding From Murphy GJ et al. Circulation 116: , 2007.
4 Blood Transfusion in Cardiac Surgery Patients: Effects on Mortality, Morbidity & Cost Overall transfusion rate: 57% From Murphy GJ et al. Circulation 116: , 2007.
5 Blood Transfusion in Cardiac Surgery Patients: Effects on Mortality, Morbidity & Cost From Murphy GJ et al. Circulation 116: , 2007.
6 Blood Transfusion in Cardiac Surgery Patients: Effects on Mortality, Morbidity & Cost From Murphy GJ et al. Circulation 116: , 2007.
7 Blood Transfusion & Postoperative Morbi- Mortality After Cardiac Surgery From Loor G et al. J Thorac Cardiovasc Surg 144:538-46, 2012.
8 Transfusion Triggers After Cardiac Surgery ü Prospective randomized controlled noninferiority trial ü Elective cardiac surgery with cardiopulmonary bypass ü Transfusion strategy: from start of surgery until ICU discharge Liberal strategy: RBC transfusion if hematocrit <30% (N=257) Restrictive strategy: RBC transfusion if hematocrit < 24% (N=255) ü Primary endpoint: : 30-day all-cause of mortality & severe morbidity (cardiogenic shock, ARDS or acute renal failure) ü Noninferiority margin was predefined at -8% From Hajjar LA et al. JAMA 304: , 2010.
9 Transfusion Triggers After Cardiac Surgery ü Prospective randomized controlled noninferiority trial ü Elective cardiac surgery with cardiopulmonary bypass ü Transfusion strategy: from start of surgery until ICU discharge Liberal strategy: RBC transfusion if hematocrit <30% (N=257) Restrictive strategy: RBC transfusion if hematocrit < 24% (N=255) 78 p< From Hajjar LA et al. JAMA 304: , 2010.
10 Transfusion Triggers After Cardiac Surgery ü Prospective randomized controlled noninferiority trial ü Elective cardiac surgery with cardiopulmonary bypass ü Transfusion strategy: from start of surgery until ICU discharge Liberal strategy: RBC transfusion if hematocrit <30% (N=257) Restrictive strategy: RBC transfusion if hematocrit < 24% (N=255) ü Independent of transfusion strategy, nb of transfused units was an independent risk factor for morbidity or death at 30 days HR for each additional unit transfused: 1.2 [ ] From Hajjar LA et al. JAMA 304: , 2010.
11 Transfusion Thresholds & Other Strategies for Guiding Allogeneic RBC Transfusion 31 trials 12,587 patients ü Results: restrictive transfusion strategies ê risk of receiving RBC transfusion (RR: 0.57; 95% CI: 0.49 to 0.65) ê volume of transfused RBCs (-1.30; 95% CI: tp -0.75) No impact on 30-day mortality (RR:0.97; 95% CI: 0.81 to1.16) No impact on cardiac events, myocardial infarction, stroke, rebleeding, sepsis / bacteremia, pneumonia / wound infection, thromboembolism, renal failure, and mental confusion Functional recovery: not assessed From Carson JL et al. Cochrane Database of Systematic Review, 2016 Oct 12, CD
12 Liberal or Restrictive Transfusion after Cardiac Surgery ü Multicenter parallel-group trial (postoperative period): Restrictive transfusion strategy: Hb < 7.5 g/dl (N=1000) Liberal transfusion strategy: Hb < 9 g/dl (N=1003) 1 outcome 2 (1-3) units (92.2%) Pre storage leukoreduced RBCs transfused unit by unit 2 (1-3) units (92.2%) HR 1.64 (95% CI 1.00 to 2.67; p= (0-2) units (53.4%) 1 (0-2) units (53.4%) ü 1 outcome: 90-day mortality + morbidity 90 day survival From Murphy GJ et al. N Engl J Med 372: , 2015.
13 ü Context-specific systematic review and meta-analysis of RCTs: effects of restrictive transfusion strategies ü Cardiac/vascular procedures (8 studies; N=3,322 patients) 1. Risk of events reflecting inadequate D0 2 : 1.09 [0.91 to 1.22] 2. Risk of mortality: 1.39 [0.95 to 2.04] 3. Composite events (1+2): From Hovaguimian F & Myles PS. Anesthesiology 125:46-61, 2016.
14 Transfusion Medicine Goodnough LT et al, NEJM 340: ,1999. «It is unlikely that any level of hemoglobin can be used as a universal threshold for transfusion». Transfusion Thresholds Barr PJ, Bailie KEM NEJM 365; 26: , «The decision to transfuse should be guided by an assessment of individual patient on the basis of a combination of symptoms, signs, lab measures and not by a single hemoglobin level».
15 Association Between Blood Transfusion & Morbi-Mortality After Major Surgery Is transfusion the causal event leading to worse outcome or rather a marker for a sicker patient population that is more likely to undergo transfusion for many reasons?
16 Incidence & Importance of Anemia in Patients Undergoing Cardiac Surgery in UK ü National service audit ( ):12/35 UK cardiac surgery centers provided data ü 20% of the patients (4754/23,800) did not have preop Hb ü Incidence of anemia (WHO definition): 31% (23 to 45%) ü Regional variation remained an independent effect ü Independent association of anemia with transfusion, mortality, and hospital stay A 10g/L ê in Hb was associated with a 43% é in the risk of transfusion and a 16% é in the risk of death (both p<0.001) From Klein AA et al. Anaesthesia 71:627-35, 2016.
17 Association of Blood Transfusion With Mortality: Cause or Confounding? ü Retrospective study of patient data (2002-8; N=2599 patients) ü Risk factors associated with in-hospital mortality o Not transfused Transfused ü Chest tube drainage was the strongest independent predictor of mortality while blood transfusion was not From Dixon B et al. Transfusion 53:19-27, 2013.
18 Tolerance to Intraoperative Hemoglobin Decrease During Cardiac Surgery ü Single-center cohort study (N=11,508): patients with normal preoperative hemoglobin ü Composite end-point: in-hospital mortality, stroke, myocardial infarction, and renal failure From Hogervorst E et al. Transfusion 54: , 2014.
19 Indications For RBC Transfusion In Pediatric Cardiac Surgery: Effects on Outcome ü Indications for RBC transfusion: To maintain a predefined hematocrit on bypass To treat perioperative blood loss and/or inadequate oxygen delivery ü Hypothesis: indication for RBC transfusion may impact the effects of transfusion on postoperative morbi-mortality in pediatric cardiac surgery From Willems A et al. Eur J Cardiothorac Surg 45:1050-7, 2014.
20 Indications For RBC Transfusion In Pediatric Cardiac Surgery: Effects on Outcome ü Retrospective cohort study ( ; N=855) ü Transfused children (N=568) Maintenance on-bypass hct of 24% ( CPB driven: N=358) Hemorrhage or O 2 delivery increase (therapeutic: N= 210) ü Primary outcome: composite measure including either hospital death and/or the presence of at least 2 of the following events: Pulmonary failure (mechanical ventilation duration > 75 th percentile) Prolonged inotropic support (inotropes > 5 µg/kg.min for more than 48h) Renal failure (reduction of postop creat clearance 75% from baseline) From Willems A et al. Eur J Cardiothorac Surg 45:1050-7, 2014.
21 Indications For RBC Transfusion In Pediatric Cardiac Surgery: Effects on Outcome ü Transfused children (N=568) Maintenance on-bypass hct of 24% ( CPB driven: N=358) Hemorrhage or O 2 delivery increase (therapeutic: N= 210) p< % 26% CPB-driven Therapeutic From Willems A et al. Eur J Cardiothorac Surg 45:1050-7, 2014.
22 Indications For RBC Transfusion In Pediatric Cardiac Surgery: Effects on Outcome ü Transfused children (N=568) Maintenance on-bypass hct of 20% ( CPB driven: N=358) Hemorrhage or O 2 delivery increase (therapeutic: N= 210) Survival probability (%) Number at risk Logrank p < 0.05 CPB driven transfusion group Therapeutic transfusion group Time (days) From Willems A et al. Eur J Cardiothorac Surg 45:1050-7, CPB driven transfusion group: Therapeutic transfusion group:
23 Indications For RBC Transfusion In Pediatric Cardiac Surgery: Effects on Outcome ü Transfused children (N=568) Maintenance on-bypass hct of 20% ( CPB driven: N=358) Hemorrhage or O 2 delivery increase (therapeutic: N= 210) ü Adjusted multivariate analysis (age, gender, preop weight, redo-surgery, RACHS-1 score, and RBC transfusion volume)
24 Does On-bypass RBC Transfusion Affect Outcome In Pediatric Cardiac Surgery ü Retrospective cohort study ( ; N=1215) ü Studied population (N=854) No transfusion (N=439) Transfused to maintain an on-bypass hct of 24% (N= 415) ü Primary outcome: composite measure including either hospital death and/or the presence of at least 2 of the following events: Pulmonary failure (mechanical ventilation duration > 75 th percentile) Prolonged inotropic support (inotropes > 5 µg/kg.min for more than 48h) Renal failure (reduction of postop creat clearance 75% from baseline) From Willems A et al. Anesth Analg 123:420-9, 2016.
25 Does On-bypass RBC Transfusion Affect Outcome In Pediatric Cardiac Surgery ü Retrospective cohort study ( ; N=1215) ü Studied population (N=854) No transfusion (N=439) Transfused to maintain an on-bypass hct of 24% (N= 415) Composite primary outcome (%) Not transfused CPB transfused P= From Willems A et al. Anesth Analg 123:420-9, 2016.
26 Transfusion & Mortality Conclusions ü The real impact of RBC transfusion on postoperative morbi-mortality remains to be determined. ü Efforts should be done to modify clinical conditions asociated with blood transfusion Preoperative anemia Perioperative blood losses
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