transfusion & mortality - uz leuven der... · from murphy gj et al. circulation 116: 2544-52,...

Philippe Van der Linden MD, PhD

Transfusion & Mortality

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

Conflict of Interest Disclosure

Blood Transfusion in Cardiac Surgery Patients: Effects on Mortality, Morbidity & Cost

From Murphy GJ et al. Circulation 116: 2544-52, 2007.

ü  Retrospective cohort study (04/1996 – 12/2003; 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



Overall transfusion rate: 57%

Blood Transfusion & Postoperative Morbi-Mortality After Cardiac Surgery

From Loor G et al. J Thorac Cardiovasc Surg 144:538-46, 2012.

Transfusion Triggers After Cardiac Surgery

From Hajjar LA et al. JAMA 304:1559-67, 2010.

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%

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)


10 11

78

47

p<0.001

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 [1.1-1.4]

Transfusion Thresholds & Other Strategies for Guiding Allogeneic

RBC Transfusion

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: -1.85 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, CD002042.

31 trials – 12,587 patients

Liberal or Restrictive Transfusion after Cardiac Surgery

From Murphy GJ et al. N Engl J Med 372:997-1008, 2015.

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)

ü 1 outcome: 90-day mortality + morbidity

Pre storage leukoreduced RBCs transfused unit by unit

2 (1-3) units (92.2%)

1 (0-2) units (53.4%)

1 outcome 2 (1-3) units (92.2%)

1 (0-2) units (53.4%)

90 day survival

HR 1.64 (95% CI 1.00 to 2.67; p=0.045

From Hovaguimian F & Myles PS. Anesthesiology 125:46-61, 2016.

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 D02: 1.09 [0.91 to 1.22] 2.  Risk of mortality: 1.39 [0.95 to 2.04] 3.  Composite events (1+2):

Transfusion Medicine Goodnough LT et al, NEJM 340:438-444,1999.

« 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: 2532-3, 2011.

« 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 ».

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?

Incidence & Importance of Anemia in Patients Undergoing Cardiac Surgery in UK

From Klein AA et al. Anaesthesia 71:627-35, 2016.

ü National service audit (2010-2012):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)

Association of Blood Transfusion With Mortality: Cause or Confounding?

From Dixon B et al. Transfusion 53:19-27, 2013.

ü  Retrospective study of patient data (2002-8; N=2599 patients) ü  Risk factors associated with in-hospital mortality

ü Chest tube drainage was the strongest independent predictor of mortality while blood transfusion was not

o  Not transfused •  Transfused

Tolerance to Intraoperative Hemoglobin Decrease During Cardiac Surgery

From Hogervorst E et al. Transfusion 54:2696-704, 2014.

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

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.

ü  Retrospective cohort study (2006-2009; N=855)

ü  Transfused children (N=568) •  Maintenance on-bypass hct of 24% ( CPB driven: N=358) •  Hemorrhage or O2 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 > 75th percentile) •  Prolonged inotropic support (inotropes > 5 µg/kg.min for more than 48h) •  Renal failure (reduction of postop creat clearance ≥ 75% from baseline)




CPB-driven Therapeutic

p<0.001

48%

26%




0 50 100 1500

50

100

150

0 5 10 15 20 25 30

86

88

90

92

94

96

98

100

Time (days)

Survival probability (%)

Number at risk

CPB driven transfusion group:

356 348 220 104 66 39 29Therapeutic transfusion group:

208 199 164 106 83 64 48

CPB driven transfusion group

Logrank p < 0.05

Therapeutic transfusion group




ü Adjusted multivariate analysis (age, gender, preop weight, redo-surgery, RACHS-1 score, and RBC transfusion volume)



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 > 75th 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.

Does On-bypass RBC Transfusion Affect Outcome In Pediatric Cardiac Surgery


ü  Studied population (N=854) •  No transfusion (N=439) •  Transfused to maintain an on-bypass hct of 24% (N= 415)

Does On-bypass RBC Transfusion Affect Outcome In Pediatric Cardiac Surgery

0

10

20

30

40

50

Composite primary outcome (%)

Not transfusedCPB transfused

P=0.538

From Willems A et al. Anesth Analg 123:420-9, 2016.

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

Transfusion & Mortality Conclusions

transfusion & mortality - uz leuven der... · from murphy gj et al. circulation 116: 2544-52,...

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