PowerPoint Presentation (PDF) - Perfusion.com

Long-term Consequences
of Blood Transfusion
Jeremiah R. Brown, Ph.D.
March 11, 2011
The Dartmouth Institute for Health Policy and Clinical Practice
Section of Cardiology, Department of Medicine, Dartmouth Medical School
Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756

No financial interests to disclose for
Jeremiah R. Brown, Ph.D.

Objectives
• The “Blood is bad” hypothesis
• Recent evidence on transfusion
• Transfusions and long-term survival

Transfusion and Cardiac Surgery
• Cardiac surgery accounts for 1/3 of all
blood use.
• Over half of transfused blood amounts
to 1-2 units, which could be foregone.
• Successful outcomes for bloodless
surgery centers.

Stored RBCs: Purpose
• RBC purpose:
to increase oxygen carrying capacity.
• No literature exists to support this use in
the very acute surgical patient.
• Stored blood has little efficacy literature.
Speiss BD, SCVA 2004 8(4):267-81

Stored RBCs: Reality
• Do not function normally
• Contain activated inflammatory cells and
mediators
• These changes cause
– limited oxygen release (binds oxygen but does not
release it)
– Impaired microcirculatory flow
– Immune suppression
– Aged RBCs stick together and form microaggregates
Speiss BD, SCVA 2004 8(4):267-81

Quality of Stored RBCs
After storage
the biconcave
disc gives way
to a spherical
shape with
specula leading
to inflexibility,
poor microcirculation
flow,
and capillary
damage.
Holme. Trans Apheres 2005 33:55-61

Ranucci, et al. Crit Care. 2009;13(6):R207

New vs. Old Blood
Crude and adjusted likelihood of experiencing major morbidity in the
group receiving blood prime.
Ranucci, et al. Crit Care. 2009;13(6):R207

New Evidence in 2010
Hajjar, L. A. et al. JAMA
2010;304:1559-1567

TRACS

Hajjar, L. A. et al. JAMA 2010;304:1559-1567
Figure 1. Study Flow

Table. Baseline
Characteristics of
Study Patients.
Hajjar, L. A. et al. JAMA 2010;304:1559-1567

Figure 2. Mean Hemoglobin Levels During the Study According to Transfusion Strategy
Hajjar, L. A. et al. JAMA 2010;304:1559-1567

Figure 3. Kaplan-Meier Estimates of 30-Day Survival by Transfusion Strategy
Hajjar, L. A. et al. JAMA 2010;304:1559-1567

Figure 4. Kaplan-Meier Estimates of 30-Day Survival Based on Number of Red Blood Cell
(RBC) Units Transfused
Hajjar, L. A. et al. JAMA 2010;304:1559-1567

Long-term Survival and
Transfusion

The Risks of RBC Transfusion
Transfusion and Long Term Survival
Observation of 1,915 CABG pts.
34% were transfused, increased risk of death for 5 years.
Engoren et al., Ann Thorac Surg. 2002; 74: 1180

Long-term Survival after pRBC
0 Units
1
2
3-5
6+
Koch CG, et al. ATS 2006 81:1650-7

Duration of RBC Storage and Postop Complications
Permission granted PS-2009-1454 Koch CG, et al., NEJM 2008 358(12):1229-39

Renal Failure
New = 1.6%
Old = 2.7%
Newer Blood
p=0.003
Older Blood
Permission granted PS-2009-1454 Koch CG. NEJM 2008 358(12):1229-39

The NNE Experience:
Transfusion

www.nnecdsg.org
Fletcher Allen
Health Care
Dartmouth-
Hitchcock
Medical
Center
Catholic
Medical Center
Eastern Maine
Medical Center
Central Maine
Medical Center
Maine Medical Center
Concord Hospital
Portsmouth Regional Hospital
Affiliates York Hospital and
Wentworth Douglass Hospital
Northern New England
Cardiovascular Disease
Study Group
The Northern New England
Cardiovascular Disease Study
Group exists to develop and
exchange information
concerning the treatment of
cardiovascular disease. It is a
regional, voluntary, multidisciplinary
group of
clinicians, hospital
administrators, and health
care research personnel who
seek to improve continuously
the quality, safety,
effectiveness, and cost of
medical interventions in
cardiovascular disease.

Percent of total RBCs given
Timing of RBCs Transfusions
When are transfused RBCs given (elective & urgent patients)?
(last 150 cases for each center)
100
80
60
40
20
0
Center
Preop Intraop Postop

Red Blood Cell Transfusions*
≥3 units
n= 728
22%
2 units
n= 493
15%
11%
52%
None
n= 1,691
1 unit
n= 370
* Excludes: emergency, and
return to OR for bleeding
Surgenor et al., Circulation. 2006; 114:I43-8

Results - overall
1.00
5 year survival by RBC use
All cardiac procedures 2001-04
0.95
0.90
0.85
log rank p value < 0.001
0.80
0 1 2 3 4 5
Survival in years
None
1-2 units
There is an early drop in survival with use of 1-2 units RBCs as well
as a continuing decline to at least 5 years

Adjusted survival curve
Adj HR = 1.16
CI95% 1.01-1.34, p=0.038
Use of 1-2 units of RBCs is associated with a significant 16%
increased risk of death over 5 years

Adjusted HRs
Adj. HR 95% CI p value
Adjusted for preop
variables*
1.16 1.01 - 1.33 0.035
Adjusted for preop and
intraop variables**
1.16 1.01 - 1.34 0.038
* Adjusted for age, diabetes, peripheral vascular disease, CHF, COPD,
preop dialysis, preop creatinine, preop WBC, preop hematocrit, ejection fraction,
preop length of stay, preop IABP, priority at surgery
** Adjusted for sex, age, peripheral vascular disease, diabetes, CHF, COPD,
preop dialysis, preop creatinine, preop WBC, preop hematocrit, ejection fraction,
number of diseased coronary arteries, preop length of stay, use of CPB,
use of aprotinin, intra- or postop IABP, use of an IMA, lowest core temperature
on CPB
Use of 1-2 units of RBCs is associated with a significant 16%
increased risk of death

Proportion surviving
Proportion surviving
Adjusted Survival by Red Blood Cell Use
Early Phase
(from surgery to 6 months)
Late Phase
(6 months to 5 years)
1
1
0 . 9 9 5
0 . 9 8
0 . 9 9
0 . 9 6
0 . 9 8 5
0 . 9 4
0 . 9 8
0 . 9 7 5
Adjusted HR = 1.67
95% CI = 1.21-2.28, p = 0.002
0 . 9 2
0 . 9
Adjusted HR = 1.06
95% CI = 0.91-1.24, p = 0.431
0 . 9 7
0 1 2 3 4 5 6
M o n t h s
0 . 8 8
0 1 2 3 4 5
Y e a r s
N O RBCs RBCs N O RBCs RBCs

Adjusted Hazard Ratios

NNE Experience Summary
• Exposure to 1 or 2 units of transfused
RBCs is associated with a decreased
long-term survival.

Transfusion Summary
• Transfusion may do more harm than good.
• Transfusion during the cardiac surgery
admission is associated worse survival.

Thank You
Jeremiah R. Brown, Ph.D.
Dartmouth-Hitchcock Medical Center
Lebanon, NH 03756
jbrown@dartmouth.edu