All Bleeding Eventually Stops:

Are Outcomes Changed by

Transfusion?

Colleen Gorman Koch, MD, MS, FACC

Cardiothoracic Anesthesia and
Outcomes Research
Cleveland Clinic
 Objectives

• To better understand risk association

between red blood cell transfusion and
morbid outcomes in cardiac surgical
patients.
• To discuss recent investigations in critically
ill surgical patients and to discuss areas for
future investigation.
•Notion that RBC beneficial to
replace lost volume and for
O2 carrying capacity
was unchallenged for years

--as advertised, saves lives

•Concept of risk changed with

infectious transmission and
association between
morbidity and RBC became focus
of research
 Limited Resource:
Challenges us to think more conservatively
 Risks

Morbidity and Mortality

Outcomes
 Morbidity and Mortality:
Cohort Investigations

Transfusion

Infection:
Mortality:
Sternal wound Pulmonary Renal
MSOF Short
Pneumonia dysfunction insufficiency
Long-term

•N, Outcome, RBC binary, heterogeneity, statistics, generalize

 Morbidity and Mortality
in (N=11,963) Isolated CABG
Koch, et al., Critical Care Medicine 2006;34:1608-1616

•Increased risk for every morbid outcome

•Dose-dependent relationship between each unit and events
Frequency Histogram for RBC Units
Transfused

•48% transfused

•Most commonly
1-2 units transfused

Koch et al., Critical Care Medicine 2006;34:1608-1616

Patient and Procedural Variables
Related to RBC Transfusion
Koch et al., Critical Care Medicine 2006;34:1608-1616

•Older, smaller,
lower pre-op HCT,
comorbidity,
clinical presentation:
emergency, NYHA,
preop IABP; reoperation
longer clamp times
 Infection:
End-points: bacteremia, septicemia,
superficial and deep sternal wound infections
Banbury, et al., JACC 2006;202:131

•N=15,592

•(55%)
transfused
•Dose-dependent
relationship

Independent risk for postoperative infection

Transfusion and Atrial Fibrillation
Koch et al., Ann Thoracic Surgery 2006;82;1747

• Evidence suggests an
inflammatory mechanism in
development of AF
• RBC: direct infusion of
inflammatory mediators and
augmentation of response to
CBP and CTS
• RBC a/c new onset AF on and
off pump patients

N=5841
 Engoren, et al. Annals of Thoracic Surgery 2002

N=1915

N=649
transfused
N=546
Propensity
matched

Risk factor for 5 year mortality after CTS

Transfusion and Long-term
Survival
Koch et al., Ann Thorac Surg 2006;81:1650-7

•Long-term survival after

controlling for early hazard and
other risk factors

•Risk is biphasic and incremental:

early phase within 6 months
higher than late phase

•Blackstone parametric
decomposition method accounts
for non-proportionality;
simultaneously models time-
N=10,289 varying hazard and risk factors
 Koch et al., Annals of Thorac Surg 2006;82:13-20

•Reductions in
functional recovery
paralleled RBC
transfused

Quality of life: DASI (N=7,321)

 N=7,321

Annals of Thorac Surg 2006;82:13-20

 Other Issues…

• Leukocyte-reduced status

• Age of red cells

• Blood substitutes
 Storage Duration:
Hemorrheological Changes
Journal of Surgical Research 2002;102:6-12

•Reversible and irreversible functional and structural changes

•May contribute to decreased microvascular flow,

local hypoxia and post-transfusion complications
Distribution of RBC Units

Exclusively blood stored <14 days (orange, N=2872) and >14 days
(blue, 3130). Distributions between 2 groups are similar.
Mean Storage duration and number of RBC units by storage duration.
 Dose-response Relationship Between Max Days
Storage and Probability of Composite Outcome

Increasing linear trend, particularly for those receiving units > 14 days storage duration
Storage Duration and Outcome
 Survival and Hazard Curves
N=2872 (yellow, younger), N=3130 (blue, older)

Those receiving older blood had reduced survival particularly

during initial follow-up and more pulmonary, renal and infectious
complications
Predicted Survival and Maximal Age with
Hazard Decomposition Model

1 day = orange; 15 days = red; 30 days = blue; and 42 days = black

Blood Substitutes
PNAS 2007;104
 Tissue Oxygenation
• Local microcirculatory control mechanisms are
important in the restoration of tissue oxygenation.
• Regulatory mechanisms for maintaining adequate
tissue oxygen concentration are not well
understood.
• Role of oxygen sensor in tissue? Red cell?
• Red cell may play a role as oxygen carrier and
oxygen sensor, during hypoxia it may modulate
flow by release of vasodilatory nitric oxide.
 Tissue Oxygenation
• New findings indicate that red cell function is
more complex than previously assumed.
• Advantage of oxygen sensing by red cells is that
allows an immediate feedback during oxygen off-
loading as hypoxic vasodilator release can directly
alter local vascular tone and hence adapt tissue
perfusion and oxygenation according to local
needs.
 Future Investigation
• Clearly we need better data to improve
management decisions related to transfusion
• Prospective cohort investigations provide a
‘starting point’ for further investigation;
(understanding limits of statistical methodology)
• Effectiveness needs to be evaluated in RCT for
given levels of anemia in specific population
New Donation Strategy?

Give Blood, Play Hockey